Consort Extension for N-Of-1 Trials (Cent) Guidelines

Abstract

Introduction: By current standards, there are frequently insufficient data about the effectiveness of health care interventions in pediatric populations. Although the randomized controlled trial (RCT) is recognized within evidence-based medicine (EBM) as the gold standard for evaluating treatment efficacy, pediatric RCTs face unique challenges: (i) as pediatric illness is relatively rare, they necessitate complex multicentre trials to address relatively common pediatric problems; (ii) RCTs most often exclude patients with co-morbid conditions or concurrent therapies, limiting their generalizability; and (iii) the feasibility of RCTs is limited for those with rare conditions or for individualized therapies, thereby creating an evidence-gap regarding best care. Also, as only a small proportion of national funding in Canada and the US is devoted to pediatric research, large scale RCTs seldom address conditions that occur in infancy, childhood and adolescence despite their potential implications later in life. One cost-effective approach that offers pediatric patients and clinicians the benefit of rigorous evaluation, such as that offered by RCTs, is the N-of-1 trial-a randomized, multiple cross-over evaluation performed in a single patient. N-of-1 trials are highly appealing to families since they offer information about treatment benefit for their child, as opposed to a population mean that may or may not be applicable. Objectives: To develop the CONSORT Extension for N-of-1 Trials (CENT). Methods: Checklist items for the CENT guidelines were derived from three ongoing systematic reviews on N-of-1 conduct, analysis and metaanalysis. A structured process of obtaining information from a group of experts began with a two round Delphi process. Participants were asked to rate the relative importance of each suggested checklist item; each questionnaire was refined based on participant feedback from the previous version. Items included after the Delphi process were be debated and the checklist finalized during the CENT meeting of an invited group of the experts in May 2009. Results: 44 unique respondents between Delphi Round 1 and Round 2. Response rate: Round 1- 75%, Round 2- 62%. 45/55 items remained after Delphi. A 25-item checklist was developed from the CENT meeting and currently undergoing refinement. Significance: CENT will facilitate critical appraisal and interpretation of N-of-1 trials by providing authors with guidance on how to improve reporting and help families, health care providers and policy-makers make informed treatment decisions.