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The spate of drug scandals may alter the relationship between manufacturers and research institutions, and reshape Japan’s clinical research industry.
Japan’s pharmaceutical industry has been littered by a spate of drug scandals in recent years. In April 2014, Takeda Pharmaceutical was questioned for a clinical research Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) for its hypotensive drug Blopress (candesartan cilexetil) regarding possible data manipulation, conflict of interest, and appropriateness of the use of study results in promotions. Investigation by a third-party organization confirmed several instances of involvement by the company in statistical analysis of this “doctor-initiated research.” Furthermore, inappropriate promotions of the study results were pointed out.
In another case, a former Novartis employee embroiled in the Diovan (valsartan) scandal has been arrested. Japan’s Ministry of Health, Labor and Welfare (MHLW) has also filed a criminal complaint against the company. A fine of $18,710 for exaggerated advertising is also highly likely to be levied against Novartis. Furthermore, the company’s recent scandal involving a failure to report the side effects of its leukemia drugs Tasigna (nilotinib) and Gleevec (imatinib) could earn more than a rebuke by the MHLW to clean up its act.
Refining clinical trials
Clinical trials have been decreasing in Japan over the past few years, falling from a peak of 375 in 2011 to 337 in 2013 according to ClinicalTrials.gov (1). This decline, however, is set to change as the country liberalizes its clinical research regulations in three key ways, according to Ang Wei Zheng, a pharmaceuticals and healthcare analyst at Business Monitor International (BMI).
Firstly, Japan is looking to relax rules that require new drug applications from outside the country to have clinical trials that use a sufficiently large number of Japanese citizens. Secondly, Japan has created new tracks for clinical research in a bid to accelerate the development of its pharmaceutical industry especially in stem cell research as echoed in its Act on Pharmaceuticals and Medical Devices (PMD), which passed in 2013. This legislation creates a separate expedited approval system for regenerative medicines where a provisional approval can be obtained after a single clinical trial as long as there is confirmed evidence of effectiveness. Thirdly, Japan has been a step ahead of the US by delineating a biosimilars regulatory pathway in 2007.
In reforming this system, Japan is following the example of European countries that face similar challenges. France, for example, requires companies to declare their links with students, associations, establishments, and the specialist press. In addition, companies have to declare all benefits provided to doctors and others. To control aggressive advertising, France also requires promotional materials to gain approval before use.
The string of drug scandals in Japan may change the relationship between drug manufacturers, doctors, and research institutions. Ang says, “We expect more scrutiny that will result in a more cautious relationship between parties involved. Eventually, this one-to-one relationship will involve more parties, including regulators, who are keen to avoid a repeat of the scandals. However, we do not expect this relationship to cease due to its symbiotic nature as research institutions require funding and drug manufacturers stand to benefit from an accelerated drug development process with these links.”
The government has adopted a proactive role to deal with the situation. On Jan. 8, 2014, MHLW sent a “Notice to comply with ethical guidelines for clinical research and epidemiologic research” to all research institutions in Japan. The Ministry of Education, Culture, Sports, Science, and Technology, which has governance over national universities, revised its guidelines for research activity misconduct measurement and reinforced the measures against research institutions.
The Japan Pharmaceutical Manufacturers Association (JPMA) issued a transparency guideline which required its members to disclose the following: fees for research and development, fees for grants for academic research, fees for writing manuscripts, fees for provision of information (e.g., speaker fee, honorarium), and other fees (e.g., entertainment). By February 2014, all 70 member companies of JPMA disclosed their own transparency policies.
Naoya Takuma, healthcare, pharmaceuticals, and life sciences lead of PricewaterhouseCoopers (PwC) Japan says, “An effective reform needs to have two components. New regulations, incentives/penalties, and government oversight over the conduct of clinical research have to be put in place. Another is to have pharmaceutical companies put in place a more robust risk and compliance governance system.”
Increasing transparency of work practices
When discussing transparency, Takuma adds, “All pharmaceutical companies, both domestic and foreign, realize now that the transparency of clinical research sponsored by pharmaceutical companies will be under close scrutiny, and that they will be required more than before to disclose not only the outcome of the research but also other factors such as planning and process of research.”
Internal measures to prevent recurrences include strengthening of the compliance system, adding new members to review materials from both a legal and medical perspective, strengthening the system for the screening and evaluation of donations and implementing information technology support for hardwiring, and monitoring payment approvals and payments to healthcare professionals. In recent years, some companies have also introduced the Medical Affairs function with Medical Science Liaisons to manage Key Opinion Leaders and to support their clinical research activities independently of the sales and marketing function.
Japan will continue to remain a key player in the pharmaceutical industry despite the drug scandals. Ang says, “The government will not impose overly onerous regulations that will derail the promotion of Japanese clinical research. From a domestic standpoint, the pharmaceutical industry remains a cornerstone for future growth in the country with regenerative medicine showing strong promise to drive the economy and meet the needs of its ageing population. It is thus unlikely that the government will risk stifling this industry and measures will always be weighed against the goal of making Japan a pharmaceutical research and development hub.”
Globally, Japan remains the second largest market in the world with pharmaceutical sales at $112.6 billion in 2013 (2). The country also ranks highly on BMI’s Risk/Reward Index for strong patent respect and political stability (3). This ranking maintains Japan as a highly attractive market for pharmaceutical companies that are looking to launch innovative drugs in the market. Moreover, the bold steps taken by the country in the field of regenerative medicine will help Japan maintain its premier position regionally against rivals like South Korea.
1. Clinicaltrials.gov, www.clinicaltrials.gov, accessed Oct. 14, 2014.
2. BMI, Pharmaceutical Sales 2014.
3. BMI, Risk/Reward Index 2014.
Article DetailsPharmaceutical Technology
Vol. 28, Issue 12
Citation: When referring to this article, please cite it as J. Wan, "Drug Scandals Impact Industry in Japan," Pharmaceutical Technology 28 (12) 2014.