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

J. Walker Blackston; Andrew G. Chapple; James M. McGree; Suzanne McDonald; Jane Nikles

doi:10.3390/healthcare7040137

Back

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

Journal article

Open access

Peer reviewed

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

J. Walker Blackston, Andrew G. Chapple, James M. McGree, Suzanne McDonald and Jane Nikles

Healthcare (Basel), Vol.7(4), pp.1-13

06/11/2019

DOI: https://doi.org/10.3390/healthcare7040137

PMCID: PMC6955665

PMID: 31698799

Files and links (2)

pdf

Comparison of Aggregated N-of-1 Trials with Parallel and Crossover Randomized Controlled Trials Using Simulation Studies1.68 MBDownload View

Published (Version of record)CC BY V4.0, Open Access

url

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

Published (Version of record)CC BY V4.0, Open

Metrics

49 File views/ downloads

11 Record Views

27 Times Cited - Web of Science

See more details

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Abstract

Health Care Sciences & Services

Health Policy & Services

Life Sciences & Biomedicine

Science & Technology

N-of-1 trial

evidence-based medicine

comparative effectiveness

clinical trial

single-case study

simulation study

statistical methods

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.

Details

Title: Comparison of Aggregated N-of-1 Trials with Parallel and Crossover Randomized Controlled Trials Using Simulation Studies
Creators: J. Walker Blackston - Tulane University
Andrew G. Chapple - Louisiana State University Health Sciences Center New Orleans
James M. McGree - Queensland University of Technology
Suzanne McDonald - University of Queensland
Jane Nikles - University of Queensland
Publication Details: Healthcare (Basel), Vol.7(4), pp.1-13
Publisher: Mdpi
Number of pages: 13
Identifiers: 991013054979202368
Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Academic Unit: Human Sciences; Faculty of Health
Language: English
Resource Type: Journal article

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

Files and links (2)

Metrics

UN Sustainable Development Goals (SDGs)

Abstract

Details

Southern Cross University Social media