title: Evaluation of exposure-specific risks from two independent samples: a simulation study.
abstract: BACKGROUND
  Previous studies have proposed a simple product-based estimator for calculating exposure-specific risks (ESR), but the methodology has not been rigorously evaluated. The goal of our study was to evaluate the existing methodology for calculating the ESR, propose an improved point estimator, and propose variance estimates that will allow the calculation of confidence intervals (CIs).
  
  
  METHODS
  We conducted a simulation study to test the performance of two estimators and their associated confidence intervals: 1) current (simple product-based estimator) and 2) proposed revision (revised product-based estimator). The first method for ESR estimation was based on multiplying a relative risk (RR) of disease given a certain exposure by an overall risk of disease. The second method, which is proposed in this paper, was based on estimates of the risk of disease in the unexposed. We then multiply the updated risk by the RR to get the revised product-based estimator. A log-based variance was calculated for both estimators. Also, a binomial-based variance was calculated for the revised product-based estimator. 95% CIs were calculated based on these variance estimates. Accuracy of point estimators was evaluated by comparing observed relative bias (percent deviation from the true estimate). Interval estimators were evaluated by coverage probabilities and expected length of the 95% CI, given coverage. We evaluated these estimators across a wide range of exposure probabilities, disease probabilities, relative risks, and sample sizes.
  
  
  RESULTS
  We observed more bias and lower coverage probability when using the existing methodology. The revised product-based point estimator exhibited little observed relative bias (max: 4.0%) compared to the simple product-based estimator (max: 93.9%). Because the simple product-based estimator was biased, 95% CIs around this estimate exhibited small coverage probabilities. The 95% CI around the revised product-based estimator from the log-based variance provided better coverage in most situations.
  
  
  CONCLUSIONS
  The currently accepted simple product-based method was only a reasonable approach when the exposure probability is small (< 0.05) and the RR is ≤ 3.0. The revised product-based estimator provides much improved accuracy.
authors.affiliation: Department of Orthopedic Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. wreichmann@partners.org
authors.forename: William M
authors.initials: WM
authors.lastname: Reichmann
authors.forename: David
authors.initials: D
authors.lastname: Gagnon
authors.forename: C Robert
authors.initials: CR
authors.lastname: Horsburgh
authors.forename: Elena
authors.initials: E
authors.lastname: Losina
mesh_terms: D015982:Bias; D016001:Confidence Intervals; D006801:Humans; D015233:Models, Statistical; D016017:Odds Ratio; D011336:Probability; D012306:Risk; D018570:Risk Assessment; D012494:Sampling Studies