Improving the efficiency of clinical trials in multiple sclerosis

BACKGROUND: Phase 3 clinical trials for disease-modifying therapies in relapsing-remitting multiple sclerosis (RRMS) have utilized a limited number of conventional designs with a high degree of success. However, these designs limit the types of questions that can be addressed, and the time and cost required. Moreover, trials involving people with progressive multiple sclerosis (MS) have been less successful. OBJECTIVE: The objective of this paper is to discuss complex innovative trial designs, intermediate and composite outcomes and to improve the efficiency of trial design in MS and broaden questions that can be addressed, particularly as applied to progressive MS. METHODS: We held an international workshop with experts in clinical trial design. RESULTS: Recommendations include increasing the use of complex innovative designs, developing biomarkers to enrich progressive MS trial populations, prioritize intermediate outcomes for further development that target therapeutic mechanisms of action other than peripherally mediated inflammation, investigate acceptability to people with MS of data linkage for studying long-term outcomes of clinical trials, use Bayesian designs to potentially reduce sample sizes required for pediatric trials, and provide sustained funding for platform trials and registries that can support pragmatic trials. CONCLUSION: Novel trial designs and further development of intermediate outcomes may improve clinical trial efficiency in MS and address novel therapeutic questions

Continuous Positive Airway Pressure: Is it a route for infection in those with Obstructive Sleep Apnoea?

Introduction: Continuous positive airway pressure (CPAP) is the standard treatment for obstructive sleep apnoea (OSA), with limited data about the prevalence of respiratory infections and microbial colonization in these patients. Objectives: The aim of this study was to determine if CPAP use is associated with respiratory infections and to identify the organisms that colonize or infect these patients. Method: A retrospective, case-controlled study in patients diagnosed with OSA was carried out. 137 patients were recruited and interviewed using a questionnaire. A nasal swab was taken from each patient. Patients using CPAP machines had swabs taken from masks and humidifiers. Results: 66 (48.2%) patients received CPAP treatment with 60.6% of them having a heated humidifier. 78.8% were male, with the majority using a full face mask (63.6%). No significant difference was seen in the prevalence of rhinosinusitis, lower respiratory tract infections and hospital admissions for pneumonia between CPAP and non-CPAP treated patients. The presence of a humidifier did not influence the prevalence of infections. Commensal flora was predominantly cultured from nasal swabs from both patient groups. Coagulase Negative Staphylococci and Diphtheroids were the main organisms cultured from masks and humidifiers respectively. Conclusions: This study shows that the use of CPAP, choice of mask and humidifier have no significant impact on the prevalence of infections and micro-organisms isolated. This is very reassuring to the physician prescribing CPAP therapy and users

Improving the efficiency of clinical trials in multiple sclerosis

Background:Phase 3 clinical trials for disease-modifying therapies in relapsing-remitting multiple sclerosis (RRMS) have utilized a limited number of conventional designs with a high degree of success. However, these designs limit the types of questions that can be addressed, and the time and cost required. Moreover, trials involving people with progressive multiple sclerosis (MS) have been less successful. Objective:The objective of this paper is to discuss complex innovative trial designs, intermediate and composite outcomes and to improve the efficiency of trial design in MS and broaden questions that can be addressed, particularly as applied to progressive MS. Methods:We held an international workshop with experts in clinical trial design. Results:Recommendations include increasing the use of complex innovative designs, developing biomarkers to enrich progressive MS trial populations, prioritize intermediate outcomes for further development that target therapeutic mechanisms of action other than peripherally mediated inflammation, investigate acceptability to people with MS of data linkage for studying long-term outcomes of clinical trials, use Bayesian designs to potentially reduce sample sizes required for pediatric trials, and provide sustained funding for platform trials and registries that can support pragmatic trials. Conclusion:Novel trial designs and further development of intermediate outcomes may improve clinical trial efficiency in MS and address novel therapeutic questions

Thrombus Distribution in Vaccine-induced immune thrombotic thrombocytopenia after ChAdOx1 nCov-19 Vaccination

This case series reports 40 patients (median age, 41 years [interquartile range (IQR) 32- 52, 22 men) with confirmed vaccine-induced immune thrombotic thrombocytopaenia after administration of their first ChAdOx1 nCov-19 (AstraZeneca) vaccine: 80% (n=32) developed symptoms within the first 14 days and 20% (n=8) within 14-28 days. The location and extent of thrombi were evaluated using CT, MRI and ultrasound. Of the 40, 73% (n=29) presented with neurological symptoms and had confirmed cerebral venous sinus thrombosis, 30% (n=12) had extension of their primary thrombus, and 20% (n=8) died. 83% of those who underwent additional imaging (25 of 30) had occult thrombosis