Alternative Approaches to Analytical Designs in Occupational Injury Epidemiology Murray A. Mittleman, MD , DrPH , 1,2 * George Maldonado, PhD 3 Susan G. Gerberich, PhD 3 Gordon S. Smith, MB, ChB, MPH 4 and Gary S. Sorock, PhD 5 In this paper, we discuss the theoretical framework upon which observational studies of occupational injuries are based. Following a general description of how causal effects are estimated, the challenges faced by researchers working in this area are outlined, with an emphasis on case-control studies. These challenges include defining the at-risk period for workers whose tasks change over time and whose hazard period may be very brief, evaluating the underreporting of both exposures and injuries, and considering the effects of multiple injuries per individual on study design and data analysis. We review both the theoretical and practical considerations in the design and conduct of traditional case-control studies, based on the collection of individual level data, as well as other approaches, such as using information culled from administrative and descriptive databases, and case-control studies in which the plant or work site is the unit of analysis. The case-crossover design is also reviewed and its utility for reducing confounding due to differences between individuals by self- matching is highlighted. While this design has not yet been applied to the work setting, its potential for increasing our understanding of the causes of acute-onset occupational injuries seems promising. Finally, a variety of hybrid designs are discussed, including combinations of case-control, case-crossover, and cohort designs. Am. J. Ind. Med. 32:129–141, 1997. r 1997 Wiley-Liss, Inc. KEY WORDS: injury; occupational; methodology; case control; case crossover INTRODUCTION Many occupational injuries have an acute onset precipi- tated by transient changes in the workplace environment. The etiology of such injuries is almost always multifactorial, involving many component causes [Rothman, 1976]. Some of these component causes are present for a relatively long time, while others are transient, with the worker exposed only intermittently. It is the study of these intermittent exposures, or triggers, that is the primary focus of this paper. In this paper, we describe the general framework upon which observational studies of occupational injuries are based. The theoretical basis for these studies is described with particular emphasis on the special challenges faced by scientists working in this area. To illustrate the approach, we describe both theoretical and practical considerations in the design and conduct of traditional case-control studies. These studies use a variety of different approaches including the collection of individual level data, information culled from administrative and descriptive databases, and studies in which the plant or work site is the unit of analysis. In addition, we describe the application of the case-crossover design, which is theoretically related to case-control studies, but uses self-matching to help reduce confounding due to differences between individuals. Finally, a variety of hybrid 1 Department of Epidemiology, Harvard School of Public Health, Boston, MA 2 Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 3 Division of Environmental and Occupational Health, University of Minnesota School of Public Health, Minneapolis, MN 4 Center for Injury Research and Policy, Johns Hopkins University School of Public Health, Baltimore, MD 5 Liberty Mutual Research Center for Safety and Health, Hopkinton, MA * Correspondence to: Murray A. Mittleman, M.D., Cardiovascular Division, Beth Israel Deaconess Medical Center, 1 Autumn Street, Boston, MA 02215; E-mail: mitm@episun1.harvard.edu Accepted 31 December 1996 AMERICAN JOURNAL OF INDUSTRIAL MEDICINE 32:129–141 (1997) r 1997 Wiley-Liss, Inc.