‘Fear’ Making FDA Approvals Restrictive: Report
A lengthy and detailed report from the George Mason University Mercatus Center says that FDA has strayed from the drug, biologic, and medical device safety and effectiveness standards set out in the law due to “fear of being blamed for the failings of approved products.” The agency now, it says, is applying standards for approval that are based on predicting the benefits and risks — clinical utility, disease outcomes, survival — that an average patient will experience. “But these outcomes are better evaluated in real-world, post-market settings, that is, in the medical marketplace, where knowledge about the value of a drug or device for different types of patients can grow over time,” it argues.
Led by Rothman Institute executive directive director Joseph V. Gulfo, the report’s authors say that FDA should return to its role as gatekeeper of safe and effective drugs and devices, and refrain from attempting to anticipate the future judgments of physicians and patients regarding benefits and risks.
In a sense, the report says, FDA has restated its mission from promoting health to protecting health, from permitting new products that can advance health to demanding certainty that products will not cause any harm. The expectation from certain areas of society, it says, is that FDA vets all potential side effects of new drugs for all people in all situations, even effects resulting from uses that are not intended and are not in conformity with approved labeling.
“Such an expectation is not just impossible to satisfy,” the authors declare, “it is entirely unreasonable. When we consider that conflicting studies continue to emerge about health outcomes related to coffee and red wine, which have been in use for thousands of years, we can see the absurdity of expecting FDA to somehow anticipate, unerringly, all possible health outcomes from the use of new drugs.”
The report gives examples that it says demonstrate that the agency is straying not only from laws passed by Congress but also from its own rules, in guidance documents that are being promulgated. “This is how the safety and effectiveness standards have been eroded over time,” it says. “Despite incessant pleas from doctors and patients for more products that might help when used appropriately, FDA continues to raise the evidentiary threshold for permitting a new product, recasting premarket approval as a venue for the practice of evidence-based medicine. This move is aimed at satisfying FDA critics, but it consumes precious time and resources, and it dissuades drug developers (and would-be developers) from pursuing projects.”
Two high-ranking FDA officials are quoted as saying in 2015 that “improving a patient’s life or lifespan must be central to the concept of drug innovation.” The authors counter that FDA is supposed to assure safety and effectiveness of drugs, but not life outcomes for patients.
“The shift in regulatory philosophy from promoting health to protecting health has not only increased the cost and time of drug development, it has also moved FDA from its proper role in making public health decisions to become an improper force driving public health decisions,” the report says. “We must change this philosophy in order for medical innovation to deliver on the potential that 21st century science and medicine has to offer. We need to bring FDA into the 21st century by bringing it back to its roots: assuring drug safety and effectiveness, not outcomes.”
With President Obama’s commitment to the Personalized Medicine Initiative, one might have expected FDA to embrace the opportunity represented by the information economy, the authors write. But instead the agency has backed away from personalized medicine, increasing its emphasis on trial results for an average patient as the standard for permitting new drugs and devices.
The report covers many ways in which the agency’s approval process has become more restrictive, and returns to the notion that the restrictiveness flows from a fear of making a mistake. It quotes the 1974 FDA commissioner, Alexander Schmidt, who said, “In all of FDA’s history I am unable to find a single instance where a congressional committee investigated the failure of FDA to approve a new drug. But the times when hearings have been held to criticize our approval of new drugs have been so frequent that we aren’t able to count them. The message to FDA staff could not be clearer.”
Another force leading the agency away from statutory requirements is evidence-based medicine, the report says. “In light of the strength of the evidence-based medicine movement, it seems reasonable to interpret, say, FDA insistence on outcomes studies as an evidence-based medicine-inspired vote of mild to little confidence in physicians and the medical marketplace,” it says.
The authors suggest that a reinvigorated medical marketplace system, with FDA back in its proper place at the top of a funnel that narrows through early-adopter doctors; doctors and patients; payers, patient advocacy and cooperative groups, and drug companies; the Internet of things, and finally widespread use, “could help realize the promise of the information economy and personalized medicine for 2015 and beyond.”
The report concludes that fixing FDA mission creep is quite easy by having Congress “guide FDA back to the letter and spirit of the Federal Food, Drug, and Cosmetic Act” by more explicitly defining safety and effectiveness through:
explicitly limiting FDA to considering the safety of intended uses, according to the label, with no agency speculation about the safety of off-label uses or uses in populations beyond those in the labeled indications; defining safety with regard to the likelihood of causing death, debilitation, or severe harm, focusing FDA reviewers on filtering out the most dangerous drugs and allowing the medical marketplace to determine appropriate uses for medicines that might be blocked under a more restrictive safety threshold; defining effectiveness as having positive activity on the disease; and requiring FDA to expand its use of surrogate endpoints in trials and reviews, including specific, actionable targets so that FDA can be held accountable by the public if it fails to take action.
“Congress should couple these reforms to the law with a strengthened norm against undue criticism of FDA by Congress,” the report concludes. “Risk cannot be eradicated from the use of drugs, and human foresight is limited; therefore, poor outcomes cannot by themselves justify the placing of blame for those outcomes upon FDA. Whenever FDA is assiduous in following the law and acting appropriately on the knowledge available at the time, then it is to be supported. Congressional leaders should vocally affirm such a norm to reduce the fear that has led FDA to a stance of excessive caution and protraction.”