Harmonization of maternal balanced energy-protein supplementation studies for individual participant data (IPD) meta-analyses – finding and creating similarities in variables and data collection

Abstract

Background Public health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems. Methods We developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies. Discussion We have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses.

Nutritious Supplemental Foods for Pregnant Women from Food Insecure Settings: Types, Nutritional Composition, and Relationships to Health Outcomes

“…However, additional research is necessary to clarify the BEP supplement composition needed to achieve positive maternal and child health outcomes, which pregnant women would benefit from such intervention, and the comparison group (only half the studies indicated giving iron or iron being part of antenatal care). In response to this need, a prospective, individual participant data meta-analysis is underway and will include new ongoing or recently completed BEP trials only, which are all compared with IFA [ 54 ]. As part of this work, BEP supplementation given in lactation will also be examined ( https://osf.io/9nq7z ).…”

Targeting strategies for balanced energy and protein (BEP) supplementation in pregnancy: study protocol for the TARGET-BEP cluster-randomized controlled trial in rural Bangladesh

“…While the main effect for SGA was a 3.1% pp reduction, the confidence intervals were wide (− 7.4, 1.2), suggesting a range of treatment efficacy possibilities. Harmonization of data across five pregnancy trials will provide additional evidence on the effects of enhanced BEP supplementation on birth outcomes [ 32 ].…”

“…Recently, a new formulation for BEP was proposed through an expert consultation for a ready-to-use BEP, fortified with micronutrients and low-dose calcium and with adequate energy (250–500 kcals) to meet the increased requirements during pregnancy and 14–18 g of high quality protein [ 31 ]. This product formulation is being tested in a number of trials in LMICs [ 32 ]. Thus, we are conducting a cluster-randomized controlled trial in rural Bangladesh to test the enhanced BEP product versus MMS as standard of care in this study area, both by applying a targeted and untargeted approach to examine their effectiveness on increasing birth weight and reducing SGA.…”

The effect of balanced energy-protein supplementation provided to lactating women on maternal and infant outcomes: study protocol for a prospectively planned individual patient data (IPD) meta-analysis

“…Furthermore, the included trials have some differences in study design, data definitions, and data collection methods. Substantial efforts were made later to harmonize the primary and secondary outcome measures, in our case, through the BEP Initiative (13). Last, studies also differ in eligibility criteria, and one study only enrolled women that were undernourished.…”

“…The panel also recommended that BEP products be developed and evaluated in both pregnant and lactating women in low-resource settings to assess health benefits. To further advance the evidence-based research, BMGF funded several independent RCTs and in 2020, convened the Maternal Nutrition Harmonization Workshop to harmonize key variables across these trials and prioritize outcomes for the IPD meta-analysis (13). This later led to the formation of the Maternal BEP Studies Harmonization Initiative (hereinafter BEP Initiative) to examine the pooled effect of BEP in pregnancy and lactation on maternal and child health.…”