Clinical Practice Guidelines in the Management of Generalized Cancer Pain: A Systematic Evaluation Using the AGREE II Instrument

Clinical Practice Guidelines in the Management of Generalized Cancer Pain: A Systematic Evaluation Using the AGREE II Instrument | 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 Article Clinical Practice Guidelines in the Management of Generalized Cancer Pain: A Systematic Evaluation Using the AGREE II Instrument Fatima Rizvi, Anza Rizvi, Kevin Chorath, Neeraj Suresh, Jinggang Ng, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3610185/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose While several clinical practice guidelines (CPGs) exist to guide clinical decision-making in patients presenting with generalized cancer pain, to date there has been no comprehensive review of their methodological rigor and quality. Our aim was to address this deficiency by using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. Methods A systematic literature search to identify relevant CPGs was performed over the following databases from inception to March 3, 2021: Embase, MEDLINE via PubMed, and Scopus. Four authors (FR, AR, JN, and JH) independently performed assessments and evaluations of the selected CPGs using the AGREE II instrument. Scaled domain percentage scores were calculated and 60% was defined as the satisfactory quality threshold. Intraclass correlation coefficients (ICCs) were also calculated to assess interrater reliability and consistency. Results 12 guidelines were selected for inclusion. Two guidelines were classified high quality, three guidelines were classified as average quality, and seven were classified as low quality. Domains 4 (clarity of presentation) and 1 (scope and purpose) received the highest mean scores (82.41% ± 18.20% and 56.48% ± 30.59%), while domains 5 (applicability) and 2 (stakeholder involvement) received the lowest (44.53% ± 26.61% and 36.81% ± 21.24%). ICC statistical analysis showed high consistency between reviewers (range 0.85–0.98). Conclusion Based on the AGREE II instrument, the majority of CPGs for generalized cancer pain were of low or average quality. Future guidelines for generalized cancer pain can be improved by better defining stakeholder involvement, rigor of development, applicability, and editorial independence during development. Generalized cancer pain Clinical practice guideline Quality Appraisal AGREE II Figures Figure 1 Introduction Cancer is a leading cause of death worldwide and continues to stand as a barrier to increasing life expectancy [ 1 ]. It is reported that by 2025, the number of new cancer cases per year is expected to rise to over 20 million [ 2 ]. Pain is a common and debilitating symptom associated with cancer and its treatment. Pain prevalence in patients with cancer was reported to be as high as 64% for patients with advanced or terminal disease, 59% for patients undergoing cancer treatment, and 33% for patients who were cured of cancer [ 3 ]. Patients suffering from cancer pain often experience decreased quality of life and increased depression and anxiety [ 4 , 5 ]. Several different subtypes and classifications of cancer pain exist such as chronic, neuropathic, mixed, and breakthrough cancer pain. Generalized cancer pain is a term that encompasses a range of different pain conditions, characteristics, and etiologies [ 6 ]. Managing generalized cancer pain can be challenging as the causes of cancer pain are multifactorial and complex, lending to different treatment approaches. A myriad of treatment options ranging from pharmacologic interventions (i.e. opioids) to nonpharmacologic integrative interventions (physical therapy, acupuncture, etc.) may be used to treat cancer pain [ 7 ]. Despite therapeutic advancements, the appropriate management of cancer pain remains difficult, and a subset of patients remain undertreated [ 8 ]. The taxing consequences and burden of cancer pain, varying treatment modalities, and undertreatment of cancer pain present a crucial need for health care providers to provide accurate and adequate cancer pain assessment and management. Clinical practice guidelines (CPGs) have been developed by various professional societies to establish standardized criteria for diagnosing and managing cancer pain. CPGs serve to provide clinicians with graded recommendations based on evidence of best practice [ 9 ]. The utilization of high-quality CPGs has the potential to make clinical practice more uniform across different medical centers, allowing for improved patient care and health outcomes. At the same time, however, it is equally important to ensure that CPGs are vetted prior to implementation in clinical settings. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument is a guideline appraisal tool developed to access the methodological quality of practice guidelines [ 10 ]. It is the most comprehensively validated CPG appraisal tool and has been widely adopted [ 11 ]. The AGREE II instrument consists of 23 items that assess CPGs across six domains (scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence). To our knowledge, a critical and comprehensive evaluation of CPGs for the assessment and management of generalized cancer pain has not been previously conducted. Therefore, our objective was to systematically identify CPGs for generalized cancer pain and to assess the quality and rigor of them using the AGREE II instrument. Methods Literature Search and Selection Criteria From inception to March 3, 2021, authors (FR and AR) performed a systematic literature search of the following databases: Embase, MEDLINE via PubMed, and Scopus. Additionally, a manual internet search was conducted to identify clinical practice guidelines not found within these databases. The following search terms were used: [(“generalized cancer pain” OR “cancer pain” OR “general cancer pain”) AND (“guideline” OR “consensus” OR “recommendation”)]. Both national and international clinical practice guidelines that addressed the diagnosis, treatment, and management of cancer pain were included. We excluded guidelines that only focused on a singular component of diagnosis and management of cancer pain. If a development group or professional society published multiple guidelines, the most recent guideline was used. Editorials, summaries, textbook chapters, and non-English language publications were excluded. The selected articles were discussed by the authors (FR, AR, KC, and KR) and any discrepancies in inclusion criteria were addressed. Data Extraction and Management The following data was extracted for each CPG: the development body, source of publication, publication year, publication country, development method, key developers, target users, number of references, and relevant funding sources. A predetermined data collection form based on the six quality appraisal domains and 23 specific items included in the AGREE II instrument (Table 1 ) was used. Table 1 Individual Components of the AGREE II Evaluation Tool Scope and Purpose 1 The overall objective(s) of the guideline is (are) specifically described. 2 The health question(s) covered by the guideline is (are) specifically described. 3 The population (patients, public, etc.) to whom the guideline is meant to apply is specifically described. Stakeholder Involvement 4 The guideline development group includes individuals from all relevant professional groups. 5 The views and preferences of the target population (patients, public, etc.) have been sought. 6 The target users of the guideline are clearly defined. Rigor of Development 7 Systematic methods were used to search for evidence. 8 The criteria for selecting the evidence are clearly described. 9 The strengths and limitations of the body of evidence are clearly described. 10 The methods for formulating the recommendations are clearly described. 11 The health benefits, side effects, and risks have been considered in formulating the recommendations. 12 There is an explicit link between the recommendations and the supporting evidence. 13 The guideline has been externally reviewed by experts prior to its publication. 14 A procedure for updating the guideline is provided. Clarity of Presentation 15 The recommendations are specific and unambiguous. 16 The different options for management of the condition or health issue are clearly presented. 17 Key recommendations are easily identifiable. Applicability 18 The guideline describes facilitators and barriers to its application. 19 The guideline provides advice and/or tools on how the recommendations can be put into practice. 20 The potential resource implications of applying the recommendations have been considered. 21 The guideline presents monitoring and/ or auditing criteria. Editorial Independence 22 The views of the funding body have not influenced the content of the guideline. 23 Competing interests of guideline development group members have been recorded and addressed. AGREE II = Appraisal of Guidelines for Research and Evaluation Quality Appraisal Per AGREE recommendations, all appraisers completed the free, online training module available on the AGREE website ( www.agreetrust.org ). Then, using the AGREE II instrument, four authors (FR, AR, JN, and JH) independently performed assessments and evaluations of the selected clinical practice guidelines. The AGREE II instrument consists of 23 items that evaluate CPGs over six domains: domain 1 (scope and purpose), domain 2 (stakeholder involvement), domain 3 (rigor of development), domain 4 (clarity of presentation), domain 5 (applicability), and domain 6 (editorial independence). Each of the 23 items was assigned a score between 1 and 7. A score of 1 (strongly disagree) was given if the item was not addressed in the guideline, whereas a 7 (strongly agree) was given if the item was comprehensively addressed. According to the formula provided by the AGREE II manual (AGREE Next Steps Consortium), scaled domain scores were obtained as such [ 10 ]: $$scaled domain score= \frac{(obtained score-minimum possible score)}{(maximum possible score-minimum possible score)}\times 100\%$$ A threshold of 60% was used to assess the quality of the guideline. CPGs were rated as high when 5 or more domains scored > 60%, average when 3 or 4 domains scored > 60%, and low if ≤ 2 domains scored > 60%. Overall quality scores for each guideline were also calculated and reported as a mean of the six scaled domain scores. Statistical Analysis To assess the interrater reliability and consistency among the four appraisers, intraclass correlation coefficients (ICCs) were calculated for each AGREE II domain using Python 3.8.2 and the ‘pingouin’ API. Per previous literature, ICCs were graded as the following: poor (< 0.20), fair (0.21–0.41), moderate (0.41–0.60), good (0.61–0.80), and very good (0.81–1.00) [ 12 – 14 ]. Results Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols, our electronic search initially yielded 5,845 citations, which were subsequently reviewed by title and abstract for inclusion criteria. Among these, 17 were reviewed in full, and 12 guidelines were selected for evaluation (Fig. 1 ). Guideline Characteristics Table 2 provides a summary of the general characteristics for each CPG such as the developing body, publication year, area of origin, development method, developers, target users, number of references, and relevant funding source. Of the 12 guidelines selected for inclusion, three were developed in the United States by the following societies or institutions: National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), and American Society of Anesthesiologists (ASA) [ 15 – 17 ]. Of the remaining guidelines, two were developed in Canada (Alberta Health Services (AHS) and Cancer Care Ontario (CCO)), one in Japan by the Japanese Society of Palliative Medicine (JSPM), one in Spain by the Spanish Society of Medical Oncology (SEOM), one in Italy by the Italian Society of Anaesthesia, Analgesia, Resuscitation and Intensive Care ( SIAARTI), one in Switzerland by the World Health Organization (WHO), one in Europe by the European Society for Medical Oncology (ESMO), and two in the Latin America region (Latin American Expert Panel (LAEP) and Latin American Guidelines (LAG)) [ 18 – 26 ]. The guidelines were published between 1996 and 2019, with all but two (SIAARTI 2003 and ASA 1996) being released within the last decade. Most were developed through a combination of expert opinion, committee consensus, and systematic literature review. Only four of the eight CPGs explicitly stated their funding sources (WHO, ESMO, LAEP, LAG). Table 2 General Characteristics of Included Clinical Practice Guidelines Journal/Source Society/ Institution Publi-cation Year Country or Region Development Method Developers Target User Number of References Funding Source Journal of the National Comprehensive Cancer Network National Comprehensive Cancer Network (NCCN) 2019 United States Consensus Authors of NCCN clinical practice guideline Healthcare providers 288 Not reported − World Health Organization (WHO) 2018 Switzerland Systematic literature review Guideline Development Group Physicians, nurses, pharmacists, and caregivers, policy and program managers, public health officials and academics 197 WHO core funds Annals of Oncology European Society for Medical Oncology (ESMO) 2018 Europe Systematic literature review The ESMO Guidelines Committee Health professionals working in the field of oncology across Europe and other parts of the world 179 None − Alberta Health Services (AHS) 2018 Canada Systematic literature review, consensus Multidisciplinary working group comprised of medical oncologists, palliative care specialists, nurse practitioners, occupational therapists, pharmacists, and a Knowledge Management Specialist from the Guideline Resource Unit Members of multidisciplinary healthcare teams who manage patients with pain associated with their cancer treatment 48 Not reported Clinical Translational Oncology Spanish Society of Medical Oncology (SEOM) 2017 Spain Systematic literature review Experts and two coordinators Professionals in Clinical Practice 68 Not reported − Cancer Care Ontario (CCO) 2017 Canada Systematic literature review Experts in pain and palliative care (nurses, physicians), health research methodologist Staff of the Patient Reported Outcomes and Symptom Management Program of CCO and staff of the Ontario Palliative Care Network; physicians, nurses, caregivers, and patients 315 Not reported Future Oncology − 2017 Latin America Expert opinion, consensus development conference Experts on cancer pain management from Costa Rica, Mexico, Chile, Colombia, Peru, Brazil, Ecuador, Spain Latin-American Countries; oncologists in pain management 47 Grünenthal Services, Incorporated Pain Management − 2017 Latin America Systematic literature review Latin American opinion leaders Physicians 55 Grünenthal Services, Incorporated Journal of Clinical Oncology American Society of Clinical Oncology (ASCO) 2016 United States Systematic literature review, expert consensus ASCO-convened expert panel Health care practitioners who provide care to cancer survivors 114 Not reported Japanese Journal of Clinical Oncology Japanese Society of Palliative Medicine (JSPM) 2013 Japan Systematic literature review, expert panel consensus 31 palliative care physicians, 15 anesthesiologists, 5 oncologists, 5 home care physicians, 25 pharmacists, 23 nurses, 1 epidemiologist, 7 other professionals Medical personnel who care for cancer patients, including palliative care physicians, oncologists, nurses, pharmacists 86 Not reported Minerva Anestesiologica Italian Society of Anaesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) 2003 Italy Consensus The SIAARTI group − 73 Not reported Anesthesiology American Society of Anesthesiologists (ASA) 1996 United States Systematic literature review, consensus American Society of Anesthesiologists task force Anesthesiologists and individuals who deliver care under the direct supervision of anesthesiologists − Not reported NCCN = National Comprehensive Cancer Network, WHO = World Health Organization, ESMO = European Society for Medical Oncology, AHS = Alberta Health Services, SEOM = Spanish Society of Medical Oncology, CCO = Cancer Care Ontario, ASCO = American Society of Clinical Oncology, JSPM = Japanese Society of Palliative Medicine, SIAARTI = Italian Society of Anaesthesia, Analgesia, Resuscitation and Intensive Care, ASA = American Society of Anesthesiologists Guideline Appraisal Table 3 highlights scaled domain scores and the overall quality assessment for each guideline according to the AGREE II instrument. Domain 4 (clarity of presentation) and domain 1 (scope and purpose) had the highest overall values with scores of 82.41% ± 18.20% and 56.48% ± 30.59%, respectively. Domain 2 (stakeholder involvement) and domain 5 (applicability) had the lowest overall scores with scores of 36.81% ± 21.24% and 44.53% ± 26.61%, respectively. Domain 1 (scope and purpose) had the highest variability among guidelines with a standard deviation of 30.59%. Of the selected guidelines, those of WHO and ASCO achieved overall high ratings per aforementioned criteria. Three guidelines received overall average quality ratings and the remaining seven received low quality ratings. Table 3 Quality Assessment of Included Clinical Practice Guidelines Domain 1 Domain 2 Domain 3 Domain 4 Domain 5 Domain 6 Society/ Institution Scope and Purpose (%) Stakeholder Involvement (%) Rigor of Development (%) Clarity of Presentation (%) Applicability (%) Editorial Independence (%) Mean Overall Score Overall Quality NCCN 31.94 19.44 27.08 100.00 46.88 58.33 47.28 Low WHO 98.61 70.83 97.40 100.00 87.50 100.00 92.39 High ESMO 19.44 9.72 38.54 91.67 36.46 41.67 39.58 Low AHS 86.11 50.00 59.90 84.72 16.67 58.33 59.29 Low SEOM 37.50 27.78 34.38 76.39 27.08 41.67 40.80 Low CCO 87.50 62.50 68.75 34.72 11.46 60.42 54.23 Average LAEP 34.72 26.39 8.85 76.39 51.04 64.58 43.66 Low LAG 30.56 15.28 22.40 73.61 31.25 79.17 42.05 Low ASCO 88.89 48.61 95.31 94.44 88.54 37.50 75.55 High JSPM 69.44 54.17 67.71 91.67 19.79 45.83 58.10 Average SIAARTI 16.67 9.72 21.35 70.83 42.71 0.00 26.88 Low ASA 76.39 47.22 64.58 94.44 75.00 0.00 59.61 Average Mean ± SD 56.48 ± 30.59 36.81 ± 21.24 50.52 ± 29.31 82.41 ± 18.20 44.53 ± 26.61 48.96 ± 28.78 NCCN = National Comprehensive Cancer Network, WHO = World Health Organization, ESMO = European Society for Medical Oncology, AHS = Alberta Health Services, SEOM = Spanish Society of Medical Oncology, CCO = Cancer Care Ontario, LAEP = Latin American Expert Panel, LAG = Latin American Guidelines, ASCO = American Society of Clinical Oncology, JSPM = Japanese Society of Palliative Medicine, SIAARTI = Italian Society of Anaesthesia, Analgesia, Resuscitation and Intensive Care, ASA = American Society of Anesthesiologists Intraclass Reliability The intraclass correlation coefficients (ICC) for each quality domain of the AGREE II instrument can be found in Table 4 . These values signify the magnitude of agreement between the four reviewers (FR, AR, JN, JH). All six domains demonstrated very good intraclass reliability per aforementioned crtieria. Table 4 Intraclass Correlation Coefficients for AGREE II Domains Agree II Domain ICC (95% CI) Domain 1: Scope and Purpose 0.96 (0.85–0.99) Domain 2: Stakeholder Involvement 0.94 (0.85–0.98) Domain 3: Rigor of Development 0.98 (0.93–0.99) Domain 4: Clarity of Presentation 0.94 (0.87–0.98) Domain 5: Applicability 0.97 (0.93–0.99) Domain 6: Editorial Independence 0.85 (0.57–0.95) AGREE II = Appraisal of Guidelines for Research and Evaluation, ICC = intraclass correlation coefficient, CI = confidence interval Discussion Using the AGREE II tool, only two out of twelve CPGs were of high quality. Our analysis depicts that CPGs for generalized cancer pain require significant improvement. Common Strengths The CPGs performed well in domain 4 (clarity of presentation) with 11 out of 12 CPGs scoring satisfactorily (> 60%) in this domain. Clarity of presentation assesses and evaluates the presentation and format of the guidelines. Across guidelines key recommendations were specific, often presented in bulleted form, flowcharts, and easily identifiable diagrams. This is a valuable strength as it allows clinicians from a variety of disciplines to understand the main points of a CPG quickly and clearly. As a result, it would serve future authors well to continue these practices when constructing updates of or new CPGs. Common Weaknesses CPGs performed poorly in domain 3 (rigor of development), which is considered the strongest predictor of overall guideline quality [ 27 ]. CPGs that performed poorly in this domain failed to employ a systematic method to search for evidence, provide inclusion and exclusion criteria, and include a description of the strengths and limitations of the body of evidence. Additionally, several guidelines were not externally reviewed by experts prior to publication and lacked explicit updating procedures. This performance is especially concerning in the context of cancer pain given its complexity and nuances in management. Specifically, if guideline recommendations are not clearly based in literature-reported evidence, sub-optimal patient care and outcomes can quickly arise [ 9 ]. We strongly recommend CPG creators more clearly delineate their systematic development strategies to ensure that CPGs stay true to their original aim—helpful tools that guide clinical decision-making based on evidence of best practice. All twelve guidelines failed to include the process by which patient values and preferences were solicited and incorporated into the guideline recommendations, resulting in low in domain 2 (stakeholder involvement) scores. Similarly, lack of discussion on how physician knowledge and beliefs, economic factors, and access to resources did or did not influence the application of guideline recommendations resulted in low domain 5 (applicability) scores. Both related domain weaknesses showcase that current generalized cancer pain CPGs are lacking in acknowledging potential bias from the guideline development board. Because although all CPGs had multidisciplinary developers from various specialists involved in the management of cancer pain (Table 2 ), the patient perspective is also critical in ensuring more implementable guidelines [ 28 ]. The patient perspective is important in guiding recommendation development as patients not only serve as their best own advocate, but also can identify issues and outcomes unbeknownst healthcare professionals [ 28 ]. Furthermore, racial and ethnic minority cancer patients could shed light on their added population-specific obstacles (delays in diagnosis and initiation of treatment, undertreatment of pain, racial biases, lack of insurance, etc.) to help lessen disparities in cancer care [ 29 , 30 ]. All future guidelines should therefore strive to include patients as important stakeholders and address educational, systemic, socioeconomic, and racial barriers involved in generalized cancer pain diagnosis and management. Lastly, CPGs had overall weak performance in domain 6 (editorial independence) due to stark differences in guideline-specific scores. This is best demonstrated by looking at the WHO, SIAARTI and, ASA guidelines which had 100%, 0%, and 0% scores for the category, respectively. Specifically, while some CPGs comprehensively and saliently listed how sources of funding and competing interests did not influence provided recommendations (i.e. WHO) others failed to mention either point altogether (SIAARTI and ASA). CPGs must provide unbiased and evidence-based recommendations to serve as effective tools for improving patient care. Otherwise, ulterior financial motives and other conflicts of interest can introduce bias and affect the quality of final recommendations [ 31 , 32 ]. Information regarding editorial independence should therefore directly be reported in guidelines themselves (and not only on publicly available on the developing bodies’ websites to which providers may not have routine access) to increase transparency and ensure patients are receiving the best evidence-based care. Guideline Recommendations A summary of the key recommendations for the management of cancer pain from the appraised guidelines is presented in Table 5 . The recommendations emphasize the importance of both pharmacological and non-pharmacological interventions. Consensus across guidelines included conducting an initial comprehensive patient evaluation [ 15 , 16 , 21 – 23 ]. The use of validated pain assessment tools such as the Visual Analogue Scale (VAS), the Verbal Rating Scale, or the Numerical Rating Scale can be used to assess pain intensity. CPG recommendations included analgesic regimen combinations of acetaminophen/paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and adjuvant analgesics. Non-opioid analgesics such as acetaminophen/paracetamol and NSAIDs should be administered to cancer patients with mild pain [ 16 , 23 ]. For moderate-to-severe pain, the use of opioids in addition to non-opioids/adjuvant analgesics was recommended [ 16 , 23 ]. An individualized approach should be taken to determine dosage and frequency of medications with the goal of achieving a balance between optimal pain relief and minimal side effects. Throughout treatment, pain assessments should be performed regularly to ensure adequate pain control is being met. Adjuvant analgesics such as antidepressants, anticonvulsants, topical agents, and corticosteroids, used in addition to non-opioid and opioid analgesics may be useful in the management of neuropathic cancer pain. Additionally, various nonpharmacologic interventions (physical, spiritual, and cognitive modalities) may also serve as valuable additions to pharmacologic interventions [ 16 , 23 ]. Table 5 Key Recommendations Key Takeaways General Principles • Goal: Optimize analgesia and minimize adverse effects • Comprehensive assessment should be performed including: a detailed review of past and current medical history, physical examination, pain assessment using an appropriate pain measurement tool • Patients should be educated about pain and pain management, allowing them to serve as informed, active participants in their own care • Non-opioid medications should be considered at every stage • Adjuvant analgesics such as anticonvulsants, antidepressants or corticosteroids may be part of the analgesic regimen for cancer patients with neuropathic pain • Non-pharmacological interventions may be integrated: o Integrative approach/therapy: massage, acupuncture, music o Physical therapy/approach: occupational therapy, individualized exercise program o Psychological approach/therapy: cognitive behavioral therapy, mindfulness relaxation, distraction training Pain Intensity-Specific Principles Mild Pain • Non-opioids, such as acetaminophen/paracetamol and NSAIDs are recommended for mild pain • Monitor for adverse effects of acetaminophen/paracetamol and NSAIDs Moderate to Severe Pain • Non-opioids and adjuvant therapies as appropriate with opioids should be administered to cancer patients with moderate to severe pain or inadequately controlled pain despite treatment with non-opioid analgesics • Oral or transdermal administration of opioids is usually preferable; however, when the oral route is not practical then subcutaneous or intravenous routes may be used • Patients should be assessed and observed for side effects of opioid therapy such as constipation NSAIDs = nonsteroidal anti-inflammatory drugs Study Limitations The goal of the AGREE II instrument is to assess the quality and methodological rigor of guidelines and provide concrete, targeted recommendations for their improvement. Although the AGREE II instrument has been proven to be reliable and valid (particularly with four independent reviewers), the tool inherently depends on subjective ratings from the reviewers. Reviewers may interpret the items and criteria differently, allowing for variations in scoring despite strong ICC values across all domains. The appraisers were also not blinded to the authors and organizations who developed the guidelines, introducing a potential source of bias. Furthermore, the AGREE II items and domains are given equal importance rather than varying individual weights. This could introduce a source of mathematical bias as previous research suggests domain 3 (rigor of development) to be the strongest indicator of guideline quality relative to other domains [ 27 ]. Therefore, in the current schema, guidelines with strong domain 3 scores but weaker remaining scores may be potentially misclassified as low or average quality and those with the reverse scenario may be misclassified as high quality. Similarly, it is important to note that the AGREE II instrument only critiques CPGs regarding their development, so low or average quality guidelines may still provide some valuable clinical insights. Finally, while the authors performed a systematic search following PRISMA protocols, some relevant non-English guidelines may have excluded and consequently introduced an element of publication bias. Conclusion Evidence-based CPGs of high quality can facilitate clinical decision-making and improve health outcomes for patients globally. CPGs are particularly applicable to the care of patients suffering from generalized cancer pain, given their complex, longitudinal multidisciplinary care and management. Based on our analysis of current CPGs using the AGREE II instrument, only two out of 12 (16.7%) guidelines received an overall quality score of high (WHO and ASCO). This indicates that there is significant room for improvement. Future authors of CPGs on diagnosing and managing generalized cancer pain would particularly benefit by enhancing relevant sections on stakeholder involvement, rigor of development, applicability, and editorial independence. Declarations Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing interests: The authors have no financial or non-financial interests to disclose. Acknowledgements: None Author Contributions: Fatima Rizvi (FR): Conceptualization, Methodology, Formal Analysis, Investigation, Data Curation, Writing - Original Draft, Writing - Review & Editing, Project Administration Anza Rizvi (AR): Conceptualization, Methodology, Formal Analysis, Investigation, Data Curation, Writing - Original Draft, Writing - Review & Editing, Project Administration Kevin Chorath (KC): Methodology, Investigation, Data Curation, Writing - Review & Editing Neeraj Suresh (NS): Methodology, Investigation, Data Curation, Writing - Review & Editing Jinggang Ng (JN): Methodology, Investigation, Data Curation, Writing - Review & Editing Jacob Harris (JH): Methodology, Investigation, Data Curation, Writing - Review & Editing Deepak Lakshmipathy (DL): Conceptualization, Validation, Writing - Review & Editing Louis-Xavier Barrette (LXB): Conceptualization, Validation, Writing - Review & Editing Karthik Rajasekaran (KR): Conceptualization, Validation, Writing - Review & Editing, Supervision References Sung, Hyuna, et al. 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Escobar Alvarez, Yolanda et al. “Cancer pain management: recommendations from a Latin-American experts panel.” Future oncology (London, England) vol. 13,27 (2017): 2455-2472. doi:10.2217/fon-2017-0288 Hoffmann-Eßer, Wiebke et al. “Guideline appraisal with AGREE II: Systematic review of the current evidence on how users handle the 2 overall assessments.” PloS one vol. 12,3 e0174831. 30 Mar. 2017, doi:10.1371/journal.pone.0174831 Armstrong, M.J., Mullins, C.D., Gronseth, G.S. et al. Impact of patient involvement on clinical practice guideline development: a parallel group study. Implementation Sci 13, 55 (2018). https://doi.org/10.1186/s13012-018-0745-6 Green, Carmen R., et al. "The Unequal Burden of Pain: Confronting Racial and Ethnic Disparities in Pain." Pain medicine (Malden, Mass.) 4.3 (2003): 277-94. Anderson, Karen O., et al. "Racial and Ethnic Disparities in Pain: Causes and Consequences of Unequal Care." The journal of pain 10.12 (2009): 1187-204. Norris SL, Holmer HK, Ogden LA et al (2012) Conflict of interest disclosures for clinical practice guidelines in the National Guideline Clearinghouse. PLoS One 7:e47343 Neuman J, Korenstein D, Ross JS, Keyhani S (2011) Prevalence of financial conflicts of interest among panel members producing clinical practice guidelines in Canada and United States: cross sectional study. BMJ 343:d5621–d5621 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3610185","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":249528355,"identity":"1b0cb94d-0561-4005-961d-504ca054dc86","order_by":0,"name":"Fatima Rizvi","email":"","orcid":"","institution":"Thomas Jefferson University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fatima","middleName":"","lastName":"Rizvi","suffix":""},{"id":249528358,"identity":"0d04a8b1-5c92-4a12-b0ef-8d0ccaee4181","order_by":1,"name":"Anza Rizvi","email":"","orcid":"","institution":"Thomas Jefferson University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Anza","middleName":"","lastName":"Rizvi","suffix":""},{"id":249528359,"identity":"14be7e45-6bf9-423a-b115-91ef513807d9","order_by":2,"name":"Kevin Chorath","email":"","orcid":"","institution":"University of Pennsylvania","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kevin","middleName":"","lastName":"Chorath","suffix":""},{"id":249528361,"identity":"d76430e7-af70-461b-aaad-01a09bf40631","order_by":3,"name":"Neeraj Suresh","email":"","orcid":"","institution":"University of Pennsylvania","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Neeraj","middleName":"","lastName":"Suresh","suffix":""},{"id":249528362,"identity":"c7122093-3370-46f0-afd5-c3f8fd787bc6","order_by":4,"name":"Jinggang Ng","email":"","orcid":"","institution":"University of Pennsylvania","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jinggang","middleName":"","lastName":"Ng","suffix":""},{"id":249528363,"identity":"3cfd1fdd-6903-4258-809c-254adf49ddad","order_by":5,"name":"Jacob Harris","email":"","orcid":"","institution":"University of Pennsylvania","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jacob","middleName":"","lastName":"Harris","suffix":""},{"id":249528364,"identity":"99859739-d15a-4f9d-8792-7732b23b3a75","order_by":6,"name":"Deepak Lakshmipathy","email":"","orcid":"","institution":"University of Pennsylvania","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Deepak","middleName":"","lastName":"Lakshmipathy","suffix":""},{"id":249528365,"identity":"1875c65e-c8f5-4016-b4be-d1ef9ebfa396","order_by":7,"name":"Louis-Xavier Barrette","email":"","orcid":"","institution":"University of 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Rajasekaran","email":"data:image/png;base64,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","orcid":"","institution":"University of Pennsylvania","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Karthik","middleName":"","lastName":"Rajasekaran","suffix":""}],"badges":[],"createdAt":"2023-11-14 12:15:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3610185/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3610185/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":46578988,"identity":"8ddbf583-2555-4b94-ad6a-581ab6d64584","added_by":"auto","created_at":"2023-11-16 16:51:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":38833,"visible":true,"origin":"","legend":"\u003cp\u003eDiagram showcasing Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol systematic search strategy\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-3610185/v1/4ba6708a3e4659581eeee6cc.png"},{"id":50951713,"identity":"43c4cc8b-a29d-4c6b-8cb2-8aa5694f221c","added_by":"auto","created_at":"2024-02-10 12:08:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":481221,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3610185/v1/77b332b6-7984-4d35-8ab0-058fb5e48114.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Practice Guidelines in the Management of Generalized Cancer Pain: A Systematic Evaluation Using the AGREE II Instrument","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCancer is a leading cause of death worldwide and continues to stand as a barrier to increasing life expectancy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It is reported that by 2025, the number of new cancer cases per year is expected to rise to over 20\u0026nbsp;million [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Pain is a common and debilitating symptom associated with cancer and its treatment. Pain prevalence in patients with cancer was reported to be as high as 64% for patients with advanced or terminal disease, 59% for patients undergoing cancer treatment, and 33% for patients who were cured of cancer [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Patients suffering from cancer pain often experience decreased quality of life and increased depression and anxiety [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral different subtypes and classifications of cancer pain exist such as chronic, neuropathic, mixed, and breakthrough cancer pain. Generalized cancer pain is a term that encompasses a range of different pain conditions, characteristics, and etiologies [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Managing generalized cancer pain can be challenging as the causes of cancer pain are multifactorial and complex, lending to different treatment approaches. A myriad of treatment options ranging from pharmacologic interventions (i.e. opioids) to nonpharmacologic integrative interventions (physical therapy, acupuncture, etc.) may be used to treat cancer pain [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Despite therapeutic advancements, the appropriate management of cancer pain remains difficult, and a subset of patients remain undertreated [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The taxing consequences and burden of cancer pain, varying treatment modalities, and undertreatment of cancer pain present a crucial need for health care providers to provide accurate and adequate cancer pain assessment and management.\u003c/p\u003e \u003cp\u003eClinical practice guidelines (CPGs) have been developed by various professional societies to establish standardized criteria for diagnosing and managing cancer pain. CPGs serve to provide clinicians with graded recommendations based on evidence of best practice [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The utilization of high-quality CPGs has the potential to make clinical practice more uniform across different medical centers, allowing for improved patient care and health outcomes. At the same time, however, it is equally important to ensure that CPGs are vetted prior to implementation in clinical settings. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument is a guideline appraisal tool developed to access the methodological quality of practice guidelines [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. It is the most comprehensively validated CPG appraisal tool and has been widely adopted [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The AGREE II instrument consists of 23 items that assess CPGs across six domains (scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence).\u003c/p\u003e \u003cp\u003eTo our knowledge, a critical and comprehensive evaluation of CPGs for the assessment and management of generalized cancer pain has not been previously conducted. Therefore, our objective was to systematically identify CPGs for generalized cancer pain and to assess the quality and rigor of them using the AGREE II instrument.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eLiterature Search and Selection Criteria\u003c/h2\u003e \u003cp\u003eFrom inception to March 3, 2021, authors (FR and AR) performed a systematic literature search of the following databases: Embase, MEDLINE via PubMed, and Scopus. Additionally, a manual internet search was conducted to identify clinical practice guidelines not found within these databases. The following search terms were used: [(\u0026ldquo;generalized cancer pain\u0026rdquo; OR \u0026ldquo;cancer pain\u0026rdquo; OR \u0026ldquo;general cancer pain\u0026rdquo;) AND (\u0026ldquo;guideline\u0026rdquo; OR \u0026ldquo;consensus\u0026rdquo; OR \u0026ldquo;recommendation\u0026rdquo;)]. Both national and international clinical practice guidelines that addressed the diagnosis, treatment, and management of cancer pain were included. We excluded guidelines that only focused on a singular component of diagnosis and management of cancer pain. If a development group or professional society published multiple guidelines, the most recent guideline was used. Editorials, summaries, textbook chapters, and non-English language publications were excluded. The selected articles were discussed by the authors (FR, AR, KC, and KR) and any discrepancies in inclusion criteria were addressed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData Extraction and Management\u003c/h2\u003e \u003cp\u003eThe following data was extracted for each CPG: the development body, source of publication, publication year, publication country, development method, key developers, target users, number of references, and relevant funding sources. A predetermined data collection form based on the six quality appraisal domains and 23 specific items included in the AGREE II instrument (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) was used.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIndividual Components of the AGREE II Evaluation Tool\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eScope and Purpose\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe overall objective(s) of the guideline is (are) specifically described.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe health question(s) covered by the guideline is (are) specifically described.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe population (patients, public, etc.) to whom the guideline is meant to apply is specifically described.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStakeholder Involvement\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe guideline development group includes individuals from all relevant professional groups.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe views and preferences of the target population (patients, public, etc.) have been sought.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe target users of the guideline are clearly defined.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRigor of Development\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSystematic methods were used to search for evidence.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe criteria for selecting the evidence are clearly described.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe strengths and limitations of the body of evidence are clearly described.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe methods for formulating the recommendations are clearly described.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe health benefits, side effects, and risks have been considered in formulating the recommendations.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThere is an explicit link between the recommendations and the supporting evidence.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe guideline has been externally reviewed by experts prior to its publication.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA procedure for updating the guideline is provided.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eClarity of Presentation\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe recommendations are specific and unambiguous.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe different options for management of the condition or health issue are clearly presented.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKey recommendations are easily identifiable.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eApplicability\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe guideline describes facilitators and barriers to its application.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe guideline provides advice and/or tools on how the recommendations can be put into practice.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe potential resource implications of applying the recommendations have been considered.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe guideline presents monitoring and/ or auditing criteria.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEditorial Independence\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe views of the funding body have not influenced the content of the guideline.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCompeting interests of guideline development group members have been recorded and addressed.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAGREE II\u0026thinsp;=\u0026thinsp;Appraisal of Guidelines for Research and Evaluation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eQuality Appraisal\u003c/h2\u003e \u003cp\u003ePer AGREE recommendations, all appraisers completed the free, online training module available on the AGREE website (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.agreetrust.org\u003c/span\u003e\u003c/span\u003e\u003cspan address=\"http://www.agreetrust.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). Then, using the AGREE II instrument, four authors (FR, AR, JN, and JH) independently performed assessments and evaluations of the selected clinical practice guidelines. The AGREE II instrument consists of 23 items that evaluate CPGs over six domains: domain 1 (scope and purpose), domain 2 (stakeholder involvement), domain 3 (rigor of development), domain 4 (clarity of presentation), domain 5 (applicability), and domain 6 (editorial independence). Each of the 23 items was assigned a score between 1 and 7. A score of 1 (strongly disagree) was given if the item was not addressed in the guideline, whereas a 7 (strongly agree) was given if the item was comprehensively addressed. According to the formula provided by the AGREE II manual (AGREE Next Steps Consortium), scaled domain scores were obtained as such [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$scaled domain score= \\frac{(obtained score-minimum possible score)}{(maximum possible score-minimum possible score)}\\times 100\\%$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eA threshold of 60% was used to assess the quality of the guideline. CPGs were rated as high when 5 or more domains scored\u0026thinsp;\u0026gt;\u0026thinsp;60%, average when 3 or 4 domains scored\u0026thinsp;\u0026gt;\u0026thinsp;60%, and low if\u0026thinsp;\u0026le;\u0026thinsp;2 domains scored\u0026thinsp;\u0026gt;\u0026thinsp;60%. Overall quality scores for each guideline were also calculated and reported as a mean of the six scaled domain scores.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eTo assess the interrater reliability and consistency among the four appraisers, intraclass correlation coefficients (ICCs) were calculated for each AGREE II domain using Python 3.8.2 and the \u0026lsquo;pingouin\u0026rsquo; API. Per previous literature, ICCs were graded as the following: poor (\u0026lt;\u0026thinsp;0.20), fair (0.21\u0026ndash;0.41), moderate (0.41\u0026ndash;0.60), good (0.61\u0026ndash;0.80), and very good (0.81\u0026ndash;1.00) [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eFollowing Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols, our electronic search initially yielded 5,845 citations, which were subsequently reviewed by title and abstract for inclusion criteria. Among these, 17 were reviewed in full, and 12 guidelines were selected for evaluation (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eGuideline Characteristics\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e provides a summary of the general characteristics for each CPG such as the developing body, publication year, area of origin, development method, developers, target users, number of references, and relevant funding source. Of the 12 guidelines selected for inclusion, three were developed in the United States by the following societies or institutions: National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), and American Society of Anesthesiologists (ASA) [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Of the remaining guidelines, two were developed in Canada (Alberta Health Services (AHS) and Cancer Care Ontario (CCO)), one in Japan by the Japanese Society of Palliative Medicine (JSPM), one in Spain by the Spanish Society of Medical Oncology (SEOM), one in Italy by the Italian Society of Anaesthesia, Analgesia, Resuscitation and Intensive Care \u003cb\u003e(\u003c/b\u003eSIAARTI), one in Switzerland by the World Health Organization (WHO), one in Europe by the European Society for Medical Oncology (ESMO), and two in the Latin America region (Latin American Expert Panel (LAEP) and Latin American Guidelines (LAG)) [\u003cspan additionalcitationids=\"CR19 CR20 CR21 CR22 CR23 CR24 CR25\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The guidelines were published between 1996 and 2019, with all but two (SIAARTI 2003 and ASA 1996) being released within the last decade. Most were developed through a combination of expert opinion, committee consensus, and systematic literature review. Only four of the eight CPGs explicitly stated their funding sources (WHO, ESMO, LAEP, LAG).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGeneral Characteristics of Included Clinical Practice Guidelines\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJournal/Source\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSociety/\u003c/p\u003e \u003cp\u003eInstitution\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePubli-cation Year\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCountry or Region\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDevelopment Method\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDevelopers\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTarget User\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNumber of References\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eFunding Source\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJournal of the National Comprehensive Cancer Network\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNational Comprehensive Cancer Network (NCCN)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUnited States\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eConsensus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAuthors of NCCN clinical practice guideline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHealthcare providers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e288\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026minus;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWorld Health Organization (WHO)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSwitzerland\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSystematic literature review\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGuideline Development Group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePhysicians, nurses, pharmacists, and caregivers, policy and program managers, public health officials and academics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e197\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eWHO core funds\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnnals of Oncology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEuropean Society for Medical Oncology (ESMO)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEurope\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSystematic literature review\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThe ESMO Guidelines Committee\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHealth professionals working in the field of oncology across Europe and other parts of the world\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026minus;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAlberta Health Services (AHS)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCanada\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSystematic literature review, consensus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMultidisciplinary working group comprised of medical oncologists, palliative care specialists, nurse practitioners, occupational therapists, pharmacists, and a Knowledge Management\u003c/p\u003e \u003cp\u003eSpecialist from the Guideline Resource Unit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMembers of multidisciplinary healthcare teams who manage patients with pain associated with their cancer treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical Translational Oncology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpanish Society of Medical\u003c/p\u003e \u003cp\u003eOncology (SEOM)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSpain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSystematic literature review\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eExperts and two coordinators\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eProfessionals in Clinical Practice\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026minus;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCancer Care Ontario (CCO)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCanada\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSystematic literature review\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eExperts in pain and palliative care (nurses, physicians), health research methodologist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eStaff of the Patient Reported Outcomes and Symptom Management Program of CCO and staff of the Ontario Palliative Care Network; physicians, nurses, caregivers, and patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e315\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFuture Oncology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLatin America\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eExpert opinion, consensus development conference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eExperts on cancer pain management from Costa Rica, Mexico, Chile, Colombia, Peru, Brazil, Ecuador, Spain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLatin-American Countries; oncologists in pain management\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eGr\u0026uuml;nenthal Services, Incorporated\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain Management\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLatin America\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSystematic literature review\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLatin American opinion leaders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePhysicians\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eGr\u0026uuml;nenthal Services,\u003c/p\u003e \u003cp\u003eIncorporated\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJournal of Clinical Oncology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmerican Society of Clinical Oncology (ASCO)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUnited States\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSystematic literature review, expert consensus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eASCO-convened expert panel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHealth care practitioners who provide care to cancer survivors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJapanese Journal of Clinical Oncology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapanese Society of Palliative Medicine (JSPM)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSystematic literature review, expert panel consensus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31 palliative care physicians, 15 anesthesiologists, 5 oncologists, 5 home care physicians, 25 pharmacists, 23 nurses,\u003c/p\u003e \u003cp\u003e1 epidemiologist, 7 other professionals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMedical personnel who care for cancer patients, including palliative care physicians, oncologists, nurses, pharmacists\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinerva Anestesiologica\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eItalian Society of Anaesthesia, Analgesia, Resuscitation and Intensive Care\u0026nbsp;(SIAARTI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eItaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eConsensus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThe SIAARTI group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026minus;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnesthesiology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmerican Society of Anesthesiologists (ASA)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1996\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUnited States\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSystematic literature review, consensus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAmerican Society of Anesthesiologists task force\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAnesthesiologists and individuals who deliver care under the direct supervision of anesthesiologists\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026minus;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eNCCN\u0026thinsp;=\u0026thinsp;National Comprehensive Cancer Network, WHO\u0026thinsp;=\u0026thinsp;World Health Organization, ESMO\u0026thinsp;=\u0026thinsp;European Society for Medical Oncology, AHS\u0026thinsp;=\u0026thinsp;Alberta Health Services, SEOM\u0026thinsp;=\u0026thinsp;Spanish Society of Medical Oncology, CCO\u0026thinsp;=\u0026thinsp;Cancer Care Ontario, ASCO\u0026thinsp;=\u0026thinsp;American Society of Clinical Oncology, JSPM\u0026thinsp;=\u0026thinsp;Japanese Society of Palliative Medicine, SIAARTI\u0026thinsp;=\u0026thinsp;Italian Society of Anaesthesia, Analgesia, Resuscitation and Intensive Care, ASA\u0026thinsp;=\u0026thinsp;American Society of Anesthesiologists\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eGuideline Appraisal\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e highlights scaled domain scores and the overall quality assessment for each guideline according to the AGREE II instrument. Domain 4 (clarity of presentation) and domain 1 (scope and purpose) had the highest overall values with scores of 82.41% \u0026plusmn; 18.20% and 56.48% \u0026plusmn; 30.59%, respectively. Domain 2 (stakeholder involvement) and domain 5 (applicability) had the lowest overall scores with scores of 36.81% \u0026plusmn; 21.24% and 44.53% \u0026plusmn; 26.61%, respectively. Domain 1 (scope and purpose) had the highest variability among guidelines with a standard deviation of 30.59%. Of the selected guidelines, those of WHO and ASCO achieved overall high ratings per aforementioned criteria. Three guidelines received overall average quality ratings and the remaining seven received low quality ratings.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eQuality Assessment of Included Clinical Practice Guidelines\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDomain 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDomain 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDomain 3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDomain 4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDomain 5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDomain 6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSociety/ Institution\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eScope and Purpose\u003c/p\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStakeholder Involvement (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRigor of Development (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eClarity of Presentation (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eApplicability (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEditorial Independence (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eMean Overall Score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eOverall Quality\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCCN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e46.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e58.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e47.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWHO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e97.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e87.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e100.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e92.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESMO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e91.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e36.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e41.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e39.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAHS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e84.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e58.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e59.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSEOM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e41.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e40.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCCO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e60.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e54.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eAverage\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLAEP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e51.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e64.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e43.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLAG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e73.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e79.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e42.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASCO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e88.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e37.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e75.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJSPM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e91.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e45.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e58.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eAverage\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSIAARTI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e70.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e42.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e26.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e59.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eAverage\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.48\u0026thinsp;\u0026plusmn;\u0026thinsp;30.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.81\u0026thinsp;\u0026plusmn;\u0026thinsp;21.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50.52\u0026thinsp;\u0026plusmn;\u0026thinsp;29.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e82.41\u0026thinsp;\u0026plusmn;\u0026thinsp;18.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e44.53\u0026thinsp;\u0026plusmn;\u0026thinsp;26.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e48.96\u0026thinsp;\u0026plusmn;\u0026thinsp;28.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eNCCN\u0026thinsp;=\u0026thinsp;National Comprehensive Cancer Network, WHO\u0026thinsp;=\u0026thinsp;World Health Organization, ESMO\u0026thinsp;=\u0026thinsp;European Society for Medical Oncology, AHS\u0026thinsp;=\u0026thinsp;Alberta Health Services, SEOM\u0026thinsp;=\u0026thinsp;Spanish Society of Medical Oncology, CCO\u0026thinsp;=\u0026thinsp;Cancer Care Ontario, LAEP\u0026thinsp;=\u0026thinsp;Latin American Expert Panel, LAG\u0026thinsp;=\u0026thinsp;Latin American Guidelines, ASCO\u0026thinsp;=\u0026thinsp;American Society of Clinical Oncology, JSPM\u0026thinsp;=\u0026thinsp;Japanese Society of Palliative Medicine, SIAARTI\u0026thinsp;=\u0026thinsp;Italian Society of Anaesthesia, Analgesia, Resuscitation and Intensive Care, ASA\u0026thinsp;=\u0026thinsp;American Society of Anesthesiologists\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eIntraclass Reliability\u003c/h2\u003e \u003cp\u003eThe intraclass correlation coefficients (ICC) for each quality domain of the AGREE II instrument can be found in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. These values signify the magnitude of agreement between the four reviewers (FR, AR, JN, JH). All six domains demonstrated very good intraclass reliability per aforementioned crtieria.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIntraclass Correlation Coefficients for AGREE II Domains\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAgree II Domain\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eICC (95% CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDomain 1: Scope and Purpose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.96 (0.85\u0026ndash;0.99)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDomain 2: Stakeholder Involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.94 (0.85\u0026ndash;0.98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDomain 3: Rigor of Development\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.98 (0.93\u0026ndash;0.99)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDomain 4: Clarity of Presentation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.94 (0.87\u0026ndash;0.98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDomain 5: Applicability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.97 (0.93\u0026ndash;0.99)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDomain 6: Editorial Independence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.85 (0.57\u0026ndash;0.95)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eAGREE II\u0026thinsp;=\u0026thinsp;Appraisal of Guidelines for Research and Evaluation, ICC\u0026thinsp;=\u0026thinsp;intraclass correlation coefficient, CI\u0026thinsp;=\u0026thinsp;confidence interval\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eUsing the AGREE II tool, only two out of twelve CPGs were of high quality. Our analysis depicts that CPGs for generalized cancer pain require significant improvement.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eCommon Strengths\u003c/h2\u003e \u003cp\u003eThe CPGs performed well in domain 4 (clarity of presentation) with 11 out of 12 CPGs scoring satisfactorily (\u0026gt;\u0026thinsp;60%) in this domain. Clarity of presentation assesses and evaluates the presentation and format of the guidelines. Across guidelines key recommendations were specific, often presented in bulleted form, flowcharts, and easily identifiable diagrams. This is a valuable strength as it allows clinicians from a variety of disciplines to understand the main points of a CPG quickly and clearly. As a result, it would serve future authors well to continue these practices when constructing updates of or new CPGs.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eCommon Weaknesses\u003c/h2\u003e \u003cp\u003eCPGs performed poorly in domain 3 (rigor of development), which is considered the strongest predictor of overall guideline quality [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. CPGs that performed poorly in this domain failed to employ a systematic method to search for evidence, provide inclusion and exclusion criteria, and include a description of the strengths and limitations of the body of evidence. Additionally, several guidelines were not externally reviewed by experts prior to publication and lacked explicit updating procedures. This performance is especially concerning in the context of cancer pain given its complexity and nuances in management. Specifically, if guideline recommendations are not clearly based in literature-reported evidence, sub-optimal patient care and outcomes can quickly arise [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. We strongly recommend CPG creators more clearly delineate their systematic development strategies to ensure that CPGs stay true to their original aim\u0026mdash;helpful tools that guide clinical decision-making based on evidence of best practice.\u003c/p\u003e \u003cp\u003eAll twelve guidelines failed to include the process by which patient values and preferences were solicited and incorporated into the guideline recommendations, resulting in low in domain 2 (stakeholder involvement) scores. Similarly, lack of discussion on how physician knowledge and beliefs, economic factors, and access to resources did or did not influence the application of guideline recommendations resulted in low domain 5 (applicability) scores. Both related domain weaknesses showcase that current generalized cancer pain CPGs are lacking in acknowledging potential bias from the guideline development board. Because although all CPGs had multidisciplinary developers from various specialists involved in the management of cancer pain (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), the patient perspective is also critical in ensuring more implementable guidelines [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The patient perspective is important in guiding recommendation development as patients not only serve as their best own advocate, but also can identify issues and outcomes unbeknownst healthcare professionals [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Furthermore, racial and ethnic minority cancer patients could shed light on their added population-specific obstacles (delays in diagnosis and initiation of treatment, undertreatment of pain, racial biases, lack of insurance, etc.) to help lessen disparities in cancer care [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. All future guidelines should therefore strive to include patients as important stakeholders and address educational, systemic, socioeconomic, and racial barriers involved in generalized cancer pain diagnosis and management.\u003c/p\u003e \u003cp\u003eLastly, CPGs had overall weak performance in domain 6 (editorial independence) due to stark differences in guideline-specific scores. This is best demonstrated by looking at the WHO, SIAARTI and, ASA guidelines which had 100%, 0%, and 0% scores for the category, respectively. Specifically, while some CPGs comprehensively and saliently listed how sources of funding and competing interests did not influence provided recommendations (i.e. WHO) others failed to mention either point altogether (SIAARTI and ASA). CPGs must provide unbiased and evidence-based recommendations to serve as effective tools for improving patient care. Otherwise, ulterior financial motives and other conflicts of interest can introduce bias and affect the quality of final recommendations [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Information regarding editorial independence should therefore directly be reported in guidelines themselves (and not only on publicly available on the developing bodies\u0026rsquo; websites to which providers may not have routine access) to increase transparency and ensure patients are receiving the best evidence-based care.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eGuideline Recommendations\u003c/h2\u003e \u003cp\u003eA summary of the key recommendations for the management of cancer pain from the appraised guidelines is presented in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. The recommendations emphasize the importance of both pharmacological and non-pharmacological interventions. Consensus across guidelines included conducting an initial comprehensive patient evaluation [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The use of validated pain assessment tools such as the Visual Analogue Scale (VAS), the Verbal Rating Scale, or the Numerical Rating Scale can be used to assess pain intensity. CPG recommendations included analgesic regimen combinations of acetaminophen/paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and adjuvant analgesics. Non-opioid analgesics such as acetaminophen/paracetamol and NSAIDs should be administered to cancer patients with mild pain [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. For moderate-to-severe pain, the use of opioids in addition to non-opioids/adjuvant analgesics was recommended [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. An individualized approach should be taken to determine dosage and frequency of medications with the goal of achieving a balance between optimal pain relief and minimal side effects. Throughout treatment, pain assessments should be performed regularly to ensure adequate pain control is being met. Adjuvant analgesics such as antidepressants, anticonvulsants, topical agents, and corticosteroids, used in addition to non-opioid and opioid analgesics may be useful in the management of neuropathic cancer pain. Additionally, various nonpharmacologic interventions (physical, spiritual, and cognitive modalities) may also serve as valuable additions to pharmacologic interventions [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eKey Recommendations\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eKey Takeaways\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGeneral Principles\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026bull; Goal: Optimize analgesia and minimize adverse effects\u003c/p\u003e \u003cp\u003e\u0026bull; Comprehensive assessment should be performed including: a detailed review of past and current medical history, physical examination, pain assessment using an appropriate pain measurement tool\u003c/p\u003e \u003cp\u003e\u0026bull; Patients should be educated about pain and pain management, allowing them to serve as informed, active participants in their own care\u003c/p\u003e\u003cp\u003e\u0026bull; Non-opioid medications should be considered at every stage\u003c/p\u003e\u003cp\u003e\u0026bull; Adjuvant analgesics such as anticonvulsants, antidepressants or corticosteroids may be part of the analgesic regimen for cancer patients with neuropathic pain\u003c/p\u003e\u003cp\u003e\u0026bull; Non-pharmacological interventions may be integrated:\u003c/p\u003e\u003cp\u003eo Integrative approach/therapy: massage, acupuncture, music\u003c/p\u003e\u003cp\u003eo Physical therapy/approach: occupational therapy, individualized exercise program\u003c/p\u003e\u003cp\u003eo Psychological approach/therapy: cognitive behavioral therapy, mindfulness relaxation, distraction training\u003c/p\u003e\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePain Intensity-Specific Principles\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMild Pain\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026bull; Non-opioids, such as acetaminophen/paracetamol and NSAIDs are recommended for mild pain\u003c/p\u003e \u003cp\u003e\u0026bull; Monitor for adverse effects of acetaminophen/paracetamol and NSAIDs\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eModerate to\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eSevere Pain\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026bull; Non-opioids and adjuvant therapies as appropriate with opioids should be administered to cancer patients with moderate to severe pain or inadequately controlled pain despite treatment with non-opioid analgesics\u003c/p\u003e \u003cp\u003e\u0026bull; Oral or transdermal administration of opioids is usually preferable; however, when the oral route is not practical then subcutaneous or intravenous routes may be used\u003c/p\u003e \u003cp\u003e\u0026bull; Patients should be assessed and observed for side effects of opioid therapy such as constipation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eNSAIDs\u0026thinsp;=\u0026thinsp;nonsteroidal anti-inflammatory drugs\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eStudy Limitations\u003c/h2\u003e \u003cp\u003eThe goal of the AGREE II instrument is to assess the quality and methodological rigor of guidelines and provide concrete, targeted recommendations for their improvement. Although the AGREE II instrument has been proven to be reliable and valid (particularly with four independent reviewers), the tool inherently depends on subjective ratings from the reviewers. Reviewers may interpret the items and criteria differently, allowing for variations in scoring despite strong ICC values across all domains. The appraisers were also not blinded to the authors and organizations who developed the guidelines, introducing a potential source of bias. Furthermore, the AGREE II items and domains are given equal importance rather than varying individual weights. This could introduce a source of mathematical bias as previous research suggests domain 3 (rigor of development) to be the strongest indicator of guideline quality relative to other domains [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Therefore, in the current schema, guidelines with strong domain 3 scores but weaker remaining scores may be potentially misclassified as low or average quality and those with the reverse scenario may be misclassified as high quality. Similarly, it is important to note that the AGREE II instrument only critiques CPGs regarding their development, so low or average quality guidelines may still provide some valuable clinical insights. Finally, while the authors performed a systematic search following PRISMA protocols, some relevant non-English guidelines may have excluded and consequently introduced an element of publication bias.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eEvidence-based CPGs of high quality can facilitate clinical decision-making and improve health outcomes for patients globally. CPGs are particularly applicable to the care of patients suffering from generalized cancer pain, given their complex, longitudinal multidisciplinary care and management. Based on our analysis of current CPGs using the AGREE II instrument, only two out of 12 (16.7%) guidelines received an overall quality score of high (WHO and ASCO). This indicates that there is significant room for improvement. Future authors of CPGs on diagnosing and managing generalized cancer pain would particularly benefit by enhancing relevant sections on stakeholder involvement, rigor of development, applicability, and editorial independence.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cu\u003eFunding:\u003c/u\u003e The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCompeting interests:\u003c/u\u003e The authors have no financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eNone\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFatima Rizvi (FR): Conceptualization, Methodology, Formal Analysis, Investigation, Data Curation, Writing - Original Draft, Writing - Review \u0026amp; Editing, Project Administration\u003c/p\u003e\n\u003cp\u003eAnza Rizvi (AR): Conceptualization, Methodology, Formal Analysis, Investigation, Data Curation, Writing - Original Draft, Writing - Review \u0026amp; Editing, Project Administration\u003c/p\u003e\n\u003cp\u003eKevin Chorath (KC): Methodology, Investigation, Data Curation, Writing - Review \u0026amp; Editing\u003c/p\u003e\n\u003cp\u003eNeeraj Suresh (NS): Methodology, Investigation, Data Curation, Writing - Review \u0026amp; Editing\u003c/p\u003e\n\u003cp\u003eJinggang Ng (JN): Methodology, Investigation, Data Curation, Writing - Review \u0026amp; Editing\u003c/p\u003e\n\u003cp\u003eJacob Harris (JH): Methodology, Investigation, Data Curation, Writing - Review \u0026amp; Editing\u003c/p\u003e\n\u003cp\u003eDeepak Lakshmipathy (DL): Conceptualization, Validation, Writing - Review \u0026amp; Editing\u003c/p\u003e\n\u003cp\u003eLouis-Xavier Barrette (LXB): Conceptualization, Validation, Writing - Review \u0026amp; Editing\u003c/p\u003e\n\u003cp\u003eKarthik Rajasekaran (KR): Conceptualization, Validation, Writing - Review \u0026amp; Editing, Supervision\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSung, Hyuna, et al. \u0026quot;Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.\u0026quot; \u003cem\u003eCA: A Cancer Journal for Clinicians\u003c/em\u003e (2021).\u003c/li\u003e\n\u003cli\u003eFerlay, J., et al. \u0026quot;Cancer Incidence and Mortality Worldwide: Sources, Methods and Major Patterns in GLOBOCAN 2012.\u0026quot; \u003cem\u003eInternational journal of cancer\u003c/em\u003e 136.5 (2015): 359.\u003c/li\u003e\n\u003cli\u003evan den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, et al. 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A Report by the American Society of Anesthesiologists Task Force on Pain Management, Cancer Pain Section.\u0026quot; \u003cem\u003eAnesthesiology (Philadelphia)\u003c/em\u003e 84.5 (1996): 1243-57.\u003c/li\u003e\n\u003cli\u003eAlberta Health Services Clinical Practice Guideline\u003c/li\u003e\n\u003cli\u003eSawhney M, Fletcher GG, Rice J, Watt-Watson J, Rawn T. Guidelines on management of pain in cancer and/or palliative care. Toronto (ON): Cancer Care Ontario; 2017 Sep 22. Program in Evidence-Based Care Evidence Summary No.: 18-4. \u003c/li\u003e\n\u003cli\u003eTakashi Yamaguchi, Yasuo Shima, Tatsuya Morita, Miki Hosoya, Motohiro Matoba, Clinical Guideline for Pharmacological Management of Cancer Pain: The Japanese Society of Palliative Medicine Recommendations, \u003cem\u003eJapanese Journal of Clinical Oncology\u003c/em\u003e, Volume 43, Issue 9, September 2013, Pages 896\u0026ndash;909, https://doi.org/10.1093/jjco/hyt099\u003c/li\u003e\n\u003cli\u003eJara, C et al. \u0026ldquo;SEOM clinical guideline for treatment of cancer pain (2017).\u0026rdquo; \u003cem\u003eClinical \u0026amp; translational oncology: official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico\u003c/em\u003e vol. 20,1 (2018): 97-107. doi:10.1007/s12094-017-1791-2\u003c/li\u003e\n\u003cli\u003eSia Ambrosio, F et al. \u0026ldquo;SIAARTI recommendations on the assessment and treatment of chronic cancer pain.\u0026rdquo; \u003cem\u003eMinerva anestesiologica\u003c/em\u003e vol. 69,9 (2003): 697-716, 717-29.\u003c/li\u003e\n\u003cli\u003eWHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents. Geneva: World Health Organization; 2018. 6, Recommendations for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents.https://www.ncbi.nlm.nih.gov/books/NBK537486/\u003c/li\u003e\n\u003cli\u003eFallon, M et al. \u0026ldquo;Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines.\u0026rdquo; \u003cem\u003eAnnals of oncology: official journal of the European Society for Medical Oncology\u003c/em\u003e vol. 29,Suppl 4 (2018): iv166-iv191. \u003c/li\u003e\n\u003cli\u003eLara-Solares, Argelia, et al. \u0026quot;Latin-American Guidelines for Cancer Pain Management.\u0026quot; \u003cem\u003ePain management (London)\u003c/em\u003e 7.4 (2017): 287-98. \u003cem\u003eCrossRef. \u003c/em\u003e\u003c/li\u003e\n\u003cli\u003eEscobar Alvarez, Yolanda et al. \u0026ldquo;Cancer pain management: recommendations from a Latin-American experts panel.\u0026rdquo; \u003cem\u003eFuture oncology (London, England)\u003c/em\u003e vol. 13,27 (2017): 2455-2472. doi:10.2217/fon-2017-0288 \u003c/li\u003e\n\u003cli\u003eHoffmann-E\u0026szlig;er, Wiebke et al. \u0026ldquo;Guideline appraisal with AGREE II: Systematic review of the current evidence on how users handle the 2 overall assessments.\u0026rdquo; \u003cem\u003ePloS one\u003c/em\u003e vol. 12,3 e0174831. 30 Mar. 2017, doi:10.1371/journal.pone.0174831\u003c/li\u003e\n\u003cli\u003eArmstrong, M.J., Mullins, C.D., Gronseth, G.S. \u003cem\u003eet al.\u003c/em\u003e Impact of patient involvement on clinical practice guideline development: a parallel group study. \u003cem\u003eImplementation Sci\u003c/em\u003e 13,\u003cstrong\u003e \u003c/strong\u003e55 (2018). https://doi.org/10.1186/s13012-018-0745-6\u003c/li\u003e\n\u003cli\u003eGreen, Carmen R., et al. \u0026quot;The Unequal Burden of Pain: Confronting Racial and Ethnic Disparities in Pain.\u0026quot; \u003cem\u003ePain medicine (Malden, Mass.)\u003c/em\u003e4.3 (2003): 277-94.\u003c/li\u003e\n\u003cli\u003eAnderson, Karen O., et al. \u0026quot;Racial and Ethnic Disparities in Pain: Causes and Consequences of Unequal Care.\u0026quot; \u003cem\u003eThe journal of pain\u003c/em\u003e 10.12 (2009): 1187-204. \u003c/li\u003e\n\u003cli\u003eNorris SL, Holmer HK, Ogden LA et al (2012) Conflict of interest disclosures for clinical practice guidelines in the National Guideline Clearinghouse. PLoS One 7:e47343\u003c/li\u003e\n\u003cli\u003eNeuman J, Korenstein D, Ross JS, Keyhani S (2011) Prevalence of financial conflicts of interest among panel members producing clinical practice guidelines in Canada and United States: cross sectional study. BMJ 343:d5621\u0026ndash;d5621\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Generalized cancer pain, Clinical practice guideline, Quality, Appraisal, AGREE II","lastPublishedDoi":"10.21203/rs.3.rs-3610185/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3610185/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eWhile several clinical practice guidelines (CPGs) exist to guide clinical decision-making in patients presenting with generalized cancer pain, to date there has been no comprehensive review of their methodological rigor and quality. Our aim was to address this deficiency by using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA systematic literature search to identify relevant CPGs was performed over the following databases from inception to March 3, 2021: Embase, MEDLINE via PubMed, and Scopus. Four authors (FR, AR, JN, and JH) independently performed assessments and evaluations of the selected CPGs using the AGREE II instrument. Scaled domain percentage scores were calculated and 60% was defined as the satisfactory quality threshold. Intraclass correlation coefficients (ICCs) were also calculated to assess interrater reliability and consistency.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e12 guidelines were selected for inclusion. Two guidelines were classified high quality, three guidelines were classified as average quality, and seven were classified as low quality. Domains 4 (clarity of presentation) and 1 (scope and purpose) received the highest mean scores (82.41% \u0026plusmn; 18.20% and 56.48% \u0026plusmn; 30.59%), while domains 5 (applicability) and 2 (stakeholder involvement) received the lowest (44.53% \u0026plusmn; 26.61% and 36.81% \u0026plusmn; 21.24%). ICC statistical analysis showed high consistency between reviewers (range 0.85\u0026ndash;0.98).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eBased on the AGREE II instrument, the majority of CPGs for generalized cancer pain were of low or average quality. Future guidelines for generalized cancer pain can be improved by better defining stakeholder involvement, rigor of development, applicability, and editorial independence during development.\u003c/p\u003e","manuscriptTitle":"Clinical Practice Guidelines in the Management of Generalized Cancer Pain: A Systematic Evaluation Using the AGREE II Instrument","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-11-16 16:51:10","doi":"10.21203/rs.3.rs-3610185/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1ca8da18-4f33-48b2-ad91-5ce8092218ba","owner":[],"postedDate":"November 16th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-10T12:00:00+00:00","versionOfRecord":[],"versionCreatedAt":"2023-11-16 16:51:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3610185","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3610185","identity":"rs-3610185","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}