Statistical inference in matched case–control studies of recurrent events

Author:

Cheung Yin Bun123ORCID,Ma Xiangmei2,Lam K F24,Li Jialiang5,Yung Chee Fu6,Milligan Paul7,Mackenzie Grant891011

Affiliation:

1. Signature Programme in Health Services & Systems Research, Duke-NUS Medical School, Singapore 169857

2. Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore 169856

3. Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere 33520, Finland

4. Department of Statistics and Actuarial Science, University of Hong Kong, Hong Kong, China

5. Department of Statistics and Applied Probability, National University of Singapore, Singapore 117546

6. Infectious Disease Service, KK Women’s and Children’s Hospital, Singapore 229899

7. Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK

8. Medical Research Council Unit The Gambia at London School of Hygiene & Tropical Medicine, PO Box 273, Fajara, The Gambia

9. New Vaccines Group, Murdoch Children’s Research Institute, Melbourne, Victoria 3052, Australia

10. Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK

11. Department of Paediatrics, University of Melbourne, Parkville, VIC 3010, Australia

Abstract

Abstract Background The concurrent sampling design was developed for case–control studies of recurrent events. It involves matching for time. Standard conditional logistic-regression (CLR) analysis ignores the dependence among recurrent events. Existing methods for clustered observations for CLR do not fit the complex data structure arising from the concurrent sampling design. Methods We propose to break the matches, apply unconditional logistic regression with adjustment for time in quintiles and residual time within each quintile, and use a robust standard error for observations clustered within persons. We conducted extensive simulation to evaluate this approach and compared it with methods based on CLR. We analysed data from a study of childhood pneumonia to illustrate the methods. Results The proposed method and CLR methods gave very similar point estimates of association and showed little bias. The proposed method produced confidence intervals that achieved the target level of coverage probability, whereas the CLR methods did not, except when disease incidence was low. Conclusions The proposed method is suitable for the analysis of case–control studies with recurrent events.

Funder

National Medical Research Council

Gavi Alliance’s PneumoADIP—Bloomberg School of Public Health

Johns Hopkins University

Bill & Melinda Gates Foundation

MRC

Publisher

Oxford University Press (OUP)

Subject

General Medicine,Epidemiology

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