In the face of the extraordinary time and cost pressures, companies are making changes to improve R&D efficiency, addressing those factors within their control, such as dumping drug candidates that clearly don’t have a chance of making it. A recent example of both a difficult disease area and hard-to-conduct clinical trials is Alzheimer’s disease, as cited in the OHE report. Last August, Pfizer and Johnson & Johnson decided to discontinue development of Alzheimer’s drug bapineuzumab after it failed in two late-stage clinical trials.
But nobody ever said drug development, especially for difficult diseases would be easy or cheap. That does not justify hiding unfavorable clinical data or stacking review panels to ensure favorable review. The rush to market has lead to an increase in misleading and/or incomplete clinical data that has, in some cases, supported marketing approval of drugs with lethal consequences.
“On the one hand, there are a lot of important industry-funded studies that are accurate, relevant, and useful,” commented Jerry Avorn M.D., a professor of medicine at Harvard Medical School and chief of the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, who has specialized in spotting adverse events from drug use. “There is also a multiyear history of abuse and distortion.”
According to a recently published article in the Washington Post that attracted a lot of attention, the government once funded the lion’s share of drug development studies. But since about the mid-1980s, research funding by pharmaceutical firms has exceeded National Institutes of Health spending. Last year, the industry spent $39 billion on research in the United States, while NIH spent $31 billion.
Over a year-long period ending last August, the article noted, the New England Journal of Medicine (NEJM) published 73 articles on original studies of new drugs, encompassing drugs approved by the FDA since 2000 and experimental drugs. Of those articles, 60 were funded by a pharmaceutical company, 50 were co-written by drug company employees, and 37 had a lead author, typically an academic, who had previously accepted outside compensation from the sponsoring drug company in the form of consultant pay, grants, or speaker fees.
Marcia Angell, retired editor of the NEJM who spent 20 years as the publication’s editor commented, “It used to be that drug companies would hand their new drug over to an academic center to have it tested, and then they sat back and waited,” she said. “Now they’re intimately involved in every step along the way, and they treat academic researchers more like hired hands.”
It’s hard to know how much this involvement influenced clinical trial result interpretations that resulted in the approval of dangerous drugs, like Avandia, for example. “If you looked closely at the data that was out there, you could see warning signs,” said Steven E. Nissen, a Cleveland Clinic cardiologist who issued one of the earliest warnings about the drug. “But they were overlooked.” A Food and Drug Administration scientist later estimated that the drug had been associated with 83,000 heart attacks and deaths.
The FDA pulled the controversial diabetes drug from retail pharmacies beginning in November 2011 due to its cardiovascular risks. Avandia remains available to patients who’ve been safely using the drug, those who have had no success in controlling their blood sugar with other diabetes medications, and patients who have been informed of the risks and still choose to take it are enrolled in a special program to qualify to receive the drug, according to the FDA.
Pharma’s hands-on practices with regard to clinical data has begun to cost the industry some big money. Last July, in a civil settlement agreement, the United States alleged that GSK promoted Avandia to physicians and other healthcare providers with false and misleading representations about the drug’s safety profile, causing false claims to be submitted to federal healthcare programs.
It also alleged that GSK stated that Avandia had a positive cholesterol profile despite having no well-controlled studies to support that message. Further, the Department of Justice said, the company sponsored programs suggesting cardiovascular benefits from Avandia therapy despite warnings on the FDA-approved label regarding cardiovascular risks.
GSK agreed to pay $657 million relating to false claims arising from misrepresentations about Avandia.