COVID-19 could have profound implications on the way rare disease researchers conduct clinical trials, long after the pandemic itself subsides.
During the pandemic, “the collaborations were incredible, and the ability to mobilize multidisciplinary groups was unlike anything I’ve ever seen before,” said Jeanine D’Armiento, MD, PhD, board chair of the Alpha-1 Foundation, a Miami, Florida-based charity that advocates for people with alpha-1 antitrypsin deficiency (AATD). “That was a result of everyone coming together for a common purpose during a critical period, that in itself we’re never going to repeat.”
Dr. D’Armiento, who also heads Columbia University’s Center for LAM and Rare Lung Disease in New York City, spoke October 18, 2021, during a session titled “Impact of COVID-19 on Rare Disease Research and Clinical Trials.” John Whyte, MD, chief medical officer at WebMD, moderated the session, which took place on the first day of the 2-day virtual National Organization for Rare Disorders (NORD) Breakthrough Summit 2021.
“Over the past year and a half, NORD has been closely monitoring the current and potential future impact of COVID-19 on rare disease research and clinical trials,” said Stephanie Christopher, NORD’s associate director of research programs. “While the pandemic has certainly brought challenges, it may also ultimately lead to some long-term efficiencies and improvements in the ways we conduct research.”
That would be particularly welcome news to people with AATD—a rare, inherited disorder that causes severe liver and lung disease if left untreated.
“We were at serious risk during COVID, and therefore there needs to be changes in the methodology by which we do clinical trials,” Dr. D’Armiento said. “Our patients could not come into the office [and] were pretty much locked down, and actually are still pretty locked down from some of the risks.”
Adapting Clinical Trials to Pandemic Realities
In the United States, clinical trials are supervised by the Food and Drug Administration (FDA). M. Khair ElZarrad, MD, MPH, directs the Office of FDA Medical Policy at the Center for Drug Evaluation and Research (CDER).
“Clinical research has been impacted across the board by COVID, with the different guidelines, quarantines, and approaches we had to employ to handle this public health emergency,” he said. “Quickly, the FDA managed to produce guidance to try to highlight certain areas where there are flexibilities, where there’s room to maneuver, to make sure clinical research can continue.”
Dr. ElZarrad said his agency’s real-world evidence program has been going on since 2018.
“This public health emergency functioned as a catalyst for a lot of our early initiatives,” he said. “We know we have to get better at clinical trials, to improve the design and conduct, and have better efficiencies. But now, because of COVID, we have to move faster [with] decentralized clinical trials, the use of digital health tools and real-world evidence.”
Dr. ElZarrad added: “We’re not just looking for the flashy items or nice designs, but how we can really improve processes” for the benefit of actual patients.
“We believe that significant advance is going to need multiple steps, and those steps will have to move together to really get us somewhere that’s helpful to the patients, the rare disease community and beyond,” he said. “But putting those solutions potentially into action has proven challenging, and I think we have an opportune time right now to push for that.”
A Changing Research Landscape
Katherine Needleman, PhD, is director of the Clinical Trials and Natural History Grants Program at the FDA Office of Orphan Products Development (OPD). She said her office launched its Unite initiative in 2020, just before the World Health Organization declared COVID-19 a pandemic.
“Our intent was to have a forum for currently funded clinical trial and natural history grantees to share their experiences and challenges, and support common solutions for rare disease research,” she said. “When COVID hit, we actually had two Unite meetings planned, but ended up adding a third, two of which were focused on COVID-19 issues.” These meetings allowed researchers from all over the world to discuss issues they were facing during the pandemic.”
Dr. Needleman said OPD “continues to look at this moving along as the landscape changes over time, with vaccines as well as COVID surges around the world. We continue to collect data and to show the impact of COVID on rare disease research and our grants—and to change the program as we need to.”
Yet Michelle McMurry-Heath, MD, PhD, president and CEO of the Biotechnology Innovation Organization (BIO), said that in the end, results are more important than buzzwords like decentralization and patient centricity.
“Basically, it comes down to whether or not we intend for these new tools and approaches to really serve patients,” she said. “And if we do, we need to take a big step backwards and say, ‘OK, let’s consider our entire clinical trial paradigm.’ What is the evidence FDA really needs to be able to make their benefit-risk judgments and calculations? And is there a new way sitting here today, post-pandemic, post-IT revolution, to start collecting some of this information, and maybe throw out our weddedness to the classic randomized, controlled, double-blind study.”
More to the point, Dr. McMurry-Heath said, “we adhere to this as though it’s gospel, and it is the only way to truly know how a new medical innovation works. But in reality, the dirty little secret is that we all know that when actual medical products get released to the general population, the results never match those pristine trials.
“And so if they don’t accurately reflect what happens in reality, then we need to ask ourselves what does,” she added. “That’s why real-world evidence and real-world data are so critical, because it reflects reality.”
Impact of COVID-19 on rare disease research, clinical trials, and drug development. Presented at: NORD Breakthrough Summit 2021: October 18, 2021; Virtual.