Platform adaptive trial of novel antivirals for early treatment of COVID-19 In the community (PANORAMIC): protocol for a randomised, controlled, open-label, adaptive platform trial of community novel antiviral treatment of COVID-19 in people at increased risk of more severe disease.

INTRODUCTION: There is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. METHODS AND ANALYSIS: PANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses. The first two interventions to be evaluated are molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid). ELIGIBILITY CRITERIA: community-dwelling within 5 days of onset of symptomatic COVID-19 (confirmed by PCR or lateral flow test), and either (1) aged 50 years and over, or (2) aged 18-49 years with qualifying comorbidities. Registration occurs via the trial website and by telephone. Recruitment occurs remotely through the central trial team, or in person through clinical sites. Participants are randomised to receive either usual care or a trial drug plus usual care. Outcomes are collected via a participant-completed daily electronic symptom diary for 28 days post randomisation. Participants and/or their Trial Partner are contacted by the research team after days 7, 14 and 28 if the diary is not completed, or if the participant is unable to access the diary. The primary efficacy endpoint is all-cause, non-elective hospitalisation and/or death within 28 days of randomisation. Multiple prespecified interim analyses allow interventions to be stopped for futility or superiority based on prespecified decision criteria. A prospective economic evaluation is embedded within the trial. ETHICS AND DISSEMINATION: Ethical approval granted by South Central-Berkshire REC number: 21/SC/0393; IRAS project ID: 1004274. Results will be presented to policymakers and at conferences, and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN30448031; EudraCT number: 2021-005748-31.

The NASSS-CAT Tools for Understanding, Guiding, Monitoring, and Researching Technology Implementation Projects in Health and Social Care: Protocol for an Evaluation Study in Real-World Settings.

BACKGROUND: Projects to implement health care and social care innovations involving technologies are typically ambitious and complex. Many projects fail. Greenhalgh et al's nonadoption, abandonment, scale-up, spread, and sustainability (NASSS) framework was developed to analyze the varied outcomes of such projects. OBJECTIVE: We sought to extend the NASSS framework to produce practical tools for understanding, guiding, monitoring, and researching technology projects in health care or social care settings. METHODS: Building on NASSS and a complexity assessment tool (CAT), the NASSS-CAT tools were developed (in various formats) in seven co-design workshops involving 50 stakeholders (industry executives, technical designers, policymakers, managers, clinicians, and patients). Using action research, they were and are being tested prospectively on a sample of case studies selected for variety in conditions, technologies, settings, scope and scale, policy context, and project goals. RESULTS: The co-design process resulted in four tools, available as free downloads. NASSS-CAT SHORT is a taster to introduce the instrument and gauge interest. NASSS-CAT LONG is intended to support reflection, due diligence, and preliminary planning. It maps complexity through stakeholder discussion across six domains, using free-text open questions (designed to generate a rich narrative and surface uncertainties and interdependencies) and a closed-question checklist; this version includes an action planning section. NASSS-CAT PROJECT is a 35-item instrument for monitoring how subjective complexity in a technology implementation project changes over time. NASSS-CAT INTERVIEW is a set of prompts for conducting semistructured research or evaluation interviews. Preliminary data from empirical case studies suggest that the NASSS-CAT tools can potentially identify, but cannot always help reconcile, contradictions and conflicts that block projects' progress. CONCLUSIONS: The NASSS-CAT tools are a useful addition to existing implementation tools and frameworks. Further support of the implementation projects is ongoing. We are currently producing digital versions of the tools, and plan (subject to further funding) to establish an online community of practice for people interested in using and improving the tools, and hold workshops for building cross-project collaborations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16861.