Many registered clinical trials appear weak in methodological approaches

Clinical studies in CV, mental health and oncology registered in ClinicalTrials.gov between 2007 and 2010 are dominated by small, single-center trials and contain significant heterogeneity in methodological approaches, including the use of randomization, masking and data monitoring committees, researchers for a new study found.

In 1997, Congress mandated the creation of the ClinicalTrials.gov registry to assist those with serious illnesses in gaining access to trials. In 2004, the International Committee of Medical Journal Editors (ICMJE) announced a policy, which took effect in 2005, requiring registration of clinical trials as a prerequisite for publication.

Researchers conducted a study to examine characteristics of clinical trials registered in the ClinicalTrials.gov database. They focused on a data set comprising 96,346 interventional trials in CV, mental health and oncology, which were entered into a relational database to analyze aggregate data. Together, these three specialties encompass the largest number of disability-adjusted life-years lost in the United States, the researchers said.

The number of registered interventional clinical trials increased from 28,881 in 2004-2007 to 40,970 in 2007-2010, and the researchers found a decline in the number of missing data elements.

Most of the interventional clinical trials registered between 2007 and 2010 were small. Ninety-six percent of trials had an anticipated enrollment of 1,000 or fewer participants, and 62% of trials had 100 or fewer participants. On average, there were 58 participants per registered, completed trial and 70 participants per registered, uncompleted trial in the database. In addition, only 34% of registered clinical trials were conducted at more than one site.

Results showed that randomization and masking were used less often in earlier phase, oncology and device trials; mental health trials were more likely to use masking. Data monitoring committees were used less often in earlier phase and mental health trials compared with CV and oncology trials. Industry-sponsored trials were also less likely to use data monitoring committees compared with NIH-sponsored trials.

Robert M. Califf, MD, of Duke Translational Medicine Institute, and colleagues said the finding of substantial differences in the use of randomization and masking across specialties raises “fundamental questions about the ability to draw reliable inferences from clinical research conducted in that arena.”

Data on funding source and number of sites were available for 37,520 of the 40,970 clinical trials registered during the 2007-2010 period. Almost half (47%) of registered trials were not funded by industry or the NIH.

“Our analysis raises questions about the best methods of 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,” the researchers wrote in the study.

In a related commentary, Kay Dickersin, MA, PhD, of the Johns Hopkins Bloomberg School of Public Health, and Drummoned Rennie, MD, of the University of California, San Francisco, said: “It appears that despite important progress ClinicalTrials.gov is coming up short, in part because not enough information is being required and collected, and even when investigators are asked for information, it is not necessarily provided. … As a consequence, users of trial registries do not know whether the information provided through ClinicalTrials.gov is valid or up to date.”

For more information:

Disclosure: See the full study for the researchers’ relevant financial disclosures. Drs. Dickersin and Rennie report no relevant financial disclosures.