Logistic, ethical, and political dimensions of stepped wedge trials: critical review and case studies.
BACKGROUND
Three arguments are usually invoked in favour of stepped wedge cluster randomised controlled trials: the logistic convenience of implementing an intervention in phases, the ethical benefit of providing the intervention to all clusters, and the potential to enhance the social acceptability of cluster randomised controlled trials. Are these alleged benefits real? We explored the logistic, ethical, and political dimensions of stepped wedge trials using case studies of six recent evaluations.


METHODS
We identified completed or ongoing stepped wedge evaluations using two systematic reviews. We then purposively selected six with a focus on public health in high, middle, and low-income settings. We interviewed their authors about the logistic, ethical, and social issues faced by their teams. Two authors reviewed interview transcripts, identified emerging issues through qualitative thematic analysis, reflected upon them in the context of the literature, and invited all participants to co-author the manuscript.


RESULTS
Our analysis raises three main points. First, the phased implementation of interventions can alleviate problems linked to simultaneous roll-out, but also brings new challenges. Issues to consider include the feasibility of organising intervention activities according to a randomised sequence, estimating time lags in implementation and effects, and accommodating policy changes during the trial period. Second, stepped wedge trials, like parallel cluster trials, require equipoise: without it, randomising participants to a control condition, even for a short time, remains problematic. In stepped wedge trials, equipoise is likely to lie in the degree of effect, effectiveness in a specific operational milieu, and the balance of benefit and harm, including the social value of better evaluation. Third, the strongest arguments for a stepped wedge design are logistic and political rather than ethical. The design is advantageous when simultaneous roll-out is impractical and when it increases the acceptability of using counterfactuals.


CONCLUSIONS
The logistic convenience of phased implementation is context-dependent, and may be vitiated by the additional requirements of phasing. The potential for stepped wedge trials to enhance the social acceptability of cluster randomised trials is real, but their ethical legitimacy still rests on demonstrating equipoise and its configuration for each research question and setting.
Institute for Global Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK. Audrey.prost@ucl.ac.uk.
Audrey
A
Prost
The Ethox Centre, University of Oxford, Oxford, UK. ariella.binik@ethox.ox.ac.uk.
Ariella
A
Binik
Public Health England (PHE), Colindale, UK. i.abubakar@ucl.ac.uk.
Ibrahim
I
Abubakar
Public Health England (PHE), Colindale, UK. Anjana.Roy@phe.gov.uk.
Anjana
A
Roy
Institute of Public Health, Faculty of Medicine, University of Heidelberg, Heidelberg, Germany. manuela.de.allegri@urz.uni-heidelberg.de.
Manuela
M
De Allegri
Hôpital des Charpennes, Hospices Civils de Lyon, Villeurbanne, France. christelle.mouchoux@chu-lyon.fr.
Christelle
C
Mouchoux
Tayside Medicines Unit, NHS Tayside, Dundee, UK. T.Dreischulte@dundee.ac.uk.
Tobias
T
Dreischulte
MRC Tropical Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. Helen@zambart.org.zm.
Helen
H
Ayles
MRC Tropical Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. James.Lewis@lshtm.ac.uk.
James J
JJ
Lewis
Institute for Global Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK. d.osrin@ucl.ac.uk.
David
D
Osrin
D006291:Health Policy / Q000331:legislation & jurisprudence; D006801:Humans; D009937:Organizational Objectives; D018579:Patient Selection / Q000941:ethics; D011050:Policy Making; D016032:Randomized Controlled Trials as Topic / Q000941:ethics / Q000331:legislation & jurisprudence / Q000379:methods*; D012107:Research Design / Q000331:legislation & jurisprudence; D012959:Socioeconomic Factors; D057212:Therapeutic Equipoise; D057188:Workflow