US FDA sets standards for medical journals and peer review

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In seeking to define standards for ‘good reprint practices’ by pharmaceutical companies seeking to provide copies of journal articles to doctors the FDA has had to grapple with the quality of articles and of journals. That they have failed is hardly a surprise, but that they even tried is quite astonishing given their intimate knowledge of the hundreds (if not thousands) of flimsy and misleading research reports submitted to the agency from these same companies seeking drug approvals, most of which are published in these same journals.

The FDA has a legislated role not only to approve new pharmaceuticals, but to do so quickly. The agency is under pressure from all sides except the ranks of the cautious and skeptical to approve drugs and new usages with minimal delay and minimum of assurance they are effective and safe. Once approved, pharmaceutical companies market these drugs to physicians and patients for use.

Pharmaceutical companies (and some physicians and sick patients) are anxious to see if drugs approved for one indication - say epilepsy in adults - might just work for other health problems - say Parkinson’s disease or among groups of individuals (such as children and pregnant women) where there are often few clinical trials.

These ‘off-label’ (non-FDA approved) uses are the target of this FDA Guidance for Industry on Good Reprint Practices for the Distribution of Journal Articles.... The guidance on good reprint practices is a set of suggestions that pharmaceutical companies should use when they are promoting drugs for unapproved uses. The FDA claims that:

“public health may be advanced by healthcare professionals’ receipt of medical journal articles ... on unapproved or new uses of approved or cleared medical products that are truthful and not misleading.”

This is ludicrous. That pharmaceutical companies would select journal articles that are “truthful and not misleading” is irrational from the companies point of view - they will select articles that support use of the product, that emphasize benefit and minimize harm - and naive or blind from the FDA point of view.

There is a wealth of evidence that the published literature looks like a shipwreck of clinical trials that have been shown to be wrong. First of all it is clear even from the perspective of the FDA that published studies sponsored by pharmaceutical companies show a terrific bias towards benefit and against harm. Studies showing benefit of a product are published, those showing no benefit or harm are not. The astonishing thing is that the FDA is intimately aware of this sham evidence base, for it has the only complete record of all clinical trials done to explore new uses of existing products.

For example of 74 clinical trials of antidepressants (involving 12 drugs for which companies sought approval 31% were never published. Published clinical trials show that the drugs are on average 31% better than the comparison drugs or placebos; however, when all the evidence is examined - published and unpublished - the 12 drugs on average showed no benefit over the comparison group.<1> Ludicrous is not too extreme an adjective to describe a belief that pharmaceutical companies will show doctors the complete evidence, on anything.

In its disconnect from reality the FDA goes further by listing a set of criteria that pharmaceutical companies can use (are not required to use) when choosing articles to flog to doctors and their patients. Under the rubric “Good Reprint Practices” we find that:

The Journal should:
1. Have an editorial board that uses experts.
2. Have an editor and board independent of the journal owners
3. Have a policy of full disclosure of conflict of interest or biases.
4. Be peer reviewed

The Journal article should not:
1. Be false or misleading
2. Be a drug company funded special supplement.
3. Have been withdrawn by the journal
4. (Promote a product) that poses a significant risk

I know of few journals that would; a) not have these policies in place; b) publish articles known to be false or misleading and; c) not know and understand that they regularly violate them all, despite their best intentions.

Even well funded journals like the New England Journal of Medicine and JAMA get duped and make mistakes. And they know that they are publishing but part of the evidence, mostly the part showing benefit.

The vast vast majority of journals, however, are small, employ a part-time editor and have but limited time and resources to provide effective oversight of the material they are publishing. They can't guarantee to effectively sort the excellent science from the sloppy, and even less to detect purposeful deceit by funding sponsors with embedded conflicts of interest. Yet, the FDA criteria render virtually all medical journals eligible for cherry picking of articles by company marketing departments and peddling of it to practicing physicians and their patients.

This is not an effective or safe way to improve the health of the public. It is a an effective and now legally protected way ("the FDA said we should") for pharmaceutical and device manufacturing companies to expand markets for unapproved uses.

Further there is no need to promote selected research publications on specific drugs to physicians. Although individual practitioners ought to be able to recognize the conflict of interest of the pharmaceutical company salesperson, they don’t. The majority continue to accept visits and advice form various peddlers. The average practitioner (and patient) has little training, experience or frankly interest in reading and understanding research articles.

In fact, individual practitioners should be encouraged to not read research articles involving randomized trials of a single drug, for there is a reasonable probability that any one study will be flawed or subsequently disproved by accumulating further evidence. Average practitioners are encouraged to stick to guidelines which while themselves are still susceptible to bias and influence by pharmaceutical companies are at least one-half degree of freedom removed from Wall Street.

The FDA criteria for choosing a journal and article do not reflect the very flawed reality of current medical publishing nor of the sad state of market driven medical research, nor of the abilities, availabilities and interests of practitioners to read an understand. The FDA does not have to cave to pressure from Wall Street to let pharmaceutical companies market directly to individual practitioners and their patients by flogging journal articles. Ethical pharmaceutical companies should act responsibly and urge the FDA to drop this guidance.

Reference

Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med 2008;358:252-60.