Faster Drug Approvals May Carry Additional Risks for Patients

The way new drugs are tested and approved for market is changing, and, according to a recent study in JAMA Internal Medicine, if you’re a patient, the change is not necessarily for the better.

As described on, “New drugs that receive expedited review by the Food and Drug Administration are being tested on fewer patients, leaving many safety questions unanswered even after they are approved, …”

It used to be, as the study authors explained, that new drugs were tested more thoroughly before the FDA granted initial approval. The standard testing process can take a long time, so now many new drugs are approved faster, and the patient population for their trials is smaller. Drugs hit the market faster with the promise that additional tests will be conducted.

The flip-flop, Reuters explains, is largely the result of efforts by patient groups, Congress and the drug industry to encourage the FDA to expedite drug reviews in order to speed new products to the market. Patients and drug manufacturers claim the benefit is getting much-needed medication to users more quickly, but critics say the FDA, by bowing to pressure, is approving products prematurely.

The JAMA study authors examined the development and clinical testing process of 20 new drugs in 2008, and the risks associated with them. Eight of the drugs got expedited review and 12 got the standard, longer review.

On average, clinical testing for the expedited drugs took slightly longer than five years before they were approved. The standard review took seven-and-a-half years. The expedited drugs were tested for efficacy among an average of 104 patients, compared with an average median of 580 patients for standard review drugs.

Some approvals were contingent on follow-up trials, but the authors say that in many cases, those safety monitoring trials either weren’t conducted, weren’t completed or weren’t submitted to the FDA. Yet the drugs remained on the market.

Of the drugs studied, the FDA required 85 follow-up safety trials; five years later, in early 2013, not even half had been completed.

The JAMA authors found “substantial additional risks” in the four years after drugs were approved.

“As many safety questions were not answered prior to drug approval, some patients may have been exposed to safety risks that had not been well characterized,” the authors wrote.

Traditionally, the FDA required two controlled clinical trials to prove a drug’s safety and efficacy. But now, in some cases, it accepts data from a single trial whose results might not actually represent the outcome hoped for, but only what’s called a “surrogate” measure. For example, tumor shrinkage might measure how well a drug attacks a tumor, but that doesn’t necessarily represent how well it fights the underlying cancer, or prolongs survival.

But for patients with few alternatives, and the Big Pharma providers that recognize a large and desperate market, surrogacy is good enough. As reported by Reuters, an FDA statement recognizes this powerful force: “In situations of serious and life-threatening diseases with unmet medical need, patients and physicians who treat them have told us repeatedly that they are willing to accept greater uncertainty about risk in order to have access to the hope of improved treatment today.”

The agency is pondering additional measures to speed the drug development process, such as so-called “enriched” trials, in which subjects are selected based on certain demographic or genetic characteristics. It’s sort of a customized trial for customized medicine for patients most likely to respond successfully.

A commentary accompanying the JAMA study called, “Can Expedited FDA Drug Approval Without Expedited Follow-Up Be Trusted?” raised concerns about the whole approach.

“The current system of accelerating drug approval in the United States can be described as a growing hodgepodge of exceptions to the rule of rigorous premarket review,” wrote Daniel Carpenter, professor of government at Harvard University. He said the FDA has few measures to ensure that drugs approved based on limited populations are marketed only to those limited groups.

“It is concerning that the FDA may alter the terms of the implicit approval contract with pharmaceutical manufacturers, that is, less clinical testing of drugs before approval with quicker review in exchange for more reliable and rigorous post-approval testing, and not enforce the post-approval requirements as it should,” Carpenter wrote.

Our advice for patients remains: Unless you really, really have no other option, avoid any new drug. In fact, the safest option is to let at least five to seven years pass before you can be confident that a drug’s safety kinks have been worked out.

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