The regulatory and financial requirements of traditional trials hinder the ability of clinicians and researchers to adapt quickly, test multiple therapies simultaneously, collaborate across care areas, and expand trial access to patients outside of academic tertiary centers. 2 (SARS-CoV-2) infection. The pandemic required health systems Tadalafil to rapidly adopt new therapies and promote social and health equity [1]. Monoclonal antibody (mAb) treatment is associated with decreased hospitalization and death in outpatients with mild to moderate coronavirus disease 2019 (COVID-19) [[2], [3], [4], [5]]. Outpatient treatments that limit progression to severe disease are of vital importance to optimise patient outcomes and public health. Monoclonal antibodies bind to and neutralize SARS-CoV-2, blocking entry of the virus into human cells. A form of passive immunity, mAb are most effective if given early after SARS-CoV-2 infection [2,3]. Randomized, clinical trials in patients with mild to moderate COVID-19 demonstrated reductions in hospitalizations and deaths with mAb treatment compared to placebo [2,3]. Subsequently, the United States Food and Drug Administration (US FDA) issued Emergency Use Authorizations (EUA) for bamlanivimab, bamlanivimab and etesevimab, casirivimab and imdevimab, and sotrovimab Tadalafil for use within 10?days of symptom onset in outpatients with risk factor(s) for progression to severe disease. 2.?Do we need an adaptive platform trial to evaluate monoclonal antibody treatment? There are many unanswered questions about mAb treatment. First, the use of mAb therapy Tadalafil remains low. Is this due to patient access GP3A barriers, operational challenges with outpatient infusions, limited awareness of efficacy data among referring clinicians, supply chain issues, or a combination of reasons? [[6], [7], [8]] Second, the published clinical trial data generated hypotheses regarding the optimal patient population for treatment, but many seek added evidence to inform mAb deployment, especially when resources are scarce. Third, while other platform trials are evaluating multiple mAb therapies in various settings (e.g., RECOVERY, ACTIV-2, ACTIV-3), there are no outpatient trials directly comparing all 3 EUA-available mAbs. Fourth, the Tadalafil spread of SARS-CoV-2 variants may impact antibody and vaccine effectiveness, and the emergence of mAb-resistant SARS-CoV-2 variants is a major concern [9]. The EUA for bamlanivimab monotherapy was revoked due to increased frequency of resistant variants and concern of decreased bamlanivimab monotherapy efficacy in this setting, and bamlanivimab and etesevimab distribution was temporarily paused and then resumed based on changing prevalence of variants of concern [10]. An adaptive platform trial could evaluate all available mAbs across subgroups of patients and generate answers to pivotal and evolving clinical questions in a rapid fashion to address these knowledge gaps. Collecting data quickly, and with rigor, would enable clinicians to rapidly adapt to the changing therapeutics landscape and pathogen evolution. 3.?A culture of learning while doing When confronted with complex patients, clinicians often perceive a conflict between the need to learn (i.e., randomize patients into clinical trials) versus do something (i.e., provide a therapeutic agent that may or may not be helpful or harmful) [11]. Traditionally, research efforts seek to create insights using highly structured settings with careful conditions to limit threats to causal inference. This approach is often costly, slow, and it may not resemble how the intervention will be used in practice. Such studies are often performed in larger hospitals with existing research infrastructure, limiting access of most patients to new treatment options and hindering the external validity of the results. We propose shifting from the traditional research model into one of care with ongoing discovery C providing new therapies to each patient while simultaneously advancing standard practice C that is learning doing [11]. In this model, we optimise the trade-off between learning and doing where little to no sacrifice is made to the conditions of high-quality research yet priority care is ensured to all patients within the system. Indeed, this approach expands the reach of robust learning while doing to many hospitals and healthcare settings often excluded from randomized trials. During the pandemic, our large, integrated healthcare system in the US approached treatment of patients with COVID-19 with two goals: i.) enhancing access to treatment, regardless of geography and socioeconomic status, and ii.) coordinating treatment through an integrated, adaptive platform trial. To accomplish these goals, clinician engagement was paramount. In addition, success required leadership investment, a robust data and analytics infrastructure, and therapeutics oversight via system-level treatment guidelines with local collaboration. 4.?Preliminary.