Inclusion of pregnant and breastfeeding women in research – efforts and initiatives

Illamola, Sílvia M.; Bucci‐Rechtweg, Christina; Costantine, Maged M.; Tsilou, Ekaterini; Sherwin, Catherine M.T.; Zajicek, Anne

doi:10.1111/bcp.13438

Cited by 55 publications

(51 citation statements)

References 50 publications

(50 reference statements)

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“…Prior to the Revitalization Act, women were largely excluded from participating in trials using pharmaceutical agents and there was growing concern that the process of drug development did not appropriately evaluate effects in female patients. 3 The systematic exclusion of women from research paralleled a similar exclusion of pediatric patients from clinical trials prior to the Best Pharmaceuticals for Children and Pediatrics Research Equity Acts of 1994. These efforts led to a dramatic shift in the culture of pediatric research.…”

Section: Discussionmentioning

confidence: 99%

“…With approximately 25% of pregnant women entering pregnancy with a medical condition or developing pregnancy-related morbidity, the rate of medication use in pregnancy has increased greatly. 3 In 2015, pregnant women were using on average four medications during pregnancy with almost half of them using four or more medications during pregnancy. [3][4][5] These factors place pregnant women at a disadvantage given that the vast majority of medications to treat nonobstetrical conditions were never tested in pregnancy.…”

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confidence: 99%

“…3 In 2015, pregnant women were using on average four medications during pregnancy with almost half of them using four or more medications during pregnancy. [3][4][5] These factors place pregnant women at a disadvantage given that the vast majority of medications to treat nonobstetrical conditions were never tested in pregnancy. 6 The current state of research in pregnancy and the pattern of excluding pregnant women from drug trials is dismal at best and has not significantly improved even with recent improvements in the regulatory area.…”

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confidence: 99%

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Exclusion of Pregnant Women from Clinical Trials during the Coronavirus Disease 2019 Pandemic: A Review of International Registries

et al. 2020

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Objective Pregnant women have been historically excluded from clinical trials for nonobstetric conditions, even during prior epidemics. The objective of this review is to describe the current state of research for pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. Study Design We conducted a search of international trial registries for trials relating to the novel coronavirus. The eligibility criteria for each trial were reviewed for inclusion/exclusion of pregnant women. Relevant data were extracted and descriptive statistics were calculated for individual and combined data. The total number of trials from each registry were compared, as well as the proportions of pregnancy-related trials within each. Results Among 621,370 trials in the World Health Organization International Clinical Trials Registry, 927 (0.15%) were COVID-19 related. Of those, the majority (52%) explicitly excluded pregnancy or failed to address pregnancy at all (46%) and only 16 (1.7%) were pregnancy specific. When categorized by region, 688 (74.2%) of COVID-19 trials were in Asia, followed by 128 (13.8%) in Europe, and 66 (7.2%) in North America. Of the COVID-19 trials which included pregnant women, only three were randomized-controlled drug trials. Conclusion Approximately 1.7% of current COVID-19 research is pregnancy related and the majority of trials either explicitly exclude or fail to address pregnancy. Only three interventional trials worldwide involved pregnant women. The knowledge gap concerning the safety and efficacy of interventions for COVID-19 created by the exclusion of pregnant women may ultimately harm them. While “ethical” concerns about fetal exposure are often cited, it is in fact unethical to habitually exclude pregnant women from research. Key Points

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Exclusion of Pregnant Women from Clinical Trials during the Coronavirus Disease 2019 Pandemic: A Review of International Registries

et al. 2020

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“…Pregnant women are excluded from most drug trials . Pharmacokinetic studies involving pregnant women represent only 1.3% of all phase I trials registered through 2013 . The general exclusion of pregnant women from clinical trials has been predicated on concerns related to the potential foetal harms of medication used during pregnancy; this fails to consider the risk of withholding optimal therapies from pregnant women because of lack of data.…”

Section: Discussionmentioning

confidence: 99%

Optimizing responses to drug safety signals in pregnancy: the example of dolutegravir and neural tube defects

et al. 2019

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Introduction The unexpected identification of a neural tube defect (NTD) safety signal with preconception dolutegravir (DTG) exposure in the Botswana Tsepamo birth outcomes study brought into sharp focus the need for reliable data on use of new antiretrovirals in pregnancy, improved pharmacovigilance systems to evaluate safety of new drugs being introduced into populations including women of reproductive potential, and balanced risk‐benefit messaging when a safety signal is identified. Discussion The Tsepamo study NTD safety signal and accompanying regulatory responses led to uncertainty about the most appropriate approach to DTG use among women of reproductive potential, affecting global DTG roll‐out plans, and limiting DTG use in adolescent girls and women. It also revealed a tension between a public health approach to antiretroviral treatment (ART) and individual choice, and highlighted difficulties interpreting and messaging an unexpected safety signal with uncertainty about risk. This difficulty was compounded by the lack of high‐quality data on pregnancy outcomes from women receiving ART outside the Tsepamo surveillance sites and countries other than Botswana, resulting in a prolonged period of uncertainty while data on additional exposures are evaluated to refute or confirm the initial safety signal. We discuss principles for evaluating and introducing new drugs in the general population that would ensure collection of appropriate data to inform drug safety in adolescent girls and women of reproductive potential and minimize confusion about drug use in this population when a safety signal is identified. Conclusions The response to a signal suggesting a possible safety risk for a drug used in pregnancy or among women who may become pregnant needs to be rapid and comprehensive. It requires the existence of appropriately designed surveillance systems with broad population coverage; data analyses that examine risk‐benefit trade‐offs in a variety of contexts; guidance to transform this risk‐benefit balance into effective and agreed‐upon policy; involvement of the affected community and other key stakeholders; and a communication plan for all levels of knowledge and complexity. Implementation of this proposed framework for responding to safety signals is needed to ensure that any drug used in pregnancy can be rapidly and appropriately evaluated should a serious safety alert arise.

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“…For ethical reasons, pregnant women have historically often been excluded from clinical trials in the drug development process, resulting in a gap of knowledge regarding both maternal and foetal drug exposure throughout gestation. However, recent reports on the importance of conducting pharmacological research in pregnancy and possible research strategies highlight that times are changing . To our knowledge, information on DAA exposure during pregnancy is currently limited to three conference abstracts.…”

Section: Placental Handling Of Direct‐acting Antiviralsmentioning

confidence: 99%

Review article: direct‐acting antivirals for the treatment of HCV during pregnancy and lactation ‐ implications for maternal dosing, foetal exposure, and safety for mother and child

Freriksen

Seyen²,

Judd

et al. 2019

Aliment Pharmacol Ther

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Summary Background With the global efforts to eradicate hepatitis C virus (HCV), treatment during pregnancy is becoming a priority for research as this, and maternal cure should reduce vertical transmission. However, as information on the efficacy and safety of direct‐acting antivirals (DAAs) in pregnancy is generally lacking, treatment of HCV infection during pregnancy is not currently recommended. Aim To provide an overview of current knowledge regarding maternal exposure, placental handling and safety of DAAs during pregnancy and lactation Methods A literature search was performed focusing on the effect of pregnancy on maternal exposure to DAAs, the placental handling of DAAs, the safety of DAAs for mother and child during pregnancy and the safety of DAAs during lactation. Results Exposure to all DAAs studied is likely to be altered during pregnancy, mostly related to pregnancy‐induced effects on drug absorption and metabolism. Although animal studies show that most DAAs are reported to cross the placenta and transfer into breast milk, most DAA combinations show a favourable safety profile. Because of the rapid viral decline after treatment initiation, and to avoid the critical period of organogenesis, treatment may be started at the end of the second trimester or early third trimester. Conclusions Treatment of HCV infection during pregnancy is realistic, as DAAs are highly effective and treatment duration is relatively short. There is an urgent need to study DAAs during pregnancy and lactation to contribute to the goal of HCV elimination.

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Inclusion of pregnant and breastfeeding women in research – efforts and initiatives

Cited by 55 publications

References 50 publications

Exclusion of Pregnant Women from Clinical Trials during the Coronavirus Disease 2019 Pandemic: A Review of International Registries

Exclusion of Pregnant Women from Clinical Trials during the Coronavirus Disease 2019 Pandemic: A Review of International Registries

Optimizing responses to drug safety signals in pregnancy: the example of dolutegravir and neural tube defects

Review article: direct‐acting antivirals for the treatment of HCV during pregnancy and lactation ‐ implications for maternal dosing, foetal exposure, and safety for mother and child

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