OBJECTIVES:  When the course of therapy is long—particularly if treatment is expensive and/or associated with significant side effects—standards of care often include an early assessment of treatment effectiveness.  If this “mid-therapy” assessment is positive, the patient is indicated to continue treatment; if negative, treatment is discontinued.  Using expected utility theory, we demonstrated previously that the availability and timing of such assessments can serve as a mechanism by which policymakers can influence patients’ treatment initiation decisions.  Here, we demonstrate the interaction between the timing of mid-therapy assessment, willingness to initiate (WTI) therapy, and treatment success using an application to hepatitis C virus (HCV) treatment. METHODS:  A simple decision tree framework was used to compare the number of treatment successes for a hypothetical population of 1000 patients when initial mid-therapy assessments are conducted at 2-weeks (wks), 4-wks, and the current standard of care, 12-wks, with and without considerations of WTI.  Test performance characteristics were based on published reports.  Hypothetical treatment initiation probabilities were derived from the expected burden of side effects and the prior probability of treatment success associated with each assessment considered.    RESULTS:  Ignoring WTI, the 12-wk strategy is associated with the most expected treatment successes (471 vs 439 and 406 for 4- and 2-wk strategies, respectively).  When WTI was inversely proportionate to expected side effect burden, the 2-wk strategy produced more treatment successes (222 vs. 190 and 141 for 4- and 12-wk strategies, respectively).  If WTI for the 2-wk assessment exceeded 115% of the WTI for 12-wks, the 2-wk strategy dominated. CONCLUSIONS:  The optimal timing of a mid-therapy assessment depends on test performance and the relative importance of side effects and treatment success to patients.  Understanding patients’ treatment preferences can help decision makers design treatment guidelines that have the greatest potential to reach public health goals.