Financial conflicts of interest and disclosure in clinical practice guidelines for bipolar disorder and major depressive disorder in Japan

doi:10.21203/rs.3.rs-3570821/v1

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Financial conflicts of interest and disclosure in clinical practice guidelines for bipolar disorder and major depressive disorder in Japan

https://doi.org/10.21203/rs.3.rs-3570821/v1

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Clinical practice guidelines (CPGs) are essential for standardizing patient care based on evidence-based medicine. However, the presence of financial conflicts of interest (COIs) among CPG authors can undermine their credibility. This cross-sectional analysis of disclosed payments from pharmaceutical companies assesses the prevalence and magnitude of personal payments for lecturing, consulting, and writing to CPGs for bipolar disorder and major depressive disorder in Japan between 2016 and 2020. This study found that 93.5% of authors received payments over a five-year period, with total payments exceeding $4 million. The median payment per author was $49,422 (interquartile range: $7,792 – $111,567), with a notable concentration of payments among a small number of authors, including the CPG chairperson. Despite these extensive financial relationships, only a fraction of authors disclosed their COIs in the CPGs. These large amounts of personal payments were made by pharmaceutical companies manufacturing new antidepressants and sleeping aids listed in the CPGs. The findings highlight deviations from international COI management standards and suggest a need for more stringent COI policies for psychiatry CPGs in Japan.

Health sciences/Medical research/Epidemiology

Health sciences/Health care

Health sciences/Health care/Health care economics

Health sciences/Health care/Health policy

Health sciences/Health care/Medical ethics

Health sciences/Health care/Public health

Conflicts of interest

pharmaceutical companies

clinical practice guideline

health policy

evidence-based medicine

ethics

depression

bipolar disorder

Clinical practice guidelines (CPGs) have been increasingly used as a tool to endorse evidence-based medicine for healthcare professionals in their clinical practice[1, 2]. CPGs are developed based on the best available evidence and include recommendations for diagnosis and treatment of specific diseases. Nevertheless, the integrity and recommendations of CPGs are frequently compromised by conflicts of interest (COIs) between the guideline authors and the pharmaceutical industry, spanning various medical specialties. In the field of psychiatry, there is substantial documentation of ghostwriting by pharmaceutical industry[3] and widespread financial COIs between CPG authors and pharmaceutical companies[4–7]. Furthermore, studies showed that financial COIs are associated with a propensity for CPGs to make recommendations favorable to the healthcare industry[4, 8]. This underscores the necessity for rigorous management of financial COIs among CPG authors, particularly in psychiatry[6, 9, 10].

To enhance the transparency of financial relationships between healthcare professionals and pharmaceutical companies, members of the Japan Pharmaceutical Manufacturers Association have voluntarily disclosed their financial interactions with healthcare professionals and organizations[11]. Subsequent research using this disclosed information has revealed that the vast majority of CPG authors in Japan received personal payments during the CPG development across various medical specialties[11–21]. However, the specifics of these financial relationships between pharmaceutical companies and Japanese CPG authors in psychiatry remain largely unexplored. Considering the patterns observed in previous studies, we hypothesized that financial COIs are widespread among psychiatry CPG authors in Japan.

Study setting, participants, and data collection

This cross-sectional analysis evaluated the extent and prevalence of financial interactions between pharmaceutical companies and authors of CPGs for major depressive disorder and bipolar disorder in Japan. The Japanese Society of Mood Disorders is responsible for the development of the sole CPGs for these conditions, namely Treatment Guideline I: Bipolar Disorder[22] and Treatment Guideline II: Major Depressive Disorder[23]. At the time of this study, the latest versions were published in June 2020 and July 2019, respectively.

The Japan Pharmaceutical Manufacturers Association, representing over 70 major pharmaceutical companies, mandates the disclosure of payments for lectures, consultancy, and writing to healthcare professionals, listing the recipients' names on company websites since 2013[24–26]. Despite annual updates and removal of previous years' data by these companies, the Medical Governance Research Institute has independently collected and disclosed this payment data on its public online database from 2016 to 2020, detailing individual physician and company contributions[27]. As the pharmaceutical companies have not individually disclosed other categories of non-research payments such as travel and accommodation fees, food and beverage fees, and royalties and ownership payments, this study incorporated all personal payments for lectures, consultancy, and writing from pharmaceutical companies to the psychiatry CPG authors from 2016 to 2020, following the approach of prior studies[28–31].

Data analysis

The study calculated the proportion of CPG authors receiving personal payments and assessed per-author payment amounts, including median, interquartile range, mean, and standard deviation. Payments were converted from Japanese yen to U.S. dollars using the 2020 average monthly exchange rate of 106.8 yen per $1. Data extraction and analyses were executed using Python 3.9.12 (Python Software Foundation, Beaverton, OR, USA), Microsoft Excel, version 16.0 (Microsoft Corp., Redmond, WA, USA), and Stata version 17.0 (StataCorp, College Station, TX, USA).

Use of large language model in the drafting

During the preparation of this work, the authors used ChatGPT version 4.0 to check and correct grammatical and spelling errors. After using this tool, the authors carefully reviewed and edited the content as needed and takes full responsibility for the content of the publication.

Ethical clearance

As a retrospective analysis of publicly available data, this study was classified as non-human subjects research and did not require institutional review board approval. The methodology adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline.

The study included 29 authors for the bipolar disorder CPG and 42 for the major depressive disorder CPG, with 25 individuals contributing to both. Consequently, 46 unique CPG authors were analyzed (Table 1). Disclosure of financial COIs within the CPGs was self-reported solely by the writing authors. All authors (100%, 4 out of 4) associated with the bipolar disorder CPG and 85.7% (12 out of 14) with the major depressive disorder CPG declared financial COIs with pharmaceutical companies.

A significant majority, 43 authors (93.5%), received personal payments for lectures, consulting, and writing from pharmaceutical companies between 2016 and 2020 (Table 2). The cumulative personal payments amounted to $4,043,436 from 55 pharmaceutical companies over this period. The median payment per author was $49,422 (IQR: $7,792 – $111,567), and the mean payment was $87,901 (SD: $111,270), indicating a skewed distribution where a few authors received disproportionately high payments. Notably, 15 authors (32.6%) received in excess of $100,000 over five years. The chairperson of the guideline development committee received the highest total payment of $506,108 for lecturing, consulting, and writing from pharmaceutical companies during this time. Payments for lecturing constituted $2.7 million (65.8% of the total), with consulting and writing making up 25.8% ($1.0 million) and 8.3% ($337,255), respectively.

Annual analysis revealed a decline in total payments to CPG authors from $959,503 in 2016 to $697,170 in 2020 (Table 2). Correspondingly, the median annual payment per author decreased from $11,865 (IQR: $1,773 – $24,498) in 2016 to $2,693 (IQR: $0 – $22,968) in 2020. The proportion of authors receiving payments also fell from 91.3% in 2017 to 73.9% in 2020, yet a majority still received at least one personal payment annually.

Payments from the top 5 and 10 pharmaceutical companies constituted 53.3% ($2.2 million) and 83.1% ($3.4 million) of the total payments, respectively (Table 3). Sumitomo Pharma was the most generous, contributing $695,031 (17.2%), followed by Eisai (10.1%, $408,323), MSD (8.8%, $357,526), Otsuka Pharmaceutical (8.8%, $354,638), and Takeda Pharmaceutical (8.3%, $337,370). Among these, MSD, Pfizer Japan, and Meiji Seika notably reduced their non-research payments from 2016 to 2020, whereas Eisai increased its payments from $45,779 in 2016 to $151,856 in 2020.

Table 4 presents the types of financial COIs self-reported by the CPG authors within each respective guideline. Among the six categories extracted from the CPG disclosures, compensation for lecturing was the most frequently declared (100% for the bipolar disorder CPG and 78.6% for the major depressive disorder CPG). This was followed by scholarship donations and participation in pharmaceutical company advisory boards. The lack of a specified declaration period precluded the assessment of the accuracy of each CPG author's self-reported COI status against the payment data released by the pharmaceutical companies.

This cross-sectional analysis of publicly disclosed payment data from pharmaceutical companies provides a detailed examination of the extent and prevalence of financial COIs among authors of the Japanese Society of Mood Disorders' Treatment Guideline I: Bipolar Disorder[22] and Treatment Guideline II: Major Depressive Disorder[23]. These CPGs are considered by physicians the authoritative and trustworthy sources for the treatment of bipolar disorder and major depressive disorder in Japan[32]. To the best of our knowledge, this is the first in-depth study to analyze the financial relationships between psychiatry CPG authors and pharmaceutical companies in Japan using disclosed payment data. The findings reveal that a significant majority (93.5%) of CPG authors received personal payments for lecturing, consulting, and writing, with a total sum of $4.0 million between 2016 and 2020. The median payment per author was $49,422, with a minority, including the CPG chairperson, receiving substantial sums. Nearly all authors involved in writing the CPGs self-reported financial COIs with pharmaceutical companies. Notably, the bulk of personal payments to CPG authors came from companies that manufacture antidepressants and sleeping pills in Japan. However, other CPG authors did not publicly disclose their financial COIs with these companies. When compared to previous studies and international COI policies for CPG authors, these findings raise concerns for physicians, patients, policymakers, and other stakeholders within and beyond Japan.

The study highlights that over 93% of the authors of CPGs for bipolar disorder and major depressive disorder had financial relationships with pharmaceutical companies. Given the publication dates of the CPGs between 2019 and 2020, these financial relationships likely occurred during the development of the CPGs. This high percentage of authors receiving personal payments aligns with findings from other specialties within Japan[11–14, 16–19, 21, 33–36], where the proportion of CPG authors with personal payments ranged from 86.4% in cardiology[37] to 94.6% in hematology[13].

In contrast, research from other developed countries, such as the United States, reports lower proportions of CPG authors with financial COIs. For instance, 67% of authors for the DSM-5 mood disorders section disclosed financial COIs with the healthcare industry[9]. Additionally, a study by Cosgrove et al. found that only 18% of major depressive disorder CPG authors across eight countries had financial COIs with pharmaceutical companies[4, 10]. In Canada, half of the authors of the CPG for depressive disorder developed by the Canadian Network for Mood and Anxiety Treatments reported financial COIs with the healthcare industry[38]. Other specialties in the United States also showed lower percentages, with 53% of gastroenterology CPG authors[39] and 59.3% of urology CPG authors receiving personal and/or research payments[40]. Moreover, Mooghali et al. reported that 73.7% of physician CPG authors in the United States received personal and/or research payments from healthcare companies[41].

Furthermore, this investigation revealed that a select group of CPG authors, including the chairperson, received substantial personal payments from pharmaceutical companies. Only authors involved in writing the CPGs were mandated to declare their financial COIs, while other contributors did not publicly disclose any financial COIs with these companies. These results indicate that authors of Japanese CPGs for bipolar disorder and major depressive disorder clearly violate international COI policies on CPG development in several respects. The U.S. National Academy of Medicine's 2011 report and the Guidelines International Network advocate for a majority of CPG authors to be free from financial COIs[1, 2]. These policies also stipulate that the chairperson of CPG development should not hold any COIs[1, 2]. The Guideline Panel Review Working Group's criteria for red flags, as published in the British Medical Journal in 2013, indicate that financial COIs held by a CPG chairperson and multiple authors are significant concerns for the trustworthiness of the CPGs[42]. The prevalence of COIs exceeding 93% in this study is not a marginal discrepancy but a significant deviation from these standards, casting doubt on the objectivity and reliability of the guidelines.

Moreover, the study uncovered that substantial payments were made by pharmaceutical companies marketing new antidepressants and sleep aids in Japan. For example, Sumitomo Pharma, the top paying company, manufactures lurasidone (brand name: Latuda), approved for bipolar disorder and schizophrenia in 2020, and co-promotes venlafaxine hydrochloride (brand name: Effexor) with Pfizer Japan since 2018. MSD, another major payer, produces suvorexant (brand name: Belsomra), the world’s first orexin receptor antagonist. Otsuka Pharmaceutical is noted for one of the major manufacturers of atypical antipsychotic medications such as aripiprazole (brand name: Abilify) and brexpiprazole (brand name: Rexulti) which are the most widely prescribed atypical antipsychotic drugs in Japan[43]. Despite these financial ties between the CPG authors and the pharmaceutical companies, the Japanese Society of Mood Disorders actively endorses adherence to these CPGs[44, 45]. Considering that the CPGs for bipolar disorder and major depressive disorder include pharmacotherapy recommendations involving drugs from these companies, it is imperative to address the close financial relationships between CPG authors and the pharmaceutical industry. We strongly recommend the Japanese Society of Mood Disorders to enforce more transparent and stringent COI management strategies in the CPG development process for bipolar disorder and major depressive disorder, ensuring the integrity and credibility of these guidelines.

This study is subject to several limitations. Primarily, the study focus on CPGs for bipolar disorder and major depressive disorder in Japan would limit the generalizability of our findings to other medical fields or countries. Additionally, the payment data were derived from a secondary source, the Medical Governance Research Institute's database, which contains payment information from member companies of the Japan Pharmaceutical Manufacturers Association for the period 2016–2020[25, 46]. Absent legal mandates for precise payment disclosures in Japan, the potential for inaccuracies or underreporting in the database cannot be discounted. Furthermore, the voluntary nature of these disclosures means that financial interactions between CPG authors and non-disclosing pharmaceutical entities may remain undetected. Nevertheless, given that the member companies account for 80% of the market share for drugs and medical products in Japan[47], the impact of financial relationships between the CPG authors and uncovered companies would be minimized.

More than 93% of the authors of the Treatment Guidelines for Bipolar Disorder and Major Depressive Disorder developed by the Japanese Society of Mood Disorders received personal payments for the reimbursement of their lecturing, consulting, and writing activities from the pharmaceutical companies manufacturing related drugs. The total amounts of personal payments to the CPG authors were more than $4.0 million over the five years. Nevertheless, the financial COIs were only declared by the limited group of CPG authors. Further transparent and rigorous COI management strategies must be warranted in the Japanese Society of Mood Disorders.

Author contribution:

A.M. contributed to data collection, resource, software, formal analysis, visualization, supervision, and study administration. All authors (A.M., H.K., and Y.S.) contributed to study conceptualization, methodology, writing the original draft, and reviewing the draft.

Conflicts of interest:

The authors declare that there were no conflicts of interest for this study.

Funding sources:

The authors declare that there were no funding sources for this study.

IRB Statement

As this study was a retrospective analysis of publicly available data and met the definition of non-human subjects research, no institutional board review and approval were required. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline.

Declaration of generative AI in scientific writing

Data availability statement:

All data used in this study is available from Yen For Docs database run by Medical Governance Research Institute (https://yenfordocs.jp/) and each pharmaceutical companies belonging to the Japan Pharmaceutical Manufacturers Association.

Acknowledgments

The authors appreciate Ms Megumi Aizawa for her dedicated support of my research project. During the preparation of this work, the authors used ChatGPT version 4.0 to check and correct grammatical and spelling errors. After using this tool, the authors carefully reviewed and edited the content as needed and takes full responsibility for the content of the publication.

Schunemann HJ, Al-Ansary LA, Forland F, Kersten S, Komulainen J, Kopp IB, et al. Guidelines International Network: Principles for Disclosure of Interests and Management of Conflicts in Guidelines. Ann Intern Med. 2015;163(7):548–53.
Institute of Medicine. Clinical Practice Guidelines We Can Trust. Graham R, Mancher M, Wolman DM, Greenfield S, Steinberg E, editors. Washington, DC: The National Academies Press; 2011. 290 p.
Roehr B. Professor files complaint of scientific misconduct over allegation of ghostwriting. BMJ. 2011;343:d4458.
Cosgrove L, Shaughnessy AF, Peters SM, Lexchin JR, Bursztajn H, Bero L. Conflicts of Interest and the Presence of Methodologists on Guideline Development Panels: A Cross-Sectional Study of Clinical Practice Guidelines for Major Depressive Disorder. Psychother Psychosom. 2017;86(3):168–70.
Cosgrove L, Krimsky S, Vijayaraghavan M, Schneider L. Financial ties between DSM-IV panel members and the pharmaceutical industry. Psychother Psychosom. 2006;75(3):154–60.
Cosgrove L, Bursztajn HJ, Krimsky S. Developing Unbiased Diagnostic and Treatment Guidelines in Psychiatry. New England Journal of Medicine. 2009;360(19):2035–6.
Cosgrove L, Bursztajn HJ, Krimsky S, Anaya M, Walker J. Conflicts of Interest and Disclosure in the American Psychiatric Association’s Clinical Practice Guidelines. Psychotherapy and Psychosomatics. 2009;78(4):228–32.
Nejstgaard CH, Bero L, Hrobjartsson A, Jorgensen AW, Jorgensen KJ, Le M, Lundh A. Association between conflicts of interest and favourable recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews: systematic review. BMJ. 2020;371:m4234.
Cosgrove L, Krimsky S. A Comparison of DSM-IV and DSM-5 Panel Members' Financial Associations with Industry: A Pernicious Problem Persists. PLOS Medicine. 2012;9(3):e1001190.
Cosgrove L, Krimsky S, Wheeler EE, Peters SM, Brodt M, Shaughnessy AF. Conflict of Interest Policies and Industry Relationships of Guideline Development Group Members: A Cross-Sectional Study of Clinical Practice Guidelines for Depression. Accountability in Research. 2017;24(2):99–115.
Murayama A, Ozaki A, Saito H, Sawano T, Shimada Y, Yamamoto K, et al. Pharmaceutical company payments to dermatology Clinical Practice Guideline authors in Japan. PLoS One. 2020;15(10):e0239610.
Kida F, Murayama A, Saito H, Ozaki A, Shimada Y, Tanimoto T. Pharmaceutical company payments to authors of the Japanese Clinical Practice Guidelines for Hepatitis C treatment. Liver Int. 2021;41(3):464–9.
Harada K, Ozaki A, Saito H, Sawano T, Yamamoto K, Murayama A, et al. Financial payments made by pharmaceutical companies to the authors of Japanese hematology clinical practice guidelines between 2016 and 2017. Health Policy. 2021;125(3):320–6.
Hashimoto T, Murayama A, Mamada H, Saito H, Tanimoto T, Ozaki A. Evaluation of financial conflicts of interest and drug statements in the coronavirus disease 2019 clinical practice guideline in Japan. Clin Microbiol Infect. 2022;28(3):460–2.
Kamamoto S, Murayama A, Kusumi E, Yoshida M, Saito H, Sawano T, et al. Evaluation of financial relationships between Japanese certified pediatric hematologist/oncologists and pharmaceutical companies: a cross-sectional analysis of personal payments from pharmaceutical companies between 2016 and 2019. Pediatr Blood Cancer. 2022;69(10):e29891.
Murayama A, Kida F, Ozaki A, Saito H, Sawano T, Tanimoto T. Financial and Intellectual Conflicts of Interest Among Japanese Clinical Practice Guidelines Authors for Allergic Rhinitis. Otolaryngol Head Neck Surg. 2022;166(5):869–76.
Murayama A, Yamada K, Yoshida M, Kaneda Y, Saito H, Sawano T, et al. Evaluation of Conflicts of Interest among Participants of the Japanese Nephrology Clinical Practice Guideline. Clin J Am Soc Nephrol. 2022;17(6):819–26.
Mamada H, Murayama A, Kamamoto S, Kaneda Y, Yoshida M, Sugiura S, et al. Evaluation of Financial and Nonfinancial Conflicts of Interest and Quality of Evidence Underlying Psoriatic Arthritis Clinical Practice Guidelines: Analysis of Personal Payments From Pharmaceutical Companies and Authors' Self-Citation Rate in Japan and the United States. Arthritis Care Res (Hoboken). 2023;75(6):1278–86.
Murayama A, Kamamoto S, Murata N, Yamasaki R, Yamada K, Yamashita E, et al. Evaluation of financial conflicts of interest and quality of evidence in Japanese gastroenterology clinical practice guidelines. J Gastroenterol Hepatol. 2023;38(4):565–73.
Murayama A. Financial Conflicts of Interest Among the Authors of the Clinical Practice Guidelines for Rheumatoid Arthritis in Japan. Cureus. 2023;15(10):e46650.
Yamamoto K, Murayama A, Ozaki A, Saito H, Sawano T, Tanimoto T. Financial conflicts of interest between pharmaceutical companies and the authors of urology clinical practice guidelines in Japan. Int Urogynecol J. 2021;32(2):443–51.
Japanese Society of Mood Disorders. Treatment Guideline I: Bipolar Disorder Online: Japanese Society of Mood Disorders; 2020 [updated June 16, 2020. 4th edition:[Available from: https://www.secretariat.ne.jp/jsmd/iinkai/katsudou/data/guideline_sokyoku2020.pdf.
Japanese Society of Mood Disorders. Treatment Guideline II: Major Depressive Disorder Online: Japanese Society of Mood Disorders; 2019 [2nd edition:[Available from: https://www.secretariat.ne.jp/jsmd/iinkai/katsudou/data/20190724-02.pdf.
Ozaki A, Saito H, Senoo Y, Sawano T, Shimada Y, Kobashi Y, et al. Overview and transparency of non-research payments to healthcare organizations and healthcare professionals from pharmaceutical companies in Japan: Analysis of payment data in 2016. Health Policy. 2020;124(7):727–35.
Murayama A, Kamamoto S, Saito H, Yamashita E, Suzuki Y, Tanimoto T, et al. Characteristics and Distribution of Scholarship Donations From Pharmaceutical Companies to Japanese Healthcare Institutions in 2017: A Cross-sectional Analysis. International Journal of Health Policy and Management. 2023;12.
Murayama A, Kamamoto S, Saito H, Yamada K, Bhandari D, Shoji I, et al. Pharmaceutical Payments to Japanese Board-Certified Infectious Disease Specialists: A Four-Year Retrospective Analysis of Payments from 92 Pharmaceutical Companies between 2016 and 2019. Int J Environ Res Public Health. 2022;19(12):7417.
Medical Governance Research Institute, Tansa. Yen For Docs [Online database]. Medical Governance Research Institute; 2023 [updated September 11, 2023. Available from: https://yenfordocs.jp/.
Murayama A, Kamamoto S, Saito H, Ozaki A. Pharmaceutical payments to Japanese board-certified dermatologists: a 4-year retrospective analysis of personal payments from pharmaceutical companies between 2016 and 2019. Sci Rep. 2023;13(1):7425.
Murayama A, Saito H, Kamamoto S, Shigeta H, Yamashita E, Tanimoto T, Ozaki A. Evaluation of non-research payments from pharmaceutical companies to urologists in Japan between 2016 and 2019. Int Urogynecol J. 2023;34(6):1285–92.
Kusumi E, Murayama A, Kamamoto S, Kawashima M, Yoshida M, Saito H, et al. Pharmaceutical payments to Japanese certified hematologists: a retrospective analysis of personal payments from pharmaceutical companies between 2016 and 2019. Blood Cancer J. 2022;12(4):54.
Murayama A, Hoshi M, Saito H, Kamamoto S, Tanaka M, Kawashima M, et al. Nature and Trends in Personal Payments Made to the Respiratory Physicians by Pharmaceutical Companies in Japan between 2016 and 2019. Respiration. 2022;101(12):1088–98.
Numata S, Nakataki M, Hasegawa N, Takaesu Y, Takeshima M, Onitsuka T, et al. Improvements in the degree of understanding the treatment guidelines for schizophrenia and major depressive disorder in a nationwide dissemination and implementation study. Neuropsychopharmacology Reports. 2021;41(2):199–206.
Murayama A, Kamamoto S, Shigeta H, Saito H, Yamashita E, Tanimoto T, Akihiko O. Undisclosed financial conflicts of interest with pharmaceutical companies among the authors of the Esophageal Cancer Practice Guidelines 2017 by the Japan Esophageal Society. Dis Esophagus. 2022;35(10).
Murayama A. Financial Conflicts of Interest Among the Authors of the Clinical Practice Guidelines for Rheumatoid Arthritis in Japan. Cureus. 2023;15(10).
Murayama A, Mamada H, Shigeta H, Yoshinaga T, Saito H, Yamashita E, et al. Financial Relationships Between Pharmaceutical Companies and Rheumatologists in Japan Between 2016 and 2019. J Clin Rheumatol. 2023;29(3):118–25.
Kamamoto S, Ozaki A, Murayama A. Assessment of Financial Relationships Between Otorhinolaryngologists and Pharmaceutical Companies in Japan Between 2016 and 2019. Cureus. 2023;15(8):e43633.
Senoo Y, Saito H, Ozaki A, Sawano T, Shimada Y, Yamamoto K, et al. Pharmaceutical company payments to authors of the Japanese guidelines for the management of hypertension. Medicine (Baltimore). 2021;100(12):e24816.
Elder K, Turner KA, Cosgrove L, Lexchin J, Shnier A, Moore A, et al. Reporting of financial conflicts of interest by Canadian clinical practice guideline producers: a descriptive study. CMAJ. 2020;192(23):E617-E25.
Combs TR, Scott J, Jorski A, Heavener T, Vassar M. Evaluation of Industry Relationships Among Authors of Clinical Practice Guidelines in Gastroenterology. JAMA Intern Med. 2018;178(12):1711–2.
Carlisle A, Bowers A, Wayant C, Meyer C, Vassar M. Financial Conflicts of Interest Among Authors of Urology Clinical Practice Guidelines. Eur Urol. 2018;74(3):348–54.
Mooghali M, Glick L, Ramachandran R, Ross JS. Financial conflicts of interest among US physician authors of 2020 clinical practice guidelines: a cross-sectional study. BMJ Open. 2023;13(1):e069115.
Lenzer J, Hoffman JR, Furberg CD, Ioannidis JP, Guideline Panel Review Working G. Ensuring the integrity of clinical practice guidelines: a tool for protecting patients. BMJ. 2013;347:f5535.
Jiho. Yakuji Handbook 2021: Jiho; 2021.
Takaesu Y, Watanabe K, Numata S, Iwata M, Kudo N, Oishi S, et al. Improvement of psychiatrists’ clinical knowledge of the treatment guidelines for schizophrenia and major depressive disorders using the ‘Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)’ project: A nationwide dissemination, education, and evaluation study. Psychiatry and Clinical Neurosciences. 2019;73(10):642–8.
Kodaka F, Ohi K, Yasuda Y, Fujimoto M, Yamamori H, Hasegawa N, et al. Relationships Between Adherence to Guideline Recommendations for Pharmacological Therapy Among Clinicians and Psychotic Symptoms in Patients With Schizophrenia. Int J Neuropsychopharmacol. 2023;26(8):557–65.
Ozieranski P, Saito H, Rickard E, Mulinari S, Ozaki A. International comparison of pharmaceutical industry payment disclosures in the UK and Japan: implications for self-regulation, public regulation, and transparency. Global Health. 2023;19(1):14.
Japan Pharmaceutical Manufacturers Association. Data Book 2023 2023 [Available from: https://www.jpma.or.jp/news_room/issue/databook/en/rfcmr00000000an3-att/DATABOOK2023_en.pdf.

Table 1. Demographic characteristics of clinical practice guideline authors for bipolar disorder and major depressive disorder

Variables	Guideline disease category		Overall
Variables	Bipolar disorder	Major depressive disorder	Overall
Number of authors	29	42	46
Role of guideline authors
Writing authors	4 (13.8)	14 (33.3)	Not calculated
Supporting authors	5 (17.2)	11 (26.2)	Not calculated
Guideline development committee authors	20 (69.0)	17 (40.5)	Not calculated
Number of authors with self-declared conflicts of interest, n (%)^a	4 (100)	12 (85.7)	Not calculated

^a Conflicts of interest were only declared by writing authors.

Table 2. Summary of personal payments from pharmaceutical companies to psychiatry clinical practice guideline authors between 2016 and 2020

Variables	2016	2017	2018	2019	2020	Total amounts
Total amount of payments, $	959,503	873,288	769,649	743,826	697,170	4,043,436
Mean payments per author (standard deviation), $	20,859 (27,155)	18,985 (24,259)	16,732 (24,649)	16,170 (21,256)	15,156 (22,221)	87,901 (111,270)
Median payments per author (interquartile range), $	11,865 (1,773 – 24,498)	10,239 (1,517 – 25,058)	2,294 (521 – 6,465)	4,476 (531 – 26,830)	2,693 (0 – 22,968)	49,422 (7,792 ‒ 111,567)
Maximum, $	120,927	100,635	114,153	107,553	94,362	506,108
Authors with payments (N=46), n (%)
Any payments	40 (87.0)	42 (91.3)	36 (78.3)	38 (82.6)	34 (73.9)	43 (93.5)
>$10,000	24 (52.2)	23 (50.0)	20 (43.5)	22 (47.8)	19 (41.3)	33 (71.7)
>$50,000	6 (13.0)	5 (10.9)	4 (8.7)	2 (4.4)	3 (6.5)	23 (50.0)
>$100,000	1 (2.2)	1 (2.2)	1 (2.2)	1 (2.2)	0 (0)	15 (32.6)
>$250,000	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	3 (6.5)

Japanese yen (¥) were converted to US dollars ($) using the 2020 average monthly exchange rate of ¥106.8 per $1.

Table 3. Payment amounts by top 10 companies.

Variables	Payment amounts (%), $
Variables	2016	2017	2018	2019	2020	Overall
Total amounts of payments	959,503 (100)	873,288 (100)	769,649 (100)	743,826 (100)	697,170 (100)	4,041,648 (100)
Top 10 companies making the largest payment amounts
Sumitomo Pharma	180,436 (18.8)	105,531 (12.1)	127,847 (16.6)	106,975 (14.4)	174,243 (25.0)	695,031 (17.2)
Eisai	45,779 (4.8)	78,418 (9.0)	52,244 (6.8)	80,026 (10.8)	151,856 (21.8)	408,323 (10.1)
MSD	122,880 (12.8)	83,528 (9.6)	79,420 (10.3)	57,679 (7.8)	14,020 (2.0)	357,526 (8.8)
Otsuka Pharmaceutical	64,794 (6.8)	73,028 (8.4)	64,161 (8.3)	86,679 (11.7)	65,976 (9.5)	354,638 (8.8)
Takeda Pharmaceutical	69,017 (7.2)	78,990 (9.0)	45,019 (5.8)	71,206 (9.6)	73,138 (10.5)	337,370 (8.3)
Pfizer Japan	78,269 (8.2)	106,973 (12.2)	65,996 (8.6)	46,086 (6.2)	14,247 (2.0)	311,571 (7.7)
Mitsubishi Tanabe Pharma	58,501 (6.1)	47,295 (5.4)	61,056 (7.9)	59,114 (7.9)	25,789 (3.7)	251,755 (6.2)
Eli Lilly Japan	56,337 (5.9)	60,899 (7.0)	59,231 (7.7)	36,314 (4.9)	38,130 (5.5)	250,910 (6.2)
Meiji Seika Pharma	75,608 (7.9)	53,110 (6.1)	57,841 (7.5)	27,228 (3.7)	24,235 (3.5)	238,023 (5.9)
Mochida Pharmaceutical	35,768 (3.7)	29,405 (3.4)	31,597 (4.1)	41,378 (5.6)	17,209 (2.5)	155,356 (3.8)

Table 4. Financial conflicts of interest self-declared by the guideline authors

Disclosure category	Number of authors reporting conflicts of interest (%), n
Disclosure category	Bipolar disorder (N=4)	Major depressive disorder (N=14)
Speaking compensation	4 (100)	11 (78.6)
Scholarship donation	3 (75.0)	6 (42.9)
Consulting payments	0 (0)	4 (28.6)
Collaborative research funds	1 (25.0)	2 (14.3)
Advisory board	2 (50.0)	1 (7.1)
Contracted research funds	1 (25.0)	0 (0)

Legends: Proportion of authors reporting conflicts of interest were number of authors reporting conflicts of interest to the total number of writing authors

No competing interests reported.

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Financial conflicts of interest and disclosure in clinical practice guidelines for bipolar disorder and major depressive disorder in Japan

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Abstract

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Study setting, participants, and data collection

Data analysis

Use of large language model in the drafting

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