January 27, 2008
A paper published January 17 in a prestigious medical journal demonstrated in the starkest of terms how pharmaceutical companies tend to publish research that's favorable to their products and leave unfavorable results tucked away in their files. It's a problem that everyone outside the industry already recognizes, but the results of this most recent study should really set off alarms.
Led by Dr. Erick Turner of the Oregon Health and Science University in Portland and published in the New England Journal of Medicine , the study took the results of 74 Food and Drug Administration (FDA)-registered trials of antidepressant medications (trials done by the companies that developed the drugs) and compared them with the results that the drug companies published in peer-reviewed medical journals. The study involved 12 antidepressants approved between 1987 and 2004.
In seeking approval of new drugs, companies are required by law to register their clinical trials with the FDA before conducting them, and then report results to the agency when they're done. Of those 74 trials, the survey found 38 that showed antidepressants to be effective, and all but one of those was duly published. But stunningly, out of 36 trials that showed the drugs to be of questionable or no benefit, the results from only 3 trials were published accurately. Of the rest, 22 were not published at all. All of the other 11 that were published concluded that the drugs did have a positive benefit, in direct contradiction of FDA's conclusion.
So, in the authors' words, "studies that the FDA judged as positive were approximately 12 times as likely to be published in a way that agreed with the FDA as were studies with nonpositive results." And it wasn't just a matter of holding back results. Trial-by-trial, the beneficial effects of antidepressants as published in medical journals were 18 percent bigger than those recorded in the official FDA data. The authors don't speculate on how this effectiveness-inflation occurred, but combined with selective publication of positive results, it made antidepressants look a lot better than they really are.
Antidepressants are the most frequently prescribed class of drugs in the US, with about 60,000 prescriptions written every working hour. Encouraged by all those favorable journal papers, doctors tripled their prescription-writing for antidepressants between 1988 and 1998 , and prescriptions had shot up another 31 percent by 2005. The greatest increase has come among doctors who are not psychiatrists. The products have become a convenient way to deal with people who find themselves in rough situations. Soldiers in Afghanistan and Iraq are reportedly being given "bags of antidepressants" and upwards of one-third of nursing-home residents are taking antidepressants at any given time.
FDA registration is designed to curtail the kind of deceptive publication practices that can boost unnecessary prescribing, and their data for more recently developed drugs are available on the agency's website. (But getting data for the eight older drugs examined by Turner and colleagues required use of the Freedom of Information Act). Most academics, journalists, and others looking to inform the public on a drug's overall usefulness rely on studies published in medical journals as being the "gold standard" for reliability. So biased publishing, coming on top of heavy advertising, overtesting , and close interaction between sales reps and doctors, is a highly effective way to improve the market for a drug.
Turner's study looked only for exaggeration of antidepressants' benefits, not at their often terrible side effects. But selective publication can also keep the public in the dark about serious harm that drugs can do. Most infamously, Merck & Co. was accused of leaving out some negative results and spinning others from trials of the pain-reliever Vioxx, when a study of the drug's association with an increased risk of heart attack was submitted to the New England Journal of Medicine. By the time Vioxx was withdrawn in 2004, FDA estimated that it had caused in the range of 25,000 to 50,000 fatal heart attacks.
Each year, the drug industry churns out enough product to fill more than 15 prescriptions per American, and that adds up to more than $200 billion in annual sales. An international survey of the medical literature showing that around 5 percent of hospital admissions result from avoidable adverse drug reactions ; that means about 2 million of the pharmaceutical industry's customers end up needlessly hospitalized each year. Countless other people are suffering side effects without even taking the drugs; they are simply living too close to pharmaceutical factories in India and other countries that export to the US.
It's a depressing situation, one that can be resolved only by taking drug testing out of the hands of the corporations themselves.
1. E.H. Turner et al., 'Selective publication of antidepressant trials and its influence on apparent efficacy', New England Journal of Medicine, 358: 252 (2008)
2. S.M. Foote and L. Etheredge, 'Increasing use of new prescription drugs: a case study', Health Affairs, Jul-Aug, 2000
3. D. Studdert et al., 'Defensive medicine among high-risk specialist physicians in a volatile malpractice environment', Journal of the American Medical Association 293: 2609 (2005) and D. Merenstein et al., 'Use and costs of nonrecommended tests during routine preventive health exams', American Journal of Preventive Medicine 30: 521 (2006).
4. H.J.M. Beijer and C.J. de Blaey, 'Hospitalisations caused by adverse drug reactions (ADR): a meta-analysis of observational studies', Pharmacy World and Science 24: 46 (2002)
Stan Cox is a plant breeder and writer in Salina, Kansas. His book Sick Planet: Corporate Food and Medicine will be published by Pluto Press in April. They can be reached at: firstname.lastname@example.org.