Sensitivity analyses of unmeasured and partially‐measured confounders using multiple imputation in a vaccine safety study

2021 ◽  
Author(s):  
Stanley Xu ◽  
Christina L. Clarke ◽  
Sophia R. Newcomer ◽  
Matthew F. Daley ◽  
Jason M. Glanz
Keyword(s):  
Multiple Imputation ◽  
Vaccine Safety ◽  
Sensitivity Analyses ◽  
Safety Study

scholarly journals Adapting Group Sequential Methods to Observational Postlicensure Vaccine Safety Surveillance: Results of a Pentavalent Combination DTaP-IPV-Hib Vaccine Safety Study

2013 ◽  
Vol 177 (2) ◽  
pp. 131-141 ◽  
Author(s):  
Jennifer C. Nelson ◽  
Onchee Yu ◽  
Clara P. Dominguez-Islas ◽  
Andrea J. Cook ◽  
Do Peterson ◽  
...  
Keyword(s):  
Vaccine Safety ◽  
Safety Study ◽  
Group Sequential ◽  
Sequential Methods ◽  
Safety Surveillance ◽  
Group Sequential Methods

scholarly journals Data Missing Not at Random in Mobile Health Research: Assessment of the Problem and a Case for Sensitivity Analyses

10.2196/26749 ◽  
2021 ◽  
Vol 23 (6) ◽  
pp. e26749
Author(s):  
Simon B Goldberg ◽  
Daniel M Bolt ◽  
Richard J Davidson
Keyword(s):  
Sensitivity Analysis ◽  
Missing Data ◽  
Maximum Likelihood ◽  
Multiple Imputation ◽  
Mixture Model ◽  
Mobile Health ◽  
Sensitivity Analyses ◽  
Research Assessment ◽  
Missing Not At Random ◽  
Pattern Mixture Model

Background Missing data are common in mobile health (mHealth) research. There has been little systematic investigation of how missingness is handled statistically in mHealth randomized controlled trials (RCTs). Although some missing data patterns (ie, missing at random [MAR]) may be adequately addressed using modern missing data methods such as multiple imputation and maximum likelihood techniques, these methods do not address bias when data are missing not at random (MNAR). It is typically not possible to determine whether the missing data are MAR. However, higher attrition in active (ie, intervention) versus passive (ie, waitlist or no treatment) conditions in mHealth RCTs raise a strong likelihood of MNAR, such as if active participants who benefit less from the intervention are more likely to drop out. Objective This study aims to systematically evaluate differential attrition and methods used for handling missingness in a sample of mHealth RCTs comparing active and passive control conditions. We also aim to illustrate a modern model-based sensitivity analysis and a simpler fixed-value replacement approach that can be used to evaluate the influence of MNAR. Methods We reanalyzed attrition rates and predictors of differential attrition in a sample of 36 mHealth RCTs drawn from a recent meta-analysis of smartphone-based mental health interventions. We systematically evaluated the design features related to missingness and its handling. Data from a recent mHealth RCT were used to illustrate 2 sensitivity analysis approaches (pattern-mixture model and fixed-value replacement approach). Results Attrition in active conditions was, on average, roughly twice that of passive controls. Differential attrition was higher in larger studies and was associated with the use of MAR-based multiple imputation or maximum likelihood methods. Half of the studies (18/36, 50%) used these modern missing data techniques. None of the 36 mHealth RCTs reviewed conducted a sensitivity analysis to evaluate the possible consequences of data MNAR. A pattern-mixture model and fixed-value replacement sensitivity analysis approaches were introduced. Results from a recent mHealth RCT were shown to be robust to missing data, reflecting worse outcomes in missing versus nonmissing scores in some but not all scenarios. A review of such scenarios helps to qualify the observations of significant treatment effects. Conclusions MNAR data because of differential attrition are likely in mHealth RCTs using passive controls. Sensitivity analyses are recommended to allow researchers to assess the potential impact of MNAR on trial results.

Unmasking in an observational vaccine safety study: Using type 2 diabetes mellitus as an example

Vaccine ◽  
2015 ◽  
Vol 33 (46) ◽  
pp. 6224-6226 ◽  
Author(s):  
Bradley K. Ackerson ◽  
Lina S. Sy ◽  
Jeff Slezak ◽  
Chun R. Chao ◽  
Rulin C. Hechter ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Vaccine Safety ◽  
Safety Study

scholarly journals Data Missing Not at Random in Mobile Health Research: Assessment of the Problem and a Case for Sensitivity Analyses (Preprint)

2020 ◽  
Author(s):  
Simon B Goldberg ◽  
Daniel M Bolt ◽  
Richard J Davidson
Keyword(s):  
Sensitivity Analysis ◽  
Missing Data ◽  
Maximum Likelihood ◽  
Multiple Imputation ◽  
Mixture Model ◽  
Mobile Health ◽  
Sensitivity Analyses ◽  
Research Assessment ◽  
Missing Not At Random ◽  
Pattern Mixture Model

BACKGROUND Missing data are common in mobile health (mHealth) research. There has been little systematic investigation of how missingness is handled statistically in mHealth randomized controlled trials (RCTs). Although some missing data patterns (ie, missing at random [MAR]) may be adequately addressed using modern missing data methods such as multiple imputation and maximum likelihood techniques, these methods do not address bias when data are missing not at random (MNAR). It is typically not possible to determine whether the missing data are MAR. However, higher attrition in active (ie, intervention) versus passive (ie, waitlist or no treatment) conditions in mHealth RCTs raise a strong likelihood of MNAR, such as if active participants who benefit less from the intervention are more likely to drop out. OBJECTIVE This study aims to systematically evaluate differential attrition and methods used for handling missingness in a sample of mHealth RCTs comparing active and passive control conditions. We also aim to illustrate a modern model-based sensitivity analysis and a simpler fixed-value replacement approach that can be used to evaluate the influence of MNAR. METHODS We reanalyzed attrition rates and predictors of differential attrition in a sample of 36 mHealth RCTs drawn from a recent meta-analysis of smartphone-based mental health interventions. We systematically evaluated the design features related to missingness and its handling. Data from a recent mHealth RCT were used to illustrate 2 sensitivity analysis approaches (pattern-mixture model and fixed-value replacement approach). RESULTS Attrition in active conditions was, on average, roughly twice that of passive controls. Differential attrition was higher in larger studies and was associated with the use of MAR-based multiple imputation or maximum likelihood methods. Half of the studies (18/36, 50%) used these modern missing data techniques. None of the 36 mHealth RCTs reviewed conducted a sensitivity analysis to evaluate the possible consequences of data MNAR. A pattern-mixture model and fixed-value replacement sensitivity analysis approaches were introduced. Results from a recent mHealth RCT were shown to be robust to missing data, reflecting worse outcomes in missing versus nonmissing scores in some but not all scenarios. A review of such scenarios helps to qualify the observations of significant treatment effects. CONCLUSIONS MNAR data because of differential attrition are likely in mHealth RCTs using passive controls. Sensitivity analyses are recommended to allow researchers to assess the potential impact of MNAR on trial results.

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