TOKYO, Feb. 20 (Kyodo) — The manipulation of clinical research data for a blood pressure drug sold by Novartis Pharma K.K. has led a special squad of Tokyo prosecutors to search the Japanese unit of the Swiss drugmaker as well as the university that conducted the research.
An industry official says the case reflects structural issues behind the relationship between doctors and the pharmaceutical industry, while a ministry survey suggests it could be just the tip of an iceberg.
"If compared with a master-slave relationship, the doctor is master and the drugmaker is slave," a former Novartis executive said. "Why do only manufacturers come under criticism?"
The health ministry filed a complaint with the Tokyo District Public Prosecutors on Jan. 9, alleging Novartis violated the Pharmaceutical Business Law with a misleading advertisement for the drug Diovan based on manipulated data.
The former Novartis official argues that it was the doctors that planned and implemented clinical studies for a research paper used in the ads. If the studies turn out to be inappropriate, it is the doctors who should be held responsible, the ex-official says.
Yet a Novartis employee was involved in the research, taking charge of data analysis. The company has also made large donations to universities, suggesting substantial involvement in research undertakings.
The former executive said, "In a way, it's a necessary evil. Without money, new research will not be conducted."
In some quarters, doubts had been expressed for several years about data that purported to show Novartis' blood-pressure lowering medicine was effective also in reducing the risk of cerebral stroke and angina.
But the company kept using the data in its advertising. The former executive said that it may be because the papers were published in prominent foreign scientific journals that rely on peer reviews.
"Because the studies were supposed to have been checked by many people, the company may have grown too confident (about the data)," the former executive said.
The credibility of the studies on Diovan was apparently called into question at a meeting at the Ministry of Health, Labor and Welfare in September.
At the meeting of the ministry's review committee on the clinical research on Diovan, a Novartis employee presented papers carried in overseas journals.
"We want you to understand that clinical research is normally accompanied by some degree of human error," the Novartis employee said at the meeting, explaining that the average margin of error in the data is 9.6 percent.
The employee's apparent attempt to justify errors drew a strong reaction from one of the committee members. "It's absolutely not within the permissible range. If it was 10 percent in error, it would not stand up as a valid scientific paper," the member said.
Meanwhile the Novartis scandal may not be exceptional. A survey by the health ministry compiled in December showed 137 cases of impropriety such as failures to comply with state ethical guidelines in clinical studies conducted by universities and hospitals across the country since April 2009.
But prosecutors were apparently unimpressed by the ministry's investigations leading to its criminal complaint filed in January, which fell short of naming any individuals responsible for publishing the ads.
"We need to examine whether there is evidence that can be used for building criminal cases outside what was brought by the health ministry," a senior prosecutor said.
The case has also generated concern about the potential impact on health insurance as a result of an increasing number of doctors being inspired by the ads to prescribe Diovan. That could lead to an expansion in insurance fees and tax-funded health care payments.
The ministry asked the advisory Central Social Insurance Medical Council to see if there was any such impact. The council has yet to draw a conclusion.
"It's hard to prove it," a ministry official said. "Even if estimate is produced, it won't confirm that there was an impact."
Some people involved in government projects promoting medical research say Novartis should not be let go scot-free because the scandal has undermined confidence in Japanese research. They suggest Diovan prices should be cut.
"There are no provisions for changing drug prices due to these issues," a senior health ministry official said. The ministry, however, appears poised to consider some form of administrative penalty on the company as prosecutors' investigations continue.