Global Insight Perspective | |
Significance | The influential Yomiuri Shimbun has called for Japan's clinical trials industry to do better; the tests that are necessary for drug registration represent a major barrier to market entry for foreign firms. |
Implications | Calls for greater action are nothing new, but Japan continues to make progress in turning the reforms of 2004 into a practical reality. However, current problems stem from a lack of technical capacity and human resources. |
Outlook | With key reforms in place and Japan now taking more of a "can-do" attitude on global trials policy, adequate resourcing is now the priority. |
Writing in the influential Yomiuri Shimbun newspaper, leading cancer expert Tadao Kakizoe has attacked the way in which clinical tests are used to support a New Drug Application (NDA) in Japan as a disgrace to patients and medical research. This part of the regulatory process (known locally as "chiken") has long been identified as the source of unnecessary expense and delay in bringing new medicines to the Japanese market. As such, foreign firms closely watch any signs of progress in this area.
In Japan, the agency charged with overseeing clinical data used to support marketing submissions, the PMDA, requires Phase I-III pharmacokinetic studies to support the registration of new medicines, in order to assess their safety and efficacy in people of a comparable ethnicity to Japanese subjects. Moreover, firms are required to conduct extensive post-marketing trials before a full commercial launch is possible, and as such Phase IV tests in fact form a core part of the regulatory process in the absence of comprehensive manufacturing provisions.
This need for extra testing is frequently blamed as the source of Japan’s notorious "drug lag", whereby new medicines arrive later in Japan than in other markets, or not at all. In an additional headache for innovators, it is estimated that on average, clinical trial costs in Japan are three to four times more expensive than in South Korea or Singapore and last more than twice as long. It is also reported that gaining approval for Good Laboratory Practice (GLP) alone can require as many as 150 documents. On the practical side, there is plenty of anecdotal evidence that the drug lag has a negative impact on drug access. For example, it is reported that Japanese regulators only recommended two new products from the U.S. pharmaceutical firm Pfizer—anti-smoking aid varenicline and sildenafil in pulmonary hypertension—for approval in November 2007, many months after approval was given in other advanced markets.
Manpower Issues
However, there is some evidence that the systemic problems in Japan's clinical trials system are not so much procedural but due to a basic lack of human resources. Recent years have seen plenty of reforms and fresh thinking; the Pharmaceutical Affairs Law was amended in 2004 to make tests on non-Japanese subjects acceptable to regulators; a report from the government’s Council for Science and Technology Policy—in collaboration with the private sector—outlined a way forward as long ago as late 2006. In fact, the problem now is a lack of manpower, and such issues are especially acute in the case of tests for new cancer drugs.
In response to the exponential rise in clinical tests for new cancer medicines in recent years, the Ministry of Health created the Japan Clinical Oncology Group (JCOG), which brings together 3,000 researchers and 170 medical institutions. The system allows for fast-track submissions of case reports across the entire spectrum of cancer drug testing, but despite successes, JCOG has not escaped criticism. According to Tadao Kakizoe, the service's data centre—which houses a national clinical trials register—is inferior and under-resourced compared with its U.S. and European counterparts. These problems are compounded by an endemic shortage of biostatisticians, clinical epidemiologists, and medical staff who are able to act as recruiters for cancer trials in hospitals.
Outlook and Implications
Kakizoe's complaints reinforce the view that while Japan is gradually succeeding in streamlining its clinical trials process, the steps that have been taken are too tentative, and while the right institutions to support this kind of medical research now exist, the government is having trouble putting its money where its mouth is. For example, three years after the creation of the PMDA and despite a huge backlog of work, the agency is only due to increase the number of review staff from 140 to 484 during this fiscal year. Moreover, it is only now that the PMDA is contemplating using the kind of rolling submissions that have helped to eliminate so much red tape on clinical trials in the United States and Europe.
Taking a longer term view, change is likely to remain incremental, to the detriment of patients. In fact, securing the appropriate human resources to support a more efficient clinical trials industry could turn out to be a more difficult challenge than rewriting laws or cutting red tape.