The U.S. Food and Drug Administration (FDA) isn’t doing so well these days. Turns out that they haven’t exactly been bothering to report findings of scientific fraud to, well, anyone:
Fifty-seven published clinical trials were identified for which an FDA inspection of a trial site had found significant evidence of 1 or more of the following problems: falsification or submission of false information, 22 trials (39%); problems with adverse events reporting, 14 trials (25%); protocol violations, 42 trials (74%); inadequate or inaccurate record-keeping, 35 trials (61%); failure to protect the safety of patients and/or issues with oversight or informed consent, 30 trials (53%); and violations not otherwise categorized, 20 trials (35%). Only 3 of the 78 publications (4%) that resulted from trials in which the FDA found significant violations mentioned the objectionable conditions or practices found during the inspection. No corrections, retractions, expressions of concern, or other comments acknowledging the key issues identified by the inspection were subsequently published.
This is a bit of a problem. In the clinical trials that the FDA investigated, issues were found ranging from alterations of medical records up to, and including, homicide.
A researcher was caught falsifying documents in a number of trials, in part because those falsifications led to the death of a patient undergoing treatment in a clinical trial comparing 2 chemotherapy regimens. The researcher had falsified laboratory test results to hide the patient’s impaired kidney and liver function, and the first dose of the treatment proved to be fatal. The researcher pleaded guilty to fraud and criminally negligent homicide and was sentenced to 71 months in prison. Although this episode is described in detail in FDA documents as well as court documents, none of the publications in the peer-reviewed literature associated with the chemotherapy study in which the patient died have any mention of the falsification, fraud, or homicide.
This is the sort of thing that you might think the FDA would want to publicize. Yet oddly enough, it failed to do so.
Now, it would be all too easy to turn this into a wild conspiracy theory, in which the FDA is in bed with the pharmaceutical industry and gives them a pass on sketchy scientific practices. That’s certainly a tempting way to look at the issue. That said, perhaps there is a simpler explanation – the Republican obsession with slashing the budgets of any governmental agency in sight. The FDA lost some $209 million due to sequestration. A decreased budget could certainly make it harder for the FDA to perform its job. On the other hand, if you take a look at their requested budget for 2014, the agency is requesting an increase, which would seem to bode well:
The U.S. Food and Drug Administration is requesting a budget of $4.7 billion to protect and promote the public health as part of the President’s fiscal year (FY) 2014 budget. Industry user fees would fund 94 percent of the proposed budget increase, including new fees to support the landmark Food Safety Modernization Act (FSMA) and strengthen the FDA’s ability to oversee imported food.
Industry user fees. Hmm. What might those be? As it turns out, regulated industries pay the FDA fees for review of covered activities, and the FDA has been increasingly reliant on these fees as a component of its budget. So the FDA is funded, in part, by the very industries it is intended to regulate. And, while there are, no doubt, all sorts of reasonable explanations for this, it does tend to make the aforementioned “wild conspiracy theories” seem a little less wild.
This failure to provide proper oversight becomes even more troubling when one considers that analysis has shown that in-house, pharmaceutical validation programs quite often end with irreproducible results:
To mitigate some of the risks of such investments ultimately being wasted, most pharmaceutical companies run in-house target validation programmes. However, validation projects that were started in our company based on exciting published data have often resulted in disillusionment when key data could not be reproduced. Talking to scientists, both in academia and in industry, there seems to be a general impression that many results that are published are hard to reproduce. However, there is an imbalance between this apparently widespread impression and its public recognition . . . and the surprisingly few scientific publications dealing with this topic.
Let me be blunt. This seems to be a recipe for disaster. We have a situation where clinical trials – run by pharmaceutical companies- are for whatever reason producing outcomes that cannot be replicated. We have an FDA that investigates clinical trials and utterly fails to publicize the issues it finds. That’s a recipe for products making it to the market that will, in the end, prove harmful. It has happened before and, under the current system, we are virtually assured that it will happen again. Whether the reason be conspiracy, lack of funding, or simple incompetence on the part of the FDA, it seems clear that the agency is certainly failing to perform a significant portion of its mission. If the agency finds issues with a clinical trial, it is certainly in the interests of public health to make those issues known. When it fails to do so, it fails the public it is sworn to protect.