Inverse probability weighted estimating equations for randomized trials in transfusion medicine

Thrombocytopenia is a condition characterized by extremely low platelet counts, which puts patients at elevated risk of morbidity and mortality because of bleeding. Trials in transfusion medicine are routinely designed to assess the effect of experimental platelet products on patients' platelet counts. In such trials, patients may receive multiple platelet transfusions over a predefined period of treatment, and a response is available from each such administration. The resulting data comprised multiple responses per patient, and although it is natural to want to use this data in testing for treatment effects, naive analyses of the multiple responses can yield biased estimates of the probability of response and associated treatment effects. These biases arise because only subsets of the patients randomized contribute response data on the second and subsequent administrations of therapy and the balance between treatment groups with respect to potential confounding factors is lost. We discuss the design and analysis issues involved in this setting and make recommendations for the design of future platelet transfusion trials.