Abstract Objective To raise awareness among clinicians and epidemiologists that single-patient (n-of-1) trials are potentially useful for informing personalized treatment decisions for patients with ...chronic conditions. Study Design and Setting We reviewed the clinical and statistical literature on methods and applications of single-patient trials and then critically evaluated the needs for further methodological developments. Results Existing literature reports application of 2,154 single-patient trials in 108 studies for diverse clinical conditions; various recent commentaries advocate for wider application of such trials in clinical decision making. Preliminary evidence from several recent pilot acceptability studies suggests that single-patient trials have the potential for widespread acceptance by patients and clinicians as an effective modality for increasing the therapeutic precision. Bayesian and adaptive statistical methods hold promise for increasing the informational yield of single-patient trials while reducing participant burden, but are not widely used. Personalized applications of single-patient trials can be enhanced through further development and application of methodologies on adaptive trial design, stopping rules, network meta-analysis, washout methods, and methods for communicating trial findings to patients and clinicians. Conclusions Single-patient trials may be poised to emerge as an important part of the methodological armamentarium for comparative effectiveness research and patient-centered outcomes research. By permitting direct estimation of individual treatment effects, they can facilitate finely graded individualized care, enhance therapeutic precision, improve patient outcomes, and reduce costs.
Randomised clinical trials are the preferred method for establishing average intervention effects for groups. Using key methodological elements of these trials, n-of-1 trials provide rigorous ...evidence of intervention effects for individuals. N-of-1 trials are particularly useful for situations where randomised clinical trials are not always feasible or appropriate, such as for individuals with rare diseases, comorbid conditions, or using concurrent treatments. N-of-1 trials enhance precision when intervention effects are heterogeneous between individuals. Here, we describe an extension to the SPIRIT (standard protocol items: recommendations for interventional trials) guideline, SPENT (SPIRIT extension for n-of-1 trials), to improve the completeness and transparency of n-of-1 trial protocols. SPENT is also aligned with the CONSORT (consolidated standards of reporting trials) extension for n-of-1 trials (CENT). The guideline development group followed the development strategy for reporting guidelines endorsed by the EQUATOR Network. SPENT began with a systematic review for n-of-1 protocol recommendations. After analysis to identify possible SPENT items, a three round Delphi process was implemented, with international participation involving researchers, patient advocates, and other stakeholders. This was followed by in-person meetings and email discussion of the SPENT group to achieve consensus. SPENT has 14 extension items specific to n-of-1 trials, a checklist for n-of-1 trial protocol abstracts, and additional guidance for eight SPIRIT items where trialists could encounter issues specific to n-of-1 trials. This paper describes the rationale and development process, and provides examples and explanations for each SPENT checklist item.
Background: N-of-1 trials (multiple crossover studies conducted in single individuals) may be ideal for determining individual treatment effects and as a tool to estimate heterogeneity of treatment ...effects (HTE) in a population. However, comprehensive data on n-of-1 trial methodology and analysis is lacking. We performed this study to describe n-of-1 trial characteristics, examine treatment changes resulting from n-of-1 trial participation, and to determine if trial reporting is adequate for estimating HTE. Methods: We undertook a systematic review of n-of-1 trials published between 1985 and December 2010. Included trials were those having individual treatment episodes as the unit of randomization and reporting individual-specific treatment effects. We abstracted trial characteristics, treatment change information, and analytic methods. Results: We included 108 trials reporting on 2154 participants. Approximately half (49%) of the trials used a statistical cutoff to determine a superior treatment, whereas the remainder used a graphical comparison (25%) or a clinical significance cutoff (20%). Sixty-seven trials, reporting on 488 people, provided treatment change information: 54% of participants had subsequent treatment decisions consistent with the results of the trial, 8% had decisions inconsistent with trial results, and 38% had ambiguous results. Less than half of the trials (45%) reported adequate information to facilitate the calculation of HTE. Conclusion: N-of-1 trials are a useful tool for enhancing therapeutic precision in a range of conditions and should be conducted more often. To facilitate future meta-analysis, and the estimation of HTE, researchers reporting n-of-1 trial results should clearly describe individual data.
Children with chronic invasive ventilator dependence living at home are a diverse group of children with special health care needs. Medical oversight, equipment management, and community resources ...vary widely. There are no clinical practice guidelines available to health care professionals for the safe hospital discharge and home management of these complex children.
To develop evidence-based clinical practice guidelines for the hospital discharge and home/community management of children requiring chronic invasive ventilation.
The Pediatric Assembly of the American Thoracic Society assembled an interdisciplinary workgroup with expertise in the care of children requiring chronic invasive ventilation. The experts developed four questions of clinical importance and used an evidence-based strategy to identify relevant medical evidence. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to formulate and grade recommendations.
Clinical practice recommendations for the management of children with chronic ventilator dependence at home are provided, and the evidence supporting each recommendation is discussed.
Collaborative generalist and subspecialist comanagement is the Medical Home model most likely to be successful for the care of children requiring chronic invasive ventilation. Standardized hospital discharge criteria are suggested. An awake, trained caregiver should be present at all times, and at least two family caregivers should be trained specifically for the child's care. Standardized equipment for monitoring, emergency preparedness, and airway clearance are outlined. The recommendations presented are based on the current evidence and expert opinion and will require an update as new evidence and/or technologies become available.
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