The use of patient-reported outcomes (PRO) within comparative effectiveness research: implications for clinical practice and health care policy.

BACKGROUND: The goal of comparative effectiveness research (CER) is to explain the differential benefits and harms of alternate methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. To inform decision making, information from the patient's perspective that reflects outcomes that patients care about are needed and can be collected rigorously using appropriate patient-reported outcomes (PRO). It can be challenging to select the most appropriate PRO measure given the proliferation of such questionnaires over the past 20 years. OBJECTIVE: In this paper, we discuss the value of PROs within CER, types of measures that are likely to be useful in the CER context, PRO instrument selection, and key challenges associated with using PROs in CER. METHODS: We delineate important considerations for defining the CER context, selecting the appropriate measures, and for the analysis and interpretation of PRO data. Emerging changes that may facilitate CER using PROs as an outcome are also reviewed including implementation of electronic and personal health records, hospital and population-based registries, and the use of PROs in national monitoring initiatives. The potential benefits of linking the information derived from PRO endpoints in CER to decision making is also reviewed. CONCLUSIONS: The recommendations presented for incorporating PROs in CER are intended to provide a guide to researchers, clinicians, and policy makers to ensure that information derived from PROs is applicable and interpretable for a given CER context. In turn, CER will provide information that is necessary for clinicians, patients, and families to make informed care decisions.

Use of effect size to determine optimal dose of duloxetine in major depressive disorder.

OBJECTIVE: At effective doses, patients with major depressive disorder (MDD) treated with duloxetine have been found to experience significant symptom improvement as measured by HAMD(17) total score. In addition, duloxetine-treated patients have significantly higher remission and response rates compared with placebo. The objective of this analysis is to determine the optimal dose of duloxetine in MDD. MATERIALS AND METHODS: Effect size for duloxetine 40mg, 60mg, 80mg, and 120mg per day were estimated using all 6 acute phase III clinical trials in patients with MDD. The tolerability of duloxetine 40mg, 60mg, 80mg, and 120mg were evaluated using pooled data from the 6 studies. The primary efficacy measure in all trials was the HAMD(17) total score, from which were determined the effect size for HAMD(17) change scores, response rates (50% reduction from baseline to endpoint), and remission rates (HAMD(17) total score < or =7). RESULTS: A total of 1619 randomized patients were included in these studies, of which 632 were treated with placebo; 177 with duloxetine 40mg/day; 251 with 60mg/day; 363 with 80mg/day; and 196 with 120mg/day. An evaluation of increments in effect size between doses consistently showed that the most notable gain in effect size for efficacy was the 40-60mg/day dosage range. All dosages from 60 to 120mg were effective. The tolerability assessment indicated duloxetine at 40-120mg/day is well tolerated. Furthermore, the initial doses of 40-80mg/day were found to have comparable tolerability. CONCLUSIONS: The effect size analyses demonstrate that duloxetine 40mg has minimum efficacy, and that duloxetine 60-120mg/day is effective in the treatment of patients with MDD. An initial dose less than 60mg/day might provide better tolerability for some patients diagnosed with MDD.