Duke-Margolis’ Mark McClellan touts the advantages networks have over individual operations, citing the dexamethasone RECOVERY trial, and notes need for real-world evidence infrastructure.
In gathering data on potential COVID-19 therapeutics, clinical trial networks can accomplish what individual study sites are unable to do, Mark McClellan, director of the Duke-Margolis Center for Health Policy at Duke University, said.
Speaking at the Drug Information Association’s virtual meeting 17 June, McClellan noted that in the early days of the pandemic, well-meaning researchers did studies at single sites that had a lot of cases at the time. But he said they could not complete the trials and get definitive results because the number of COVID-19 cases declined.
“Many other places just didn’t set up clinical trials because they are hard to do,” McClellan said. “This is where clinical trial networks can make a big difference.”
McClellan said networks are able to get important evidence out faster and study a larger number of patients than operations working on their own. He noted that the Duke-Margolis Center is working in collaboration with the Clinical Trials Transformation Initiative (CTTI), a public-private collaboration supported by the US Food and Drug Administration, to expand the use of clinical trial networks.
“We really need them right now to get to more definitive evidence faster on COVID-19,” he said.
[Editor’s note: The challenges of clinical trials in the coronavirus era will be among the topics of a webinar event on July 21 addressing the impacts of COVID-19 and what has been learned so far. For 24 hours, executives, regulators and key opinion leaders will give you an exclusive view into how industry has responded and adapted to the pandemic. Registration for the webinars, sponsored by Informa Pharma Intelligence, is free.]
Value Of Dexamethasone Study
McClellan cited the RECOVERY randomized clinical trial of dexamethasone, conducted by Martin Landray and his colleagues at the University of Oxford, as an example of the information a network can gather. The university announced on 16 June that the study showed the steroid reduced deaths by one-third in hospitalized COVID-19 patients requiring ventilation. (Also see “Dexamethasone COVID-19 Findings Leave Authorities Bracing for Yet Another Demand Surge” – Pink Sheet, 16 Jun, 2020.)
“It’s I think by some people’s standard what you’d call a pragmatic trial, which may be a euphemism for people who are more of clinical trial purists saying, ‘Well, they only collected a limited amount of data,'” and did not include every single comorbidity and every single possible feature that could influence outcomes for patients, McClellan said. “But the flip side of that is that Martin was able to enroll a huge share of UK hospitals in this study,” which included the sickest patients.
He noted two other networks in the US that are conducting SARS-CoV-2 studies: the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership, and the I-SPY network, which is known for its master protocol for breast cancer therapies and is now being used for COVID-19 studies.
ACTIV has selected the first therapeutic agents to study in master protocol clinical trials. (Also see “ACTIV Picks Potential COVID-19 Therapeutics To Be Tested In Master Protocol Trials” – Pink Sheet, 16 Jun, 2020.) In April, I-SPY COVID launched a trial to evaluate both repurposed and novel drugs for their ability to decrease the number of critically ill patients who require mechanical ventilation or die. (Also see “For COVID, Consensus On Value Of Platform Trials, But A Confusion Of Consortia” – Pink Sheet, 1 Jun, 2020.)
Real-World Evidence Infrastructure
McClellan also emphasized the importance of conducting real-world studies after products are approved to fill in gaps from clinical trials, such as their effects on subgroups and minority populations.
We’d like to know more about access to those treatments “and about how they are actually performing in the real world,” he said. “Are we getting the doses right? Do we need a 10-day course [or] would a 5-day course be sufficient? When is the optimal time to do it? How do these treatments work in combination?”
He noted that there are the makings of networks in the US and elsewhere that could potentially develop data from routine electronic data systems and possibly electronic medical records systems on the inpatient side, and from insurance claims, ambulatory record data, and information from outpatients. But he said it requires an infrastructure to pull the data together and have common, shared approaches across multiple different systems even if they do not share their own data for proprietary or confidentiality reasons.
McClellan said we have the capacity to put in place steps to have an infrastructure that assures the quality of real-world evidence. He noted the FDA is supporting this through its COVID-19 Evidence Accelerator, a project it launched with the Reagan-Udall Foundation and Friends of Cancer Research. (Also see “US FDA Looking To Real-World Evidence To Fill in Gaps On COVID-19 Vaccines” – Pink Sheet, 11 Jun, 2020.)
“The idea is to go from single studies that individuals are trying to do using their sources of data and their analytic capabilities, to a common model for approaching these studies in the same way and maybe even getting to something like an aligned master protocol, just like we’re seeing make such a difference on the clinical side,” McClellan said.
He said the FDA is trying to make sure that real-world data are answering questions not only for regulatory purposes but also for comparative effectiveness and to understand the impact in specific patients, the “things that payers, clinicians and patients care about beyond the FDA regulatory framework.”