Tuesday, April 24, 2007

With Drug Studies, Read Between the Lines

With Drug Studies, Read Between The Lines

News flash: When the drug industry pays for research on new drugs, the findings are more likely to be favorable than when the same sorts of studies are funded by those with no financial ties to the industry, such as Cochrane Collaboration reviews. This was the conclusion of a recent "study of studies" (called a meta-analysis) by the British Medical Journal. Researchers compared reviews from the Cochrane Collaboration -- an international, not-for-profit, independent body that critiques health-care outcomes -- with industry-supported studies. It may not be that the findings that were supported by industry were falsified or otherwise tampered with, but rather that critical information on methodology limitations and other aspects of the study design and certain results were less likely to be included in the published report -- and that's a potentially dangerous problem since it is here that knowledgeable experts are likely to see red flags that raise important questions.

HOW DOES THIS HAPPEN?
A meta-analysis of this kind comes along every few years, says Jay S. Cohen, MD (www.medicationsense.com), author of What You Must Know About Statin Drugs & Their Natural Alternatives (Square One) and Over Dose: The Case Against the Drug Companies (Tarcher/Penguin). In his expert view, the results come as no surprise. Always anxious to introduce and sell new drugs, pharmaceutical companies seem to persistently slant the research their way, maximizing the positive aspects of its exciting new products and minimizing those of concern, he says. "It should be called the drug sales industry, not the drug industry," muses Dr. Cohen. We talked more about the inherent conflict of interest, and why it is so important for consumers to know about it.

AN OBVIOUS CONFLICT OF INTEREST
Drug companies clearly have a vested interest -- hundreds of millions of dollars worth -- in developing, receiving approval for and marketing a new drug. As brand-name drugs that drug companies had exclusive rights to market go "off patent" and become available in cheaper generic versions, the ability to develop "new" drugs -- even though many of these drugs differ little from earlier drugs -- enables Big Pharma to continue to pull in the mind-numbing profits that dwarf those of most other industries. Not surprisingly, it is believed there is considerable pressure on drug-company-paid researchers to accentuate the positive results and minimize the negative ones, even though this demonstrates an obvious conflict of interest.

In contrast, the Cochrane Collaboration reviews are conducted without industry support from drug companies, and its reviews and database are considered a gold standard for analyses by the medical establishment. Studies by such independent groups, in general, are more likely than industry-sponsored research to identify and address the issue of bias. Using this more systematic and critical approach, independent reviews are not apt to simply rubberstamp products. (Unfortunately, Big Pharma's tentacles extend into doctors' offices and their affiliated medical schools, with promises of free samples, seminars in exotic locales and academic grants, resulting in a large number of independent doctors with links to drug companies.)

PLAYING DODGEBALL WITH LIFE-THREATENING DRUG RISKS
Dr. Cohen points out that this over-reliance on industry-sponsored studies has already had serious and harmful consequences. There's the case of the arthritis drug, Vioxx (rofecoxib), which was withdrawn from the market in 2004 because of increased risk of heart attack and stroke. In 2005, a New York Times article reported that manufacturer Merck was well aware of increased cardiovascular risks, yet covered them up... documents that emerged during trial revealed that Merck scientists were concerned about increased heart risks as far back as 1997, two years before Vioxx was even approved. However, the drug giant downplayed these negative studies, and one marketing document even advised sales reps to play "Dodgeball" -- that is, dodge questions from doctors concerned about Vioxx's risks. In another egregious instance, Merck funded and approved the design of the study of Vioxx at Boston's Brigham and Women's Hospital, only to discredit researchers' conclusions (and insist that a Merck employee remove her name from the study) when the research revealed increased heart attack risk. Months later, the company was finally compelled to remove Vioxx from the market due to safety concerns and an increase in cardiovascular events.

Dr. Cohen is also worried about a recent study of a best-selling drug, Lipitor (atorvastatin). Pfizer has significantly raised its profits by aggressively promoting high-dose Lipitor -- which costs one-third more than the low dose -- along with new uses for this cholesterol-lowering statin. A Pfizer-sponsored study reported in The New England Journal of Medicine (August 10, 2006) suggests that Lipitor should be taken by people at risk of a second stroke, or a stroke after a transient ischemic attack (TIA), even if they don't have heart disease. But, notes Dr. Cohen, in this study overall mortality stayed the same, whether they took Lipitor or not. While it's true that cardiovascular deaths dropped in the study, other deaths rose, so despite Pfizer's positive spin on the research -- which earned them front-page headlines across the country -- it didn't really connote success. This raises serious concerns about safety, says Dr. Cohen, since Lipitor -- especially at high doses -- is a potent drug with powerful side effects. Authors of this study had financial ties to Pfizer, and several were Pfizer employees, facts that raise red flags about potential conflicts of interest.

GREATER TRANSPARENCY REQUIRED ACROSS THE BOARD
Interestingly, while I was writing this story, a news report came out on a similar study revealing the same research bias in the food industry. In a review of 24 industry-backed studies of soft drinks, milk and juices, 21 (88%) had results favorable or neutral to food manufacturers. Of 52 independent studies without industry financing, only 32 (62%) were favorable or neutral, and 20 (38%) were unfavorable.

What should you do with all this information? The Cochrane Collaboration recommends that doctors and consumers learn to view industry-supported studies with greater caution. In particular, always examine study author's company affiliations, advises Dr. Cohen. Take into account whether researchers are affiliated with or paid by the manufacturer of the drug being studied. Because of recent concerns, medical journals increasingly require this information of contributors and share it with readers. For greater reliability, Dr. Cohen urges greater transparency overall, including more information on methodology and estimated effects of drugs. And, whenever possible, it is wisest to base health-care decisions on unbiased studies without industry sponsoring.

Note:
To read about more practical strategies for safe and effective use of drugs (exercise health skepticism about new drugs, ask about generics, etc.), see the Daily Health News article from February 2, 2006.

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