N-of-1 randomized trials for psychological and health behavior outcomes: a systematic review protocol

Shaffer et al. Systematic Reviews (2015) 4:87 DOI 10.1186/s13643-015-0071-x PROTOCOL Open Access N-of-1 randomized trials for psychological and health behavior outcomes: a systematic review protocol Jonathan A. Shaffer1*, Louis Falzon1, Ken Cheung2 and Karina W. Davidson1 Abstract Background: Randomized controlled trials are the sine qua non of causal inference; however, heterogeneity of treatment effects for many chronic conditions and for many symptoms often limits their utility. Single-patient studies in which patients select a treatment after trying a randomized sequence of treatments (i.e., multiple crossover trials) offer an alternative to traditional randomized controlled trials by providing scientifically valid results in a practical manner that can be used by patients and their providers to decide upon their personally optimal treatment. Although N-of-1 trials have been used in the medical literature, their use for interventions that consist of psychological or health behavior outcomes is unknown. This systematic review thus aims to describe the interventions and outcomes and assess the quality of N-of-1 trials for psychological or health behavior outcomes. Methods/Design: Electronic databases (Ovid MEDLINE, EMBASE, CINAHL, PsycINFO, and the six databases in the Cochrane Library) will be searched using all relevant subject headings and free-text terms to represent N-of-1 trials and psychological or behavioral interventions. Full text review and bibliography searching will be conducted. Unpublished studies will be sought by searching trial registries and contacting authors of included studies. Eligibility criteria are the following: population, all human participants for whom N-of-1 trials with psychological or health behavior outcomes have been conducted; interventions, all interventions for which N-of-1 trials have been conducted; comparison, placebo or active treatment control; and outcome, psychological and health behavior outcomes including self-perceived disease severity and psychological phenomena such as mood and affect. Studies that do not contain sufficient trial detail, describe only design or statistical analytic issues in N-of-1 trials without presentation of an N-of-1 trial itself, and/or are not written in the English language are ineligible. Screening, data extraction, and quality assessment will be conducted by two independent reviewers with disagreements resolved through discussion. Discussion: This systematic review will describe the interventions and outcomes and assess the quality of N-of-1 trials for psychological or health behavior outcomes. The results will clarify the use of this research methodology in the health psychology and behavioral medicine literature and may pave the way for additional N-of-1 trials to be conducted. Systematic review registration: PROSPERO CRD42015017853 Keywords: N-of-1, Crossover, Within-subject, Health psychology, Behavioral medicine * Correspondence: 1 Department of Medicine, Columbia University Medical Center, 622 West 168th Street, PH9 West, Room 318, New York, NY 10032, USA Full list of author information is available at the end of the article © 2015 Shaffer et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Shaffer et al. Systematic Reviews (2015) 4:87 Background Despite their commonly lauded role as the gold standard of causal inference and the cornerstone of evidence-based medicine, randomized controlled trials (RCT) often fail to provide evidence for individualized therapeutic decisions. Indeed, heterogeneity of treatment effects (HTE) is evident for many RCTs for many chronic conditions and for many symptoms, such that some RCT-supported treatments can have huge benefits for some patients but can be minimally effective or even harmful for others [1, 2]. Further, traditional, two-arm, parallel group RCTs can be costly to conduct, leaving clinicians and researchers to rely on clinical experience rather than strong experimental evidence [3]. As these conventional RCTs provide only the average treatment effect of an intervention for a group of patients, patients and clinicians need additional information about the effect of a specific treatment for a specific patient for a specific problem [2]. The Evidence-Based Medicine Working Group suggested that N-of-1 trials “provide the strongest evidence for the decisions of patients [4].” N-of-1 trials are singlepatient studies in which patients select a treatment after trying a series of treatments (i.e., multiple crossover trials) to determine the relative benefits and harms of each treatment for themselves [1]. They focus on the individual patient by randomizing comparative treatments across time within each patient, rather than randomizing different patients to different comparative treatments as is done in a traditional RCT. Thus, instead of using the results of a conventional or between-patient RCT to choose the best treatment for a patient, the N-of-1 trial methodology can provide scientifically valid results and therefore valuable information in a practical manner that can be used by patients and providers to decide upon a personally optimal treatment and so overcome HTE. In this way, N-of-1 trials are the foundational design for a truly patient-centered comparative effectiveness method. Further, N-of-1 trials are specifically designed to help patients make healthcare decisions that are informed by high-integrity, evidencebased information that is uniquely relevant to their important outcomes and values [5]. In a series of demonstration trials, N-of-1 designs have led to valuable changes in treatment, cessation of treatment, or confirmation of the original treatment [6–10]. For example, in one series of 71 N-of-1 trials for patients with either chronic pain or osteoarthritis, 46 patients (65 %) decided to change their pain medication as a result of the information from the trials, and of the 37 patients using an NSAID or Cox-2 inhibitor drug for pain management before their trials, 12 (32 %) decided that the medication was not helping and stopped it, as a result of their trial results. Notwithstanding the proliferation of N-of-1 trials in the medical literature, randomized N-of-1 trials have only sporadically been used for treatments that target Page 2 of 7 psychological or health behavior outcomes. Furthermore, among those N-of-1 studies that have considered psychological or health behavior outcomes, information regarding study quality and methods for assessing study quality is limited. This gap in knowledge is peculiar given the abu (...truncated)