Fair Inclusion of Pregnant Women in Clinical Research

Background: There has always been a reluctance to include pregnant women in clinical research, due to a fear of harm to the foetus. At the same time, there is a need for evidence-based information on medications and treatments for pregnant women who are or become ill during their pregnancy, which can only be gathered through research in the population of pregnant women. For this reason, inclusion of pregnant women has been promoted in the last decades by bioethicists, pharmacologists, regulators and researchers. Yet despite efforts to include pregnant women in clinical research, they are still underrepresented. There are a number of open issues and it is likely that there are ethical reasons underlying the continuous underrepresentation of pregnant women. Addressing these ethical reasons may change the status quo. The four main issues that are addressed in this thesis are: i) acceptable level of risk, ii) vulnerability, iii) fair inclusion, and iv) research design. The main objective of this thesis is to challenge the underrepresentation of pregnant women by developing a normative framework specifying the conditions under which pregnant women could be included in clinical research. Methods: In this thesis we used an empirical-ethical approach, combining empirical data with normative reflection. Empirical study of established ethical issues may clarify the extent of real and perceived problems and the way people think about them in relation to inclusion of pregnant women in clinical research. Normative evaluation of these problems may contribute to fair inclusion of pregnant women in research. The mixed-methods approach is supported by the sound methodology of the Normative-Empirical Reflective Equilibrium. Results: Through reflection on the four ethical issues and the main findings of this thesis we developed a normative framework in which we specify four normative considerations under which pregnant women may be included in clinical research: i) acceptable levels of risk for pregnant women should be formulated through a deliberative process balancing risks and benefits and the outcome should henceforth be respected, ii) pregnant women should only be deemed vulnerable when they encounter a higher exposure to risk due to a lack of scientific knowledge, iii) fair inclusion of pregnant women implies that separate trials in pregnant women should be promoted and that prioritising their research interests is a shared responsibility of all actors involved in the research process, and iv) pregnant women may be early included in the drug development process, provided that prerequisites and safety and efficacy data are adequately addressed and safeguarded throughout the process. Conclusions: With regard to the inclusion of pregnant women in clinical research, this thesis has answered ethical questions relating to acceptable levels of risk, vulnerability, fair inclusion and research design. At the same time, we have indicated issues that may need further ethical exploration. As underrepresentation of pregnant women in itself remains an ethical issue, the way forward also requires a focus on the practical application of fair inclusion