Factors associated with study protocol adherence and bio banking participation in reproductive medicine clinical trials and their relationship to live birth

Abstract

Study question: What demographic and baseline characteristics are predictive of adherence to reproductive medicine clinical trial protocols, live birth or participation in genetic studies?

Summary answer: Race, BMI and lower income are associated with likelihood of non-adherent to reproductive medicine clinical trial protocols, while race influences collection of biological samples and non-adherent to study protocols is associated with lower probability of live birth.

What is known already: Although aspects of adherence to study protocol have previously been evaluated as individual factors in infertile women, the factors that affect overall non-adherent to study protocol have not been previously evaluated.

Study design, size, duration: A secondary data analysis of 1650 participants from two prospective multicenter, double-blind controlled studies was carried out: Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS).

Participants/materials, setting, methods: The participants were women aged 18-40 years old with either polycystic ovary syndrome (PCOS) with ovulatory dysfunction in combination with either hyperandrogenemia and/or polycystic ovarian morphology (PPCOS II), or regular ovulatory cycles with unexplained infertility (AMIGOS). The study was carried out in 14 clinical sites in the USA. Non-adherence to clinical trial protocol was chosen as the primary outcome for this analysis. To evaluate whether demographic and baseline characteristics were predictive of adherence to study protocols, live birth or participation in blood sampling for DNA and repository, and pregnancy registry, these putative factors were compared between the outcome measures. Logistic regression was used to establish a prediction model using the putative predictors introduced above.

Main results and the role of chance: Women who self-identified as African American or Asian and those with higher BMI and lower household income were less likely to adhere to protocol. Non-adherence to the study protocol was associated with a lower probability of live birth (odds ratio: 0.180, 95% CI: 0.120, 0.272, P < 0.001). African Americans or Asians were less likely to participate in optional study DNA collection compared to Whites. Participants who were African American or with high annual income or from the Southwest sites or had PCOS were less likely to participate in the blood repository studies.

Limitations, reasons for caution: Race and ethnicity were self-reported and such self-classification to strict race and ethnicity may not always be representative of a whole racial or ethnic group. This study included two US multicenter trials and therefore the findings may not be extrapolated to international trials.

Wider implications of the findings: Identification of populations with low participation is an important initial step, as further investigation can develop specific measures to improve adherence to study protocols and participation in biospecimen banking and thereby extend the representativeness of reproductive medicine clinical trial findings.

Study funding/competing interest(s): Supported by NIH Eunice Kennedy Shriver NICHD Grants: U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936, U10HD055925, PPCOSII: U10 HD27049, U10 HD38992, U10 HD055925, U10 HD39005, U10 HD38998, U10 HD055936, U10 HD055942, U10 HD055944; Clinical Reproductive Endocrine Scientist Training Program (CREST): R25HD075737. Outside this study, M.P.D. received NIH/NIHCD research grant and R.S.L. received research grant from Ferring and was consultant for Bayer, Kindex, Odega, Millendo and AbbVie.

Trial registration number: ClinicalTrials.gov number: NCT00719186; NCT01044862.

Keywords: adherence to study protocol; biospecimen banking; dropout; ethnicity; live birth; medication compliance; non-adherence; pregnancy registry; race; randomized controlled trial.