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.

Assessing perspectives of disease burden and clinically meaningful changes using the Spinal Muscular Atrophy Health Index in adolescents and young adults.

INTRODUCTION/AIMS: Spinal muscular atrophy (SMA) treatment may increase survival and improve physical function among adolescents and young adults. Validated patient-reported outcome measures are needed to understand which treatment benefits are clinically meaningful and to develop targeted resources for this population. To date, use of the SMA Health Index (SMA-HI) in pediatric and young adult populations has been limited. Here, we report results from a survey of adolescents and young adults with SMA to quantifiably understand individuals' perceptions of disease burden. METHODS: Participants aged 12-25 y with a self-reported diagnosis of SMA completed an online survey containing demographic questions and the SMA-HI, a patient-reported outcome measure that assesses individuals' perceptions of disease burden in 15 symptomatic areas. RESULTS: Eighty-eight participants completed the survey. Total SMA-HI scores and SMA-HI subscale scores including shoulder and arm function; back, chest, and abdominal function; activity participation; hand and finger strength; swallowing function; gastrointestinal function; respiratory function; mobility and ambulation, and total disease burden were significantly higher (greater disease burden) in patients with poorer motor function and severe SMA. SMA-HI total and subscale scores were generally lower in adolescents (12-17 y old) versus adults (18-25 y old), suggesting a possible progression of symptomatic disease burden over time. DISCUSSION: This study demonstrates the utility of the SMA-HI for measuring clinically relevant disease burden in adolescents and young adults with SMA. This study demonstrates how disease burden varies by age, SMA type, and other demographics.

Investigating attitudes toward prenatal diagnosis and fetal therapy for spinal muscular atrophy.

OBJECTIVE: In utero SMA treatment could improve survival and neurologic outcomes. We investigated the attitudes of patients and parents with SMA regarding prenatal diagnosis, fetal therapies, and clinical trials. METHODS: A multidisciplinary team designed a questionnaire that Cure SMA electronically distributed to parents and patients (>18 years old) affected by SMA. Multivariable ordinal logistic regression was used to analyze associations between respondent characteristics and attitudes. RESULTS: Of 114 respondents (60% of whom were patients), only 2 were prenatally diagnosed. However, 91% supported prenatal testing and 81% felt there had been a delay in their diagnosis. Overall, 55% would enroll in a phase I trial for fetal antisense oligonucleotide (ASO) while 79% would choose an established fetal ASO/small molecule therapy. Overall, 61% would enroll in fetal gene therapy trials and 87% would choose fetal gene therapies. Patients were less likely to enroll in a fetal gene therapy trial than parents enrolling a child (OR 0.31, p < 0.05). Older parental age and believing there had been excessive delay in diagnosis were associated with an interest in enrolling in a fetal ASO trial (OR 1.04, 7.38, respectively, p < 0.05). CONCLUSION: In utero therapies are promising for severe genetic diseases. Patients with SMA and their parents view prenatal testing and therapies positively, with gene therapy being favored.

Understanding the relationship between the 32-item motor function measure and daily activities from an individual with spinal muscular atrophy and their caregivers' perspective: a two-part study.

BACKGROUND: The 32-item Motor Function Measure (MFM32) is a clinician-reported outcome measure used to assess the functional abilities of individuals with neuromuscular diseases, including those with spinal muscular atrophy (SMA). This two-part study explored the relationship between the functional abilities assessed in the MFM32 and activities of daily living (ADLs) from the perspective of individuals with Type 2 and Type 3 (non-ambulant and ambulant) SMA and their caregivers through qualitative interviews and a quantitative online survey. METHODS: In-depth, semi-structured, qualitative interviews were conducted with individuals with SMA and caregivers from the US. Subsequently, a quantitative online survey was completed by individuals with SMA or their caregivers from France, Germany, Italy, Poland, Spain, Canada, the United States (US) and the UK. In both parts of the study, participants were asked to describe the ADLs considered to be related to the functional abilities assessed in the MFM32. Results from the qualitative interviews informed the content of the quantitative online survey. RESULTS: Qualitative interviews were conducted with 15 adult participants, and 217 participants completed the quantitative online survey. From the qualitative interviews, all of the functional abilities assessed in the patient-friendly MFM32 were deemed as related to one or more ADL. The specific ADLs that participants considered related to the patient-friendly MFM32 items could be grouped into 10 key ADL domains: dressing, mobility/transferring, self-care, self-feeding, reaching, picking up and holding objects, physical activity, writing and technology use, social contact/engagement, toileting and performing work/school activities. These results were confirmed by the quantitative online survey whereby the ADLs reported to be related to each patient-friendly MFM32 item were consistent and could be grouped into the same 10 ADL domains. CONCLUSION: This study provides in-depth evidence from the patient/caregiver perspective supporting the relevance of the patient-friendly MFM32 items to the ADLs of individuals with Type 2 and Type 3 SMA.

Awareness screening and referral patterns among pediatricians in the United States related to early clinical features of spinal muscular atrophy (SMA).

BACKGROUND: Spinal Muscular Atrophy (SMA), a leading genetic cause of death in infants, is an autosomal recessive neuromuscular disease characterized by progressive muscle weakness and atrophy. While early diagnosis of SMA is critical to modifying disease progression and improving outcomes, serious diagnostic delays persist. There is a need to improve SMA awareness, screening, and referral patterns. METHODS: Two online surveys, developed by Cure SMA for general pediatricians, were distributed by Medscape Education via email (September 2018, n = 300, December 2019, n = 600). The surveys asked about adherence to the American Academy of Pediatrics (AAP) developmental screening and surveillance guidelines, comfort with identification of early signs of neuromuscular disease (NMD), familiarity with SMA, and barriers to timely referral. RESULTS: In 2018, 70.3% of survey respondents indicated comfort in identifying early signs of NMD and 67.3% noted familiarity with SMA. 52.7% correctly indicated the need for genetic testing to make a definitive diagnosis of SMA, 74.0% meet or exceed developmental screening recommendations, and 52.0% said they would immediately refer to a specialist. In 2019, with a larger sample, 73.0% adhere to developmental screening guidelines, and awareness of the genetic testing requirement for SMA was significantly lower by 7.7% (p < 0.03). Specialist wait times emerged as a barrier to referral, with 64.2% of respondents citing wait times of 1-6 months. CONCLUSIONS: Many pediatricians underutilize developmental screening tools and lack familiarity with diagnostic requirements for SMA. Continuing efforts to expand awareness and remove barriers to timely referral to SMA specialists, including reducing appointment wait times, are needed.

Barriers and facilitators to clinical trial participation among parents of children with pediatric neuromuscular disorders.

BACKGROUND/AIMS: Pediatric rare disease presents a challenging situation of high unmet need and a limited pool of potential clinical trial participants. Understanding perspectives of parents of children who have not participated in trials may facilitate approaches to optimize participation rates. The objective of this study was to explore factors associated with parental interest in enrolling children with pediatric neuromuscular disorders in clinical trials. METHODS: Parents of individuals with Duchenne or Becker muscular dystrophy and spinal muscular atrophy were recruited through advocacy organizations, a registry, and clinics. These parents ( N = 203) completed a questionnaire including assessments of barriers and facilitators to clinical trial participation, parents' interest in trial participation, and their perceptions of others' views about participation in a clinical trial. RESULTS: Trial interest in participating parents was high (64% combined group). The most highly endorsed barrier to participation was the possibility of receiving placebo, followed by not having enough information on risks and trial procedures. Compared to parents of children with Duchenne or Becker muscular dystrophy, parents of children with spinal muscular atrophy endorsed significantly more information and knowledge barriers. The greatest facilitators of participation were (1) confidence in improving disease understanding and (2) guarantee to receive the treatment after a successful trial. A logistic regression model, χ2 (4, n = 188) = 80.64, p < .001, indicated that higher perceived barriers and more frequent trial communication by the provider were associated with lower interest, while positive trial perceptions by the child's providers and concordance in trial perceptions among those close to the decision-maker were associated with higher interest. CONCLUSION: We found high parental interest in pediatric neuromuscular trials that was tempered by concerns about the potential for randomization to a placebo arm. Participants perceived that their trial participation would be facilitated by additional education and guidance from their clinicians. Yet, intentions were negatively associated with frequency of provider communication, perhaps reflecting waning parental interest with a greater understanding of limitations in trial access, increased sophistication in their understanding of trial design, and appreciation of potential burden. To support parents' informed decisions, it is important to educate them to evaluate the quality of research, as well as providing lay information explaining the use of placebo, trial processes, and potential barriers to long-term drug access. Our findings should inform the development of targeted educational content, clinician training, and decision support tools.

An Evidence-Based, Community-Engaged Approach to Develop an Interactive Deliberation Tool for Pediatric Neuromuscular Trials.

Duchenne/Becker muscular dystrophy (DBMD) and spinal muscular atrophy (SMA) are rare neuromuscular disorders that present challenges to therapeutic and clinical trial decision making. We developed an interactive, evidence-based online tool designed to encourage thoughtful deliberation of the pros and cons of trial participation and to inform meaningful discussions with healthcare providers. Prior research demonstrates the importance of tool availability at the time each family is considering trial participation, which may be prior to the informed consent process. The tool is intended to be easily modified to other pediatric disease communities. Tool development was informed by prior qualitative research, literature reviews, and stakeholder input. Specific items were derived based on an online exploratory questionnaire of parents whose children participated in a trial for DBMD or SMA to understand motivations for participation. Parent participants in the exploratory survey reported strong impact of altruistic and individual benefit motivations and placed much greater emphasis on anticipated trial benefits than on harms when making participation decisions. We used this data to develop the evidence-based deliberation tool using a community-engaged approach. We initially targeted the tool for DBMD while using SMA survey data to evaluate ease of transition to that population. We conducted two iterative sets of activities to inform development and refinement of the tool: (1) community engagement of key stakeholders and (2) user experience testing. These activities suggest that the tool may increase deliberation and the weighing of benefits and harms. Ongoing evaluation will determine the acceptability and efficacy of this online intervention.

A qualitative study of perceptions of meaningful change in spinal muscular atrophy.

BACKGROUND: This qualitative study examined how individuals with Spinal Muscular Atrophy (SMA), their caregivers, and clinicians defined meaningful change, primarily in the Type II and non-ambulant type III patient populations, associated with treatment of this condition. In addition, we explored participants' views about two measures of motor function routinely used in clinical trials for these SMA subtypes, namely the expanded version of the Hammersmith Functional Motor Scale (HFMSE) and the Upper Limb Module (ULM). METHODS: The 123 participants (21 with SMA, 64 parents, and 11 clinicians), recruited through SMA advocacy organizations, participated in one of 16 focus groups or 37 interviews. The sessions were audio-recorded, and verbatim transcripts were analyzed using a grounded theory approach. RESULTS: For the participants, meaningful change was relative to functional ability, and small changes in motor function could have an important impact on quality of life. Because patients and families feared progressive loss of functional ability, the participants saw maintenance of abilities as a meaningful outcome. They believed that measures of motor function covered important items, but worried that the HFMSE and ULM might not be sensitive enough to capture small changes. In addition, they felt that outcome measures should assess other important features of life with SMA, including the ability to perform daily activities, respiratory function, swallowing, fatigue, and endurance. CONCLUSIONS: Given the heterogeneity of SMA, it is important to expand the assessment of treatment effects to a broader range of outcomes using measures sensitive enough to detect small changes.

The DcpS inhibitor RG3039 improves survival, function and motor unit pathologies in two SMA mouse models.

Spinal muscular atrophy (SMA) is caused by insufficient levels of the survival motor neuron (SMN) protein due to the functional loss of the SMN1 gene and the inability of its paralog, SMN2, to fully compensate due to reduced exon 7 splicing efficiency. Since SMA patients have at least one copy of SMN2, drug discovery campaigns have sought to identify SMN2 inducers. C5-substituted quinazolines increase SMN2 promoter activity in cell-based assays and a derivative, RG3039, has progressed to clinical testing. It is orally bioavailable, brain-penetrant and has been shown to be an inhibitor of the mRNA decapping enzyme, DcpS. Our pharmacological characterization of RG3039, reported here, demonstrates that RG3039 can extend survival and improve function in two SMA mouse models of varying disease severity (Taiwanese 5058 Hemi and 2B/- SMA mice), and positively impacts neuromuscular pathologies. In 2B/- SMA mice, RG3039 provided a >600% survival benefit (median 18 days to >112 days) when dosing began at P4, highlighting the importance of early intervention. We determined the minimum effective dose and the associated pharmacokinetic (PK) and exposure relationship of RG3039 and DcpS inhibition ex vivo. These data support the long PK half-life with extended pharmacodynamic outcome of RG3039 in 2B/- SMA mice. In motor neurons, RG3039 significantly increased both the average number of cells with gems and average number of gems per cell, which is used as an indirect measure of SMN levels. These studies contribute to dose selection and exposure estimates for the first studies with RG3039 in human subjects.

Understanding the experiences and needs of individuals with Spinal Muscular Atrophy and their parents: a qualitative study.

BACKGROUND: The clinical features of SMA, which range along a spectrum of severity, are relatively well described. In contrast, the literature on how individuals with SMA and their families experience this condition is limited. To address this gap, we undertook a qualitative study with individuals affected by SMA Types I, II and III, parents of those affected, and clinicians. METHODS: We completed 16 focus group sessions and 37 interviews in the US with 96 participants including: 21 with individuals with SMA; 64 parents of individuals affected by SMA; and 11 clinicians who specialize in the care of SMA patients. RESULTS: The Diagnostic Journey: Families reported substantial diagnostic delays owing to: 1) lack of awareness and knowledge about SMA; 2) the difficulty of distinguishing normal from abnormal development; and 3) the challenge of differential diagnosis. Lack of sensitivity in how clinicians communicated this potentially devastating diagnosis compounded parents' negative impressions. Newborn Screening: Parents generally held positive views about adding SMA to newborn screening panels. For example, it would: 1) enable earlier access to care; 2) shorten the diagnostic journey; and 3) give families more time to prepare to care for a disabled child. Some noted negative outcomes such as prematurely affecting a parent's relationship with a child before symptoms are evident. The Psychosocial Impact of Living with SMA: Ten thematic areas characterized the impact: 1) confronting premature death; 2) making difficult treatment choices; 3) fearing the loss of functional ability; 4) coming to terms with lost expectations; 5) loss of sleep and stress; 6) stigma; 7) limitations on social activities; 8) independence; 9) uncertainty and helplessness; and 10) family finances. CONCLUSIONS: The results of this study suggest high levels of burden experienced by individuals with SMA and their families. The difficulties of living with SMA begin with the long and often arduous process of finding a diagnosis for their child. Newborn screening for SMA is seen as an important step toward shortening this journey. The psychosocial effects of coping with SMA are substantial and wide ranging both for the individual living with this condition and family members of affected individuals.

Assessment of Barriers to Referral and Appointment Wait Times for the Evaluation of Spinal Muscular Atrophy (SMA): Findings from a Web-Based Physician Survey.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive muscle weakness and atrophy. Clinical trial data suggest early diagnosis and treatment are critical. The purpose of this study was to evaluate neurology appointment wait times for newborn screening identified infants, pediatric cases mirroring SMA symptomatology, and cases in which SMA is suspected by the referring physician. Approaches for triaging and expediting referrals in the US were also explored. METHODS: Cure SMA surveyed healthcare professionals from two cohorts: (1) providers affiliated with SMA care centers and (2) other neurologists, pediatric neurologists, and neuromuscular specialists. Surveys were distributed directly and via Medscape Education, respectively, between July 9, 2020, and August 31, 2020. RESULTS: Three hundred five total responses were obtained (9% from SMA care centers and 91% from the general recruitment sample). Diagnostic journeys were shorter for infants eventually diagnosed with SMA Type 1 if they were referred to SMA care centers versus general sample practices. Appointment wait times for infants exhibiting "hypotonia and motor delays" were significantly shorter at SMA care centers compared to general recruitment practices (p = 0.004). Furthermore, infants with SMA identified through newborn screening were also more likely to be seen sooner if referred to a SMA care center versus a general recruitment site. Lastly, the majority of both cohorts triaged incoming referrals. The average wait time for infants presenting at SMA care centers with "hypotonia and motor delay" was significantly shorter when initial referrals were triaged using a set of "key emergency words" (p = 0.036). CONCLUSIONS: Infants directly referred to a SMA care center versus a general sample practice were more likely to experience shorter SMA diagnostic journeys and appointment wait times. Triage guidelines for referrals specific to "hypotonia and motor delay" including use of "key emergency words" may shorten wait times and support early diagnosis and treatment of SMA.

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.

Identifying Biomarkers of Spinal Muscular Atrophy for Further Development.

BACKGROUND: Spinal muscular atrophy (SMA) is caused by bi-allelic, recessive mutations of the survival motor neuron 1 (SMN1) gene and reduced expression levels of the survival motor neuron (SMN) protein. Degeneration of alpha motor neurons in the spinal cord causes progressive skeletal muscle weakness. The wide range of disease severities, variable rates of decline, and heterogenous clinical responses to approved disease-modifying treatment remain poorly understood and limit the ability to optimize treatment for patients. Validation of a reliable biomarker(s) with the potential to support early diagnosis, inform disease prognosis and therapeutic suitability, and/or confirm response to treatment(s) represents a significant unmet need in SMA. OBJECTIVES: The SMA Multidisciplinary Biomarkers Working Group, comprising 11 experts in a variety of relevant fields, sought to determine the most promising candidate biomarker currently available, determine key knowledge gaps, and recommend next steps toward validating that biomarker for SMA. METHODS: The Working Group engaged in a modified Delphi process to answer questions about candidate SMA biomarkers. Members participated in six rounds of reiterative surveys that were designed to build upon previous discussions. RESULTS: The Working Group reached a consensus that neurofilament (NF) is the candidate biomarker best poised for further development. Several important knowledge gaps were identified, and the next steps toward filling these gaps were proposed. CONCLUSIONS: NF is a promising SMA biomarker with the potential for prognostic, predictive, and pharmacodynamic capabilities. The Working Group has identified needed information to continue efforts toward the validation of NF as a biomarker for SMA.

Effects of 2,4-diaminoquinazoline derivatives on SMN expression and phenotype in a mouse model for spinal muscular atrophy.

Proximal spinal muscular atrophy (SMA), one of the most common genetic causes of infant death, results from the selective loss of motor neurons in the spinal cord. SMA is a consequence of low levels of survival motor neuron (SMN) protein. In humans, the SMN gene is duplicated; SMA results from the loss of SMN1 but SMN2 remains intact. SMA severity is related to the copy number of SMN2. Compounds which increase the expression of SMN2 could, therefore, be potential therapeutics for SMA. Ultrahigh-throughput screening recently identified substituted quinazolines as potent SMN2 inducers. A series of C5-quinazoline derivatives were tested for their ability to increase SMN expression in vivo. Oral administration of three compounds (D152344, D153249 and D156844) to neonatal mice resulted in a dose-dependent increase in Smn promoter activity in the central nervous system. We then examined the effect of these compounds on the progression of disease in SMN lacking exon 7 (SMNDelta7) SMA mice. Oral administration of D156844 significantly increased the mean lifespan of SMNDelta7 SMA mice by approximately 21-30% when given prior to motor neuron loss. In summary, the C5-quinazoline derivative D156844 increases SMN expression in neonatal mouse neural tissues, delays motor neuron loss at PND11 and ameliorates the motor phenotype of SMNDelta7 SMA mice.

Knowledge of genetic test results among caregivers and individuals with spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a progressive recessive genetic disease. Early identification is critical for achieving maximal treatment benefit. Survival motor neuron (SMN) 2 copy number may be a needed descriptor of disease severity than SMA type. Therefore, we assessed knowledge of SMN2 copy number among those with SMA and their caregivers via a phone survey. Only patients with SMA (or their caregivers) registered in the Cure SMA database with no SMN2 copy number on file were eligible. Descriptive results are reported. Backward stepwise multinomial logistic regressions determined if specific factors predicted knowledge of SMN2 copy number. Engagement with the SMA community (odds ratio [OR] 1.82; p<0.0001), ability to walk (OR 1.74; p = 0.006), and current age at time of survey (OR = 0.98; p<0.0001) each positively predicted knowledge of SMN2 copy number. Of 806 completed surveys, the majority (n = 452; 56.3%) did not know SMN2 copy numbers for themselves (n = 190; 62.5%) or their loved ones (n = 261; 52.4%). Of these, 66 respondents (8.2%) said genetic testing had not been done. Motor function increased linearly with increasing SMN2 copy number. SMN2 copy number is emerging as a critical descriptor of severity for SMA as type becomes more obsolete with early drug treatment. Communication of SMN2 copy numbers is recommended as a standard part of the treatment plan.

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.

"I have SMA, SMA doesn't have me": a qualitative snapshot into the challenges, successes, and quality of life of adolescents and young adults with SMA.

BACKGROUND: With the approval of three treatments for spinal muscular atrophy (SMA) and several promising therapies on the horizon, the SMA adolescent and young adult populations are expected to evolve in the coming years. It is imperative to understand this cohort as it exists today to provide optimal care and resources, as well as to assess possible treatment effects over time. In 2018, Cure SMA launched two initiatives geared towards understanding adolescents and young adults with SMA, ages 12-25. First, Cure SMA launched a Quality of Life (QoL) survey to capture quantitative and qualitative information on this specific age demographic. Concurrently, Cure SMA invited SMA-affected individuals, ages 12-25, to create a three-minute video on their everyday experiences living with SMA. An inductive thematic analysis of the free-text survey questions along with the video contest findings are reported here. RESULTS: Eighty-five individuals-6 type Is, 58 type IIs, and 21 type IIIs-completed the Quality of Life free-response, while six individuals participated in the SMA awareness video contest. In both settings, individuals detailed a variety of challenges, including but not limited to forming or maintaining close relationships, experiencing feelings of isolation, challenges with accessibility, independence, and dealing with the stigma of being perceived as mentally disabled. Individuals also discussed their successes, including but not limited to higher education enrollment and attendance, development of quality friendships, and perseverance through obstacles. Additionally, notably in the survey, 39% of respondents requested the creation of an SMA peer support group in efforts to connect with each other as well as collectively navigate the aforementioned challenges they face. CONCLUSION: Together, these findings provide a rare glimpse into the unique mindsets, challenges and motivations of SMA adolescents and young adults, via patient-reported measures instead of caregiver proxy. The adolescent and young adult age demographics assessed represent a critical transition period in life and in SMA care. No one understands the needs of an adolescent or young adult with SMA better than the individuals themselves, and it is critical to encapsulate their insights to affect change.