Phase 3 Trials Significantly Rising in Complexity, Says CSDD
The scope and burden of conducting late-stage trials is rapidly growing, research from Tufts University’s Center for the Study of Drug Development (CSDD) finds, with the average number of phase 3 endpoints having increased 37 percent since 2015.
According to CSDD’s latest Impact Report, a typical phase 3 trial conducted between 2016 and 2021 employed an average of 25.8 endpoints, up from 19.5 in the previous five-year period.
CSDD also found the number of phase 3 trial procedures grew 42 percent from 2016 to 2021, while phase 2 procedures increased 18 percent. The total number of phase 2 endpoints, however, slightly decreased. The researchers pointed out that approximately one in four procedures in phase 2 and 3 protocols supported ancillary secondary, tertiary and exploratory endpoints.
In another finding, CSDD discovered that phase 3 studies were conducted across 13 countries on average, a 39 percent uptick since 2015, while the average number of investigative sites per phase 2 and 3 trial increased 25 percent.
“Wide variation in the mean number of countries observed in the more recent vs. earlier time period suggests less consistent country selection and management practices by sponsors,” determined the report, adding that, despite this, phase 2 studies were conducted in “six to seven countries on average in 2016-2021, a number that has not changed since 2015.”
The researchers noted that the average number of trial participants screened and enrolled in phase 3 trials has decreased to 1,466.9 volunteers from 1,613.5 volunteers in 2015, “in part due to the growing proportion of late-stage protocols targeting rare diseases and more narrowly defined patient communities.”
Phase 2 trials experienced a 3 to 5 percent growth in the mean number of study participants since 2015.
CSDD found the length of study startup — from protocol approval to first patient visit — for both phase 2 and 3 studies has shot up since 2015. Specifically, phase 3 trial startup times have gone from 162.9 days on average in 2011-2015 to 211 days in 2016-2021, while phase 2 times have risen from 141.5 days to 204.4 days in those same time periods.
Similarly, the mean overall duration of clinical trials — from protocol approval to database lock — increased by 11 percent for phase 2 trials and by 7 percent for phase 3 trials. Phase 3 study closeout times fell by 14 percent, whereas phase 2 study closeout times grew by nearly 6 percent.
And since 2015, the average number of planned visits per study volunteer, a measure used to determine study execution burden, saw a 37 percent uptick for phase 3 trials and a 13 percent increase for phase 2 trials, the report found.
In addition, the researchers found that phase 3 trials of new small molecule chemical entities used a larger number of sites to screen and enroll nearly 35 percent more patients than trials of large molecule biologics.
Access the report here: https://bit.ly/41vQ6sO.