Bustamante Christian, Martinez Juan F, Navarro Alexander, Lopera Margarita, Villegas Gustavo, Duque Sindy, Acosta-Baena Natalia, Ríos-Romenets Silvia, Lopera Francisco
Neurosciences Group of Antioquia, University of Antioquia, Medellin, Colombia.
Clin Trials. 2025 Feb;22(1):116-125. doi: 10.1177/17407745241264217. Epub 2024 Aug 14.
BACKGROUND/AIMS: Including women of childbearing age in a clinical trial makes it necessary to consider two factors from a bioethical perspective: first, the lack of knowledge about the potential teratogenic effects of an investigational product, and also, the principle of justice not to exclude any population from the benefits of research. The most common way to address this issue is by requiring volunteers to use contraceptives before, during, and a few weeks after the clinical trial. This work presents all the strategies used to promote contraception use and prevent pregnancy during the Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease (API ADAD) Colombia clinical trial. Two characteristics of this trial make it of special interest for closely monitoring contraception use. One is that the trial lasted more than 7 years, and the other is that participants could be carriers of the E280A PSEN1 mutation, leading to a mild cognitive impairment as early as their late 30s.
An individual medical evaluation to select the contraception method that best fits the volunteer was carried out during the screening visit, remitting to the gynecologist when necessary. All non-surgical contraception methods were supplied by the sponsor. Staff were trained on contraception counseling, correctly dispensing contraceptive drugs to volunteers, and identifying, reporting, and following up on pregnancies. Two comprehensive educational campaigns on contraception use were performed, and the intervention included all volunteers. In addition, volunteers were asked on an annual survey to evaluate the dispensing procedure. Finally, the effectiveness of these strategies was retrospectively evaluated, comparing by extrapolation the number of pregnancies presented throughout the trial with the General Fertility Rate in Colombia.
A total of 159 female volunteers were recruited. All strategies were implemented as planned, even during the COVID-19 contingency. Ten pregnancies occurred during the evaluation period (2015-2021). Two were planned; the rest were associated with a potential therapeutic failure or incorrect use of contraceptive methods for a contraceptive failure of 0.49% per year. Sixty percent of pregnancies led to an abortion, either miscarriage or therapeutic abortion. However, there was not enough data to associate the pregnancy outcome with the administration of the investigational product. Finally, we observed a lower fertility rate in women participating in the trial compared to the Colombian population.
The lower rates of contraceptive failure and the decrease in the incidence of pregnancies in women participating in the trial compared to the Colombian population across the 7 years of evaluation suggest that the strategies used in API ADAD Colombia were adequate and effective in addressing contraception use.
背景/目的：在临床试验中纳入育龄女性，从生物伦理角度来看有两个因素需要考虑：其一，对研究产品潜在致畸作用缺乏了解；其二，公正原则要求不让任何人群被排除在研究益处之外。解决这个问题最常见的方法是要求志愿者在临床试验前、期间及之后几周使用避孕药具。本文介绍了在哥伦比亚进行的阿尔茨海默病预防倡议常染色体显性遗传性阿尔茨海默病（API ADAD）临床试验中用于促进避孕药具使用和预防怀孕的所有策略。该试验的两个特点使其在密切监测避孕药具使用方面特别值得关注。一是试验持续了7年多，另一个是参与者可能携带E280A PSEN1突变，早在30多岁后期就会导致轻度认知障碍。
在筛查访视期间进行个体医学评估，以选择最适合志愿者的避孕方法，必要时转诊给妇科医生。所有非手术避孕方法均由申办方提供。工作人员接受了避孕咨询、向志愿者正确发放避孕药具以及识别、报告和跟踪怀孕情况的培训。开展了两次关于避孕药具使用的全面教育活动，干预对象包括所有志愿者。此外，每年对志愿者进行一次调查，以评估发放程序。最后，回顾性评估这些策略的有效性，通过外推法比较整个试验期间出现的怀孕次数与哥伦比亚的一般生育率。
共招募了159名女性志愿者。所有策略均按计划实施，即使在新冠疫情期间也是如此。评估期间（2015 - 2021年）发生了10次怀孕。其中2次是计划内的；其余与潜在的治疗失败或避孕药具使用不当有关，每年的避孕失败率为0.49%。60%的怀孕导致流产，包括自然流产或治疗性流产。然而，没有足够的数据将怀孕结局与研究产品的给药联系起来。最后，我们观察到参与试验的女性生育率低于哥伦比亚人群。
在7年的评估期内，与哥伦比亚人群相比，参与试验的女性避孕失败率较低且怀孕发生率下降，这表明哥伦比亚API ADAD试验中使用的策略在解决避孕药具使用问题方面是充分且有效的。
