The new NIH policy on consideration of sex as a biological variable in NIH-funded research and the 2014 FDA Action Plan to Enhance the Collection and Availability of Demographic Subgroup Data are ushering in an era in which the biology of sex requires consideration at all stages of medical research. This is a welcome development for a CRO like Health Decisions that has long focused on indications in women’s health.
The case for consideration of the biology of sex in medical research is overwhelming. Perhaps the most powerful illustration is the importance of sex differences in prevalence of some diseases. The most obvious examples of diseases that affect women disproportionately include thyroid disease, hypertension, stroke, Alzheimer’s disease, migraine, gall stones, irritable blow syndrome, urinary tract infections, osteoporosis, multiple sclerosis, lupus erythematosus, rheumatoid arthritis, myasthenia gravis and many others. Other diseases affect more men than women, including Parkinson’s disease, amyotrophic lateral sclerosis, lung cancer and skin cancer.
Biological and Behavioral Factors
In some cases, behavioral differences such as a greater likelihood of tobacco use or tendency to spend more time outdoors account at least in part for differences in disease prevalence. However, in many cases the explanation must come from biology. NIH and FDA policies will do much to elucidate differences in sex-specific vulnerability to many diseases and open new avenues for basic research.
The implications of the NIH and FDA emphasis on considering the biology of sex in medical research are likely to be most striking in indications that affect both males and females but in which clinical studies have traditionally recruited disproportionately male populations. Fortunately, some lessons from women’s health studies will now be useful in increasing female participation in studies across the therapeutic spectrum.
Practical Lessons from Experience in Women’s Health Studies
FDA and other sources have provided information on techniques for increasing participation of women and other important subgroups in clinical trials. Experience has taught us at Health Decisions that successful, efficient execution of studies involving female subjects requires recognizing a variety of factors, including:
- The importance of addressing child care and transportation in recruitment
- The often critical role of investigator-patient relationships in both recruitment and subject retention
- The need to express appreciation to subjects for their participation in a research project
- The power of subject motivation based on the potential to improve future healthcare for the subject herself, her daughters and her friends
- The importance of reasonably assessing the burden of study participation from a woman’s perspective, including differences in different situations and life stages, ranging from sexually active youth to challenges in conception to prenatal and postpartum care and menopausal and postmenopausal stages
- Similarly, a full appreciation of the variability in subject motivation in different situations and life stages
- The importance of determining a subject stipend that reflects the burden of study participation and is acceptable to Institutional Review Boards
- The role that advocacy organizations can sometimes play in supporting study participation.
For sponsors not previously focused on recruitment of female subjects, welcome to the new era in which female participation is important in studies in many indications because of increased institutional recognition that the biology of sex often affects disease processes.