'Accelerated approval' drugs: How well are they studied?

When an investigational prescription drug shows promise for treating a serious illness or filling an unmet medical need, the Food and Drug Administration (FDA) has special programs available to expedite its clinical testing and approval. One is the "Accelerated Approval" pathway, in which the FDA will accept weaker-than-usual evidence of the drug's efficacy from its pre-clinical trials. In exchange, the FDA requires that the manufacturer conduct post-approval confirmatory studies.

To understand how this pathway is implemented, in a recent study published in JAMA, researchers at Brigham and Women's Hospital and the London School of Economics and Political Science (LSE) examined the pre-approval and post-approval clinical trials of drugs granted FDA Accelerated Approval between 2009 and 2013. During that time, the FDA granted 22 drugs Accelerated Approval and ordered 38 post-approval studies to confirm the safety and efficacy of these drugs. Three years after the last drug's approval, the researchers found that only half of those post-approval studies had been completed. They also found that the characteristics of those completed studies did not differ much from the pre-approval studies. The researchers found that the proportion of randomized or blinded trials didn't differ and that many of the confirmatory trials still relied on surrogate measures of effect--that is, blood tests or radiological studies that may not correlate with real clinical endpoints.

"One might expect Accelerated Approval confirmatory trials to be much more rigorous than the pre-approval trials," said Aaron S. Kesselheim, MD, JD, MPH, of the BWH Division of Pharmacoepidemiology and Pharmacoeconomics and senior author of the study. "But we found that there were few differences in these key design features of the trials conducted before or after approval." In 17 out of the 18 completed studies, surrogate measures were still the primary endpoints of the studies.

"It is important to use clinical endpoints in testing investigational drugs whenever possible because there are numerous cases of drugs approved on the basis of a surrogate measure that turn out to later not effect actual clinical outcomes--or even make them worse," said Kesselheim.

To address these issues and improve the quality of Accelerated Approval confirmatory studies, Kesselheim suggests that the FDA clearly describe the limitations in the pre-approval data that will need to be addressed in post-approval studies and that they work with manufacturers to ensure that post-approval studies are conducted using design features that will be optimally useful for confirming the efficacy of the drug.

Naci H, Smalley KR, Kesselheim AS.
Characteristics of Preapproval and Postapproval Studies for Drugs Granted Accelerated Approval by the US Food and Drug Administration.
JAMA. 2017;318(7):626–636. doi: 10.1001/jama.2017.9415.

Most Popular Now

In wine, there's health: Low levels of alcohol goo…

While a couple of glasses of wine can help clear the mind after a busy day, new research shows that it may actually help clean the mind as well. The new study, which appe...

Sanofi to acquire Ablynx for €3.9 Billion

Sanofi and Ablynx, a biopharmaceutical company engaged in the discovery and development of Nanobodies®, entered into a definitive agreement under which Sanofi will offer ...

Repurposed drug found to be effective against Zika…

In both cell cultures and mouse models, a drug used to treat Hepatitis C effectively protected and rescued neural cells infected by the Zika virus - and blocked transmiss...

Interim publications of randomized trials make new…

Early results from randomized trials are sometimes published before the trial is completed. The results of such interim publications may generate a great deal of interest...

More stroke patients may receive crucial treatment…

More patients could be eligible for critical treatments to remove or dissolve blood clots that cause strokes, according to a new treatment guideline issued by the America...

Drug trial protocol redactions by industry sponsor…

New research published by the Journal of the Royal Society of Medicine exposes the extent of redactions in protocols for industry-sponsored randomised drug trials. Trial ...

Advanced Accelerator Applications receives FDA ap…

Novartis AG (NYSE: NVS) announced that Advanced Accelerator Applications, a subsidiary of Novartis Groupe S.A., has received US Food and Drug Administration (FDA) approva...

Blood vessel-on-a-chips show anti-cancer drug effe…

Researchers at the Institute of Industrial Science (IIS), the University of Tokyo, CNRS and INSERM, report a new organ-on-a-chip technology for the study of blood vessel ...

Guidelines extended to improve the use of feedback…

Researchers have recommended changes to international guidelines used in the development of clinical trials in an effort to gain information about the impact of the treat...

Roche reports good results in 2017

In 2017, Group sales rose 5% to CHF 53.3 billion. Core operating profit grew 3% and Core EPS increased 5%, reflecting the good underlying business performance. On an IFRS...

Brilinta significantly reduces CV events and coron…

AstraZeneca today announced results from a new sub-analysis of the Phase III PEGASUS-TIMI 54 trial, demonstrating a risk reduction of 19% in MACE (the composite of CV dea...

FDA approves new treatment for certain digestive t…

The U.S. Food and Drug Administration today approved Lutathera (lutetium Lu 177 dotatate) for the treatment of a type of cancer that affects the pancreas or gastrointesti...

Pharmaceutical Companies

[ A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Z ]