Use of the TwiCs design
Use of the TwiCs design is growing. Studies using the TwiCs design have obtained funding and research ethics board approval in: Australia, Brazil, Canada, China, Congo and Uganda, Denmark, Finland, France, Germany, India, Iran, Ireland Italy, Norway, Mexico, Netherlands, Spain, Switzerland, USA.
For examples of studies using the TwiCs approach see this scoping review (Nickolls BJ et al, BMJ Open 2024).
Australia
Generation Victoria (GenV)
Generation Victoria is a large population-based cohort study in Victoria, Australia and is proposing to integrate trials within and alongside the cohort.
https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-020-01111-x
Behavioural interventions for low back pain patients who are obese or overweight
This study aims to determine if a telephone based lifestyle behavioural intervention is effective in reducing pain intensity in overweight or obese patients with low back pain, compared to usual care. The study protocol was published here. The protocol for a causal mediation analysis of two trials in the project is here.
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Canada​
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WrapAround Care Study
This pilot study protocol is for a wraparound care model for youth visiting an emergency department in Winnipeg, Canada due to injury by violence. The intervention is initiated at the time of their visit to the emergency department and delivered by a support worker with lived experience with violence, supported by social workers and links to multiple community partners. The objective of the pilot study is to determine the feasibility of a larger trial which will explore if the intervention reduces incidence of subsequent violent injury.
https://bmjopen.bmj.com/content/5/5/e008088
Nutrition Recommendation Intervention trialS in children’s Healthcare (NuRISH)
NuRISH is an ongoing factorial TwiC which leverages The Applied Research Group for Kids (TARGet Kids!) cohort. Its aim is to determine whether support from a lactation consultant from 0-6 months of age and access to high quality childcare can prevent childhood obesity, and improve cardiovascular, development and mental health at 2 years of age. TAGet Kids! is being used as a platform for other TwiCs.
https://www.targetkids.ca/nurish
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Optimising Brain Health in HIV
This study aims to provide a better understanding of the relationship between cognitive complaints, depression and HIV, and to facilitate trials of interventions to improve brain health in HIV. The protocol for the study can be found here. The trials nested within this cohort are registered as Clinicaltrials.gov NCT02571504 and NCT02571595. For more information contact: Nancy E Mayo
FORBOW (Families Overcoming Risks and Building Opportunities)
This project is recruiting the offspring of parents with severe mental illness including schizophrenia, bipolar disorder and severe depression. It aims to test multiple interventions to reduce the risk of developing mood or psychotic disorders. The study began recruiting young people at risk in Canada in 2013. The link to the published protocol can be found here. For more information contact Rudolf Uher.
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The Cedar Project
An ongoing longitudinal cohort study addressing HIV and Hepatitis C vulnerability among young indigenous people who use drugs in Vancouver and Prince George, Brisith Columbia, Canada.The first trial use the cmRCT/ TwiCs approach is testing the impact of mHealth for HIV Prevention Among Young Indigenous People Who Use Illicit Drugs. The protocol for the trial (described as a multi-site Zelen pre-randomised trial) is published by BMC Central and the Clinical Trials registration can be found here.​
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SPIN Scleroderma Patient-Centred Intervention Network
This CIHR funded study is recruiting an international cohort of people with the rare disease - scleroderma (Canada, France, USA, UK, France, Mexico) . Over 1400 people have enrolled to date (August 2016). Four trials of interventions to help people manage this condition are ongoing. The protocol can be found here. Funding for two further trials was obtained in July 2016. For more information contact Brett Thombs​
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Collaborative Care for Diabetes and Ddepression
The Alberta's Caring for Diabetes (ABCD) Cohort Study is being used to test interventions for patients with diabetes and depression. https://pubmed.ncbi.nlm.nih.gov/26243463/.
Denmark
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Motor skills in PreSchool (MiPS) study
A preschool based cohort study with 12 years of follow-up in Denmark. A cluster RCT was conducted within the cohort with an intervention to develop motor skills, body awareness, and improve children’s development.
https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-017-2143-9#author-information
Finland
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FIDELITY
The Finnish Degenerative Meniscal Lesion Study (FIDELITY) This multi centre trial aims to determine whether arthroscopic partial meniscectomy of patients with degenerative meniscus injury is improved by a number of different types of surgery. For further information contact Teppo Jarvinen.
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Lesotho
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Community Based chronic disease Care Lesotho (ComBaCaL)
ComBaCaL is a cohort study which includes inhabitants of 103 randomly selected villages in rural Lesotho. Two cluster TwiCs will be conducted for those with uncontrolled and controlled arterial hypertension. The intervention is lay village health workers offering lifestyle counseling, basic guidelines-directed antihypertensive, lipid-lowering, and antiplatelet treatment supported by a tablet-based decision support application with the primary outcome being controlled blood pressure levels after 12 months.
Netherlands
Cohort Multiple Randomized Controlled Trial in Pediatric Asthma (CIRCUS)
The CIRCUS study is a cohort which will test multiple eHealth interventions in eligible asthmatic children treated in Medisch Spectrum Twente at Enschede (Netherlands) to improve pediatric asthma care.
https://classic.clinicaltrials.gov/ct2/show/NCT06278662
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A group based in Utrech in the Netherlands led by Helena Verkooijen have established ten hospital based cancer cohorts using the TwiCs approach including Breast, Rectal, Colorectal, Bone metastases, Lymph node metastases, Brain metastases, Prostate, Lung.
UMBRELLA
The Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion'. This study is based in the Department of Radiotherapy, University Medical Center in Utrecht, The Netherlands. The link to the study protocol can be found here. Email for more information. Here are the results of the latest trial embedded within this cohort Hyperbaric Oxygen Therapy and Late Local Toxic Effects in Patients with Irradiated Breast Cancer: A randomised clinical trial. Mink van der Molen et al, 2024. Plus an interesting editorial by Hahn et al.
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​PRESENT – Bone metastases
This ongoing study is based at the University Medical Centre in Untrech. The protocol for the first trial based in the cohort comparing conventional radiotherapy with stereotactic body radiotherapy in patients with spinal metastases can be found here. Email for more information.
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Prospective National Colo-rectal Cancer Cohort - Website
This ongoing study is based in the University Medical Center, Utrecht, The Netherlands. The study started life as the ProspectIve data CollectioN Initiative on Colorectal cancer (PICNIC) study – a prospective observational cohort study. This study is now national and has changed its name and now has 59 participating centres throughout the Netherlands and almost 10,000 participants. The links to the study protocol can be found here. Email more information.​
United Kingdom
OptiBreech
Participants in the cohort in England were randomized to standard care or OptiBreech care. OptiBreech care includes counselling by a member of the OptiBreech team and being offered the option of planning a vaginal breech birth with OptiBreech support, attempting an external cephalic version, or planning a pre-labour caesarean birth from 39 weeks gestation.
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QIST (Quality Improvement for Surgical Teams) Collaborative - A collaborative, longitudinal observational cohort study (Arthroplasty Research Cohort) of 5000+ patients undergoing primary hip and knee replacement in the United Kingdom. For more information contact mike.reed@nhs.net
BLADDER CANCER - Graham Roberts Study protocol: first ‘trials within cohort study’ for bladder cancer
For more information contact charlotte.moss@kcl.ac.uk
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RENAL CANCER - Nephron-sparing treatment for small renal masses - https://www.isrctn.com/ISRCTN18156881
For more information contact maxine.tran@nhs.net
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Sheffield Treatments for ADHD Research (STAR)
The STAR cohort was set up to improve the outcomes for those with ADHD. Stage one was a three-arm internal pilot study with randomization to either adjunctive treatment by homeopaths, adjunctive treatment by nutritional therapists, or usual care.
https://link.springer.com/article/10.1007/s00431-019-03374-z
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ASSESS-meso
This is a prospective, observational cohort study aiming to collect information on 700 patients diagnosed with mesothelioma over the next ten years. This will provide a much-needed picture of the natural history of the disease, as well as symptom course and outcomes. The study is sites across the UK. ASSESS-meso is funded by the Avon Mesothelioma Foundation. Within ASSESS-meso, we have designed TILT – a Trial of Intra-pleural bacteriaL immunoTherapy, using the TwiC approach. This is an NIHR-funded feasibility study of a novel treatment, with embedded qualitative interviews to explore participants' experiences. Recruitment opened 2017. For information on either study, please Anna Bibby.
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COVIDENCE
The COVIDENCE UK Research Study was launched in May 2020 in response to the outbreak of coronavirus disease (COVID-19). A total of 19981 participants enrolled and consented to 5-year follow-up with medical record linkage. This population based cohort study has the capacity to support trial-within-cohort studies to evaluate interventions for prevention of COVID-19 and other acute respiratory illnesses. The first COVIDENCE trial 'CORONAVIT' was launched in October 2020.
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Cystic Fibrosis Healthhub Data Observatory
This UK (NIHR funded) quality improvement project and Trials within Cohorts platform for Cystic Fibrosis (CF) aims to recruit 6,000 adults with CF to help research projects including trials of interventions for CF. Email for more information. The protocol and PIS are available here.
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Yorkshire Health Study
Ongoing population based regional cohort aiming to improve long term health of the region. Recruitment initally through GP practices in South Yorkshire, then widened to the Yorkshire region. Two waves of data collection (2010-2012, and 2013-2015), further waves planned. 22 studies have recruited through the cohort including several trials (DEPSY)
For more information contact Clare Relton.
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DEPSY
This pragmatic trial using the ‘cohort multiple randomised controlled trial’ design tested the effectiveness of adjunctive treatment by homeopaths compared to usual care alone, over a period of twelve months in 577 patients with self-reported depression. This is the first published completed trial using the cmRCT design (link). To read about the benefits and challenges experienced in the use of this trial design see the link to this article published in the journal Trials.
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Menopausal Hot Flush Study
This was the first (partial) pilot of the cmRCT design. A small cohort of women with severe/ frequent menopausal hot flushes were recruited to the observational study and one RCT conducted testing the effectiveness of the offer of a course of treatment by a homeopath compared to no offer. The trial was published in Contemporary Clinical Trials..
For more information contact Clare Relton.
CLASSIC (Comprehensive Longitudinal Assessment of Salford Integrated Care) study
This NIHR funded study tested the implementation and effectiveness of new models of care for people with long term conditions. The cohort of 4,000 was recruited through GP practices in the Salford area of the UK. The study protocol can be found here. For more information please contact Peter Bower.
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BIBBS (Born in Bradford Better Start Study)
An experimental birth cohort study designed to evaluate the impact of early life interventions. The cohort plans to recruit 5,000 babies and their mothers and mother's partners over five years by 2020 and test a number of interventions to improve health and social outcomes during the critical early years. For more information contact Josie Dickerson.
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CARE (The Yorkshire & Humber Community Ageing Research Study)
This cohort is recruiting 1,000 patients over 75 years registered with GP practices in the Yorkshire & Humber area of the UK. The researchers plan to trial interventions to improve health and wellbeing in this population. This study is funded by the NIHR CLAHRC YH. The study is registered here and the study website is here. For more information contact: Andrew Clegg or Anne Heaven.
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REFORM
This cohort was initially formed in order to conduct a cmRCT of a multifaceted podiatry intervention for the prevention of falls in older people. The study originally recruited 2,600 people from routine podiatry clinics to the REFORM cohort. During 2016-17, this cohort is being utilised to test a second intervention to prevent falls in the elderly – details of which can be found here. The link to the original REFORM cohort study and trial protocol is here. The study is led by David Torgerson at York University in the UK. The results of this trial are now published.