PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Wide variation found in quality of evidence used by FDA for approval of new drugs

2014-01-22
(Press-News.org) Contact information: Karen Peart
karen.peart@yale.edu
203-432-1326
The JAMA Network Journals
Wide variation found in quality of evidence used by FDA for approval of new drugs Clinical trials used by the Food and Drug Administration (FDA) to approve new drugs between 2005 and 2012 vary widely in their characteristics, according to a study in the January 22/29 issue of JAMA.

"FDA review of new drug applications is guided by the Federal Food, Drug, and Cosmetic Act, which requires 'adequate and well controlled investigations' to determine efficacy," according to background information in the article. "Many patients and physicians assume that the safety and effectiveness of newly approved therapeutic agents is well understood; however, the strength of the clinical trial evidence supporting approval decisions by the U.S. FDA has not been evaluated."

Nicholas S. Downing, A.B., of the Yale University School of Medicine, New Haven, Conn., and colleagues evaluated the strength of clinical trial evidence supporting FDA approval decisions for new therapeutic agents by characterizing key features of pivotal efficacy trials (clinical trials that serve as the basis of FDA approval), such as trial size, design, duration, and end points.

The researchers used publicly available FDA documents to identify 188 novel therapeutic agents approved between 2005 and 2012 for 206 indications on the basis of 448 pivotal efficacy trials. The vast majority of pivotal trials were randomized (89 percent) and double-blinded (79.5 percent). More than half of the trials used a placebo for comparison (55 percent), and 32 percent used an active (such as another drug) comparator, and 13 percent had no comparator.

The median (midpoint) number of patients enrolled per indication among all pivotal trials was 760. Among 201 indications, 74 (37 percent) were approved on the basis of a single trial, 77 (38 percent) on 2, and 50 (25 percent) on 3 or more. Trials using surrogate end points as their primary outcome formed the exclusive basis of approval for 91 indications (45 percent).

At least 1 pivotal trial with a duration of 6 months or greater supported the approval of 68 indications (34 percent). Trial features differed by therapeutic and indication characteristics, such as therapeutic area, expected length of treatment, orphan status (drug used to treat rare medical condition), and accelerated approval.

"The variation in the [amount and type] of clinical trial evidence used by the FDA to assess the efficacy of novel therapeutic agents highlights the agency's flexible standards for approval," the authors write. "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. These approvals can be made without requiring costly and time-consuming randomized, double-blinded, controlled trials, although these trials are regarded as the gold standard for evaluation."

The researchers note that understanding the clinical trial evidence underlying newly approved therapeutic agents has important implications for patients and physicians. "When medications become available on the market, decisions must be made about their use, likely informed by how well safety and effectiveness are understood. Comparative effectiveness information, which is not required as part of FDA approval and involves comparison of an intervention with an active control, was available for less than half of indications, consistent with prior research, but leaving uncertainty about the benefits and safety of these medications when compared with other available therapeutic agents."

The authors write that the wide variation in clinical trial evidence "has the potential to inform current FDA regulatory approval standards and postmarket surveillance initiatives." (doi:10.1001/jama.2013.282034; 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.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, January 21 at this link.

Editorial: Opening the FDA Black Box

In an accompanying editorial, Steven N. Goodman, M.D., M.H.S., Ph.D., of Stanford University, Stanford, Calif., and Rita F. Redberg, M.D., M.Sc., of the University of California, San Francisco, and Editor, JAMA Internal Medicine, comment on the three studies in this issue of JAMA that examine the FDA approval process.

"Although these reports represent important steps in improving understanding of FDA decision making, further commitment to and progress toward ensuring transparency, including reducing report redactions, is needed to help the scientific community and other interested parties answer the questions these studies raise, thereby helping the FDA in its mission to find the right balance between allowing innovation and protecting the public's health." (doi:10.1001/jama.2013.283946; Available pre-embargo to the media at http://media.jamanetwork.com)

Editor's Note: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Redberg reported being a member of the U.S. Food and Drug Administration Circulatory System Devices Panel and a member of the California Technology Assessment Forum. No other conflicts of interest were reported.


ELSE PRESS RELEASES FROM THIS DATE:

Study examines reasons for delay, denial of new drugs by FDA

2014-01-22
Study examines reasons for delay, denial of new drugs by FDA Several potentially preventable deficiencies, including failure to select optimal drug doses and suitable outcome measures for a study, accounted for significant delays in the approval of new drugs ...

Biomarkers in blood show potential as early detection method of pancreatic cancer

2014-01-22
Biomarkers in blood show potential as early detection method of pancreatic cancer Researchers have identified diagnostic microRNA panels in whole blood that had the ability to distinguish, to some degree, patients with and without pancreatic cancer, according ...

Many CV devices approved by process that often does not require new clinical data

2014-01-22
Many CV devices approved by process that often does not require new clinical data Many cardiac implantable electronic device models currently in use were approved via a Food and Drug Administration review process in which the models were assumed safe and effective ...

Mediterranean diet associated with lower risk of peripheral artery disease

2014-01-22
Mediterranean diet associated with lower risk of peripheral artery disease A multicenter study that previously reported a reduction in heart attack and stroke with a Mediterranean diet supplemented with extra-virgin olive oil or with nuts now also reports a ...

Deaths higher for heart attack patients at night and weekends

2014-01-22
Deaths higher for heart attack patients at night and weekends Research: Off-hour presentation and outcomes in patients with acute myocardial infarction: systematic review and meta-analysis Mortality is higher, and emergency treatment takes longer, for ...

Long term exposure to air pollution linked to coronary events

2014-01-22
Long term exposure to air pollution linked to coronary events Association persists at levels of exposure below current European limits Long term exposure to particulate matter in outdoor air is strongly linked to heart attacks and angina, and this association ...

Losing a family member in childhood associated with psychotic illness

2014-01-22
Losing a family member in childhood associated with psychotic illness Highest risk seen in children who experience suicide in close family members Experiencing a family death in childhood is associated with a small but significant increase in risk of psychosis, ...

Fast eye movements: A possible indicator of more impulsive decision-making

2014-01-22
Fast eye movements: A possible indicator of more impulsive decision-making Using a simple study of eye movements, Johns Hopkins scientists report evidence that people who are less patient tend to move their eyes with greater speed. The findings, the researchers say, ...

Most high-risk cardiac devices in use today approved as modifications to previously-approved devices

2014-01-22
Most high-risk cardiac devices in use today approved as modifications to previously-approved devices Device 'supplement' applications are generally not accompanied by new clinical testing, with implications for patient safety Boston – The Food and Drug Administration ...

New sequencing tools give up close look at yeast evolution

2014-01-22
New sequencing tools give up close look at yeast evolution Highlights in this week's Molecular Biology and Evolution The baker's yeast Saccharomyces cerevisiae has been associated with human activities for thousands of ...

LAST 30 PRESS RELEASES:

Boston University professor to receive 2025 Eugene Braunwald Academic Mentorship Award

Pusan National University researchers reveal how forest soil properties influence arsenic mobility and toxicity in soil organisms

Korea University researchers find sweet taste cells resist nerve damage through c-Kit protein

HealthFORCE, AAPA, and West Health release “Aging Well with AI” – first in a two part series on AI and the healthcare workforce

The real reasons Endurance sank — study finds Shackleton knew of ship’s shortcomings

Marine heatwaves have hidden impacts on ocean food webs and carbon cycling

Order from disordered proteins

Rocket test proves bacteria survive space launch and re-entry unharmed

New wheat diversity discovery could provide an urgently-needed solution to global food security

Could reducing inflammation help combat fatigue in people with early-stage breast cancer?

Traumatic brain injuries in older adults linked to increased risk of dementia

New intervention helps pediatricians promote early peanut introduction to prevent peanut allergy

New survey: Most Americans believe plasma donation saves lives, yet few have donated

New tools boost pediatricians’ adherence to peanut allergy guidelines 15-fold

Research unearths origins of Ancient Egypt’s Karnak Temple

Reevaluating nonoperative management for pediatric uncomplicated acute appendicitis

Metabolically active visceral fat linked to aggressive endometrial cancer, new study reveals

Scientists glimpse how enzymes “dance” while they work, and why that’s important

California partnership aided COVID-19 response and health equity, report finds

University of Oklahoma secures $19.9 million for revolutionary radar technology

Study finds restoring order to dividing cancer cells may prevent metastasis

High-accuracy tumor detection with label-free microscopy and neural networks

Wayne State research reveals fetuses exposed to Zika virus have long-term immune challenges

Researchers deconstruct chikungunya outbreaks to improve prediction and vaccine development

Study finds one-year change on CT scans linked to future outcomes in fibrotic lung disease

Discovery of a novel intracellular trafficking pathway in plant cells

New tool helps forecast volcano slope collapses and tsunamis

Molecular coating cleans up noisy quantum light

From Parkinson's to rare diseases, discovered a key switch for cellular health

Tiny sugars in the brain disrupt emotional circuits, fueling depression

[Press-News.org] Wide variation found in quality of evidence used by FDA for approval of new drugs