Authors: Adrian Billings is the Associate Dean of Rural Health Professions at Tech University Health Sciences Center – Permian Basin. Muhammad Ahmad…
Balancing Risk and Equity: Involvement of Pregnant Women in Novel Vaccine and Drug Trials
Author: Tila Khan is DBT/Wellcome Trust India Alliance Early Career Fellow in Clinical and Public Health Research, School of Medical Science & Technology, Indian Institute of Technology-Kharagpur, Kharagpur, India.
The first reports of the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) came in December 2019, from Wuhan, China. The disease rapidly spread across the globe, assuming pandemic proportions a little over a year ago.1 While it was first recognized in India on 30th January 2020, it was not until March 2020, that it became a bigger threat to the Indian public health system, forcing the government to introduce the largest lockdown covering 1.37 billion people.
The pandemic touched every life and had an especially enormous impact on maternal and child health, particularly affecting the antenatal care program, institutional deliveries and routine immunizations. Although recognized as a priority high-risk group in India, pregnant women were faced a changing and strained health care system with disruption of antenatal care services and public transport system. This resulted in missed antenatal care visits, increase in home deliveries, decreased skilled care and hospitalization during labour.2 Even in past pandemics of influenza (1918, 1957, 2009),3 4 or Zika virus,5 maternal, perinatal and neonatal outcomes suffered globally.
A living systematic review and a nationwide COVID-19 surveillance by the Center for Disease Control (CDC), USA, provided a comprehensive synthesis of evidence demonstrating the extent of severe COVID-19 illness in pregnancy.6 7 Their findings suggested that symptomatic pregnant women with COVID-19 were at increased need of intensive care, invasive ventilation and death compared to non-pregnant women, particularly those having pre-existing co-morbidities.6 7 Further, pregnant women with COVID-19 were more likely to give birth prematurely, and the newborns were at greater risk for subsequent hospital or NICU admissions.8
Despite their risk of suffering severe COVID-19, pregnant women were generally not included in the initial COVID-19 vaccine studies globally.9 The exclusion has been partly due to concerns surrounding adverse effects on the fetus due to the new vaccines which were developed at an unprecedented pace, and the conflicting evidence on the impact of COVID-19 on pregnancy and its outcomes derived mainly from case reports, case studies and systematic reviews of these reports with biased estimates, no comparators and wide heterogeneity in testing strategies.6 10
Although initially the recommendations did not include pregnant women, recent evidence indicates that the vaccines are safe and trigger strong immune response in both mothers and newborn children. WHO and CDC initially provided the choice for vaccination to only those pregnant women at high risk but more recent recommendations have removed such restrictions. Exclusion of pregnant women from initial vaccine trials was also observed for ongoing drug therapy trials for COVID-19. Including pregnant women in vaccine or drug trials with products whose effect on the fetus are not entirely documented is a risk and needs to be balanced against the issue of depriving them from access to essential vaccines and drugs against diseases that may worsen maternal and child health outcomes. If pregnant women are not given an opportunity to participate in the vaccine trials, then the evaluation of safety and effectiveness of available vaccines in this high-risk group will not be available for informing policy decisions in a timely fashion hampering equitable and transparent access to vaccines and therapeutics.
India has the world’s largest annual birth cohort of 27 million children and the maternal mortality rate ratios are on an accelerated decline. The COVID-19 vaccination drive is rapidly getting scaled up. Concurrently, India has started providing vaccines to partner countries under the GAVI’s COVAX facility, including commercial exports. Despite these encouraging trends, ethical frameworks need to be developed to guide future efforts so that pregnant women and other vulnerable and high-risk groups can be equitably included in trials of vaccines and novel therapeutic agents after appropriate safety evaluations.
There is a need for global response and call for action towards inclusion of pregnant women in phase III trials of novel vaccines and therapeutic agents. In the absence of such robust data, usually, pregnant women are deprived of effective preventive or curative options. With the political will to reduce maternal mortality and a strong vaccine production infrastructure, India must take the lead in including pregnant women in future vaccine trials to generate evidence for guideline developers and policy makers for making recommendations on equitable access of this high-risk group to COVID-19 vaccines.
This post was developed as part of the course titled “The COVID-19 Response in India: Impact on Women and Children’s Health and Wellbeing”, which was delivered by the Maternal and Child Health Center, India, which was launched by the International Vaccine Access Center at the Johns Hopkins Bloomberg School of Public Health.
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