The idea of enrolling pregnant women into a clinical trial has been a delicate issue for many researchers. The prospect of causing permanent bodily harm to both the mother and unborn baby has excluded the group in medical research for many decades. Nonetheless, an increasing number of critics began to protest that such pervasive exclusion of pregnant women in clinical trials is, in fact, unethical.

The origin of the current protectionism orientation over pregnant women stems from previous disastrous attempts to medicate them – in the case of thalidomide, a morning sickness medication that caused tens of thousands of birth defects in the 1950s and the early 1960s. It is understandable that researchers would rather not risk exposing pregnant women to untested medication.

Nonetheless, such exclusion has resulted in a substantial knowledge gap in this area – causing pregnant women to consume medication blindly. Recent studies also noted a marked increase in the first trimester use of prescription medication, and that as many as one in two women took at least one medication during pregnancy.

Learning from past mistakes

As the medical community reflects on the aftermath of the thalidomide tragedy, there are signs that the current protectionism attitude is changing. There is an upcoming dire need to re-evaluate, through an evidence-based method, whether clinical trials are broadly detrimental to pregnant women.

It is important to highlight that thalidomide was put on the market without stringent clinical studies. Had the pharmaceutical company that marketed thalidomide in the 1950s put the compound through current regulatory frameworks, the disaster could have been averted. Furthermore, the teratogenicity of thalidomide, or any other compound with medicinal properties, can only be discovered through proper trials and experimentations.

Unfortunately, the knowledge doctors and patients are desperately seeking is not fulfilled by the research community. In addition to the widespread fear of putting pregnant women on new treatment – the risk of potential litigation is too great for many pharmaceutical companies to take on. Some bioethicists also argue that reticence shown by the pharmaceutical industry is not surprising – given the heavy financial penalty that could be imposed on them.

Many children in the 1960s, like Phillipa Brandbourne (pictured above), were born with phocomelia as a side effect of the drug thalidomide, resulting in the shortening or absence of limbs. Photo credit: Alliance for Human Research Protection (AHRP)
Many children in the 1960s, like Phillipa Brandbourne (pictured above), were born with phocomelia as a side effect of the drug thalidomide, resulting in the shortening or absence of limbs. Photo credit: Alliance for Human Research Protection (AHRP)

Re-categorising pregnant women in research

Thanks to the considerable effort from the US government and the academia, the "dark age" of clinical research in pregnant women is coming to an end. After the passing of the 21st Century Cures Act, the US Secretary of Health and Human Services established the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC) to identify knowledge gaps, and to research safe and effective treatments for these specific groups of patients. The task force has been holding public meetings to gather feedback and comment from the community.

The NIH Office of Research on Women's Health also suggested that pregnant women, as a group, should not be systematically categorised as "vulnerable population" – usually children, prisoners or cognitively impaired individuals – in research. Such standard would imply that these women do not have sufficient capacity to protect their own interests and provide informed consent.

Instead, pregnant women would be better categorised as "scientifically complex". This new description takes on a more appropriate interpretation of the physiological and ethical complexity of women and their unborn baby against the research backdrop.

Researchers still need to demonstrate the necessary benefits and safety of the clinical intervention before enrolling any pregnant woman, but it is hoped that the shift in the language, and the resultant perception of the group, would encourage more research in this field.

It is crucial to recognise that clinical data from pregnant women is as important as any other patient sub-groups – and pregnancy does not necessarily revoke the woman's right to participate in a clinical trial.

Perhaps a fundamental change in the attitude and perception of the research community is what is needed to remedy the situation and put a stop to the potentially erroneous practice of extrapolating results from trials conducted in physiologically different populations. MIMS

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