Introduction to Target Trial Emulation in Rehabilitation: A Systematic Approach to Emulate a Randomized Controlled Trial Using Observational Data

Article type
Authors
Wong J1, Negrini S2, Donzelli S3, Kiekens C4, Arienti C5, Ceravolo M6, Gross D7, Battel I8, Ferriero G9, Lazzarini S5, Dan B10, Shearer H1, Côté P11
1Ontario Tech University, Oshawa, Ontario, Canada; Canadian Memorial Chiropractic College, Toronto, Ontario, Canada
2University “La Statale”, Milan, Italy; IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
3University Medical Center (UMC) Utrecht, Utrecht, Netherland; Harvard TH CHAN School of Public Health, Boston, Massachusetts , USA
4IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
5IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy
6Politecnica delle Marche University, Ancona, Italy
7University of Alberta, Edmonton, Alberta, Canada
8University “La Statale”, Milan, Italy
9University of Insubria, Varese, Italy; Scientific Institute of Tradate IRCCS, Istituti Clinici Scientifici Maugeri, Varese, Italy
10Université Libre de Bruxelles, Brussels, Belgium; Inkendaal Rehabilitation Hospital, Vlezenbeek, Belgium
11Ontario Tech University, Oshawa, Ontario, Canada
Abstract
"Background: Rehabilitation providers and policymakers need valid evidence to make informed decisions about the healthcare needs of populations. Whenever possible, these decisions should be informed by randomized controlled trials (RCTs). However, there are circumstances when evidence needs to be generated rapidly, or when RCTs are not ethical or feasible. These situations apply to studying the effects of complex interventions, including rehabilitation. Therefore, it is necessary to consider how alternative designs to RCTs can provide valid estimates of the cause-and-effect relationship between rehabilitation interventions and functioning.

Objectives: We aim to explore the target trial emulation framework by Hernán and colleagues to obtain valid estimates of the causal effects of rehabilitation when RCTs cannot be conducted. We outline the methodology of designing cohort and quasi-experimental studies based on target trial emulation, including protocol development and observational data necessary to make causal inferences.

Methods: Target trial emulation guides the design and analysis of non-randomized comparative effectiveness studies using observational data, by emulating a hypothetical RCT. Cochrane Rehabilitation defines rehabilitation as a multimodal, person-centered, and collaborative process targeting a person's capacity or contextual factors related to performance to optimize functioning. In the context of rehabilitation, we outline steps of target trial emulation: 1) Articulating the causal question and protocol; 2) Emulating the components of a protocol representing the target trial (Figure-1). We discuss counterfactual theory as foundational to estimating causal effects, methodological considerations (e.g., advanced analytic methods to achieve comparability at baseline), limitations and mitigating strategies (e.g., quantitative bias analyses to examine potential impact of unmeasured confounding).

Conclusions: This methodological paper describes target trial emulation by Hernán and colleagues applied to rehabilitation. This approach is important to obtain valid estimates of the causal effects of rehabilitation when evidence needs to be generated rapidly or RCTs are not ethical or feasible. Despite some limitations, target trial emulation is a methodologically robust option to RCTs, and this approach informs future work in systematic reviews and risk-of-bias assessments concerning treatment effectiveness of rehabilitation. Relevance for patients: We are strengthening methodological approaches to estimating causal effects of rehabilitation when RCTs cannot be conducted for more robust evidence production."