Telemedicine Use, Comfort, and Perceived Effectiveness in the Spinal Muscular Atrophy Community.

Background: Telemedicine may increase access to clinical care, particularly for mobility-limited communities such as the spinal muscular atrophy (SMA) community. However, much of the information on exposure to and attitudes toward telemedicine in neuromuscular diseases generally and SMA specifically is anecdotal or from focus groups. Gaining greater insight into patient perspectives is important, given telemedicine's potential for expanding access to care and growing use of telemedicine as a result of technology advances and the COVID-19 pandemic. Methods: Cure SMA collected information on the SMA community's exposure to, comfort with, and perceived effectiveness of telemedicine through its 2021 Community Update Survey. The final analytic sample represented 463 SMA-affected individuals, resident in the United States. Descriptive analyses, correlations, and ordered logit regression models were used to characterize the sample and identify predictors of exposure, comfort, and perceived effectiveness. Data were analyzed on weighted and unweighted bases to account for differences between the survey sample and the SMA community. Stratified analyses were used to compare self-completed surveys with caregiver-completed surveys. Results: 463 individuals answered questions about telemedicine. Approximately four-fifths of these respondents had used telemedicine previously. Factors predicting greater likelihood of prior telemedicine use included male gender, increasing income, having received drug treatment for SMA, history of mental illness, and having non-neutral views regarding comfort and perceived effectiveness of telemedicine. Several factors were also significant predictors of comfort with and perceived effectiveness of telemedicine. Stratified analyses indicated differences between self-completed and caregiver-completed surveys. Conclusion: These results can provide insight into patient experiences with telemedicine and can inform approaches to its use by health care professionals and clinical trial sponsors.

Evaluating Perceived Fatigue within an Adult Spinal Muscular Atrophy Population.

INTRODUCTION: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive muscle weakness and atrophy. While chronic fatigue is a common manifestation of SMA, the field lacks comprehensive data to assess the extent of its impact. Cure SMA, an SMA patient advocacy organization, conducted an online survey of its adults with SMA community members to measure the impact of fatigue. METHODS: All survey respondents were asked to complete questions on demographics, use of SMA treatment, and quality of life, but respondents were randomized to receive three of the following fatigue instruments: the Modified Fatigue Impact Scale (MFIS), Multidimensional Fatigue Inventory (MFI), Fatigue Severity Scale (FSS), PedsQL™ Multidimensional Fatigue (PedsQL MF) Scale, and Spinal Muscular Atrophy Health Index (SMA-HI) fatigue modules. Scales were evaluated for reliability and overall fatigue scores were evaluated by multivariate regression models to determine which variables were related to the final scores of each instrument. RESULTS: A total of 253 adults completed the online survey. When measured against the general population, statistically significant differences were found among adults with SMA for certain variables within each measurement instrument. However, there did not appear to be differences in fatigue levels among key subgroups within the SMA population. CONCLUSIONS: This was the first use of more than two fatigue questionnaires simultaneously in SMA. The lack of a consistent relationship between SMA severity and fatigue levels was surprising. This may be related to the lack of specificity of the instruments for this population. An SMA-specific scale is needed to evaluate differences in fatigue impact across the SMA population.

Effects of the COVID-19 Pandemic on SMA Screening and Care: Physician and Community Insights.

OBJECTIVE: As part of efforts to reduce diagnostic delays and enhance clinical trials, Cure SMA evaluated the effects of COVID-19 on SMA care and clinical trial conduct. INTRODUCTION: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive, potentially debilitating muscle weakness and atrophy. Uninterrupted access to early diagnosis, disease-modifying treatment, and care for SMA is vital to avoiding irreversible motor neuron death and achieving optimal patient outcomes. METHODS: Two surveys were conducted: a provider survey and a community survey. The Provider Impact Survey, distributed from November 24, 2020, through March 8, 2021, assessed COVID-19's effects on referrals for evaluation of suspected SMA, cancellations and delays of SMA-related care, and clinical trials. The Community Impact Survey was fielded in three waves between April 7, 2020 and July 19, 2021, in tandem with Cure SMA COVID-19 support programs. RESULTS: A total of 48 completed provider surveys (22 from care sites, 26 from care-and-trial sites) reflected decreases in referrals for suspected SMA, increases in appointment cancellations and delays, and patient reluctance to attend in-person visits due to COVID-19. One-third of care-and-trial sites reported trial recruitment delays, and one-quarter reported pausing trial enrollment. Results of the Community Impact Survey, completed by 2047 individuals, showed similar disruptions, with 55% reporting changes or limitations in accessing essential SMA-related services. CONCLUSIONS: This research evaluates the pandemic's interruption of SMA care and research. These insights can help mitigate and increase preparedness for future disruptive events. Expanded use of virtual tools including telehealth and remote monitoring may enhance continuity and access. However, additional research is required to evaluate their effectiveness. While this research was specific to SMA, its findings may have relevance for other patient communities.

Clinical and Research Readiness for Spinal Muscular Atrophy: The Time Is Now for Knowledge Translation.

Disease-modifying therapies for spinal muscular atrophy (SMA) are rapidly changing the outlook for many individuals by substantially altering the clinical course, phenotypic expression, and functional outcomes. Physical therapists have played critical roles in the effective conduct and execution of clinical trials leading to the approval of these therapies. Given the treatment landscape, educating practicing clinicians to understand best practice is of great importance, and a timely call to action to facilitate knowledge translation from SMA researchers to clinicians is necessary. The SMA Clinical Trial Readiness Program engaged clinical and research centers, identified physical therapy knowledge gaps related to evaluation and outcomes assessment, and provided educational resources, including the development of a SMA Best Practices Clinical Evaluator Toolkit. Toolkit content synthesizes evidence and covers a breadth of issues relevant to practice, including background on SMA and the drug pipeline; therapist roles and responsibilities related to research; clinical and research evaluation; and useful materials and resources for additional education, training, and professional development. Surveys and telephone interviews were conducted with physical therapists managing individuals with SMA to determine their SMA practice experience and educational needs. Their recommendations, along with synthesized SMA research evidence, provided input into toolkit content development and assisted in identifying gaps important to address. Impact was assessed over time via utilization feedback surveys downloaded by clinicians across various settings. Open-ended feedback supported beneficial use of the toolkit for clinicians and researchers working with individuals with SMA. Next steps should include timely dissemination to bring this resource and others into practice in a systematic, efficacious, and engaging manner. As the treatment landscape for SMA evolves, the therapist's role in multidisciplinary care and research is of great importance, and a call to action for the development, implementation, evaluation and reporting of informed knowledge using evidence-based knowledge translation strategies is critical. IMPACT: Partnership among patient advocacy groups, industry collaborators, and key opinion leaders/experts can optimize essential resource development to address the knowledge gap for best practices in physical therapy. This partnership model can be replicated for other diseases, providing an efficient way to support clinical trial readiness and target early development of evidence-based content and resources related to both research and best practice clinical evaluation for physical therapist researchers, clinicians, and patients. While identifying knowledge gaps and resource development are initial steps toward change in SMA practice, a rapidly changing rehabilitation outlook warrants a call to action for enhanced efforts aimed at improving rehabilitation evaluation, assessment, and care for this population. It is critical to forge a timely path forward for development, implementation, and sustainability of effective knowledge translation to practice for SMA.

The Cure SMA Clinical Trial Experience Survey: A Study of Trial Participant Perspectives on Clinical Trial Management and Patient-Centric Management Practices.

INTRODUCTION: Understanding clinical trial experiences can illuminate opportunities to optimize trial design and management, with potential benefits for recruitment and retention. This study sought to better understand clinical trial participant experiences and attitudes within spinal muscular atrophy (SMA), and how the evolving treatment landscape and participant characteristics may predict attitudes. METHODS: A survey was developed following a review of published literature and discussions with caregivers of SMA trial participants. This was distributed via email to known trial participants in Cure SMA's database, announcements in Cure SMA's newsletter, and emails to SMA clinical trial principal investigators. RESULTS: Seventy complete surveys reflecting unique clinical trial experiences were included in analysis. Responses revealed positive attitudes about clinical trial management overall. Top motivators for trial participation included clinical benefit, investigational drug access, and the opportunity to help others. Top concerns were safety, whether benefits would justify risks, and concerns about pain accompanying tests. The greatest stressors were fear of pain, adverse event concerns, and challenges managing medical complications of SMA. Top benefits of trial participation were hope for a better future, helping others, and relationships with the study team. In regression analysis, participant gender, age, and race all emerged as significant predictors (p < 0.05) of motivators, concerns, stressors, and benefits, as did respondent type, knowledge about SMA, distance to the trial site, and treatment era. Top recommendations for improving study management all related to receiving more information. CONCLUSION: This research provides new perspective on patient experiences in SMA clinical trials. It underscores the importance of information and efforts to anticipate and accommodate participant needs. These findings may inform study design and interactions with research participants. They may become especially important in supporting recruitment and retention as more treatment options become available.

Clinical trials can be stressful experiences for patients and their caregivers, especially when participants are affected by serious diseases. By understanding trial participants' attitudes and experiences, researchers may be better able to accommodate their interests when designing and conducting research studies. This study sought insight into attitudes and experiences of spinal muscular atrophy (SMA) clinical trial participants by surveying people who participated in SMA clinical trials in the USA. The data used in analysis reflected 70 unique clinical trial experiences. Survey responses revealed positive attitudes about clinical trial management overall. Top motivators for trial participation included clinical benefit, investigational drug access, and the opportunity to help others. Top concerns were safety, whether benefits would justify risks, and concerns about pain accompanying tests. The greatest stressors were fear of pain, adverse event concerns, and challenges managing medical complications of SMA. Top benefits of trial participation were hope for a better future, helping others, and relationships with the study team. Whether or not specific motivators, concerns, stressors, and benefits were important was predicted by participant gender, age, and race, as well as respondent type (participant or caregiver), knowledge about SMA, distance to the trial site, and treatment era. Top recommendations for improving study management all related to receiving more information. This research provides new perspective on patient experiences in SMA clinical trials, and may be used to inform future study design and interactions with research participants.

The SMA Clinical Trial Readiness Program: creation and evaluation of a program to enhance SMA trial readiness in the United States.

Spinal muscular atrophy (SMA) is a rare neuromuscular disease with a rapidly evolving treatment landscape. To better meet the needs of trial sponsors and the patient community in the United States (US) in this evolving context, Cure SMA established a clinical trial readiness program for new and prospective SMA clinical trial sites. Program development was informed by a review of the SMA clinical trial landscape, successful NMD trial and care networks, and factors important to effective trial conduct in SMA. The program was piloted in 2018 with a virtual site readiness evaluation, a trial readiness toolkit, and a readiness program for physical therapists and clinical evaluators. Nine US research hospitals participated in the pilot. Cure SMA evaluated the pilot program and resources through feedback surveys, which supported the program's relevance and value. Since 2018, the program has been expanded with additional sites, new best practices toolkits, and workshops. In partnership with Cure SMA, SMA Europe is also extending programming to European countries. The program is significant as an example of a patient advocacy group working successfully with pharmaceutical companies, other patient advocacy organizations, and research hospitals to promote trial readiness, and may serve as a model for organizations in other regions and diseases.

The Progressive Multifocal Leukoencephalopathy Consortium as a Model for Advancing Research and Dialogue on Rare Severe Adverse Drug Reactions.

Progressive multifocal leukoencephalopathy (PML) is a rare but serious disease. Caused by the JC virus (JCV), it occurs in individuals with weakened immune systems and is a potential adverse reaction for certain immunomodulatory drugs. The PML Consortium was created to find better methods to predict, prevent, and treat PML. The Consortium brought together the pharmaceutical industry with academic, regulatory, and patient communities to advance research and dialogue on PML through a not-for-profit, collaborative approach involving a grant program, scientific workshops and conferences, and disease awareness efforts. Over nearly a decade, the Consortium contributed to the PML and JCV fields by advancing research, scientific exchange, and awareness of PML. In addition to advancing knowledge and helping to build cross-sector consensus on research priorities, the Consortium's grant program filled a funding gap and brought new investigators into PML and JCV research. Additionally, the Consortium's workshops and conferences created platforms for exchange that drove dialogue on knowledge gaps and future research directions. The Consortium also contributed to the scientific knowledge base with two literature reviews, one on PML treatment studies and a second on T cell deficiencies as a risk factor for PML and the brain as a site for conversion of harmless JCV into a pathogenic virus. Finally, the Consortium addressed a significant information gap with its disease awareness website for healthcare professionals, patients, and caregivers. Beyond its impact on the PML and JCV fields, the PML Consortium is important because it provides a precedent for how the pharmaceutical industry, academic researchers, patient organizations, and government can work together to address rare diseases, in particular rare adverse events. This kind of collaboration could be replicated to speed progress in addressing other rare diseases and adverse events, with significant potential benefits for the scientific, medical, and patient communities. FUNDING: PML Consortium (PML Consortium, Washington, DC).

T cell deficiencies as a common risk factor for drug associated progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a disease of the central nervous system caused by neuropathogenic prototypes of ubiquitous community-acquired JC virus (JCV). The disease became of particular concern following its association with certain therapies that modulate immune system function without heavy immunosuppression. Due to lack of prophylactic/treatment options and poor outcomes, which often include severe disability or death, PML is a considerable concern for development of new drugs that interfere with immune system functions. In this review of clinical and research findings, we discuss the evidence that deficiencies in CD4+ T helper cells, cytotoxic CD8+ T cells, and interferon gamma are of crucial importance for development of PML under a variety of circumstances, including those associated with use of various drugs, regardless of differences in their mechanisms of action. These deficiencies apparently enable transformation of the harmless JCV archetype into neuropathogenic prototypes, but the site(s), and the mechanisms, of this transformation are yet to be elucidated. Here we discuss the evidence for brain as one of the sites of this transformation, and propose a model of PML pathogenesis that emphasizes the central role of T cell deficiencies in the two life cycles of the JCV, one non-pathogenic and one neuropathogenic. Finally, we conclude that the development of clinical grade T cell functional tests and more consistent use of already available laboratory tests for T cell subset analysis would greatly aid the effort to more accurately predict and assess the magnitude of PML risk for concerned therapeutic interventions.

Equivalence considerations for orally inhaled products for local action-ISAM/IPAC-RS European Workshop report.

The purpose of this article is to document the discussions at the 2010 European Workshop on Equivalence Determinations for Orally Inhaled Drugs for Local Action, cohosted by the International Society for Aerosols in Medicine (ISAM) and the International Pharmaceutical Consortium on Regulation and Science (IPAC-RS). The article summarizes current regulatory approaches in Europe, the United States, and Canada, and presents points of consensus as well as ongoing debate in the four major areas: in vitro testing, pharmacokinetic and pharmacodynamic studies, and device similarity. Specific issues in need of further research and discussion are also identified.