The effect of different sensitivity, specificity and cause-specific mortality fractions on the estimation of differences in cause-specific mortality rates in children from studies using verbal autopsies

Background. Verbal autopsies (VA) are increasingly being used in developing countries to determine causes of death, but little attention is generally given to the misclassification effects of the VA. This paper considers the effect of misclassification on the estimation of differences in cause-specific mortality rates between two populations, Methods. The bias in the percentage difference in cause-specific mortality between two populations has been explored under two different models: i) assuming that mortality from all other causes does not differ between the two populations; ii) allowing for a difference in mortality from all other causes. The bias is described in terms of the sensitivity and specificity of the VA diagnosis and the proportion of mortality due to the cause of interest. Methods for adjustment of sample size and adjusting the estimate of effect are also explored. Results. The results are illustrated for a range of plausible values for these parameters. The bias is more extreme as both sensitivity and specificity fall, and is particularly affected even by a small loss of specificity. The bias also increases as the proportion of all deaths due to the cause of interest decreases, and is affected by the size of the true change in mortality due to the cause of interest relative to the change in mortality from other causes. Calculations from existing data suggest prohibitively large sample sizes may often be required to detect important differences in cause-specific mortality rates in studies using existing VA. Conclusions. Highly specific VA tools are needed before observed differences in cause-specific mortality can be interpreted. Loss of power due to misclassification may obscure real differences in cause-specific mortality.