Abstract
Hart T, Bagiella E. Design and implementation of clinical trials in rehabilitation
research.
The growth of evidence-based medicine means that both researchers and clinicians must
grasp the complex issues involved in implementing clinical trials, which are especially
challenging for the behavioral (experience-based) treatments that predominate in rehabilitation.
In this article we discuss selected issues germane to the design, implementation,
and analysis of group-level clinical trials in rehabilitation. We review strengths,
weaknesses, and best applications of 1-sample, between-subjects, and within-subjects
study designs, including newer models such as practical clinical trials and point-of-care
trials. We also discuss the selection of appropriate control conditions against which
to test rehabilitation treatments, as well as issues related to trial blinding. In
a section on treatment definition, we discuss the challenges of specifying the active
ingredients in the complex interventions that are widely used in rehabilitation, and
present an illustration of 1 approach to defining treatments via the learning mechanisms
that underlie them. Issues related to treatment implementation are also discussed,
including therapist allocation and training, and assessment of treatment fidelity.
Finally we consider 2 statistical topics of particular importance to many rehabilitation
trials: the use of multiple or composite outcomes, and factors that must be weighed
in estimating sample size for clinical trials.
Key Words
List of Abbreviations:
CONSORT (Consolidated Standards of Reporting Trials), FDR (false discovery rate), PCT (practical clinical trial), RCT (randomized controlled trial), UC (usual care)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Archives of Physical Medicine and RehabilitationAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Rating the methodological quality of single-subject designs and n-of-1 trials: introducing the Singe-Case Experimental Design (SCED) Scale.Neuropsychol Rehabil. 2008; 18: 385-401
- Single-subject research in rehabilitation: a review of studies using AB, withdrawal, multiple baseline, and alternating treatments designs.Arch Phys Med Rehabil. 1997; 78: 1145-1153
- Practice based evidence: incorporating clinical heterogeneity and patient-reported outcomes for comparative effectiveness research.Med Care. 2010; 48: S17-S22
- Experimental and quasi-experimental designs for generalized causal inference.Houghton Mifflin, Boston2002
- Experimental and quasi-experimental designs for research.Rand McNally, Chicago1963
- Foundations of clinical research: applications to practice.3rd ed. Pearson Education, Upper Saddle River2009
- A phased developmental approach to rehabilitation research: the science of knowledge building.Arch Phys Med Rehabil. 2009; 90: S3-S10
- Advancing the evidence base of rehabilitation treatments: a developmental approach.Arch Phys Med Rehabil. 2012; 93: S101-S110
- Cognitive rehabilitation: the role of theoretical rationales and respect for the maturational process needed for our evidence.J Head Trauma Rehabil. 2006; 21: 194-197
- Anger self-management training for people with traumatic brain injury: a preliminary investigation.J Head Trauma Rehabil. 2011 Mar 14; ([Epub ahead of print])
- The utility of futility.Stroke. 2005; 36: 2331-2332
- Applying a phase II futility study design to therapeutic stroke trials.Stroke. 2005; 36: 2410-2414
- A medical/vocational case coordination system for persons with brain injury: an evaluation of employment outcomes.Arch Phys Med Rehabil. 2000; 81: 1007-1015
- Vocational rehabilitation.in: High W.M. Sander A.M. Struchen M.A. Hart K.A. Rehabilitation for traumatic brain injury. Oxford Univ Pr, New York2005: 176-201
- Effectiveness of attention rehabilitation after an acquired brain injury: a meta-analysis.Neuropsychology. 2001; 15: 199-210
- Fundamentals of clinical trials.Springer, New York2010
- Promoting walking as an adjunct intervention to group cognitive behavioural therapy for anxiety disorders–a pilot group randomized trial.J Anxiety Disord. 2008; 22: 959-968
- Bias in recruitment to cluster randomized trials: a review of recent publications.J Eval Clin Pract. 2011 Jun 20; ([Epub ahead of print])
- Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy.JAMA. 2003; 290: 1624-1632
- A randomized controlled trial of holistic neuropsychologic rehabilitation after traumatic brain injury.Arch Phys Med Rehabil. 2008; 89: 2239-2249
- Supported employment: evidence for an evidence-based practice.Psychiatr Rehabil J. 2004; 27: 345-359
- A point-of-care clinical trial comparing insulin administered using a sliding scale versus a weight-based regimen.Clin Trials. 2011; 8: 183-195
- Reducing everyday memory and planning problems by means of a paging system: a randomised control crossover study.J Neurol Neurosurg Psychiatry. 2001; 70: 477-482
- The dilemma of the control condition in experience-based cognitive and behavioral treatment research.Neuropsychol Rehabil. 2008; 18: 1-21
- The selection and design of control conditions for randomized controlled trials of psychological interventions.Psychother Psychosom. 2009; 78: 275-284
- Selecting control interventions for clinical outcome studies.West J Nurs Res. 2005; 27: 346-363
- Control groups appropriate for behavioral interventions.Gastroenterology. 2004; 126: S159-S163
- Ethical issues in psychosocial interventions research involving controls.Ethics Behav. 2002; 12: 87-101
- Characteristic and incidental (placebo) effects in complex interventions such as acupuncture.Br Med J. 2009; 330: 1202-1205
- Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study.BMJ. 2008; 336: 601-605
- Longer versus shorter mental practice sessions for affected upper extremity movement after stroke: a randomized controlled trial.Clin Rehabil. 2011; 25: 627-637
Fregni F, Imamura M, Chien HF, et al. Challenges and recommendations for placebo controls in randomized trials in physical and rehabilitation medicine: a report of the international placebo symposium working group. Am J Phys Med Rehabil;89:160-72.
- Treatment definition in complex rehabilitation interventions.Neuropsychol Rehabil. 2009; 19: 824-840
- Team functioning and patient outcomes in stroke rehabilitation.Arch Phys Med Rehabil. 2005; 86: 403-409
- Team training and stroke rehabilitation outcomes: a cluster randomized trial.Arch Phys Med Rehabil. 2008; 89: 10-15
- A grand unified theory of rehabilitation (we wish!).Arch Phys Med Rehabil. 2008; 89: 203-209
- Principles of learning in TBI rehabilitation.J Head Trauma Rehabil. 2011; 26: 179-181
- Self-regulation and goal theories in brain injury rehabilitation.J Head Trauma Rehabil. 2006; 21: 142-155
- Effects of training in time-limited dynamic psychotherapy: changes in therapist behavior.J Consult Clin Psychol. 1993; 61: 434-440
- The rocks and hard places in psychotherapy outcome research.J Trauma Stress. 2007; 20: 779-792
- The evolution of psychotherapy training: reflections on manual-based learning and future alternatives.J Clin Psychol. 2000; 56: 309-318
- The effects of manual-based training on treatment fidelity and outcome: a review of the literature on adult individual psychotherapy.Psychotherapy. 2002; 39: 184-198
- The revised CONSORT statement for reporting randomized trials: explanation and elaboration.Ann Intern Med. 2001; 134: 663-694
- Methods and processes of the CONSORT Group: example of an extension for trials assessing nonpharmacologic treatments.Ann Intern Med. 2008; 148: W60-W66
- Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration.Ann Intern Med. 2008; 148: 295-309
- Improving the reporting of pragmatic trials: an extension of the CONSORT statement.Br Med J. 2008; 337: a2390
- CONSORT statement: extension to cluster randomised trials.Br Med J. 2004; 328: 702-708
- Enhancing treatment fidelity in health behavior change studies: best practices and recommendations from the NIH Behavior Change Consortium.Health Psychol. 2004; 23: 443-451
- Major ingredients of fidelity: a review and scientific guide to improving quality of intervention research implementation.Clin Psychol Rev. 2011; 31: 79-88
- Fair test of clinical trials: a treatment implementation model.Advances in Behavior Research and Therapy. 1994; 16: 1-29
- Monitoring treatment fidelity in a randomized controlled trial of a complex intervention.J Adv Nurs. 2007; 60: 343-352
- Methods for exploring implementation variation and local context within a cluster randomised community intervention trial.J Epidemiol Community Health. 2004; 58: 788-793
- The analysis of multiple endpoints in clinical trials.Biometrics. 1987; 43: 487-498
- Measuring outcome in traumatic brain injury treatment trials: recommendations from the traumatic brain injury clinical trials network.J Head Trauma Rehabil. 2010; 25: 375-382
- Procedures for two sample comparisons with multiple endpoints controlling for the experimentwise error rate.Biometrics. 1991; 47: 511-521
- Controlling the false discovery rate: a practical and powerful approach to multiple testing.J R Stat Soc Series B Stat Methodol. 1995; 57: 289-300
Article info
Footnotes
Supported in part by the National Institute on Disability and Rehabilitation Research (grant no. H133A080053) and the National Institutes of Health (grant no. R24HD050836).
No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated.
Reprints are not available from the author.
Identification
Copyright
© 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
