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Jong-Tae Lee,¹ Ho Kim,² and Joel Schwartz³

¹Department of Preventive Medicine and Public Health, College of Medicine, Yonsei University, Seoul, Korea
²Department of Epidemiology and Biostatistics and Institute of Public Health, School of Public Health, Seoul National University, Seoul, Korea
³Environmental Epidemiology Program, Harvard School of Public Health, Boston, Massachusetts, USA

Abstract

The case-crossover design compares exposures during the period of time of failure with one or more periods when failure did not occur and evaluates the potential excess risk using conditional logistic regression. In this simulation study, we applied several control sampling approaches to control for confounding by various temporal patterns of an exposure variable and evaluated the usefulness of symmetric bidirectional control strategies. We simulated true relative risks (RRs ; true ß = 0.001) of deaths of 1.051 per 50-ppb increase of sulfur dioxide and included confounding by right- or left-skewed seasonal waves, linear long-term time trends, or a combination of both. The range of the estimated RRs from symmetric bidirectional control sampling approaches was 1.044~1.056 at either a long-term trend or any skewed seasonal wave of SO₂ levels, which indicated the bidirectional control sampling methods would successfully control confounding by design. The simulations with bidirectional sampling, however, show that biases may occur if waves are incomplete (20-43% underestimated RRs) . In conclusion, our simulations show that the symmetric bidirectional case-crossover design can substantially control for confounding by linear long-term trends and/or seasonality of an exposure variable by design as well. However, unidirectional control sampling would fail to control confounding by those variations of air pollution. Simulation results also show that even the bidirectional case-crossover design can be biased in a situation where the exposure variable shows incomplete cyclic waves, and therefore it cannot completely control for temporal confounding. Key words: air pollution, case-crossover designs, control sampling strategy, epidemiologic methods. Environ Health Perspect 108:1107-1111 (2000) [Online 1 November 2000].

http://ehpnet1.niehs.nih.gov/docs/2000/108p1107-1111lee/ abstract.html

Address correspondence to J-T. Lee, Department of Preventive Medicine and Public Health, College of Medicine, Yonsei University, Shinchon-Dong 134, Seodaemun-Gu, Seoul 120-752, Korea. Telephone: (822) 361-5357. Fax: (822) 392-0239. E-mail: jlee@yumc.yonsei.ac.kr

This work was financially supported by a G-7 Environmental Engineering Technology Development Project from the Department of Environment, Republic of Korea, and was also partially supported by Ministry of Health and Welfare, Republic of Korea (HMP-99-M-09-0007) .

Received 23 May 2000 ; accepted 10 July 2000.