Lessons Learned from National Heart, Lung, and Blood Institute Covid-19 Clinical Trials.

AbstractIn response to the Covid-19 pandemic, the National Heart, Lung, and Blood Institute launched five multisite clinical trials testing candidate host tissue-directed medical interventions to hasten recovery, improve function, and reduce morbidity and mortality. Speed, flexibility, and collaboration were essential. This article from the Steering and Executive committees describes the Collaborating Network of Networks for Evaluating Covid-19 and Therapeutic Strategies (CONNECTS) research program that enrolled 6690 participants and evaluated 18 intervention strategies using 10 molecular agents across the care continuum (outpatient, inpatient, and post discharge), and reports lessons learned from this initiative.

Assessment of North American Clinical Research Site Performance During the Start-up of Large Cardiovascular Clinical Trials.

Importance: Randomized clinical trials (RCTs) are critical in advancing patient care, yet conducting such large-scale trials requires tremendous resources and coordination. Clinical site start-up performance metrics can provide insight into opportunities for improved trial efficiency but have not been well described.

Objective: To measure the start-up time needed to reach prespecified milestones across sites in large cardiovascular RCTs in North America and to evaluate how these metrics vary by time and type of regulatory review process.

The use of electronic health records for recruitment in clinical trials: a mixed methods analysis of the Harmony Outcomes Electronic Health Record Ancillary Study.

Background: The electronic health record (EHR) contains a wealth of clinical data that may be used to streamline the identification of potential clinical trial participants. However, there is little empirical information on site-level facilitators of and barriers to optimal use of EHR systems with respect to trial recruitment.

Methods: We conducted qualitative focus groups and quantitative surveys as part of the EHR Ancillary Study, which is being conducted alongside the multicenter, global, Harmony Outcomes Trial comparing albiglutide to standard care for the prevention of cardiovascular events in type 2 diabetes.

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.

Background: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy.

Methods: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis.

Rationale and Design of the Aspirin Dosing-A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) Trial.

Importance: Determining the right dosage of aspirin for the secondary prevention treatment of atherosclerotic cardiovascular disease (ASCVD) remains an unanswered and critical question.

Objective: To report the rationale and design for a randomized clinical trial to determine the optimal dosage of aspirin to be used for secondary prevention of ASCVD, using an innovative research method.

Design, Setting, And Participants: This pragmatic, open-label, patient-centered, randomized clinical trial is being conducted in 15 000 patients within the National Patient-Centered Clinical Research Network (PCORnet), a distributed research network of partners including clinical research networks, health plan research networks, and patient-powered research networks across the United States.