Increasing Trends of Pharmaceutical Payments to Breast Cancer Specialists in Japan: A Retrospective Study from 2016 to 2019

Increasing Trends of Pharmaceutical Payments to Breast Cancer Specialists in Japan: A Retrospective Study from 2016 to 2019 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Increasing Trends of Pharmaceutical Payments to Breast Cancer Specialists in Japan: A Retrospective Study from 2016 to 2019 Yudai Kaneda, Erika Yamashita, Hiroaki Saito, Kenji Gonda, Masahiro Wada, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3915980/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: The interplay between pharmaceutical companies and healthcare professionals is a critical facet of modern medicine, with financial relationships often influencing clinical practice. This study examines its impact on clinical practice in Japan, particularly in breast cancer treatment. It aims to uncover the prevalence, magnitude, and trends of payments made to breast cancer specialists by the pharmaceutical industry, thereby increasing transparency in these financial interactions. Methods: A retrospective analysis included breast cancer specialists certified by the Japanese Breast Cancer Society as of May 2023. Payment data from 2016 to 2019 were collected from 93 pharmaceutical companies in the Japan Pharmaceutical Manufacturers Association, focusing on payments for lecturing, writing, and consulting. Results: The analysis revealed an upward trend in pharmaceutical payments, with a total of USD 13,329,910.57 between 2016 and 2019, reflecting an average annual growth rate of 10.1%. The majority of these payments (81.4%) were for speaking engagements. The top 10 pharmaceutical companies made 89.5% of the total payments, with a spike in payments following the introduction of new drugs. Payment distribution was highly concentrated, as evidenced by a high Gini index, indicating a skew towards a few specialists. Conclusion: From 2016 to 2019, there was a notable rise in pharmaceutical payments to Japanese breast cancer specialists, paralleling the introduction of new drugs. The study highlights the need for continuous monitoring of these financial relationships to ensure unbiased clinical decisions and uphold healthcare integrity. Transparent and fair financial practices are essential for maintaining trust in healthcare and prioritizing patient care. Pharmaceutical Payments Breast Cancer Specialists Financial Transparency Clinical Decision-Making Japan Figures Figure 1 Figure 2 Figure 3 Introduction The primary concern of healthcare professionals (HCPs) and healthcare organizations (HCOs) is the health and well-being of patients, and patient-centered care is a fundamental concept in contemporary medicine. 1,2 However, financial relationships with pharmaceutical companies can pose significant financial conflicts of interest (FCOIs) for HCPs and HCOs, 3–5 making the management of such relationships a crucial aspect of healthcare policy. In fact, financial ties between medical professionals and pharmaceutical companies have been reported to potentially influence physicians' prescribing patterns, clinical guideline recommendations, and clinical research unintentionally, necessitating proper COI management. 6–11 Rather than prohibiting interactions outright, promoting transparency is seen as a pragmatic approach, and many high-income countries have implemented transparency initiatives based on self-regulation or legal frameworks. 12–17 In Japan as well, to enhance transparency regarding financial COIs in healthcare, the Japan Pharmaceutical Manufacturers Association (JPMA), the largest pharmaceutical industry association in the country, has mandated since 2013 that all member companies disclose all payments to physicians, including for lectures, writing, and consulting, on their respective websites, listing individual names, affiliations, and payment amounts, similar to the U.S. Sunshine Act. 18 In Japan, the breast cancer incidence has been rising, with 95,620 cases recorded in 2018, making it the most common cancer among Japanese women. 19,20 Recent advancements include treatments like Lynparza (olaparib) available for patients with BRCA mutations, CDK4/6 inhibitors (abemaciclib, palbociclib, and ribociclib) for hormone receptors positive diseases, and antibody-drug conjugates (trastuzumab deruxtecan, sacituzumab govitecan, and trastuzumab emtansine). 21–23 Therapies responsive to neoadjuvant chemotherapy, exemplified by CREATE-X and KATHERINE Trial, are becoming mainstream, especially for TNBC and HER2-positive breast cancer subtypes. 24–26 Given the high incidence and prevalence of breast cancer, increased R&D investments, advancements in oncology and pharmacology, and drug development, the breast oncology sector is anticipated to be a growing market for pharmaceutical companies. 27 Indeed, the global breast cancer market is projected to reach approximately $ 73.68 billion by 2032, with a compound annual growth rate (CAGR) of 9.9% from 2023. 28 Similarly in Japan, the industry share for breast cancer treatments is expected to grow at a CAGR of 9.6%, reaching over $ 2 billion by 2028. 29,30 Furthermore, while early diagnosis and treatment through mammography have been shown to reduce breast cancer mortality by about 15%, 31–33 Japan's mammography market is also projected to grow at a CAGR of 8.84%, reaching $ 193.09 million by 2028. 27 In this context, payments from pharmaceutical companies are anticipated to increasingly concentrate on breast oncology specialists in Japan, similar to other specialties such as hematology and respiratory. 34,35 However, in Japan, there is no research evaluating the scale and trends of payments from pharmaceutical companies to breast oncology specialists. The primary aims of this study were to elucidate the prevalence of board-certified breast cancer specialists receiving payments, the magnitude of these payments, and the payment trend in recent years. Methods Participants: This retrospective study considered all of the breast cancer specialists certified by the Japanese Breast Cancer Society (JBCS) as of May 2023. The name list of specialists from previous years was not publicly available from the JBCS. Therefore, we used the latest version of the name list at the JBCS website at the data extraction for this study. It is a primary and large professional society in breast cancer treatment in Japan, with 8,552 JBCS members as of 2023, including 7,147 physicians and 1,405 non-physicians. The JBCS contributes to training and certifying physicians specializing in breast cancer in Japan, with the latest name list of the specialists publicly disclosed on the Society's webpage. The JBCS also contributes to the development of clinical practice guidelines for breast cancer, promoting research and continuing medical education (CME) in breast cancer, and publishing several academic journals such as Breast Cancer, which is issued six times a year and available online. Data Collection: Data collection involved gathering names, affiliations, and other details of these specialists from the webpage of the JBCS. The payment data, covering the period from 2016 to 2019, was extracted from 93 pharmaceutical companies affiliated with the Japan Pharmaceutical Manufacturers Association (JPMA), a major trade organization of Japanese pharmaceutical companies. Data Analysis: The analysis focused on payments related to lecturing, writing, and consulting, as per the JPMA transparency guidelines. These guidelines require member companies to disclose payments to healthcare professionals, including individual consent for disclosure in advance. The study did not include personal payments for meals, education, travel, and accommodations, as these were aggregated by each company. Descriptive analyses of the payment values and counts were conducted, focusing on both the specialists and the pharmaceutical companies involved. The study utilized the Gini index to assess the concentration of payments and examined geographical variations in payments at the prefecture and region levels. Statistical analyses included the use of population-averaged generalized estimating equations to evaluate the trend of payment values per specialist and the number of specialists receiving payments over the four-year period. The analysis also accounted for companies that did not have complete data over the four years, focusing only on those with complete data. For the purpose of the study, Japanese yen (¥) was converted into US dollars ( $ ) using the 2019 average monthly exchange rate of ¥109.0 per $ 1. Ethical Approval: This study was approved by the Ethics Committee of the Medical Governance Research Institute (approval number: MG2018-04-20200605; approval date: June 5, 2020). Since this study involved a retrospective analysis of publicly available information from pharmaceutical companies and the Society's webpage, the Ethics Committee waived the requirement for informed consent. Results Table 1 shows the overview of the obtained data. The data spanned from 2016 to 2019, captured 18,501 transactions from 64 pharmaceutical companies, accumulating a substantial USD 13,329,910.57. 81.4% of these financial interactions were attributed to speaking engagements. Figure 1 shows the overall payments trend during the study period, indicating a monotonic increase in the amounts. Figure 1 delineates the ascending trajectory of overall payments from pharmaceutical companies to physicians over the study period, portraying a continuous upward trend in financial figures. In 2016, the total payments commenced at USD 2,857,414 (JPY 311,458,105). This initial sum experienced a year-on-year augmentation, rising to USD 3,016,587 (JPY 328,807,944) in 2017, followed by an increment to USD 3,558,368 (JPY 387,862,074) in 2018. The progression persisted, culminating in a sum of USD 3,798,523 (JPY 414,038,985) by 2019. This consistent expansion of financial outlay resulted in an average annual growth rate of 10.1% over the four years. Figure 2 displays the total and changes over four years for the top 10 companies with the largest monetary values. Among the 64 pharmaceutical companies providing payments to specialists, the contributions from the top 10 companies constituted 89.5% of the total payments, amounting to USD 11,932,018 between 2016 and 2019. Chugai Pharmaceutical Co., Ltd. led the list, followed by Eisai Co., Ltd., and AstraZeneca plc. Notably, Pfizer Inc. experienced a notable increase in its payment amounts in the year 2018. Similarly, Eli Lilly and Company also augmented payments to specialists with a discernible rise in payments observed from the year 2018. Figure 3 illustrates the relationship with the sales of new drugs. Palbociclib was introduced to the Japanese market in 2017, followed by an increase in Pfizer Japan Inc.'s total payment value in 2018. Similarly, abemaciclib was introduced to the Japanese market in 2018, followed by an increase in Eli Lily Japan K.K's total payment value in 2018 and 2019. There were no such tendencies among an introduction of olaparib and the payment value of the AstraZeneca plc. Table 2 outlines the payment data to breast cancer specialists from pharmaceutical companies across four years. The aggregate payment amounts exhibited an upward trajectory, escalating from USD 2,883,954 in the year 2016 to USD 3,037,888 in 2017, further augmenting to USD 3,589,583 in 2018, and culminating at USD 3,820,041 in 2019. In 2016, the median payment per specialist was USD 1,136 with an interquartile range (IQR) of USD 511 to USD 2,646. By 2019, this median increased to USD 1,237 with an IQR of USD 536 to USD 3,195. This shift represents a annual increase rate of 8.6% in payments per specialist and a 1.4% increase in the number of specialists receiving payments. Among the 64 companies that made payments to specialists, 30 were excluded from the analysis due to the absence of 4-year payment data. The analysis thus focused on the remaining 34 companies with complete 4-year data, which showed significant annual increases of 8.6% in payments and 1.5% in the number of specialists with payments. These figures indicate a growing financial engagement between pharmaceutical companies and breast cancer specialists over the years. Table3 shows the temporary trends of the pharmaceutical payment breakdowns during the study period. Average individual payment increased over the study periods while other indicators were relatively consistent. Discussion The increasing financial relationships between pharmaceutical companies and breast cancer specialists in Japan, as highlighted in this study, represent a significant trend in the pharmaceutical payments coming into the breast cancer care in Japan. The overall rise in payments, with a notable average annual growth of 10.1%, reflects the pharmaceutical industry's strategic efforts to engage healthcare professionals more deeply, as there has been a downward trend in HCP contact in the pharmaceutical industry in recent years, with HCPs becoming more selective in their interactions with pharmaceutical companies. 36 This increase is particularly pronounced in companies such as Pfizer Inc. and Eli Lily Japan K.K's, which have expanded their payment allocations substantially. Specifically, Pfizer's payments surged following the September 2017 introduction of Ibrance (palbociclib), 37 and Eli Lilly's payments increased significantly after introducing Verzenio (abemaciclib) in November 2018. 38 These increments, captured in the total payment growth from USD 2,857,414 in 2016 to USD 3,798,523 in 2019, underscore the competitive dynamics within the oncology sector, particularly in the domain of CDK4/6 inhibitors. Despite the similar therapeutic applications of these drugs to existing treatments, 39 their aggressive promotion can be attributed to the marginal but clinically significant benefits they offer over competitors, a factor crucial in a highly competitive oncology market. 40,41 On the other hand, in the context of Chugai Pharmaceutical's financial engagements, their consistent high payments can largely be attributed to their portfolio of established therapies, particularly for HER2-targeting drugs such as Herceptin (trastuzumab), Perjeta (pertuzumab), and Kadcyla (trastuzumab emtansine), as well as Avastin (bevacizumab) for HER2-negative cases. This may be the primary reason why a launch of Tecentriq (atezolizumab) did not increase the payments in 2019. 42 However, the evolving competitive landscape, with new entrants like Enhertu manufactured by Daiichi Sankyo, will pose a potential challenge to established players like Chugai Pharmaceutical. Enhertu has been approved not only for HER2-enriched breast cancer but also for low-HER2 breast cancer, positioning it as a competitor in both segments. 43,44 Thus, there is a possibility that Chugai Pharmaceutical would increase its payments to the HCPs to protect its sales and share against Daiichi Sankyo. Similarly, Pfizer's BRCA-targeted agent talazoparib, which has been approved in Japan in January 2024, does not have a clear advantage over AstraZeneca's Lynparza and may prompt increased investments by AstraZeneca. 45 The already escalating and likely to further increase payments in the pharmaceutical sector are contributing to further complexities in market dynamics. This trend underscores the need for a comprehensive analysis of promotional strategies and their implications for treatment decisions and guideline recommendations. Intriguingly, the most recent 2022 guidelines continue to endorse drugs such as Tecentriq and Avastin despite their withdrawal from the market in the United States. 46 Furthermore, this study revealed a concerning trend in the field of breast surgery, akin to or potentially more pronounced than in other areas such as dermatology and respiratory medicine, 34,35 where payments are disproportionately concentrated among a select group of specialists. This skewed distribution raises the possibility that the recommendations in clinical guidelines might be influenced by authors who maintain robust relationships with pharmaceutical companies, thereby potentially affecting the objectivity of guideline recommendations. Of note, pharmaceutical companies' promotional strategies heavily favor lecture-based engagements. This method enables the wide dissemination of information through a singular, concerted effort, providing a pragmatic approach for the involved companies. Indeed, such approaches have become vital for interaction and information acquisition among regional healthcare providers. However, reliance on these strategies raises substantial concerns regarding their broader impact on the medical community. Furthermore, an important point to consider is the potential contribution of these strategies to the male-dominated nature of breast surgery. Specifically, given that over 90% of surgeons in Japan are male, yet the female proportion in breast surgery approximates 40%, the conventional scheduling of post-clinical evening lectures significantly hinders the participation of female physicians. 47 This scheduling conflict, juxtaposed with the dual demands of professional obligations and familial roles, often precludes Japanese women doctors from attending such events, thereby exacerbating gender disparities within the medical community. It is essential to explore more inclusive and accessible approaches to organizing educational events, ensuring equitable participation across genders and accommodating the diverse needs of the medical community. This study has several limitations. First, the payment data was manually collected from 93 pharmaceutical companies, which introduces the possibility of errors in data gathering and reporting. Second, our focus was on direct payments for lecturing, writing, and consulting, excluding indirect financial relationships like meals, travel, and research grants, potentially underrepresenting the total financial engagements. Additionally, the study used the most current list of breast cancer specialists without historical data for previous years, which might affect the accuracy of trend analyses. Also, the lack of detailed information on the purpose of payments and the specific drugs involved limits the depth of our analysis. Finally, the absence of a strict monitoring system for the accuracy of disclosed payments by pharmaceutical companies may question the reliability of the data, given the lack of penalties for non-disclosure under JPMA guidelines. Conclusion The period from 2016 to 2019 marked a significant increase in payments from pharmaceutical companies to breast cancer specialists in Japan, reflecting both the introduction of new therapeutic agents and the ongoing value placed on established treatments. This study's findings, particularly the notable increases attributed to companies like Pfizer and Eli Lilly following the introduction of their CDK4/6 inhibitors, underscore the competitive dynamics within the oncology sector. The concentration of payments among a small group of specialists, as indicated by the Gini index, and the overall rise in individual payments raise important considerations regarding the influence of pharmaceutical funding on clinical decision-making. As the breast oncology field continues to evolve, with new treatments and therapeutic strategies emerging, the management of financial relationships between healthcare professionals and the pharmaceutical industry remains a critical issue. Ensuring transparency and equity in these relationships is essential to maintain trust and integrity in the healthcare system, ultimately ensuring that patient care remains the foremost priority. Declarations Dr. Ozaki received personal fees from Medical Network Systems, Kyowa Kirin Inc., Becton, Dickinson and Company, Pfizer Inc, and Taiho Pharmaceutical Co., Ltd., outside the scope of the submitted work. Hiroaki Saito received personal fees from Taiho Pharmaceutical Co. Ltd. outside the scope of the submitted work. Tetsuya Tanimoto received personal fees from Medical Network Systems and Bionics Co. Ltd., outside the scope of the submitted work. All remaining authors have nothing to disclose. Regarding non-financial conflicts of interest among the study authors, Dr. Ozaki is engaged in ongoing research examining financial and non-financial conflicts of interest among healthcare professionals and pharmaceutical companies in Japan and other countries. Acknowledgment We express our gratitude to Mr Kohki Yamada for his constructive help on our analysis. Funding sources: This study was funded in part by the Medical Governance Research Institute. This non-profit enterprise receives donations from a dispensing pharmacy, namely Ain Pharmacies, Inc.; other organizations; and private individuals. This study also received support from Tansa (formerly known as the Waseda Chronicle), an independent nonprofit news organization dedicated to investigative journalism. There was no grant number for the donation to the Medical Governance Research Institute. Author contributions: Conception and designing of the study: Akihiko Ozaki Writing this paper: Yudai Kaneda Data Curation and Analysis: Yudai Kaneda, Erika Yamashita, Akihiko Ozaki Critical revision of the paper: Hiroaki Saito, Kenji Gonda, Masahiro Wada, Tetsuya Tanimoto All the authors read the final draft and approved submission. References Fickweiler F, Fickweiler W, Urbach E (2017) 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 Sep 27(9):e016408. 10.1136/bmjopen-2017-016408 Kumagai N, Nishimura S, Jakovljevic M (2023) Could high continuity of care (COC) have a negative impact on subjective health of hypertensive patients? A Japanese perspective. Cost Eff Resour Alloc Jun 21(1):39. 10.1186/s12962-023-00448-6 Liang BA, Mackey T (2010) Confronting conflict: addressing institutional conflicts of interest in academic medical centers. Am J Law Med 36(1):136–187. 10.1177/009885881003600103 Ozaki A, Harada K, Murayama A et al (2023) Japan's valsartan clinical trials shambles; time for fundamental changes. Int J Health Plann Manage May 38(3):557–568. 10.1002/hpm.3618 Ozaki A, Murayama A, Harada K et al (2021) How Do Institutional Conflicts of Interest Between Pharmaceutical Companies and the Healthcare Sector Become Corrupt? A Case Study of Scholarship Donations Between Department of Clinical Anesthesiology, Mie University, and Ono Pharmaceutical in Japan. Front Public Health 9:762637. 10.3389/fpubh.2021.762637 DeJong C, Aguilar T, Tseng CW, Lin GA, Boscardin WJ, Dudley RA (2016) Pharmaceutical Industry-Sponsored Meals and Physician Prescribing Patterns for Medicare Beneficiaries. JAMA Intern Med . Aug 1. ;176(8):1114–1122. 10.1001/jamainternmed.2016.2765 Ozaki A (2018) Conflict of Interest and the CREATE-X Trial in the New England Journal of Medicine. Sci Eng Ethics Dec 24(6):1809–1811. 10.1007/s11948-017-9966-3 Wilson JM (2009) Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency. Mol Genet Metab Apr 96(4):151–157. 10.1016/j.ymgme.2008.12.016 Murayama A, Yamada K, Yoshida M et al (2022) Evaluation of Conflicts of Interest among Participants of the Japanese Nephrology Clinical Practice Guideline. Clin J Am Soc Nephrol Jun 17(6):819–826. 10.2215/CJN.14661121 Mamada H, Murayama A, Kamamoto S et al (2023) 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) Jun 75(6):1278–1286. 10.1002/acr.25032 Nejstgaard CH, Bero L, Hrobjartsson A et al (2020) Association between conflicts of interest and favourable recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews: systematic review. BMJ Dec 9:371:m4234. 10.1136/bmj.m4234 McCartney M (2016) Margaret McCartney: Optional disclosure of payments is pointless. BMJ Jul 1 354:i3692. 10.1136/bmj.i3692 Rosenthal MB, Mello MM (2013) Sunlight as disinfectant–new rules on disclosure of industry payments to physicians. N Engl J Med May 30(22):2052–2054. 10.1056/NEJMp1305090 Pham-Kanter G, Mello MM, Lehmann LS, Campbell EG, Carpenter D (Jul 2017) Public Awareness of and Contact With Physicians Who Receive Industry Payments: A National Survey. J Gen Intern Med 32(7):767–774. 10.1007/s11606-017-4012-3 Kanter GP, Carpenter D, Lehmann LS, Mello MM (2019) US Nationwide Disclosure of Industry Payments and Public Trust in Physicians. JAMA Netw Open Apr 5(4):e191947. 10.1001/jamanetworkopen.2019.1947 Kanter GP, Carpenter D, Lehmann L, Mello MM (2019) Effect of the public disclosure of industry payments information on patients: results from a population-based natural experiment. BMJ Open Mar 1(2):e024020. 10.1136/bmjopen-2018-024020 Pham-Kanter G (2014) Act II of the Sunshine Act. PLoS Med Nov 11(11):e1001754. 10.1371/journal.pmed.1001754 Ozaki A, Saito H, Senoo Y et al (2020) 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 Jul 124(7):727–735. 10.1016/j.healthpol.2020.03.011 Tada K, Kumamaru H, Miyata H et al (2023) Mar. Characteristics of female breast cancer in japan: annual report of the National Clinical Database in 2018. Breast Cancer . ;30(2):157–166. 10.1007/s12282-022-01423-4 Nakamura K, Okada E, Ukawa S et al Characteristics and prognosis of Japanese female breast cancer patients: The BioBank Japan project. J Epidemiol. 2017/03/01/ 2017;27(3, Supplement):S58–S64. https://doi.org/10.1016/j.je.2016.12.009 DiSilvestro P, Banerjee S, Colombo N et al (2023) Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial. J Clin Oncol Jan 20(3):609–617. 10.1200/JCO.22.01549 O’Sullivan CC, Clarke R, Goetz MP, Robertson J (2023) Cyclin-Dependent Kinase 4/6 Inhibitors for Treatment of Hormone Receptor–Positive, ERBB2-Negative Breast Cancer: A Review. JAMA Oncol 9(9):1273–1282. 10.1001/jamaoncol.2023.2000 Mark C, Lee JS, Cui X, Yuan Y (2023) Antibody-Drug Conjugates in Breast Cancer: Current Status and Future Directions. Int J Mol Sci Sep 6(18). 10.3390/ijms241813726 Masuda N, Lee SJ, Ohtani S et al (2017) Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med Jun 1(22):2147–2159. 10.1056/NEJMoa1612645 Ochi T, Tsunoda H, Matsuda N et al (2021) Accuracy of morphologic change measurements by ultrasound in predicting pathological response to neoadjuvant chemotherapy in triple-negative and HER2-positive breast cancer. Breast Cancer . /07/01 2021;28(4):838–847. 10.1007/s12282-021-01220-5 von Minckwitz G, Huang CS, Mano MS et al (2019) Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med Feb 14(7):617–628. 10.1056/NEJMoa1814017 Mordor Intelligence, BREAST CANCER THERAPY MARKET, SIZE & SHARE ANALYSIS - GROWTH TRENDS & FORECASTS (2023) (2023–2028). Accessed October 4, https://www.mordorintelligence.com/industry-reports/breast-cancer-therapeutics-market Precedence Research. Breast Cancer Market (By Therapy: Targeted Therapy, Hormonal Therapy, Surgery and radiation therapy, Biologic therapy; By Cancer Type: Hormone Receptor, HER2+; By Distribution Channel: Hospital Pharmacies, Retail Pharmacies, Online Pharmacies, Others) - Global Industry Analysis, Size, Share, Growth, Trends, Regional Outlook, and Forecast 2023–2032. Accessed October 4 (2023) https://www.precedenceresearch.com/breast-cancer-market Graphical Research. Asia Pacific Breast Cancer Therapeutics Market Forecast (2028) By Therapy (Targeted Therapy, Hormonal Therapy, Chemotherapy, Immunotherapy), Research Report, Country Outlook (U.S., Canada), COVID-19 Impact Statistics, Price Trends, Historic Data, Growth Prospects, Competitive Industry Share. Accessed October 4, 2023. https://www.graphicalresearch.com/industry-insights/2071/asia-pacific-breast-cancer-therapeutics-market Research and Markets. Japan Breast Cancer Therapeutics Market 2019–2025. Accessed October 4 (2023) https://www.researchandmarkets.com/reports/5116713/japan-breast-cancer-therapeutics-market-2019-2025 Coleman C (2017) Early Detection and Screening for Breast Cancer. Semin Oncol Nurs May 33(2):141–155. 10.1016/j.soncn.2017.02.009 Nelson HD, Fu R, Cantor A, Pappas M, Daeges M, Humphrey L (2016) Effectiveness of Breast Cancer Screening: Systematic Review and Meta-analysis to Update the 2009 U.S. Preventive Services Task Force Recommendation. Ann Intern Med Feb 16(4):244–255. 10.7326/M15-0969 Gotzsche PC, Jorgensen KJ (2013) Screening for breast cancer with mammography. Cochrane Database Syst Rev Jun 4(6):CD001877. 10.1002/14651858.CD001877.pub5 Kusumi E, Murayama A, Kamamoto S et al (2022) Pharmaceutical payments to Japanese certified hematologists: a retrospective analysis of personal payments from pharmaceutical companies between 2016 and 2019. Blood Cancer J Apr 7(4):54. 10.1038/s41408-022-00656-y Murayama A, Hoshi M, Saito H et al (2022) Nature and Trends in Personal Payments Made to the Respiratory Physicians by Pharmaceutical Companies in Japan between 2016 and 2019. Respiration 101(12):1088–1098. 10.1159/000526576 Mireku A (2024) Pharma’s engagement with healthcare providers has slipped in recent years. Accessed January 26, https://www.pharmaceutical-technology.com/news/pharmas-engagement-with-healthcare-providers-has-slipped-in-recent-years/?cf-view Masuda N, Kosaka N, Iwata H, Toi M (2021) Palbociclib as an early-line treatment for Japanese patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: a review of clinical trial and real-world data. Int J Clin Oncol Dec 26(12):2179–2193. 10.1007/s10147-021-02013-8 Takahashi M, Tokunaga E, Mori J et al (2022) Japanese subgroup analysis of the phase 3 MONARCH 3 study of abemaciclib as initial therapy for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Breast Cancer Jan 29(1):174–184. 10.1007/s12282-021-01295-0 George MA, Qureshi S, Omene C, Toppmeyer DL, Ganesan S (2021) Clinical and Pharmacologic Differences of CDK4/6 Inhibitors in Breast Cancer. Front Oncol 11:693104. 10.3389/fonc.2021.693104 Wang H, Ba J, Kang Y et al (2023) Recent Progress in CDK4/6 Inhibitors and PROTACs. Molecules 28(24):8060 Lai H, Jiang W, Zhao J et al (2021) Global Trend in Research and Development of CDK4/6 Inhibitors for Clinical Cancer Therapy: A Bibliometric Analysis. J Cancer 12(12):3539–3547. 10.7150/jca.51609 Schmid P, Adams S, Rugo HS et al (2018) Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med Nov 29(22):2108–2121. 10.1056/NEJMoa1809615 Modi S, Jacot W, Yamashita T et al (2022) Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med Jul 7(1):9–20. 10.1056/NEJMoa2203690 Cortes J, Kim SB, Chung WP et al (2022) Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med Mar 24(12):1143–1154. 10.1056/NEJMoa2115022 Litton JK, Rugo HS, Ettl J et al (2018) Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med Aug 23(8):753–763. 10.1056/NEJMoa1802905 Kaneda Y, Maeda H, Ozaki A, Higuchi Y, Tanimoto T (2023) Comparing cancer drug approval systems in the United States and Japan. Health Sci Rep May 6(5):e1265. 10.1002/hsr2.1265 Sasaki A Until I have decided to join the department of breast and thyroid surgery the choice of a female surgeon (2022) Official J Japan Association Endocr Surg Japanese Soc Thyroid Surg 39(2):70–75 Tables Table 1 Overview of the Obtained Data Variables Values Total payments Payment values, USD 13329910 Counts, n 18501 Companies, n 64 Category of payments, USD (%) consulting 1260781(9.5) other 715043(5.4) speaking 10849291(81.4) writing 506342(3.8) Table 2 Payment data to breast cancer specialists from pharmaceutical companies across four years Variables Values Average per specialist ± SD Payment values, USD 7692 ± 24162 Counts, n 14 ± 26 Companies, n 9.0 Median (IQR) Payment values, USD 2884(1022–7882) Counts, n 6(2–14) Companies, n 5(2–12) Range Payment values, USD 102-520314 Counts, n 1-303 Companies, n 1–90 Physicians with specific payments, n (%) Any payments 1306(75.4) Payments > USD 500 1189(68.6) Payments > USD 1000 1001(57.8) Payments > USD 5000 468(27.0) Payments > USD 10000 266(15.3) Payments > USD 50000 53(3.1) Payments > USD 100000 27(1.6) Gini index 0.994 Table 3 Trends of the pharmaceutical payment breakdowns across four years Variables 2016 2017 2018 2019 Average yearly change % All pharmaceutical companies Total payments, USD (JPY) 2883945 (314350000) 3037888 (331129838) 3589583 (391264579) 3820041 (416384464) 10 Average payments ± SD, USD 3169 ± 7652 3242 ± 7346 3881 ± 8452 4034 ± 9292 8.6 Median payments, USD 1136(511–2646) 1124(525–2802) 1334(525–3340) 1237(536–3195) Payment range, USD 102-134164 102-126022 92-129453 102-130675 Gini index 0.993 0.993 0.994 0.993 Physicians with specific payments, n(%) Any payments 910(52.5) 937(54.1) 925(53.4) 947(54.6) 1.4 Payments > USD 500 752(43.4) 783(45.2) 788(45.5) 844(48.7) 4 Payments > USD 1000 518(29.9) 531(30.6) 566(32.7) 572(33.0) 3.4 Payments > USD 5000 123(7.1) 120(6.9) 161(9.3) 149(8.6) 8.1 Payments > USD 10000 56(3.2) 63(3.6) 80(4.6) 83(4.8) 14.4 Payments > USD 50000 5(0.3) 3(0.2) 6(0.3) 5(0.3) 14.4 Payments > USD 100000 1(0.1) 1(0.1) 1(0.1) 1(0.1) 0 Pharmaceutical companies with 4-year payment data Total payments, USD (JPY) 2857414 (311458105) 3016587 (328807944) 3558368 (387862074) 3798523 (414038985) 10.1 Average payments ± SD, USD 3175 ± 7678 3240 ± 7352 3868 ± 8440 4037 ± 9301 8.6 Median payments, USD 1150(511–2624) 1095(525–2808) 1336(525–3319) 1239(536–3202) Payment range, USD 102-134164 102-126022 92-129453 102-130675 Gini index 0.992 0.993 0.994 0.993 Physicians with specific payments, n(%) Any payments 900(51.9) 931(53.7) 920(53.1) 941(54.3) 1.5 Payments > USD 500 747(43.1) 780(45.0) 785(45.3) 839(48.4) 4 Payments > USD 1000 517(29.8) 526(30.4) 561(32.4) 567(32.7) 3.2 Payments > USD 5000 121(7.0) 120(6.9) 160(9.2) 148(8.5) 8.3 Payments > USD 10000 56(3.2) 62(3.6) 79(4.6) 82(4.7) 14 Payments > USD 50000 5(0.3) 3(0.2) 6(0.3) 5(0.3) 14.4 Payments > USD 100000 1(0.1) 1(0.1) 1(0.1) 1(0.1) 0 Additional Declarations Competing interest reported. Dr. Ozaki received personal fees from Medical Network Systems, Kyowa Kirin Inc., Becton, Dickinson and Company, Pfizer Inc, and Taiho Pharmaceutical Co., Ltd., outside the scope of the submitted work. Hiroaki Saito received personal fees from Taiho Pharmaceutical Co. Ltd. outside the scope of the submitted work. Tetsuya Tanimoto received personal fees from Medical Network Systems and Bionics Co. Ltd., outside the scope of the submitted work. All remaining authors have nothing to disclose. Regarding non-financial conflicts of interest among the study authors, Dr. Ozaki is engaged in ongoing research examining financial and non-financial conflicts of interest among healthcare professionals and pharmaceutical companies in Japan and other countries. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Kaneda","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYPACm/o29uaDDz4AmWzsBFUzg4g0xj6eY8mGM0BamInTcphxnkSOmTQPXAAPMGc/f0y6ooKZmY3ngLGxza9t8nzMDIwfPubg1mLZk8wmeeYMGxsbe0Pi49y+24ZtzAzMkjO34dZicACopbGNhwdoy2Hj3J7bjEAtbMy8+LScfwzU8k9Cgk0isU3asue2PWEtN0C2NBgYsEkks0kz/LidSISWx8aWDccSEth4jjEb9jbcTm5jZmzG75fziQ9vNtT8T5Bv7//44Mef27bz25sPfviIRwsqYGwDkw3EqgeBP6QoHgWjYBSMgpECACYOTkFx/ISQAAAAAElFTkSuQmCC","orcid":"","institution":"Hokkaido University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Yudai","middleName":"","lastName":"Kaneda","suffix":""},{"id":270585126,"identity":"18417243-3097-43a7-92ab-859e2cc15fc5","order_by":1,"name":"Erika Yamashita","email":"","orcid":"","institution":"Medical Governance Research Institute","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Erika","middleName":"","lastName":"Yamashita","suffix":""},{"id":270585127,"identity":"b8a41070-0be7-4582-bab0-1a3bdd17af90","order_by":2,"name":"Hiroaki Saito","email":"","orcid":"","institution":"Soma Central Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hiroaki","middleName":"","lastName":"Saito","suffix":""},{"id":270585128,"identity":"f1a82900-bd2f-4c91-a4dd-253441734e57","order_by":3,"name":"Kenji Gonda","email":"","orcid":"","institution":"Jyoban Hospital of Tokiwa Foundation","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kenji","middleName":"","lastName":"Gonda","suffix":""},{"id":270585129,"identity":"3a19359d-c220-4adf-afb8-ecaa71e73733","order_by":4,"name":"Masahiro Wada","email":"","orcid":"","institution":"Utsunomiya Central Clinic","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Masahiro","middleName":"","lastName":"Wada","suffix":""},{"id":270585130,"identity":"f4a92ffc-8c82-4b5a-9e0a-7f15f8c130a3","order_by":5,"name":"Tetsuya Tanimoto","email":"","orcid":"","institution":"Medical Governance Research Institute","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tetsuya","middleName":"","lastName":"Tanimoto","suffix":""},{"id":270585131,"identity":"298c3f8d-d9cc-44b5-bdd2-2a44e93e649d","order_by":6,"name":"Akihiko Ozaki","email":"","orcid":"","institution":"Medical Governance Research Institute","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Akihiko","middleName":"","lastName":"Ozaki","suffix":""}],"badges":[],"createdAt":"2024-02-01 04:45:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3915980/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3915980/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50674671,"identity":"bdf8961b-dcb4-49e0-a27b-bb6e62c128ce","added_by":"auto","created_at":"2024-02-05 15:11:29","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":26255,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"fig1totalpaymentsyear.png","url":"https://assets-eu.researchsquare.com/files/rs-3915980/v1/56232cdf6e22a387237ff72f.png"},{"id":50674550,"identity":"3743c858-ef99-4956-be7c-1bf61e708a4d","added_by":"auto","created_at":"2024-02-05 15:11:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":28840,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"fig2top10payingcompanies1.png","url":"https://assets-eu.researchsquare.com/files/rs-3915980/v1/efdc5823c9b0b06aebce8988.png"},{"id":50674607,"identity":"e6a5cdd5-27ab-485d-8425-3396c5cab9ac","added_by":"auto","created_at":"2024-02-05 15:11:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":25183,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"fig3lineplotnewdrugsumusdallmarkerfig31.png","url":"https://assets-eu.researchsquare.com/files/rs-3915980/v1/277c7508db65af7328bb14bb.png"},{"id":50820039,"identity":"e9ad5a98-0ff4-47d7-90df-807a54aa5867","added_by":"auto","created_at":"2024-02-07 20:36:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":512179,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3915980/v1/b3e1b731-2e60-43c8-b558-044d0797977c.pdf"}],"financialInterests":"Competing interest reported. Dr. Ozaki received personal fees from Medical Network Systems, Kyowa Kirin Inc., Becton, Dickinson and Company, Pfizer Inc, and Taiho Pharmaceutical Co., Ltd., outside the scope of the submitted work. Hiroaki Saito received personal fees from Taiho Pharmaceutical Co. Ltd. outside the scope of the submitted work. Tetsuya Tanimoto received personal fees from Medical Network Systems and Bionics Co. Ltd., outside the scope of the submitted work. All remaining authors have nothing to disclose. \nRegarding non-financial conflicts of interest among the study authors, Dr. Ozaki is engaged in ongoing research examining financial and non-financial conflicts of interest among healthcare professionals and pharmaceutical companies in Japan and other countries.","formattedTitle":"Increasing Trends of Pharmaceutical Payments to Breast Cancer Specialists in Japan: A Retrospective Study from 2016 to 2019","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe primary concern of healthcare professionals (HCPs) and healthcare organizations (HCOs) is the health and well-being of patients, and patient-centered care is a fundamental concept in contemporary medicine.\u003csup\u003e1,2\u003c/sup\u003e However, financial relationships with pharmaceutical companies can pose significant financial conflicts of interest (FCOIs) for HCPs and HCOs,\u003csup\u003e3\u0026ndash;5\u003c/sup\u003e making the management of such relationships a crucial aspect of healthcare policy. In fact, financial ties between medical professionals and pharmaceutical companies have been reported to potentially influence physicians' prescribing patterns, clinical guideline recommendations, and clinical research unintentionally, necessitating proper COI management.\u003csup\u003e6\u0026ndash;11\u003c/sup\u003e Rather than prohibiting interactions outright, promoting transparency is seen as a pragmatic approach, and many high-income countries have implemented transparency initiatives based on self-regulation or legal frameworks.\u003csup\u003e12\u0026ndash;17\u003c/sup\u003e In Japan as well, to enhance transparency regarding financial COIs in healthcare, the Japan Pharmaceutical Manufacturers Association (JPMA), the largest pharmaceutical industry association in the country, has mandated since 2013 that all member companies disclose all payments to physicians, including for lectures, writing, and consulting, on their respective websites, listing individual names, affiliations, and payment amounts, similar to the U.S. Sunshine Act.\u003csup\u003e18\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e In Japan, the breast cancer incidence has been rising, with 95,620 cases recorded in 2018, making it the most common cancer among Japanese women.\u003csup\u003e19,20\u003c/sup\u003e Recent advancements include treatments like Lynparza (olaparib) available for patients with BRCA mutations, CDK4/6 inhibitors (abemaciclib, palbociclib, and ribociclib) for hormone receptors positive diseases, and antibody-drug conjugates (trastuzumab deruxtecan, sacituzumab govitecan, and trastuzumab emtansine).\u003csup\u003e21\u0026ndash;23\u003c/sup\u003e Therapies responsive to neoadjuvant chemotherapy, exemplified by CREATE-X and KATHERINE Trial, are becoming mainstream, especially for TNBC and HER2-positive breast cancer subtypes.\u003csup\u003e24\u0026ndash;26\u003c/sup\u003e Given the high incidence and prevalence of breast cancer, increased R\u0026amp;D investments, advancements in oncology and pharmacology, and drug development, the breast oncology sector is anticipated to be a growing market for pharmaceutical companies.\u003csup\u003e27\u003c/sup\u003e Indeed, the global breast cancer market is projected to reach approximately \u003cspan\u003e$\u003c/span\u003e73.68\u0026nbsp;billion by 2032, with a compound annual growth rate (CAGR) of 9.9% from 2023.\u003csup\u003e28\u003c/sup\u003e Similarly in Japan, the industry share for breast cancer treatments is expected to grow at a CAGR of 9.6%, reaching over \u003cspan\u003e$\u003c/span\u003e2\u0026nbsp;billion by 2028.\u003csup\u003e29,30\u003c/sup\u003e Furthermore, while early diagnosis and treatment through mammography have been shown to reduce breast cancer mortality by about 15%,\u003csup\u003e31\u0026ndash;33\u003c/sup\u003e Japan's mammography market is also projected to grow at a CAGR of 8.84%, reaching \u003cspan\u003e$\u003c/span\u003e193.09\u0026nbsp;million by 2028.\u003csup\u003e27\u003c/sup\u003e \u003c/p\u003e \u003cp\u003eIn this context, payments from pharmaceutical companies are anticipated to increasingly concentrate on breast oncology specialists in Japan, similar to other specialties such as hematology and respiratory.\u003csup\u003e34,35\u003c/sup\u003e However, in Japan, there is no research evaluating the scale and trends of payments from pharmaceutical companies to breast oncology specialists. The primary aims of this study were to elucidate the prevalence of board-certified breast cancer specialists receiving payments, the magnitude of these payments, and the payment trend in recent years.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eParticipants:\u003c/h2\u003e \u003cp\u003eThis retrospective study considered all of the breast cancer specialists certified by the Japanese Breast Cancer Society (JBCS) as of May 2023. The name list of specialists from previous years was not publicly available from the JBCS. Therefore, we used the latest version of the name list at the JBCS website at the data extraction for this study. It is a primary and large professional society in breast cancer treatment in Japan, with 8,552 JBCS members as of 2023, including 7,147 physicians and 1,405 non-physicians. The JBCS contributes to training and certifying physicians specializing in breast cancer in Japan, with the latest name list of the specialists publicly disclosed on the Society's webpage. The JBCS also contributes to the development of clinical practice guidelines for breast cancer, promoting research and continuing medical education (CME) in breast cancer, and publishing several academic journals such as Breast Cancer, which is issued six times a year and available online.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData Collection:\u003c/h2\u003e \u003cp\u003eData collection involved gathering names, affiliations, and other details of these specialists from the webpage of the JBCS. The payment data, covering the period from 2016 to 2019, was extracted from 93 pharmaceutical companies affiliated with the Japan Pharmaceutical Manufacturers Association (JPMA), a major trade organization of Japanese pharmaceutical companies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis:\u003c/h2\u003e \u003cp\u003eThe analysis focused on payments related to lecturing, writing, and consulting, as per the JPMA transparency guidelines. These guidelines require member companies to disclose payments to healthcare professionals, including individual consent for disclosure in advance. The study did not include personal payments for meals, education, travel, and accommodations, as these were aggregated by each company.\u003c/p\u003e \u003cp\u003eDescriptive analyses of the payment values and counts were conducted, focusing on both the specialists and the pharmaceutical companies involved. The study utilized the Gini index to assess the concentration of payments and examined geographical variations in payments at the prefecture and region levels.\u003c/p\u003e \u003cp\u003eStatistical analyses included the use of population-averaged generalized estimating equations to evaluate the trend of payment values per specialist and the number of specialists receiving payments over the four-year period. The analysis also accounted for companies that did not have complete data over the four years, focusing only on those with complete data.\u003c/p\u003e \u003cp\u003eFor the purpose of the study, Japanese yen (\u0026yen;) was converted into US dollars (\u003cspan\u003e$\u003c/span\u003e) using the 2019 average monthly exchange rate of \u0026yen;109.0 per \u003cspan\u003e$\u003c/span\u003e1.\u003c/p\u003e \u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the Medical Governance Research Institute (approval number: MG2018-04-20200605; approval date: June 5, 2020). Since this study involved a retrospective analysis of publicly available information from pharmaceutical companies and the Society\u0026apos;s webpage, the Ethics Committee waived the requirement for informed consent.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eTable 1 shows the overview of the obtained data. The data spanned from 2016 to 2019, captured 18,501 transactions from 64 pharmaceutical companies, accumulating a substantial USD 13,329,910.57. 81.4% of these financial interactions were attributed to speaking engagements.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFigure 1 shows the overall payments trend during the study period, indicating a monotonic increase in the amounts. Figure 1 delineates the ascending trajectory of overall payments from pharmaceutical companies to physicians over the study period, portraying a continuous upward trend in financial figures. In 2016, the total payments commenced at USD 2,857,414 (JPY 311,458,105). This initial sum experienced a year-on-year augmentation, rising to USD 3,016,587 (JPY 328,807,944) in 2017, followed by an increment to USD 3,558,368 (JPY 387,862,074) in 2018. The progression persisted, culminating in a sum of USD 3,798,523 (JPY 414,038,985) by 2019. This consistent expansion of financial outlay resulted in an average annual growth rate of 10.1% over the four years.\u003c/p\u003e\n\u003cp\u003eFigure 2 displays the total and changes over four years for the top 10 companies with the largest monetary values. Among the 64 pharmaceutical companies providing payments to specialists, the contributions from the top 10 companies constituted 89.5% of the total payments, amounting to USD 11,932,018 between 2016 and 2019. Chugai Pharmaceutical Co., Ltd. led the list, followed by Eisai Co., Ltd., and AstraZeneca plc. Notably, Pfizer Inc. experienced a notable increase in its payment amounts in the year 2018. Similarly, Eli Lilly and Company also augmented payments to specialists with a discernible rise in payments observed from the year 2018.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFigure 3 illustrates the relationship with the sales of new drugs. Palbociclib was introduced to the Japanese market in 2017, followed by an increase in Pfizer Japan Inc.\u0026apos;s total payment value in 2018. Similarly, abemaciclib was introduced to the Japanese market in 2018, followed by an increase in Eli Lily Japan K.K\u0026apos;s total payment value in 2018 and 2019. There were no such tendencies among an introduction of olaparib and the payment value of the AstraZeneca plc.\u003c/p\u003e\n\u003cp\u003eTable 2 outlines the payment data to breast cancer specialists from pharmaceutical companies across four years. The aggregate payment amounts exhibited an upward trajectory, escalating from USD 2,883,954 in the year 2016 to USD 3,037,888 in 2017, further augmenting to USD 3,589,583 in 2018, and culminating at USD 3,820,041 in 2019. In 2016, the median payment per specialist was USD 1,136 with an interquartile range (IQR) of USD 511 to USD 2,646. By 2019, this median increased to USD 1,237 with an IQR of USD 536 to USD 3,195. This shift represents a annual increase rate of 8.6% in payments per specialist and a 1.4% increase in the number of specialists receiving payments. Among the 64 companies that made payments to specialists, 30 were excluded from the analysis due to the absence of 4-year payment data. The analysis thus focused on the remaining 34 companies with complete 4-year data, which showed significant annual increases of 8.6% in payments and 1.5% in the number of specialists with payments. These figures indicate a growing financial engagement between pharmaceutical companies and breast cancer specialists over the years.\u003c/p\u003e\n\u003cp\u003eTable3 shows the temporary trends of the pharmaceutical payment breakdowns during the study period. Average individual payment increased over the study periods while other indicators were relatively consistent.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe increasing financial relationships between pharmaceutical companies and breast cancer specialists in Japan, as highlighted in this study, represent a significant trend in the pharmaceutical payments coming into the breast cancer care in Japan. The overall rise in payments, with a notable average annual growth of 10.1%, reflects the pharmaceutical industry's strategic efforts to engage healthcare professionals more deeply, as there has been a downward trend in HCP contact in the pharmaceutical industry in recent years, with HCPs becoming more selective in their interactions with pharmaceutical companies.\u003csup\u003e36\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eThis increase is particularly pronounced in companies such as Pfizer Inc. and Eli Lily Japan K.K's, which have expanded their payment allocations substantially. Specifically, Pfizer's payments surged following the September 2017 introduction of Ibrance (palbociclib),\u003csup\u003e37\u003c/sup\u003e and Eli Lilly's payments increased significantly after introducing Verzenio (abemaciclib) in November 2018.\u003csup\u003e38\u003c/sup\u003e These increments, captured in the total payment growth from USD 2,857,414 in 2016 to USD 3,798,523 in 2019, underscore the competitive dynamics within the oncology sector, particularly in the domain of CDK4/6 inhibitors. Despite the similar therapeutic applications of these drugs to existing treatments,\u003csup\u003e39\u003c/sup\u003e their aggressive promotion can be attributed to the marginal but clinically significant benefits they offer over competitors, a factor crucial in a highly competitive oncology market.\u003csup\u003e40,41\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eOn the other hand, in the context of Chugai Pharmaceutical's financial engagements, their consistent high payments can largely be attributed to their portfolio of established therapies, particularly for HER2-targeting drugs such as Herceptin (trastuzumab), Perjeta (pertuzumab), and Kadcyla (trastuzumab emtansine), as well as Avastin (bevacizumab) for HER2-negative cases. This may be the primary reason why a launch of Tecentriq (atezolizumab) did not increase the payments in 2019.\u003csup\u003e42\u003c/sup\u003e However, the evolving competitive landscape, with new entrants like Enhertu manufactured by Daiichi Sankyo, will pose a potential challenge to established players like Chugai Pharmaceutical. Enhertu has been approved not only for HER2-enriched breast cancer but also for low-HER2 breast cancer, positioning it as a competitor in both segments.\u003csup\u003e43,44\u003c/sup\u003e Thus, there is a possibility that Chugai Pharmaceutical would increase its payments to the HCPs to protect its sales and share against Daiichi Sankyo. Similarly, Pfizer's BRCA-targeted agent talazoparib, which has been approved in Japan in January 2024, does not have a clear advantage over AstraZeneca's Lynparza and may prompt increased investments by AstraZeneca.\u003csup\u003e45\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eThe already escalating and likely to further increase payments in the pharmaceutical sector are contributing to further complexities in market dynamics. This trend underscores the need for a comprehensive analysis of promotional strategies and their implications for treatment decisions and guideline recommendations. Intriguingly, the most recent 2022 guidelines continue to endorse drugs such as Tecentriq and Avastin despite their withdrawal from the market in the United States.\u003csup\u003e46\u003c/sup\u003e Furthermore, this study revealed a concerning trend in the field of breast surgery, akin to or potentially more pronounced than in other areas such as dermatology and respiratory medicine,\u003csup\u003e34,35\u003c/sup\u003e where payments are disproportionately concentrated among a select group of specialists. This skewed distribution raises the possibility that the recommendations in clinical guidelines might be influenced by authors who maintain robust relationships with pharmaceutical companies, thereby potentially affecting the objectivity of guideline recommendations.\u003c/p\u003e\n\u003cp\u003eOf note, pharmaceutical companies' promotional strategies heavily favor lecture-based engagements. This method enables the wide dissemination of information through a singular, concerted effort, providing a pragmatic approach for the involved companies. Indeed, such approaches have become vital for interaction and information acquisition among regional healthcare providers. However, reliance on these strategies raises substantial concerns regarding their broader impact on the medical community.\u003c/p\u003e\n\u003cp\u003eFurthermore, an important point to consider is the potential contribution of these strategies to the male-dominated nature of breast surgery. Specifically, given that over 90% of surgeons in Japan are male, yet the female proportion in breast surgery approximates 40%, the conventional scheduling of post-clinical evening lectures significantly hinders the participation of female physicians.\u003csup\u003e47\u003c/sup\u003e This scheduling conflict, juxtaposed with the dual demands of professional obligations and familial roles, often precludes Japanese women doctors from attending such events, thereby exacerbating gender disparities within the medical community. It is essential to explore more inclusive and accessible approaches to organizing educational events, ensuring equitable participation across genders and accommodating the diverse needs of the medical community.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, the payment data was manually collected from 93 pharmaceutical companies, which introduces the possibility of errors in data gathering and reporting. Second, our focus was on direct payments for lecturing, writing, and consulting, excluding indirect financial relationships like meals, travel, and research grants, potentially underrepresenting the total financial engagements. Additionally, the study used the most current list of breast cancer specialists without historical data for previous years, which might affect the accuracy of trend analyses. Also, the lack of detailed information on the purpose of payments and the specific drugs involved limits the depth of our analysis. Finally, the absence of a strict monitoring system for the accuracy of disclosed payments by pharmaceutical companies may question the reliability of the data, given the lack of penalties for non-disclosure under JPMA guidelines.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe period from 2016 to 2019 marked a significant increase in payments from pharmaceutical companies to breast cancer specialists in Japan, reflecting both the introduction of new therapeutic agents and the ongoing value placed on established treatments. This study's findings, particularly the notable increases attributed to companies like Pfizer and Eli Lilly following the introduction of their CDK4/6 inhibitors, underscore the competitive dynamics within the oncology sector. The concentration of payments among a small group of specialists, as indicated by the Gini index, and the overall rise in individual payments raise important considerations regarding the influence of pharmaceutical funding on clinical decision-making. As the breast oncology field continues to evolve, with new treatments and therapeutic strategies emerging, the management of financial relationships between healthcare professionals and the pharmaceutical industry remains a critical issue. Ensuring transparency and equity in these relationships is essential to maintain trust and integrity in the healthcare system, ultimately ensuring that patient care remains the foremost priority.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eDr. Ozaki received personal fees from Medical Network Systems, Kyowa Kirin Inc., Becton, Dickinson and Company, Pfizer Inc, and Taiho Pharmaceutical Co., Ltd., outside the scope of the submitted work. Hiroaki Saito received personal fees from Taiho Pharmaceutical Co. Ltd. outside the scope of the submitted work. Tetsuya Tanimoto received personal fees from Medical Network Systems and Bionics Co. Ltd., outside the scope of the submitted work. All remaining authors have nothing to disclose.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRegarding non-financial conflicts of interest among the study authors, Dr. Ozaki is engaged in ongoing research examining financial and non-financial conflicts of interest among healthcare professionals and pharmaceutical companies in Japan and other countries.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe express our gratitude to Mr Kohki Yamada for his constructive help on our analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding sources:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded in part by the Medical Governance Research Institute. This non-profit enterprise receives donations from a dispensing pharmacy, namely Ain Pharmacies, Inc.; other organizations; and private individuals. This study also received support from Tansa (formerly known as the Waseda Chronicle), an independent nonprofit news organization dedicated to investigative journalism. There was no grant number for the donation to the Medical Governance Research Institute.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception and designing of the study: Akihiko Ozaki\u003c/p\u003e\n\u003cp\u003eWriting this paper: Yudai Kaneda\u003c/p\u003e\n\u003cp\u003eData Curation and Analysis: Yudai Kaneda, Erika Yamashita, Akihiko Ozaki\u003c/p\u003e\n\u003cp\u003eCritical revision of the paper: Hiroaki Saito, Kenji Gonda, Masahiro Wada, Tetsuya Tanimoto\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll the authors read the final draft and approved submission.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFickweiler F, Fickweiler W, Urbach E (2017) 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 Sep 27(9):e016408. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmjopen-2017-016408\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eKumagai N, Nishimura S, Jakovljevic M (2023) Could high continuity of care (COC) have a negative impact on subjective health of hypertensive patients? A Japanese perspective. Cost Eff Resour Alloc Jun 21(1):39. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12962-023-00448-6\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eLiang BA, Mackey T (2010) Confronting conflict: addressing institutional conflicts of interest in academic medical centers. Am J Law Med 36(1):136\u0026ndash;187. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/009885881003600103\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eOzaki A, Harada K, Murayama A et al (2023) Japan's valsartan clinical trials shambles; time for fundamental changes. Int J Health Plann Manage May 38(3):557\u0026ndash;568. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/hpm.3618\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eOzaki A, Murayama A, Harada K et al (2021) How Do Institutional Conflicts of Interest Between Pharmaceutical Companies and the Healthcare Sector Become Corrupt? A Case Study of Scholarship Donations Between Department of Clinical Anesthesiology, Mie University, and Ono Pharmaceutical in Japan. Front Public Health 9:762637. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fpubh.2021.762637\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eDeJong C, Aguilar T, Tseng CW, Lin GA, Boscardin WJ, Dudley RA (2016) Pharmaceutical Industry-Sponsored Meals and Physician Prescribing Patterns for Medicare Beneficiaries. \u003cem\u003eJAMA Intern Med\u003c/em\u003e. Aug 1. ;176(8):1114\u0026ndash;1122. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamainternmed.2016.2765\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eOzaki A (2018) Conflict of Interest and the CREATE-X Trial in the New England Journal of Medicine. Sci Eng Ethics Dec 24(6):1809\u0026ndash;1811. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11948-017-9966-3\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eWilson JM (2009) Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency. Mol Genet Metab Apr 96(4):151\u0026ndash;157. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ymgme.2008.12.016\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eMurayama A, Yamada K, Yoshida M et al (2022) Evaluation of Conflicts of Interest among Participants of the Japanese Nephrology Clinical Practice Guideline. Clin J Am Soc Nephrol Jun 17(6):819\u0026ndash;826. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2215/CJN.14661121\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eMamada H, Murayama A, Kamamoto S et al (2023) 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) Jun 75(6):1278\u0026ndash;1286. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/acr.25032\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eNejstgaard CH, Bero L, Hrobjartsson A et al (2020) Association between conflicts of interest and favourable recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews: systematic review. BMJ Dec 9:371:m4234. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmj.m4234\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eMcCartney M (2016) Margaret McCartney: Optional disclosure of payments is pointless. BMJ Jul 1 354:i3692. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmj.i3692\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eRosenthal MB, Mello MM (2013) Sunlight as disinfectant\u0026ndash;new rules on disclosure of industry payments to physicians. N Engl J Med May 30(22):2052\u0026ndash;2054. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMp1305090\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003ePham-Kanter G, Mello MM, Lehmann LS, Campbell EG, Carpenter D (Jul 2017) Public Awareness of and Contact With Physicians Who Receive Industry Payments: A National Survey. J Gen Intern Med 32(7):767\u0026ndash;774. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11606-017-4012-3\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eKanter GP, Carpenter D, Lehmann LS, Mello MM (2019) US Nationwide Disclosure of Industry Payments and Public Trust in Physicians. JAMA Netw Open Apr 5(4):e191947. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamanetworkopen.2019.1947\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eKanter GP, Carpenter D, Lehmann L, Mello MM (2019) Effect of the public disclosure of industry payments information on patients: results from a population-based natural experiment. BMJ Open Mar 1(2):e024020. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmjopen-2018-024020\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003ePham-Kanter G (2014) Act II of the Sunshine Act. PLoS Med Nov 11(11):e1001754. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pmed.1001754\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eOzaki A, Saito H, Senoo Y et al (2020) 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 Jul 124(7):727\u0026ndash;735. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.healthpol.2020.03.011\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eTada K, Kumamaru H, Miyata H et al (2023) Mar. Characteristics of female breast cancer in japan: annual report of the National Clinical Database in 2018. \u003cem\u003eBreast Cancer\u003c/em\u003e. ;30(2):157\u0026ndash;166. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12282-022-01423-4\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eNakamura K, Okada E, Ukawa S et al Characteristics and prognosis of Japanese female breast cancer patients: The BioBank Japan project. J Epidemiol. 2017/03/01/ 2017;27(3, Supplement):S58\u0026ndash;S64. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.je.2016.12.009\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eDiSilvestro P, Banerjee S, Colombo N et al (2023) Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial. J Clin Oncol Jan 20(3):609\u0026ndash;617. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1200/JCO.22.01549\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eO\u0026rsquo;Sullivan CC, Clarke R, Goetz MP, Robertson J (2023) Cyclin-Dependent Kinase 4/6 Inhibitors for Treatment of Hormone Receptor\u0026ndash;Positive, ERBB2-Negative Breast Cancer: A Review. JAMA Oncol 9(9):1273\u0026ndash;1282. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamaoncol.2023.2000\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eMark C, Lee JS, Cui X, Yuan Y (2023) Antibody-Drug Conjugates in Breast Cancer: Current Status and Future Directions. Int J Mol Sci Sep 6(18). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/ijms241813726\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eMasuda N, Lee SJ, Ohtani S et al (2017) Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med Jun 1(22):2147\u0026ndash;2159. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa1612645\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eOchi T, Tsunoda H, Matsuda N et al (2021) Accuracy of morphologic change measurements by ultrasound in predicting pathological response to neoadjuvant chemotherapy in triple-negative and HER2-positive breast cancer. \u003cem\u003eBreast Cancer\u003c/em\u003e. /07/01 2021;28(4):838\u0026ndash;847. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12282-021-01220-5\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003evon Minckwitz G, Huang CS, Mano MS et al (2019) Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med Feb 14(7):617\u0026ndash;628. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa1814017\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eMordor Intelligence, BREAST CANCER THERAPY MARKET, SIZE \u0026amp; SHARE ANALYSIS - GROWTH TRENDS \u0026amp; FORECASTS (2023) (2023\u0026ndash;2028). Accessed October 4, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.mordorintelligence.com/industry-reports/breast-cancer-therapeutics-market\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003ePrecedence Research. Breast Cancer Market (By Therapy: Targeted Therapy, Hormonal Therapy, Surgery and radiation therapy, Biologic therapy; By Cancer Type: Hormone Receptor, HER2+; By Distribution Channel: Hospital Pharmacies, Retail Pharmacies, Online Pharmacies, Others) - Global Industry Analysis, Size, Share, Growth, Trends, Regional Outlook, and Forecast 2023\u0026ndash;2032. Accessed October 4 (2023) \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.precedenceresearch.com/breast-cancer-market\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eGraphical Research. Asia Pacific Breast Cancer Therapeutics Market Forecast (2028) By Therapy (Targeted Therapy, Hormonal Therapy, Chemotherapy, Immunotherapy), Research Report, Country Outlook (U.S., Canada), COVID-19 Impact Statistics, Price Trends, Historic Data, Growth Prospects, Competitive Industry Share. Accessed October 4, 2023. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.graphicalresearch.com/industry-insights/2071/asia-pacific-breast-cancer-therapeutics-market\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eResearch and Markets. Japan Breast Cancer Therapeutics Market 2019\u0026ndash;2025. Accessed October 4 (2023) \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.researchandmarkets.com/reports/5116713/japan-breast-cancer-therapeutics-market-2019-2025\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eColeman C (2017) Early Detection and Screening for Breast Cancer. Semin Oncol Nurs May 33(2):141\u0026ndash;155. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.soncn.2017.02.009\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eNelson HD, Fu R, Cantor A, Pappas M, Daeges M, Humphrey L (2016) Effectiveness of Breast Cancer Screening: Systematic Review and Meta-analysis to Update the 2009 U.S. Preventive Services Task Force Recommendation. Ann Intern Med Feb 16(4):244\u0026ndash;255. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7326/M15-0969\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eGotzsche PC, Jorgensen KJ (2013) Screening for breast cancer with mammography. Cochrane Database Syst Rev Jun 4(6):CD001877. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/14651858.CD001877.pub5\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eKusumi E, Murayama A, Kamamoto S et al (2022) Pharmaceutical payments to Japanese certified hematologists: a retrospective analysis of personal payments from pharmaceutical companies between 2016 and 2019. Blood Cancer J Apr 7(4):54. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41408-022-00656-y\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eMurayama A, Hoshi M, Saito H et al (2022) Nature and Trends in Personal Payments Made to the Respiratory Physicians by Pharmaceutical Companies in Japan between 2016 and 2019. Respiration 101(12):1088\u0026ndash;1098. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000526576\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eMireku A (2024) Pharma\u0026rsquo;s engagement with healthcare providers has slipped in recent years. Accessed January 26, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.pharmaceutical-technology.com/news/pharmas-engagement-with-healthcare-providers-has-slipped-in-recent-years/?cf-view\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eMasuda N, Kosaka N, Iwata H, Toi M (2021) Palbociclib as an early-line treatment for Japanese patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: a review of clinical trial and real-world data. Int J Clin Oncol Dec 26(12):2179\u0026ndash;2193. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10147-021-02013-8\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eTakahashi M, Tokunaga E, Mori J et al (2022) Japanese subgroup analysis of the phase 3 MONARCH 3 study of abemaciclib as initial therapy for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Breast Cancer Jan 29(1):174\u0026ndash;184. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12282-021-01295-0\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eGeorge MA, Qureshi S, Omene C, Toppmeyer DL, Ganesan S (2021) Clinical and Pharmacologic Differences of CDK4/6 Inhibitors in Breast Cancer. Front Oncol 11:693104. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fonc.2021.693104\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eWang H, Ba J, Kang Y et al (2023) Recent Progress in CDK4/6 Inhibitors and PROTACs. Molecules 28(24):8060\u003c/li\u003e\n\u003cli\u003eLai H, Jiang W, Zhao J et al (2021) Global Trend in Research and Development of CDK4/6 Inhibitors for Clinical Cancer Therapy: A Bibliometric Analysis. J Cancer 12(12):3539\u0026ndash;3547. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7150/jca.51609\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eSchmid P, Adams S, Rugo HS et al (2018) Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med Nov 29(22):2108\u0026ndash;2121. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa1809615\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eModi S, Jacot W, Yamashita T et al (2022) Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med Jul 7(1):9\u0026ndash;20. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa2203690\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eCortes J, Kim SB, Chung WP et al (2022) Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med Mar 24(12):1143\u0026ndash;1154. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa2115022\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eLitton JK, Rugo HS, Ettl J et al (2018) Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med Aug 23(8):753\u0026ndash;763. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa1802905\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eKaneda Y, Maeda H, Ozaki A, Higuchi Y, Tanimoto T (2023) Comparing cancer drug approval systems in the United States and Japan. Health Sci Rep May 6(5):e1265. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/hsr2.1265\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eSasaki A Until I have decided to join the department of breast and thyroid surgery the choice of a female surgeon (2022) Official J Japan Association Endocr Surg Japanese Soc Thyroid Surg 39(2):70\u0026ndash;75\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":" \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eOverview of the Obtained Data\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eVariables\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eValues\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eTotal payments\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayment values, USD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e13329910\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCounts, n\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e18501\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCompanies, n\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e64\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCategory of payments, USD (%)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003econsulting\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1260781(9.5)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eother\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e715043(5.4)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003espeaking\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e10849291(81.4)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ewriting\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e506342(3.8)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayment data to breast cancer specialists from pharmaceutical companies across four years\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eVariables\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eValues\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAverage per specialist\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayment values, USD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e7692\u0026thinsp;\u0026plusmn;\u0026thinsp;24162\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCounts, n\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e14\u0026thinsp;\u0026plusmn;\u0026thinsp;26\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCompanies, n\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e9.0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMedian (IQR)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayment values, USD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2884(1022\u0026ndash;7882)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCounts, n\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e6(2\u0026ndash;14)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCompanies, n\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e5(2\u0026ndash;12)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eRange\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayment values, USD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e102-520314\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCounts, n\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1-303\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCompanies, n\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u0026ndash;90\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003ePhysicians with specific payments, n (%)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAny payments\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1306(75.4)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 500\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1189(68.6)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 1000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1001(57.8)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 5000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e468(27.0)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 10000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e266(15.3)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 50000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e53(3.1)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 100000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e27(1.6)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eGini index\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.994\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eTrends of the pharmaceutical payment breakdowns across four years\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eVariables\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2016\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2017\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e2018\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e2019\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eAverage yearly change %\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAll pharmaceutical companies\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eTotal payments, USD (JPY)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2883945 (314350000)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3037888 (331129838)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e3589583 (391264579)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e3820041 (416384464)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e10\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAverage payments\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, USD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e3169\u0026thinsp;\u0026plusmn;\u0026thinsp;7652\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3242\u0026thinsp;\u0026plusmn;\u0026thinsp;7346\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e3881\u0026thinsp;\u0026plusmn;\u0026thinsp;8452\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e4034\u0026thinsp;\u0026plusmn;\u0026thinsp;9292\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e8.6\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMedian payments, USD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1136(511\u0026ndash;2646)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1124(525\u0026ndash;2802)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1334(525\u0026ndash;3340)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1237(536\u0026ndash;3195)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayment range, USD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e102-134164\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e102-126022\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e92-129453\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e102-130675\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eGini index\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.993\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.993\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.994\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.993\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePhysicians with specific payments, n(%)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAny payments\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e910(52.5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e937(54.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e925(53.4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e947(54.6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.4\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 500\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e752(43.4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e783(45.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e788(45.5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e844(48.7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 1000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e518(29.9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e531(30.6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e566(32.7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e572(33.0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e3.4\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 5000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e123(7.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e120(6.9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e161(9.3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e149(8.6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e8.1\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 10000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e56(3.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e63(3.6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e80(4.6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e83(4.8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e14.4\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 50000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e5(0.3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3(0.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e6(0.3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e5(0.3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e14.4\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 100000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1(0.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1(0.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1(0.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1(0.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003ePharmaceutical companies with 4-year payment data\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eTotal payments, USD (JPY)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2857414 (311458105)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3016587 (328807944)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e3558368 (387862074)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e3798523 (414038985)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e10.1\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAverage payments\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, USD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e3175\u0026thinsp;\u0026plusmn;\u0026thinsp;7678\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3240\u0026thinsp;\u0026plusmn;\u0026thinsp;7352\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e3868\u0026thinsp;\u0026plusmn;\u0026thinsp;8440\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e4037\u0026thinsp;\u0026plusmn;\u0026thinsp;9301\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e8.6\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMedian payments, USD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1150(511\u0026ndash;2624)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1095(525\u0026ndash;2808)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1336(525\u0026ndash;3319)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1239(536\u0026ndash;3202)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayment range, USD\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e102-134164\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e102-126022\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e92-129453\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e102-130675\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eGini index\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.992\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.993\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.994\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.993\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePhysicians with specific payments, n(%)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAny payments\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e900(51.9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e931(53.7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e920(53.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e941(54.3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e1.5\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 500\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e747(43.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e780(45.0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e785(45.3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e839(48.4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 1000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e517(29.8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e526(30.4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e561(32.4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e567(32.7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e3.2\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 5000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e121(7.0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e120(6.9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e160(9.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e148(8.5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e8.3\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 10000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e56(3.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e62(3.6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e79(4.6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e82(4.7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e14\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 50000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e5(0.3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e3(0.2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e6(0.3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e5(0.3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e14.4\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePayments\u0026thinsp;\u0026gt;\u0026thinsp;USD 100000\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1(0.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e1(0.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1(0.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e1(0.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Pharmaceutical Payments, Breast Cancer Specialists, Financial Transparency, Clinical Decision-Making, Japan","lastPublishedDoi":"10.21203/rs.3.rs-3915980/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3915980/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e \u003cp\u003eThe interplay between pharmaceutical companies and healthcare professionals is a critical facet of modern medicine, with financial relationships often influencing clinical practice. This study examines its impact on clinical practice in Japan, particularly in breast cancer treatment. It aims to uncover the prevalence, magnitude, and trends of payments made to breast cancer specialists by the pharmaceutical industry, thereby increasing transparency in these financial interactions.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eA retrospective analysis included breast cancer specialists certified by the Japanese Breast Cancer Society as of May 2023. Payment data from 2016 to 2019 were collected from 93 pharmaceutical companies in the Japan Pharmaceutical Manufacturers Association, focusing on payments for lecturing, writing, and consulting.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eThe analysis revealed an upward trend in pharmaceutical payments, with a total of USD 13,329,910.57 between 2016 and 2019, reflecting an average annual growth rate of 10.1%. The majority of these payments (81.4%) were for speaking engagements. The top 10 pharmaceutical companies made 89.5% of the total payments, with a spike in payments following the introduction of new drugs. Payment distribution was highly concentrated, as evidenced by a high Gini index, indicating a skew towards a few specialists.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eFrom 2016 to 2019, there was a notable rise in pharmaceutical payments to Japanese breast cancer specialists, paralleling the introduction of new drugs. The study highlights the need for continuous monitoring of these financial relationships to ensure unbiased clinical decisions and uphold healthcare integrity. Transparent and fair financial practices are essential for maintaining trust in healthcare and prioritizing patient care.\u003c/p\u003e","manuscriptTitle":"Increasing Trends of Pharmaceutical Payments to Breast Cancer Specialists in Japan: A Retrospective Study from 2016 to 2019","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-05 15:08:04","doi":"10.21203/rs.3.rs-3915980/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7397b1ca-4231-4dc9-ae73-28222efacfa7","owner":[],"postedDate":"February 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-07T20:36:08+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-05 15:08:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3915980","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3915980","identity":"rs-3915980","version":["v1"]},"buildId":"CiT4i_kKBbxQbnFL0ufpk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}