Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial delivery (RAPPORT)
Background Rheumatoid arthritis is a chronic disease of immune dysregulation affecting 1% of United Kingdom adults at an estimated cost to the taxpayer exceeding £5B per annum. Recently, enhanced pathophysiological understanding and a growing array of rational therapeutic candidates have converged o...
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NIHR Journals Library
2025-02-01
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| Series: | Efficacy and Mechanism Evaluation |
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| Online Access: | https://doi.org/10.3310/ASHG1864 |
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| author | Michelle Bardgett Marie Falahee Gwenda Simons John D Isaacs Luke Ouma James MS Wason Arthur G Pratt |
| author_facet | Michelle Bardgett Marie Falahee Gwenda Simons John D Isaacs Luke Ouma James MS Wason Arthur G Pratt |
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| description | Background Rheumatoid arthritis is a chronic disease of immune dysregulation affecting 1% of United Kingdom adults at an estimated cost to the taxpayer exceeding £5B per annum. Recently, enhanced pathophysiological understanding and a growing array of rational therapeutic candidates have converged on the potential to intercept rheumatoid arthritis before clinically manifest arthritis occurs, raising the possibility of delaying or even preventing disease. The National Institute for Health and Care Research Efficacy and Mechanism Evaluation Acceleration Award provided 12-month support to accelerate the development of an international precision medicine platform study, within remit of the Medical Research Council-National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme. To this end, Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial proposed a pan-European precision medicine platform trial for preventative interventions in people at risk of rheumatoid arthritis. Challenges of delivering a trial of this nature led by a United Kingdom Sponsor, as well as those specific to the delivery of Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial, were addressed. Objectives The overarching aim of Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial was to submit a stage 1 application for the Efficacy and Mechanism Evaluation call: 23/15 precision medicine platform studies to efficiently evaluate the efficacy of interventions. In delivering this, we met the following objectives: Understand optimal sponsorship, governance and funding models for international platform trials by synthesising relevant literature in the form of systematic review. Convene and engage an international at risk of rheumatoid arthritis Precision Platform Trial Management Group with expertise in the pathobiological understanding and therapeutic management of at risk of rheumatoid arthritis, as well as the design and delivery of interception trials, with a view to developing a master protocol. Convene and consult a Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial Public Advisory Group to directly inform trial design, including a strategy for mapping the level of rheumatoid arthritis progression risk to lifestyle and/or pharmacological interventions. Identify interventions to be evaluated in a platform trial, engaging appropriately with industry partners. Identify optimal clinical and/or immunological biomarkers for participant stratification. Outcomes Five work streams were set up to target delivery of the aforementioned objectives. A systematic review entitled ‘Operational complexities in international clinical trials: a systematic review of challenges and proposed solutions’ has been registered with the Open Science Framework, completed and submitted for publication. Linked to this, a working group was established to identify barriers and solutions to acting as Sponsor for Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial; purposeful interactions with European Union and United Kingdom partner sites helped prioritise governance and funding models to enable delivery, and have informed local standard operating procedures for sponsoring international trials. A patient and public involvement Advisory group was formed, and a series of events and programme of work undertaken to feed into all aspects of Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial. A range of potential interventions, non-pharmacological and pharmacological, were considered and prioritised for inclusion in Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial’s design. A funding framework supported by industry partners, incorporating one lifestyle and two drug interventions, was developed, along with a strategy for prioritising future interventions. A working group was furthermore convened for the management of biological samples to be collected for research in biomarker evaluations. A stage 1 application for the 23/15 Efficacy and Mechanism Evaluation call was submitted in May 2023. Limitations In its first iteration, the substantive clinical trial proposal proposed as a result of the Accelerator award reported herein was not funded by National Institute for Health and Care Research. In part this was due to the approach adopted to address the ‘precision medicine’ element of the brief. Other challenges include the assembly of geographically diverse patient partners for an international study given time constraints, and logistical complexity in international trial design. Future work Efforts to fund the work described in amended form are ongoing. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme as award number NIHR153955.
Plain language summary Rheumatoid arthritis is a common long-term condition in which the immune system causes joint damage, leading to pain and reduced well-being. Some people who develop musculoskeletal pain and are found to have abnormalities in their immune systems on blood testing are at increased risk of rheumatoid arthritis. Researchers suspect certain treatments could relieve their symptoms and prevent them from developing the disease. This could have major benefits for society. A few clinical trials have tried to test whether taking certain drugs for a limited period might delay or prevent rheumatoid arthritis. However, it can prove difficult to find enough participants from routine rheumatology clinics to carry out such studies. In addition, people’s risk of developing rheumatoid arthritis varies: a person at slightly increased risk might not want a drug that could cause side effects, but a person at very high risk might. More ‘personalised’ trial designs are therefore needed. The National Institute for Health and Care Research Efficacy and Mechanism Evaluation Acceleration Award provided 12 months of support to address these challenges. We proposed a Newcastle-led, international ‘platform trial’. In platform trials, different treatments can be tested in different sections (arms) of a single trial. Treatments can be added or removed as results come in, without needing to start up a new trial each time. In Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial, an international team came together, including experts in trial design and people with lived experience of being at risk of rheumatoid arthritis and/or trial participation. Working with partners in the pharmaceutical industry, we submitted a National Institute for Health and Care Research proposal. In it, we wanted to test a non-drug treatment in a ‘low-risk’ arm (for people at only slightly increased risk of rheumatoid arthritis), and a drug treatment in the ‘high-risk’ arm, for those at higher risk. The ultimate aim was to bring about a step change in the management of rheumatoid arthritis that recognises prevention is better than cure. |
| format | Article |
| id | doaj-art-c8199648d5ae42118bcd7031c13f27ca |
| institution | OA Journals |
| issn | 2050-4373 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | NIHR Journals Library |
| record_format | Article |
| series | Efficacy and Mechanism Evaluation |
| spelling | doaj-art-c8199648d5ae42118bcd7031c13f27ca2025-08-20T02:00:33ZengNIHR Journals LibraryEfficacy and Mechanism Evaluation2050-43732025-02-0110.3310/ASHG1864NIHR136248Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial delivery (RAPPORT)Michelle Bardgett0Marie Falahee1Gwenda Simons2John D Isaacs3Luke Ouma4James MS Wason5Arthur G Pratt6Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UKInstitute of Inflammation and Ageing, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UKInstitute of Inflammation and Ageing, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UKTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UKPopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UKPopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UKTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UKBackground Rheumatoid arthritis is a chronic disease of immune dysregulation affecting 1% of United Kingdom adults at an estimated cost to the taxpayer exceeding £5B per annum. Recently, enhanced pathophysiological understanding and a growing array of rational therapeutic candidates have converged on the potential to intercept rheumatoid arthritis before clinically manifest arthritis occurs, raising the possibility of delaying or even preventing disease. The National Institute for Health and Care Research Efficacy and Mechanism Evaluation Acceleration Award provided 12-month support to accelerate the development of an international precision medicine platform study, within remit of the Medical Research Council-National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme. To this end, Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial proposed a pan-European precision medicine platform trial for preventative interventions in people at risk of rheumatoid arthritis. Challenges of delivering a trial of this nature led by a United Kingdom Sponsor, as well as those specific to the delivery of Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial, were addressed. Objectives The overarching aim of Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial was to submit a stage 1 application for the Efficacy and Mechanism Evaluation call: 23/15 precision medicine platform studies to efficiently evaluate the efficacy of interventions. In delivering this, we met the following objectives: Understand optimal sponsorship, governance and funding models for international platform trials by synthesising relevant literature in the form of systematic review. Convene and engage an international at risk of rheumatoid arthritis Precision Platform Trial Management Group with expertise in the pathobiological understanding and therapeutic management of at risk of rheumatoid arthritis, as well as the design and delivery of interception trials, with a view to developing a master protocol. Convene and consult a Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial Public Advisory Group to directly inform trial design, including a strategy for mapping the level of rheumatoid arthritis progression risk to lifestyle and/or pharmacological interventions. Identify interventions to be evaluated in a platform trial, engaging appropriately with industry partners. Identify optimal clinical and/or immunological biomarkers for participant stratification. Outcomes Five work streams were set up to target delivery of the aforementioned objectives. A systematic review entitled ‘Operational complexities in international clinical trials: a systematic review of challenges and proposed solutions’ has been registered with the Open Science Framework, completed and submitted for publication. Linked to this, a working group was established to identify barriers and solutions to acting as Sponsor for Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial; purposeful interactions with European Union and United Kingdom partner sites helped prioritise governance and funding models to enable delivery, and have informed local standard operating procedures for sponsoring international trials. A patient and public involvement Advisory group was formed, and a series of events and programme of work undertaken to feed into all aspects of Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial. A range of potential interventions, non-pharmacological and pharmacological, were considered and prioritised for inclusion in Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial’s design. A funding framework supported by industry partners, incorporating one lifestyle and two drug interventions, was developed, along with a strategy for prioritising future interventions. A working group was furthermore convened for the management of biological samples to be collected for research in biomarker evaluations. A stage 1 application for the 23/15 Efficacy and Mechanism Evaluation call was submitted in May 2023. Limitations In its first iteration, the substantive clinical trial proposal proposed as a result of the Accelerator award reported herein was not funded by National Institute for Health and Care Research. In part this was due to the approach adopted to address the ‘precision medicine’ element of the brief. Other challenges include the assembly of geographically diverse patient partners for an international study given time constraints, and logistical complexity in international trial design. Future work Efforts to fund the work described in amended form are ongoing. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme as award number NIHR153955. Plain language summary Rheumatoid arthritis is a common long-term condition in which the immune system causes joint damage, leading to pain and reduced well-being. Some people who develop musculoskeletal pain and are found to have abnormalities in their immune systems on blood testing are at increased risk of rheumatoid arthritis. Researchers suspect certain treatments could relieve their symptoms and prevent them from developing the disease. This could have major benefits for society. A few clinical trials have tried to test whether taking certain drugs for a limited period might delay or prevent rheumatoid arthritis. However, it can prove difficult to find enough participants from routine rheumatology clinics to carry out such studies. In addition, people’s risk of developing rheumatoid arthritis varies: a person at slightly increased risk might not want a drug that could cause side effects, but a person at very high risk might. More ‘personalised’ trial designs are therefore needed. The National Institute for Health and Care Research Efficacy and Mechanism Evaluation Acceleration Award provided 12 months of support to address these challenges. We proposed a Newcastle-led, international ‘platform trial’. In platform trials, different treatments can be tested in different sections (arms) of a single trial. Treatments can be added or removed as results come in, without needing to start up a new trial each time. In Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial, an international team came together, including experts in trial design and people with lived experience of being at risk of rheumatoid arthritis and/or trial participation. Working with partners in the pharmaceutical industry, we submitted a National Institute for Health and Care Research proposal. In it, we wanted to test a non-drug treatment in a ‘low-risk’ arm (for people at only slightly increased risk of rheumatoid arthritis), and a drug treatment in the ‘high-risk’ arm, for those at higher risk. The ultimate aim was to bring about a step change in the management of rheumatoid arthritis that recognises prevention is better than cure.https://doi.org/10.3310/ASHG1864platform trialat-risk rheumatoid arthritisoperational challengeseuropeanstratifiedbiomarkers |
| spellingShingle | Michelle Bardgett Marie Falahee Gwenda Simons John D Isaacs Luke Ouma James MS Wason Arthur G Pratt Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial delivery (RAPPORT) Efficacy and Mechanism Evaluation platform trial at-risk rheumatoid arthritis operational challenges european stratified biomarkers |
| title | Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial delivery (RAPPORT) |
| title_full | Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial delivery (RAPPORT) |
| title_fullStr | Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial delivery (RAPPORT) |
| title_full_unstemmed | Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial delivery (RAPPORT) |
| title_short | Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial delivery (RAPPORT) |
| title_sort | rheumatoid arthritis prevention catalysing platform trial delivery rapport |
| topic | platform trial at-risk rheumatoid arthritis operational challenges european stratified biomarkers |
| url | https://doi.org/10.3310/ASHG1864 |
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