NIH Study Tracks Clinical Trials Outcomes to Preregistration Requirement

A new study looking at large-scale clinical trials funded by NIH shows the number reporting positive results dropped precipitously in the years since they were required to preregister on the clinicaltrials.gov website.

Of 55 clinical trials funded by the National Heart, Lung and Blood Institute between 1970 and 2012, 17 of 30 published prior to 2000 — when sponsors had to begin preregistering on the clinicaltrials.gov website — showed significant benefits. By contrast, only two of 25 trials showed significant benefits after that date, according to research published in PLOS ONE. Most trials showed no effect on patients, while only one showed harmful effects.

Authors Robert Kaplan and Veronica Irvin point out that the earlier studies had more flexibility in reporting successful outcomes because they weren’t tied to establishing specific primary and secondary outcomes during the preregistration process. Of the 25 trials after 2000, nearly half might have been able to file a positive report had they not been required to declare a primary outcome in advance, as 12 reported significant, positive effects for cardiovascular-related variables.

Advances in medical care and supportive therapy, along with a decline in the approval of new cardiovascular drugs, also could have affected the trials’ outcomes, the authors say. They also considered NHLBI’s involvement, noting that the institute participated in nearly 80 percent of trials published after 2000, while most of the earlier trials were investigator-initiated.

While having many trials show no effect could be disappointing to investigators, it could benefit science. “Transparent and impartial reporting of clinical trial results will ultimately identify the treatments most likely to maximize benefit and reduce harm,” the authors conclude.

Read the study here: www.fdanews.com/08-07-15-plosone.pdf. — John Bechtel