Executive Summary

Among hundreds of trials underway on potential therapeutics, only about 6% of study arms are expected to yield actionable data because most are nonrandomized, underpowered or underenrolled, Operation Warp Speed’s Janet Woodcock says, renewing her pitch for adoption of master protocols and other approaches to streamline studies and improve efficiency.

The COVID-19 pandemic is highlighting longstanding inefficiencies in the US clinical trials enterprise, the result being that only a small fraction of ongoing studies for potential therapeutics are expected to produce actionable data, Operation Warp Speed’s Janet Woodcock says.

Woodcock, who is on temporary leave as director of the Food and Drug Administration’s Center for Drug Evaluation and Research to head up COVID-19 therapeutics development for OWS, has long called for better coordination of the fragmented clinical trials system in the US and encouraged the use of master protocols to increase the efficiency of studies.

“Right now the situation with clinical trials for this disease is like starvation in the midst of plenty. We have competition for patients at major medical centers, and yet people are sick and dying all over the country and they don’t have access to clinical trials.” – OWS’ Janet Woodcock

At the Friends of Cancer Research’s 24th annual cancer leadership reception on 29 September, she suggested the pandemic will force a reckoning in how drug clinical trials are designed and conducted in the US.

“I think that we need to do some very serious soul searching after this is over,” Woodcock said in an exchange with Mark McClellan, director of the Duke-Margolis Center for Health Policy and a former FDA commissioner.

“Right now the situation with clinical trials for this disease is like starvation in the midst of plenty,” she said. “We have competition for patients at major medical centers, and yet people are sick and dying all over the country and they don’t have access to clinical trials.”

Little ‘Actionable Data’ Expected

There also are a large number of therapeutic trials underway that are not going to yield useful information, she said.

“From FDA, we’ve looked at this and we think only about 6% of all the trial arms that are going on will yield actionable data,” Woodcock said. She attributed this low percentage to the fact that many trials are not randomized, meaning that firm conclusions cannot be drawn from their results. In addition, many trials are underpowered or underenrolled, resulting in very small studies, she said.

“I think we really need to think about how we have a much more robust, standardized process in the United States for gathering clinical evidence,” she said.

According to the FDA’s Coronavirus Treatment Acceleration Program website, there were more than 70 early-stage trials and 240 late-stage trials of potential COVID-19 therapeutics ongoing as of 31 August.

Early in the pandemic Woodcock warned that the clinical trial research enterprise could be overwhelmed if it did not adopt master protocols, other platform approaches and adaptive designs to assess the efficacy and safety of potential COVID-19 therapeutics. (Also see “Woodcock Warns Research Apparatus Could Be Overwhelmed If Coronavirus Trials Don’t Use Master Protocols” – Pink Sheet, 27 Apr, 2020.)

Her call for better coordination and streamlining of COVID-19 therapeutic trials has been echoed by McClellan, former commissioner Scott Gottlieb (see sidebar), and other experts in the US and abroad. (Also see “For COVID, Consensus On Value Of Platform Trials, But A Confusion Of Consortia” – Pink Sheet, 1 Jun, 2020.)

However, FDA guidance on drug and biologic development to treat COVID-19 takes a cautious approach to the use of decentralized and platform trials. (Also see “US FDA Welcomes Variety Of Phase II/III Trial Designs For COVID-19 Therapies, But With Standards” – Pink Sheet, 13 May, 2020.)

ACTIV’s Master Protocols

Woodcock noted the National Institutes of Health’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) partnership is making use of the master protocol approach.

ACTIV is a public-private partnership to develop a coordinated research strategy for prioritizing and speeding development of the most promising treatments and vaccines for the disease caused by the novel coronavirus. (Also see “ACTIV Picks Potential COVID-19 Therapeutics To Be Tested In Master Protocol Trials” – Pink Sheet, 16 Jun, 2020.)

There are four ACTIV master protocols in place for therapeutic candidates:

• ACTIV-1 – Immune modulators in hospitalized patients;

• ACTIV-2 – Monoclonal antibodies and other therapies in the outpatient setting;

• ACTIV-3 – Monoclonal antibodies and other therapies for hospitalized patients; and

• ACTIV-4 – Antithrombotics, including three adaptive platform trials encompassing inpatient, outpatient and convalescent patients.

Eli Lilly and Company/AbCellera Biologics Inc.’s monoclonal antibody LY-Cov555 is being studied in the ACTIV-2 and 3 protocols. (Also see “Lilly’s EUA Timeline For COVID-19 Combo Antibody Depends On Safety Data, Manufacturing” – Pink Sheet, 7 Oct, 2020.)

In ACTIV-4, Bristol Myers Squibb Company/Pfizer Inc.’s oral anticoagulant Eliquis (apixaban) and aspirin are being evaluated in the outpatient trial; unfractionated and low molecular weight heparin are under study in the inpatient trial.

Running studies under the ACTIV master protocols allows different investigational therapeutics to share the same control group and is “more efficient, but no corners are cut there,” Woodcock said.

“We plan to test multiple agents and we’re putting government resources into that so we can make those trials as large as possible, enroll as many people as possible, which is a very good thing to do anyway but then that will get us the data that we need to show whether or not these work well enough and how safe they are.”

https://pink.pharmaintelligence.informa.com/PS143029/COVID19-Should-For…