Immortal time is a span of cohort follow-up during which, because of exposure definition, the outcome under study could not occur. Bias from immortal time was first identified in the 1970s in epidemiology in the context of cohort studies of the survival benefit of heart transplantation. It recently resurfaced in pharmaco-epidemiology, with several observational studies reporting that various medications can be extremely effective at reducing morbidity and mortality. These studies, while using different cohort designs, all involved some form of immortal time and the corresponding bias. In this paper, the author describes various cohort study designs leading to this bias, quantifies its magnitude under different survival distributions, and illustrates it by using data from a cohort of lung cancer patients. The author shows that for time-based, event-based, and exposure-based cohort definitions, the bias in the rate ratio resulting from misclassified or excluded immortal time increases proportionately to the duration of immortal time. The bias is more pronounced with a decreasing hazard function for the outcome event, as illustrated with the Weibull distribution compared with a constant hazard from the exponential distribution. In conclusion, observational studies of drug benefit in which computerized databases are used must be designed and analyzed properly to avoid immortal time bias.

Immortal time in observational studies can bias the results in favour of the treatment group, but it is not difficult to identify and avoid

To determine the frequency of and risk factors for falls and injurious falls in the noninstitutionalized elderly, the authors conducted a follow-up study of 409 community-dwelling persons aged 65 years or more in west-central Montreal, Quebec, Canada, from May 1987 to October 1988. Following an initial at-home interview, each subject was telephoned every 4 weeks for 48 weeks for collection of data on falls experienced since the last contact. Each of the 12 follow-up interviews was completed by at least 90% of the subjects eligible for interview. Data were also collected in the follow-up interviews on time-varying exposures. Twenty-nine percent of the subjects fell during follow-up; 17.6% fell once, and 11.5% fell two or more times. The incidence rate for falls was 41.4 falls per 1,000 person-months. The majority of falls resulted in no injury or in minor injury only. Potential risk factors investigated included sociodemographic variables, physical activity, alcohol consumption, acute and chronic health problems, dizziness, mobility, and medications. Multivariate analyses showed that the following factors were statistically significantly associated with an increased rate of falls: dizziness (incidence rate ratio (IRR) = 2.0), frequent physical activity (IRR = 2.0), having days on which activities were limited because of a health problem (IRR = 1.8), having trouble walking 400 m (IRR = 1.6), and having trouble bending down (IRR = 1.4). Factors which were protective included diversity of physical activities (IRR = 0.6), daily alcohol consumption (IRR = 0.5), having days spent in bed because of a health problem (IRR = 0.5), and taking heart medication (IRR = 0.6). Risk factors for injurious falls were similar.