A dozen years and a billion or more dollars —that is what it typically takes to bring a new drug from the lab to your medicine cabinet. Testing medications on patients has become a slow, arduous process. People, even those who are desperate to participate, often have to travel long distances to a study site and make the trip over and over again. For scientists, coordinating the paperwork among a large number of research centers can be extremely laborious and time-consuming.
But the urgency of the pandemic and the dangers it presents are forcing needed changes. For example, investigators have turned to remote data collection methods that are safer and more convenient for participants. John H. Alexander, a cardiologist and senior researcher at the Duke Clinical Research Institute, says this kind of access and other improvements are long overdue. Alexander is steeped in the world of medical research, but he is also a thoughtful critic of how it is done. He is co-chair of the Clinical Trials Transformation Initiative (CTTI), a public-private partnership founded by Duke University and the U.S. Food and Drug Administration, and has long advocated for reforms that would make research smarter, faster and more accessible to patients without sacrificing quality. In an interview with contributing editor Claudia Wallis, Alexander described how the pandemic is beginning to make clinical research better—and how much more needs to be done.
[An edited transcript of the interview follows.]
How has COVID begun to challenge “research as usual”?
All of a sudden we had a new disease and no idea how to treat it. COVID urgently highlighted our need for quick, big, rigorous randomized clinical trials, and it showed that fast is possible. There were multicenter clinical trials with thousands of patients with COVID that were started in a week—a week from the idea to enrolling patients. That is ungodly fast!
Why was it so hard to conduct trials quickly and efficiently prior to the pandemic?
The clinical trials enterprise is just hopelessly complicated. Over the years we have added and added and added. Now there are things that have become the norm, and they cost a fortune, and we have no idea if they add value. There are two key goals in a clinical trial: one is to protect participants and not put them at unnecessary risk; the other is to collect high-integrity data to answer the research question. There are just dozens of things that we have layered on that don’t achieve either of those goals.
Such as what, for example?
More and more investigator training is required by institutions and funders for each study, so researchers are doing this training multiple times —with no evidence that it has much value in terms of avoiding fraud, protecting patients or improving scientific integrity.
Clinical trials were already beginning to use some remote methods of monitoring participants. How has the pandemic accelerated that?
COVID created an imperative to do things remotely. It raised the question: what is it in a research visit that is essential to be in-person? I can’t draw blood over the phone or video. I can’t really examine someone over video, although you’d be surprised. I have examined the swelling in a patient’s ankles on a video call. There’s a lot that can be done remotely.
One example that I’m involved with is an almost completely virtual clinical trial to compare warfarin [which prevents blood clots] with another oral anticoagulant, apixaban, for patients with a certain type of prosthetic aortic valve. People give their consent to participate over the phone. The study drug is shipped directly to the patient. As long as they are doing well, there is no reason for participants to come on-site. Everything is done over the phone. It’s going great.
Should virtual trials continue when we are no longer worried about participants catching COVID?
Yes, definitely. It empowers participation. We’ve put in place too many barriers. If people want to participate in trials, we should make it easy for them. For example, our IRB [institutional review board] and our institutional lawyers aren’t really comfortable with me recruiting people who have no relationship with the Duke health system. The concern is: “What if something goes wrong? Where would they go?” Well, they’d go to their doctor or hospital nearby.
So much of clinical research is built around the investigative site—a site contract, the site IRB, and the site medical records that are used as documentation for the research visit. This new paradigm [of remote trials] starts to question all of that.
Do you see other ways to make research better for participants?
If we could make it easier and less duplicative to be in trials, we would get more participation. For instance, do we really need a whole separate clinical research workforce? My clinical nurses don’t generally think research is part of their jobs, and my research coordinators don’t think clinical care is part of their jobs. Why don’t we try to make research and clinical care more seamless and integrated so participation in research is less of a burden on the patients and the entire system?
What other changes could make research more efficient and less burdensome?
One is to reform IRBs. I run big cardiology clinical trials, partnering with industry to study drugs that are regulated by the FDA and other regulatory authorities. There was one trial where we had more than 1,000 clinical sites in 37 countries. Every site had its own IRB, so you had 1,000 IRBs reviewing this protocol. Let’s say each IRB has 10 people, that’s 10,000 people reviewing this protocol. It’s already been reviewed and finalized by the sponsors, an academic steering committee, and the FDA and other regulators. The local IRBs can’t change the protocol. All they can do is decide to participate or not and to make minor changes to the local consent forms. So what is the value of having 1,000 IRBs review the protocol?
Every IRB (appropriately) charges money to review a protocol; they want $1,000 or $2,000, so that’s a lot of money and a lot of time. All these smart reviewers have opinions, and those opinions have to be dealt with. Let’s say you could really take out all but one IRB for a large multicenter clinical trial. That’s a huge opportunity for efficiency.
Would more efficiency free up resources to pursue additional research?
Yes, but the key to this transformation is the pursuit of quality and efficiency together. Both really matter. Because of our cumbersome, inefficient processes and the time, manpower and other resources they demand, we have too few clinical trials. Many trials that are conducted are too small to answer important questions. If we streamline research infrastructure, we could accomplish so much more to move medical science and patient care forward.
Are you hopeful that changes in trials will endure after the pandemic?
Clinical research is a high-stakes, highly regulated enterprise, and change in a system like this is difficult. There are people who would lose out, people whose jobs are mostly doing what we are discussing as inefficiencies. There is a CRO [contract research organization] industry, and much of their work would go away. They do all the operational stuff that is needed if you want to get 1,000 IRB reviews completed. COVID has highlighted the need for change and jump-started us some, but I think there’s a risk that we drift back when the pandemic ends.