Q&A: Ways to mitigate underrepresentation of women in stroke clinical trials
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Women are underrepresented in stroke clinical trials due to factors influenced by both investigators and patients.
In a commentary published in Stroke, Cheryl Carcel, MD, PhD, senior research fellow in the Stroke and Women’s Health Program and conjoint senior lecturer at the University of New South Wales in Sydney, and Mathew J. Reeves, BVSc, PhD, FAHA, professor of epidemiology and biostatistics at Michigan State University, provided background on these sex inequities and offered recommendations to mitigate disparities in clinical research.
Healio spoke with Reeves about the underlying causes behind the low enrollment of women in stroke clinical trials and the underrepresentation of women in research, as well as choices that trial leadership can make to boost representation of women.
Question: What are some of the drivers of low inclusion of women in stroke trials, both on a patient and investigator level?
Reeves: As far as investigator-related causes, the main contributor is trial design, specifically the choice of inclusion and exclusion criteria, which directly impacts who gets enrolled in a particular trial. Many inclusion/exclusion criteria are justified to ensure the safety of the trial, but some appear to be used more for the convenience of the trial investigators. Given the older age distribution of strokes in women, using age-based exclusion criteria (eg, > 80 years of age) has serious consequences on the number of women who are eligible. We believe that blanket age restrictions should be avoided.
We know less about the drivers of inclusion of women at the patient level, but as our report notes, there are data showing that women may be more risk-averse and less likely to agree to be experimented on (which is what you are agreeing to when you enroll in a trial). There are also data showing that practical concerns such as the greater caregiving responsibilities and poor access to transportation affects the willingness of women to participate.
Q: Could you explain the significance of boosting the number of women in these trials?
Reeves: On the technical/statistical side, the primary advantage of having equal numbers of men and women in a trial is that it maximizes the amount of information available to examine if the effects of the treatment being tested differ between men and women (referred to as sex-by-treatment interaction). Studies will have the most power to detect theses interactions when there are approximately equal numbers of men and women in the data.
Outside of these technical/statistical concerns, increasing the number of women in trials so that they better reflect the number of stroke events in the population at large has a more important effect on the representativeness and generalizability of the trial results. Having a trial with numbers that are equally representative of men and women indicates that the trial was carried out equitably, and that there were no overt or covert factors influencing who participated. This in turn gives greater confidence to the validity of the trial and its results.
Q: What are your recommendations for addressing patient-specific factors such as interest in trial participation?
Reeves: First, we need to do more studies to determine if women really do have less interest in participating in stroke trials, and if they do, understand why this is. This work needs to be done at two levels, we need to study this in the general population using surveys that include both men and women. We need to determine, No. 1, if women differ from men in their attitudes toward participation in stroke trials; No. 2, if women have greater barriers to participation; and No. 3, what are these barriers and how do we fix them?
Then I think we need to repeat these studies in populations that are actually having, or have had, a stroke event. This is harder to do, but it’s important to figure out if the same barriers reported in the general population are active when someone is actually having a stroke. We also need to do a much better job of finding out who is actually being screened for inclusion in the trials that are being conducted, and whether women are being screened out too early. This will require trials to do a much better job of completing the screening logs that are used to document who is being screened and then approached to discuss participation.
Q: What is the primary takeaway for study investigators and those who design trials in stroke research?
Reeves: Unequal enrollment of patients, whether resulting in disparities by gender or age or race, is not acceptable. More awareness for how study inclusion criteria can lead to women being excluded from trials is needed when designing trials, and more efforts should be expended during the conduct phase of the trial itself to ensure women are being enrolled equally.
Q: What is the significance of promoting women researchers in these trials?
Reeves: We are not sure if this will have a direct effect on the enrollment of women in stroke trials, but having more diverse trial leadership who are designing and running trials has to be something that the stroke community should embrace.
For more information:
Mathew J. Reeves, BVSc, PhD, FAHA, can be reached at reevesm@msu.edu; Twitter: @msuepibio.
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