Enhancing involvement of people with multiple sclerosis in clinical trial design

Background: Although often overlooked, patient and public involvement (PPI) is vital when considering the design and delivery of complex and adaptive clinical trial designs for chronic health conditions such as multiple sclerosis (MS). Methods: We conducted a rapid review to assess current status of PPI in the design and conduct of clinical trials in MS over the last 5 years. We provide a case study describing PPI in the development of a platform clinical trial in progressive MS. Results: We identified only eight unique clinical trials that described PPI as part of articles or protocols; nearly, all were linked with funders who encourage or mandate PPI in health research. The OCTOPUS trial was co-designed with people affected by MS. They were central to every aspect from forming part of a governance group shaping the direction and strategy, to the working groups for treatment selection, trial design and delivery. They led the PPI strategy which enabled a more accessible, acceptable and inclusive design. Conclusion: Active, meaningful PPI in clinical trial design increases the quality and relevance of studies and the likelihood of impact for the patient community. We offer recommendations for enhancing PPI in future MS clinical trials

Optimising recruitment in clinical trials for progressive multiple sclerosis: observational analysis from the MS-SMART and MS-STAT2 randomised controlled trials

BACKGROUND: Slower than planned recruitment is a major factor contributing to the delay or failure of randomised controlled trials to report on time. There is a limited evidence base regarding the optimisation of recruitment strategies. Here we performed an observational review of our experience in recruitment for two large randomised controlled trials for people with secondary progressive multiple sclerosis. We aimed to explicitly determine those factors which can facilitate trial recruitment in progressive neurodegenerative disease. METHODS: Recruitment data from the sequential MS-SMART [NCT01910259] and MS-STAT2 [NCT03387670] UK randomised controlled trials was reviewed from the largest recruiting site, University College London (UCL). The trial population was similar which allowed comparison over the two recruitment periods of 2015-2016 and 2018-2021. This included sources of referral, progress through stages of recruitment, reasons for participant ineligibility and the impact of publicity events upon recruitment. RESULTS: In MS-SMART, 18% of patients contacted were enrolled, compared to 27% for MS-STAT2. Online registration of interest portals provided the greatest number of referrals (76% in MS-SMART, and 51% in MS-STAT2), with publicity in national media outlets producing a demonstrable increase in the number of potential participants. The introduction of an online self-screening questionnaire for MS-STAT2 resulted in 67% of potential participants (3080 of 4605) automatically determining their own ineligibility. In both studies, however, around 60% of those directly telephoned to discuss the study were not eligible, with difficulties related to travel to trial visits, or excluded medication, being the most common issues. Eighty-four percent of those deemed potentially eligible following telephone calls were enrolled in the MS-STAT2 study, compared to only 55% for MS-SMART. CONCLUSIONS: Through a detailed review of recruiting participants at the largest centre into two large randomised controlled trials with similar entry criteria, we have identified a number of approaches that may improve recruitment efficiency. We highlight here the importance of mandatory online self-screening questionnaires, a coordinated publicity campaign, and simple interventions such as eligibility checklists and appointment reminders. Recruitment approaches should be further assessed through a studies within a trial (SWAT) design. TRIAL REGISTRATION: MS-SMART: NCT01910259 ; registered July 2013 and MS-STAT2: NCT03387670 ; registered Jan 2018

Enhancing involvement of people with multiple sclerosis in clinical trial design

Background: Although often overlooked, patient and public involvement (PPI) is vital when considering the design and delivery of complex and adaptive clinical trial designs for chronic health conditions such as multiple sclerosis (MS). Methods: We conducted a rapid review to assess current status of PPI in the design and conduct of clinical trials in MS over the last 5 years. We provide a case study describing PPI in the development of a platform clinical trial in progressive MS. Results: We identified only eight unique clinical trials that described PPI as part of articles or protocols; nearly, all were linked with funders who encourage or mandate PPI in health research. The OCTOPUS trial was co-designed with people affected by MS. They were central to every aspect from forming part of a governance group shaping the direction and strategy, to the working groups for treatment selection, trial design and delivery. They led the PPI strategy which enabled a more accessible, acceptable and inclusive design. Conclusion: Active, meaningful PPI in clinical trial design increases the quality and relevance of studies and the likelihood of impact for the patient community. We offer recommendations for enhancing PPI in future MS clinical trials

Some Nova Scotia Women Artists

Sparling notes questions raised by the exhibition of works by 23 Nova Scotia artists. Statement by some of the artists. Biographical notes

Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis.

OBJECTIVE: To establish a rigorous, expert-led, evidence-based approach to the evaluation of licensed drugs for repurposing and testing in clinical trials of people with progressive multiple sclerosis (MS). METHODS: We long-listed licensed drugs with evidence of human safety, blood-brain barrier penetrance and demonstrable efficacy in at least one animal model, or mechanistic target, agreed by a panel of experts and people with MS to be relevant to the pathogenesis of progression. We systematically reviewed the preclinical and clinical literature for each compound, condensed this into a database of summary documents and short-listed drugs by scoring each one of them. Drugs were evaluated for immediate use in a clinical trial, and our selection was scrutinised by a final independent expert review. RESULTS: From a short list of 55 treatments, we recommended four treatments for immediate testing in progressive MS: R-α-lipoic acid, metformin, the combination treatment of R-α-lipoic acid and metformin, and niacin. We also prioritised clemastine, lamotrigine, oxcarbazepine, nimodipine and flunarizine. CONCLUSIONS: We report a standardised approach for the identification of candidate drugs for repurposing in the treatment of progressive MS.JB received expense payments from Novartis for speaking as patient representative during Siponimod licensing. AJC receives funding from the MRC and MS Society UK. DF is funded by the Wellcome and BBSRC, and has a project with Sangamo. A.G. de la Fuente has been supported by the ECTRIMS postdoctoral fellowship during this period. GG declares current research funding from Merck KGa (CLAD-B study), Roche (ORATORIO-HAND study) and Takeda (SIZOMUS Study). DM received funding previously from Biogen, MedDay and SanofiGenzyme. BN received funding from the Cambridge Centre for Myelin Repair, funded by MS Society UK. SP declares current funding from Italian and US Multiple Sclerosis Societies. LP has been supported by a senior research fellowship FISM - Fondazione Italiana Sclerosi Multipla - cod. 2017/B/5 and financed or co financed with the ‘5 per mille' public funding, by the Isaac Newton Trust RG 97440 and the Addenbrooke’s Charitable Trust RG 97519. KS declares current funding from Fondation Leducq, Multiple Sclerosis Society, Rosetrees Trust. A. Wilkins received a research grant from Sanofy (2018). A. Williams declares funding from MS Society UK, Roche, MRC, Lifearc

Minimalism

A reappraisal of Minimalism from a contemporary perspective, this book documents the careers of its leading figures as well as the practices of other associated artists. Meyer surveys its development within a broad historical and cultural context, defining Minimalism as a debate rather than a movement. Reproductions of the most significant Minimal art works, exhibitions, and contemporaries’ work are included, along with the key critical texts, artists’ statements, reviews and commentary on the movement. 330 bibl. ref. Biographical notes. Bibl. 3 p. Index of names and artworks, 5 p

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes