Clinical trials drive medical advancement, but cancer clinical trials seldom meet their goals in recruiting patients. Experts discuss causes, consequences, and actions being taken to meet needs.
- Dr. David Ahern, Director, Program in Behavioral Informatics and EHealth, Brigham & Women’s Hospital, Assistant Professor of Psychology, Harvard Medical School, and co-author, Oncology Informatics: Using Health Information Technology to Improve Processes and Outcomes in Cancer
- Dr. Bradford Hesse, Chief of Health Communication Informatics, National Cancer Institute and co-author, Oncology Informatics: Using Health Information Technology to Improve Processes and Outcomes in Cancer
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Clinical Trial Recruitment
Reed Pence: Clinical trials are the lifeblood of the advancement of medical science. Until we know that a treatment works, doctors can’t use it. Cancer patients often hope that the results of a clinical trial may provide them with a chance to be cured. However, especially when it comes to cancer trials, doctors have a hard time recruiting patients to participate. Two-thirds of cancer clinical trials never meet their recruitment goals.
Dr. David Ahern: With respect to recruiting adults for cancer clinical trials less than five percent of potentially eligible patients participate or become enrolled in clinical trials historically.
Pence: Dr. David Ahern is director of the program in behavioral informatics and e-health at Brigham and Women’s Hospital in Boston, assistant professor of psychology at the Harvard Medical School and co-author of the book, Oncology Informatics: Using Health Information Technology to Improve Processes and Outcomes in Cancer.
Ahern: Unfortunately the trials that don’t meet their recruitment targets, and there are many unfortunately that don’t, they are considered failed trials. And as a consequence, they often, because they don’t have sufficient participants, the sample size is too small to have a credible evaluation of the hypothesis of the question that the study was attempting to address. Unfortunately there’s very little that can be done to shed light on that question if the sample sizes are too small. That has repercussions in terms of slowing down the process of research, which builds on evidence as studies are done. There’s the cost factor, there’s the investment of dollars that don’t see a return on investment. It’s a big issue and it’s one that has been highlighted as part of the reason why it takes so long for the evidence when studies are done to get into practice, because they take so long.
Dr. Bradford Hesse: We know that if we want to understand more about rare cancers, we need to understand more in the world of precision medicine for how to treat patients from different diverse backgrounds we’re going to have to bump up that kind of recruitment level pretty dramatically.
Pence: Ahern’s co-author is Dr. Bradford Hesse, chief of health communication informatics research at the National Cancer Institute.
Hesse: It takes us longer to create discoveries. It takes us longer to find out what may be effective in some of the treatments that we’ve used. And it slows us down dramatically in being able to get to the point where we’re really making an impact on some of these cancers that are perplexing to us and have been bothering us for a long time. So it’s that slowing us down piece that we care about so much. As we’ve moved towards a strategy to accelerate or get done in five years what would otherwise take us ten, then we know we have to expand the base of people who could be eligible for a clinical trial and who know about a clinical trial and are engaged and want to participate.
Pence: Hesse says that often, trials end up in a race between getting enough participants and running out of money. A trial may limp home with just enough patients to report only some results on some groups that were well enough represented.
Hesse: We can get into just maybe one small group of people, and these are maybe well-educated individuals high FEF kind of folks [the amount of a fluid that passes through an organ or part in a specified time;
forced expiratory flow] and we can learn what’s happening with them, but gosh, we don’t know what’s happening with people perhaps of an Asian American heritage and have a slightly different physiology and slightly different understanding of what their environment might be doing to impinge on their treatment. We need to be able to expand that out, I think.
Pence: That’s important because some groups respond differently to certain drugs than other groups do. Dr. Julie Brahmer is director of the thoracic oncology program at Johns Hopkins University’s Sidney Kimmel Comprehensive Cancer Center.
Dr. Julie Brahmer: The most common example that we see for different drugs having different effects inpatients come from, at least in lung cancer patients, come from differences in drug metabolism or how drugs are degraded in our bodies. Patients who are of Asian descent or who live in Asia tend to have a slower metabolism of certain drugs, and so they can be more prone to side effects from those type of drugs if their levels are higher. So when we’re developing drugs we do have to be aware of that as well. I think this really does have real world application.
Pence: Studies funded by the National Institutes of Health require minority participation, but those trials make up less than 10 percent of clinical trials in the United States. Overall, Asians, African Americans and other minorities are especially underrepresented in cancer clinical studies. Two large trials in immunotherapy are a fairly recent example, according to an analysis in the New York Times. Roughly 90 percent of participants in both trials were white. And in one of the studies, only one percent was black. Minorities face extra hurdles to getting into trials. Brahmer says a big one is proximity.
Brahmer: So if someone has to drive a long ways to get to a place that has a clinical trial, or if they don’t have the available transportation, if they don’t have a car and can’t drive and then they are relying on public transportation, they have to be able to get to a place that is on their public transportation line. So we have to be aware of that. And here at Hopkins we’re trying to do things that make it easier for patients to get here.
Pence: Brahmer says some minority populations have a higher incidence of serious disorders such as heart and kidney disease, which would disqualify them for a clinical trial. And some doctors simply assume that minorities would not be interested. But Ahern says the biggest obstacle, for them or for any patient, is simply making them aware that studies exist that are appropriate for them. Money for promotion is scarce.
Ahern: There is a clinicaltrials.gov web site supported by NIH and NCI, which does provide information on trials. That’s been a helpful addition. But even with that there’s a challenge for patients with cancers who might benefit becoming aware and then being able to follow through on the enrollment, meet the criteria and be enrolled. We live in a disconnected health care system where right now we don’t have the right processes in place so that we can reach out to a provider, make it very easy for a provider to say, here is a blue plate of possible relevant kinds of clinical trials that you would be eligible for and we can match you to that pretty easily.
Pence: Information on clinical trials is fragmented now. Oncologists are busy, and while they know about many trials, technology could make the process much easier and more complete. Hesse sees it coming.
Hesse: One thing that’s going to happen is as we start moving information in and out we can create channels to deliver information right at that encounter with the patient when an oncologist is sitting down and looking at the characteristics of their particular cancer and eligibility for enrollment in a clinical trial. That information can be served up immediately and there’s no longer delay of saying well what you can do is you can go to the web and learn about clinical trials. It can be a reminder that’s set right into the interface of the client’s health record. It’s the same way that I can use something like my mobile or my iPod to make sense of the geography around me when I’m doing a GPS and it’s taking me from one step to the next. I think what you want to do is you want to get a GPS for clinical trials. We want to make it very easy for people to say I know in this time of crisis how to navigate this and get asked the right questions and present information in the right way.
Ahern: We have startup companies actually that have taken on the challenge of trying to frame these clinical trials in terms that patients would have a better understanding of whether they are a good fit for a trial and what the experience of being in a trial might be like.
Pence: Many patients also can’t get into trials because the enrollment criteria are too strict. Ahern and Hesse say doctors are working on that, too.
Ahern: Many times the nature of the study requires very clear specific criteria for eligibility or enrollment. So age in many ways has been a criterion limiting upper age limits we, by virtue of that have ended up having results about populations that don’t necessarily include an older population, say 75 or older, and we have found that produces some limitations in the generalized availability of the information that’s been learned from the trial. That’s a balancing act – the science often requires that we define the eligibility so we understand the populations that are being recruited and I think it has maybe been a bit restrictive in the past.
Hesse: Eventually if you get more people involved because you’ve lowered those bars of eligibility, then you don’t have to answer questions in such a specific way, but you can start using the power of a lot of people coming into the study to start teasing out statistically what would have been a notion of reactivity. You can learn in a broader sense I think, and so that’s one of the reasons folks have talked about lowering the bar to clinical trials.
Pence: Hesse and Ahern say there are also societal biases against clinical trials, and misinformation about how cancer trials are conducted. Many people believe that the new treatment will be compared against no treatment. And who wants to risk being the person getting a placebo?
Hesse: When you ask the normal person on the street about a clinical trial, what they tend to think is in fact that you would get a placebo that someone is getting a life saving benefit and they may not. There’s a 50/50 chance that they’re not. And what they don’t understand is the idea that they’re going to get best standard of care regardless, and the experimental condition is something that’s built on top of that and it’s a necessary step for us to move forward. If we find out it’s working then very quickly we’ll be able to help all those that have been participating in the trial.
Ahern: There is a general stigma against trials I think that has probably emerged over time both — I’m not getting active treatment — which is a misunderstanding of cancer, but also the idea that maybe my doc’s given up on me, that this is now a last resort. I think we need to change the mindset about that, so not so much last resort, but innovative opportunities, maybe actually a preferred model and also make the benefits of participating more salient to the eligible patient.
Pence: However, what may make the biggest difference in getting enough people into research is a fundamental change in the very basics of clinical trials. Ahern says it’s coming.
Ahern: Instead of thinking about a relatively small number of large scale trials that have to recruit thousands of patients, there’s a movement towards — and this dovetails with the precision medicine initiative and more targeted therapy development — is constructing smaller trials, meaning they need fewer participants and are done in a more rapid deployment evaluation mode. That may also lead to a greater proliferation of trials for which patients could be eligible and less of a challenge in recruiting the kind of samples, and sample sizes, that are needed to answer the research questions that the trials are designed to address.
Pence: However, doctors can learn from more than just clinical trials. Every cancer patient carries potential data in their treatment. With paper records, sharing it is very hard. But not with electronic records.
Ahern: If that data that’s being collected on that patient for what they may have been treated for could be shared in a de-identified way with other patients who are similar across the country where information sharing is part of the goal of the moonshot, then could learn literally from the experience of care delivery from patient to patient and not only rely on the clinical trials research model, which it isn’t meant to be replaced by this model of each patient becoming a learning opportunity for the field, it’s really a complement to it.
Pence: Doctors need to emphasize the benefits of participating in clinical trials. It’s a chance to advance medical science and help others… and have access to treatment that they otherwise couldn’t receive. In some cases, it could be lifesaving.
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I’m Reed Pence.