Last month, our trust in the objectivity of medical research was violated. The New York Times reported that a study showing that annual CT scans of smokers for lung cancer could remarkably reduce deaths from the disease was surreptitiously paid for by the tobacco industry. The 2006 study, published in the New England Journal of Medicine, was in part funded by an obscure charity, the Foundation for Lung Cancer, which, it turns out, got its money from the parent company of Liggett Group Inc., a cigarette manufacturer. A critic’s designation of this funding as “blood money” quickly crisscrossed the country.
The potentially tainted lung cancer study raises a question that should give us a painful knot in our collective abdomen. What don’t we know about clinical research in the U.S. that could be bad for our health?
With federal funding for research declining, private industry has stepped forward to fill the money vacuum, and many clinical investigators have eagerly accepted the largesse.
We usually think of “industry” in terms of pharmaceutical companies. But research is also paid for by food companies, disease-oriented organizations such as the American Diabetes Assn. and foundations with impressive but ambiguous names whose motives are as obscure as their titles.
The episode that first highlighted how financial conflicts of interest might be harmful to patients’ health involved Jesse Gelsinger, an 18-year-old with a mild form of a genetic disorder that made him deficient in a protein essential for metabolism. Still, he was healthy because he could manage his condition through diet and medication.
In 1999, he volunteered for a research study at the University of Pennsylvania. The scientists conducting the study replaced the gene responsible for Jesse’s protein deficiency by attaching it to a common cold virus and then infecting him with the “harmless” virus. In four days, Jesse was dead.
It was subsequently disclosed that the virus-carrier technique used to treat the teenager had been patented, and that both the study’s lead scientist and the medical center where it was conducted held stock in the company that owned the patent.
The scientist denied that his use of the gene therapy technique was premature. But critics wondered whether his financial interests and those of the medical center had influenced the decision to push the experiment forward before there was sufficient evidence of the technique’s lack of toxicity.
Unfortunately, there are many other clinical research studies in which the participants’ financial interests may have played a role. In 2003, the British Medical Journal published a summary of dozens of clinical studies on the effect of various drugs on patients. The summary showed that drug studies funded by pharmaceutical companies were about four times more likely to have outcomes favorable to the companies than similar ones paid for by such noncommercial entities as the National Institutes of Health. An analysis of more than 200 research articles on the effects of milk, soft drinks and juices on health, published in the Public Library of Science/Medicine in 2007, produced a similar conclusion. Studies paid for by milk and beverage companies were four to eight times more likely to be favorable to them than those funded by noncommercial entities.
It’s not only clinical research that is corruptible. Clinical-practice guidelines for the recommended treatment of various diseases -- such as those produced by the American Heart Assn. or the American Society of Nephrology -- may also in part reflect the financial interests of contributors.
Guidelines on the use of statin drugs to lower cholesterol, nicotine patches to stop smoking, Epogen to treat anemia and testosterone to boost the energy of tired, elderly men were tainted by the participation of physicians who had accepted speaking or consulting fees from companies that stood to benefit from their recommendations, according to numerous newspaper stories, some published by The Times.
Evidence unearthed in lawsuits and by investigative reporters shows that some Food and Drug Administration panels stacked with members deemed friendly to drug companies made questionable judgments about drug approvals. One such drug was Rezulin, which is used to treat diabetes. The drug was kept on the market despite accumulating evidence that it was causing liver failure in some patients and killing others.
What are the possible consequences of financial bias in clinical research and practice guidelines? One is that physicians may be more likely to prescribe a drug for a condition that should first be treated with non-pharmacologic remedies. Another is that prescribing the newest, research-touted drug may expose patients to side effects not fully recognized in the drug’s clinical trials. Still another is that new drugs are the most expensive on the market, even though they may be no more effective than cheaper, generic substitutes. Cost is especially relevant when treatment requires diagnostic tests such as CT scans, MRIs and biopsies. These tests are expensive, and some can be risky. Experience shows that once such tests are approved by the FDA for use in a single clinical condition, they are quickly used by doctors in many others.
So what can be done about our conflict-riddled system? Most of the brouhaha has been over the failure of physicians conducting research projects to disclose the sponsors of their studies or their personal financial ties to the companies whose drugs, techniques or devices they are testing. Some say that requiring them to reveal the financial interests would be a great disinfectant. But this is magical thinking. For instance, if I had known that the researchers at Weill Cornell Medical College conducting the CT scans of smokers were in part funded by a cigarette manufacturer, would I have automatically concluded that they might rig the study to produce a favorable outcome?
Maybe, if I were a soothsayer. In fact, disclosure of financial ties may give a scientist or researcher a clean conscience, but that doesn’t erase the possibility of a conflict. The point is that disclosure may be necessary, but it is not sufficient to resolve the complex financial relationships often found buried in clinical studies.
What then do we do? For starters, editors of medical journals must thoroughly vet the funding sources of -- and possible financial conflicts of interests of their authors in -- the studies they approve for publication. They should not be able to hide behind their personal judgments that financial relationships involved in a study had no consequences for the outcome. Second, academic medical centers should pay more attention to their researchers’ financial conflicts of interest and the possible financial benefits to medical centers of researchers’ inventions. Finally, practice-guideline committees and FDA panels should reduce their reliance on financially conflicted physicians when they select doctors and panel members. This would reassure the public that they are producing clinical policies untainted by financial ties to drug or device companies.
For some years, I have believed that the medical profession should reform itself by devising its own policies for dealing with its conflicts of interest. But the efforts so far have been superficial. Some academic medical centers have eliminated gifts or resident and staff lunches paid for by pharmaceutical companies. But they have continued to allow drug companies to pay staff members for work as consultants or speakers, which may introduce bias in their decision-making. Few have addressed possible institutional conflicts resulting from patents.
Sensing public concern, Congress has recently stepped into the fray by holding hearings on pharmaceutical and device companies’ payments to individual physicians. But congressional staffers are already beginning to ask the next question: How is this money being used? What influence does it have on researchers and the policies of medical centers and professional societies? Are their decisions blemished by such donations? These questions will not go away.