Drug Approvals Take Customized Approach Based on Disease

Drugmakers can gain U.S. approval for medicines based on a wide variety of evidence the treatments work and are safe, including a single clinical trial, researchers said.

Almost as many novel drugs approved from 2005 to 2012 were based on one study as those using two clinical trials, an analysis in the Journal of the American Medical Association found. Researchers from Yale University’s School of Medicine reviewed 188 novel therapies approved by the Food and Drug Administration for 206 uses during the time period.

Clinical trials where people are randomly assigned to treatment groups, and double-blinded, meaning the patients and researchers don’t know who is taking the experimental medication, are considered the gold standard. Eighty-nine percent of pivotal trials were randomized and 80 percent were double-blinded, according to the study.

“Such regulatory flexibility allows for a customized approach to approval, including the ability to rapidly approve potentially effective therapies for life-threatening diseases, such as certain cancers, or those diseases for which there is no existing effective treatment, such as orphan diseases,” the authors wrote.

An advisory panel to the FDA voted last week to back Chelsea Therapeutics International Ltd.’s Northera for approval against sudden drops in blood pressure related to neurologic disorders, a rare disease known as neurogenic orthostatic hypotension that can cause dizziness and fainting. The panel’s 16-1 vote in favor of the drug came even as the FDA has twice expressed concern about Northera’s effectiveness.

Different Standards

“I tend to lower the standard a little bit if there’s nothing else that really works,” said Michael Proschan, a panelist who is a mathematical statistician at the National Institute of Allergy and Infectious Diseases, after the vote Jan. 14.

Three phases of clinical trials, including two rounds that assess the effectiveness of the medication against disease, typically are required for a new drug to gain FDA approval.

The JAMA paper also found that approval of the medicines for 45 percent of the 206 illnesses were based on trials that relied on an assessed benefit that is reasonably likely to prove the drug works, such as a shrinking tumor, instead of a goal with a stronger correlation to effectiveness such as longer survival.

“This reliance on surrogate outcomes leaves patients and physicians to extrapolate clinical benefits from trials, again raising questions about the certainty of medications’ benefits in practice,” the authors wrote.

The paper advocates a “life-cycle” approach under which the FDA monitors and evaluates the benefits and risks of therapies while they’re on the market, not only prior to approval. The agency has the authority to require post-approval studies and often does, though most likely for safety reasons.

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