Former medical journal editor details why doctors can’t rely on medical literature for valid and reliable information

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Some of you may have noticed that there has been a move in healthcare towards evidence-based medicine. And at least part of this concerns basing treatment regimes and recommendations on what scientific evidence appears to show. A big chunk of medical research is devoted to the gauging the effectiveness of pharmceutical drugs. And if we have a few trials which show that, say, drug X is effective for some a condition, then our doctors can confidently recommend it to their patients, often with the blessing of our governments and health agencies.

But how much can we trust the evidence on which health decisions are so often based? In this week’s edition of the Journal of the American Association, a former editor of the New England Journal of Medicine details in excruciating details the myriad of ways in which pharmaceutical companies can conspire to produce results that make their products look better and safer.

The author, Marcia Angell, starts by writing about how the drug company Merck manipulated data in two studies in an effort to mask the increased mortality associated with its drug rofecoxib. Let’s not sugar-coat the likely effect of this subterfuge: people died (unnecessarily).

Angell goes on to lament how prior to the 1980s, that when industry funded research, it was still the doctors and scientists conducting the research who were responsible for designing the study, analyzing and interpreting the data, as well as its writing up. Now though, all to often drug companies are initimately involved in all of these processes, to the extent that sometimes study authors may not even have access to all the data the study generated.

Part of the problem here, according to Angell, is that academic research centres now have to compete with what are known as contract research organisations (companies specialising in patients for clinical trials through a network of doctors). Contract research organisations are often only too happy to agree to the conditions dictated by those who pay them (the drug companies). Now, it seems, many academic medical centres are prepared to do the same or risk not getting the research bucks in.

It goes deeper than this, though, because as Angell points out, many academic centres have financial links with the drug companies whose products they assess. According to Angell, a recent review found that about two-thirds of academic medical centers hold equity interest (shares) in companies that sponsor research within the same institution. ,And a study of medical school department chairs found that two-thirds received departmental income from drug companies and three-fifths received personal income. In addition to grant support, study investigators often have other financial ties to the sponsors of their research, such as being paid consultants and members of advisory committees as well as sometimes having shares in company whose products they test.

Angell goes on to write: Given the conflicts of interest that permeate the clinical
research enterprise, it is not surprising that industry-sponsored research has consistently been shown to favor the sponsor’s drug”partly because negative results are often not published, partly because positive results are repeatedly published in slightly different forms, and partly because a positive spin is put on even negative results.

She cites examples too such as the study (reported here) which showed that
74 clinical trials of antidepressants found that 37 of 38 positive studies were
published, while 33 of 36 negative studies were either not published or were somehow portrayed in a positive light.

Angell also describes what a number of techniques that drug companies and scientists can use to help ensure studies produce the results the drug companies want. These include:

Comparing a drug to a competitor drug which is used a too low a dose (to make the sponsor’s drug look for effective)

Comparing a drug to a competitor drug which is used a too high a dose (to make the sponsor’s drug look safer)

Comparing a drug to placebo when it would be more appropriate to assess whether it works better than an existing drug

Choosing lots of different outcomes to measure and then selecting the best results for publication and highlighting

And then Angell asks questions of the independence of the professional and governemental organizations who we trust to set medical practice guidelines. In a study of more than 200 panels that issued practice guidelines, more than a thrd of the authors acknowledged that they had some financial interest in the drugs they recommended. She also mentions specifically the fact that of the 9 members of the National Cholesterol Education Program responsible for the latest (ever lower) cholesterol recommendations, 8 had financial ties to companies that make cholesterol-reducing statins. I mentioned this sorry state of affairs in a recent blog here.

Angell goes on to say : Looking at this picture altogether, it would be naive to
conclude that bias is only a matter of a few isolated instances. It permeates the entire system. Physicians can no longer rely on the medical literature for valid and reliable information. This is the conclusion I reluctantly reached toward the end of my 2 decades as an editor of the New England Journal of Medicine, and it has been reinforced in subsequent years. Clinicians just do not know anymore how safe and effective prescription drugs really are, but these products are probably nowhere near as good as the published literature indicates.

And after this sad indictment of the state of academic medical research Angell goes on to lament the fact that the biased literature it gives us causes doctors to practice a very drug-intensive style of medicine. Angell adds: Even when lifestyle changes would be more effective, physicians and their patients often believe that for every ailment and discontent there is a drug. Physicians are also led to believe that the newest, most expensive brand-name drugs are superior to older drugs or generics, even though there is seldom any evidence to that effect because sponsors do not usually compare their drugs with old drugs at equivalent doses. And finally, physicians learn to use drugs for off-label uses without good evidence of effectiveness. Although it is illegal for companies to market drugs for off-label uses, faculty thought leaders on company speakers’ bureaus regularly promote off-label uses in the guise of education or research.

Angells round off by suggesting that it is absurd to expect investor-owned drug companies to produce unbiased evaluations of their own products. And of course she’s right. And she’s right about another thing too when she suggests that reform of the system is required not just for the sake of appearances, but because it is a matter or public health.


Marcia Angell. Industry-Sponsored Clinical Research – A Broken System. JAMA 2008;300(9):1069-1071.

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