The Impact of Regression to the Mean on Economic Evaluation in Quasi-Experimental Pre-Post Studies: The Example of Total Knee Replacement Using Data from the Osteoarthritis Initiative.

Many treatments are evaluated using quasi-experimental pre-post studies susceptible to regression to the mean (RTM). Ignoring RTM could bias the economic evaluation. We investigated this issue using the contemporary example of total knee replacement (TKR), a common treatment for end-stage osteoarthritis of the knee. Data (n = 4796) were obtained from the Osteoarthritis Initiative database, a longitudinal observational study of osteoarthritis. TKR patients (n = 184) were matched to non-TKR patients, using propensity score matching on the predicted hazard of TKR and exact matching on osteoarthritis severity and health-related quality of life (HrQoL). The economic evaluation using the matched control group was compared to the standard method of using the pre-surgery score as the control. Matched controls were identified for 56% of the primary TKRs. The matched control HrQoL trajectory showed evidence of RTM accounting for a third of the estimated QALY gains from surgery using the pre-surgery HrQoL as the control. Incorporating RTM into the economic evaluation significantly reduced the estimated cost effectiveness of TKR and increased the uncertainty. A generalized ICER bias correction factor was derived to account for RTM in cost-effectiveness analysis. RTM should be considered in economic evaluations based on quasi-experimental pre-post studies.