Preparing for a Sequential Multiple Assignment Randomized Trial for Developing an Adaptive Treatment Strategy: Designing a SMART Pilot Study

Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
Statistics in Medicine (Impact Factor: 1.83). 07/2012; 31(17):1887-902. DOI: 10.1002/sim.4512
Source: PubMed


There is growing interest in how best to adapt and readapt treatments to individuals to maximize clinical benefit. In response, adaptive treatment strategies (ATS), which operationalize adaptive, sequential clinical decision making, have been developed. From a patient's perspective an ATS is a sequence of treatments, each individualized to the patient's evolving health status. From a clinician's perspective, an ATS is a sequence of decision rules that input the patient's current health status and output the next recommended treatment. Sequential multiple assignment randomized trials (SMART) have been developed to address the sequencing questions that arise in the development of ATSs, but SMARTs are relatively new in clinical research. This article provides an introduction to ATSs and SMART designs. This article also discusses the design of SMART pilot studies to address feasibility concerns, and to prepare investigators for a full-scale SMART. We consider an example SMART for the development of an ATS in the treatment of pediatric generalized anxiety disorders. Using the example SMART, we identify and discuss design issues unique to SMARTs that are best addressed in an external pilot study prior to the full-scale SMART. We also address the question of how many participants are needed in a SMART pilot study. A properly executed pilot study can be used to effectively address concerns about acceptability and feasibility in preparation for (that is, prior to) executing a full-scale SMART.

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    • "This study will determine whether augmentation of the implementation strategy is needed (e.g., REP + EF/IF) or whether in some circumstances withholding augmentation may result in a delayed implementation effect of REP + EF alone among non-responsive sites. Second, this study will utilize a novel SMART design developed by the study investigators [51] to accomplish this implementation trial. SMARTs allow efficient comparison of the overall impact of receiving different intervention augmentation strategies over time and incremental costs of one intervention strategy over another in improved outcomes among non-responsive sites. "
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    ABSTRACT: Background Despite the availability of psychosocial evidence-based practices (EBPs), treatment and outcomes for persons with mental disorders remain suboptimal. Replicating Effective Programs (REP), an effective implementation strategy, still resulted in less than half of sites using an EBP. The primary aim of this cluster randomized trial is to determine, among sites not initially responding to REP, the effect of adaptive implementation strategies that begin with an External Facilitator (EF) or with an External Facilitator plus an Internal Facilitator (IF) on improved EBP use and patient outcomes in 12 months.Methods/DesignThis study employs a sequential multiple assignment randomized trial (SMART) design to build an adaptive implementation strategy. The EBP to be implemented is life goals (LG) for patients with mood disorders across 80 community-based outpatient clinics (N¿=¿1,600 patients) from different U.S. regions. Sites not initially responding to REP (defined as <50% patients receiving ¿3 EBP sessions) will be randomized to receive additional support from an EF or both EF/IF. Additionally, sites randomized to EF and still not responsive will be randomized to continue with EF alone or to receive EF/IF. The EF provides technical expertise in adapting LG in routine practice, whereas the on-site IF has direct reporting relationships to site leadership to support LG use in routine practice. The primary outcome is mental health-related quality of life; secondary outcomes include receipt of LG sessions, mood symptoms, implementation costs, and organizational change.DiscussionThis study design will determine whether an off-site EF alone versus the addition of an on-site IF improves EBP uptake and patient outcomes among sites that do not respond initially to REP. It will also examine the value of delaying the provision of EF/IF for sites that continue to not respond despite EF.Trial identifier: NCT02151331.
    Implementation Science 09/2014; 9(1):132. DOI:10.1186/s13012-014-0132-x · 4.12 Impact Factor
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    • "The individually customized statistical causal model can then provide guidance for matching treatment to patients. Similarly, the sequential multiple assignment randomization trials (SMART) [121] approach, in which patients undergo multiple randomization to sequential treatments, may provide adaptive analyses of efficacy at the individual patient level that could help establish the most effective clinical algorithm. Given the heterogeneous treatment responses, these approaches may greatly enhance the ability to produce clinically significant and relevant evidence in FMS clinical research. "
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    ABSTRACT: Fibromyalgia syndrome (FMS) is a common chronic musculoskeletal pain disorder of unknown etiology and characterized by generalized body pain, hyperalgesia, and other functional and emotional comorbidities. Despite extensive research, no treatment modality is effective for all FMS patients. In this paper, we briefly review the history of FMS and diagnostic criteria, and potential pathophysiological mechanisms including central pain modulation, neurotransmitters, sympatho-adrenal and hypothalamic-pituitary-adrenal systems and peripheral muscle issues. The primary focus of the paper is to review treatment options for managing fibromyalgia symptoms. We will discuss FDA-approved medications and other pharmacologic agents, and non-pharmacologic treatments that have shown promising effects.
    12/2013; 2(2):87-104. DOI:10.1007/s40122-013-0016-9
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    • "In response to these challenges, we describe a new approach to implementation interventions. Increasingly used in clinical research, adaptive interventions guide the decisions to augment (change or adapt) existing interventions given signs of non-response (or other intermediate outcomes) during treatment [38-41]. When applied to implementation intervention studies, adaptive interventions allow sites that are not responding to an initial implementation strategy to receive an augmented implementation intervention. "
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    ABSTRACT: Persons with serious mental illness are disproportionately burdened by premature mortality. This disparity is exacerbated by poor continuity of care with the health system. The Veterans Health Administration (VA) developed Re-Engage, an effective population-based outreach program to identify veterans with SMI lost to care and to reconnect them with VA services. However, such programs often encounter barriers getting implemented into routine care. Adaptive designs are needed when the implementation intervention requires augmentation within sites that do not initially respond to an initial implementation intervention. This protocol describes the methods used in an adaptive implementation design study that aims to compare the effectiveness of a standard implementation strategy (Replicating Effective Programs, or REP) with REP enhanced with External Facilitation (enhanced REP) to promote the uptake of Re-Engage.Methods/design: This study employs a four-phase, two-arm, longitudinal, clustered randomized trial design. VA sites (n = 158) across the United States with a designated Re-Engage provider, at least one Veteran with SMI lost to care, and who received standard REP during a six-month run-in phase. Subsequently, 88 sites with inadequate uptake were stratified at the cluster level by geographic region (n = 4) and VA regional service network (n = 20) and randomized to REP (n = 49) vs. enhanced REP (n = 39) in phase two. The primary outcome was the percentage of veterans on each facility outreach list documented on an electronic web registry. The intervention was at the site and network level and consisted of standard REP versus REP enhanced by external phone facilitation consults. At 12 months, enhanced REP sites returned to standard REP and 36 sites with inadequate participation received enhanced REP for six months in phase three. Secondary implementation outcomes included the percentage of veterans contacted directly by site providers and the percentage re-engaged in VA health services. Adaptive implementation designs consisting of a sequence of decision rules that are tailored based on a site's uptake of an effective program may produce more relevant, rapid, and generalizable results by more quickly validating or rejecting new implementation strategies, thus enhancing the efficiency and sustainability of implementation research and potentially leading to the rollout of more cost-efficient implementation strategies.Trial registration: Current Controlled Trials ISRCTN21059161.
    Implementation Science 11/2013; 8(1):136. DOI:10.1186/1748-5908-8-136 · 4.12 Impact Factor
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