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

• Published in: Clinical therapeutics 2024-01, Vol.46 (1), p.40-49
• Main Authors: Campbell, Heather M., Murata, Allison E., Henrie, Adam M., Conner, Todd A.
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - epidemiology; Aged; Angiotensin; Angiotensin-Converting Enzyme Inhibitors; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Clinical medicine; Combination therapy; Communication; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - drug therapy; Directors; Double-blind studies; Drug dosages; Drug stores; Enzyme inhibitors; Executives; Female; Health care; Humans; Hyperkalemia; Hyperkalemia - chemically induced; Hyperkalemia - complications; Hyperkalemia - epidemiology; Implementation Study; Injury prevention; Interrupted Time Series Analysis; Iterative methods; Kidney diseases; Kidneys; Leadership; Male; Management services; Patient Safety; Patients; Peptidyl-dipeptidase A; Pharmacovigilance; Pharmacy; Practice Patterns, Physicians; Product safety; Therapy; Time series; United States
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2023.10.009

•It seems VA implemented findings into practice immediately after trial showed harm.•Overall, there was a 30% relative decrease in combination therapy use at six months.•We observed a sustained reduction in combination therapy for eighteen months.•The same pattern emerged within each subgroup.•VA communication policies may be a model for other healthcare organizations. : It takes 17 years, on average, for trial results to be implemented in practice. Using data from the Department of Veterans Affairs (VA), the purpose was to assess the potential impact of a randomized controlled trial's findings of combination therapy causing excess harm in clinical practice; communication between research and VA Pharmacy Benefits Management (PBM) provided the impetus for PBM's communication about the trial's findings with clinical practice in accordance with policy. : This de-implementation study used interrupted time series analysis to assess prescribing patterns and adverse clinical events before and after dissemination of trial findings. The de-implementation strategy was multicomponent and multilevel. Strategies aligned with the following categories as 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 1-3, and moderately- or severely- increased albuminuria who received care between July 2008 and November 2017 were included. Patients were subgrouped if they received angiotensin-converting enzyme inhibitor (ACEI)- angiotensin receptor blocker (ARB) combination therapy. The primary outcome was prevalence of combination therapy use. Secondary outcomes were incidences of acute kidney injury (AKI) and hyperkalemia. : This study followed 712,245 patients, 9,297 of whom used combination therapy. Pre- and post- intervention, there were 428,535 and 283,710 patients, 8,324 and 973 patients who used combination therapy, a median age of 66 and 68 years, and 96.92% and 98.82% who were male, respectively. One month following PBM's communication about the trial's findings there were 331.94 (95% CI: 500.27, 163.32, p