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Industry must act now to minimize effects of COVID-19 on clinical research.
The COVID-19 pandemic has wreaked global havoc, with millions of lives lost. The effects of the pandemic on health care workers have been especially severe in terms of mortality, burnout, and diversion from non-pandemic critical work. This impact has also been felt in clinical research, just as the importance of clinical research has become obvious to the general public from the wide reporting of trials of drugs and vaccines for SARS-CoV-2 control. We became concerned that clinical research would be negatively impacted long-term, first by the interruption of the ability of research participants to be examined in person due to social distancing requirements, and then by the damage done by the pandemic to women clinical investigators, who play a vital role in clinical research. These issues were brought to the Clinical Research Forum, an organization formed to support academic clinical research, and the Board constituted an Academic Advancement Committee to consider the problem. One of the products of that committee was a Commentary recently published in Nature Medicine on the impact of the pandemic on women in clinical research.1 We served as members of that committee.
The pandemic has had a disproportionate impact on women physicians and researchers, exacerbating long-standing issues of gender inequality in medicine. In the arena of clinical research,gender equity accelerates research excellence: we need multiple perspectives and all the brain power we can muster to maximize research productivity and quality. Moreover, women physician investigators enhance enrollment of women as participants in clinical trials, which is crucial to our ability to generalize from the data and to maintain the health of women. The upheaval wrought by the pandemic, which threatens the activity of women investigators in clinical research, also offers an opportunity to address the barriers faced by women in medicine.
For women researchers in the pandemic, rapidly shifting demands in clinical work, teaching, and mentoring hindered productivity at work. At home women have always borne a larger share of child care and domestic duties, with early career women physicians spending an average of 8.5 hours per week more than men,2 so women caregivers were most impacted by the abrupt closure of schools and child care facilities. Within months the disparities became evident in differences in publications submitted by women compared with men since the start of the pandemic.3-9 The disproportionate impact of the pandemic on women faculty is superimposed upon long-standing gender disparities in medicine. Although women now constitute over 50% of the entering class in medical school, and have been more than 40% of medical school applicants for over 30 years,10 progressive attrition occurs in the ranks so that only 27% of full professors and 18% of department chairs and deans are women.11
There are many reasons for this loss, some of them readily apparent and correctable.Women are paid less than men in academic medicine, even accounting for differences in specialty, academic rank, work hours, and academic productivity.12,13 Women achieve academic promotion more slowly than men, partly because they are accorded fewer opportunities for recognition in their fields. Women are underrepresented among academic grand rounds speakers,14 speakers at medical conferences15 and award recipients from medical specialty societies.16 Time pressure is especially intense on young women faculty. Besides spending more time on domestic chores, they spend more time at work on teaching, service and mentoring. On top of all of this, women face more frequent sexual harassment.17 Not surprisingly, female physicians report higher rates of burnout.18 Women from minority populations face amplified disparities.19 Within six years of completing clinical training, 22.6% of women physicians are no longer working full-time, compared with only 3.6% of male physicians. This gap becomes even more pronounced (30.6% of women vs 4.6% of men) among physicians with children.20 Women who belong to groups that are underrepresented in medicine are even more likely to leave academic medicine than white women.21
Attrition of women physicians directly impacts patient care because studies suggest women physicians may have better clinical outcomes. Female primary care physicians spend more time with patients.22 Elderly hospitalized patients treated by female internists experience lower mortality and readmission rates.23 Patients undergoing coronary artery bypass grafting had shorter hospital length of stay when treated by an all-female physician team as compared with an all-male team.24 Female patients treated by male physicians following acute myocardial infarction have higher mortality than those treated by female physicians.25 Sex discordance between patient and surgeon is associated with increased likelihood of adverse postoperative outcomes—and that observation that is driven by worse outcomes for female patients treated by male physicians.26
Clinical trials play a fundamental role in bringing new medications and interventions to our patients, yet women have often been excluded from participation. Motivated in part by the thalidomide tragedy, in 1977 the Food and Drug Administration recommended banning women of childbearing potential from Phase I and early Phase II drug trials. However, prescribing medications to women based on clinical trial results obtained in men can miss important differences in drug metabolism that are not solely attributable to differences in average body size. Women experience adverse drug reactions almost twice as often as men, and sex differences in pharmacokinetics predict sex-specific adverse drug reactions.27 A US Government Accountability Office report noted that of 10 FDA-approved that were withdrawn from the US market between 1997-2001, eight posed greater health risks for women than for men.28 In 1991 Dr. Bernadine Healy became the first female director of the National Institutes of Health (NIH), and launched the Women’s Health Initiative that included over 150,000 postmenopausal women as participants. The inclusion of women in clinical research finally became law with the NIH Revitalization Act of 1993.29
Adequate representation of women as participants in clinical trials is essential, and promoted by NIH, yet we still have a long way to go. Among 60 randomized clinical trials of lipid lowering therapies reported between 1990 and 2018, there was a modest increase in enrollment of women over time, but women remain underrepresented compared with the relative burden of disease.30 In another study of 317 randomized clinical trials of heart failure with reduced ejection fraction published in high impact journals over the past 20 years, only 25% of participants overall were female, and females were under-enrolled in 72% of these trials. Notably, under-enrollment of female participants was associated with men in first or last authorship position of the resulting publications.31
Given the importance of including women as participants in clinical trials, it is critical that women be well represented among clinical investigators, but participation lags in this arena. Women comprise only approximately 10% of authors of major clinical trials of cardiovascular medications.32,33 Among almost 500 randomized clinical trials in oncology, in only 17.9% were corresponding authors women.34 Of clinical trials relating to COVID-19 registered on clinicaltrials.gov, only 27.8% of principal investigators were women.35
It is not merely to improve recruitment of women as participants in clinical trials that we need to maintain and increase the participation of women in academic clinical research. A diversity of perspectives in research makes for richness of thought, greater excellence in studies, improved creativity in studies, and better collaboration.
If we do not take action to address gender inequity in medicine, now being further amplified by the disproportionate impact of the COVID-19 pandemic, we could find that current attrition will become a mass exodus of women from academic medicine. In a survey of COVID-related stress and work intentions among US health care workers, 31.4% of physicians intend to reduce work hours and 23.8% intend to leave their practice within 2 years.36 The proportions are bound to be higher among women physicians.37
The Clinical Research Forum provides a forum to discuss the unique and complex challenges in performing clinical and translational research, to advocate for support for clinical research, and to recommend improvements in our approach to clinical research. Last year, the Forum convened an Academic Achievement Committee to address the impact of the COVID-19 pandemic on women in clinical research. As members of that committee, we and colleagues prepared a framework for action, recently published in Nature Medicine, in which we highlight financial, cultural, and operational changes that institutions, professional societies, foundations, and funding agencies can take to retain women in academic medicine.1 Perhaps other creative solutions can be found as well. For example, clinical trials organizations and NIH-sponsored clinical trials can seek out women as principal investigators, require appropriate enrollment of women in their trials and strongly recommend appropriate inclusion of women investigators on the trial teams. It may be that additional support is required to assure such participation. We must act now, otherwise the benefits for clinical research that come with gender equity in medicine will only become even more difficult to achieve.
Joy Y. Wu, Department of Medicine, Stanford University School of Medicine, Stanford, CA, and Pamela B. Davis, Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland OH