ACTIV trials: Lessons learned in trial design in the setting of an emergent pandemic.

Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally.

Leveraging information from secondary endpoints to enhance dynamic borrowing across subpopulations.

Randomized trials seek efficient treatment effect estimation within target populations, yet scientific interest often also centers on subpopulations. Although there are typically too few subjects within each subpopulation to efficiently estimate these subpopulation treatment effects, one can gain precision by borrowing strength across subpopulations, as is the case in a basket trial. While dynamic borrowing has been proposed as an efficient approach to estimating subpopulation treatment effects on primary endpoints, additional efficiency could be gained by leveraging the information found in secondary endpoints.

Impact of Baseline SARS-CoV-2 Load in Plasma and Upper Airways on the Incidence of Acute Extrapulmonary Complications of COVID-19: A Multicentric, Prospective, Cohort Study.

Background: Extrapulmonary complications (EPCs) are common in patients hospitalized for coronavirus disease 2019 (COVID-19), but data on their clinical consequences and association with viral replication and systemic viral dissemination are lacking.

Methods: Patients hospitalized for COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 (TICO) platform trial at 114 international sites between August 2020 and November 2021 were included in a prospective cohort study. We categorized EPCs into 39 event types within 9 categories and estimated their frequency through day 28 and their association with clinical outcomes through day 90.

Commentary on Chen et al. (2022): The need for continued methodological research on leveraging information in secondary endpoints for more efficient RCTs.

Chen et al. (2022) recently proposed a set of estimating equations that incorporate data from secondary endpoints to improve precision in parameter estimates related to a primary endpoint. We were motivated to translate their methodology to the context of randomized controlled trials to gain precision in treatment effect estimation using data from secondary endpoints.

Sodium-glucose co-transporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors on major liver outcomes in metabolic dysfunction-associated steatotic liver disease.

Aim: To compare the effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2is) with dipeptidyl peptidase-4 inhibitors (DPP4is) on major liver outcomes (MLO) in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD).

Materials And Methods: We included adult patients with T2D and MASLD, using metformin without specific liver conditions or surgeries, from the Merative MarketScan database. Patients initiating SGLT2is or DPP4is from 1 January 2014 to 31 December 2022 were identified.