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A new study published in Journal of Medical Ethics by van der Zande et al 1 further highlights why classifying pregnant women as a ‘vulnerable population’ in the context of research is deeply problematic. Because the designation of ‘vulnerable’ is otherwise applied to populations whose decision-making capacity about research participation is somehow compromised—such as children and adults of limited cognitive ability—many of us have been arguing for some time that using this designation for pregnant women is inappropriate and disrespectful.2–4 There is nothing about the state of pregnancy that renders pregnant women incapable of offering valid research consents or refusals. Moreover, rather than protecting the health interests of pregnant women and their offspring, this designation has had the opposite effect. It has contributed to the widespread exclusion of pregnant women from research activities, which is itself pernicious to the health of pregnant women.5
We know that pregnant women encounter a range of health needs across their pregnancies. In the USA, for example, approximately 9 out of every 10 women use some kind of medication during pregnancy to manage health conditions.6 Yet because pregnant women have largely been excluded from the clinical research enterprise, in part due to being considered a ‘vulnerable population’ in need of protection from research, we often lack the necessary evidence to inform what medications can be safely and effectively used in pregnancy and at what dose. Most medications have been approved with limited to no data on potential teratogenicity. For instance, of the 172 drugs approved by the US Food and Drug Administration between 2000 and 2010, more than 97% had an ‘undetermined’ risk for use in pregnancy.7 This means that pregnant women and their clinicians must make difficult care decisions in the face of poor data, often resulting in great anxiety about the potential harms associated with using drugs and preventives, inappropriate dosing to safely and effectively manage health conditions, or foregoing certain care altogether.8 What’s more, the average time to generate the evidence base on the safety of these treatments in pregnancy postlicensure is an astounding 27 years.7
To make matters worse, the lack of previous inclusion of pregnant women in research further stifles new research studies from including them. This is because without much existing data to draw upon, it is difficult to assess potential risks to pregnant women or their offspring in clinical trials of new medical interventions. In our work exploring barriers to appropriately including pregnant women in HIV research, one clinical investigator identified this as a ‘Catch-22 dilemma: limited safety data on HIV-related drugs in pregnancy sparks concerns about unknown potential maternal-fetal exposure risks; this leads to reluctance to study pregnant women, in turn perpetuating the lack of safety data that could inform next steps for research.’9 The new study by van der Zande et al further corroborates this vicious cycle, noting that the only reason pregnant women may be vulnerable in the context of clinical research is precisely because they will have to face potentially higher and/or unknown risks in new studies due to the current lack of scientific knowledge.
There is a desperate need to shift the paradigm to protect pregnant women through research, not just from research.
The good news is that progress is being made to move towards more equitable inclusion of pregnant women in the biomedical research agenda. Both the Council for International Organizations of Medical Sciences (CIOMS) and the US Federal Policy for the Protection of Human Subjects have been recently updated to acknowledge that pregnancy itself does not make a woman ‘vulnerable’ in the context of research participation.10 The revised 2016 CIOMS guidelines explicitly state that ‘pregnant women must not be considered vulnerable simply because they are pregnant’ and the recently adopted updates to the Federal Policy for the Protection of Human Subjects affirm that ‘the final rule no longer includes pregnant women… as examples of populations that are potentially vulnerable to coercion or undue influence,’ effective January 2018.8 11 Furthermore, an increasing number of influential organisations now recognise the importance, both scientifically and ethically, of involving pregnant women in research.8 12 13
As the world encounters new health challenges and the research enterprise responds with novel interventions to combat them, we must ensure that pregnant women are not overlooked and that they and their offspring fairly benefit from these advances in medicine. With the recent emergence of the Zika crisis and the rapid pace of vaccine development, we have a critical opportunity to demonstrate what proactive and intentional inclusion of pregnant women’s interests in the R&D agenda looks like. In our recently released guidance, ‘Pregnant Women & the Zika Virus Vaccine Research Agenda: Ethics Guidance on Priorities, Inclusion, and Evidence Generation,’ we explicitly reject the designation of pregnant women as ‘vulnerable.’ We provide concrete recommendations for how the global research community working on Zika virus vaccines can be responsive to the needs of pregnant women and their offspring. You can find this guidance and more information about our work at: www.zikapregnancyethics.org.
Contributors CBK drafted the commentary with substantive input and edits from RRF.
Funding The work referenced in this commentary was supported by the Wellcome Trust (grant number: 203160/Z/16/Z) and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (award number: R01 AI108368-01A1). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Wellcome Trust.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.
Correction notice This article has been corrected since it was published Online First. Funding information have been added.