Cost-Related Medication Nonadherence in Canada: A Systematic Review of Prevalence, Predictors, and Clinical Impact

Cost-Related Medication Nonadherence in Canada: A Systematic Review of Prevalence, Predictors, and Clinical Impact | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Cost-Related Medication Nonadherence in Canada: A Systematic Review of Prevalence, Predictors, and Clinical Impact Anne Marie Holbrook, Mei Wang, Munil Lee, Zhiyuan Chen, Michael Garcia, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-27665/v2 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Jan, 2021 Read the published version in Systematic Reviews → Version 2 posted 4 You are reading this latest preprint version Show more versions Abstract Background Cost-related nonadherence to medications (CRNA) is common in many countries and thought to be associated with adverse outcomes. The characteristics of CRNA in Canada, with its patchwork coverage of increasingly expensive medications, is unclear. Objectives Our objective in this systematic review was to summarize the literature evaluating CRNA in Canada in three domains: prevalence, predictors, and effect on clinical outcomes. Methods We searched MEDLINE, Embase, Google Scholar, and the Cochrane Library from 1992 to December 2019 using search terms covering medication adherence, costs, and Canada. Eligible studies, without restriction on design, had to have original data on at least one of the three domains specifically for Canadian participants. Articles were identified and reviewed in duplicate. Risk of bias was assessed using design-specific tools. Results: Twenty-six studies of varying quality (n=483,065 Canadians) were eligible for inclusion. Sixteen studies reported on the overall prevalence of CRNA, with population-based estimates ranging from 5.1% to 10.2%. Factors predicting CRNA included high out of pocket spending, low income or financial flexibility, lack of drug insurance, younger age, and poorer health. A single randomized trial of free essential medications with free delivery in Ontario improved adherence but did not find any change in clinical outcomes at one year. Conclusion: CRNA affects many Canadians. The estimated percentage depends on the sampling frame, the main predictors tend to be financial, and its association with clinical outcomes in Canada remains unproven. Clinical Pharmacology Medication adherence medication costs Canada systematic review Figures Figure 1 Figure 2 Background Medication cost-related nonadherence (CRNA) is defined as taking less medication than prescribed because of cost, such as delaying or failing to fill prescriptions, or skipping or lowering medication doses.(1-3) International estimates of the incidence and prevalence vary but are thought to be particularly high in the United States where many citizens are uninsured or under-insured.(4-7) Several factors have been found to be associated with nonadherence, including poor health, low household income, and disease burden.(1, 8) Cost-related factors proposed include lack of prescription drug coverage, high monthly medication cost, and high out-of-pocket costs.(1, 8-12) As for patient outcomes associated with CRNA, increased cost sharing was associated with increased use of health services such as hospitalization and Emergency Department (ED) visits among patients with a number of chronic conditions.(9, 13-15) Treatment choices that patients at risk of CRNA face may lead to priorities that do not optimize health, such as choosing medications providing symptom relief only rather than important clinical benefit.(16) Other studies have suggested that higher medication adherence is associated with better outcomes and lower healthcare costs across many disease states and populations, including children.(17-19) However, all of these studies are susceptible to confounding due to their lower quality design and the ‘healthy user effect’—the likelihood that adherent individuals have other unmeasured healthy behaviours.(17) Indeed, randomized trial evidence that removing financial barriers to essential medication access improves clinical outcomes, is lacking. The landmark MI-FREEE trial showed that randomization to full coverage of key cardiac medications for patients post-myocardial infarction improved adherence but made no difference in the primary outcome of vascular events.(20) Although CRNA is well described in the United States and documented in other countries such as the UK and other European countries, it has not been as well characterized in Canada. (21-23) (21-23) Total health expenditure in Canada was estimated to be $242 billion in 2017, with drugs accounting for 16.4% of the total and increasing at a faster rate than other sectors.(24) Furthermore, Canadians face some of the highest medication charges in the world, and while many individuals have private coverage, provincial-territorial public plans include some with very high co-pays and deductibles.(25, 26) Considering the effect that CRNA may have on patient outcomes and health care spending, knowledge of its prevalence, predictors and clinical effects could help clinicians and policymakers to improve the effectiveness and cost-effectiveness of patient care. National Pharmacare themes under active discussion include national formulary creation, size and reimbursement options.(27, 28) Given the current debate on medication costs, adherence, and Pharmacare policy nationally, we aimed to systematically review the literature to determine the prevalence, predictors and clinical outcomes of CRNA in Canada. Our research question was ‘Amongst Canadians of any age, what is the prevalence of CRNA, what are its predictors using multivariable analysis, and what are the resultant clinical outcomes of CRNA? Methods This systematic review was designed in accordance with the most recent PRISMA statement (checklist attached) but a review protocol was not registered.(29, 30) Eligible studies had to provide original data on at least one of the three stated objectives involving CRNA and Canadians. The following databases were searched since inception to the week of December 9, 2019: MEDLINE, Embase, Cochrane Library, and Google Scholar. The initial search terms used for MEDLINE and Embase were: prescription fees, drug adj costs, exp patient compliance, medication adherence, cost sharing, health expenditures, and Canada/ or Canada. The Cochrane library search began with the terms "cost related adherence" and "Canada" and then limited, if needed, to include only studies involving Canada. For Google Scholar, the following searches were performed: "Cost-related nonadherence" and ‘Canada’ combined with ‘medications’ or ‘drugs’ or ‘prescriptions’. No language restriction was applied. Authors of key studies were surveyed for information on studies missed by our search or published since. The search strategy for MEDLINE is provided in Appendix 1. Two authors screened the retrieved titles and abstracts. Articles were only included if they 1) directly measured CRNA (ie, not just adherence) prevalence. Studies examining predictors of CRNA had to have used a multi-variable analysis that adjusted for multiple factors or measured differences in adherence in a randomized trial of an intervention directly targeting CRNA, or measured change in adherence immediately before and after a policy change where a change in patient costs or out-of-pocket expenses for medications is reasonably implicated. Studies examining the impact of CRNA were required to examine clinical outcomes such as hospitalization, adverse events, or disease. For example, self-reported increased health care utilization did not count. We included studies of any design without restriction on medication, age, sex, outcome, or measure of adherence. Studies were excluded if they did not report original data, were conference abstracts, or did not involve an identifiable Canadian population whose results were specified. Articles passing through title and abstract screening underwent full text screening then subsequent data extraction using pre-piloted forms. We extracted data on study design, sample size, CRNA definition, predictors, clinical outcomes, risk of bias, and statistical analysis. Two reviewers carried out duplicate full text screening and data extraction independently, with differences resolved by consensus. Risk of bias assessment was conducted using study design-specific tools. Surveys were rated on representativeness of the sample, adequacy of response rate, missing data, pilot testing, and validity of the survey instrument, using a tool from Evidence Partners.(31) Qualitative studies were assessed using the Critical Appraisal Skills Program (CASP) checklist which asks about appropriateness of qualitative design, recruitment, researcher-participant relationship, and data collection and analysis.(32) For pre-post studies, we assessed intervention effect on the rate of outcomes over time, confounding, missing data, and selective reporting, using the Cochrane risk of bias criteria for interrupted time series studies.(33) An overall risk of bias rating was calculated for each study based on the percentage of low risk of bias items (70-100% = low risk of bias, 31-69% = moderate risk; 0-30% = high risk). A Summary Risk of Bias chart was created based on the Cochrane tool, showing each study as low, moderate or high risk of bias.(34) Analyses planned included descriptive details of each study addressing at least one of our three components of CRNA, with additional focus on population-based studies (as opposed to disease- or drug-specific results) Quantitative data pooling of prevalence results was planned where permissible by availability of compatible data, otherwise qualitative summaries of prevalence, predictors and outcomes. Results Study Characteristics Of 1,390 articles identified by the literature searches and additional checks, 1,321 were excluded based on their titles and abstracts (Figure 1. Study Flow Chart). Sixty-nine studies were screened in full text with 43 eliminated at this stage, leaving 26 included studies (study details in Table 1).(2, 3, 35-58) Since several of these studies used the same source survey.(3, 38, 39, 43, 45, 46, 54, 55) the total sample size of unique participants across all 26 studies is uncertain. Assuming that each study’s participant is a unique individual, the total sample size is 497,534. All but one of the studies were observational, varying from surveys to large healthcare database time series, to qualitative designs. The summary risk of bias was rated as low for eight studies, moderate for nine, and high for nine studies (details in Figure 2). All studies reported only on adults, except two studies based on the Canadian Community Health Survey (CCHS)(40, 54) which included those at least 12 years of age. Definitions of CRNA in surveys and the RCT generally included not filling a prescription or skipping doses because of cost, while the health administrative database studies assumed that declines in utilization shortly after drug policy changes implied CRNA. Table 1. Study Characteristics and Results Study ID, Design Demographics Definition of CRNA Prevalence of CRNA Predictors of CRNA a Impact on Clinical Outcomes Brand 1977 (35) Survey with in-person interviews over a 3-month period, year unspecified N=225 patients discharged from hospital in Halifax, NS (mean age 57.0) Not complying with > 1 physician order(s) due to cost of drugs 13.8% ‘Cost of drugs’ (p 18 yrs. Failure to obtain a prescribed medication due to cost 5.1% No Canada-specific data N/A Hirth 2008 (37) 2002 – 2004 DOPPS patient questionnaires N=503 Canadian adult hemodialysis patients from 20 facilities (mean age 62.1, SD 14.7) Not purchasing medication due to cost 12.9% Out-of-pocket spending burden (R 2 =0.44) N/A Kennedy 2009 (38) 2007 IHP phone survey N=2,980 Canadian adults > 18 yrs. Not filling a prescription or skipping doses of medication due to cost during the previous 12 months 8.0% Younger (< 65 yrs.), multiple chronic conditions, lower household income, each p 18 yrs. (median age 50, SE 0.3) Not filling a prescription or skipping doses of medication due to cost during the previous 12 months 8.0% Younger age RR=3.9 (95% CI 2.2 – 6.9); Income below average RR=3.1 (95% CI 2.1 – 4.7); High out of pocket prescription costs (RR=4.6 (95% CI 3.8–6.7); First Nations RR=2.1 (95% CI 1.4 – 3.2); Self-reported poor health status RR=1.5 (95% CI 1.2–2.0); Not feeling involved in treatment decisions RR=1.3 (95% CI 1.1–1.4) N/A Law 2012 (40) 2007 CCHS phone survey N=5,732 community-dwelling Canadians > 12 yrs. who received a prescription in previous year Altering a prescription to make it last longer or not filling a new prescription or renewing an ongoing prescription, due to cost Canadian sample: 9.6% (95% CI 8.4-10.7%); QB: 7.2% (4.5 – 9.8); ON: 9.1% (7.2 – 11.0%); BC: 17.0% (12.6 – 21.4%) Younger age OR=4.70 (95% CI 2.91–7.60); Low household income OR=3.29 (95% CI 2.03 – 5.33); Lack of insurance coverage for drugs OR=4.52 (95% CI 3.29–6.20); Several chronic health conditions OR=1.61 (95% CI 1.07 – 2.43); Fair or poor self-assessed health status OR=2.64 (95% CI 1.77–3.94); Residing in BC (compared to Ontario) OR=2.56 (95% CI 1.49–4.42) N/A Zheng 2012 (41) Cross-sectional survey with in-person interviews between March 10-April 19, 2011 N=60 adult patients attending a general internal medicine rapid assessment outpatient clinic in Hamilton, ON (mean age 60.3, SD 14.3) Left prescriptions unfilled, delayed filling prescriptions, took prescriptions with reduced frequency or lowered dosages in the previous year because of the cost 15.0% No drug insurance OR=20.7 (95% CI 1.46-292.75); High Out of pocket expenses OR=42.52 (95% CI 2.02-894.03) N/A Hunter 2015 (42) HHiT study in-person interviews between Jan.-Dec. 2009 N=716 homeless or vulnerably housed single adults in Vancouver, Toronto and Ottawa and prescribed > 1 current medication Not actually taking a current medication prescribed by a doctor as “the medication is too expensive” 3.6% N/A N/A Hennessy 2016 (2) BCPCHC survey between Feb. 2011-Mar. 2012 N=1,849 > 40 yr from BC, AB, SK or MB who reported having heart disease, stroke, diabetes or hypertension (mean age 65.1, 95% CI 64.3-65.9) For the previous 12 months, due to cost, either a) not getting necessary prescription medication or b) stopping one or more prescribed drug for a week or more 4.1% (95% CI 2.6%-6.3%) Out-of-pocket spending greater than 5% of household income (Prevalence RR=2.6; 95% CI 1.0-6.4) N/A Lee 2017 (43) 2014 IHP phone survey N=4,690 community-dwelling Canadians > 55 yrs. Not filling a prescription or skipping doses within the last 12 months because of out-of-pocket costs 8.3% QC (compared to ON) adjusted OR=0.49 (95% CI: 0.29–0.82); Younger age (compared to > 65y): 55-64 yrs. OR=3.13 (95% CI 2.27–5.40); Poor health status OR=1.75 (95% CI 1.12–2.38); Low income OR=3.59 (95% CI 2.32–5.55); Lack of private insurance OR=2.33, (95% CI 1.56–3.10) N/A Morgan 2017 (3) 2014 IHP phone survey N=4,696 community-dwelling Canadians > 55 yrs. Not filling a prescription or skipped doses within the last 12 months because of out-of-pocket costs 8.3% Canadians (compared to UK) adjusted OR=2.25, 95% CI (1.08-4.69); Lower income (compared to UK) OR=1.23 (95% CI 0.64- 2.40) N/A Sarnak 2017 (44) OECD data, 2016 IHP phone survey and other sources N=4,547 Canadian adults > 18 yrs. Not filling/collecting a prescription for medicine or skipped doses because of cost in the past 12 months Overall: 10.2%; 0 chronic diseases 5.0% vs 1 chronic disease 12.0% vs 2+ chronic diseases 16.0% N/A N/A Soril 2017 (45) 2004-14 IHP phone surveys (selected years) N=25,740 Canadian adults > 18 yrs. Not filling a prescription because of costs in the previous 12 months Overall: range 7.1% - 8.2%; Older/sicker adult cohort: range 6.5% - 19.8% N/A N/A Law 2018 (46) 2016 CCHS phone survey N=28,091 community-dwelling Canadians > 12 yrs. Skipping or reducing dosages, or delaying refill prescriptions or not filling prescriptions at all to reduce drug costs 5.5% (95% CI: 5.1%-6.0%) Younger adult (P<0.001); Out-of-pocket prescription drug spending (P<0.001); Lack of drug insurance (P<0.001); Lower income (P<0.001); Poorer health status (P 12 yrs old with > 2 chronic conditions Skipping or reducing dosages, delaying refill prescriptions or not filling prescriptions at all to reduce drug costs 10.2% (95% CI 8.6–11.9%); 15.2% (95% CI 11.6–18.8)) for respiratory and 16.6% (95% CI 13.2–9.9%) for mental health disorders Age between 19 and 44 years (OR 2.74 95%CI 1.76, 4.26); out of pocket spending on prescription medicines > CAD500 OR 2.56, 95%CI 1.49, 4.40; lack of drug insurance (OR) 3.26, 95%CI 2.12,4.80; fair to poor health status OR 3.42, 95%CI 1.46, 8.02; residing in certain provinces, eg, BC OR 4.20, 95%CI 2.55, 6.91. N/A Men 2019 (55) 2016 CCHS phone survey N = 11,172 community-dwelling Canadians with a prescription within previous year and answering a food security questionnaire Skipping or reducing dosages, or delaying refill prescriptions or not filling prescriptions at all to reduce drug costs 8.3% Household food insecurity adjusted for sociodemographic factors, associated with CRN - RR 1.82 (95% CI 1.00 to 3.31), 3.83 (95% CI 2.44 to 6.03) and 5.05 (95% CI 3.27 to 7.81) for marginally, moderately and severely food-insecure households, respectively, compared to those with no food insecurity N/A Monagle 2018 (56) Phone survey of one anticoagulant clinic N = 110 adult patients newly started on oral anticoagulants in Hamilton, ON Leaving a prescription unfilled or delaying filling a prescription or taking less of a medication, due to cost. Warfarin users were more likely to report CRN than NOAC users (40% vs 13%, p = 0.02) N/A N/A Yao 2018 (47) Retrospective pre-post database study 2005-09 pre- and post-Seniors’ Drug plan policy change (max. out-of-pocket $15 per prescription for patients > 65 yrs.) vs concurrent control patients 40-64 yr not affected by policy N=188,109 observed patients in SK CRNA assumed if adherence post-policy improved compared pre-period and to unaffected control. N/A Odds of optimal medication adherence: Post-SDP (compared to pre-SDP) OR=1.08 (95% CI: 1.04 to 1.11), but only where OOP costs > $15 per prescription, for prevalent users, for some medication classes. Not compared directly to concurrent control. N/A Dormuth 2006 (48) Retrospective pre-post database study between Jun. 1997-04 with monthly time series pre- (full coverage) vs. post-policy (copayment) N=55,752 BC residents > 65 yrs. not in a nursing home, dispensed inhaled corticosteroids (ICS) in 2001 (mean age 75.5) CRNA assumed if use of respiratory inhalers declined after policy increasing out-of-pocket expenses N/A Initiation of ICS for new diagnosis of asthma or COPD compared to pre-policy reduced by 25% (95% CI: 14% – 31%); Discontinuation of ICS was increased 47% (40%-55%) in copayment group N/A Schneeweiss 2007 (49) Retrospective pre-post database study 2000-04 with repeated measures design, monthly adherence measurement pre- (full coverage) vs. post-policy (copayment) N=41,561 seniors in BC who were new users of statin drugs CRNA assumed if use of statins declined after policy increasing out-of-pocket expenses N/A Paying 100% out-of-pocket (compared to pre-policy) OR=1.94 (95% CI 1.82 - 2.08); Patients post-myocardial infarction or post-revascularization (higher risk) OR=0.63 (95% CI 0.59 – 0.68) N/A Schneeweiss 2007 (50) Retrospective pre-post database study 2000-04 with repeated measures design, monthly adherence measurement pre- (full coverage) vs. post-policy (copayment) N=13,193 seniors from BC who were new users of β- blockers CRNA assumed if use of beta-blockers declined after policy increasing out-of-pocket expenses N/A Post-policy cohort (compared to pre-policy) associated with 1.3% decline in adherence (95% CI 2.5 - 0.04) N/A Goldsmith 2017 (51) Qualitative study with semi-structured interviews of CRNA experience from patients’ perspective 2014-15 N=35 adults in BC and ON who reported CRNA Patient self-report of skipping doses, splitting pills, or not filling their prescriptions due to out-of-pocket costs N/A Type of insurance; individual's overall financial flexibility; the burden of drug cost on the individual's budget; perceived importance of the importance of the drug N/A Gupta 2019 (57) Qualitative study with semi-structured interviews of strategies used to deal with cost burden N = 12 adult Canadians with spinal cord injuries who reported CRNA N/A N/A Out-of-pocket cost of medication; perceived importance of the drug; lack of drug insurance; competing financial needs, eg, food, housing; inability to discuss with physicians. N/A Tamblyn 2001 (52) Retrospective database study with interrupted monthly time-series 1993-97 pre (full-coverage for welfare and low-income seniors; $2 copayment for all other seniors) vs post-policy (25% coinsurance and deductible) N=70,801 elderly and 25,820 welfare recipients using ‘essential drugs’ in QC CRNA assumed if post- policy decrease in use of essential drugs N/A Increase in cost sharing associated with decrease in essential drug use by elderly by 9.1% (95% CI 8.7 – 9.6) and by welfare recipients by 14.4% (95% CI 13.3 – 15.6%) Net increase in serious adverse events by 6.8 and 12.9 per 10,000/mo; in ED visits by 14.2 and 54.2 per 10,000/mo for elderly and for welfare recipients respectively Pilote 2002 (53) Retrospective database study with time series analysis 1994-1998 pre- (full-coverage for welfare and low-income seniors and $2 copayment for all other seniors) vs. post-policy (25% coinsurance and deductible) N=22,066 patients > 65 yrs. admitted to a QC hospital for a first acute myo-cardial infarction and discharged alive CRNA assumed if proportion of patients who filled at least one prescription during the year after discharge, declined post-policy change N/A N/A as no change in adherence pre- vs. post-policy No differences in readmission for cardiac complications, mortality rate, or use of outpatient physician or ED services Persaud 2019 (58, 65) Randomized open label trial 2016-2017 with free access including free delivery of prescribed essential medication, compared to usual care N = 786 adults > 18 yr old in 9 primary care practices in ON who reported CRNA (mean age 51.7 yr, 55.9% female) Self-reported not filling a prescription or making a prescription last longer because of the cost within the previous 12 months N/A No variation in adherence by income No difference in rates of hospitalization, serious adverse events or deaths. a Using adjusted or multivariable analyses. CRNA=cost-related non-adherence; N/A= Data not available; BCPCHC=Barriers to Care for People with Chronic Health Conditions; DOPPS= Dialysis Outcomes and Practice Patterns study; HHiT=Health and Housing in Transition; IHP=International Health Policy; CCHS=Canadian Community Health Survey; OECD= Organization for Economic Co-operation and Development ; ICS=Inhaled corticosteroids; SDP=Seniors’ Drug Plan; BC=British Columbia; AB=Alberta; SK=Saskatchewan; MB=Manitoba; ON=Ontario; QC=Quebec. NNT = Number needed to treat. Prevalence of Medication CRNA in Canada Sixteen studies, excluding a medication-specific survey(56), addressed the prevalence of CRNA (n = 105,109 potential participants) (Table 1).(2, 3, 35-46, 54, 55) Using somewhat differing definitions for CRNA and different sampling frames, these studies suggested prevalence between 3.6% and 15.0%.(2, 3, 35-46, 54, 55) Ten of these studies providing more generalizable and population-level analyses (ie, not highly selected sub-groups such as the homeless or those with several chronic conditions) based on large national or international surveys suggested rates of 5.1% to 10.2%.(3, 36, 38-40, 43-46, 55) The Joint Canada-US Survey of Health telephone survey in 2002 included 3505 Canadian adults, 5.1% of whom reported CRNA.(36) In the International Health Policy telephone surveys, 8.0% of the sampled Canadian adults reported CRNA in 2007, and 10.2% in 2016.(38, 39, 44) The CRNA section of the Canadian Community Health Surveys (CCHS) found that 9.6% of adults who received a prescription reported CRNA in 2007 compared to 5.5% overall in 2016.(40, 46) The 2007 analysis suggested geographic variability, with higher rates of CRNA in British Columbia than other regions.(46) Two studies examined different subgroups of the 2016 CCHS.(54, 55) Two additional studies estimated CRNA in specific sub-groups groups of Canadian patients, and reported rates of 10.2% in Canadians with comorbidities and 8.3% in participants with food insecurity.(37, 41) Predictors of CRNA Nineteen studies (n = 440,064 potential participants) provided information on the predictors of CRNA (details in Table 1).(2, 3, 35, 37-41, 43, 46-52, 54, 55, 57, 58) Thirteen studies (n = 70,636) analyzed multiple potential factors based on direct reporting from study participants. (2, 3, 35, 37-41, 43, 46, 51, 54, 55) Five additional studies (n = 369,416) involving large administrative databases used time series methods with or without pre-post analyses of policies which changed the amount of patient cost-sharing in provinces, to suggest that increased out-of-pocket expenditures for drugs is a predictor of non-adherence assumed to be CRNA.(47-50, 52) Several factors emerged as independent predictors in the studies using multivariable analyses. In order of high to low frequency of mention, these were: high out-of-pocket expenses on medication, lower household income or financial flexibility, lack of drug insurance, younger age, poor self-reported health, province of residence, and miscellaneous (Table 2). (2, 3, 35-41, 43, 46-55, 57) The analysis of the CRNA module within the 2007 CCHS was the largest and most detailed, showing a prevalence of 11.4% for the 35 to 44 years age group compared to 4.8% for subjects older than 65 years.(40) In the multivariable analysis, odds ratios were 4.5 for lack of drug insurance, 3.3 for low household income. 20.1% of participants reporting poor health also reported CRNA compared to 10.4% of subjects reporting good health (OR 2.64, 95% CI 1.77 - 3.94).(40) Finally, factors which may reflect differences amongst jurisdictions including their policies, were also independent predictors. Amongst those younger than 65 years, respondents in the 2014 International Health Policy Survey (IHPS) who were from Quebec were less likely to report CRNA than those residing in Ontario (OR 0.5, 95% CI 0.3-0.8).(43) At the time, while drug insurance was compulsory in Quebec, Ontario reimbursed non-seniors only for those who were socially disadvantaged or had very high medication costs.(43) In the 2007 CCHS, residence in British Columbia where a significant portion of public drug coverage has income-based deductibles was associated with more CRNA compared with Ontario (OR 2.56, 95% CI 1.49–4.42).(40)The IHPS segment of Canadians self-identifying as First Nations, Inuit or Metis, were at higher risk of CRNA (RR 2.1, 95% CI 1.4 – 3.2).(39) Although the publicly funded Non-insured Health Benefits Program includes drug benefits without co-payment or deductible, these apply only to those considered ‘status Indians’ or Inuk and require providers to register with the program to avoid initial self-pay.(59) Table 2. Predictors of CRNA in Canada Predictor # Articles Reporting Significance Citation Higher out-of-pocket costs* 13 (2), (3), (37), (39), (40), (41), (47), (48), (49), (50), (52), (54), (57) Lower income or low financial flexibility 9 (3) , (38), (39) , (40), (43), (46),(51) (55), (57) Lack of drug insurance 7 (40) , (41), (43) , (46) , (51), (54), (57) Younger age 6 (38), (39), (40), (43), (46), (54) Poor self-reported health status 5 (39) , (40) , (43) , (46), (54) Province of residence (eg, Ontario instead of Quebec, or British Columbia instead of Ontario or Quebec) 4 (38), (43), (46), (54) Several chronic health conditions 2 (38), (46) High cost of drugs 2 (35), (51) Low/medium drug importance from individual’s perspective 2 (51), (57) Not feeling involved in treatment decisions 2 (39), (57) First Nations status 1 (39) *includes studies comparing rates of CRNA pre- and post- copayment policy Three studies in BC using a similar cohort with similar methodology examined the influence of increased out-of-pocket expense by analyzing the effect of changes in drug insurance coverage on adherence measured by prescription dispensing intervals.(48-50) The utilization of maintenance respiratory inhalers declined by approximately 5.8 to 12.3% (p<0.001), the rate of full adherence to statins decreased by 5.4% (95% CI, 6.4% to 4.4%) but adherence to beta-blockers was only modestly reduced (approximately 1%) compared to full coverage.(48-50) Non-adherence was associated with higher out-of-pocket expenditures, with beta-blockers thought to be less affected because of their low cost compared to the other drug groups at the time of the study.(50) For statins, adherence was better in high risk patients with prior vascular events compared to the entire group.(49) An analysis of a policy change to lower seniors’ out of pocket prescription drug costs in Saskatchewan in 2007, found a small increase in optimal medication adherence after the policy change.(47) CRNA Association with Clinical Outcomes Only three studies measured clinical outcomes potentially related to CRNA (Table 1; n = 93,653).(52, 53, 58) The highest quality study was a recent randomized controlled trial involving patients in primary care in Ontario who reported that they did not fill a prescription or changed regimens to make their supply last longer because of the cost. The study found that the intervention group provided free, mailed prescriptions deemed essential, reported better adherence, improved perceived care, and less concern about making ends meet at 12 months follow-up. Several surrogate outcomes were followed, with improvement in blood pressure in the intervention group for those requiring anti-hypertensives but no significant improvement in A1C or cholesterol. However, there was no difference in hospitalizations, serious adverse events or death. The introduction of a drug policy in Quebec in the nineties increased out-of-pocket costs for all residents. In one retrospective study, this led to a decrease in the overall number of drugs used per day by the elderly and by welfare recipients, including ‘essential’ medications such as aspirin and furosemide (decrease of 9.1% - 14.4%) as well as symptomatic but potentially harmful drugs such as benzodiazepines (decrease of 15.1% - 22.4%). The decline in use of essential drugs was associated with a small increase in serious adverse events including death, hospital or nursing home admission, or emergency department visits.(52)In a second retrospective study, there was no change in adherence to post-myocardial infarction medication adherence and no change in clinical outcomes after the policy compared to pre-policy.(53) Discussion We believe that this is the first systematic review to focus on the relationship between medication costs and medication adherence in Canada. All but one of the studies in our review were observational therefore susceptible to bias and confounders. We found rates of CRNA range from 5.1% to 10.2% in general surveys of the population over time, suggesting that an important minority of the population is experiencing problems with prescription medication adherence due to their medication cost.The range is likely explained by differing sampling frames, questions, definitions of CRNA and statistical uncertainty. The international studies in our review suggest that Canadian rates of CRNA are in the middle other developed countries. In the IHPS survey, the rate of CRNA in Canada (8%) was in the middle of seven countries, with the Netherlands having the lowest rate (3%) and the US having the highest rate (20%).(39) In the dialysis study, the rate of CRNA in Canada (12.9%) was similar to the overall rate of CRNA among 12 countries (13.4 %), with Japan being the lowest rate (3.2%) and the US being the highest rate (29.2%).(38) Overall, predictors for CRNA in Canada revolved around lack of affordability, younger age, chronic illness, private insurance coverage, and province of residence. This likely reflects characteristics of the different public drug plan coverage programs and different financial capability to afford medicines in different provinces. None of the studies developed or used a clinical prediction rule, which would examine risk factors together to determine how their quantitative combination influences risk.(60) This is a well-established method to refine population risk to individual risk. Both qualitative studies found that patients weighed their financial obligations against the perceived importance of the medication(s) in making their adherence decisions, and recognized that they sometimes were making decisions that might adversely affect their health.(51) The lack of current information on the association of CRNA with clinical outcomes in Canada is very troubling, as this is the primary question of interest both for clinicians and policy makers. Although low adherence to beneficial medications has previously been linked to increased mortality, the data may be biased due to the ‘healthy user’ effect.(17) Randomized trials show that interventions to improve adherence do so only modestly and do not seem to improve patient outcomes.(61) Two recent randomized controlled trials (RCTs) in the United States directly address whether removing medication cost improves clinical outcomes. The aforementioned MI FREEE RCT found that free coverage for essential cardiovascular medications post-myocardial infarction increased adherence by 4 to 6% (p < 0.001), but did not improve the primary outcome of first major vascular event or procedure.(20) More recently, the ARTEMIS trial also found that provision of free access to P2Y 12 inhibiting anti-platelet agents for a year increased adherence by a small amount (2.3%) but there was no difference in major adverse cardiovascular events.(62) In addition, since patients are frequently taking medications that are not essential and may be harmful, decreased adherence to these medications may not lead to adverse outcomes. Two of our studies suggested that participants reported increased health care utilization as a result of their CRNA, but did not actually measure clinical outcomes or healthcare utilization.(46, 57) The sole RCT in our SR found that the free provision and delivery of essential medications increased adherence by 10% and improved one of three clinical surrogates at 12 months follow-up, but did not improve clinical outcomes.(58) In summary, the relationship between medication costs, medication adherence and patient outcomes is more complex than originally thought. This systematic review has limitations worth noting. First, since studies varied in their methods of measurement, quantitative pooling was not possible. Second, there is no gold standard measure for medication adherence, so there are likely measurement errors with each of the methods used. Third, questionnaire studies are susceptible to responder and recall bias, and the studies examining adherence before and after policy changes are somewhat indirect inferences regarding the impact of costs. Fourth, we were unable to find information on how different types of insurance – co-pays, deductibles, annual maximums, etc – influence the prevalence of CRNA. Finally, since multiple behavioural attributes are associated with non-adherence, it would take a very large prospective study to determine the specific impact of medication cost on adherence. The findings of this systematic review have several implications. First, as CRNA may affect a large number of Canadians, communication between providers and patients regarding affordability of prescribed medications is essential and may play an important role in the reduction of CRNA. Second, the evidence summarized here will be useful to inform the debate on a national Pharmacare program where proponents cite estimates of higher health care utilization because of patient burden of medication costs while opponents cite lack of evidence that removal of patient-borne costs improves outcomes.(63, 64) Modelling of a universal drug benefit program would benefit from better estimates of the impact on CRNA on health care utilization and clinical outcomes.(28) The association of high out-of-pocket medication costs with lower adherence might argue for improved drug coverage for those with low incomes. However, the high quality evidence so far suggests that more research is required to determine for which people, which drugs, which situations, and how much cost relief might be required to improve clinical outcomes. Conclusion Our systematic review suggests that an important minority of Canadians may not be adherent to medications because of their costs. Financial factors appear to be the main predictors of CRNA, suggesting that drug program design and coverage have a significant influence on CRNA rates. However, consistent with international evidence to date, removal of all medication cost for essential drugs for patients with CRNA has not been shown to improve clinical outcomes. List Of Abbreviations CRNA - Cost-Related Nonadherence ED - Emergency Department CCHS - Canadian Community Health Survey IHPS - International Health Policy Survey Declarations Ethics approval and consent to participate Not Applicable. Consent for publication Not Applicable. Availability of data and material All data generated or analysed during this study are included in this published article and its supplementary information files. Competing interests Michael Law has consulted for Health Canada and the Health Employees’ Union, and provided expert witness testimony for the Attorney General of Canada. Anne Holbrook has served as an expert policy advisor for national, provincial and local hospital public drug plans for several decades. All other authors report no relevant competing interests. Funding Funded by the Canadian Institutes of Health Research (CIHR) Grant MOP-126020, Principal Investigator Dr Michael Law and CIHR Grant FRN-148803, Principal Investigator Dr Anne Holbrook. Dr. Law received salary support through a Canada Research Chair and a Michael Smith Foundation for Health Research Scholar Award. Authors' contributions AH was responsible for conception and design of the work. AH, MW, ML, NC, LN, MG, SM, AF contributed to acquisition and analysis of the data, all authors contributed to the interpretation of data, AH wrote each draft and the final manuscript. All authors contributed to revisions of drafts. All authors read and approved the final manuscript. Acknowledgements Not Applicable. References Briesacher BA, Gurwitz JH, Soumerai SB. 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Towards Implementation of National Pharmacare Discussion Paper 2018 [Available from: https://www.canada.ca/content/dam/hc-sc/documents/corporate/publications/council_on_pharmacare_EN.PDF . Acri K. The Unintended Consequences of National Pharmacare Programs: The Experiences of Australia, New Zealand, and the UK 2018 [Available from: https://www.fraserinstitute.org/studies/unintended-consequences-of-national-pharmacare-programs . Krol BL. The Effect of Free Distribution of Essential Medicines on Adherence by Income Sources and Level: University of Toronto; 2019 Appendix APPENDIX 1. MEDLINE Search Strategy Database: OVID Medline Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1946 to Present Search Strategy: -------------------------------------------------------------------------------- 1 *Medication Adherence/ (8545) 2 Patient Compliance/ (54949) 3 persisten$.mp. (286317) 4 adheren$.mp. (159735) 5 complian$.mp. (157679) 6 1 or 2 or 3 or 4 or 5 (572582) 7 Drug Costs/ (14578) 8 Prescription Fees/ (1123) 9 Fees, Pharmaceutical/ (1269) 10 cost sharing.mp. (3230) 11 co-pay.mp. (78) 12 "Deductibles and Coinsurance"/ (1631) 13 self-pay.mp. (575) 14 out-of-pocket.mp. (4212) 15 Insurance Coverage/ (11433) 16 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 (34851) 17 exp Canada/ (145847) 18 canadian$.mp. (52774) 19 (British Columbia$ or alberta$ or saskatchewan$ or manitoba$).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms] (31518) 20 (ontari$ or quebec$ or new brunswick$ or nova scotia$).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms] (59631) 21 (prince edward island$ or newfoundland$ or yukon$ or northwest territor$ or nunavut$).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms] (4260) 22 17 or 18 or 19 or 20 or 21 (188579) 23 6 and 16 and 22 (66) *************************** Supplementary Files CRNCanadaSRmanuscriptPRISMAchecklistapril2020.pdf Cite Share Download PDF Status: Published Journal Publication published 06 Jan, 2021 Read the published version in Systematic Reviews → Version 2 posted Editorial decision: Accept 13 Dec, 2020 Editor assigned by journal 03 Nov, 2020 Submission checks completed at journal 03 Nov, 2020 Editor invited by journal 03 Nov, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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1","display":"","copyAsset":false,"role":"figure","size":66180,"visible":true,"origin":"","legend":"Study Flow Chart","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-27665/v2/f28167fb85b2765b17d3f303.jpg"},{"id":3511358,"identity":"f0616c14-b66f-4c16-a4e0-beed76c442f6","added_by":"auto","created_at":"2020-11-11 14:46:55","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":298453,"visible":true,"origin":"","legend":"The summary risk of bias was rated as low for eight studies, moderate for nine, and high for nine studies","description":"","filename":"2final.jpg","url":"https://assets-eu.researchsquare.com/files/rs-27665/v2/3bb60087d46d6814d20108c9.jpg"},{"id":13613031,"identity":"4883d0cd-d1a9-4864-b6ee-93bc893985c2","added_by":"auto","created_at":"2021-09-17 06:35:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":492444,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-27665/v2/cea081d7-f2ef-41c5-b92f-d91ec9b71e0a.pdf"},{"id":3511356,"identity":"1d5569c9-9c97-49ba-8584-9a04d1bb2a5f","added_by":"auto","created_at":"2020-11-11 14:46:55","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":99600,"visible":true,"origin":"","legend":"","description":"","filename":"CRNCanadaSRmanuscriptPRISMAchecklistapril2020.pdf","url":"https://assets-eu.researchsquare.com/files/rs-27665/v2/42d7d886fcf1f7cc948d0b27.pdf"}],"financialInterests":"","formattedTitle":"Cost-Related Medication Nonadherence in Canada: A Systematic Review of Prevalence, Predictors, and Clinical Impact","fulltext":[{"header":"Background","content":"\u003cp\u003eMedication cost-related nonadherence (CRNA) is defined as taking less medication than prescribed because of cost, such as delaying or failing to fill prescriptions, or skipping or lowering medication doses.(1-3) International estimates of the incidence and prevalence vary but are thought to be particularly high in the United States where many citizens are uninsured or under-insured.(4-7) Several factors have been found to be associated with nonadherence, including poor health, low household income, and disease burden.(1, 8) Cost-related factors proposed include lack of prescription drug coverage, high monthly medication cost, and high out-of-pocket costs.(1, 8-12) As for patient outcomes associated with CRNA, increased cost sharing was associated with increased use of health services such as hospitalization and Emergency Department (ED) visits among patients with a number of chronic conditions.(9, 13-15)\u0026nbsp;Treatment choices that patients at risk of CRNA face may lead to priorities that do not optimize health, such as choosing medications providing symptom relief only rather than important clinical benefit.(16) \u0026nbsp;Other studies have suggested that higher medication adherence is associated with better outcomes and lower healthcare costs across many disease states and populations, including children.(17-19) However, all of these studies are susceptible to\u0026nbsp; confounding due to their lower quality design and the \u0026lsquo;healthy user effect\u0026rsquo;\u0026mdash;the likelihood that adherent individuals have other unmeasured healthy behaviours.(17) Indeed, randomized trial evidence that removing financial barriers to essential medication access improves clinical outcomes, is lacking. The landmark MI-FREEE trial showed that randomization to full coverage of key cardiac medications for patients post-myocardial infarction improved adherence but made no difference in the primary outcome of vascular events.(20)\u003c/p\u003e\n\u003cp\u003eAlthough CRNA is well described in the United States and documented in other countries such as the UK and other European countries, it has not been as well characterized in Canada. (21-23) (21-23) \u0026nbsp;Total health expenditure in Canada was estimated to be $242 billion in 2017, with drugs accounting for 16.4% of the total and increasing at a faster rate than other sectors.(24)\u003csup\u003e\u0026nbsp; \u003c/sup\u003eFurthermore, Canadians face some of the highest medication charges in the world, and while many individuals have private coverage, provincial-territorial public plans include some with very high co-pays and deductibles.(25, 26) Considering the effect that CRNA may have on patient outcomes and health care spending, knowledge of its prevalence, predictors and clinical effects could help clinicians and policymakers to improve the effectiveness and cost-effectiveness of patient care. National Pharmacare themes under active discussion include national formulary creation, size and reimbursement options.(27, 28)\u003c/p\u003e\n\u003cp\u003eGiven the current debate on medication costs, adherence, and Pharmacare policy nationally, we aimed to systematically review the literature to determine the prevalence, predictors and clinical outcomes of CRNA in Canada. Our research question was \u0026lsquo;Amongst Canadians of any age, what is the prevalence of CRNA, what are its predictors using multivariable analysis, and what are the resultant clinical outcomes of CRNA?\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis systematic review was designed in accordance with the most recent PRISMA statement (checklist attached) but a review protocol was not registered.(29, 30) Eligible studies had to provide original data on at least one of the three stated objectives involving CRNA and Canadians. The following databases were searched since inception to the week of December 9, 2019: MEDLINE, Embase, Cochrane Library, and Google Scholar. The initial search terms used for MEDLINE and Embase were: prescription fees, drug adj costs, exp patient compliance, medication adherence, cost sharing, health expenditures, and Canada/ or Canada. The Cochrane library search began with the terms \"cost related adherence\" and \"Canada\" and then limited, if needed, to include only studies involving Canada. For Google Scholar, the following searches were performed: \"Cost-related nonadherence\" and \u0026lsquo;Canada\u0026rsquo; combined with \u0026lsquo;medications\u0026rsquo; or \u0026lsquo;drugs\u0026rsquo; or \u0026lsquo;prescriptions\u0026rsquo;. No language restriction was applied. Authors of key studies were surveyed for information on studies missed by our search or published since. The search strategy for MEDLINE is provided in Appendix 1.\u003c/p\u003e\n\u003cp\u003eTwo authors screened the retrieved titles and abstracts. Articles were only included if they 1) directly measured CRNA (ie, not just adherence) prevalence. Studies examining predictors of CRNA had to have used a multi-variable analysis that adjusted for multiple factors or measured differences in adherence in a randomized trial of an intervention directly targeting CRNA, or measured change in adherence immediately before and after a policy change where a change in patient costs or out-of-pocket expenses for medications is reasonably implicated. \u0026nbsp;Studies examining the impact of CRNA were required to examine clinical outcomes such as hospitalization, adverse events, or disease. For example, self-reported increased health care utilization did not count. We included studies of any design without restriction on medication, age, sex, outcome, or measure of adherence. Studies were excluded if they did not report original data, were conference abstracts, or did not involve an identifiable Canadian population whose results were specified.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eArticles passing through title and abstract screening underwent full text screening then subsequent data extraction using pre-piloted forms. We extracted data on study design, sample size, CRNA definition, predictors, clinical outcomes, risk of bias, and statistical analysis. Two reviewers carried out duplicate full text screening and data extraction independently, with differences resolved by consensus.\u003c/p\u003e\n\u003cp\u003eRisk of bias assessment was conducted using study design-specific tools. Surveys were rated on representativeness of the sample, adequacy of response rate, missing data, pilot testing, and validity of the survey instrument, using a tool from Evidence Partners.(31) Qualitative studies were assessed using the Critical Appraisal Skills Program (CASP) checklist which asks about appropriateness of qualitative design, recruitment, researcher-participant relationship, and data collection and analysis.(32) For pre-post studies, we assessed intervention effect on the rate of outcomes over time, confounding, missing data, and selective reporting, using the Cochrane risk of bias criteria for interrupted time series studies.(33) An overall risk of bias rating\u0026nbsp; was calculated for each study based on the percentage of low risk of bias items (70-100% = low risk of bias, 31-69% = moderate risk; 0-30% = high risk). A Summary Risk of Bias chart was created based on the Cochrane tool, showing each study as low, moderate or high risk of bias.(34)\u003c/p\u003e\n\u003cp\u003eAnalyses planned included descriptive details of each study addressing at least one of our three components of CRNA, with additional focus on population-based studies (as opposed to disease- or drug-specific results) Quantitative data pooling of prevalence results was planned where permissible by availability of compatible data, otherwise qualitative summaries of prevalence, predictors and outcomes.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003eStudy Characteristics\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eOf 1,390 articles identified by the literature searches and additional checks, 1,321 were excluded based on their titles and abstracts (Figure 1. Study Flow Chart). Sixty-nine studies were screened in full text with 43 eliminated at this stage, leaving 26 included studies (study details in Table 1).(2, 3, 35-58) Since several of these studies used the same source survey.(3, 38, 39, 43, 45, 46, 54, 55) the total sample size of unique participants across all 26 studies is uncertain. Assuming that each study\u0026rsquo;s participant is a unique individual, the total sample size is 497,534. All but one of the studies were observational, varying from surveys to large healthcare database time series, to qualitative designs. The summary risk of bias was rated as low for eight studies, moderate for nine, and high for nine studies (details in Figure 2). \u0026nbsp;All studies reported only on adults, except two studies based on the Canadian Community Health Survey (CCHS)(40, 54) which included those at least 12 years of age. Definitions of CRNA in surveys and the RCT generally included not filling a prescription or skipping doses because of cost, while the health administrative database studies assumed that declines in utilization shortly after drug policy changes implied CRNA.\u003c/p\u003e\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:16px;line-height:115%;\"\u003eTable 1. Study Characteristics and Results\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width:678.75pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 28.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"line-height:115%;\"\u003eStudy ID, Design\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: 1pt solid black;border-right: 1pt solid black;border-bottom: 1pt solid black;border-image: initial;border-left: none;background: silver;padding: 0in 5.4pt;height: 28.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"line-height:115%;color:black;\"\u003eDemographics\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: 1pt solid black;border-right: 1pt solid black;border-bottom: 1pt solid black;border-image: initial;border-left: none;background: silver;padding: 0in 5.4pt;height: 28.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"line-height:115%;color:black;\"\u003eDefinition of CRNA\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: 1pt solid black;border-right: 1pt solid black;border-bottom: 1pt solid black;border-image: initial;border-left: none;background: silver;padding: 0in 5.4pt;height: 28.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"line-height:115%;color:black;\"\u003ePrevalence of CRNA\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: 1pt solid black;border-right: 1pt solid black;border-bottom: 1pt solid black;border-image: initial;border-left: none;background: silver;padding: 0in 5.4pt;height: 28.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"line-height:115%;color:black;\"\u003ePredictors of CRNA\u003csup\u003ea\u003c/sup\u003e\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: 1pt solid black;border-right: 1pt solid black;border-bottom: 1pt solid black;border-image: initial;border-left: none;background: silver;padding: 0in 5.4pt;height: 28.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"line-height:115%;color:black;\"\u003eImpact on Clinical Outcomes\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eBrand 1977\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e(35)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eSurvey with in-person interviews over a 3-month period, year unspecified\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN=225 patients discharged from \u0026nbsp;hospital in Halifax, NS (mean age 57.0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eNot complying with \u003cu\u003e\u0026gt;\u003c/u\u003e 1 physician order(s) due to cost of drugs\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e13.8%\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026lsquo;Cost of drugs\u0026rsquo; (p\u0026lt;0.001)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eKennedy 2006\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e(36)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e2002-03 Joint Canada-US Survey of Health\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN=3,505 Canadian adults \u003cu\u003e\u0026gt;\u003c/u\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:#222222;\"\u003e18 yrs.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eFailure to obtain a prescribed medication due to cost\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e5.1%\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e\u0026nbsp;No Canada-specific data\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eHirth 2008\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e(37)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e2002 \u0026ndash; 2004 DOPPS patient questionnaires\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN=503 Canadian adult hemodialysis patients from 20 facilities (mean age 62.1, SD 14.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eNot purchasing medication due to cost\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e12.9%\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eOut-of-pocket spending burden \u0026nbsp;(R\u003csup\u003e2\u003c/sup\u003e=0.44)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eKennedy 2009\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e(38)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e2007 IHP phone survey\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN=2,980 Canadian adults\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:#222222;\"\u003e\u0026nbsp;\u003c/span\u003e\u003cu\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e\u0026gt;\u003c/span\u003e\u003c/u\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:#222222;\"\u003e18 yrs.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eNot filling a prescription or skipping doses of medication due to cost during the previous 12 months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e8.0%\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eYounger (\u0026lt; 65 yrs.), multiple chronic conditions, lower household income, each p \u0026lt; 0.01 (OR not reported); Quebec (compulsory coverage) compared to Ontario OR=0.5 (95% CI: 0.3-0.8)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eKemp 2010\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e(39)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e2007 IHP phone survey\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN=2,183 Canadian adults\u003cspan style=\"color:#222222;\"\u003e\u0026nbsp;\u003c/span\u003e\u003cu\u003e\u0026gt;\u003c/u\u003e \u003cspan style=\"color:#222222;\"\u003e18 yrs.\u003c/span\u003e (median age 50, SE 0.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eNot filling a prescription or skipping doses of medication due to cost during the previous 12 months\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e8.0% \u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eYounger age \u0026nbsp;RR=3.9 (95% CI 2.2 \u0026ndash; 6.9); Income below average RR=3.1 (95% CI 2.1 \u0026ndash; 4.7); High out of pocket prescription costs (RR=4.6 (95% CI 3.8\u0026ndash;6.7); First Nations RR=2.1 (95% CI 1.4 \u0026ndash; 3.2); Self-reported poor health status RR=1.5 (95% CI 1.2\u0026ndash;2.0); Not feeling involved in treatment decisions RR=1.3 (95% CI 1.1\u0026ndash;1.4)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eLaw 2012\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e(40)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e2007 CCHS phone survey\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN=5,732 community-dwelling Canadians \u003cu\u003e\u0026gt;\u003c/u\u003e 12 yrs. who received a prescription in previous year\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eAltering a prescription to make it last longer or not filling a new prescription or renewing an ongoing prescription, due to cost\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eCanadian sample: 9.6% (95% CI 8.4-10.7%);\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eQB: 7.2% (4.5 \u0026ndash; 9.8); ON: 9.1% (7.2 \u0026ndash; 11.0%); BC: 17.0% (12.6 \u0026ndash; 21.4%)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eYounger age \u0026nbsp;OR=4.70 (95% CI 2.91\u0026ndash;7.60); Low household income OR=3.29 (95% CI 2.03 \u0026ndash; 5.33); Lack of insurance coverage for drugs OR=4.52 (95% CI 3.29\u0026ndash;6.20); Several chronic health conditions OR=1.61 (95% CI 1.07 \u0026ndash; 2.43); Fair or poor self-assessed health status OR=2.64 (95% CI 1.77\u0026ndash;3.94); Residing in BC (compared to Ontario) OR=2.56 (95% CI 1.49\u0026ndash;4.42)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eZheng 2012\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e(41)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eCross-sectional survey with in-person interviews between March 10-April 19, 2011\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN=60 adult patients attending a general internal medicine rapid assessment outpatient clinic in Hamilton, ON (mean age 60.3, SD 14.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eLeft prescriptions unfilled, delayed filling prescriptions,\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003etook prescriptions with reduced frequency or lowered dosages in the previous year because of the cost\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e15.0%\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eNo drug insurance OR=20.7 (95% CI 1.46-292.75); High Out of pocket expenses OR=42.52 (95% CI 2.02-894.03)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eHunter 2015\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e(42)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eHHiT study in-person interviews between Jan.-Dec. 2009\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN=716 homeless or vulnerably housed single adults in Vancouver, Toronto and Ottawa and prescribed \u003cu\u003e\u0026gt;\u0026nbsp;\u003c/u\u003e1 current medication\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eNot actually taking a current medication prescribed by a doctor as \u0026ldquo;the medication is too expensive\u0026rdquo;\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e3.6%\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eHennessy 2016\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e(2)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eBCPCHC survey between Feb. 2011-Mar. 2012\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN=1,849 \u003cu\u003e\u0026gt;\u003c/u\u003e 40 yr from BC, AB, SK or MB who reported having heart disease, stroke, diabetes or hypertension (mean age 65.1, 95% CI 64.3-65.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eFor the previous 12 months, due to cost, either a) not getting necessary prescription medication or b) stopping one or more prescribed drug for a week or more\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e4.1% (95% CI 2.6%-6.3%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eOut-of-pocket spending greater than 5% of household income (Prevalence RR=2.6; 95% CI 1.0-6.4)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 13pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eLee 2017\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e(43)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e2014 IHP phone survey\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN=4,690 community-dwelling Canadians \u003cu\u003e\u0026gt;\u0026nbsp;\u003c/u\u003e55 yrs.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eNot filling a prescription or skipping doses within the last 12 months because of out-of-pocket costs\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e8.3%\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eQC (compared to ON) adjusted OR=0.49 (95% CI: 0.29\u0026ndash;0.82); Younger age (compared to \u003cu\u003e\u0026gt;\u0026nbsp;\u003c/u\u003e65y): 55-64 yrs. OR=3.13 (95% CI 2.27\u0026ndash;5.40); Poor health status OR=1.75 (95% CI 1.12\u0026ndash;2.38); Low income OR=3.59 (95% CI 2.32\u0026ndash;5.55); Lack of private insurance OR=2.33, (95% CI 1.56\u0026ndash;3.10)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eMorgan 2017\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e(3)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e2014 IHP phone survey\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;border:none;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;N=4,696 community-dwelling Canadians \u003cu\u003e\u0026gt;\u003c/u\u003e 55 yrs.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eNot filling a prescription or skipped doses within the last 12 months because of out-of-pocket costs\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e8.3%\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eCanadians (compared to UK) adjusted OR=2.25, 95% CI (1.08-4.69); Lower income (compared to UK) OR=1.23 (95% CI 0.64- 2.40)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eSarnak 2017\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e(44)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:#222222;\"\u003eOECD data, 2016 IHP phone survey and other sources\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:#222222;\"\u003eN=4,547 Canadian adults\u0026nbsp;\u003c/span\u003e\u003cu\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e\u0026gt;\u003c/span\u003e\u003c/u\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:#222222;\"\u003e18 yrs.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eNot filling/collecting a prescription for medicine or skipped doses because of cost in the past 12 months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eOverall: 10.2%;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e0 chronic diseases 5.0% vs 1 chronic disease 12.0% vs 2+ chronic diseases 16.0%\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eSoril 2017\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e(45)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e2004-14 IHP phone surveys (selected years)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN=25,740 Canadian adults \u003cu\u003e\u0026gt;\u003c/u\u003e \u003cspan style=\"color:#222222;\"\u003e18 yrs.\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eNot filling a prescription because of costs in the previous 12 months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eOverall: range 7.1% - 8.2%;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eOlder/sicker adult cohort: range 6.5% - 19.8%\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eLaw 2018\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e(46)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e2016 CCHS phone survey\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN=28,091 community-dwelling Canadians \u003cu\u003e\u0026gt;\u0026nbsp;\u003c/u\u003e12 yrs.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eSkipping or reducing dosages, or delaying refill prescriptions or not filling prescriptions at all to reduce drug costs\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e5.5% (95% CI: 5.1%-6.0%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eYounger adult (P\u0026lt;0.001); Out-of-pocket prescription drug spending (P\u0026lt;0.001); Lack of drug insurance (P\u0026lt;0.001); Lower income (P\u0026lt;0.001); Poorer health status (P\u0026lt;0.001)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eLaba 2018\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e(54)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e2016 CCHS phone survey\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN = 8420 community-dwelling Canadians \u003cu\u003e\u0026gt;\u003c/u\u003e 12 yrs old with \u003cu\u003e\u0026gt;\u0026nbsp;\u003c/u\u003e2 chronic conditions\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eSkipping or reducing dosages, delaying refill prescriptions or not filling prescriptions at all to reduce drug costs\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e10.2% (95% CI 8.6\u0026ndash;11.9%); 15.2% (95% CI 11.6\u0026ndash;18.8)) for respiratory and 16.6% (95% CI 13.2\u0026ndash;9.9%) for mental health disorders\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eAge between 19 and 44 years (OR 2.74 95%CI 1.76, 4.26); out of pocket spending on prescription medicines \u0026gt; CAD500 OR 2.56, 95%CI 1.49, 4.40; lack of drug insurance (OR) 3.26, 95%CI 2.12,4.80; fair to poor health status OR 3.42, 95%CI 1.46, 8.02; residing in certain provinces, eg, BC OR 4.20, 95%CI 2.55, 6.91.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eMen 2019\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e(55)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e2016 CCHS phone survey\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN = 11,172 community-dwelling Canadians with a prescription within previous year and answering a food security questionnaire\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eSkipping or reducing dosages, or delaying refill prescriptions or not filling prescriptions at all to reduce drug costs\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e8.3%\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eHousehold food insecurity adjusted for sociodemographic factors, associated with CRN - RR\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e\u0026nbsp;1.82 (95% CI 1.00 to 3.31), 3.83 (95% CI 2.44 to 6.03) and 5.05 (95% CI 3.27 to 7.81) for marginally, moderately and severely food-insecure households, respectively, compared to those with no food insecurity\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eMonagle 2018\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e(56)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003ePhone survey of one anticoagulant clinic\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN = 110 adult patients newly started on oral anticoagulants in Hamilton, ON\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eLeaving a prescription\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eunfilled or delaying filling a prescription\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;or taking less of a medication, due to cost.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eWarfarin users were more likely to report CRN than NOAC users (40% vs 13%, p = 0.02)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eYao 2018\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e(47)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eRetrospective pre-post database study 2005-09 pre- and post-Seniors\u0026rsquo; Drug plan policy change (max. out-of-pocket \u0026nbsp; \u0026nbsp; $15 per prescription for patients \u003cu\u003e\u0026gt;\u003c/u\u003e\u0026nbsp; 65 yrs.) vs concurrent control patients 40-64 yr not affected by policy\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN=188,109 observed patients in SK\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eCRNA assumed if adherence post-policy improved compared pre-period and to unaffected control.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eOdds of optimal medication adherence: Post-SDP (compared to pre-SDP) OR=1.08 (95% CI: 1.04 to 1.11), but only where OOP costs \u0026gt; $15 per prescription, for prevalent users, for some medication classes. Not compared directly to concurrent control.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eDormuth 2006\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e(48)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eRetrospective pre-post database study between Jun. 1997-04 with monthly time series pre- (full coverage) vs. post-policy (copayment)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN=55,752 BC residents \u003cu\u003e\u0026gt;\u003c/u\u003e 65 yrs. not in a nursing home, dispensed inhaled corticosteroids (ICS) in 2001 (mean age 75.5)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eCRNA assumed if use of respiratory inhalers declined after policy increasing out-of-pocket expenses\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eInitiation of ICS for new diagnosis of asthma or COPD compared to pre-policy reduced by 25% (95% CI: 14% \u0026ndash; 31%); Discontinuation of ICS was increased 47% (40%-55%) in copayment group\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eSchneeweiss 2007\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e(49)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eRetrospective pre-post database study 2000-04 with repeated measures design, monthly adherence measurement pre- (full coverage) vs. post-policy (copayment)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN=41,561 seniors in BC who were new users of statin drugs\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eCRNA assumed if use of statins declined after policy increasing out-of-pocket expenses\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003ePaying 100% out-of-pocket (compared to pre-policy) OR=1.94 (95% CI 1.82 - 2.08); Patients post-myocardial infarction or post-revascularization (higher risk) OR=0.63 (95% CI 0.59 \u0026ndash; 0.68)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eSchneeweiss 2007\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e(50)\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eRetrospective pre-post database study 2000-04 with repeated measures design, monthly adherence measurement pre- (full coverage) vs. post-policy (copayment)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN=13,193 seniors from BC who were new users of \u0026beta;- blockers\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eCRNA assumed if use of beta-blockers declined after policy increasing out-of-pocket expenses\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003ePost-policy cohort (compared to pre-policy) associated with 1.3% decline in adherence (95% CI 2.5 - 0.04)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eGoldsmith 2017\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e(51)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eQualitative study with semi-structured interviews of CRNA experience from patients\u0026rsquo; perspective 2014-15\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN=35 adults in BC and ON who reported CRNA\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003ePatient self-report of skipping doses, splitting pills, or not filling their prescriptions due to out-of-pocket costs\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eType of insurance; individual\u0026apos;s overall financial flexibility; the burden of drug cost on the individual\u0026apos;s budget; perceived importance of the importance of the drug\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eGupta 2019\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e(57)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eQualitative study with semi-structured interviews of strategies used to deal with cost burden\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN = 12 adult Canadians with spinal cord injuries who reported CRNA\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eOut-of-pocket cost of medication; perceived importance of the drug; lack of drug insurance; competing financial needs, eg, food, housing; inability to discuss with physicians.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eTamblyn 2001\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e(52)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eRetrospective database study with interrupted monthly time-series 1993-97 \u0026nbsp;pre (full-coverage for welfare and low-income seniors; $2 copayment for all other seniors) vs post-policy (25% coinsurance and deductible)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN=70,801 elderly and 25,820 welfare recipients using \u0026lsquo;essential drugs\u0026rsquo; in QC\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eCRNA assumed if \u0026nbsp;post- policy decrease in use of essential drugs\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eIncrease in cost sharing associated with decrease in essential drug use by elderly by 9.1% (95% CI 8.7 \u0026ndash; 9.6) and by welfare recipients by 14.4% (95% CI 13.3 \u0026ndash; 15.6%)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eNet increase in serious adverse events by 6.8 and 12.9 per 10,000/mo; in ED visits by 14.2 and 54.2 per 10,000/mo for elderly and for welfare recipients respectively\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003ePilote 2002\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e(53)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eRetrospective database study with time series analysis 1994-1998 pre- (full-coverage for welfare and low-income seniors and \u0026nbsp;$2 \u0026nbsp;copayment for all other seniors) vs. post-policy (25% coinsurance and deductible)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN=22,066 patients \u003cu\u003e\u0026gt;\u0026nbsp;\u003c/u\u003e65 yrs. admitted to a QC hospital for a first acute myo-cardial infarction and discharged alive\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eCRNA assumed if proportion of patients who filled at least one prescription during the year after discharge, declined post-policy change\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eN/A as no change in adherence pre- vs. post-policy\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003eNo differences in readmission for cardiac complications, mortality rate, or use of outpatient physician or ED services\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 147.15pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003ePersaud 2019\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003e(58, 65)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eRandomized open label trial 2016-2017 with free access including free delivery of prescribed essential medication, compared to usual care\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN = 786 adults \u003cu\u003e\u0026gt;\u003c/u\u003e 18 yr old in 9 primary care practices in ON who reported CRNA (mean age 51.7 yr, 55.9% female)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 88.5pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eSelf-reported\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003enot filling a prescription or\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003emaking a prescription last longer because of the cost within the previous 12 months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.85pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eN/A\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198.2pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eNo variation in adherence by income\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 14pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size:12px;line-height:115%;color:black;\"\u003eNo difference in rates of hospitalization, serious adverse events or deaths.\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003csup\u003e\u003cspan style=\"font-size:11px;\"\u003ea\u0026nbsp;\u003c/span\u003e\u003c/sup\u003e\u003cspan style=\"font-size:11px;\"\u003eUsing adjusted or multivariable analyses. CRNA=cost-related non-adherence; N/A= Data not available;\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:11px;\"\u003eBCPCHC=Barriers to Care for People with Chronic Health Conditions;\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:11px;\"\u003eDOPPS=\u003c/span\u003e\u003cspan style=\"font-size:11px;\"\u003eDialysis Outcomes and Practice Patterns study; HHiT=Health and Housing in Transition;\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:11px;\"\u003eIHP=International Health Policy; CCHS=Canadian Community Health Survey;\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:11px;\"\u003eOECD=\u003cspan style=\"color:#222222;\"\u003eOrganization for Economic Co-operation and Development\u003c/span\u003e\u003c/span\u003e\u003cspan style=\"font-size:11px;\"\u003e; ICS=Inhaled corticosteroids; SDP=Seniors\u0026rsquo; Drug Plan; BC=British Columbia; AB=Alberta; SK=Saskatchewan; MB=Manitoba; ON=Ontario; QC=Quebec. NNT = Number needed to treat.\u003c/span\u003e\u003c/p\u003e\u003cbr\u003e\u003cp\u003e\u003cem\u003ePrevalence of Medication CRNA in Canada\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSixteen studies, excluding a medication-specific survey(56), addressed the prevalence of CRNA (n = 105,109 potential participants) (Table 1).(2, 3, 35-46, 54, 55) Using somewhat differing definitions for CRNA and different sampling frames, these studies suggested prevalence between 3.6% and 15.0%.(2, 3, 35-46, 54, 55) Ten of these studies providing more generalizable and population-level analyses (ie, not highly selected sub-groups such as the homeless or those with several chronic conditions) based on large national or international surveys suggested rates of 5.1% to 10.2%.(3, 36, 38-40, 43-46, 55) The Joint Canada-US Survey of Health telephone survey in 2002 included 3505 Canadian adults, 5.1% of whom reported CRNA.(36) In the International Health Policy telephone surveys, 8.0% of the sampled Canadian adults reported CRNA in 2007, and 10.2% in 2016.(38, 39, 44) The CRNA section of the Canadian Community Health Surveys (CCHS) found that 9.6% of adults who received a prescription reported CRNA in 2007 compared to 5.5% overall in 2016.(40, 46) \u0026nbsp;The 2007 analysis suggested geographic variability, with higher rates of CRNA in British Columbia than other regions.(46) Two studies examined different subgroups of the 2016 CCHS.(54, 55) Two additional studies estimated CRNA in specific sub-groups groups of Canadian patients, and reported rates of 10.2% in Canadians with comorbidities and 8.3% in participants with food insecurity.(37, 41)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePredictors of CRNA\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNineteen studies (n = 440,064 potential participants) provided information on the predictors of CRNA (details in Table 1).(2, 3, 35, 37-41, 43, 46-52, 54, 55, 57, 58) Thirteen studies (n = 70,636) analyzed multiple potential factors based on direct reporting from study participants. (2, 3, 35, 37-41, 43, 46, 51, 54, 55) \u0026nbsp;Five additional studies (n = 369,416) involving large administrative databases used time series methods with or without pre-post analyses of policies which changed the amount of patient cost-sharing in provinces, to suggest that increased out-of-pocket expenditures for drugs is a predictor of non-adherence assumed to be CRNA.(47-50, 52)\u003c/p\u003e\n\u003cp\u003eSeveral factors emerged as independent predictors in the studies using multivariable analyses. In order of high to low frequency of mention, these were: high out-of-pocket expenses on medication, lower household income or financial flexibility, lack of drug insurance, younger age, poor self-reported health, province of residence, and miscellaneous (Table 2). (2, 3, 35-41, 43, 46-55, 57) The analysis of the CRNA module within the 2007 CCHS was the largest and most detailed, showing a prevalence of 11.4% for the 35 to 44 years age group compared to 4.8% for subjects older than 65 years.(40) In the multivariable analysis, odds ratios were 4.5 for lack of drug insurance, 3.3 for low household income. 20.1% of participants reporting poor health also reported CRNA compared to 10.4% of subjects reporting good health (OR 2.64, 95% CI 1.77 - 3.94).(40) Finally, factors which may reflect differences amongst jurisdictions including their policies, were also independent predictors. Amongst those younger than 65 years, respondents in the 2014 International Health Policy Survey (IHPS) who were from Quebec were less likely to report CRNA than those residing in Ontario (OR 0.5, 95% CI 0.3-0.8).(43) \u0026nbsp;At the time, while drug insurance was compulsory in Quebec, Ontario reimbursed non-seniors only for those who were socially disadvantaged or had very high medication costs.(43) In the 2007 CCHS, residence in British Columbia where a significant portion of public drug coverage has income-based deductibles was associated with more CRNA compared with Ontario (OR 2.56, 95% CI 1.49\u0026ndash;4.42).(40)The IHPS segment of Canadians self-identifying as First Nations, Inuit or Metis, were at higher risk of CRNA (RR 2.1, 95% CI 1.4 \u0026ndash; 3.2).(39) Although the publicly funded Non-insured Health Benefits Program includes drug benefits without co-payment or deductible, these apply only to those considered \u0026lsquo;status Indians\u0026rsquo; or Inuk and require providers to register with the program to avoid initial self-pay.(59)\u003csup\u003e \u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003eTable 2. Predictors of CRNA in Canada\u003c/p\u003e\n\u003ctable style=\"width:488.8pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:262.0pt;border:solid windowtext 1.0pt;background:#E7E6E6;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;line-height: 115%;\"\u003ePredictor\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:99.25pt;border:solid windowtext 1.0pt;border-left: none;background:#E7E6E6;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;line-height: 115%;color:black;\"\u003e# Articles Reporting Significance\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:127.55pt;border:solid windowtext 1.0pt;border-left: none;background:#E7E6E6;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;line-height: 115%;color:black;\"\u003eCitation\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003eHigher out-of-pocket costs*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e(2),\u0026nbsp;(3),\u0026nbsp;(37),\u0026nbsp;(39),\u0026nbsp;(40),\u0026nbsp;(41),\u0026nbsp;(47),\u0026nbsp;(48),\u0026nbsp;(49),\u0026nbsp;(50),\u0026nbsp;(52),\u0026nbsp;(54),\u0026nbsp;(57)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003eLower income or low financial flexibility\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e(3)\u0026nbsp;,\u0026nbsp;(38),\u0026nbsp;(39)\u0026nbsp;,\u0026nbsp;(40),\u0026nbsp;(43),\u0026nbsp;(46),(51)\u0026nbsp;\u0026nbsp;(55),\u0026nbsp;(57)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003eLack of drug insurance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e(40)\u0026nbsp;,\u0026nbsp;(41), \u0026nbsp;(43)\u0026nbsp;,\u0026nbsp;(46)\u0026nbsp;,\u0026nbsp;(51),\u0026nbsp;(54),\u0026nbsp;(57)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003eYounger age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e(38),\u0026nbsp;(39),\u0026nbsp;(40),\u0026nbsp;(43),\u0026nbsp;(46),\u0026nbsp;(54)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003ePoor self-reported health status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e(39)\u0026nbsp;,\u0026nbsp;(40)\u0026nbsp;,\u0026nbsp;(43)\u0026nbsp;,\u0026nbsp;(46), \u0026nbsp;(54)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003eProvince of residence (eg, Ontario instead of Quebec, or British Columbia instead of Ontario or Quebec)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e(38),\u0026nbsp;(43),\u0026nbsp;(46),\u0026nbsp;(54)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003eSeveral chronic health conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e(38),\u0026nbsp;(46)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003eHigh cost of drugs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e(35),\u0026nbsp;(51)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003eLow/medium drug importance from individual\u0026rsquo;s perspective\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e(51),\u0026nbsp;(57)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003eNot feeling involved in treatment decisions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e(39),\u0026nbsp;(57)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003eFirst Nations status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:115%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e(39)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003cp\u003e\u003cspan style='font-size:15px;line-height:115%;font-family:\"Calibri\",sans-serif;'\u003e*includes studies comparing rates of CRNA pre- and post- copayment policy\u003c/span\u003e\u003c/p\u003e\n\u003cbr\u003e\u003cp\u003eThree studies in BC using a similar cohort with similar methodology examined the influence of increased out-of-pocket expense by analyzing the effect of changes in drug insurance coverage on adherence measured by prescription dispensing intervals.(48-50) The utilization of maintenance respiratory inhalers declined by approximately 5.8 to 12.3% (p\u0026lt;0.001), the rate of full adherence to statins decreased by 5.4% (95% CI, 6.4% to 4.4%) but adherence to beta-blockers was only modestly reduced (approximately 1%) compared to full coverage.(48-50) Non-adherence was associated with higher out-of-pocket expenditures, with beta-blockers thought to be less affected because of their low cost compared to the other drug groups at the time of the study.(50)\u0026nbsp; For statins, adherence was better in high risk patients with prior vascular events compared to the entire group.(49) An analysis of a policy change to lower seniors\u0026rsquo; out of pocket prescription drug costs in Saskatchewan in 2007, found a small increase in optimal medication adherence after the policy change.(47)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCRNA Association with Clinical Outcomes\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eOnly three studies measured clinical outcomes potentially related to CRNA (Table 1; n = 93,653).(52, 53, 58) The highest quality study was a recent randomized controlled trial involving patients in primary care in Ontario who reported that they did not fill a prescription or changed regimens to make their supply last longer because of the cost. The study found that the intervention group provided free, mailed prescriptions deemed essential, reported better adherence, improved perceived care, and less concern about making ends meet at 12 months follow-up. Several surrogate outcomes were followed, with improvement in blood pressure in the intervention group for those requiring anti-hypertensives but no significant improvement in A1C or cholesterol. However, there was no difference in hospitalizations, serious adverse events or death.\u003c/p\u003e\n\u003cp\u003eThe introduction of a drug policy in Quebec in the nineties increased out-of-pocket costs for all residents. In one retrospective study, this led to a decrease in the overall number of drugs used per day by the elderly and by welfare recipients, including \u0026lsquo;essential\u0026rsquo; medications such as aspirin and furosemide (decrease of 9.1% - 14.4%) as well as symptomatic but potentially harmful drugs such as benzodiazepines (decrease of 15.1% - 22.4%). The decline in use of essential drugs was associated with a small increase in serious adverse events including death, hospital or nursing home admission, or emergency department visits.(52)In a second retrospective study, there was no change in adherence to post-myocardial infarction medication adherence and no change in clinical outcomes after the policy compared to pre-policy.(53)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe believe that this is the first systematic review to focus on the relationship between medication costs and medication adherence in Canada. All but one of the studies in our review were observational therefore susceptible to bias and confounders. We found rates of CRNA range from 5.1% to 10.2% in general surveys of the population over time, suggesting that an important minority of the population is experiencing problems with prescription medication adherence due to their medication cost.The range is likely explained by differing sampling frames, questions, definitions of CRNA and statistical uncertainty. The international studies in our review suggest that Canadian rates of CRNA are in the middle other developed countries. In the IHPS survey, the rate of CRNA in Canada (8%) was in the middle of seven countries, with the Netherlands having the lowest rate (3%) and the US having the highest rate (20%).(39) In the dialysis study, the rate of CRNA in Canada (12.9%) was similar to the overall rate of CRNA among 12 countries (13.4 %), with Japan being the lowest rate (3.2%) and the US being the highest rate (29.2%).(38)\u003c/p\u003e\n\u003cp\u003eOverall, predictors for CRNA in Canada revolved around lack of affordability, younger age, chronic illness, private insurance coverage, and province of residence. \u0026nbsp;This likely reflects characteristics of the different public drug plan coverage programs and different financial capability to afford medicines in different provinces.\u0026nbsp; None of the studies developed or used a clinical prediction rule, which would examine risk factors together to determine how their quantitative combination influences risk.(60) \u0026nbsp;This is a well-established method to refine population risk to individual risk. Both qualitative studies found that patients weighed their financial obligations against the perceived importance of the medication(s) in making their adherence decisions, and recognized that they sometimes were making decisions that might adversely affect their health.(51)\u003c/p\u003e\n\u003cp\u003eThe lack of current information on the association of CRNA with clinical outcomes in Canada is very troubling, as this is the primary question of interest both for clinicians and policy makers. Although low adherence to beneficial medications has previously been linked to increased mortality, the data may be biased due to the \u0026lsquo;healthy user\u0026rsquo; effect.(17) Randomized trials show that interventions to improve adherence do so only modestly and do not seem to improve patient outcomes.(61) Two recent randomized controlled trials (RCTs) in the United States directly address whether removing medication cost improves clinical outcomes. The aforementioned MI FREEE RCT found that free coverage for essential cardiovascular medications post-myocardial infarction increased adherence by 4 to 6% (p \u0026lt; 0.001), but did not improve the primary outcome of first major vascular event or procedure.(20) More recently, the ARTEMIS trial also found that provision of free access to P2Y\u003csub\u003e12 \u003c/sub\u003einhibiting anti-platelet agents for a year increased adherence by a small amount (2.3%) but there was no difference in major adverse cardiovascular events.(62) In addition, since patients are frequently taking medications that are not essential and may be harmful, decreased adherence to these medications may not lead to adverse outcomes. Two of our studies suggested that participants reported increased health care utilization as a result of their CRNA, but did not actually measure clinical outcomes or healthcare utilization.(46, 57) The sole RCT in our SR found that the free provision and delivery of essential medications increased adherence by 10% and improved one of three clinical surrogates at 12 months follow-up, but did not improve clinical outcomes.(58) In summary, the relationship between medication costs, medication adherence and patient outcomes is more complex than originally thought.\u003c/p\u003e\n\u003cp\u003eThis systematic review has limitations worth noting. First, since studies varied in their methods of measurement, quantitative pooling was not possible.\u0026nbsp; Second, there is no gold standard measure for medication adherence, so there are likely measurement errors with each of the methods used. Third, questionnaire studies are susceptible to responder and recall bias, and the studies examining adherence before and after policy changes are somewhat indirect inferences regarding the impact of costs. Fourth, we were unable to find information on how different types of insurance \u0026ndash; co-pays, deductibles, annual maximums, etc \u0026ndash; influence the prevalence of CRNA. Finally, since multiple behavioural attributes are associated with non-adherence, it would take a very large prospective study to determine the specific impact of medication cost on adherence.\u003c/p\u003e\n\u003cp\u003eThe findings of this systematic review have several implications.\u0026nbsp; First, as CRNA may affect a large number of Canadians, communication between providers and patients regarding affordability of prescribed medications is essential and may play an important role in the reduction of CRNA. Second, the evidence summarized here will be useful to inform the debate on a national Pharmacare program where proponents cite estimates of higher health care utilization because of patient burden of medication costs while opponents cite lack of evidence that removal of patient-borne costs improves outcomes.(63, 64) Modelling of a universal drug benefit program would benefit from better estimates of the impact on CRNA on health care utilization and clinical outcomes.(28) The association of high out-of-pocket medication costs with lower adherence might argue for improved drug coverage for those with low incomes. However, the high quality evidence so far suggests that more research is required to determine for which people, which drugs, which situations, and how much cost relief might be required to improve clinical outcomes. \u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur systematic review suggests that an important minority of Canadians may not be adherent to medications because of their costs. Financial factors appear to be the main predictors of CRNA, suggesting that drug program design and coverage have a significant influence on CRNA rates. However, consistent with international evidence to date, removal of all medication cost for essential drugs for patients with CRNA has not been shown to improve clinical outcomes.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eCRNA - Cost-Related Nonadherence\u003c/p\u003e\n\u003cp\u003eED - Emergency Department\u003c/p\u003e\n\u003cp\u003eCCHS - Canadian Community Health Survey\u003c/p\u003e\n\u003cp\u003eIHPS - International Health Policy Survey\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and material\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article and its supplementary information files.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eMichael Law has consulted for Health Canada and the Health Employees\u0026rsquo; Union, and provided expert witness testimony for the Attorney General of Canada. Anne Holbrook has served as an expert policy advisor for national, provincial and local hospital public drug plans for several decades. All other authors report no relevant competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFunded by the Canadian Institutes of Health Research (CIHR) Grant MOP-126020, Principal Investigator Dr Michael Law and CIHR Grant FRN-148803, Principal Investigator Dr Anne Holbrook. Dr. Law received salary support through a Canada Research Chair and a Michael Smith Foundation for Health Research Scholar Award.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors' contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAH was responsible for conception and design of the work. AH, MW, ML, NC, LN, MG, SM, AF contributed to acquisition and analysis of the data, all authors contributed to the interpretation of data, AH wrote each draft and the final manuscript. All authors contributed to revisions of drafts. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBriesacher BA, Gurwitz JH, Soumerai SB. Patients At-Risk for Cost-Related Medication Nonadherence: A Review of the Literature. Journal of General Internal Medicine. 2007;22(6):864-71.\u003c/li\u003e\n\u003cli\u003eHennessy DA, Sanmartin C, Ronksley P, Weaver R, Campbell D, Manns B, et al. Out-of-pocket spending on drugs and pharmaceutical products and cost-related prescription non-adherence among Canadians with chronic disease: Statistics Canada; 2016.\u003c/li\u003e\n\u003cli\u003eMorgan SG, Lee A. Cost-related non-adherence to prescribed medicines among older adults: a cross-sectional analysis of a survey in 11 developed countries. 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Cost-related nonadherence to medicines in people with multiple chronic conditions. Research in Social and Administrative Pharmacy. 2020;16(3):415-21.\u003c/li\u003e\n\u003cli\u003eMen F, Gundersen C, Urquia ML, Tarasuk V. Prescription medication nonadherence associated with food insecurity: a population-based cross-sectional study. CMAJ open. 2019;7(3):E590-E7.\u003c/li\u003e\n\u003cli\u003eMonagle SR, Hirsh J, Bhagirath VC, Ginsberg JS, Bosch J, Kruger P, et al. Impact of cost on use of non-vitamin K antagonists in atrial fibrillation patients in Ontario, Canada. Journal of Thrombosis and Thrombolysis. 2018;46(3):310-5.\u003c/li\u003e\n\u003cli\u003eGupta S, McColl MA, Guilcher SJT, Smith K. Managing Medication Cost Burden: A Qualitative Study Exploring Experiences of People with Disabilities in Canada. International Journal of Environmental Research and Public Health. 2019;16(17):3066.\u003c/li\u003e\n\u003cli\u003ePersaud N, Bedard M, Boozary AS, Glazier RH, Gomes T, Hwang SW, et al. Effect on Treatment Adherence of Distributing Essential Medicines at No Charge: The CLEAN Meds Randomized Clinical Trial. JAMA Internal Medicine. 2020;180(1):27-34.\u003c/li\u003e\n\u003cli\u003eGovernment of Canada. Non-insured health benefits for First Nations and Inuit [Available from: \u003ca href=\"https://www.canada.ca/en/indigenous-services-canada/services/non-insured-health-benefits-first-nations-inuit.html\"\u003ehttps://www.canada.ca/en/indigenous-services-canada/services/non-insured-health-benefits-first-nations-inuit.html\u003c/a\u003e.\u003c/li\u003e\n\u003cli\u003eAlba AC, Agoritsas T, Walsh M, Hanna S, Iorio A, Devereaux PJ, et al. Discrimination and Calibration of Clinical Prediction Models: Users\u0026rsquo; Guides to the Medical Literature. JAMA. 2017;318(14):1377-84.\u003c/li\u003e\n\u003cli\u003eNieuwlaat R, Wilczynski N, Navarro T, Hobson N, Jeffery R, Keepanasseril A, et al. Interventions for enhancing medication adherence. The Cochrane database of systematic reviews. 2014;11:CD000011.\u003c/li\u003e\n\u003cli\u003eWang TY, Kaltenbach LA, Cannon CP, Fonarow GC, Choudhry NK, Henry TD, et al. Effect of Medication Co-payment Vouchers on P2Y12 Inhibitor Use and Major Adverse Cardiovascular Events Among Patients With Myocardial Infarction: The ARTEMIS Randomized Clinical TrialEffect of Co-payment Vouchers on Antiplatelet Adherence and CVD EventsEffect of Co-payment Vouchers on Antiplatelet Adherence and CVD Events. JAMA. 2019;321(1):44-55.\u003c/li\u003e\n\u003cli\u003eCanada Go. Towards Implementation of National Pharmacare Discussion Paper 2018 [Available from: \u003ca href=\"https://www.canada.ca/content/dam/hc-sc/documents/corporate/publications/council_on_pharmacare_EN.PDF\"\u003ehttps://www.canada.ca/content/dam/hc-sc/documents/corporate/publications/council_on_pharmacare_EN.PDF\u003c/a\u003e.\u003c/li\u003e\n\u003cli\u003eAcri K. The Unintended Consequences of National Pharmacare Programs: The Experiences of Australia, New Zealand, and the UK 2018 [Available from: \u003ca href=\"https://www.fraserinstitute.org/studies/unintended-consequences-of-national-pharmacare-programs\"\u003ehttps://www.fraserinstitute.org/studies/unintended-consequences-of-national-pharmacare-programs\u003c/a\u003e.\u003c/li\u003e\n\u003cli\u003eKrol BL. The Effect of Free Distribution of Essential Medicines on Adherence by Income Sources and Level: University of Toronto; 2019\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Appendix","content":"\u003cp\u003eAPPENDIX 1. MEDLINE Search Strategy\u003c/p\u003e\n\u003cp\u003eDatabase: OVID Medline Epub Ahead of Print, In-Process \u0026amp; Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1946 to Present\u003c/p\u003e\n\u003cp\u003eSearch Strategy:\u003c/p\u003e\n\u003cp\u003e--------------------------------------------------------------------------------\u003c/p\u003e\n\u003cp\u003e1\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; *Medication Adherence/ (8545)\u003c/p\u003e\n\u003cp\u003e2\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Patient Compliance/ (54949)\u003c/p\u003e\n\u003cp\u003e3\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; persisten$.mp. (286317)\u003c/p\u003e\n\u003cp\u003e4\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; adheren$.mp. (159735)\u003c/p\u003e\n\u003cp\u003e5\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; complian$.mp. (157679)\u003c/p\u003e\n\u003cp\u003e6\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 1 or 2 or 3 or 4 or 5 (572582)\u003c/p\u003e\n\u003cp\u003e7\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Drug Costs/ (14578)\u003c/p\u003e\n\u003cp\u003e8\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Prescription Fees/ (1123)\u003c/p\u003e\n\u003cp\u003e9\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Fees, Pharmaceutical/ (1269)\u003c/p\u003e\n\u003cp\u003e10\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; cost sharing.mp. (3230)\u003c/p\u003e\n\u003cp\u003e11\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; co-pay.mp. (78)\u003c/p\u003e\n\u003cp\u003e12\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; \"Deductibles and Coinsurance\"/ (1631)\u003c/p\u003e\n\u003cp\u003e13\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; self-pay.mp. (575)\u003c/p\u003e\n\u003cp\u003e14\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; out-of-pocket.mp. (4212)\u003c/p\u003e\n\u003cp\u003e15\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Insurance Coverage/ (11433)\u003c/p\u003e\n\u003cp\u003e16\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 (34851)\u003c/p\u003e\n\u003cp\u003e17\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; exp Canada/ (145847)\u003c/p\u003e\n\u003cp\u003e18\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; canadian$.mp. (52774)\u003c/p\u003e\n\u003cp\u003e19\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; (British Columbia$ or alberta$ or saskatchewan$ or manitoba$).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms] (31518)\u003c/p\u003e\n\u003cp\u003e20\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; (ontari$ or quebec$ or new brunswick$ or nova scotia$).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms] (59631)\u003c/p\u003e\n\u003cp\u003e21\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; (prince edward island$ or newfoundland$ or yukon$ or northwest territor$ or nunavut$).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms] (4260)\u003c/p\u003e\n\u003cp\u003e22\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 17 or 18 or 19 or 20 or 21 (188579)\u003c/p\u003e\n\u003cp\u003e23\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 6 and 16 and 22 (66)\u003c/p\u003e\n\u003cp\u003e***************************\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Medication adherence, medication costs, Canada, systematic review","lastPublishedDoi":"10.21203/rs.3.rs-27665/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-27665/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003eCost-related nonadherence to medications (CRNA) is common in many countries and thought to be associated with adverse outcomes. The characteristics of CRNA in Canada, with its patchwork coverage of increasingly expensive medications, is unclear. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eObjectives \u003c/strong\u003eOur objective in this systematic review was to summarize the literature evaluating CRNA in Canada in three domains: prevalence, predictors, and effect on clinical outcomes.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eWe searched MEDLINE, Embase, Google Scholar, and the Cochrane Library from 1992 to December 2019 using search terms covering medication adherence, costs, and Canada. Eligible studies, without restriction on design, had to have original data on at least one of the three domains specifically for Canadian participants. Articles were identified and reviewed in duplicate. Risk of bias was assessed using design-specific tools.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eTwenty-six studies of varying quality (n=483,065 Canadians) were eligible for inclusion. Sixteen studies reported on the overall prevalence of CRNA, with population-based estimates ranging from 5.1% to 10.2%. Factors predicting CRNA included high out of pocket spending, low income or financial flexibility, lack of drug insurance, younger age, and poorer health. A single randomized trial of free essential medications with free delivery in Ontario improved adherence but did not find any change in clinical outcomes at one year.\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eCRNA affects many Canadians. The estimated percentage depends on the sampling frame, the main predictors tend to be financial, and its association with clinical outcomes in Canada remains unproven.\u003c/p\u003e","manuscriptTitle":"Cost-Related Medication Nonadherence in Canada: A Systematic Review of Prevalence, Predictors, and Clinical Impact","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2020-11-11 14:45:53","doi":"10.21203/rs.3.rs-27665/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accept","date":"2020-12-14T00:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-11-04T00:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-11-03T23:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-11-03T23:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2020-05-14 21:11:12","doi":"10.21203/rs.3.rs-27665/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2020-09-28T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-06-09T12:00:00+00:00","index":2,"fulltext":"Recommendation: Major Revision\nForm responses:\n---\n\nComments to Author:\n---\nThank you for allowing me to review the article. The following are my comments.\n\n1. Authors highlight the existing heterogeneity in the included studies which negates ability to pool prevalence data across study. Authors do present prevalence rate of individual studies in Table 1 Study Characteristics\n\n2. Authors describe clinical outcomes of interest on Pg 5 Para 1. They report clinical outcome data (where available) in Table 1 Study Characteristics, and they identify poor reporting of clinical outcomes as an important finding in their review.\n\nOverall, this study is a very well designed systematic review. However, this study would be much clear to readers if the outcomes are only limited to prevalence (? frequency?) and predictors of CRNA without association with clinical outcomes.* Level of interest: **An article whose findings are important to those with closely related research interests**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: **\nI agree to the open peer review policy of the journal**\n* Were you mentored through this peer review?: **No**\n"},{"type":"reviewerAgreed","content":"","date":"2020-05-26T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-05-25T12:00:00+00:00","index":1,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-05-25T12:00:00+00:00","index":1,"fulltext":"Recommendation: Minor Revision\nForm responses:\n---\n\nComments to Author:\n---\nI would like to mention the following comments:\n\n1- There is no explanation about the independency of two reviewers.\n\n2- Authors can choose to include any study type to address their research questions so unclear why including both quant and qual study designs might be consider unreliable?\n\n3- Inclusion of a search strategy for one of the database in an appendix is appropriate\n\n4- Authors describe process for conducting Risk of Bias assessment and include a table outlining Risk of bias findings.\n\n5- The name of figures must be at the bottom of each figure.\n\n6- Tables 1: Many studies had N/A. How is reliable the combination of them with complete studies?\n\nGood Luck* Level of interest: **An article of importance in its field that should be highlighted to relevant networks**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: **\nI agree to the open peer review policy of the journal**\n* Were you mentored through this peer review?: **No**\n"},{"type":"reviewersInvited","content":"","date":"2020-05-24T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-05-17T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-05-16T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-05-08T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2020-05-06T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1c7a2d88-8482-4fbd-85e0-d4206f7bd9c3","owner":[],"postedDate":"November 11th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":100670,"name":"Clinical Pharmacology"}],"tags":[],"updatedAt":"2021-01-10T15:06:26+00:00","versionOfRecord":{"articleIdentity":"rs-27665","link":"https://doi.org/10.1186/s13643-020-01558-5","journal":{"identity":"systematic-reviews","isVorOnly":false,"title":"Systematic Reviews"},"publishedOn":"2021-01-06 15:04:36","publishedOnDateReadable":"January 6th, 2021"},"versionCreatedAt":"2020-11-11 14:45:53","video":"","vorDoi":"10.1186/s13643-020-01558-5","vorDoiUrl":"https://doi.org/10.1186/s13643-020-01558-5","workflowStages":[]},"version":"v2","identity":"rs-27665","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-27665","identity":"rs-27665","version":["v2"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}