- Posted By: Ines Rombach
I recently attended the “Introduction to Trials within Cohorts (TwiCs)” course at Queen Mary University London. The course was run by Clare Relton, Petter Viksveen and Philippa Fibert.
The course was aimed at anyone who is starting to work on TwiCs, and was attended by trial managers, clinicians, statisticians and other researchers. The presentations were engaging and interactive, used many examples and drew on participants’ own experiences, plans and questions.
Randomised controlled trials (RCTs) are the gold standard for assessing treatment efficiency, although their design and conduct is often not without limitations, including
• Recruitment: many trials fail to recruit to time and target
• Lack of similarity to clinical practice: In clinical practice, patients are not commonly told about other treatment alternatives that their clinicians cannot provide them with certainty, nor would patients expect their treatment to be decided by chance (i.e. randomisation)
• Patient preference: Where trials compare a “new” intervention with “standard care” available outside the trial, the main incentive for many participants to enter the trial is to receive the “new” intervention. Randomisation to the control may result in withdrawal or disappointment bias when reporting trial results
The key design features of TwiCs, which are aimed to compare standard care to other interventions, can help avoid the challenges listed above:
• A large observational cohort is set up in patients with the condition of interest
• Outcomes are assessed regularly, including those that would be relevant in RCTs
• The cohort can form the basis for recruitment to (several) trials
For each trial:
• Easy identification of all eligible patients from the cohort
• “Patient centred consent”: all participants have consented to provide observational data. Participants randomised to standard care continue to be followed up within the cohort. Participants randomised to an intervention are offered to try this intervention. This process replicates routine clinical care, where patients are given information on only the relevant treatment when they require it.
The greater similarity to clinical care is thought to be likely to increase the generalisability of the trial results.
• The cohort embedded design allows for easy comparison of participants selected to the trial vs. the cohort, and comparison between participants who consent to the intervention, compared to those who do not.
The speakers also discussed the following topics:
• Consent requirements and feedback from ethics committees
• Examples of where and how TwiCs have been used/ are to be used
• Ethics, efficiency and acceptability of TwiCs
• Funding implications
• Introduction to analysis of TwiCs – intention to treat (ITT) and complier average causal effects (CACE) analyses, sample size considerations, and how to handle participants who do not take up the offered intervention
Opportunities was given to all participants to present their own work on TwiCs, and raise any queries that came up in their own work.
Links to relevant articles:
Rethinking pragmatic randomised controlled trials: introducing the “cohort multiple randomised controlled trial” design:
https://www.bmj.com/content/340/bmj.c1066
Brief Report: Staged-informed Consent in the Cohort Multiple Randomized Controlled Trial Design:
https://journals.lww.com/epidem/fulltext/2016/05000/Brief_Report___Stage...
Ethics and practice of Trials within Cohorts: An emerging pragmatic trial design:
https://www.ncbi.nlm.nih.gov/pubmed/29224380