1 October 2024
Trials within cohorts (TwiCs): A new type of study design
Randomised controlled trials (RCTs) are considered the gold standard in clinical research. However, they are often associated with high expenses and a complex recruitment process. Moreover, their findings are only partially applicable to everyday clinical practice. Many of these challenges can be overcome with a new study methodology approach.
The idea of TwiCs is to integrate randomised studies into a cohort study using the existing infrastructure for recruiting and following up study participants: Participants give their consent for any randomisation in an embedded TwiCs (randomisation consent) at the same time as they give their consent for prospective data collection for the cohort (cohort consent). Those participants who are randomised into an intervention group of a TwiC are offered the intervention to be tested, which they can either accept or reject (intervention consent). Participants who are assigned to a control group of a TwiC, on the other hand, do not have to be contacted again. They continue to receive treatment according to the standards of the cohort.
In this way, TwiCs are efficient and can save expenses. As people in the control groups do not need to be informed about intervention options, there is no problem of them withdrawing their participation, disappointed at not receiving a potentially beneficial new treatment. The collection of all endpoints for a TwiCs takes place as part of the cohort studies. This means that the intervention is also tested in a setting comparable to routine clinical practice, which improves the transferability of the results to everyday clinical practice.
Pioneers in Switzerland and Lesotho
In Switzerland, the Division of Clinical Epidemiology at the Department of Clinical Research (DKF) plays a pioneering role in the implementation and execution of TwiCs. Felix Gerber, MD-PhD student, has set up the "Community-Based Chronic Care Lesotho(ComBaCaL)" TwiCs cohort study under the supervision of Prof. Niklaus Labhardt and Dr. Alain Amstutz. The ComBaCaL study, with around 15,000 participants from over 100 villages, investigates chronic diseases and their risk factors in rural regions in Lesotho, a developing country where the population has difficult access to health services and which, with the second-highest HIV prevalence in the world, is confronted with an increasing prevalence of non-communicable chronic diseases such as hypertension and diabetes.
Currently, two cluster-randomized TwiCs within the ComBaCaL cohort1 are investigating whether the provision of first-line treatment for hypertension and diabetes by village health workers can improve treatment outcomes compared to conventional hospital-based treatment.
Prof. Matthias Briel's DKF research group is investigating the use of TwiCs in Switzerland. As part of his MD-PhD work, Christof Schönenberger, under the supervision of Prof. Matthias Briel and Dr. Alain Amstutz, is driving forward the implementation of TwiCs in the Swiss HIV Cohort Study – a national research platform founded in 1988. It is the first cohort study in Switzerland to adapt its protocol to enable TwiCs in the future. The implementation process of the randomisation consensus is currently underway. The start of the first TwiCs study in Switzerland is planned for early 2025, which will investigate a new concept for smoking cessation2.
[1] https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-024-08226-2 and
https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07729-8
[2] Reduce tobacco use in people living with HIV in Switzerland: A pragmatic randomised trial within the Swiss HIV Cohort Study (RETUNE).
Trials within cohorts – the advantages:
- Better applicability of the results
The stepwise consent process enables randomised comparisons without a consent procedure directly before study participation, and thus in a setting that is often more similar to routine clinical practice than in conventional RCTs.
- Efficient recruitment
A cohort is used as a recruitment platform. This allows a better estimation of the recruitment potential based on the existing cohort data, and efficient recruitment within the cohort studies.
- Efficient use of existing data
Existing data from the cohort can be used for randomised analyses, saving time and expenses.
- Multiple TwiCs within a cohort
If the TwiCs design is implemented in a cohort, it is easier to conduct multiple randomised studies in the same cohort without having to set up a new infrastructure each time.