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 almost all scenarios. We also analyze a two-arm trial to estimate vitamin-A supplementation effect on childhood mortality after addressing nonadherence.
Conclusions: Understanding finite sample characteristics of these methods will guide future researchers in determining suitable analysis strategies. Since assumptions are different and often untestable for IP-weighted PP and IV methods, we suggest analyzing data using both IP-weighted PP and IV approaches in search of a robust conclusion.
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http://dx.doi.org/10.1186/s12874-022-01518-8 | DOI Listing |
Crit Care
December 2024
Division of Anesthesia, Critical Care, Pain and Emergency Medicine, UR‑UM103 IMAGINE, University of Montpellier, Nimes University Hospital, Nîmes, France.
Background: In septic shock, the classic fluid resuscitation strategy can lead to a potentially harmful positive fluid balance. This multicenter, randomized, single-blind, parallel, controlled pilot study assessed the effectiveness of a restrictive fluid strategy aiming to limit daily volume.
Methods: Patients 18-85 years' old admitted to the ICU department of three French hospitals were eligible for inclusion if they had septic shock and were in the first 24 h of vasopressor infusion.
Clin Neurol Neurosurg
December 2024
Case Western Reserve University School of Medicine, Cleveland, OH, United States; Department of Neurological Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, United States. Electronic address:
Background: Degenerative cervical myelopathy is one of the most common causes of spinal cord dysfunction. Cervical laminoplasty is an excellent surgical procedure that address the underlying pathology along with motion preservation with various advantages over other surgical options. While the advantages are intuitive and are being proven in multiple recent studies, concerns regarding failure still remains precluding wider utilization despite evidence to the contrary.
View Article and Find Full Text PDFEur J Nutr
December 2024
Humanify Centro de Bienestar Integral, Instituto de Investigación Nutricional - IIN, Lima, Peru.
Background And Purpose: Bioavailability studies and observational evidence suggest that heme iron (HI) may have greater impact on iron status indicators compared with non-heme iron (NHI). This systematic review and meta-analysis aimed to review the current evidence on the effect of the administration of HI compared with NHI for improving iron status in non-hospitalized population groups.
Methods: We searched Pubmed, CENTRAL, Scopus, Web of Science, and LILACS from inception to July 2024.
Ann Gen Psychiatry
December 2024
Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, China.
Background: Mood instability, characterized by sudden and unpredictable mood shifts, is prevalent in psychiatric disorders and as a personality trait. Its association with gastrointestinal diseases has been recognized but remains poorly understood in terms of causality.
Methods: This study aims to investigate the causal relationship between mood instability and a spectrum of gastrointestinal diseases by univariable and multivariable mendelian randomization analysis.
Parkinsonism Relat Disord
December 2024
Neurology Unit and Neurobiorepository and Laboratory of Advanced Biological Markers, Department of Clinical and Experimental Sciences, University of Brescia, And Department of Continuity of Care and Frailty, ASST Spedali Civili Brescia Hospital, Brescia, Italy.
Background: Progressive Supranuclear Palsy (PSP) is a rare, heterogeneous neurodegenerative disease for which no treatment is currently available. In the context of clinical trials, the representativeness of the included patients is crucial for the generalizability of the results. Herein, we present results from a multicenter perspective study to identify the most restrictive criteria for patient selection and to assess the representativeness of eligible patients.
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