Evaluation of financial relationships between Japanese certified pediatric hematologist/oncologists and pharmaceutical companies: a cross-sectional analysis of personal payments from pharmaceutical companies between 2016 and 2019

1 INTRODUCTION

Among various types of pediatricians, pediatric hematologist-oncologists (PHOs) received the largest amount of personal payments from pharmaceutical companies according to a study in the United States.¹ Plausible explanation for this is the increasing emergence of new oncology drugs over the past two decades.² In addition, the entire pediatrics field has been characterized by fewer rigorous clinical trials and subsequent off-label prescribing worldwide including Japan compared with those for adults.^3-5 Appropriate collaboration with the industry is essential in elucidating diseases and developing treatment especially for rare diseases such as pediatric cancer. However, unlike payments for clinical trials and research, personal payments such as lecturing reimbursement, consulting payments, and meal and beverages may undermine patient trust and influence physicians’ treatment choices.^6-11 As oncologists and hematologists have been increasingly targeted by pharmaceutical companies over the past few years mainly reported by studies in the United States,^12-14 it is particularly important to properly manage financial conflicts of interest (FCOI) in order to prevent undue influence on patient care by financial interests from pharmaceutical companies and to build patients’ trust among the PHOs.¹⁵ This trend in the financial relationship between PHOs and pharmaceutical companies could also apply to the situation in Japan, the third world-largest pharmaceutical market. However, there has been a lack of evidence on the magnitude of personal payments made by pharmaceutical companies to PHOs in Japan. This study aimed to evaluate the magnitude of pharmaceutical payments among Japanese PHOs board-certified by the Japanese Society of Pediatric Hematology/Oncology (JSPHO) as well as the extent of payments to key opinion leaders.

2 METHODS

3 RESULTS

4 DISCUSSION

In this study, we found that 70.0% of all Japanese PHOs increasingly received personal payments from pharmaceutical companies between 2016 and 2019. The median annual payments per PHO was less than 1% of their annual income ($110 092 for the average annual income of Japanese pediatricians in 2021). This study was the second study assessing board-certified specialists in Japan, only following Ozaki et al.¹³ Compared with their findings, the median payments to PHOs were lower than those to the board-certified oncologists in Japan ($715 among the PHOs in 2016 vs $1101 among the board-certified oncologists in 2016). Considering that the number of pediatric cancer patients accounts for only about 0.2% of the total number of new cancer patients in Japan annually,²⁸ it is reasonable that the payments to PHOs were lower than those to general oncologists.¹³ Meanwhile, given that the number of board-certified PHOs was smaller than that of oncologists (307 PHOs vs 1080 oncologists) in Japan, the relatively high payment amount and prevalent PHOs’ acceptance of personal payments from the pharmaceutical companies could not be understated.

Comparing our findings with other studies outside Japan, Parikh et al. reported that 36.2% of the PHOs in the United States received median annual payments of $189 (IQR: $71-$1870) from the industry majorly for foods and beverages.²⁹ Similarly, Karas et al. found that pediatricians who specialize in hematology and oncology received a median personal payment of $55 (IQR: $17-$213) in the United States.¹ Both studies from the United States reported that PHOs in the United States received much lower personal payments than those made by Japanese board-certified PHOs. This difference could be due to the inclusion of PHOs board-certified by the JSPHO, who are required to complete several years of clinical experience and training, while the studies in the United States included PHOs whose specialty was self-declared by the physician and who did not receive board certification.

The results implicated that the payments to board-certified PHOs were significantly higher for university professors, JSPHO board members, and guideline authors than those to PHOs who are not. The high concentration of payments to these leading physicians is consistent with the fact that these positions are commonly known as “key opinion leaders,” indicating that pharmaceutical companies are likely to make payments to recruit them for lectures and consulting. This trend has been reported both domestically and internationally. In Japan, Saito et al. reported that more than 85% of executive board members of Japanese professional medical societies (PMSs) received payments from pharmaceutical companies in 2016.³⁰ Furthermore, 89.3% of executive board members in the Japan Pediatric Society received payments with a median of $3853 (IQR: 2734-11 552).³⁰ Considering international reports, 24.4% of leaders of PMSs received payments in Australia,²⁷ and 72% of board members of PMS received payments in the United States.²⁶ Unlike leading physicians conducting clinical trials and research sponsored by industries, the key opinion leaders in influential and public positions included in this study, such as the university professors, board members, and the guideline authors, should be impartial and avoid potential FCOI. As shown by a number of cases, inappropriate and substantial payments from the industry to such key opinion leaders as board members and guideline authors have jeopardized physicians’ clinical practice and downstream patient care.^{17, 31-34} One recent systematic review by Nejstgaard et al. elucidated that conflicts of interest with the industry associated with more favorable recommendations directing pharmacotherapy and interventions in clinical practice guidelines and opinion statements endorsed by PMSs.³⁵ The key opinion leaders influential and in public positions such as the board members and clinical practice guideline authors should be safeguards of patients preventing from undue influence and pressure of the industry and achieve patient-centered care by managing their own FCOIs with the industry. At least full disclosure of these personal payments among the key opinion leaders should be ensured, as among the clinical practice guideline authors.

Additionally, we found that the median personal payments and total payments had increased over the four years. The increase in the median payment could be attributed to the fierce marketing competition for new drugs in the field of hematology and oncology.^{2, 36} Our systematic review of all drugs newly approved and gained additional indication between 2015 and 2019 (one year before and during the study period) found that there were 96 new approved or added indication drugs in the field of hematology and oncology in Japan (Supporting Information Material S4). About 40% (38 out of 96) of drugs noted the pediatric dosage in the medication package insert. Especially, among the top five companies, while the total payments from Kyowa Kirin and Sumitomo Dainippon Pharma remained constant or decreased, the payments from Chugai, Takeda, and Bayer continuously increased over the four years. All three companies had novel drugs approved for hemophilia A during the four years such as emicizumab (HEMLIBRA approved in May 2018) from Chugai Pharmaceutical; rurioctocog alfa pegol (ADYNOVATE approved in December 2017) and rurioctocog alfa (ADVATE approved in August 2019) from Takeda Pharmaceutical; octocog alfa (KOVALTRY approved in March 2016) and damoctocog alfa pegol (JIVI approved in September 2018) from Bayer Yakuhin. These newly approved drugs for hemophilia A, which is known for its high drug prices may account for the recent increased trend in pharmaceutical payments.

This study included several limitations. First, the manual collection of payment data from pharmaceutical companies may include human error. Second, as the JPMA does not require the member companies to disclose common types of payments such as meal, accommodation, travel, and education on the individual physician level,³⁷ this nondisclosure could have led to underestimated payment values among the Japanese PHOs.^{13, 16, 17} Third, as the current payment disclosure scheme in Japan does not include information on drug and product names associated with the payments, this study could not assess the direct association between payments and specific drugs. Fourth, as the JSPHO did not publicly disclose the name lists of board-certified PHOs for previous years, our study might have included physicians who did not receive the board certification in PHO during the payment period.

Despite several limitations, this study elucidated that the majority of Japanese PHOs received increasingly larger amounts of personal payments from pharmaceutical companies for the reimbursement of lecturing, writing, and consulting between 2016 and 2019. These payments substantially concentrated on a small number of PHOs at leading positions such as university professors, society board members, and clinical practice guideline authors.

CONFLICTS OF INTEREST

Dr. Kusumi received personal fees from Otsuka Pharmaceutical Co. Ltd outside the scope of the submitted work. Dr. Saito received personal fees from TAIHO Pharmaceutical Co. Ltd outside the scope of the submitted work. Drs. Ozaki and Tanimoto received personal fees from Medical Network Systems outside the scope of the submitted work. Dr. Tanimoto also received personal fees from Bionics Co. Ltd, outside the scope of the submitted work. Regarding nonfinancial conflicts of interest among the study authors, all are engaged in ongoing research examining financial and nonfinancial conflicts of interest among healthcare professionals and pharmaceutical companies in Japan. Among their previous articles, the authors have self-cited several articles in this study to gain deeper insights and explain the context of financial conflicts of interest among healthcare professionals in Japan. Dr. Kusumi was a hematology specialist board certified by the Japanese Society of Hematology.

AUTHOR CONTRIBUTIONS

Ms. Kamamoto conceptualized and designed the study, collected the data, analyzed data, drafted the initial manuscript, and revised the manuscript. Mr. Murayama conceptualized and designed the study and the data collection instruments, collected data, carried out the initial analyses, drafted the initial manuscript, reviewed and revised the manuscript, and supervised the study. Dr. Kusumi conceptualized and designed the study and the data collection instruments, collected data, drafted the initial manuscript, and reviewed and revised the manuscript. Mr. Yoshida conceptualized and designed the study, collected the data, and drafted the initial manuscript. Drs. Saito, Sawano, and Ms. Yamashita conceptualized and designed the study and critically reviewed and revised the manuscript for important intellectual content. Drs. Tanimoto and Ozaki conceptualized and designed the study, coordinated and supervised data collection, and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.