Clinical Trial Design, Composition Has Undergone Major Changes

August 31, 2020 - From 2000 to 2019, composition and design of clinical trials changed substantially by sponsor type, suggested a need for increased funding for larger randomized trials , a JAMA Network Open study found.

Out of 245,999 clinical trials started over the nine-year period, just 54.9 percent were completed, 11.4 were incomplete, 20.2 percent were active, and 4.6 had unknown status.

From 2000 to 2019, fewer drug trials have been conducted over time. This shift could be explained by the increased uptake in registration for these trials, expansion of clinical trial definition, or increasing interest in other intervention types in recent years, researchers said.

The decreasing percentages of trials that involved drugs may also be associated with increased costs and challenges associated with conducting Phase 3 to 4 drug trials.

The cross-sectional study also included clinical trials registered in ClinicalTrials.gov from January 1, 2000, through December 31, 2019.

The majority of these trials were randomized (65.6 percent), while some were single center (61.3 percent) and others were Phase 1 to 2 (35.5 percent) or did not have FDA-defined phase (38.4 percent).

The trials were separated by lead sponsor of the trial, including the National Institutes of Health (NIH) and other US government agencies, industry, and other sources, including foundations, universities, hospitals, clinics, and others.

The NIH or a US government agency sponsored 3.8 percent of the trials, 36 percent were sponsored by industry, and 60.2 percent were sponsored by other sources.

The NIH and US government agencies were the lead sponsors for a larger percentage of completed Phase 1 to 2 trials, and industry was the lead sponsor for more Phase 3 to 4 trials completed over time.

Over nine years, the median times to completion by lead sponsor were 3.4 years for NIH or US government-sponsored trials, 1.2 years for industry trials, and 2.1 years for trials sponsored by other sources, researchers said.

More specifically, the median time for NIH and US government agencies to complete a Phase 3 to 4 trial was 5.4 years in 2000, 3.8 years in 2005, 3.7 years in 2010, and 3.2 years in 2015.

Additionally, time to completion for industry-sponsored Phase 3 to 4 trials was relatively steady over the nine years.

Specifically, the average completion time was 3.2 years in 2000, 1.7 years in 2005, 1.7 years in 2010, and 1.6 years in 2015. Times to completion for Phase 3 to 4 trials sponsored by other sources were 6.0 years in 2000, 3.1 years in 2005, 3.0 years in 2010, and 1.6 years in 2015.

In 2007, posting clinical trial results became required. Over the nine years, the percentage of completed trials posting results by agency was 47.7 percent for NIH and government-sponsored trials, 37.8 for industry-sponsored trials, and 16 percent for trials sponsored by other sources.

“Overall, trial sample sizes decreased over time and took less time to complete. Median times to trial completion varied by sponsor type and phase. Industry completed trials at faster rates compared with the NIH and US government and other funders, possibly in association with more efficient trial startup processes and higher recruitment rates,” researchers explained.

One possible reason for the decrease could include changes in the types of outcomes being used, such as surrogate outcomes and biomarkers, and patient-reported outcomes. Additionally, increasing trial-associated costs and greater budget constraints are potential reasons for the decline as well.

“The findings suggest that registration and reporting systems could be further improved. There appears to be a need for ClinicalTrials.gov to modify its registration system to accommodate the broader range of trials being conducted and the collaborative arrangements involved,” researchers concluded.