Selected Results From Trials
Should it grant a license, the FDA publishes a “Summary Basis of Approval,” which as its names suggests, summarizes the evidence that the FDA used to judge a drug as worthy of a license. However, these summaries contain only selected results from the trials submitted to the FDA, and scientists have recently questioned whether such selected publication data might give a somewhat skewed picture of the value and safety of a drug.
In order to investigate this matter, three researchers from the University of California, San Francisco, looked at the data supporting 90 drugs licensed by the FDA between 1999 and 2000. In all, the researchers identified 909 trials that had been submitted in support of these drugs. Of these, though, a mere 43 percent had been published in medical journals over the next 5 1/2 to 8 1/2 years. Perhaps not surprisingly, those studies with statistically significant results were more than twice as likely to be published as those that did not produce statistically significant results.
Favorable Data
This is an example of “publication bias”: Drug companies publish the data that puts their product in a favorable light, but may neglect to do so for less-favorable data. This can give an inaccurate picture of how effective a drug really is. It can ultimately lead doctors to rush to prescribe a new drug that is not materially better than an existing (and often cheaper) alternative.
Suppressed Safety Risks
Even worse, it might cause doctors to prescribe drugs that are more toxic and hazardous than existing therapies. The authors of the paper highlight a “string of recent controversies” in which it appears that drug companies suppressed the safety risks of drugs such as rosiglitazone (for diabetes), paroxetine (an antidepressant), and rofecoxib (a painkiller).
New Legislation
On the plus side, a new law was passed recently in the United States that mandates that all FDA-approved drugs and devices must have the “basic results” of all supporting trials published by the National Institutes of Health. This appears to be a step in the right direction.
However, the authors of the review ask whether this law might actually increase rather than decrease publication bias. Specifically, they ask: “Might sponsors feel less compelled to publish equivocal trials because the basic results will already be in the public domain?”
They also question whether the time pressures of publication soon after approval might result in focusing drug company efforts even more on submitting positive trials and trials of greatest interest to the journals.
The review not only highlights the problem of publication bias in medical research, but also serves as some sort of benchmark against which we can judge the effect of the new legislation regarding publication of trial data. Let’s hope that the new legislation leads to more publication of trial data and as a result, allows stakeholders to form truly informed opinions regarding the effectiveness and safety of newly licensed drugs.
References:
Kee K, et al. Publication of Clinical Trials Supporting Successful New Drug Applications: A Literature Analysis. PLoS Med 5(9): e191 doi: 10.1371/journal.pmed.0050191
Dr. John Briffa is a London-based physician and author with an interest in nutrition and natural medicine.
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