Bias from outcome misclassification in immunization schedule safety research

Area of Science:

• Epidemiology
• Biostatistics
• Public Health

Background:

• Observational studies are recommended for childhood immunization schedule safety.
• Outcome misclassification can introduce bias and lead to incorrect inferences in these studies.

Purpose of the Study:

• To evaluate outcome positive predictive values (PPVs) as indicators of bias in exposure-outcome associations.
• To assess the effectiveness of quantitative bias analyses (QBA) for correcting bias in immunization safety research.

Main Methods:

• Simulations based on Vaccine Safety Datalink studies.
• Modeling of non-differential and differential outcome misclassification.
• Calculation of PPVs, relative risks (RR), Type 1 error, and QBA-corrected RRs.

Main Results:

• PPVs ranged from 34% to 98%.
• Non-differential misclassification showed bias toward the null, severity dependent on PPV.
• Differential misclassification led to poor PPV reflection of bias and high Type 1 error; QBA was generally effective in bias correction.

Conclusions:

• Outcome PPVs are poor indicators of bias in individual immunization schedule safety studies.
• QBA is a valuable tool for correcting misclassification bias in this research area.
• Support for the use of QBA in immunization schedule safety research is recommended.