The COVID-19 pandemic has created unique and unprecedented challenges for the clinical research world, with potentially long-lasting consequences.
A new analysis of the extent of disruption shows that the average rate of stopped trials nearly doubled during the first 5 months of 2020, compared with the 2 previous years.
“Typically, clinical research precedes clinical practice by several years, so this disruption we’re seeing now will be felt for many years to come,” said Mario Guadino, MD, from the Weill Cornell Medicine, New YorkCity.
The analysis was published online July 31 in the Journal of the American College of Cardiology.
The researchers used Python software to query meta-data from all trials reported on ClinicalTrials.gov. Of 321,218 non-COVID-19 trials queried, 28,672 (8.9%) were reported as stopped, defined as a switch in trial status from “recruiting” to “active and not recruiting,” “completed,” “suspended,” “terminated,” or “withdrawn”.
The average rate of discontinuation was 638 trials/month from January 2017 to December 2019, rising to 1147 trials/month between January 2020 and May 2020 (P < .001 for trend).
Once stopped (as opposed to paused), restarting a trial is a tricky prospect, said Guadino. “You can’t stop and restart a trial because it creates a lot of issues, so we should expect many of these stopped trials to never be completed.”
He said these figures likely represent an underestimate of the true impact of the pandemic because there is typically a delay in the updating of the status of a trial on ClinicalTrials.gov.
“We are likely looking only at the tip of the iceberg,” he added. “My impression is that the number of trials that will be affected and even cancelled will be very high.”
As for cardiology trials, one of the report’s authors, Deepak Bhatt, MD, Brigham and Women’s Hospital, Boston, without naming specific trials, had this to say: “Several cardiovascular trials were paused, and some were permanently discontinued. It may be a while before we fully appreciate just how much information was lost and how much might be salvaged.”
He’s not worried, however, that upcoming cardiology meetings, which have moved online for the foreseeable future, might get a bit boring. “Fortunately, there is enough good work going on in the cardiovascular and cardiometabolic space that I believe there will still be ample randomized and observational data of high quality to present at the major meetings,” Bhatt said in an email.
The researchers found a weak correlation between the national population-adjusted numbers of COVID-19 cases and the proportion of non-COVID trials stopped by country.
Even for trials that stopped recruiting for a period of time but are continuing, there are myriad issues involving compliance, data integrity, statistical interpretability, etc.
“Even if there is just a temporary disruption, that will most likely lead to reduced enrollment, missing follow-up visits, and protocol deviations, all things that would be red flags during normal times and impact the quality of the clinical trial,” said Guadino.
“And if your outcome of interest is mortality, well, how exactly do you measure that during a pandemic?” he added.
Stopped for Lack of Funding
Besides the logistical issues, another reason trials may be in jeopardy is funding. A warning early in the pandemic from the research community in Canada that funding was quickly drying up, leaving both jobs and data at risk, led to an aid package from the government to keep the lights on.
The National Institutes of Health (NIH), the Canadian Institutes of Health Research, and similar groups “have devoted large sums of money to research in COVID, which is of course very appropriate, but that clearly reduces the amount of funding that is available for other researchers,” said Guadino.
Some funding agencies around the world have cancelled or put on hold all non-COVID clinical trials still at the design state, Guadino told theheart.org | Medscape Cardiology.
The NIH, he stressed, has not canceled funding and has been “extremely open and cooperative” in trying to help trialists navigate the many COVID-generated issues. They’ve even issued guidance on how to manage trials during COVID-19.
Of note, in the survey, the majority of the trials stopped (95.4%) had non-governmental funding.
“The data are not very granular, so we’re only able to make some very simple, descriptive comments, but it does seem like the more fragile trials — those that are smaller and industry-funded — are the ones more likely to be disrupted,” said Guadino.
In some cases, he said, priorities have shifted to COVID. “If a small company is sponsoring a trial and they decide they want to sponsor something related to COVID, or they realize that because of the slow enrolment, the trial becomes too expensive to complete, they may opt to just abandon it,” said Guadino.
At what cost? It will take years to sort that out, he said.
This study received no funding. Guadino and Bhatt are both active trialists, participating in both industry- and government-sponsored clinical research.
J Am Coll Cardiol. Published online July 31, 2020. Article
Medscape Medical News © 2020