Method - Design
Lead Research Organisation:
University College London
Department Name: UNLISTED
Abstract
Randomised trials are the best way to find out what treatments work, but they can be slow and expensive. We are inventing new and efficient ways to design randomised trials that can give clear answers, often answering multiple questions within the same trial. This work is supported by detailed statistical modelling to show how to analyse the new designs while strictly controlling the risk of wrongly concluding that a treatment is effective when in truth it isn’t. The new designs are implemented in our own trials, and this helps us to refine the designs and demonstrate their value for other trials.
Our novel designs are for
1. trials to evaluate whether it is safe to shorten the duration of treatment or use a treatment with fewer side effects;
2. trials to evaluate multiple treatments, where we can drop treatments that are found to be ineffective, adopt the use of treatments that are found to be effective, and start evaluating new promising treatments;
3. trials that work even when the benefit of treatment is short-term or delayed;
4. trials where groups of patients are randomised rather than individual patients;
5. trials specifically designed to evaluate treatments tailored to specific types of patient; and
6. trials comparing a number of treatments, where some patients cannot receive some of the treatments.
The results of our work are that treatments can be evaluated faster, more effectively and more cost-effectively.
Our novel designs are for
1. trials to evaluate whether it is safe to shorten the duration of treatment or use a treatment with fewer side effects;
2. trials to evaluate multiple treatments, where we can drop treatments that are found to be ineffective, adopt the use of treatments that are found to be effective, and start evaluating new promising treatments;
3. trials that work even when the benefit of treatment is short-term or delayed;
4. trials where groups of patients are randomised rather than individual patients;
5. trials specifically designed to evaluate treatments tailored to specific types of patient; and
6. trials comparing a number of treatments, where some patients cannot receive some of the treatments.
The results of our work are that treatments can be evaluated faster, more effectively and more cost-effectively.
Technical Summary
The design programme aims to improve the efficiency and resilience of randomised trials by proposing new trial designs. Efficiency is the ability to identify a treatment effect (or lack of effect) quickly with best use of resources. Resilience is the ability to reach credible answers when design assumptions turn out to be inaccurate. We do this pro-actively and in response to emerging challenges in our trials, and we implement solutions first in our trials and then more widely. New design methodology usually requires new software, and we provide user-friendly software packages for internal and external use. We also improve some existing trial designs in a similar manner.
Our main areas of work are
1. Durations design and non-inferiority trials. Non-inferiority trials are widely used and are often the best way to improve outcomes, especially in tuberculosis and anti-microbial resistance. However, they are hard to implement and often lacking in resilience. We are developing ways to choose a shortened treatment regimen (the Durations Design), and ways to address particular problems that occur in sensitivity to non-adherence and to small changes in the control event rate.
2. Multi-arm multi-stage (MAMS) platform trials. To speed up the evaluation of new therapies and improve success rates in identifying effective ones, we pioneered the development and implementation of the MAMS design and wrote the nstage software suite in Stata for sample size calculation. A MAMS platform trial generally has a single master protocol in which multiple treatments are evaluated over time, and offers flexible features such as early stopping of accrual to treatments for lack of benefit, and adding new treatments to be tested during the course of a trial. We have nearly 20 years’ practical experience of designing and running such trials and we are extending the underlying methodology to increase the efficiency of the design and to broaden its application to a wide range of disease areas and types of outcome measure.
3. Non-proportional hazards. Trials with a time-to-event outcome are usually designed and analysed assuming the treatment effect remains stable over time (proportional hazards). However, non-proportional hazards (non-PH) is more common than previously thought, e.g. due to therapy ‘wearing off’ or taking time to work. If unrecognised and unaccommodated, non-PH may impact the success or failure of a trial. We are developing ways to design trials to anticipate possible non-PH.
4. Cluster randomised and stepped wedge trials. These are designs where clusters of individuals are randomised to treatment or control. We aim to optimise the design of these trials by minimising the number of clusters and/or measurements required, and also to show new ways to understand these trials.
5. Trials for stratified medicine. Our focus is on understanding how to design a trial when a treatment is suspected to work best in a particular subgroup, but this knowledge is not secure and may evolve during the trial.
6. The new “PRACTical” trial design. This is intended for situations where a number of treatments are available but typically the treatments are not appropriate for all patients, for example because of their other medical conditions. We propose to randomise each patient between the treatments that are potentially appropriate to them. We are developing suitable ways to design and analyse such a trial.
Our main areas of work are
1. Durations design and non-inferiority trials. Non-inferiority trials are widely used and are often the best way to improve outcomes, especially in tuberculosis and anti-microbial resistance. However, they are hard to implement and often lacking in resilience. We are developing ways to choose a shortened treatment regimen (the Durations Design), and ways to address particular problems that occur in sensitivity to non-adherence and to small changes in the control event rate.
2. Multi-arm multi-stage (MAMS) platform trials. To speed up the evaluation of new therapies and improve success rates in identifying effective ones, we pioneered the development and implementation of the MAMS design and wrote the nstage software suite in Stata for sample size calculation. A MAMS platform trial generally has a single master protocol in which multiple treatments are evaluated over time, and offers flexible features such as early stopping of accrual to treatments for lack of benefit, and adding new treatments to be tested during the course of a trial. We have nearly 20 years’ practical experience of designing and running such trials and we are extending the underlying methodology to increase the efficiency of the design and to broaden its application to a wide range of disease areas and types of outcome measure.
3. Non-proportional hazards. Trials with a time-to-event outcome are usually designed and analysed assuming the treatment effect remains stable over time (proportional hazards). However, non-proportional hazards (non-PH) is more common than previously thought, e.g. due to therapy ‘wearing off’ or taking time to work. If unrecognised and unaccommodated, non-PH may impact the success or failure of a trial. We are developing ways to design trials to anticipate possible non-PH.
4. Cluster randomised and stepped wedge trials. These are designs where clusters of individuals are randomised to treatment or control. We aim to optimise the design of these trials by minimising the number of clusters and/or measurements required, and also to show new ways to understand these trials.
5. Trials for stratified medicine. Our focus is on understanding how to design a trial when a treatment is suspected to work best in a particular subgroup, but this knowledge is not secure and may evolve during the trial.
6. The new “PRACTical” trial design. This is intended for situations where a number of treatments are available but typically the treatments are not appropriate for all patients, for example because of their other medical conditions. We propose to randomise each patient between the treatments that are potentially appropriate to them. We are developing suitable ways to design and analyse such a trial.
Organisations
- University College London (Lead Research Organisation)
- World Health Organization (WHO) (Collaboration)
- National Institute for Health Research (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
- UNIVERSITY OF OXFORD (Collaboration)
- Alan Turing Institute (Collaboration)
- London School of Hygiene and Tropical Medicine (LSHTM) (Collaboration)
- UNIVERSITY OF BIRMINGHAM (Collaboration)
- HEALTH DATA RESEARCH UK (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- Radboud Institute for Health Sciences (Collaboration)
- Cytel (Collaboration)
Publications
Bazo-Alvarez JC
(2021)
Cardiovascular outcomes of type 2 diabetic patients treated with DPP-4 inhibitors versus sulphonylureas as add-on to metformin in clinical practice.
in Scientific reports
Billot L
(2024)
How should a cluster randomized trial be analyzed?
in Journal of epidemiology and population health
Buckman JEJ
(2023)
Predicting prognosis for adults with depression using individual symptom data: a comparison of modelling approaches.
in Psychological medicine
Choodari-Oskooei B
(2022)
Multi-arm Multi-stage (MAMS) Platform Randomized Clinical Trials
Choodari-Oskooei B
(2023)
Facilities for optimizing and designing multiarm multistage (MAMS) randomized controlled trials with binary outcomes
in The Stata Journal: Promoting communications on statistics and Stata
Choodari-Oskooei B
(2023)
Treatment selection in multi-arm multi-stage designs: With application to a postpartum haemorrhage trial.
in Clinical trials (London, England)
Clark TP
(2022)
Estimands: bringing clarity and focus to research questions in clinical trials.
in BMJ open
Clements MN
(2022)
Improving clinical trial interpretation with ACCEPT analyses.
in NEJM evidence
Copas AJ
(2021)
Optimal design of cluster randomized trials allowing unequal allocation of clusters and unequal cluster size between arms.
in Statistics in medicine
Cro S
(2022)
Evaluating how clear the questions being investigated in randomised trials are: systematic review of estimands.
in BMJ (Clinical research ed.)
Related Projects
Project Reference | Relationship | Related To | Start | End | Award Value |
---|---|---|---|---|---|
MC_UU_00004/01 | 31/03/2021 | 30/03/2026 | £5,186,000 | ||
MC_UU_00004/02 | Transfer | MC_UU_00004/01 | 31/03/2021 | 30/03/2026 | £4,446,000 |
MC_UU_00004/03 | Transfer | MC_UU_00004/02 | 31/03/2021 | 30/03/2026 | £4,999,000 |
MC_UU_00004/04 | Transfer | MC_UU_00004/03 | 31/03/2021 | 30/03/2026 | £5,315,000 |
MC_UU_00004/05 | Transfer | MC_UU_00004/04 | 31/03/2021 | 30/03/2026 | £3,107,000 |
MC_UU_00004/06 | Transfer | MC_UU_00004/05 | 31/03/2021 | 30/03/2026 | £2,889,000 |
MC_UU_00004/07 | Transfer | MC_UU_00004/06 | 31/03/2021 | 30/03/2026 | £2,369,000 |
MC_UU_00004/08 | Transfer | MC_UU_00004/07 | 31/03/2021 | 30/03/2026 | £2,270,000 |
MC_UU_00004/09 | Transfer | MC_UU_00004/08 | 31/03/2021 | 30/03/2026 | £2,160,000 |
Description | Application of the MAMS design to several disease area |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Contribution to new or improved professional practice |
Impact | The uptake of MAMS platform designs has made a huge contribution to testing new treatments in an efficient manner in many disease areas, as listed above. It allowed the investigators to weed out the ineffective treatments as early as possible and focus on treatments that can be potentially effective. The MAMS framework also allowed new treatment arms to be added to enhance the efficiency of the design. |
Description | Application of the re-randomisation design in respiratory medicine |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Contribution to new or improved professional practice |
Impact | New interventions ca be used to safely reduce systemic glucocorticoid use in clinical practice. |
URL | https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(23)00298-9/fulltext |
Description | Development of guidelines to reduce, handle and report missing data in palliative care trials: A multi-stakeholder modified nominal group technique |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | The guidelines show how a range of stakeholders can help to reduce, handle and report missing data in palliative care trials. They have been widely distributed and presented at an NCRI workshop, https://conference.ncri.org.uk/events/missing-data-in-clinical-trials-how-to-reduce-it-handle-it-and-report-it/ |
URL | https://www.equator-network.org/reporting-guidelines/development-of-guidelines-to-reduce-handle-and-... |
Description | Duration of antibiotic therapy on effectiveness of antibiotic resistance in adult women |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Contribution to new or improved professional practice |
Impact | This will help to find an optimal duration of treatment intervention. |
URL | https://www.phctrials.ox.ac.uk/studies/duration-uti-trial |
Description | IW on CRUK funding panel |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | MRC CTU only trials unit mentioned in O'Shaughnessy report |
Geographic Reach | National |
Policy Influence Type | Citation in other policy documents |
URL | https://www.gov.uk/government/publications/commercial-clinical-trials-in-the-uk-the-lord-oshaughness... |
Description | Membership of two IDMCs for two trials using MAMS-ROCI designs, DURATION UTI and CURLY. |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | Enhanced the uptake of novel efficient designs such as the MAMS-ROCI design. |
Description | NewDAWN |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
URL | https://www.diabetes.org.uk/about_us/news/funding-new-type-2-diabetes-remission-research-NewDAWN |
Description | Optimal duration of cefalexin therapy for the treatment of febrile urinary tract infections in children. |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Contribution to new or improved professional practice |
Impact | The trial is still ongoing. |
URL | https://www.curly.digitrial.com |
Description | SPIRIT/CONSORT meeting 1-2/3/2023 |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | TMRP Doctoral Training Programme |
Amount | £2,518,806 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2021 |
End | 09/2026 |
Title | DURATIONS trial design |
Description | REFINE trial uses the novel DURATIONS design. REduced Frequency ImmuNE (REFINE) is a multi-arm phase II basket protocol which tests reduced intensity immunotherapy across different cancers |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | The REFINE trial aims to asses whether giving an immunotherapy drug less-often to patients with advanced cancer, results in fewer side effects whilst continuing to be an effective treatment. The question will be assessed in different tumour types by means of different cohorts within an overarching trial protocol. |
URL | https://clinicaltrials.gov/ct2/show/study/NCT04913025 |
Title | DURATIONS trial design |
Description | REFINE-LUNG trial uses the novel DURATIONS design. Lung cancer is the most common cause of cancer related death. Over 85% of cases are due to non small cell lung cancer (NSCLC). Most patients present with inoperable advanced disease that is incurable with chemotherapy and/or radiotherapy. Recently, more effective medicines have been found that work by activating the body's immune cells to attack the cancer. These include medicines such as pembrolizumab (pembro). For patients who benefit from pembro, an effect is usually seen within 3-6 months of starting treatment. However, treatment is usually continued every 3 weeks and more recently every 6 weeks (standard treatment) for two years or until it stops working. There are several reasons to think 2 years of standard treatment may be unnecessary. For example, many people who respond to treatment and stop early because of side-effects or when the course finishes at 2 years, continue to benefit from pembro long afterwards, i.e. their disease does not grow back. This may be because pembro continues to work on immune cells long after it can't be detected in the blood. Taken together, we think that pembro can be given less frequently after patients have achieved benefit. If pembro can be given less frequently, it would result in fewer hospital visits and potentially reduced side effects resulting in improved quality of life. Reducing the cost of therapy would free up resources to support other new treatments. REFINE-Lung is a randomised open-label phase III trial of REduced Frequency pembrolizumab ImmuNothErapy for first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) utilising a novel multi-arm frequency-response optimisation design. |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | The aim is to determine the longest dose frequency of pembrolizumab with non-inferior survival compared to control 6 wkly therapy. Our secondary goals are to determine the cost, toxicity and quality of life benefits of reduced frequency therapy. |
URL | https://fundingawards.nihr.ac.uk/award/NIHR133011 |
Title | DURATIONS trial design |
Description | T4P trial uses the novel DURATIONS design. It was funded by HTA in 2021, with the trial starting in 2022. Its aim is to discover the platelet count below which patients requiring Intensive Care should be given platelets to have a procedure that may cause bleeding. It is lead by Oxford University, with collaboration with ICNARC. |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | This trial finds the optimal threshold for platelet administration. |
URL | https://fundingawards.nihr.ac.uk/award/NIHR131822 |
Title | MAMS-ROCI (DURATIONS) trial design. |
Description | MAMS-ROCI is a novel trial design that has been developed for situations where the goal is to optimise some continuous aspect of treatment administration, like duration or frequency. It is mainly based on two ideas: randomising patients to multiple arms across the continuum and using flexible regression models to share information across arms. |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | UNITE4TB (European Consortium), PediCAP, REFINE, T4P, REFINE-Lung, CURLY and DURATION-UTI. |
URL | https://journals.sagepub.com/doi/full/10.1177/1740774520944377 |
Title | PRACTical trial design |
Description | The PRACTical trial design is a new trial design for a clinical setting where several treatments are available with little evidence to choose between them, but many or all patients in the target population have characteristics that make some of the treatments unsuitable. The motivating example is in carbapenem-resistant infections, where antibiotic therapy needs to be personalised based on antimicrobial susceptibility testing and tolerance of toxicity. Traditional two-arm trials, recruiting only patients eligible for both treatments, only address part of the question and recruit poorly, while a multi-arm trial where patients must be eligible for all arms would have even greater recruitment challenges. Trials are urgently needed to answer clinical questions such as whether high-dose carbapenem might overcome resistance, whether older, potentially toxic drugs are more effective in combination with other drugs, and whether newer drugs could be beneficial. Similar issues arise in other diseases, such as TB. Our proposal is to draw up a "personal randomisation list" for each patient, consisting of all the treatments that are potentially suitable, and to randomise the patient between these treatments. Designing a trial in this way should help to overcome recruitment problems. If all patients with the same personal randomisation list are considered as a separate sub-trial, then the idea is akin to network meta-analysis. The idea is to pool information across sub-trials and thus gain efficiency compared to separately analysing each sub-trial. Put differently, we obtain both direct evidence (head-to-head comparisons) and indirect evidence (comparing via a third treatment) about treatment effects. We then combine them, bearing in mind that using direct evidence alone may suffer a large loss of efficiency and may yield incoherent treatment recommendations, while indirect evidence may be of lower validity. |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | A trial is in set-up, NeoSEP1, using this design. NeoSEP1 explores best antibiotic treatment for newborn babies who are in hospital with severe sepsis (https://www.isrctn.com/ISRCTN48721236). A second trial is being developed using this design to compare anti-venoms for snake bites. |
URL | https://www.sciencedirect.com/science/article/pii/S147330992030791X?dgcid=author |
Title | Additional file 1 of Planning a method for covariate adjustment in individually randomised trials: a practical guide |
Description | Additional file 1 Stata code to generate Fig. 1. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_1_of_Planning_a_method_for_cova... |
Title | Additional file 1 of Planning a method for covariate adjustment in individually randomised trials: a practical guide |
Description | Additional file 1 Stata code to generate Fig. 1. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_1_of_Planning_a_method_for_cova... |
Title | Additional file 2 of Planning a method for covariate adjustment in individually randomised trials: a practical guide |
Description | Additional file 2 Stata code for the analysis of the GetTested trial (Assumes the data file journal.pmed.1002479.s001.xls has been downloaded from https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002479#sec020 ). |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_2_of_Planning_a_method_for_cova... |
Title | Additional file 2 of Planning a method for covariate adjustment in individually randomised trials: a practical guide |
Description | Additional file 2 Stata code for the analysis of the GetTested trial (Assumes the data file journal.pmed.1002479.s001.xls has been downloaded from https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002479#sec020 ). |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_2_of_Planning_a_method_for_cova... |
Description | Alan Turing Institute and AI |
Organisation | Alan Turing Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | ATI will provide funding for project work for the week |
Collaborator Contribution | Developed project idea which will be taken into Alan Turing Institute Hackathon week |
Impact | (none yet) |
Start Year | 2019 |
Description | Alan Turing Institute and AI |
Organisation | Health Data Research UK |
Country | United Kingdom |
Sector | Private |
PI Contribution | ATI will provide funding for project work for the week |
Collaborator Contribution | Developed project idea which will be taken into Alan Turing Institute Hackathon week |
Impact | (none yet) |
Start Year | 2019 |
Description | Collaboration with Cytel, manufacturers of East software |
Organisation | Cytel |
Country | United Kingdom |
Sector | Private |
PI Contribution | We have formed a collaboration with Cytel, manufacturers of East software for designing adaptive trials, with the aim of getting our novel MAMS methods implemented in East and conversely using East to validate our software. Based on our experience with Stampede and other MAMS trials, we provide advice on how to develop a suitable user interface in East, as well as implementing our methods both analytically and via simulation. |
Collaborator Contribution | Based on our input and advice, Cytel will develop prototypes for us to try them out and gives us feed-back so that we know what does or does not work. |
Impact | This is multi-disciplinary collaboration which includes both the development of statistical methodology as well as implementing those in East. |
Start Year | 2019 |
Description | Collaboration with Oxford and Cambridge university on MAMS platform trial in early psychotic disorders (2022 - Still Active) |
Organisation | University of Cambridge |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Advise on the design, conduct and analysis of new proposal for a MAMS platform trial. |
Collaborator Contribution | The main applicant on a new grant proposal to be submitted to Wellcome Trust. |
Impact | setting up a new MAMS platform trial in early psychotic disorders. |
Start Year | 2023 |
Description | Collaboration with WHO on complex adaptive trial designs |
Organisation | World Health Organization (WHO) |
Country | Global |
Sector | Public |
PI Contribution | We designed mlti-arm multi-stage (MAMS) selection trial in postpartum haemorrhage. It is planned to be conducted in middlle and low income countries in Africa and South East Asia. |
Collaborator Contribution | WHO will conduct the trial with the technical/statistical support of the MRC CTU. |
Impact | Conference presentation, and a (working) design article. |
Start Year | 2020 |
Description | IW advisor to Suzie Cro |
Organisation | Imperial College London |
Department | Imperial Clinical Trials Unit (ICTU) |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Advised on development and submission of a successful NIHR Advanced Fellowship application |
Collaborator Contribution | Developed and submitted the successful NIHR Advanced Fellowship application |
Impact | Workshop planned April 2022 to improve how UK clinical trials units approach estimands. |
Start Year | 2019 |
Description | NIHR & MRC Trials Methodology Research Parternship Executive Group |
Organisation | Medical Research Council (MRC) |
Country | United Kingdom |
Sector | Public |
PI Contribution | Intellectual input and plans for further collaboration on future projects Member of Executive Group (Coordinated from University of Liverpool) Co-chair of Health Informatics Working Group (Co-chaired from University of Leeds) Co-chair of Statistical Analysis Working Group (Co-chaired from Kings College London) |
Collaborator Contribution | 25 partner organisations around UK (not all listed at this stage) Intellectual input and plans for further collaboration on future projects |
Impact | (none yet) |
Start Year | 2019 |
Description | NIHR & MRC Trials Methodology Research Parternship Executive Group |
Organisation | National Institute for Health Research |
Department | National Institute for Health Research (NIHR) BioResource |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Intellectual input and plans for further collaboration on future projects Member of Executive Group (Coordinated from University of Liverpool) Co-chair of Health Informatics Working Group (Co-chaired from University of Leeds) Co-chair of Statistical Analysis Working Group (Co-chaired from Kings College London) |
Collaborator Contribution | 25 partner organisations around UK (not all listed at this stage) Intellectual input and plans for further collaboration on future projects |
Impact | (none yet) |
Start Year | 2019 |
Description | REFINE-Lung - A randomsied trial to find the optimal frequency of immunotherapy treatment for patients with lung cancer |
Organisation | Imperial College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | MRC CTU designed of the trial, which uses a MAMS-ROCI design. |
Collaborator Contribution | All the remaining aspects related to design and conduct of the trial. |
Impact | The design of the phase 2C trial has been finalised, and a design paper has been accepted for publication in LANCET Oncology. |
Start Year | 2021 |
Description | ROSSINI 2 MAMS Trial Collaboartion |
Organisation | University of Birmingham |
Department | Birmingham Clinical Trials Unit |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We design this flagship MAMS trial. |
Collaborator Contribution | Desining multi-arm multi-stage (MAMS) randomised clinical trials in surgical wound infection. This is the first MAMS trial in surgery. |
Impact | (none yet) |
Start Year | 2021 |
Description | T4P - A randomised trial to seek the optimal platelet threshold below which transfusions may be beneficial |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | MRC CTU advised on the design, as the trial uses a MAMS-ROCI design. |
Collaborator Contribution | Design and conduct of the trial. |
Impact | The design of the trial has been finalised, the trial is recruiting and a design paper has been drafted. |
Start Year | 2021 |
Description | UNITE4TB - A IMI EU consortium to develop novel TB treatment regimens |
Organisation | London School of Hygiene and Tropical Medicine (LSHTM) |
Department | Department of Global Health and Development |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | MRC CTU designs the Phase 2C trials in this project, whose aim is to select the most promising duration(s) of the most promising treatment(s) to bring forward to a later phase 3 trial. |
Collaborator Contribution | The whole collaboration has 10 work packages, which will focus on the most wide ranging issues about TB, including microbiology, biomarkers, pharmacology, artificial intelligence and biosample sharing. |
Impact | The design of the phase 2C trial has been finalised, and a design paper has been drafted. |
Start Year | 2021 |
Description | UNITE4TB - A IMI EU consortium to develop novel TB treatment regimens |
Organisation | Radboud Institute for Health Sciences |
Country | Netherlands |
Sector | Hospitals |
PI Contribution | MRC CTU designs the Phase 2C trials in this project, whose aim is to select the most promising duration(s) of the most promising treatment(s) to bring forward to a later phase 3 trial. |
Collaborator Contribution | The whole collaboration has 10 work packages, which will focus on the most wide ranging issues about TB, including microbiology, biomarkers, pharmacology, artificial intelligence and biosample sharing. |
Impact | The design of the phase 2C trial has been finalised, and a design paper has been drafted. |
Start Year | 2021 |
Title | artbin Stata software |
Description | artbin estimates power or total sample size for trials with binary outcomes. |
Type Of Technology | Software |
Year Produced | 2021 |
Impact | artbin has been created to assist the design of clinical trials, but it can also be used in the design of observational studies to explore a protective or harmful factor. |
Title | artcat |
Description | artcat is a program for calculating the sample size required in a clinical trial with an ordered categorical outcome. It runs in the statistical package Stata. |
Type Of Technology | Software |
Year Produced | 2022 |
Open Source License? | Yes |
Impact | None as yet |
URL | https://github.com/UCL/artcat |
Description | IW speak at TB prevention trials workshop 15-17/9/2021 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited speaker at WHO Technical Consultation: Innovative clinical trial designs for the evaluation of new TB preventive treatment |
Year(s) Of Engagement Activity | 2021 |
Description | Invited talk at International Biometrics Conference 2022 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Two Invited speakers (Babak Choodari-Oskooei and Matteo Quartagno) at International Biometrics Conference: Innovative Complex Designs for Confirmatory Clinical Trials |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.youtube.com/watch?v=6uaGHo80UcQ&t=177s |
Description | MRC CTU Design symposium 2023 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | 250 people attended a symposium on Innovative phase III randomised clinical trial designs. They were clinicians, statisticians and other researchers working on clinical trials, patient representatives, and representatives of funding bodies and regulators. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.mrcctu.ucl.ac.uk/our-research/methodology/design/multi-arm-multi-stage-mams-platform-tri... |
Description | Missing data in clinical trials: how to reduce it, handle it and report it |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The workshop helped participants to have a clearer understanding of how to improve their processes related to clinical trials data collection and impact the practice of all involved including patients/carers, clinicians, trialists and statisticians, resulting in higher quality data to inform clinical practice. |
Year(s) Of Engagement Activity | 2022 |
URL | https://conference.ncri.org.uk/events/missing-data-in-clinical-trials-how-to-reduce-it-handle-it-and... |
Description | Pre-conference workshop on the design and analysis of multi-arm multi-stage (MAMS) platform trials |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | More than 40 participants attended the workshop |
Year(s) Of Engagement Activity | 2022 |
Description | UCL health methods software showcase |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Online workshop for all UCL staff writing software for statistics-related applicatins in health |
Year(s) Of Engagement Activity | 2021 |