Calculating the Pandemic’s Toll on Clinical Trials

It’s been clear from the stream of press releases and financial announcements that the COVID-19 pandemic has had an impact on clinical trials, but the reporting has been anecdotal. It is rare that I will speak to a biopharmaceutical executive and hear that a company’s clinical trials have been unimpeded, except for companies developing COVID-19 therapies and vaccines.

Benjamin Gregory Carlisle, a research fellow at the Berlin Institute of Health, has tried to quantify the impact that the pandemic has had on disrupting clinical studies. In an early draft paper of ongoing research published online, he finds that of 2,522 clinical trial entries on ClinicalTrials.gov for trials that have been suspended, terminated, or withdrawn between December 1, 2019 and May 5, 2020, 1,099 (44 percent) provided an explanation for stopping the study that mentioned COVID-19.

For a comparator arm, Carlisle broke down the number of stopped trials during the same period two years earlier. There was a total of 1,233 trials stopped during that time.

The studies that stopped due to COVID-19 had a combined actual enrollment of 39,405 patients and anticipated enrollment of more than 4 million patients.

One notable difference between the two groups is that that 97 percent of the trials stopped because of the pandemic were suspended rather than terminated or withdrawn. That compared to just 18 percent of the trials in the comparator arm. Most of the trials stopped in the comparator arm were either terminated (47 percent) or withdrawn (34 percent).

That, however, may change.

“While many clinical trials were suspended with the intention of restarting after the Covid-19 pandemic,” wrote Carlisle, “the prospect of starting again is far from certain for any clinical trial that has stopped, and even in cases where a clinical trial resumes after the pandemic, there may be reduced statistical power, more funding needed, or changes to the protocol to accommodate for the interruption.”

Carlisle doesn’t break down the number of rare disease trials affected by the pandemic, but he does offer a breakdown by broad indication. This includes 125 cardiovascular studies (11 percent), 93 neurologic studies (8.5 percent), and 308 oncology studies (28 percent).

Among the clinical trials that were stopped with a reason citing Covid-19, 504 trials were testing drugs or biologicals. The remainder were testing procedures, devices, behavioral interventions, laboratory analyses, diagnostic tests, or other things.

For patients who were enrolled in studies, Carlisle notes they may not receive the treatment they had anticipated, and they may not make the contribution to advancing medical knowledge as they may have hoped. He noted the pandemic has also caused a setback for entire research programs and could delay the advent of new therapies.

While the human and economic toll have been apparent from the pandemic, the impact on biomedical research has not only been obscured, but the extent of the damage remains an open question. One reasonable bet is that the longer it takes to restore trials, the more lasting the impact will be.

“Clinical trials that were stopped and do not start again may be unable to answer the questions they set out to answer,” writes Carlisle. “and even in cases where they do start again, it may take greater resources to make up for data that can no longer be included in analys[es] due to the interruption.” 

Much is still unanswered about the ultimate impact the pandemic will have on clinical trials. That’s because it is unclear how many of these studies will eventually restart and how long it will be before they begin. What Carlisle has documented suggests that the pandemic’s impact on drug developmental is broad. The question that remains is how deep it will be.