Analysis approaches to address treatment nonadherence in pragmatic trials with point-treatment settings: a simulation study
department or school: Medicine, Faculty of
department or school: Science, Faculty of
department or school: Population and Public Health (SPPH), School of
department or school: Statistics, Department of
data provider: DSpace
identifier citation: BMC Medical Research Methodology. 2022 Feb 16;22(1):46
rights copyright: The Author(s)
creator: Hossain, Md. Belal
creator: Mosquera, Lucy
creator: Karim, Mohammad Ehsanul
issued: 2022-03-11T17:50:08Z
issued: 2022-02-16
description: Background Two-stage least square [2SLS] and two-stage residual inclusion [2SRI] are popularly used instrumental variable (IV) methods to address medication nonadherence in pragmatic trials with point treatment settings. These methods require assumptions, e.g., exclusion restriction, although they are known to handle unmeasured confounding. The newer IV-method, nonparametric causal bound [NPCB], showed promise in reducing uncertainty compared to usual IV-methods. The inverse probability-weighted per-protocol [IP-weighted PP] method is useful in the same setting but requires different assumptions, e.g., no unmeasured confounding. Although all of these methods are aimed to address the same nonadherence problem, comprehensive simulations to compare performances of them are absent in the literature. Methods We performed extensive simulations to compare the performances of the above methods in addressing nonadherence when: (1) exclusion restriction satisfied and no unmeasured confounding, (2) exclusion restriction is met but unmeasured confounding present, and (3) exclusion restriction is violated. Our simulations varied parameters such as, levels of adherence rates, unmeasured confounding, and exclusion restriction violations. Risk differences were estimated, and we compared performances in terms of bias, standard error (SE), mean squared error (MSE), and 95% confidence interval coverage probability. Results For setting (1), 2SLS and 2SRI have small bias and nominal coverage. IP-weighted PP outperforms these IV-methods in terms of smaller MSE but produces high MSE when nonadherence is very high. For setting (2), IP-weighted-PP generally performs poorly compared to 2SLS and 2SRI in term of bias, and both-stages adjusted IV-methods improve precision than naive IV-methods. For setting (3), IV-methods perform worst in all scenarios, and IP-weighted-PP produces unbiased estimates and small MSE when confounders are adjusted. NPCB produces larger uncertainty bound width in alm…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/80943
note: Hossain et al. BMCMedical ResearchMethodology (2022) 22:46 https://doi.org/10.1186/s12874-022-01518-8RESEARCH Open AccessAnalysis approaches to addresstreatment nonadherence in pragmatic trialswith point-treatment settings: a simulationstudyMd. Belal Hossain1, Lucy Mosquera2 and Mohammad Ehsanul Karim1,3*AbstractBackground: Two-stage least square [2SLS] and two-stage residual inclusion [2SRI] are popularly used instrumentalvariable (IV) methods to address medication nonadherence in pragmatic trials with point treatment settings. Thesemethods require assumptions, e.g., exclusion restriction, although they are known to handle unmeasuredconfounding. The newer IV-method, nonparametric causal bound [NPCB], showed promise in reducing uncertaintycompared to usual IV-methods. The inverse probability-weighted per-protocol [IP-weighted PP] method is useful inthe same setting but requires different assumptions, e.g., no unmeasured confounding. Although all of thesemethods are aimed to address the same nonadherence problem, comprehensive simulations to compareperformances of them are absent in the literature.Methods: We performed extensive simulations to compare the performances of the above methods in addressingnonadherence when: (1) exclusion restriction satisfied and no unmeasured confounding, (2) exclusion restriction ismet but unmeasured confounding present, and (3) exclusion restriction is violated. Our simulations varied parameterssuch as, levels of adherence rates, unmeasured confounding, and exclusion restriction violations. Risk differences wereestimated, and we compared performances in terms of bias, standard error (SE), mean squared error (MSE), and 95%confidence interval coverage probability.Results: For setting (1), 2SLS and 2SRI have small bias and nominal coverage. IP-weighted PP outperforms theseIV-methods in terms of smaller MSE but produces high MSE when nonadherence is very high. For setting (2),IP-weighted-PP generally performs poorly compared to 2SLS and 2…
has type: Article
is shown at: 10.14288/1.0407133
language: eng
peer review status: Reviewed
provider: Vancouver : University of British Columbia Library
publisher: BioMed Central
publisher DOI: 10.1186/s12874-022-01518-8
rights: Attribution 4.0 International (CC BY 4.0)
rights URI: http://creativecommons.org/licenses/by/4.0/
scholar level: Faculty
scholar level: Researcher
subject: Pragmatic trials
subject: Nonadherence
subject: Simulation
subject: Unmeasured confounding
type: Text
identifier URI: http://hdl.handle.net/2429/80943