Design issues for conducting cost-effectiveness analyses alongside clinical trials

In response to rising demands for timely economic data on new medical techn ologies, cost-effectiveness studies are increasingly being conducted alongs ide clinical trials. Because of the historical differences in perspective a nd methods between cost-effectiveness studies and clinical trials, the desi gn phase of these hybrid trials requires special consideration. Cost-effect iveness studies require more comprehensive evaluations of outcomes than the endpoints typically measured in clinical trials. Often, these comprehensiv e outcome measures (such as quality of life) prove useful for interpreting the other endpoints measured in the trial, as well as for estimating the co st-effectiveness of the intervention. In this manuscript, we discuss severa l aspects related to the design of joint clinical/economic trials, includin g study perspective, hypothesis testing, sample size estimation, and method s for collecting cost and outcome data. We also discuss issues that may lim it the external validity of the cost-effectiveness results of these trials. Many potential threats to external validity can be successfully addressed if they are identified and accounted for in the design phase of the study.