Fresh Doubts Cast Over Post-Marketing Trials

Criticisms of the pharmaceutical industry's real motives for undertaking post-marketing studies have been made by a special report in the British Medical Journal.

"These studies are challenging because of their observational nature, very different from the controlled settings of Phase II and III clinical trials. In theory, post-marketing studies are primarily used to answer an important clinical question: is this drug effective and safe in a non-controlled, real life setting? However, some of the studies I worked on were not designed to determine the overall risk/benefit balance of the drug in the general population. They were designed to support and disseminate a marketing message," noted the author of an editorial published on June 12, 2012 ("Post-Marketing Observational Studies: My Experience in the Drug Industry," BMJ, http://www.bmj.com/content/344/bmj.e3990).

The writer—who wishes to remain anonymous, and is referred to only as a former industry employee—admits to "playing" with the data. Other questionable practices are described, including the use of key opinion leaders to add credibility to the results and to influence decision makers and other prescribers.

Although the medical department developed the publication plans, designed the study, performed the statistical analysis, and wrote the final paper, the marketing team responsible for the product was directly involved in all stages and closely supervised the content of other educational scientific materials produced in the medical department and intended for potential prescribers, according to the author.

"Instructions from marketing to the medical staff involved were clear: to ensure that the benefits of the drug were emphasized and the disadvantages were minimized where possible," the writer stated. "Allowing companies to focus more time and efforts on drug development, or increasing transparency by encouraging industry authors to disclose the fact that the research has commercial objectives (as long as these are balanced with scientific value) would definitely help to develop better drugs for patients. And by better, I mean innovative, more effective, and safer drugs, not necessarily just more profitable."

Two other articles published by BMJ on the same day raise specific concerns about the motives behind post-marketing studies of new treatments for diabetes, and call for better regulation to ensure "a proper balance" between the commercial and clinical functions of these studies. These studies are also fuelling "catastrophic health expenditure" in low income countries by promoting new, more expensive treatments and influencing the prescribing habits of physicians, wrote the authors.

Edwin Gale, Emeritus Professor of Diabetic Medicine at the University of Bristol, UK, is worried about the role and legitimacy of post-marketing studies for new insulins, and has analyzed their use by the three main insulin manufacturers: Eli Lilly, Novo Nordisk and Sanofi-Aventis.

New analog insulins can cost up to four times as much as conventional human insulin, and although evidence suggests that they offer little benefit to most people with type 2 diabetes, Gale found that nearly 400,000 people worldwide have been recruited into post-marketing studies of insulin analogues since 2005.

One company recruited nearly 360,000 individuals. Most studies were carried out in middle- or low-income countries, had limited scientific value, and promoted wider use of more expensive insulins, and furthermore, most patients are likely to remain on the new insulins at the end of the studies, he noted.

It seems reasonable to ask whether a company would invest in such large-scale activities without a good commercial rationale, he continued. Although physicians may participate in good faith, the patient or healthcare system pays for a more expensive agent instead of one that is cheaper and equally effective, and the public is offered misleading claims of comparative merit based on studies of limited scientific value, wrote Gale.

John Yudkin, Emeritus Professor of Medicine at University College London, argues that post-marketing studies contribute to rising health expenditure. He points to Novo Nordisk's PREDICTIVE study, which paid doctors in 26 countries to start 47,565 people with diabetes on the company's insulin analog, Levemir.

Yudkin calculates that in India—where 3,435 patients were enrolled in the study and where patients must cover drug costs themselves—the annual cost of Levemir would be eight times more than a generic human insulin.

Novo Nordisk can be justifiably proud of some of their social responsibility initiatives over the past 10 years, but it now needs to reclaim the moral high ground, he wrote.