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Stat Methods Med Res. 2018 Jun;27(6):1818-1829. doi: 10.1177/0962280216669744. Epub 2016 Sep 21.

Feasibility of reusing time-matched controls in an overlapping cohort.

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1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
2 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
3 Department of Mathematics and Statistics, La Trobe University, Victoria, Australia.
4 Department of Surgery, University of California, San Francisco, CA, USA.


The methods developed for secondary analysis of nested case-control data have been illustrated only in simplified settings in a common cohort and have not found their way into biostatistical practice. This paper demonstrates the feasibility of reusing prior nested case-control data in a realistic setting where a new outcome is available in an overlapping cohort where no new controls were gathered and where all data have been anonymised. Using basic information about the background cohort and sampling criteria, the new cases and prior data are "aligned" to identify the common underlying study base. With this study base, a Kaplan-Meier table of the prior outcome extracts the risk sets required to calculate the weights to assign to the controls to remove the sampling bias. A weighted Cox regression, implemented in standard statistical software, provides unbiased hazard ratios. Using the method to compare cases of contralateral breast cancer to available controls from a prior study of metastases, we identified a multifocal tumor as a risk factor that has not been reported previously. We examine the sensitivity of the method to an imperfect weighting scheme and discuss its merits and pitfalls to provide guidance for its use in medical research studies.


GLM weights; Kaplan–Meier type weights; Nested case-control; cost-efficiency; secondary analysis; weighted Cox regression


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