Welcome to the TwiCs network where we share information about the Trials within Cohorts (TwiCs) approach for designing and conducting practical randomised controlled trials.
The TwiCs approach uses infrastructures (cohorts) to facilitate the conduct of multiple randomised controlled trials. The TwiCs approach is used by researchers working in diverse healthcare settings.
Key features of the TwiCs approach
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A large observational cohort of people with the condition(s) of interest
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Repeated measurement of outcomes for the whole cohort
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Capacity for multiple randomised controlled trials over time
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Patient-centred informed consent
TwiCs today
The TwiCs approach was developed in 2005-2006, well before the wide scale adoption of electronic health record (EHR) systems. Growing maturity in IT is now enabling the integration of clinical trial infrastructures into EHR systems.
Several innovative trial designs capitalising on this new landscape by embedding the randomisation process into the EHR architecture, linking randomisation to the moment of clinical decision making. Here are some examples of these exciting innovative designs: ePOCR (electronic Point Of Care Randomisation) trials - Wilson et al, 2022; DARTs (Decision Architecture Randomised Trials) - Flory et al, 2023; RISATs - Random Invitation Single Arm Trials - Jauniad et al, 2025.
These designs exhibit key features of the TwiCs approach and offer the potential for rapid and efficient routine treatment comparisons at scale by streamlining trial processes within EHR systems (participant screening, consent, enrolment, randomisation, intervention delivery and data collection/ outcome ascertainment).
Informed Consent
The TwiCs design advocated a 'patient centred' approach to informed consent for research participants (patients and clinicians). However, implementation of this approach is often challenging. Our informed consent guidance page describes some of the ways we have been exploring ways to ensure that this approach is implemented efficiently and ethically.
NEWS
Developing guidance for informed consent for trials with usual care group - see link.
First pan-european TwiCs clinical trial activated in the Oligo-Care Cohort, EORTC, 2025.
Randomised trials conducted using cohorts: a scoping review. Nickolls BJ et al, BMJ Open 2024.
SYMPOSIUM: Staged and tailored informed consent, 13th September 2023
The TwiCs approach
The term 'TwiCs' was coined at the first symposium on the 'cohort multiple RCT' (cmRCT) design. This approach to trial design (the cmRCT design) was first described in the BMJ in 2010 article in the context of healthcare.
Key features of the TwiCs approach are:
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A large observational cohort of people with the condition
-
Repeated measurement of outcomes for the whole cohort
-
Capacity for multiple randomised controlled trials over time
-
Patient-centred informed consent
The advantages are that the cohort serves as a representative pool from which eligible people can be selected and approached for trial participation. This provides a platform for testing multiple interventions.
The standard approach to informed consent is the 'everything up front' approach. The TwiCs approach advocates the use of a patient-centred approach to informed consent procedure - one which is more similar to how information is provided in healthcare settings where information is staged in order to maximise relevance for the patient.
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More than 80 studies have or are using the design. Researchers in the UK, Canada, USA, France, Netherlands, Finland, and Australia; are use the TwiCs design approach to help address questions in a variety of fields (breast cancer, bone metastases, rectal cancer, mental health, care of the elderly, rare diseases, etc). The design is now being used to trial both medicinal products (CTIMPs) and non-medicinal products.
This website describes key features of the TwiCs approach. There is a list of examples of use of the TwiCs approach in hospital, primary care and population settings. There are also articles discussing methodological issues, reporting guidelines, ethical questions, and the role of the TwiCs approach in relation to the development of Learning Health Systems.
Though originating in healthcare, the TwiCs approach to trial design can be used to inform decision making in any area, e.g. education, social care, crime, energy use.
