The second wave: Toward responsible inclusion of pregnant women in research

Abstract

Though much progress has been made on inclusion of non-pregnant women in research, thoughtful discussion about including pregnant women has lagged behind. We outline resulting knowledge gaps and their costs and then highlight four reasons why ethically we are obliged to confront the challenges of including pregnant women in clinical research. These are: the need for effective treatment for women during pregnancy, fetal safety, harm from the reticence to prescribe potentially beneficial medication, and the broader issues of justice and access to benefits of research participation. Going forward requires shifting the burden of justification from inclusion to exclusion and developing an adequate ethical framework that specifies suitable justifications for excluding pregnant women from research.

Safe Use of Drugs During Pregnancy in Focus of International Practice of Pharmacovigilance System and Teratological Information Service Organization

“…К ним относятся, например, Reprotox (www.reprotox.org), Каталог тератогенных веществ Шепарда и информационная система о тератогенных свойствах веществ (Shepard's Catalog of Teratogenic Agents, and Teratogen Information System, TERIS) (www.depts.washington.edu/~terisweb/teris). Кроме того, имеются доказательства, что отсутствие лечения ряда заболеваний матери во время беременности может привести к росту фетальных рисков, включая врожден-ные уродства, прекращение внутриутробного развития и мертворождаемость [11]. Оптимальная терапия вклю-чает оценку результатов непрерывного использования безопасных ЛС или прекращение использования либо небезопасных, либо несущественных медикаментов [8].…”

Modern Paradigm of the Pregnant-Involving Pharmacological Study: Risk Assessment, Ethical Principles and Regulatory Aspect

“…Although a slight step forward has been made regarding involvement of non-pregnant women in studies, there is almost no progress even in the discussion of involvement of pregnant women in clinical studies of drugs. It ought to be especially mentioned that the thalidomide tragedy was not caused by the involvement of pregnant women in clinical studies, but resulted from at least partially inadequate regulatory standards of the studies preceding distribution and marketing of the drug [1,41,51]. As drugs may produce an irreversible effect on fetal development by means of fetal-maternal exchange, the existing practice of labeling drugs for use during pregnancy concerns only the issues of fetal safety and does not involve information on their PK, PD and efficacy.…”

“…The third argument appears to be the most convincing: doctors often leave pregnant patients undertreated or women withdraw intake of life-saving drugs themselves due to the absence of proved data. And the fourth argument concentrates on resolving legal issues, where a permission to be involved in studies is not only a protection against risks, but also a considerable amount of ethical responsibilities regulating clinical studies [1]. Without any doubt, guidelines on conducting gestational studies should include carefully selected specific criteria for protecting fetal well-being.…”

“…On the other hand, refusal to use drugs during pregnancy may result in harm to health not only of mothers, but also of their unborn r newborn children caused by the disease-associated pathological alterations [1,2]. Risk/benefit balance of drug therapy is not always clear both for a mother and her fetus; it is circumstantial and specific in every woman [3].…”

What Vulnerability? Whose Vulnerability? Conflict of Understandings in the Debate on Vulnerability

“…One of her examples is the shift from the statement ‗those living below the poverty line are vulnerable to disease' to the belief ‗the poor are dirty, incapable of caring for themselves' (Gilson, 2011: 311). Uncritical acceptance of the call for special protection can open the path to stereotyping and stigmatization (Levine et al, 2004;Lange et al, 2013;Lyerly et al, 2008;Grady, 2009;Wild, 2012;Zagorac, 2016).…”