Combination Therapy Use and Associated Events in Clinical Practice Following Dissemination of Trial Findings: A De-Implementation Study Using Interrupted Time Series Analysis.

Purpose: It takes 17 years, on average, for trial results to be implemented into practice. Using data from the Department of Veterans Affairs (VA), this study assessed the potential impact on clinical practice of the dissemination of findings from a randomized, controlled trial reporting harm with the use of combination therapy. Communication between research and VA Pharmacy Benefits Management Services (PBM)  provided the impetus for communication from the PBM about the findings of the trial in accordance with policy.

Methods: In this de-implementation study, interrupted time series analysis was used for assessing prescribing patterns and adverse clinical events before and after the dissemination of the trial findings. The de-implementation strategy was multicomponent and multilevel. Strategies were aligned with categories outlined in the Expert Recommendations for Implementing Change: train and educate stakeholders, use evaluative and iterative strategies, develop stakeholder inter-relationships, change infrastructure, provide interactive assistance, and engage consumers. VA patients with type 2 diabetes mellitus, chronic kidney disease stages 1 to 3, and a moderate or severe albuminuria who received care between July 2008 and November 2017 were included. Patients were subgrouped according to treatment with an angiotensin-converting enzyme inhibitor + angiotensin receptor blocker. The primary end point was the prevalence of combination therapy use. Secondary end points were the incidences of acute kidney injury and hyperkalemia.

Findings: This study followed 712,245 patients, 9297 of whom used combination therapy. Data were available from 428,535 and 283,710 patients pre- and post-intervention, respectively; among these, 8324 and 973 patients used combination therapy, the median ages were 66 and 68 years, and 96.92% and 98.82% were men. One month following communication from the PBM, the reductions in combination therapy users, acute kidney injury events, and hyperkalemia were 331.94 (95% CI, 500.27-163.32), 36.58% (95% CI, 31.90%-41.95%), and 25.49% (95% CI, 14.17%-36.07%) per 100,000 patients per month, respectively (all, P < 0.001), whereas before the communication, these changes were +14.84 (95% CI, 10.27-19.42), -3.46% (95% CI, 3.18-3.74), and -3.27% (95% CI, 2.66%-3.87%) (all, P < 0.001).

Implications: The apparent speed and impact of the implementation of changes resulting from the dissemination of trial findings into VA clinical practice are encouraging. The speed of implementation was much faster than average for health care providers in the United States. Established communications between research and clinical practice, as well as established policy and communications between PBM and clinical practice, may be a model for other health care organizations.