Replication of randomized clinical trial results using real-world data: paving the way for effectiveness decisions.

The FDA is preparing guidance about using real-world evidence (RWE) to support decisions about product effectiveness. Several ongoing efforts aim to replicate randomized clinical trial (RCT) results using RWE with the intent of identifying circumstances and methods that provide valid evidence of drug effects. Lack of agreement may not be due to faulty methods but rather to the challenges with emulating RCTs, differences in healthcare settings and patient populations, differences in effect measures and data analysis, bias, and/or the efficacy-effectiveness gap. In fact, for some decisions, RWE may lead to better understanding of how treatments work in usual care settings than a more constrained view from RCTs. Efforts to reconcile the role and opportunities for generating complementary evidence from RWE and RCTs will advance regulatory science.

Development of the influence, motivation, and patient activation in diabetes (IMPACT-D™) measure.

AIMS: We sought to create a new research and clinical instrument -the Influence and Motivation for Patient ACTivation in Diabetes care (IMPACT-D™) - to measure the degree to which patients with type 2 diabetes (T2DM) value health and believe they can influence it. METHODS: Candidate items were generated via a literature review, expert opinion, and qualitative interviews and focus groups with T2DM patients in Chicago, IL and Chapel Hill, NC. Psychometric testing guided by item response theory was conducted among an online panel of 500 English-speaking adults with T2DM. Differential item functioning analyses evaluated item performance across key participant characteristics. To determine construct validity, IMPACT-D™ scores were compared to other general measures of personality and patient activation. A second study among 300 patients recruited from two internal medicine clinics further assessed associations between the IMPACT-D™ and health outcomes. Cognitive interviews confirmed patient understanding of IMPACT-D™ items and instructions. RESULTS: Exploratory factor analyses revealed a single-factor solution that included 6 items. The IMPACT-D™ demonstrated adequate reliability (α = 0.72) and moderate construct validity with patient activation (r = 0.51, p < 0.001) and personality-conscientiousness subscales (r = 0.29, p < 0.001). Higher scores on the IMPACT-D™ were associated with better physical health (r = 0.17, p = 0.003) and lower severity of depressive (r = -0.35, p < 0.001) and anxiety (r = -0.28, p < 0.001) symptoms. There were no significant differences by blood pressure (r = -0.0021, p = 0.9) or haemoglobin A1c (r = -0.069p = 0.2). CONCLUSIONS: The IMPACT-D holds potential for use in both clinical care and research applications. Future studies should evaluate how to best operationalize its use for both settings.