Pregnant women in clinical research

Last updated July 03, 2024

Pregnant women have historically been excluded from clinical research due to ethical concerns about harming the fetus or the perception of increased risk to the woman. Excluding pregnant women from research has also been called unethical, as it results in a scarcity of data about how therapies affect pregnant women and their fetuses. Despite consensus from bioethicists, researchers, and regulators that pregnant women should be included in clinical research, up to 95% of Phase IV clinical trials that could have included pregnant women did not, according to a 2013 review.

Ethical considerations

There are several points of concern regarding clinical research with pregnant women. Some concern is related to the idea that the fetus cannot give consent to participate in the research.^[1] Some clinical research could also result in unexpected harm to the fetus.^[2] Other concerns are that pregnant women are potentially more vulnerable to negative side effects than other populations. It has also been hypothesized that pregnant women could be more susceptible to coercion than non-pregnant adults. There is insufficient data to support either of these two latter concerns, according to a 2020 review.^[3]

Conversely, the exclusion of pregnant women from clinical research has also been called unethical. The data regarding drug use and pregnancy is scarce and of poor quality. Therefore, pregnant women do not necessarily have the same access to informed, effective healthcare as other populations.^[2]

Limiting participation

Due to complications from the drugs thalidomide and diethylstilbestrol in women in the 1960s and 1970s, the US Food and Drug Administration (FDA) enacted protections to limit reproductive-age women's exposure to substances that may cause birth defects. However, the guidelines were interpreted to exclude pregnant women from any clinical trial.^[1] Despite a 1994 National Academy of Medicine Report Ethical and Legal Issues of Including Women in Clinical Studies concluding that "pregnant women should be presumed to be eligible for participation in biomedical research", a 2013 publication noted that about 95% of Phase IV clinical trials that could have included pregnant women instead excluded them.^[3] note that this “review” is not linked to in this article and that [3] is a study about testing during an Ebola outbreak.

Effects

As a result of excluding pregnant women from clinical trials, the safety and efficacy of therapies cannot be evaluated for them. Over 80% of pregnant women are regularly prescribed therapies that are untested in pregnant populations.^[1] A study of medications approved by the FDA from 1980 to 2010 showed that 91% of medications for adults lacked data about the safety and efficacy for pregnant women, or determinations of risk to the fetus.^[2] In the case of highly lethal illnesses like Ebola and HIV/AIDS before the development of effective therapies, the exclusion of pregnant women from potentially life-saving clinical therapies results in them being "protected to death".^[3]

Promoting participation

Regulators, researchers, and bioethicists generally agree that clinical trials should include pregnant women. Because pregnancy changes the way the body metabolizes drugs, it is otherwise difficult to predict how drugs tested in non-pregnant adults will affect pregnant women. In order to treat illness in pregnant women, clinical research must involve them.^[2]

Several projects and coalitions have formed to promote the inclusion of pregnant women in clinical research. These include the Coalition to Advance Maternal Therapeutics, which consists of twenty member organizations,^[4] and the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT), a project that sought to increase the inclusion of pregnant women in vaccine trials during epidemics.^[3]

Related Research Articles

Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted.

Diethylstilbestrol (DES), also known as stilbestrol or stilboestrol, is a nonsteroidal estrogen medication, which is presently rarely used. In the past, it was widely used for a variety of indications, including pregnancy support for those with a history of recurrent miscarriage, hormone therapy for menopausal symptoms and estrogen deficiency, treatment of prostate cancer and breast cancer, and other uses. By 2007, it was only used in the treatment of prostate cancer and breast cancer. In 2011, Hoover and colleagues reported on adverse health outcomes linked to DES including infertility, miscarriage, ectopic pregnancy, preeclampsia, preterm birth, stillbirth, infant death, menopause prior to age 45, breast cancer, cervical cancer, and vaginal cancer. While most commonly taken by mouth, DES was available for use by other routes as well, for instance, vaginal, topical, and by injection.

Human subject research is systematic, scientific investigation that can be either interventional or observational and involves human beings as research subjects, commonly known as test subjects. Human subject research can be either medical (clinical) research or non-medical research. Systematic investigation incorporates both the collection and analysis of data in order to answer a specific question. Medical human subject research often involves analysis of biological specimens, epidemiological and behavioral studies and medical chart review studies. On the other hand, human subject research in the social sciences often involves surveys which consist of questions to a particular group of people. Survey methodology includes questionnaires, interviews, and focus groups.

Selective reduction is the practice of reducing the number of fetuses in a multiple pregnancy, such as quadruplets, to a twin or singleton pregnancy. The procedure is also called multifetal pregnancy reduction. The procedure is most commonly done to reduce the number of fetuses in a multiple pregnancy to a safe number, when the multiple pregnancy is the result of use of assisted reproductive technology; outcomes for both the mother and the babies are generally worse the higher the number of fetuses. The procedure is also used in multiple pregnancies when one of the fetuses has a serious and incurable disease, or in the case where one of the fetuses is outside the uterus, in which case it is called selective termination.

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In a clinical trial, the investigators must specify inclusion and exclusion criteria for participation in the study.

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HIV in pregnancy is the presence of an HIV/AIDS infection in a woman while she is pregnant. There is a risk of HIV transmission from mother to child in three primary situations: pregnancy, childbirth, and while breastfeeding. This topic is important because the risk of viral transmission can be significantly reduced with appropriate medical intervention, and without treatment HIV/AIDS can cause significant illness and death in both the mother and child. This is exemplified by data from The Centers for Disease Control (CDC): In the United States and Puerto Rico between the years of 2014–2017, where prenatal care is generally accessible, there were 10,257 infants in the United States and Puerto Rico who were exposed to a maternal HIV infection in utero who did not become infected and 244 exposed infants who did become infected.

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References

1 2 3 Heyrana, Katrina; Byers, Heather M.; Stratton, Pamela (2018). "Increasing the Participation of Pregnant Women in Clinical Trials". JAMA. 320 (20): 2077–2078. doi:10.1001/jama.2018.17716. PMID 30422300. S2CID 53293199.
1 2 3 4 Van Der Graaf, Rieke; Van Der Zande, Indira S. E.; Den Ruijter, Hester M.; Oudijk, Martijn A.; Van Delden, Johannes J. M.; Oude Rengerink, Katrien; Groenwold, Rolf H. H. (2018). "Fair inclusion of pregnant women in clinical trials: An integrated scientific and ethical approach". Trials. 19 (1): 78. doi: 10.1186/s13063-017-2402-9 . PMC 5789693 . PMID 29378652.
1 2 3 4 Edwards, Kathryn M.; Kochhar, Sonali (2020). "Ethics of Conducting Clinical Research in an Outbreak Setting". Annual Review of Virology. 7 (1): 475–494. doi: 10.1146/annurev-virology-013120-013123 . PMID 32212920.
↑ Malhamé, Isabelle; d'Souza, Rohan; Cheng, Matthew P. (2020). "The Moral Imperative to Include Pregnant Women in Clinical Trials of Interventions for COVID-19". Annals of Internal Medicine. 173 (10): 836–837. doi:10.7326/M20-3106. PMC 7384266 . PMID 32598164.

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[Heyrana-1] 1 2 3 Heyrana, Katrina; Byers, Heather M.; Stratton, Pamela (2018). "Increasing the Participation of Pregnant Women in Clinical Trials". JAMA. 320 (20): 2077–2078. doi:10.1001/jama.2018.17716. PMID 30422300. S2CID 53293199.

[Van_Der_Graaf-2] 1 2 3 4 Van Der Graaf, Rieke; Van Der Zande, Indira S. E.; Den Ruijter, Hester M.; Oudijk, Martijn A.; Van Delden, Johannes J. M.; Oude Rengerink, Katrien; Groenwold, Rolf H. H. (2018). "Fair inclusion of pregnant women in clinical trials: An integrated scientific and ethical approach". Trials. 19 (1): 78. doi: 10.1186/s13063-017-2402-9 . PMC 5789693 . PMID 29378652.

[Edwards-3] 1 2 3 4 Edwards, Kathryn M.; Kochhar, Sonali (2020). "Ethics of Conducting Clinical Research in an Outbreak Setting". Annual Review of Virology. 7 (1): 475–494. doi: 10.1146/annurev-virology-013120-013123 . PMID 32212920.

[4] Malhamé, Isabelle; d'Souza, Rohan; Cheng, Matthew P. (2020). "The Moral Imperative to Include Pregnant Women in Clinical Trials of Interventions for COVID-19". Annals of Internal Medicine. 173 (10): 836–837. doi:10.7326/M20-3106. PMC 7384266 . PMID 32598164.

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