Trial design and methodology for a non-restricted sequential multiple assignment randomized trial to evaluate combinations of perinatal interventions to optimize women's health

Abstract

Pre-pregnancy overweight/obesity and excessive gestational weight gain (GWG) independently predict negative maternal and child health outcomes. To date, however, interventions that target GWG have not produced lasting improvements in maternal weight or health at 12-months postpartum. Given that interventions solely aimed at addressing GWG may not equip women with the skills needed for postpartum weight management, interventions that address health behaviors over the perinatal period might maximize maternal health in the first postpartum year. Thus, the current study leveraged a sequential multiple assignment randomized trial (SMART) design to evaluate sequences of prenatal (i.e., during pregnancy) and postpartum lifestyle interventions that optimize maternal weight, cardiometabolic health, and psychosocial outcomes at 12-months postpartum. Pregnant women (N=300; ≤16 weeks pregnant) with overweight/obesity (BMI ≥25 kg/m 2 ) are being recruited. Women are randomized to intervention or treatment as usual on two occasions: (1) early in pregnancy, and (2) prior to delivery, resulting in four intervention sequences. Intervention during pregnancy is designed to moderate GWG and introduce skills for management of weight as a chronic condition, while intervention in the postpartum period addresses weight loss. The primary outcome is weight at 12-months postpartum and secondary outcomes include variables of cardiometabolic health and psychosocial well-being. Analyses will evaluate the combination of prenatal and postpartum lifestyle interventions that optimizes maternal weight and secondary outcomes at 12-months postpartum. Optimizing the sequence of behavioral interventions to address specific needs during pregnancy and the first postpartum year can maximize intervention potency and mitigate longer-term cardiometabolic health risks for women.

Optimizing adaptive stepped-care interventions to change adults’ health behaviors: A systematic review

“…All included projects utilized Sequential Multiple Assignment Randomized Trials (SMARTs) or singly randomized trials (SRTs; an experimental design where participants are randomized once over the course of treatment – here mid-way through treatment) [19]. Every project but one [20] tested intermediary tailoring for treatment nonresponders based on progress towards the primary outcome. No studies evaluated change in hypothesized behavioral mediators as indicative of nonresponse to the intervention to inform tailoring.…”

“…The median [IQR] sample size of protocols is 400 [190, 800]. Protocols are posing questions during the first phase of treatment regarding modality of delivery or theoretical orientation [21,31,39,40,43], benefit of adding treatment to standard care [20,34,36,38,42], implementation strategies [37], or duration of time to tailoring [23]. Additionally, most studies are using subsequent randomization for treatment nonresponders.…”

“…Corbin and colleagues randomize participants to one of three diets and rerandomize treatment nonresponders to unassigned diets resulting in participants being exposed to between one and three diets depending on treatment response [44]. Finally, Germeroth and colleagues are using a design where everyone is rerandomized, regardless of response status, such that some individuals remain with their original treatment assignment and others swap [20].…”

“…Protocol Context. Protocols are set to test a variety of health behaviors including smoking cessation [23,[36][37][38], medication adherence [21,39,40], physical activity [42,43], glycemic management [44], weight management [20,34], and cocaine abstinence [31]. All protocols are set in outpatient or community settings.…”

An international, Delphi consensus study to identify priorities for methodological research in behavioral trials in health research

“…The SMART design allows evaluation of adaptive interventions in which the type or dose of treatment is individually tailored based on the patient's needs [2,37]. A SMART design has been used in a number of areas; for example, to evaluate alternative combinations of perinatal interventions and sequencing patterns to optimize women's health outcomes [14]. These approaches are still in their infancy and behavioral scientists should use and develop these frameworks to enhance the quality of behavioral intervention research.…”