Making drug studies objective

Pharmaceutical firms provide hundreds of billions of yen each year in donations and other forms of payments to medical researchers. They play a key role in studies by the researchers on the effects of the drugs sold by them and use the data to advertise their products as more effective than those marketed by rival firms. Such ties of mutual dependency between drugmakers and researchers at university hospitals have been highlighted by the problems over clinical studies on drugs marketed by Novartis Pharma K.K.

The Japanese sales arm of the Swiss-based pharmaceutical giant Novartis is suspected of engaging in exaggerated advertising, using research papers based on falsified data on the effects of a popular drug to lower blood pressure. Based on a criminal accusation filed by the Health, Labor and Welfare Ministry, the Tokyo District Public Prosecutor’s Office has been interrogating people at Novartis Pharma and at five university hospitals involved in clinical research on the drug.

Suspicions have also surfaced that Takeda Pharmaceutical Co., Japan’s largest drugmaker, used inappropriate data for advertising the effects of its own blood pressure-lowering medicine, and a third-party investigation by a law office is now looking into the case.

Novartis is the world’s second-largest pharmaceutical company. The University of Tokyo Hospital was among the medical institutions that were involved in clinical research using Novartis products in which employees’ conduct was deemed questionable. It’s possible that similar problems exist at other drugmakers and research institutions. Clinical trials for obtaining data on new drugs to get official approval for marketing them are regulated by the law on pharmaceutical affairs, and drugmakers are bound by the rules under the law. But currently there are no legal rules to regulate clinical research by doctors to examine the effects and side effects on patients of drugs that are already approved and available.

Pharmaceutical companies make large donations to doctors who lead clinical studies at medical institutions. The money is meant to be used to promote research and education, and how to spend it is left up to the doctors’ discretion. It’s a convenient source of funding for laboratories at university hospitals. Drugmakers expect to use the data from such clinical studies to promote the sales of their products if their efficacy is proven by the research.

In one case of clinical research led by the University of Tokyo Hospital on a leukemia drug sold by Novartis, a third-party probe has found that Novartis employees were in fact deeply involved in planning the research as well as in collecting and analyzing clinical data on patients who were given the drug. The company effectively sponsored the clinical research for the benefit of its marketing activities.

The Novartis employees were reportedly involved in setting up the research procedure, creating documents, communicating with other institutions taking part in the study as well as preparing materials to be used by the doctors when presenting the research results at academic conferences.

They kept photocopies of the results of the hospital’s questionnaires on patients who took the drugs — in possible violation of the law on protection of private information.

Their failure to report to the health ministry information concerning the drug’s side effects on patients could constitute violation of the pharmaceutical affairs law.

The probe concluded that the researchers went along with the practice because they wanted the funding and other services provided by the drugmaker. Novartis is found to have donated ¥8 million over three years to the University of Tokyo laboratory involved in the leukemia drug study. The researchers were also found to have used Novartis employees as “staff,” asking them to add side-effect information to their reports.

While the investigation said it has not found evidence that the Novartis workers tampered with the data, no system appears to have been in place to prevent manipulation of the research outcome to the advantage of the drugmaker.

In the separate case of the firm’s blood-pressure lowering drug, data on the effects of the drug was found to have been falsified in clinical research by university hospitals in which a Novartis employee took part in data analysis, although it has not been determined who manipulated the data. Three of the five medical institutions that took part in clinical studies on the drug have retracted their research papers — which were used by Novartis as a marketing tool after the papers were carried in overseas medical journals.

Both pharmaceutical companies and medical institutions need to terminate practices that raise serious doubts about the neutrality of clinical studies on drugs.

The health ministry in April began discussions on whether legal regulations with punitive measures would be necessary to ensure ethical clinical research, and plans to reach conclusion by this fall. The agenda of its discussions will reportedly include the quality of research, management of the health of patients taking part in studies as well as the degree of involvement of pharmaceutical firms in the research.

Novartis has said it will start to sign formal contracts with doctors who conduct clinical studies on its products so that its relations with researchers become more transparent.

The Japan Pharmaceutical Manufacturers Association has issued a directive to its member firms banning the offer of donations to university hospitals and other institutions as a means of supporting researchers who conduct clinical studies on their products. Funding and the supply of materials to support studies must be based on contracts with institutions involved, the directive says.

These efforts may serve to make the ties between drugmakers and medical institutions more transparent. But to ensure neutrality in clinical studies of drugs, the government needs to expand its support for researchers so that they don’t have to rely on money from the pharmaceutical industry.

Researchers, instead, should use public funding for research aimed at aiding patients without the risk of having the results dictated by the interests of drugmakers.