Department of Obstetrics and Gynecology, University of Connecticut School of Medicine, Farmington, CT, USA.
Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA.
Hum Reprod. 2020 Dec 1;35(12):2819-2831. doi: 10.1093/humrep/deaa232.
What demographic and baseline characteristics are predictive of adherence to reproductive medicine clinical trial protocols, live birth or participation in genetic studies?
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.
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.
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.
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.
ClinicalTrials.gov number: NCT00719186; NCT01044862.
哪些人口统计学和基线特征与生殖医学临床试验方案、活产或参与遗传研究的依从性相关？
种族、体重指数和低收入与生殖医学临床试验方案不依从的可能性相关，而种族影响生物样本的收集，不依从研究方案与较低的活产概率相关。
尽管以前已经评估了不孕女性在遵守研究方案方面的某些方面作为个体因素，但以前没有评估过影响整体不遵守研究方案的因素。
研究设计、规模、持续时间：对来自两项前瞻性多中心、双盲对照研究的 1650 名参与者进行了二次数据分析：多囊卵巢综合征 II 妊娠研究（PPCOS II）和卵巢刺激下多胎妊娠评估（AMIGOS）。
参与者/材料、地点、方法：参与者为年龄在 18-40 岁之间的女性，患有排卵功能障碍性多囊卵巢综合征（PCOS），伴有高雄激素血症和/或多囊卵巢形态（PPCOS II），或排卵正常的不明原因不孕（AMIGOS）。该研究在美国 14 个临床地点进行。选择不遵守临床试验方案作为该分析的主要结局。为了评估人口统计学和基线特征是否与遵守研究方案、活产或参与 DNA 采样和储存库以及妊娠登记有关，将这些假定因素与结局指标进行比较。使用上述假定预测因子，使用逻辑回归建立预测模型。
自我认同为非裔美国人或亚裔、体重指数较高和家庭收入较低的女性不太可能遵守方案。不遵守研究方案与较低的活产概率相关（比值比：0.180，95%置信区间：0.120，0.272，P<0.001）。非裔美国人和亚洲人参与可选的研究 DNA 收集的可能性低于白人。非裔美国人和年收入较高或来自西南地区的参与者或患有 PCOS 的参与者参与血液储存库研究的可能性较低。
局限性、谨慎的原因：种族和民族是自我报告的，这种对严格种族和民族的自我分类可能并不总是代表整个种族或民族群体。本研究包括两项美国多中心试验，因此研究结果可能不适用于国际试验。
确定低参与人群是一个重要的初始步骤，因为进一步的研究可以制定具体措施，以提高对研究方案的依从性和参与生物标本库，从而扩大生殖医学临床试验结果的代表性。
研究资助/利益冲突：由 NIH Eunice Kennedy Shriver NICHD 资助：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；临床生殖内分泌科学家培训计划（CREST）：R25HD075737。在本研究之外，M.P.D. 获得 NIH/NIHCD 研究资助，R.S.L. 获得 Ferring 的研究资助，并担任 Bayer、Kindex、Odega、Millendo 和 AbbVie 的顾问。
临床试验.gov 编号：NCT00719186；NCT01044862。
