Johns Hopkins Bloomberg School of Public Health researchers want to know if giving pregnant women daily calcium, low-dose aspirin, and multiple micronutrients (CAMMS) will improve pregnancy and birth outcomes.
To test their hypothesis, they are preparing randomized controlled trials in Burkina Faso, Pakistan and Zimbabwe. In each country, there will be two groups or “arms” of the study: one group of pregnant women will receive daily iron and folic acid (IFA) tablets, which is standard-of-care in each country, and another group will receive the regimen of CAMMS tablets. Researchers will follow the study participants throughout their pregnancies and assess any differences between the groups, such as the prevalence of babies born too early or too small and other complications.
One of the biggest potential barriers to determining if taking CAMMS improves birth outcomes compared to taking IFA is ensuring that women in both arms of the clinical trial are, in fact, taking their tablets every day. If significant numbers of women forget to take their pills or decide not to take them regularly, researchers won’t know which regimen is actually better for mothers and their babies.
Enter the Johns Hopkins Center for Communication Programs. Before any of the tablets are distributed, the sponsors of the trial – the Bill & Melinda Gates Foundation and Children’s Investment Fund Foundation – have brought on CCP to leverage human-centered design, by using a design-thinking process to develop the best possible adherence interventions. In other words, they hope to develop the best methods to encourage women to take their pills as directed, whether IFA or CAMMS.
“If only half of the women in the study who are supposed to be taking the pills actually take them, you’re not going to be able to see the impact of either treatment,” says CCP’s Danielle Piccinini Black, who heads the center’s human-centered design work. “That’s why we need to work directly with the stakeholders in all three countries to learn from and co-design the best possible methods for helping women remember to take their pills.”
Most low- and middle-income countries promote iron and folic acid (IFA), an important prenatal supplement that supports both moms’ and babies’ nutritional status and health. Research suggests that providing an integrated intervention of calcium, low-dose aspirin, and a multiple micronutrient supplement (MMS) containing iron, folic acid, and several other vitamins and minerals can improve maternal and neonatal health. Each of these (calcium, low-dose aspirin, and MMS) has been studied separately and demonstrated a unique biological pathway to improving maternal and/or neonatal outcomes. Never before have all three been studied together.
The hypothesis for this study is that if CAMMS is taken by pregnant women, there will be a greater reduction in the prevalence of preterm birth compared to the group of women taking IFA. Globally, pre-term birth is now the leading cause of mortality among children under five years. Preterm birth has been a stubborn problem to solve – and indeed in many countries the problem is increasing.
Medication adherence has long been a challenge. Adherence to therapies is a primary determinant of treatment success, and rates vary widely by country. In fact, even though IFA supplements are already the standard of care, adherence also vary. Most studies have found only 40 percent to 70 percent of pregnant women take the supplements as directed. So even though the supplements have been recommended, many women don’t take them often enough to reap the benefits.
The reasons for low adherence also vary widely and may include forgetfulness, concerns about side effects, stockouts in clinics and pharmacies and a lack of understanding of the health benefits of the supplement.
In partnership with the Bloomberg School of Public Health, Institut de Recherche en Sciences de la Sante in Burkina Faso, Department of Community Health Sciences at Aga Khan University in Pakistan, and Zvitambo Institute for Maternal and Child Health Research in Zimbabwe, CCP will engage groups of stakeholders – including pregnant women, mothers of young children, their partners and family members, health providers, and other influential members of the community – to develop the solutions that they believe will work best in their communities.
The research institutes will work with end-users and key stakeholders to create prototypes of their ideas, which will be tested in the real world. The prototypes will be reworked based on feedback until they have created a final package of adherence support interventions. Those solutions – which may be different in each country – will then be made part of the clinical trial protocol when it begins next year.
“Beyond the obvious benefits of creating good adherence support so that the trial actually produces viable results, the adherence interventions we develop can also help support other programs where we encourage prenatal care and consistent use of prenatal nutritional supplements,” says Cassandra Mickish Gross, director of new business development at CCP.
Mickish Gross says the solutions that the CCP team develops need to be practical and possible to scale-up.
“If what we come up with for adherence is too difficult or too expensive, it will counteract our work,” she says. “We need to make sure it will work in the real world. If you make something work in the lab but not in the real world, it doesn’t matter. It will not be successful.”