Malaria is a major public health problem. An effective vaccine against malaria is actively being sought. We formulate a potential outcomes definition of the efficacy of a malaria vaccine for preventing fever. A challenge in estimating this efficacy is that there is no sure way to determine whether a fever was caused by malaria. We study the properties of two approaches for estimating efficacy: (1) use a deterministic case definition of a malaria caused fever as the conjunction of fever and parasite density above a certain cutoff; (2) use a probabilistic case definition in which the probability that each fever was caused by malaria is estimated. We compare these approaches in a simulation study and find that both approaches can potentially have large biases. We suggest a strategy for choosing an estimator based on the investigator's prior knowledge about the area in which the trial is being conducted and the range of vaccine efficacies over which the investigator would like the estimator to have good properties.
Keywords: attributable fraction; case definition; causal inference.