In a study published in Clinical Infectious Diseases, researchers hypothesized that the underrepresentation of women in HIV intervention trials in the United States may be a result of higher clinical trial screen-out rates in women compared with men. Although they found that screen-out rates did not differ by sex, researchers highlighted that the results underscored the need to recruit more women to HIV trials in order to bridge the knowledge gap between women and men.
Because sex and gender can have a significant effect on disease course and response to therapy, federal law in the United States requires that research funded through the National Institutes of Health include women as equal participants in studies on HIV. However, a 2016 systematic review demonstrated that the median percentage of women as participants in HIV treatment and cure trials were 19.2% and 9.9%, respectively. Researchers postulated that because eligibility for inclusion in HIV treatment research can be founded on concern for the teratogenicity of study treatments, inclusion criteria may create a higher barrier to recruitment of women in such trials.
In this retrospective cross-trial analysis of people living with HIV, researchers analyzed 10,744 screenings over a 10-year period from 31 trials conducted by the AIDS Clinical Trials Group at 99 network-affiliated clinical research sites in 28 states, the District of Columbia, and Puerto Rico. The main outcome measure was screen-out, defined as an individual formally screening to a trial who did not subsequently enroll. They characterized the major reasons for screen-out and explored whether these reasons varied by sex.
Of the 10,744 screenings, 18.4% were women. Of the 2871 people formally screened who did not subsequently enroll, the percentage of women screening out was 27.9% compared with 26.5% of men. While the screen-out rate was 1.4% higher among women than men, the difference was statistically insignificant (P =.19) and further did not vary by race (P =.99), ethnicity (P =.15), or age group (P =.06). In addition, in >1500 screenings among women age <50 years, fewer than 10 cases of screen-out were reported to be due to pregnancy, breastfeeding, and contraceptive requirements.
Reasons for screen-out were: HIV disease-related eligibility criteria, non-HIV-related eligibility criteria, personal choice, comorbidity that is a contraindication to study treatments, and administrative reason. With the exception of administrative reasons, reasons for not enrolling did not differ by sex.
Because the AIDS Clinical Trials Group trials have 2-stage screening procedures (informal and formal), researchers noted the availability of screening data from only the formal stage as a study limitation. Selection bias by sex could potentially have occurred in the informal stage; thus, further research is “needed to identify factors like implicit bias that may influence the first, informal stage of screening,” the researchers noted.
In addition, because there was no significant difference of screen out by sex, “improving enrollment of women requires increasing outreach activities that identify, invite and eventually screen more women for trial participation,” hypothesized the researchers. “Qualitative research such as interviews or open-ended surveys with members of trial teams who have successfully enrolled higher numbers of women may provide additional contextual data to inform this issue,” they added.
Disclosure: Susan L. Koletar, MD, and Ann C. Collier, MD, declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Smeaton LM, Kacanek D, Mykhalchenko K, et al. Screening and enrollment by sex in HIV clinical trials in the United States [published online September 29, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz959