Regulatory Focus™ > News Articles > Study: Many Clinical Trials Small, of Poor Quality

Study: Many Clinical Trials Small, of Poor Quality

Posted 02 May 2012 | By Alexander Gaffney, RAC 

Amidst an explosion in the number of clinical trials registered with US regulatory authorities, a new study analyzing clinical trials conducted in the US has found most of them to be relatively small and of inconsistent-and often poor-quality.

The study, Characteristics of Clinical Trials Registered in, 2007-2010, was published in the Journal of the American Medical Association (JAMA) on 2 May 2012.

"Clinical trials registered in are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and Data Monitoring Committees (DMCs)," explained lead authors Robert Califf of the Duke Translational Medicine Institute and Deborah Zarin of the National Library of Medicine, who also is the Director of

The authors note the number of trials has gone up significantly in recent years. Approximately 28,900 trials were registered between 2004 and 2007, increasing to nearly 41,000 between 2007 and 2010.

Most of these interventional trials enrolled fewer than 100 patients each (62%), were based at just one center (66%) and were industry-supported (47%).

The use of some tools commonly associated with high-quality clinical trials was inconsistent, the authors said.

"For example, reported use of DMCs was less common in industry-sponsored vs. National Institutes of Health (NIH)-sponsored trials, earlier-phase vs. phase 3 trials, and mental health trials vs. those in the other two specialties. In similar comparisons, randomization and blinding were less frequently reported in earlier-phase, oncology, and device trials."

The authors concluded these inconsistencies raise "fundamental questions about the ability to draw reliable inferences from clinical research conducted in that arena."

Small trials, particularly ones used to support medical treatment policies, may be inappropriate in many cases, wrote the authors.

"[S]mall trials are unlikely to be informative in many other settings, such as establishing the effectiveness of treatments with modest effects and comparing effective treatments to enable better decisions in practice."

"Our analysis raises questions about the best methods for generating evidence, as well as the capacity of the clinical trials enterprise to supply sufficient amounts of high-quality evidence needed to ensure confidence in guideline recommendations," explained the authors.

"Given the deficit in evidence to support key decisions in clinical practice guidelines as well as concerns about insufficient numbers of volunteers for trials, the desire to provide high-quality evidence for medical decisions must include consideration of a comprehensive redesign of the clinical trial enterprise," they concluded.

Read more:

JAMA - Characteristics of Clinical Trials Registered in, 2007-2010

Examination of registered clinical trials suggests weakness in size and methodology of many studies

Reuters - Drug and device trials vary in size, quality: study

Medscape News - Many Clinical Trials Unable to Supply High-Quality Evidence

Medical Daily - Large-Scale Analysis Finds Majority of Clinical Trials Don't Provide Meaningful Evidence

Med Page Today - Federal Registry Gets More Trials, Data Still Short

Health Day - Analysis Finds Clinical Trials Often Small, of Poor Quality

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