Mid-Study Updates Delay Trials At Least a Month, CSDD Report Finds
Data management professionals at sponsors and CROs say their biggest pain point is pausing trials mid-study for interim assessment or amendments, which typically adds at least a month to the trial timeline.
More than half (56.5 percent) of respondents to a new global survey say planned updates to electronic data capture (EDC) systems or protocols are their biggest data management challenge, while 48.4 percent cite unplanned updates.
According to a global survey by the Tufts Center for the Study of Drug Development (CSDD) published last week, larger companies take 35 to 40 days to resume a clinical trial after a planned or unplanned mid-study update, delaying trial closeout. Smaller companies report taking 25 days on average. The survey also found that companies report an average of four such disruptions per clinical trial.
The findings come as the clinical trials industry begins shifting to a postpandemic mindset, contemplating ways to simplify and accelerate trials once the urgency has passed. CSDD Director Ken Getz said mid-study updates are just one example of how trials are becoming more complex and longer. Speaking at the 2021 SCOPE Summit last week, Getz warned that the issue of updates needs to be addressed, or else measures taken during the pandemic to make trials more streamlined and patient-centric could end up being a one-time occurrence.
The pandemic, he says, “created a willingness to collaborate between the regulatory community and industry, between all different sectors within the clinical research ecosystem … that we have not seen. Which of these changes will stick? That’s really the question we’re all asking right now.”
Smaller companies reported faster restarts but slower closeouts — it took on average about 21 days for smaller companies to close a study, compared to about 15 days for large companies. CSDD also found that planned mid-study updates take 1.5 fewer days to complete than unplanned mid-study updates.
Survey respondents who were more satisfied with their EDC system’s ability to manage mid-study updates reported a five-day advantage in resuming a clinical trial. CSDD said most respondents to its survey — which was conducted between September and October 2020, with collaboration and funding from IBM Watson Health — were satisfied with their EDC solutions and providers (CenterWatch Weekly, Feb. 22, 2021).
Getz said an excellent example of decreasing complexity and increasing trial speed is the federal Operation Warp Speed, which he notes achieved a 75 percent to 80 percent reduction in time needed to move COVID-19 vaccines through clinical testing. But the industry is still waiting to see what actions would continue postpandemic.
“There’s a lot of resistance to seeing a lot of this translate into ongoing long-term behavior,” Getz said, adding that trials are including many customizations. Support for hybrid and remote trials, coupled with new eligibility criteria to improve diversity and inclusion “are all design elements that really can challenge our cycle time and often raise the cost of drug development and challenge efficiency as well.”
Speaking about patient-centric trials, he pointed out that evidence of their efficiency is still uncertain. Certain practices — such as offering conveniences so patients can participate in a trial from their home or with handheld devices — are still being done primarily on a pilot basis, but some were in a proof-of-concept phase. “Unfortunately, we don’t really have a good read on whether they are impacting our cycle times because they’re still relatively new and isolated more to anecdotal cases,” he said.
But Getz said CSDD has observed that the conduct phase of trials is evolving, with patient input into trial design and a larger number of advisory board meetings resulting in fewer substantial amendments and improved cycle times. “We also have seen recent studies indicating that the more transparency and disclosure in communicating our trial results and communicating our informed consent in plain language, these tend to have a positive relationship with retention rates in our studies and a higher level of satisfaction in our trials.”
Leonard Sacks, associate director for clinical methodology in the FDA Center for Drug Evaluation and Research’s Office of Medical Policy, who also spoke at the SCOPE Summit, says guidances issued by the FDA during the pandemic support measures taken by drugmakers during the health crisis and allow deferred reporting of such modifications to the agency. “These are likely to be enduring plans that will be applied increasingly to trials in the future,” he says.
Sacks added that allowing trial-related activities to take place at or close to patients’ homes is likely to have a very big impact in the future. He called decentralized clinical trial-related approaches, such as remote visits and the use of local healthcare providers to perform some study-related functions, “the most important building blocks of a decentralized clinical trial.”