How COVID-19 Has Changed Clinical TrialsJuly 16, 2021 - Todd Ackerman
The COVID-19 pandemic changed almost every aspect of life the past year, including the way physicians conducted the testing of new treatments.
Edward A. Jones, president and chief executive officer of the Houston Methodist Research Institute, spoke to us about clinical trials' best and worst moments, the lessons learned and whether they can be sustained and applied to other diseases.
Q: How did the pandemic change clinical trials?
Jones: It accelerated trial approvals. People on both sides, trial sponsors and researchers, compromised more. In order for us to test promising COVID-19 therapies, we were far more willing to accept the proposed terms. Most weren't far off from our normal stance, but both of us were willing to bend on contracts and meet in the middle. You didn't see the negotiations that can sometimes go back and forth.
Q: Is that sustainable?
Jones: As we're coming out of the pandemic, we're seeing some of the old habits creep back in. We're trying to not do that because speed is important, the time for the therapeutic to the patient. The quicker we get patients on a study, the quicker we can answer study questions.
Q: What still needs to change? What was exposed by the pandemic?
Jones: The way we think about clinical trials and health systems. Clinical trials would have been far more effective had sponsors looked at us as a system rather than a site. When studies opened, they almost universally opened at the Texas Medical Center, maybe occasionally added the West Houston campus. But the drug companies wouldn't let us add other sites, even though, for example, we had a large population of COVID-19 patients at Sugar Land. That's something that we desperately need to change to accrue more patients, answer questions, go on to the next studies. We have to leverage the value of a "health system," not an individual location. To me, that is the most fundamental thing that needs to change.
Q: Anything surprise you?
Jones: Some study designs were weak. They weren't the true placebo-controlled designs that one needs to run enough to answer study questions and stand behind scrutiny. Questions about hydroxychloroquine, for instance, were never fully answered. The consensus was it doesn't work or we'd have a signal it did. But that was accepted because of the assembly of a lot of information out there rather than a definitive study design. This was especially important early in the pandemic. That was a real takeaway from the pandemic — that the discipline around robust study design and enrolling enough patients to definitively answer the question cannot be understated. We must perform high quality science if we want the public to "trust the science."
Q: What's the single best thing that came out of the clinical trial response to the pandemic?
Jones: The good thing is we saw what we can do, how we can mobilize, how dedicated our teams are. We saw the potential, which was greater than we ever envisioned. We saw medicine, science, regulatory, finance, legal and business domains work tirelessly together to find solutions. We saw everyone rally together to try and conquer this disease. It was incredibly rewarding.
Q: How about the worst?
Jones: The worst part was the politicizing of medicine and science that occurred. The virus has one job and that's to continue to propagate, which it's still trying to do. Watching people politicize or pick apart the messy process by which science learns from new data was disheartening. People were so unforgiving about science changing its mind in response to new data. I scratch my head at it. Science didn't "change its mind;" it learned from new data.
Q: What's a good example of that?
Jones: Masking. We didn't think initially masks were that important, then they became really important. They're a good example of learning as we went along. We essentially did a 180, which creates skepticism, but you have to be able to adjust as you learn new data.
Q: How about pre-print publications? I recall some criticism of them.
Jones: Yes, everybody was trying to put information out. Some of it was responsible, some wasn't. Some pre-prints reinforced people's beliefs and got picked up even though they weren't that sound, then continued to be cited for a long time even after they were retracted. We also didn't do a good job separating out what was more subjective and editorial versus hard data from the highest standard of scientific inquiry. The two domains kind of got blended together. It was important to put out early hypotheses and thoughts, but too many times those hypotheses came off as fact.
Q: Did we discover anything new about how digital technology can transform research?
Jones: It definitely opened up the imagination to what we can do. Can we get a drone to drop this off? Can we use video? For example, we were able to consent patients in an infectious disease unit without needing to cross the physical barrier by using IRB-approved informed consent with video proctoring for COVID-19 trials. That technology can just as easily cross the barrier of rural parts of Texas. We no longer have to think about research being done within walls of our health system.
Q: Is urgency about pandemic research still there or is it kind of over now?
Jones: It's dropped off. We're just not conducting that many new COVID-19 studies now. Review committee looked at one last week, compared to, say, seven to 10 a week during the pandemic. Conducting trials depends on the number of patients in the hospital so our ability to run a lot of studies now is pretty low. But this may change as new variants emerge.
Q: Can the lessons learned during COVID-19 be continued or are we likely to go back to business as usual?
Jones: I hope we don't go back to business as usual. I think there have been lessons learned that we should hold on to. Obviously, we can't have people working seven days a week, 20 hours a day, the sort of war-time stress the pandemic brought, but we've seen the speed at which we can conduct trials, and have learned how to leverage the resources that are available. We need to translate that to other diseases rather than become complacent when the pandemic is over. It really shined a bright light on the opportunities and demonstrated the importance of our continued investment in academic medicine.