背景:由于孕妇在临床研究中的代表性严重不足,许多人认为,除非有令人信服的“科学理由”将孕妇排除在研究之外,否则必须有正当理由。然而,这种方法是否使孕妇的研究公平值得怀疑。本文分析和评估了什么时候对孕妇的研究可以被认为是公平的,什么构成了排除的科学原因。
方法:公平包容的概念伦理和方法学分析与评价。
结果:对孕妇的公平包容意味着(1)有资格的孕妇不仅因怀孕而被排除在外,(2)孕妇的研究兴趣被优先考虑,这意味着他们应该得到更多的关注。公平并不意味着孕妇应该被包括在几乎每个研究项目中,因为在仅由妇女组成的人口中仅包括少数孕妇将无助于确定孕妇治疗的有效性和安全性。一旦我们假设,对孕妇进行单独试验可能会更可取,或者知道,干预措施对孕妇的影响与其他亚人群的影响不同,或者当我们假设,或者知道,没有区别。在后一种情况下,最好进行上市后研究或建立登记处。如果没有确凿的证据表明孕妇和非孕妇之间的效果差异或等效,然而,似乎不太可能存在重大差异或完全等同,包括孕妇应该是足够的。根据研究问题,这归结为孕妇和非孕妇比例的代表性,或者过度采样孕妇。
结论:在研究中公平地将孕妇纳入研究意味着应推广单独的孕妇试验。纳入孕妇必须在研究过程的最早阶段实现。除了研究人员和研究伦理委员会,科学顾问委员会,资助者,药品监管机构,制药公司,杂志编辑和其他人有共同责任进一步发展孕妇吸毒的证据基础。
BACKGROUND: Since pregnant women are severely underrepresented in clinical research, many take the position that the exclusion of pregnant women from research must be justified unless there are compelling \"scientific reasons\" for their exclusion. However, it is questionable whether this approach renders research with pregnant women fair. This paper analyzes and evaluates when research with pregnant women can be considered as fair and what constitutes scientific reasons for exclusion.
METHODS: Conceptual ethical and methodological analysis and evaluation of fair inclusion.
RESULTS: Fair inclusion of pregnant women means (1) that pregnant women who are eligible are not excluded solely for being pregnant and (2) that the research interests of pregnant women are prioritized, meaning that they ought to receive substantially more attention. Fairness does not imply that pregnant women should be included in virtually every research project, as including only a few pregnant women in a population consisting only of women will not help to determine the effectiveness and safety of a treatment in pregnant women. Separate trials in pregnant women may be preferable once we assume, or know, that effects of interventions in pregnant women differ from the effects in other subpopulations, or when we assume, or know, that there are no differences. In the latter case, it may be preferable to conduct post-marketing studies or establish registries. If there is no conclusive evidence indicating either differences or equivalence of effects between pregnant and non-pregnant women, yet it seems unlikely that major differences or exact equivalence exist, the inclusion of pregnant women should be sufficient. Depending on the research question, this boils down to representativeness in terms of the proportion of pregnant and non-pregnant women, or to oversampling pregnant women.
CONCLUSIONS: Fair inclusion of pregnant women in research implies that separate trials in pregnant women should be promoted. Inclusion of pregnant women has to be realized at the earliest phases of the research process. In addition to researchers and research ethics committees, scientific advisory councils, funders, drug regulatory agencies, pharmaceutical companies, journal editors and others have a joint responsibility to further develop the evidence base for drug use in pregnant women.