Real-world studies of Amwell’s SilverCloud internet-enabled cognitive behavioural therapy (CBT) for adults with depression or generalised/unspecified anxiety disorders compared to individual or group low-intensity CBT to estimate their comparative effectiveness, cost-effectiveness, and inequalities in outcomes: the SilverCloud Target Trials

Research question.

Among NHS Talking Therapies for anxiety and depression (TTad) service clients, how effective and cost-effective is internet-delivered cognitive behavioural therapy (iCBT) compared to low-intensity individual or group CBT for depression or generalised/unspecified anxiety disorders, and are there outcome inequalities?

Background. Depression and anxiety disorders affect ≈18%-population, with high-levels of years lived with disability. NHS TTad-services offer evidence-based psychological therapies with 1.8-million referrals during 2022/23.

Amwell s SilverCloud iCBT platforms, Space from Depression and Space from Anxiety , are currently provided across 72% of TTad-services. However, within-service, iCBT represents only ∼3% of first-line low-intensity treatments used.

The National Institute for Health and Care Excellence s (NICE s) early value assessment (EVA) process requested real-world evidence (RWE) based on real-world data (RWD) to support SilverCloud iCBT use in the NHS. Aim.

To produce RWE to fill SilverCloud iCBT evidence gaps, for public and NHS benefit by answering our research question as refined with PPI input.

Objectives Ensure patient-centred research throughout, including research question and study design refinement, and dissemination; SilverCloud iCBT RWD-study analysis of benefits and costs to patients and the NHS, utilising NICE s RWE framework; Evaluate current SilverCloud implementation with NHS staff and patients, to identify facilitators and barriers to enhance adoption; Harness stakeholder experience for commercial success by mapping stakeholder analysis, generating a commercialisation/dissemination plan, and detail generalisable learnings.

Methods. We will use de-identified, routinely recorded data covering April-2021 to March-2024. An initial regional study will use data from 14 London TTad-services to develop and refine our methodology.

The national study will use NHS England s linked national TTad-service, mental health service, secondary (hospital) care, and community pharmacy data.

Routinely collected outcomes include patient-reported TTad-service metrics (e.g., recovery and reliable improvement), safety (e.g., adverse events), and longer-term outcomes (e.g., proxy relapse rates).

As recommended within NICE s RWE framework, we will use structural (e.g., Target Trial emulation) and analytical (e.g., g-methods and E-values) methods to aid reduce or explain bias within our comparative causal effectiveness and cost-effectiveness estimates.

Implementation research will provide a deeper understanding to our causal estimates, alongside detailing iCBT use and barriers.

Our commercial and adoption work-packages will utilise our mixed-methods evidence to support increased within TTad-service iCBT use and broader NHS adoption. Delivery timelines. Seven work-packages (WPs) over 36-months.

WP1 (Project management), WP2 (PPI), WP6 (IP, Commercialisation, and Value Proposition) and WP7 (Adoption, Dissemination, and Generalisable Learnings) run throughout the 36-months. WP5 (Implementation Research) key activities occur in Year-2.

WP3 (RWD-study preparation) runs parallel to WP4 (RWD-study) data cleaning and structuring (Regional, Year-1; National, Year-2), before WP4 analyses (Regional, Year-2; National, Year-3). Year-3 includes robust reporting and quality assurance processes. Anticipated Impact and Dissemination.

Initial impact will predominantly be for adults with common mental disorders, TTad-services, broader NHS, and commissioners.

The findings will influence NICE EVA processes and recommendations, methodological development and trust in RWE, leading to patient and service benefits.

Our plans and results will be shared widely including with patient groups, via a study website and newsletter, presented at national and international meetings and via open-access high-impact publications.