Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review

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Managing CNMP often involves prescribing analgesics which carry risks such as dependency and adverse outcomes. Interactions between healthcare professionals (HCPs) and the pharmaceutical industry, including financial incentives, gifts, and sponsored education, may influence analgesic prescribing practices. Understanding these dynamics is essential for promoting ethical, evidence-based prescribing and ensuring patient safety. Therefore, the aim is to assess how pharmaceutical industry interactions with HCPs affect the prescribing of analgesics, specifically in the context of CNMP management. Methods This is a protocol for a systematic review, which is also prospectively registered on PROSPERO (Registration Number: CRD42024627184) and is reported according to PRISMA-P guidelines. A systematic search will be performed across MEDLINE, EMBASE, CINAHL, PsycINFO, and Web of Science. Observational studies (e.g., cross-sectional, cohort) evaluating the association between pharmaceutical industry interactions and HCPs’ prescribing patterns for CNMP management will be included. Primary outcomes include analgesic prescribing patterns, such as rate, volume, and cost. Secondary outcomes involve patient safety measures and HCP attitudes towards prescribing. Titles, abstracts, and full texts will be screened according to the inclusion criteria. Data extraction will utilize a standardized form, and the methodological quality will be evaluated using the ROBINS-I tool. Screening, data extraction and quality appraisal will be conducted by two reviewers, independently, resolving any discrepancies with the help of a third reviewer. Should there be sufficient homogeneity in the results data, a meta-analysis will be conducted; if not, the findings will be presented in a narrative synthesis. The strength of evidence will be assessed using the GRADE approach. Discussion The findings could inform strategies to enhance unbiased and evidence-based prescribing in CNMP management, promoting better patient care. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://hrbopenresearch.org/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://hrbopenresearch.org/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://hrbopenresearch.org/articles/8-15", "name": "Associations between pharmaceutical industry interactions and prescribing..." } } ] } Home Browse Associations between pharmaceutical industry interactions and prescribing... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Gharbia M, Iladiva L, Moriarty F et al. Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review [version 1; peer review: 1 approved, 1 not approved] . HRB Open Res 2025, 8 :15 ( https://doi.org/10.12688/hrbopenres.14071.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Study Protocol Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review [version 1; peer review: 1 approved, 1 not approved] Mohammed Gharbia https://orcid.org/0009-0003-1713-0696 1 , Lydia Iladiva 2 , Frank Moriarty 3 , Tom Fahey 1 , James Larkin https://orcid.org/0000-0003-4339-5623 1 Mohammed Gharbia https://orcid.org/0009-0003-1713-0696 1 , Lydia Iladiva 2 , [...] Frank Moriarty 3 , Tom Fahey 1 , James Larkin https://orcid.org/0000-0003-4339-5623 1 PUBLISHED 29 Jan 2025 Author details Author details 1 Department of General Practice, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Dublin, Ireland 2 Department of General Practice, University College Cork, Cork, Ireland 3 School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Dublin, Ireland Mohammed Gharbia Roles: Conceptualization, Methodology, Project Administration, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Lydia Iladiva Roles: Writing – Review & Editing Frank Moriarty Roles: Conceptualization, Funding Acquisition, Methodology, Project Administration, Supervision, Visualization, Writing – Review & Editing Tom Fahey Roles: Conceptualization, Funding Acquisition, Methodology, Project Administration, Supervision, Visualization, Writing – Review & Editing James Larkin Roles: Conceptualization, Funding Acquisition, Methodology, Project Administration, Supervision, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Introduction Chronic non-malignant pain (CNMP) represents a major global health issue and is a primary reason for disability worldwide. Managing CNMP often involves prescribing analgesics which carry risks such as dependency and adverse outcomes. Interactions between healthcare professionals (HCPs) and the pharmaceutical industry, including financial incentives, gifts, and sponsored education, may influence analgesic prescribing practices. Understanding these dynamics is essential for promoting ethical, evidence-based prescribing and ensuring patient safety. Therefore, the aim is to assess how pharmaceutical industry interactions with HCPs affect the prescribing of analgesics, specifically in the context of CNMP management. Methods This is a protocol for a systematic review, which is also prospectively registered on PROSPERO (Registration Number: CRD42024627184) and is reported according to PRISMA-P guidelines. A systematic search will be performed across MEDLINE, EMBASE, CINAHL, PsycINFO, and Web of Science. Observational studies (e.g., cross-sectional, cohort) evaluating the association between pharmaceutical industry interactions and HCPs’ prescribing patterns for CNMP management will be included. Primary outcomes include analgesic prescribing patterns, such as rate, volume, and cost. Secondary outcomes involve patient safety measures and HCP attitudes towards prescribing. Titles, abstracts, and full texts will be screened according to the inclusion criteria. Data extraction will utilize a standardized form, and the methodological quality will be evaluated using the ROBINS-I tool. Screening, data extraction and quality appraisal will be conducted by two reviewers, independently, resolving any discrepancies with the help of a third reviewer. Should there be sufficient homogeneity in the results data, a meta-analysis will be conducted; if not, the findings will be presented in a narrative synthesis. The strength of evidence will be assessed using the GRADE approach. Discussion The findings could inform strategies to enhance unbiased and evidence-based prescribing in CNMP management, promoting better patient care. READ ALL READ LESS Keywords Chronic non-malignant pain, analgesics, prescribing practices, pharmaceutical industry, systematic review Corresponding Author(s) Mohammed Gharbia ( [email protected] ) Close Corresponding author: Mohammed Gharbia Competing interests: No competing interests were disclosed. Grant information: Health Research Board [HRB SPHeRE 3 - 2022/1]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2025 Gharbia M et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Gharbia M, Iladiva L, Moriarty F et al. Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review [version 1; peer review: 1 approved, 1 not approved] . HRB Open Res 2025, 8 :15 ( https://doi.org/10.12688/hrbopenres.14071.1 ) First published: 29 Jan 2025, 8 :15 ( https://doi.org/10.12688/hrbopenres.14071.1 ) Latest published: 29 Jan 2025, 8 :15 ( https://doi.org/10.12688/hrbopenres.14071.1 ) Introduction Chronic non-malignant pain (CNMP) is a pervasive and debilitating condition that affects an estimated 20% of the global population, impacting approximately 1.5 billion people worldwide 1 . Its management often relies on pharmacological interventions, including opioids and non-opioid analgesics 2 . While these medications play a critical role in alleviating pain, their use is often complicated by issues such as dependency, misuse, other adverse effects, and the societal impact of overprescribing 3 . Amid growing concerns about the safe and effective management of CNMP, understanding the factors influencing prescribing behaviors is essential 4 . Interactions between healthcare professionals (HCPs) and pharmaceutical companies significantly affect prescribing practices 5 , often leading to increased utilization of branded or more costly medications, which may not always align with evidence-based practices 6 . These interactions range from financial incentives, gifts, and sponsorships to more subtle forms of engagement, such as participation in industry-sponsored education and access to promotional materials 7 . The association between pharmaceutical industry interactions and prescribing behaviors has been extensively documented across various medical fields 8 . For example, studies have highlighted how industry payments are correlated with increased prescription volumes of opioids and other high-cost medications 9 . Analysis of databases like the United States Open Payments Program has further revealed trends in how industry engagement is distributed among HCPs, with some groups, such as pain medicine specialists, being particularly targeted 10 . Additionally, such interactions have raised concerns about potential conflicts of interest, patient safety, and healthcare costs, especially in the context of the opioid crisis 11 . Despite these concerns, the specific impact of pharmaceutical industry interactions on analgesic prescribing in CNMP management has not been systematically synthesized. Existing studies often vary in scope, methodology, and focus, complicating efforts to draw generalized conclusions 12 . Observational studies have been particularly valuable in shedding light on the influence on real-world prescribing practices, yet their findings are often limited by methodological heterogeneity and potential biases 13 . This systematic review aims to fill this critical gap by comprehensively examining the influence of pharmaceutical industry interactions on HCP analgesic prescribing patterns for CNMP management. By synthesizing data from primary studies, this review seeks to elucidate the extent and nature of these interactions and their implications on analgesics prescriptions. This evidence will provide a foundation for informing policy and practice, ensuring that analgesic prescribing aligns with ethical and evidence-based care. Moreover, the findings will offer insights into strategies for mitigating undue influence, promoting transparency, and safeguarding patient outcomes in the management of CNMP. Review question In healthcare professionals who prescribe analgesics, how do interactions with the pharmaceutical industry influence the prescribing patterns of analgesics for chronic non-malignant pain management, compared to healthcare professionals with no or minimal pharmaceutical industry interactions? Methods This systematic review has been registered with PROSPERO (Registration Number: CRD42024627184) and will follow the methodologies outlined in the Cochrane Handbook for Systematic Reviews of Interventions 14 . It adheres to the reporting standards set by the PRISMA-P guidelines 15 . Eligibility criteria The eligibility criteria are outlined in Table 1 . This review will include primary studies that evaluate the association between healthcare professionals’ interactions with the pharmaceutical industry and their prescribing of analgesics for chronic non-malignant pain management. Observational studies, including cross-sectional and cohort designs, will be included as they provide insights into prescribing practices. Excluded publications will include conference abstracts and letters (not reporting results of primary research), commentaries, news releases, and study protocols, as they typically do not present empirical findings. Table 1. Study Eligibility Criteria. Criteria Inclusion Exclusion Population Healthcare professionals involved in prescribing analgesics, including physicians, nurse practitioners, and pharmacists. Studies may analyze individual practitioners or organizations such as clinics and hospitals. Studies focusing only on acute or chronic malignant pain, or opioid use disorder. Intervention Interactions between healthcare professionals and the pharmaceutical industry, including financial incentives (payments, sponsorships, gifts: including meals and free drug samples), participation in industry-sponsored education (CME), etc.. Studies examining healthcare professional interactions with industries or entities other than the pharmaceutical industry, such as medical device companies, insurance providers, or health technology firms. Comparator The absence of or lower levels of interaction with the pharmaceutical industry. Studies without a comparator group will also be included. Not applicable. Outcomes Primary outcomes include patterns of analgesic prescribing, such as frequency, magnitude, volumes, and costs of prescriptions. Secondary outcomes include patient-focused outcomes (e.g., adverse drug reactions, medication adherence) and healthcare professionals’ knowledge, attitudes, and reliance on pharmaceutical companies, only if they are reported in concerning patterns of analgesic prescription. Studies solely assessing general health outcomes, clinical drug efficacy, or patient satisfaction, without direct relevance to pharmaceutical interactions influencing prescribing practices. Setting Studies conducted in inpatient, outpatient, or community healthcare settings. No geographic or timeframe restrictions. Studies set in unrelated settings to chronic non-malignant pain management, such as dental surgeries, nursing homes, or explicitly focused on acute or cancer pain. We will adopt an inclusive approach, excluding only those where the specific type of pain treated is clearly defined as non-chronic, or malignant. Study Design Observational studies encompass cross-sectional and cohort studies. Conference abstracts, or letters (not reporting primary research), commentaries, news releases, study protocols, and descriptive designs (e.g., case reports). Publication No restrictions on language or publication date. Studies are still in progress but not yet published. Search strategy An information specialist from the host institution’s library with expertise in systematic reviews is involved in developing the search strategies. A systematic search will be conducted in the following databases: MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCOhost), PsycINFO (EBSCOhost), and Web of Science, covering studies from inception to the present with no restrictions placed on language or year of publication. Search terms include controlled vocabulary (e.g., MeSH, Emtree) and free-text keywords covering three primary concepts: i) Pharmaceutical industry interactions, using terms such as “pharmaceutical industry,” “pharmaceutical payment*,” and “corporate sponsorship*”; ii) Analgesic prescribing, including terms such as “pain management,” “opioid*,” and “pain medication*”; iii) Healthcare professionals and healthcare settings, using terms such as “physician*,” “nurse*,” “clinic*,” and “hospital*.” The full electronic search strategies, including all terms and database-specific details, are documented in supplementary materials to ensure transparency and reproducibility. Study selection Identified studies will be exported to EndNote (Version 21) for reference management, which will be used to remove duplicate records. After duplicates are removed, the remaining references will be transferred to Covidence systematic review software. Necessary licenses for both EndNote and Covidence have been secured. Initially, a pilot phase will be conducted where two reviewers independently screen the same 50 studies to ensure consistent application of the eligibility criteria. Following the pilot phase, titles and abstracts of the identified records will be screened by the reviewers to eliminate studies that do not meet the inclusion criteria. Full-text articles of the remaining studies will then be reviewed independently by the reviewers to assess their suitability for inclusion. The rationale for excluding studies during the full-text review phase will be documented and reported using a PRISMA flow diagram. Reviewers will be blinded to each other’s decisions during the screening process to minimize potential bias and ensure impartial evaluation. If there are disagreements at any stage, they will be settled through discussion. If disagreements cannot be resolved through discussion, then a third reviewer will be consulted. Data extraction and management Data extraction will be conducted using a standardized Excel form, initially tested on five studies independently by the reviewers. Following this, the reviewers will convene to discuss and resolve any discrepancies, ensuring consistent data extraction procedures. The form will collect study details (e.g., setting, design, publication year), population characteristics, intervention details (e.g., pharmaceutical interactions), comparison groups, outcome measures, and results. Fields will also capture funding sources, exposure levels, types of analgesics prescribed, and relevant statistical data. The full data extraction table is provided in the supplementary materials. Two reviewers will independently extract data to reduce bias and enhance accuracy. Discrepancies will be addressed through discussion, and if necessary, a third reviewer will be consulted. Efforts will be made to contact lead authors of primary studies to retrieve unavailable or incomplete data. Methodological quality assessment While the risk of bias assessment will not be used to exclude studies, it will shape our understanding by highlighting potential biases that could affect the outcomes. The Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool for evaluating observational studies 16 will be employed. This instrument evaluates seven bias domains: confounding, participant selection, intervention classification, deviations from planned interventions, missing data, outcome measurement, and choice of reported results. This assessment will guide our interpretation and the weight given to each study's results in our overall analysis. Two independent reviewers will assess each study and assign ratings of “low,” “moderate,” “serious,” or “critical” for each domain. Disagreements will be resolved by discussion or, if needed, by consulting a third reviewer. Two reviewers will assess the reliability of the cumulative evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach 17 . This will involve evaluating study limitations, results consistency, effect estimate precision, evidence directness, and publication bias. Results will be summarized in GRADE tables to present the strength of evidence for each finding. Analysis We will conduct a narrative synthesis of the included studies, structured according to the Synthesis Without Meta-Analysis (SWiM) reporting guideline 18 . Studies will be grouped based on key characteristics, including the type of pharmaceutical industry interaction, healthcare setting, professional group, and prescribing outcomes. The rationale for these groupings is to ensure conceptual clarity and comparability across diverse data sources. We will describe and justify the synthesis methods used to summarize the associations between pharmaceutical industry interactions and prescribing practices. This will include calculating summary statistics (e.g., ranges, medians, interquartile ranges) for key prescribing-related outcomes where appropriate and using vote counting based on the direction of effect to interpret patterns in cases where quantitative effect estimates cannot be pooled. Findings will be presented in tables and visual summaries, such as effect direction plots, to provide a clear and systematic representation of the results. The narrative will explore the broader implications of these findings on healthcare professionals’ knowledge, attitudes, and patient outcomes, identifying patterns and contrasts across study groups. Limitations of the synthesis, including heterogeneity in study design and outcome reporting, will be transparently documented. A quantitative synthesis (meta-analysis) will be conducted if at least two homogeneous studies examining the same outcomes in comparable settings are found 19 . If meta-analysis is undertaken, a random-effects model will be used to account for expected heterogeneity among study findings. The generic inverse variance method will be used to aggregate relative risks for binary outcomes and mean differences or standardized mean differences for continuous outcomes. Initially, meta-analyses will aggregate data across all types of interactions. Subsequently, to refine our understanding of their distinct impacts, we will perform stratified meta-analyses by interaction type, such as financial incentives or gifts. We will evaluate data heterogeneity both visually using forest plots and through a logical assessment of differences in study characteristics, such as design, to understand their impact on the results. Statistical heterogeneity will be quantified using the I² statistic, with values exceeding 50% indicating substantial heterogeneity 20 . When the meta-analysis includes ten or more studies, funnel plots will be employed to assess potential publication bias. This threshold is chosen because it typically provides a stable evaluation of funnel plot asymmetry and sufficient power to detect bias 21 . Unavailable outcome data will be recorded on the data extraction form and included in the risk of bias table. If primary outcomes cannot be assessed due to unavailable data and unsuccessful attempts to contact study authors, these studies will be reported separately. The reasons for excluding studies from meta-analysis will be described in the results and presented in a supplementary table. Subgroup analyses will explore the relationship between pharmaceutical industry interactions and prescribing patterns for specific groups. Subgroups of interest include healthcare professional types (e.g., physicians, nurse practitioners, pharmacists), medication class (e.g., opioids, gabapentinoids), and healthcare settings (e.g., hospital-based, general practice). These analyses aim to identify patterns and differences that may inform more tailored and context-specific conclusions. Discussion Prescribing practices in CNMP management are increasingly complex, particularly as the prevalence of multimorbidity and polypharmacy grows 22 . These complexities raise the potential for adverse outcomes, such as inappropriate medication use, dependency, or inadequate pain relief, which carry both economic and social consequences for patients and the broader healthcare system 23 . Addressing these challenges requires a concerted effort to promote safe and evidence-based prescribing practices, particularly in light of external influences that may further compromise patient safety such as pharmaceutical industry interactions. While it has been suggested that industry-sponsored education, for example, can improve prescribing knowledge, concerns remain about bias and over-reliance on industry-derived information 24 . Therefore, exploring these dynamics through a systematic review will provide valuable insights into how analgesic prescribing practices are shaped and will help inform the development of policies and guidelines that prioritize patient safety and evidence-based care. Strengths and limitations This systematic review will adhere to Cochrane guidance 14 , ensuring rigor and methodological integrity throughout the review process. To enhance transparency and mitigate the risk of selective reporting, the review has been prospectively registered on PROSPERO. Comprehensive searches will be conducted to reduce the potential impact of publication bias. Screening of titles and abstracts, full-text reviews, and methodological quality assessments will be conducted by two independent reviewers blinded to each other’s evaluations. This method reduces the potential for bias and decreases the chance of errors in the selection and evaluation of studies. This review acknowledges certain limitations inherent to the nature of observational studies it will include. Such studies may be subject to various biases, including selection and reporting biases, and often exhibit methodological heterogeneity. This variability can impact the consistency and generalizability of findings across different studies. While the review will seek to mitigate these issues through advanced meta-analytical techniques that adjust for study variability and potential biases, the heterogeneity of observational studies may still limit the ability to perform a quantitative synthesis of the findings. Potential implications for future research, policy and clinical practice This systematic review has the potential to identify significant gaps in the current understanding of how pharmaceutical industry interactions influence prescribing behaviors. These findings can guide future research efforts, particularly in developing interventions to mitigate undue industry influence on healthcare professionals. The review’s results may inform policy initiatives aimed at enhancing transparency and accountability in pharmaceutical industry engagements with healthcare professionals. Such policies could include stricter regulations on financial interactions or improved reporting mechanisms, fostering more ethical prescribing practices. For clinical practice, this review will provide a synthesized understanding of the dynamics between industry interactions and analgesic prescribing for chronic pain management. By highlighting both the benefits and risks of these interactions, healthcare professionals can make more informed decisions regarding the acceptance of industry support, ultimately improving prescribing quality, patient safety, and outcomes. Data availability Underlying data No data are associated with this article. Extended data Open Science Framework: Associations between Pharmaceutical Industry Interactions and Prescribing Practices in Chronic Non-Malignant Pain Management: A Protocol for a Systematic Review. Extended data. https://doi.org/10.17605/OSF.IO/DE32S 25 This project contains the following extended data: - Supplementary file 1: Search strategy. - Supplementary file 2: PRISMA-P 2015 checklist. - Supplementary file 3: Data extraction form. Reporting guidelines Open Science Framework: PRISMA-P checklist for ‘Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review’. https://doi.org/10.17605/OSF.IO/DE32S 25 Data are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication). Software availability Endnote and Covidence are proprietary software. Alternatives available for reference management and conducting literature and systematic reviews include Zotero and Rayyan, respectively. Acknowledgments We would like to acknowledge the support with developing the search string provided by Mr. Killian Walsh, Education, Research and Clinical Support, RCSI library. Faculty Opinions recommended References 1. Gureje O, Von Korff M, Simon GE, et al. : Persistent pain and well-being: a World Health Organization study in primary care. JAMA. 1998; 280 (2): 147–51. PubMed Abstract | Publisher Full Text 2. Surrey Clinical Commissioning Group: Guidelines for the pharmacological management of Chronic Non-Malignant Pain in primary care. 3. Birnbaum HG, White AG, Schiller M, et al. : Societal costs of prescription opioid abuse, dependence, and misuse in the United States. Pain Med. 2011; 12 (4): 657–67. PubMed Abstract | Publisher Full Text 4. Rufener L, Akre C, Rodondi PY, et al. : Management of chronic non-cancer pain by primary care physicians: a qualitative study. PLoS One. 2024; 19 (7): e0307701. PubMed Abstract | Publisher Full Text | Free Full Text 5. Brax H, Fadlallah R, Al-Khaled L, et al. : Association between physicians’ interaction with pharmaceutical companies and their clinical practices: a systematic review and meta-analysis. PLoS One. 2017; 12 (4): e0175493. PubMed Abstract | Publisher Full Text | Free Full Text 6. Zarei E, Ghaffari A, Nikoobar A, et al. : Interaction between physicians and the pharmaceutical industry: a scoping review for developing a policy brief. Front Public Health. 2023; 10 : 1072708. PubMed Abstract | Publisher Full Text | Free Full Text 7. Vajinepalli S: The hidden manipulation: the influence of pharmaceutical companies on physicians and researchers. New Brunswick (NJ): Rutgers University, 2020. Reference Source 8. Lundh A, Lexchin J, Mintzes B, et al. : Industry sponsorship and research outcome. Cochrane Database Syst Rev. 2017; 6 (2): MR000033. PubMed Abstract | Publisher Full Text | Free Full Text 9. Hadland SE, Cerdá M, Li Y, et al. : Association of pharmaceutical industry marketing of opioid products to physicians with subsequent opioid prescribing. JAMA Intern Med. 2018; 178 (6): 861–3. PubMed Abstract | Publisher Full Text | Free Full Text 10. Goel V, Patwardhan AM, Ibrahim M, et al. : Industry payments to pain medicine physicians: an analysis of the centers for medicare and medicaid services open payments program. Pain Med. 2021; 22 (6): 1376–86. PubMed Abstract | Publisher Full Text 11. Kolodny A, Courtwright DT, Hwang CS, et al. : The prescription opioid and heroin crisis: a public health approach to an epidemic of addiction. Annu Rev Public Health. 2015; 36 (1): 559–74. PubMed Abstract | Publisher Full Text 12. Fickweiler F, Fickweiler W, Urbach E: Interactions between physicians and the pharmaceutical industry generally and sales representatives specifically and their association with physicians’ attitudes and prescribing habits: a systematic review. BMJ Open. 2017; 7 (9): e016408. PubMed Abstract | Publisher Full Text | Free Full Text 13. A Learning Health System Activity, Roundtable on Value and Science-Driven Health Care; Institute of Medicine: Observational Studies in a Learning Health System: Workshop Summary. Washington (DC): National Academies Press (US), 2013. PubMed Abstract | Publisher Full Text 14. Higgins JPT, Thomas J, Chandler J, et al. : (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.5 (updated August 2024). Cochrane, 2024. Reference Source 15. Moher D, Shamseer L, Clarke M, et al. : Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement. Syst Rev. 2015; 4 (1): 1. PubMed Abstract | Publisher Full Text | Free Full Text 16. Sterne JA, Hernán MA, Reeves BC, et al. : ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016; 355 : i4919. PubMed Abstract | Publisher Full Text | Free Full Text 17. Schünemann H: Handbook for Grading the Quality of Evidence and the Strength of Recommendations Using the GRADE Approach. The GRADE Working Group, 2013. Reference Source 18. Campbell M, McKenzie JE, Sowden A, et al. : Synthesis Without Meta-Analysis (SWiM) in systematic reviews: reporting guideline. BMJ. 2020; 368 : l6890. PubMed Abstract | Publisher Full Text | Free Full Text 19. Deeks J, Higgins J, Altman D: Chapter 10: analysing data and undertaking meta-analyses. Cochrane Handbook for Systematic Reviews of Interventions . Reference Source 20. Chapter 9.5.2: Identifying and measuring heterogeneity. Cochrane Handbook for Systematic Reviews of Interventions. Reference Source 21. Chapter 10.4.3.1: Recommendations on testing for funnel plot asymmetry. Cochrane Handbook for Systematic Reviews of Interventions. Reference Source 22. Kennedy MC, Henman MC, Cousins G: General practitioners and Chronic Non-Malignant Pain management in older patients: a qualitative study. Pharmacy (Basel). 2016; 4 (1): 15. PubMed Abstract | Publisher Full Text | Free Full Text 23. Paulina Z: Chronic Non-Malignant Pain's impact on medical costs and work-related disability. J Pain Manage Ther. 2023; 7 (4): 153. Reference Source 24. Infeld M, Bell A, Marlin C, et al. : Continuing Medical Education and the marketing of fentanyl for breakthrough pain: marketing messages in an industry-funded CME module on breakthrough pain. World Medical & Health Policy. 2019; 11 (1): 43–58. Publisher Full Text 25. Gharbia M: Associations between Pharmaceutical Industry Interactions and Prescribing Practices in Chronic Non-Malignant Pain Management: A Protocol for a Systematic Review. [Dataset], Extended data, 2025. http://www.doi.org/10.17605/OSF.IO/DE32S Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 29 Jan 2025 ADD YOUR COMMENT Comment Author details Author details 1 Department of General Practice, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Dublin, Ireland 2 Department of General Practice, University College Cork, Cork, Ireland 3 School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Dublin, Ireland Mohammed Gharbia Roles: Conceptualization, Methodology, Project Administration, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Lydia Iladiva Roles: Writing – Review & Editing Frank Moriarty Roles: Conceptualization, Funding Acquisition, Methodology, Project Administration, Supervision, Visualization, Writing – Review & Editing Tom Fahey Roles: Conceptualization, Funding Acquisition, Methodology, Project Administration, Supervision, Visualization, Writing – Review & Editing James Larkin Roles: Conceptualization, Funding Acquisition, Methodology, Project Administration, Supervision, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information Health Research Board [HRB SPHeRE 3 - 2022/1]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (1) version 1 Published: 29 Jan 2025, 8:15 https://doi.org/10.12688/hrbopenres.14071.1 Copyright © 2025 Gharbia M et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics VIEWS $counts.viewCount downloads Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Gharbia M, Iladiva L, Moriarty F et al. Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review [version 1; peer review: 1 approved, 1 not approved] . HRB Open Res 2025, 8 :15 ( https://doi.org/10.12688/hrbopenres.14071.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 29 Jan 2025 Views 0 Cite How to cite this report: Nadeau SE. Reviewer Report For: Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review [version 1; peer review: 1 approved, 1 not approved] . HRB Open Res 2025, 8 :15 ( https://doi.org/10.21956/hrbopenres.15454.r50643 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-15/v1#referee-response-50643 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 22 Oct 2025 Stephen E. Nadeau , University of Florida, Gainesville, FL, USA Not Approved VIEWS 0 https://doi.org/10.21956/hrbopenres.15454.r50643 Gharbia and colleagues provide a protocol for systematic review and possibly meta-analysis of pharmaceutical industry impact on prescription of drugs for chronic non-malignant pain (CNMP). The impact of pharmaceutical industry promotions among clinicians and direct to consumer ... Continue reading READ ALL Gharbia and colleagues provide a protocol for systematic review and possibly meta-analysis of pharmaceutical industry impact on prescription of drugs for chronic non-malignant pain (CNMP). The impact of pharmaceutical industry promotions among clinicians and direct to consumer advertising certainly warrants thorough study to determine its effects on prescribing patterns. Just the impact of the industry on prescribing of drugs under patent in lieu of mechanistically comparable generic drugs could have major economic implications. Gharbia describe standard and well-accepted methodology for pursuing the systematic review and possible meta-analysis. It appears to me to be in order but I am not an expert on meta-analysis. I do have several concerns about the proposed study: 1. The prescription of drugs for CNMP in the United States is severely constrained by health care provider institutions (which can readily sever clinical privileges if prescriber practices deviate from the CDC Guidelines), the threat of DEA prosecution, laws passed by state legislatures, pharmacies, and health insurance companies. This raises the question: how much remaining variance is there that could possibly be impacted by pharmaceutical company promotion? 2. The number of analgesics, including opioids and gabapentinoids, has been static for some time and all of the drugs in common use are generic and inexpensive. To my knowledge, the last major drug that was introduced and promoted by Purdue Pharmaceuticals (while under patent) was Oxycontin. I cannot imagine that this drug is still under patent but even as a generic, the cost remains very high. Pharmaceutical companies have no financial interest in promoting inexpensive generics. 3. Table 1 explicitly states that studies will we included regardless of language or publication date. This is problematic. The United States, Canada, and European countries have somewhat differing approaches to use of opioids or other pharmaceuticals in treatment of CNMP. Furthermore, in the US, the closing of the pill mills by the states in 2010-2012 resulted in a sea change in prescribing patterns. Early studies suggested that the introduction of Oxycontin had a major impact but in retrospect, it is difficult to differentiate the influence of Purdue from the impact of pill mill practices. It is also now known that Mallinckrodt shipped 30 times as much opioids as did Purdue. Constraint of prescribing by pharmacies became evident in the late aughts and continues unabated to this date. The DEA, which for years eschewed any role in controlling physician practice, has grown very aggressive in prosecuting clinicians since CDC 2016. In short, constraints on clinician treatment of CNMP have been continuously evolving, even since 2012. All of this considered, I think the investigators should limit their study to publications dated later than 2012, and perhaps break this interval into two epochs, e.g., 2012-2018 and 2018-2025. They also would be well advised to limit their literature search to one country, e.g., the US. 4. The planned analysis is insufficiently specific. I strongly recommend that the investigators analyze a number of papers using the search terms they have list to better understand what they might be up against. In particular, the specific methodology of a meta-analysis, if it proves feasible, needs to be spelled out. 5. In the first paragraph of the introduction, the authors cite a 2011 reference (Birnbaum et al.) that seemed to anticipate the position the CDC Guideline, published in 2016. CDC 2016 was essentialy a political document masquerading as science (the authorship details are now pretty well known) and the document completely ignored the large body of robust science that bore on the subject of opioid use to treat CNMP. The CDC even ignored its own data [1] The investigators may want to take a look at three papers to get a completely scientific perspective: Nadeau SE, Lawhern RA. The two opioid crises. Problems, causes, and potential solutions: an analytic review. Medical Research Archives. 2023;11(12). Doi: 10.18103/mra.v11i12.4846; Nadeau SE, Lawhern RA. Use of opioids for chronic noncancer pain: a recapitulation of the science. Medical Research Archives. 2025;13(3). Doi: 10.18103/mra.v13i3.6412; Nadeau SE, Wu JK, Lawhern RA. Opioids and chronic pain: an analytic review of the clinical evidence. Frontiers in Pain Research. 2021;2(721357). Doi 10.3389/fpain.2021.721357). 6. p5 column 1 para 4: “vote counting.” I am unfamiliar with this as a scientific method. 7. p5 column 2 para 4. Citing a 2016 reference, the investigators state “Prescribing practices in CNMP management are increasingly complex, particularly as the prevalence of multimorbidity and polypharmacy grows.” I think a pretty good argument could be made to the contrary. Hemmed in by CDC Guideline limits and pressure from multiple other sources (cited above), even pain management physicians have retreated to rather stereotyped and limited regimens. Buprenorphine and buprenorphine/naloxone are ever more often prescribed because they tend to be safe harbors from the various authorities governing clinician behavior. The highly individualized, careful titration of opioids in an effort to maximize benefit and assure safety has given way to the CDC one-size fits all fiction. Gabapentinoids are ever more commonly used, even though multiple randomized controlled trials have shown lack of efficacy for chronic somatic pain. NSAID use as a “substitute” for opioids is very common. There has been a major shift to interventional pain techniques (epidural steroid injections, lateral branch blocks, spinal cord stimulators, etc.). Depression remains vastly under-detected and under-treated. Since CDC 2016 thoroughly stigmatized benzodiazepines for treatment of anxiety and insomnia (on the basis of no science at all), their use has become close to anathema. Likewise the use of often effective muscle relaxants such as carisoprodol. SUMMARY: I think there is a great deal of theoretical merit to this proposal but the potentially very serious problems detailed above need to be considered carefully and the proposal refined accordingly. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? No Are the datasets clearly presented in a useable and accessible format? No References 1. Aubry L, Carr B: Overdose, opioid treatment admissions and prescription opioid pain reliever relationships: United States, 2010–2019. Frontiers in Pain Research . 2022; 3 . Publisher Full Text 2. Nadeau S, Lawhern R: The Two Opioid Crises Problems, Causes, and Potential Solutions: An Analytic Review. Medical Research Archives . 2023; 11 (12). Publisher Full Text 3. Nadeau S, Lawhern R: Use of Opioids for Chronic Noncancer Pain. A Recapitulation of the Science. Medical Research Archives . 2025; 13 (3). Publisher Full Text 4. Nadeau S, Wu J, Lawhern R: Opioids and Chronic Pain: An Analytic Review of the Clinical Evidence. Frontiers in Pain Research . 2021; 2 . Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Cognitive neuroscience, computational neuroscience, treatment of chronic pain, basis for drug addiction I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Nadeau SE. Reviewer Report For: Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review [version 1; peer review: 1 approved, 1 not approved] . HRB Open Res 2025, 8 :15 ( https://doi.org/10.21956/hrbopenres.15454.r50643 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-15/v1#referee-response-50643 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Goetschi AN. Reviewer Report For: Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review [version 1; peer review: 1 approved, 1 not approved] . HRB Open Res 2025, 8 :15 ( https://doi.org/10.21956/hrbopenres.15454.r50641 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-15/v1#referee-response-50641 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 22 Oct 2025 Aljoscha Noël Goetschi , Bern University Hospital,, Bern, Switzerland Approved VIEWS 0 https://doi.org/10.21956/hrbopenres.15454.r50641 Review of the protocol: “Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review” by Gharbia et al. Thank you for the opportunity to review ... Continue reading READ ALL Review of the protocol: “Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review” by Gharbia et al. Thank you for the opportunity to review this protocol. The proposed systematic review aims to identify studies examining the association between prescribing patterns of analgesics and interactions with the pharmaceutical industry. This is an important topic, and the proposed methodology appears sound and well-conceived. I have a few minor comments, which I outline below. Introduction The introduction provides a concise yet comprehensive overview of the topic. I would suggest adding that pharmacological therapies are typically considered second-line therapy options in the management of chronic non-malignant pain. Emphasising this point could further highlight the importance of the review question, as pharmacological treatments in this context may often offer limited benefit or represent low-value care. Methods The methods are clearly described, appropriate, and provide sufficient detail to understand the planned review. However, I have two minor suggestions for clarification: It would be helpful to specify how analgesics will be defined. Based on the search strategy, it appears that co-analgesics (e.g., gabapentin) will also be included. Given that the classification of certain agents as co-analgesics can be ambiguous (e.g., bisphosphonates), clarification on inclusion criteria would strengthen the protocol. Do you plan to conduct any citation chasing or to search for grey literature to ensure a more comprehensive evidence base? Discussion The discussion adequately presents the potential impact of the review and appropriately addresses its strengths and limitations. I have no further comments in this section. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Chronic non-malignant pain, clinical pharmacy, geriatrics, implementation science, pharmacoepidemiology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Goetschi AN. Reviewer Report For: Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review [version 1; peer review: 1 approved, 1 not approved] . HRB Open Res 2025, 8 :15 ( https://doi.org/10.21956/hrbopenres.15454.r50641 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-15/v1#referee-response-50641 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 29 Jan 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 29 Jan 25 read read Aljoscha Noël Goetschi , Bern University Hospital,, Bern, Switzerland Stephen E. Nadeau , University of Florida, Gainesville, USA Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Nadeau S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 22 Oct 2025 | for Version 1 Stephen E. Nadeau , University of Florida, Gainesville, FL, USA 0 Views copyright © 2025 Nadeau S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Gharbia and colleagues provide a protocol for systematic review and possibly meta-analysis of pharmaceutical industry impact on prescription of drugs for chronic non-malignant pain (CNMP). The impact of pharmaceutical industry promotions among clinicians and direct to consumer advertising certainly warrants thorough study to determine its effects on prescribing patterns. Just the impact of the industry on prescribing of drugs under patent in lieu of mechanistically comparable generic drugs could have major economic implications. Gharbia describe standard and well-accepted methodology for pursuing the systematic review and possible meta-analysis. It appears to me to be in order but I am not an expert on meta-analysis. I do have several concerns about the proposed study: 1. The prescription of drugs for CNMP in the United States is severely constrained by health care provider institutions (which can readily sever clinical privileges if prescriber practices deviate from the CDC Guidelines), the threat of DEA prosecution, laws passed by state legislatures, pharmacies, and health insurance companies. This raises the question: how much remaining variance is there that could possibly be impacted by pharmaceutical company promotion? 2. The number of analgesics, including opioids and gabapentinoids, has been static for some time and all of the drugs in common use are generic and inexpensive. To my knowledge, the last major drug that was introduced and promoted by Purdue Pharmaceuticals (while under patent) was Oxycontin. I cannot imagine that this drug is still under patent but even as a generic, the cost remains very high. Pharmaceutical companies have no financial interest in promoting inexpensive generics. 3. Table 1 explicitly states that studies will we included regardless of language or publication date. This is problematic. The United States, Canada, and European countries have somewhat differing approaches to use of opioids or other pharmaceuticals in treatment of CNMP. Furthermore, in the US, the closing of the pill mills by the states in 2010-2012 resulted in a sea change in prescribing patterns. Early studies suggested that the introduction of Oxycontin had a major impact but in retrospect, it is difficult to differentiate the influence of Purdue from the impact of pill mill practices. It is also now known that Mallinckrodt shipped 30 times as much opioids as did Purdue. Constraint of prescribing by pharmacies became evident in the late aughts and continues unabated to this date. The DEA, which for years eschewed any role in controlling physician practice, has grown very aggressive in prosecuting clinicians since CDC 2016. In short, constraints on clinician treatment of CNMP have been continuously evolving, even since 2012. All of this considered, I think the investigators should limit their study to publications dated later than 2012, and perhaps break this interval into two epochs, e.g., 2012-2018 and 2018-2025. They also would be well advised to limit their literature search to one country, e.g., the US. 4. The planned analysis is insufficiently specific. I strongly recommend that the investigators analyze a number of papers using the search terms they have list to better understand what they might be up against. In particular, the specific methodology of a meta-analysis, if it proves feasible, needs to be spelled out. 5. In the first paragraph of the introduction, the authors cite a 2011 reference (Birnbaum et al.) that seemed to anticipate the position the CDC Guideline, published in 2016. CDC 2016 was essentialy a political document masquerading as science (the authorship details are now pretty well known) and the document completely ignored the large body of robust science that bore on the subject of opioid use to treat CNMP. The CDC even ignored its own data [1] The investigators may want to take a look at three papers to get a completely scientific perspective: Nadeau SE, Lawhern RA. The two opioid crises. Problems, causes, and potential solutions: an analytic review. Medical Research Archives. 2023;11(12). Doi: 10.18103/mra.v11i12.4846; Nadeau SE, Lawhern RA. Use of opioids for chronic noncancer pain: a recapitulation of the science. Medical Research Archives. 2025;13(3). Doi: 10.18103/mra.v13i3.6412; Nadeau SE, Wu JK, Lawhern RA. Opioids and chronic pain: an analytic review of the clinical evidence. Frontiers in Pain Research. 2021;2(721357). Doi 10.3389/fpain.2021.721357). 6. p5 column 1 para 4: “vote counting.” I am unfamiliar with this as a scientific method. 7. p5 column 2 para 4. Citing a 2016 reference, the investigators state “Prescribing practices in CNMP management are increasingly complex, particularly as the prevalence of multimorbidity and polypharmacy grows.” I think a pretty good argument could be made to the contrary. Hemmed in by CDC Guideline limits and pressure from multiple other sources (cited above), even pain management physicians have retreated to rather stereotyped and limited regimens. Buprenorphine and buprenorphine/naloxone are ever more often prescribed because they tend to be safe harbors from the various authorities governing clinician behavior. The highly individualized, careful titration of opioids in an effort to maximize benefit and assure safety has given way to the CDC one-size fits all fiction. Gabapentinoids are ever more commonly used, even though multiple randomized controlled trials have shown lack of efficacy for chronic somatic pain. NSAID use as a “substitute” for opioids is very common. There has been a major shift to interventional pain techniques (epidural steroid injections, lateral branch blocks, spinal cord stimulators, etc.). Depression remains vastly under-detected and under-treated. Since CDC 2016 thoroughly stigmatized benzodiazepines for treatment of anxiety and insomnia (on the basis of no science at all), their use has become close to anathema. Likewise the use of often effective muscle relaxants such as carisoprodol. SUMMARY: I think there is a great deal of theoretical merit to this proposal but the potentially very serious problems detailed above need to be considered carefully and the proposal refined accordingly. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? No Are the datasets clearly presented in a useable and accessible format? No References 1. Aubry L, Carr B: Overdose, opioid treatment admissions and prescription opioid pain reliever relationships: United States, 2010–2019. Frontiers in Pain Research . 2022; 3 . Publisher Full Text 2. Nadeau S, Lawhern R: The Two Opioid Crises Problems, Causes, and Potential Solutions: An Analytic Review. Medical Research Archives . 2023; 11 (12). Publisher Full Text 3. Nadeau S, Lawhern R: Use of Opioids for Chronic Noncancer Pain. A Recapitulation of the Science. Medical Research Archives . 2025; 13 (3). Publisher Full Text 4. Nadeau S, Wu J, Lawhern R: Opioids and Chronic Pain: An Analytic Review of the Clinical Evidence. Frontiers in Pain Research . 2021; 2 . Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Cognitive neuroscience, computational neuroscience, treatment of chronic pain, basis for drug addiction I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Nadeau SE. Peer Review Report For: Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review [version 1; peer review: 1 approved, 1 not approved] . HRB Open Res 2025, 8 :15 ( https://doi.org/10.21956/hrbopenres.15454.r50643) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://hrbopenresearch.org/articles/8-15/v1#referee-response-50643 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Goetschi A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 22 Oct 2025 | for Version 1 Aljoscha Noël Goetschi , Bern University Hospital,, Bern, Switzerland 0 Views copyright © 2025 Goetschi A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Review of the protocol: “Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review” by Gharbia et al. Thank you for the opportunity to review this protocol. The proposed systematic review aims to identify studies examining the association between prescribing patterns of analgesics and interactions with the pharmaceutical industry. This is an important topic, and the proposed methodology appears sound and well-conceived. I have a few minor comments, which I outline below. Introduction The introduction provides a concise yet comprehensive overview of the topic. I would suggest adding that pharmacological therapies are typically considered second-line therapy options in the management of chronic non-malignant pain. Emphasising this point could further highlight the importance of the review question, as pharmacological treatments in this context may often offer limited benefit or represent low-value care. Methods The methods are clearly described, appropriate, and provide sufficient detail to understand the planned review. However, I have two minor suggestions for clarification: It would be helpful to specify how analgesics will be defined. Based on the search strategy, it appears that co-analgesics (e.g., gabapentin) will also be included. Given that the classification of certain agents as co-analgesics can be ambiguous (e.g., bisphosphonates), clarification on inclusion criteria would strengthen the protocol. Do you plan to conduct any citation chasing or to search for grey literature to ensure a more comprehensive evidence base? Discussion The discussion adequately presents the potential impact of the review and appropriately addresses its strengths and limitations. I have no further comments in this section. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise Chronic non-malignant pain, clinical pharmacy, geriatrics, implementation science, pharmacoepidemiology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Goetschi AN. Peer Review Report For: Associations between pharmaceutical industry interactions and prescribing practices in chronic non-malignant pain management: A protocol for a systematic review [version 1; peer review: 1 approved, 1 not approved] . HRB Open Res 2025, 8 :15 ( https://doi.org/10.21956/hrbopenres.15454.r50641) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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