ETHICally sound inclusion of PREGnant women in MEdical research - PREGMETHICs study

Historically, pregnant women have been routinely excluded from research participation for reasons of harm to the fetus. As a result, pregnant women are underrepresented in medical research which has led to suboptimal care for mother and fetus. Currently, many argue that not only inclusion of pregnant women should be justified, but also exclusion. At the same time, pregnant women remain underrepresented in medical research, but it is unclear why. Apart from historical reluctance, for instance because of the thalidomide tragedy which led to exclusion of pregnant women in drug studies, there may also be ethical reasons that may lead to barriers for inclusion. From an ethical perspective it is unclear when in and exclusion of pregnant women in drug studies counts as fair. There are at least five open issues: 1. Limited empirical data on women’s and obstetricians’/midwifes’ motivations for participating in drug studies and including pregnant women in research; 2. The justification for labeling pregnant women as a vulnerable study group in need of special protections, which sometimes leads to a priori exclusion because of the vulnerability label; 3. what counts as an acceptable level of risks in order to test the safety and efficacy of drugs in pregnant women and whether the risks regarded as acceptable for the pregnant woman may be in conflict with the risks for the fetus in drug research, and if so whose interests should prevail in the case of a conflict; 4. what fair inclusion of pregnant women in drug research means from a distributive justice-based perspective, and 5. what counts as ethically and statistically optimized designs for fair inclusion of pregnant women, including what counts as ethically sound initiating and stopping of clinical trials with pregnant women. In the PREGMETHICs study we aim to contribute to the process of fair inclusion by addressing these five open issues. The project has an empirical and a normative part. In the empirical part we will collect data on women’s and obstetricians’/midwifes’ views on enrolling pregnant women in drug research by means of literature reviews and semi-structured interviews on two current drug studies with pregnant women in the Netherlands. In the normative part we will develop a normative framework based on an evaluation of the findings of the empirical part and conceptual analyses of vulnerability of pregnant women as research participants, acceptable level of risk in drug studies, and fair inclusion. The conceptual analyses will be performed from an applied perspective, meaning a further specification of the state of the debate to the context of pregnant women in drug research. We will also perform a normative-biostatistical evaluation of ethically optimized designs for pregnant women in drug studies. Eventually, the empirical data and the normative data gathered will be brought into reflective equilibrium. The reflective equilibrium is a process of moral deliberation in which we will go back and forth between the various elements. The aim of this process is to fit the elements into a coherent view. The outcome will provide us with a normative framework for fair inclusion of pregnant women in medical research. These findings have both academic and social value for policy and guideline makers, pharmacologists, obstetricians, midwifes, trial designers and pregnant women and fetuses at a national and international level.