THE VALUE OF RE-USING PRIOR NESTED CASE-CONTROL DATA IN NEW STUDIES WITH DIFFERENT OUTCOME

Abstract

Background: As nested case-control (NCC) design is becoming more popularly used in epidemiological and genetic studies, the need of methods that allows the re-use of NCC data is greater than ever. However, due to the incidence density sampling, re-using data from NCC studies for analysis of secondary outcomes is not straightforward. Several recent methodological developments have opened the possibility for prior NCC data to be used as complement controls in a current study thereby improving study efficiency. However, practical guidelines on the effectiveness of prior data relative to newly sampled subjects and the potential power gains are still lacking. Objective: The goal of this thesis is to investigate how the precision of the variance estimates of the hazard ratios varies with the study size and number of controls per case when we re-use prior nested case-control (NCC) data to supplement a new NCC study in different simulation settings, such as different levels of overlaps in matching variables. We want to demonstrate the feasibility and efficiency of conducting a new study using only incident cases and prior data and to apply the method to two different sets of real data. In addition, we would like to give some practical guidance regarding the possible power gain in re-using prior NCC data. Methods: We simulate the study data of one prior and one current or new NCC studies in the same cohort and estimate hazard ratios using weighted log-likelihood with the weight given by the inverse of the probability of inclusion in either study. We also express the contribution of prior controls to the new study in terms of ¿effective number of controls¿. Based on this effective number of controls idea, we show how researchers can assess the potential power gains from re-using prior NCC data. We apply the method to analyses of anorexia and contra-lateral breast cancer in the Swedish population and show how power calculations can be done using publicly available software. Results and Conclusion: We have demonstrated the feasibility of conducting a new study using only incident cases and prior data. The combined analysis of new and prior data gives unbiased estimates of hazard ratio, with efficiency depending on study size and number of controls per case in the prior study. We have also investigated in detail the impact of the number of controls per case in the prior and current studies on the relative efficiency when re-using prior subjects in a nested case-control study. For a fixed number of controls in the prior study, the relative reduction in the variance decreases as we increase the number of controls in the new study. The ability to re-use NCC data offers researchers several cost-saving strategies when designing a new study. This work has important applications in all areas of epidemiology but especially in genetic and molecular epidemiology, to make optimal use of costly exposure measurements.