DIA: Woodcock, other top officials tout benefits of master protocols, want momentum to continue post-COVID

Regulatory NewsRegulatory News | 02 July 2021 |  By 

Top officials from the US Food and Drug Administration (FDA) exhort the benefits of master protocols and hope the momentum of using these protocols continues in the post-COVID-19 era. Officials also say the pandemic has not dampened the enthusiasm for gene therapy development as the agency continues to receive a healthy number of investigational new drug applications (INDs) for these therapies.
These were some of the learnings imparted by agency officials in discussing the effects of the COVID-19 pandemic at a 1 July virtual town hall convened by the Drug Information Association during its annual meeting.  A good part of the one-hour town hall addressed the use of master protocols as the way forward for clinical trials because of their ability to study large, diverse patient populations with efficacy rates mirroring real world use.
The use of these protocols was strongly supported by FDA Acting Commissioner Janet Woodcock, Patrizia Cavazzoni, the director of the Center for Drug Evaluation and Research (CDER), and Peter Marks, the director of the Center for Biologics Evaluation and Research (CBER).
COVID “turbo charges” master protocols
Cavazzoni said that before the pandemic, sponsors had very limited experience with master protocols, yet COVID-19 changed things as more sponsors were adopting this design.
Before the pandemic, “protocols from platform trials were very limited, and the COVID experience was a learning curve and gave a boost to CDER to evaluate the trials,” said Cavazzoni.  “I think it has been a very important experience because it has turbo charged the utilization of master protocols.”
She added that while FDA’s new guidance on master protocols “is still labeled a COVID-19 guidance” she said that “I have every expectation and hope that this will be an approach that will be used to a much greater extent in the post-COVID arena.”
In May, FDA released a guidance addressing how master protocols can be used in developing drugs to treat or prevent COVID-19. (RELATED: FDA issues new COVID-19 master protocol guidance, Regulatory Focus 17 May 2021).
Woodcock: master protocols more complicated
Woodcock observed that that while master protocols are more “complicated” and may take longer to set up then conventional trials, they can “evaluate multiple agents efficiently” once they’re up and running. “What we found is that the master protocols — from discovery to active trials to repurposed trials — are able to perform very well.” and can impart “actionable data.”
Woodcock said that a recent FDA study showed that a “disproportionate” amount of the “adequately powered and randomized” clinical trial data generated for therapeutics emanate from master protocols. She noted that “many of the obstacles to getting master protocols going that were there before the pandemic still remain, and we have to overcome that.”
Woodcock has long advocated for the benefit of master protocols. In 2017, she co-authored a New England Journal of Medicine  piece advocating for the use of platform trials for efficient  generation of evidence in precision medicine. (RELATED: FDA officials: master protocols needed for precision medicine, Regulatory Focus, 7 July 2017)
Strong correlations between clinical trial and real-world data
Marks elaborated on the “robust” data emanating from COVID-19 trials and attributes this to the strong correlation between clinical trials data and real-world data, with trial populations largely mirroring the overall population.
He said that COVID-19 mRNA vaccine trials are showing 94 to 95% efficacy in preventing the cirus, which mirrors the 94 to 97% efficacy in the real world.
The strong correlation between clinical trial efficacy and real-world efficacy, he said “is something that should be fostered and something to move forward with after the pandemic.”
“The better evidence we can collect and the more robust it is the better it will be. That is the reason we are seeing such great correlations between the real-world effectiveness of the mRNA vaccines and the clinical trials,” said Marks.
Woodcock: pushing for research out of the ‘ivory tower’
Woodcock said that because of these benefits and efficiencies of studying drugs in large patient populations, she will be “pushing” for larger trials run out of community-based sites.
She said that “we need to have master protocols that are run by the community because there are so many remaining questions about the treatment policy for most diseases. What should you start with? Which disease should you use? Which doses should you use and how can you personalize this? This should be answered by expert opinions and not data. We need to get clinical research out of the ivory tower and into the communities of everyone who gets medical care.”
She cited some of the inefficiencies of cancer trials, noting that only about 8% of patients with cancer are actually enrolled in trials, although the treatments in these trials could help most cancer patients.
As part of the effort to move more clinical trials out of academic medical centers and boost community enrollment, Cavazzoni said that FDA is working on a guidance on decentralized trials for remote data assessment targeting community-based sites.
Robust gene therapy development despite pandemic
In other areas, the pandemic has not dampened interest in new cell and gene therapy development, said Marks. He said that the number of cell and gene therapy INDs submitted to the agency increased by 20% this past year, showing that there is a “tremendous amount of work going on.”
He said that “we predicted that by 2025 we would approve between five and ten gene therapies a year. I don’t think we will be that far off despite the pandemic slowing things down a little bit. There are still a healthy number of applications.”
Currently, some sponsors are experiencing “speed bumps” with their data as some toxicity issues have emerged, but the agency is working with sponsors to help resolve these issues, said Marks.
Additionally, Marks noted that many clinical trial sponsors experienced significant disruption of their programs during the height of the pandemic, when many patients could not travel. “We will have to work with them on a case-by-case basis and salvage what we can,” said Marks. 
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Tags: FDA, Master, protocols

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