[Ip-health] Large-Scale Analysis Finds Majority of Clinical Trials Don't Provide Meaningful Evidence

Riaz K Tayob riaz.tayob at gmail.com
Thu May 3 05:39:59 PDT 2012

[Let us just forget the ethics of some of BigPharma in Africa, like 
Pfizer and meningitis in Nigeria... perhaps the push to not hold 
companies liable for shoddy work will gain more momentum... ]

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

ScienceDaily (May 1, 2012) --- The largest comprehensive analysis of 
Clinicaltrials.gov finds that clinical trials are falling short of 
producing high-quality evidence needed to guide medical decision-making.

The analysis, published May 1 in the/Journal of the American Medical 
Association/, found the majority of clinical trials is small, and there 
are significant differences among methodical approaches, including 
randomizing, blinding and the use of data monitoring committees.

"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 to ensure confidence 
in guideline recommendations," said Robert Califf, MD, first author of 
the paper, vice chancellor for clinical research at Duke University 
Medical Center, and director of the Duke Translational Medicine Institute.

The analysis was conducted by the Clinical Trials Transformation 
Initiative (CTTI), a public-private partnership founded by the Food and 
Drug Administration (FDA) and Duke. It extends the usability of the data 
in Clinicaltrials.gov for research by placing the data through September 
27, 2010 into a database structured to facilitate aggregate analysis. 
This publically accessible database facilitates the assessment of the 
clinical trials enterprise in a more comprehensive manner than ever 
before and enables the identification of trends by study type.

The National Library of Medicine (NLM), a part of the National 
Institutes of Health, developed and manages Clinicaltrials.gov. This 
site maintains a registry of past, current, and planned clinical 
research studies.

"Since 2007, the Food and Drug Administration Amendment Act has required 
registration of clinical trials, and the expanded scope and rigor of 
trial registration policies internationally is producing more complete 
data from around the world," stated Deborah Zarin, MD, director, 
Clinicaltrials.gov, and assistant director for clinical research 
projects, NLM. "We have amassed over 120,000 registered clinical trials. 
This rich repository of data has a lot to say about the national and 
international research portfolio."

This CTTI project was a collaborative effort by informaticians, 
statisticians, and project managers from NLM, FDA and Duke. CTTI 
comprises more than 60 member organizations with the goal of identifying 
practices that will improve the quality and efficiency of clinical trials.

"Since the Clinicaltrials.gov registry contains studies sponsored by 
multiple entities, including government, industry, foundations and 
universities, CTTI leaders recognized that it might be a valuable source 
for benchmarking the state of the clinical trials enterprise," stated 
Judith Kramer, MD, executive director of CTTI.

The project goal was to produce an easily accessible database 
incorporating advances in informatics to permit a detailed 
characterization of the body of clinical research and facilitate 
analysis of groups of studies by therapeutic areas, by type of sponsor, 
by number of participants and by many other parameters.

"Analysis of the entire portfolio will enable the many entities in the 
clinical trials enterprise to examine their practices in comparison with 
others," says Califf. "For example, 96 percent of clinical trials have 
?1000 participants, and 62 percent have ? 100. While there are many 
excellent small clinical trials, these studies will not be able to 
inform patients, doctors, and consumers about the choices they must make 
to prevent and treat disease."

The analysis showed heterogeneity in median trial size, with 
cardiovascular trials tending to be twice as large as those in oncology 
and trials in mental health falling in the middle. It also showed major 
differences in the use of randomization, blinding, and data monitoring 
committees, critical issues often used to judge the quality of evidence 
for medical decisions in clinical practice guidelines and systematic 

"These results reinforce the importance of exploration, analysis and 
inspection of our clinical trials enterprise," said Rachel Behrman 
Sherman, MD, associate director for the Office of Medical Policy at the 
FDA's Center for Drug Evaluation and Research. "Generation of this 
evidence will contribute to our understanding of the number of studies 
in different phases of research, the therapeutic areas, and ways we can 
improve data collection about clinical trials, eventually improving the 
quality of clinical trials."

An analysis-ready copy of the ClinicalTrials.gov 
<http://ClinicalTrials.gov> database is now available at 
www.ctti-clinicaltrials.org <http://www.ctti-clinicaltrials.org>/. 
/Specialists from numerous therapeutic areas are now scrutinizing the 
contents to better understand how the number and characteristics of 
clinical trials match the perceived needs of the research communities.

This dataset will be useful for academic institutions and also for 
pharmaceutical and device companies to produce reports showing the 
completeness of their data entry compared to other institutions. 
Advocacy groups can chronicle the number and types of trials in their 
area of interest.

Data quality is likely to improve as a function of the accountability 
fostered by this transparency.

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