(Press-News.org) An examination of the potential interaction between pharmaceutical companies and the U.S. Food and Drug Administration (FDA) to discuss future studies finds that one-quarter of recent new drug approvals occurred without any meeting, and when such meetings occurred, pharmaceutical companies did not comply with one-quarter of the recommendations made by the FDA regarding study design or primary outcome, according to a study in the November 26 issue of JAMA.
To enhance protocol quality, federal regulations encourage but do not require meetings between pharmaceutical companies and the FDA during the design phase of pivotal studies assessing drug efficacy and safety for the proposed indication. These meetings often generate FDA recommendations for improving research, although companies are not bound to follow them, according to background information in the article.
Steven Woloshin, M.D., M.S., of the Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, N.H., and colleagues reviewed and analyzed approximated 200 FDA documents (memos; meeting minutes; filing checklists; and medical, statistical, and summary reviews) for 35 new drugs approved between February 1, 2011, and February 29, 2012. The researchers identified all FDA comments and analyzed recommendations about pivotal study design or primary outcomes and characterized the effect of recommendations on study quality.
Of 35 new drug approvals, companies met with the FDA to discuss pivotal studies for 28. The FDA made 53 recommendations about design (e.g., controls, doses, study length) or primary outcome for 21 approvals. Fifty-one recommendations were judged as increasing study quality (e.g., adding controls, blinding, or specific measures and frequency for toxicity assessments, lengthening studies to assess outcome durability) and two as having an uncertain effect. Companies complied with 40 of the 53 recommendations. Examples of non-compliance include a request for randomized trials of brentuximab and crizotinib, but the companies conducted uncontrolled studies. Other cases included primary outcome choice (e.g., progressionfree instead of overall survival) and drug (active comparator) doses tested.
Companies can also request FDA review of pivotal trial protocols. If FDA endorses the protocol it agrees not to object to any study design issues when reviewing the drug for approval. Companies requested protocol review for only 21 of the 35 new drug approvals - and FDA endorsed the protocol for 12.
The authors write that instituting mandatory FDA review of pivotal trial protocols with the power to issue binding recommendations could be an effective way to optimize study quality. They believe that such review may be even more important with increasingly flexible approval pathways. "An independent FDA-commissioned report suggested that stronger early FDA involvement could avoid deficiencies that delay approval of effective drugs and more clearly identify ineffective or harmful ones."
INFORMATION:
(doi:10.1001/jama.2014.13329; Available pre-embargo to the media at http://media.jamanetwork.com)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
As the U.S. Thanksgiving holiday approaches this Thursday, November 27, NOAA's GOES-East and GOES-West satellites are keeping a weather eye out for storms that may affect early travelers. In an image from Nov. 25, the satellites show an active weather pattern is in place for travelers across the central and eastern U.S.
NOAA's GOES-East satellite provides visible and infrared images over the eastern U.S. and the Atlantic Ocean, while NOAA's GOES-West satellite covers the western U.S. and Pacific Ocean from its fixed orbit in space. Data from both satellites were combined ...
November 25, 2014--(BRONX, NY)--A study combining tumor cells from patients with breast cancer with a laboratory model of blood vessel lining provides the most compelling evidence so far that a specific trio of cells is required for the spread of breast cancer. The findings could lead to better tests for predicting whether a woman's breast cancer will spread and to new anti-cancer therapies. The study, led by researchers at the NCI-designated Albert Einstein Cancer Center and Montefiore Einstein Center for Cancer Care(MECCC), was published online today in Science Signaling.
According ...
PHILADELPHIA - New Penn Medicine research has found that elevated levels in the blood of the brain-enriched protein calpain-cleaved αII-spectrin N-terminal fragment, known as SNTF, shortly after sports-related concussion can predict the severity of post-concussion symptoms in professional athletes. The complete findings were released today in the Journal of Neurotrauma.
This new study builds on previous research from this group showing that elevated blood levels of SNTF on the day of a mild traumatic brain injury treated in the emergency room predicted those ...
TORONTO, Nov. 29, 2014--A chemical produced in the pancreas that prevented and even reversed Type 1 diabetes in mice had the same effect on human beta cells transplanted into mice, new research has found.
GABA, or gamma-aminobutryic acid, is an amino acid produced by the same beta cells that make and secrete insulin.
Drs. Gerald Prud'homme and Qinghua Wang of the Keenan Research Centre for Biomedical Sciences of St. Michael's Hospital published a paper in 2011 showing for the first time that GABA injections not only prevented Type 1 diabetes in mice, but even reversed ...
LIVERMORE, Calif. - Nanoporous metals -- foam-like materials that have some degree of air vacuum in their structure -- have a wide range of applications because of their superior qualities.
They posses a high surface area for better electron transfer, which can lead to the improved performance of an electrode in an electric double capacitor or battery. Nanoporous metals offer an increased number of available sites for the adsorption of analytes, a highly desirable feature for sensors.
Lawrence Livermore National Laboratory (LLNL) and the Swiss Federal Institute of ...
WACO, Texas (Nov. 25, 2014) - Note to venture capitalists: Entrepreneurs are watching to see if you're naughty or nice.
A recently published study of more than 550 decisions and responses from 144 experienced entrepreneurs reveals that "knowledge of explicit ethical or unethical behavior (by venture capitalists) profoundly shapes the entrepreneurs' willingness to partner."
Baylor University researcher Matthew S. Wood, Ph.D., assistant professor of entrepreneurship in Baylor's Hankamer School of Business, co-authored the study, "Take the money or run? Investors' ethical ...
A measles vaccine made of fine dry powder and delivered with a puff of air triggered no adverse side effects in early human testing and it is likely effective, according to a paper to be published November 28 in the journal Vaccine. The paper is now available online.
In 2013, measles killed 145,700 people, most of them children, according to the World Health Organization. That's despite the fact that the conventional injectable vaccine against the measles virus is effective.
"Delivering vaccines in the conventional way, with needle injections, poses some serious challenges, ...
Treatment for obstructive sleep apnea with continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) can lead to modest improvements in depressive symptoms, according to a study published by Marcus Povitz, Carmelle Bolo, and colleagues from University of Calgary, Canada, in this week's PLOS Medicine.
The researchers identified 22 randomized controlled trials that investigated the effects of CPAP or MAD treatment on patients with obstructive sleep apnea and that measured depressive symptoms before and after treatment. By pooling the results from ...
HOUSTON - (Nov. 25, 2014) - An international collaboration of scientists including Baylor College of Medicine has completed the first genome sequence of a myriapod, Strigamia maritima - a member of a group venomous centipedes that care for their eggs - and uncovered new clues about their biological evolution and unique absence of vision and circadian rhythm.
Over 100 researchers from 12 countries completed the project. They published their work online today in the journal PLOS Biology.
"This is the first myriapod and the last of the four classes of arthropods to have ...
The arthropods are one of Earth's real success stories, with more species of arthropod than in any other animal phylum, but our knowledge of arthropod genomes has been heavily skewed towards the insects. Recent work has furnished us with the genome sequences of an arachnid and a crustacean, but the myriapods (centipedes and millipedes) have remained the one class of arthropods whose genomes are still in the dark.
An international team of scientists (over 100 from 15 countries) with Stephen Richards (Baylor College of Medicine) as senior author has now sequenced the genome ...
