Comparison of Aggregated N-of-1 Trials with Parallel and Crossover Randomized Controlled Trials Using Simulation Studies

Blackston, J. Walker and Chapple, Andrew G. and McGree, James M. and McDonald, Suzanne ORCID: https://orcid.org/0000-0002-1745-4987 and Nikles, Jane (2019) Comparison of Aggregated N-of-1 Trials with Parallel and Crossover Randomized Controlled Trials Using Simulation Studies. Healthcare, 7 (4 - Article 137). pp. 1-13.

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Abstract

Background: N-of-1 trials offer an innovative approach to delivering personalized clinical care together with population-level research. While increasingly used, these methods have raised some statistical concerns in the healthcare community. Methods: We discuss concerns of selection bias, carryover effects from treatment, and trial data analysis conceptually, then rigorously evaluate concerns of effect sizes, power and sample size through simulation study. Four variance structures for patient heterogeneity and model error are considered in a series of 5000 simulated trials with 3 cycles, which compare aggregated N-of-1 trials to parallel randomized controlled trials (RCTs) and crossover trials. Results: Aggregated N-of-1 trials outperformed both traditional parallel RCT and crossover designs when these trial designs were simulated in terms of power and required sample size to obtain a given power. N-of-1 designs resulted in a higher type-I error probability than parallel RCT and cross over designs when moderate-to-strong carryover effects were not considered or in the presence of modeled selection bias. However, N-of-1 designs allowed better estimation of patient-level random effects. These results reinforce the need to account for these factors when planning N-of-1 trials. Conclusion: N-of-1 trial designs offer a rigorous method for advancing personalized medicine and healthcare with the potential to minimize costs and resources. Interventions can be tested with adequate power with far fewer patients than traditional RCT and crossover designs. Operating characteristics compare favorably to both traditional RCT and crossover designs.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Faculty/School / Institute/Centre: Historic - Institute for Resilient Regions - Centre for Health, Informatics and Economic Research (1 Aug 2018 - 31 Mar 2020)
Faculty/School / Institute/Centre: Historic - Institute for Resilient Regions - Centre for Health, Informatics and Economic Research (1 Aug 2018 - 31 Mar 2020)
Date Deposited: 02 Feb 2020 23:03
Last Modified: 09 Feb 2020 23:26
Uncontrolled Keywords: N-of-1 trial; evidence-based medicine; comparative effectiveness; clinical trial; single-case study; simulation study; statistical methods
Fields of Research : 01 Mathematical Sciences > 0104 Statistics > 010401 Applied Statistics
Identification Number or DOI: 10.3390/healthcare7040137
URI: http://eprints.usq.edu.au/id/eprint/37827

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