Article
Health Care Sciences & Services
Mohammod Mostazir, Gordon Taylor, William Edward Henley, Edward Robert Watkins, Rod S. Taylor
Summary: The study aimed to compare treatment effects estimated by ITT and PP methods in RCTs, finding that PP estimates were significantly higher than ITT estimates. PP analysis is not recommended for assessing protocol non-adherence impact in RCTs, and alternative causality-based methods like CACE should be considered.
JOURNAL OF CLINICAL EPIDEMIOLOGY
(2021)
Editorial Material
Medicine, General & Internal
David E. Scheim, Colleen Aldous, Barbara Osimani, Edmund J. Fordham, Wendy E. Hoy
Summary: Under certain circumstances, per-protocol (PP) analysis provides a more accurate reflection of the real-world benefits of a medical intervention compared to intention-to-treat (ITT) analysis. Three randomized clinical trials (RCTs) demonstrate the inconsistencies between PP and ITT analysis and highlight the importance of data transparency when discrepancies arise.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Health Care Sciences & Services
Anthony D. Bai, Adam S. Komorowski, Carson K. L. Lo, Pranav Tandon, Xena X. Li, Vaibhav Mokashi, Anna Cvetkovic, Aidan Findlater, Laurel Liang, George Tomlinson, Mark Loeb, Dominik Mertz
Summary: Contrary to common belief, ITT analysis was found to be more conservative than PP analysis in the majority of antibiotic non-inferiority trials, with a larger variance and wider confidence intervals. This finding suggests that ITT analysis should be considered as a mandatory analysis method in non-inferiority trials.
BMC MEDICAL RESEARCH METHODOLOGY
(2021)
Article
Medicine, General & Internal
Ugwu Omale, Richard L. Ewah, Chidinma Amuzie, Cordis O. Ikegwuonu, Glory E. Nkwo, Chimaobi C. Iwegbulam, Louisa C. Ekwuazi
Summary: This study aims to evaluate the effectiveness of a hybrid intervention involving parents and healthcare workers in increasing childhood immunization coverage in Ebonyi state, Nigeria. The study will use a cluster-randomized controlled trial and measure outcomes through household surveys and questionnaires.
Article
Mathematical & Computational Biology
Nicole Heussen, Ralf-Dieter Hilgers, William F. Rosenberger, Xiao Tan, Diane Uschner
Summary: This article describes two approaches to imputing missing data that preserve the randomization distribution and compares them to population-based and parametric imputation methods. The study concludes that randomization-based methods are a reasonable approach to missing data and perform comparably to population-based methods.
STATISTICS IN BIOPHARMACEUTICAL RESEARCH
(2023)
Article
Rehabilitation
Susan Armijo-Olivo, Bruno R. da Costa, Christine Ha, Humam Saltaji, Greta G. Cummings, Jorge Fuentes
Summary: This study aimed to examine the association between biases related to attrition, missing data, intention to treat, and changes in effect size estimates in physical therapy randomized trials. The findings suggest that trials that did not adhere to the intention-to-treat principle or had inadequate control of incomplete outcome data tended to underestimate treatment effects. Researchers and clinicians should be aware of these methodological issues to avoid inaccurate effect estimates.
AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
(2022)
Article
Statistics & Probability
Chan Park, Hyunseung Kang
Summary: This article presents two assumption-lean methods for analyzing ITT effects and network effects in CRTs, and reanalyzes a study on the effect of face masks and hand sanitizers on the transmission of 2008 interpandemic influenza in Hong Kong.
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
(2023)
Article
Psychology, Mathematical
Mirjam Moerbeek
Summary: This paper investigates the impact of missing data on design efficiency in multi-period trials, finding that efficiency increases with the number of subjects per day and number of weeks, but decreases due to missing data and dropout, especially when there are few subjects per day and many weeks.
BEHAVIOR RESEARCH METHODS
(2021)
Review
Oncology
Ghulam Rehman Mohyuddin, Tahani Atieh, Nausheen Ahmed, Douglas Sborov, Brian McClune, Al-Ola Abdallah, Aaron M. Goodman, Muhammad Aziz, Isabel Allen, Vinay Prasad
Summary: Chimeric antigen receptor T-cell therapy (CART) has revolutionized the treatment of hematological malignancies. However, the current reporting methodology using modified intention-to-treat analysis (mITT) tends to overestimate efficacy. Through meta-analysis of CD19 and B-cell maturation antigen (BCMA) CART trials, it was found that there is a difference of up to 8-12% in the overall response rate (ORR) between modified and intention-to-treat (iTT) analyses, with limited information on reasons for patients not receiving intended study treatment.
EUROPEAN JOURNAL OF CANCER
(2021)
Editorial Material
Pharmacology & Pharmacy
Oliver Keene
Summary: Treatment effects in clinical trials are commonly described as ITT or per-protocol effects. However, this dichotomy is unhelpful and the ICH E9 (R1) estimands framework provides an improved alternative. Properly defining estimands according to this framework is crucial when designing a trial.
PHARMACEUTICAL STATISTICS
(2023)
Article
Medicine, Research & Experimental
Mia S. Tackney, Derek G. Cook, Daniel Stahl, Khalida Ismail, Elizabeth Williamson, James Carpenter
Summary: This study discusses the use of wearable devices in clinical trials to evaluate the impact of interventions on physical activity. The proposed analysis framework defines missing data based on wear time and suggests a multiple imputation approach for handling partially observed daily step counts.
Article
Mathematical & Computational Biology
Chia-Rui Chang, Yue Song, Fan Li, Rui Wang
Summary: Covariate adjustment is important in analyzing data from randomized clinical trials, but missing data can be a barrier. This study reviews different covariate adjustment methods with incomplete covariate data. The researchers propose a weighting approach that combines inverse probability weighting and overlap weighting to adjust for missing outcomes and covariates, and conduct comprehensive simulation studies to evaluate the performance of the methods.
STATISTICS IN MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Anthony P. Carnicelli, Anne S. Hellkamp, Kenneth W. Mahaffey, Daniel E. Singer, Gunter Breithardt, Jonathan L. Halperin, Graeme J. Hankey, Jonathan P. Piccini, Richard C. Becker, Christopher C. Nessel, Scott D. Berkowitz, Keith A. A. Fox, Robert M. Califf, Manesh R. Patel
Summary: This study compared the effect of tracking primary efficacy events in the per-protocol cohort and the intention-to-treat cohort using data from the ROCKET AF trial. It was found that clinical trial termination based on event accrual in the ITT cohort versus the per-protocol cohort may have important implications on trial results depending on rates of study drug discontinuation and event rates off treatment.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Cardiac & Cardiovascular Systems
Felice Gragnano, Marcel Zwahlen, Pascal Vranckx, Dik Heg, Kurt Schmidlin, Christian Hamm, Philippe Gabriel Steg, Giuseppe Gargiulo, Eugene P. McFadden, Yoshinobu Onuma, Ply Chichareon, Edouard Benit, Helge Mollmann, Luc Janssens, Sergio Leonardi, Aleksander Zurakowski, Alessio Arrivi, Robert Jan van Geuns, Kurt Huber, Ton Slagboom, Paolo Calabro, Patrick W. Serruys, Peter Juni, Marco Valgimigli, Stephan Windecker
Summary: The reanalysis of the GLOBAL LEADERS trial showed that ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1-year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting in patients who complied with the study protocol.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Pharmacology & Pharmacy
Anastasia Ivanova, Seth Lederman, Philip B. Stark, Gregory Sullivan, Ben Vaughn
Summary: This paper describes a randomization test for clinical trials using multiple imputation to handle missing data, illustrated with two post-traumatic stress disorder trials and Fisher's combining function applied to individual scores.
JOURNAL OF BIOPHARMACEUTICAL STATISTICS
(2022)
