Methodological Challenges and Statistical Approaches in the COMprehensive Post-Acute Stroke Services Study

BACKGROUND: The COMprehensive Post-Acute Stroke Services study was a cluster-randomized pragmatic trial designed to evaluate a comprehensive care transitions model versus usual care. The data collected during this trial were complex and analysis methodology was required that could simultaneously account for the cluster-randomized design, missing patient-level covariates, outcome nonresponse, and substantial nonadherence to the intervention. OBJECTIVE: The objective of this study was to discuss an array of complementary statistical methods to evaluate treatment effectiveness that appropriately addressed the challenges presented by the complex data arising from this pragmatic trial. METHODS: We utilized multiple imputation combined with inverse probability weighting to account for missing covariate and outcome data in the estimation of intention-to-treat effects (ITT). The ITT estimand reflects the effectiveness of assignment to the COMprehensive Post-Acute Stroke Services intervention compared with usual care (ie, it does not take into account intervention adherence). Per-protocol analyses provide complementary information about the effect of treatment, and therefore are relevant for patients to inform their decision-making. We describe estimation of the complier average causal effect using an instrumental variables approach through 2-stage least squares estimation. For all preplanned analyses, we also discuss additional sensitivity analyses. DISCUSSION: Pragmatic trials are well suited to inform clinical practice. Care should be taken to proactively identify the appropriate balance between control and pragmatism in trial design. Valid estimation of ITT and per-protocol effects in the presence of complex data requires application of appropriate statistical methods and concerted efforts to ensure high-quality data are collected

Data science · Health services research · MEDLINE · Political science · Public health · Stroke (engine) · Acute Ischemic Stroke Management · Advanced Causal Inference Techniques · Computer Science · Engineering · Medicine · Nursing · Stroke Rehabilitation and Recovery

• Patient-Centered Approaches to Transitional Care Research and Implementation

  Open Access•Carly Parry, Michelle Johnston-Fleece et al.•Medical Care•2021

  Añadir item

• The stepped wedge cluster randomised trial

  Open Access•Karla Hemming, Timothy Haines et al.•BMJ•2015

  Añadir item

• Multiple imputation of discrete and continuous data by fully conditional specification

  Open Access•Stef Van Buuren•Statistical Methods in Medical…•2007

  Añadir item

• Heart Disease and Stroke Statistics—2017 Update

  Emelia J Benjamin, Michael J Blaha et al.•Circulation•2017

  Añadir item

• Principal Stratification in Causal Inference

  Open Access•Constantine Frangakis, Constantine E Frangakis et al.•Biometrics•2002

  Añadir item

• The PRECIS-2 tool

  Open Access•Kirsty Loudon, Shaun Treweek et al.•BMJ•2015

  Añadir item

• A Review of Hot Deck Imputation for Survey Non‐response

  Open Access•Rebecca R Andridge, Roderick J A Little et al.•International Statistical Review•2010

  Añadir item