Harmonization of maternal balanced energy-protein supplementation studies for individual participant data (IPD) meta-analyses – finding and creating similarities in variables and data collection
Authors: Gernand Alison D. , Gallagher Kelly , Bhandari Nita , Kolsteren Patrick , Lee Anne CC , Shafiq Yasir , Taneja Sunita , Tielsch James M. , Abate Firehiwot Workneh , Baye Estifanos , Berhane Yemane , Chowdhury Ranadip , Dailey-Chwalibóg Trenton , de Kok Brenda , Dhabhai Neeta , Jehan Fyezah , Kang Yunhee , Katz Joanne , Khatry Subarna , Lachat Carl , Mazumder Sarmila , Muhammad Ameer , Nisar Muhammad Imran , Sharma Sitanshi , Martin Leigh A. , Upadhyay Ravi Prakash , Christian Parul ,   Maternal BEP Studies Harmonization Initiative, Chan Grace J. , Derebe Mulatu M. , Van Dyk Fred , Mullany Luke C. , Erchick Daniel , Eglovitch Michelle S. , Lu Chunling , North Krysten , Olson Ingrid E. , Fasil Nebiyou , Kidane Workagegnehu T. , Shiferie Fisseha , Shiferaw Tigest , Tsegaye Fitsum , Tsegaye Sitota , Isanaka Sheila , Molina Rose L. , Stojanov Michele D. , Wylie Blair J. , Tadesse Amare W. , Huybregts Lieven , Toe Laeticia C. , Argaw Alemayehu , Hanley-Cook Giles , Dewan Rupali , Mittal Pratima , Chellani Harish , Lama Tsering P. , Baloch Benazir , Ciulei Mihaela A. 
Published: February 2023

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.