User-only design to assess drug effectiveness in clinical practice: application to bisphosphonates and secondary prevention of fractures

Purpose: Different strategies applicable to control for confounding by indication in observational studies were compared in a large population-based study regarding the effect of bisphosphonates (BPs) for secondary prevention of fractures. Methods: The cohort was drawn from healthcare utilization databases of 13 Italian territorial units. Patients aged 55years or more who were hospitalized for fracture during 2003-2005 entered into the cohort. A nested case-control design was used to compare BPs use in cohort members who did (cases) and who did not experience (controls) a new fracture until 2007 (outcome). Three designs were employed: conventional-matching (D1), propensity score-matching (D2), and user-only (D3) designs. They differed for (i) cohort composition, restricted to patients who received BPs straight after cohort entry (D3); (ii) using propensity score for case-control matching (D2); and (iii) compared groups of BPs users versus no users (D1 and D2) and long-term versus short-term users (D3). Results: Bisphosphonate users had odds ratios (95% confidence interval) of 1.20 (1.01 to 1.44) and 0.95 (0.74 to 1.24) by applying D1 and D2 designs, respectively. Statistical evidence that long-term BPs use protects the outcome onset with respect to short-term use was observed for user-only design (D3) being the corresponding odds ratio (95% confidence interval) 0.64 (0.44 to 0.93). Conclusions: User-only design yielded closer results to those seen in RCTs. This approach is one possible strategy to account for confounding by indication. © 2014 John Wiley & Sons, Ltd.