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 the impact of grief on quality of life, work productivity, and health outcomes for parents bereaved from SMA: A study protocol.

BACKGROUND: U.S. cost-effectiveness recommendations suggest that analyses should include all costs and effects relevant to the decision problem [1]. However, in many diseases, including spinal muscular atrophy (SMA), few studies have evaluated bereaved family outcomes after a child has died, neglecting potential impacts on their health-related quality of life (HRQoL), work productivity, and mental health. Additionally, grief-related outcomes are rarely included in economic evaluations. This manuscript outlines the protocol of a study that will estimate the HRQoL, work functioning, and mental health of bereaved parents of children with SMA type 1 to determine how outcomes vary based on parent's sex and the time since a child's death. METHODS: This study will involve two phases. In Phase 1, we will conduct a literature review to identify prior research that has measured how parental grief impacts HRQoL, work productivity, and mental health. We will also interview four bereaved parents of children with SMA type 1, stratified by parent sex and time since their child's death, and analyze findings using a thematic analysis. In Phase 2, we will develop a survey draft based on Phase 1 findings. Parents bereaved from SMA type 1 will review our survey draft and we will revise the survey based on their feedback. We will send a cross-sectional survey to approximately 880 parents bereaved from SMA type 1. We will analyze findings from the survey to investigate whether the severity of grief symptoms is correlated with HRQoL, productivity, depression and anxiety symptom severity. We will also evaluate whether the mean scores of grief and each of the outcomes vary significantly when stratified by parent sex and the time since the child's death. DISCUSSION: Our results will provide preliminary information on how parental grief can impact HRQoL, productivity, and mental health outcomes over time. Increasing the availability of family outcomes data will potentially assist organizations performing health economic evaluations, such as the Institute of Clinical and Economic Review (ICER) in the U.S. This research will also help to inform the development of future economic guidelines on this topic.

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.

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.

Older Adult Preferences of Mobile Application Functionality Supporting Medication Self-Management.

Health systems and insurers alike are increasingly interested in leveraging mHealth (mobile health) tools to support patient health-related behaviors including medication adherence. However, these tools are not widely used by older patients. This study explores patient preferences for functionality in a smartphone application (app) that supports medication self-management among older adults with multiple chronic conditions. We conducted six discussion groups in Chicago, Miami, and Denver (N = 46). English-speaking older adults (55 and older) who owned smartphones and took five or more prescription medicines were invited to participate. Discussions covered familiarity with and use of current apps and challenges with taking multidrug regimens. Participants reviewed a range of possible mobile app functions and were asked to give feedback regarding the acceptability and desirability of each to support medication management. Very few participants (n = 3) reported current use of a mobile app for medication support, although all were receptive. Challenges to medication use were forgetfulness, fear of adverse events, and managing medication information from multiple sources. Desired features included (1) a list and consolidated schedule of medications, (2) identification and warning of unsafe medication interactions, (3) reminder alerts to take medicine, and (4) the ability record when medications were taken. Features relating to refill ordering, pharmacy information, and comparing costs for medication were not considered to be as important for an app.

Comparative effectiveness of patient-centered strategies to improve FDA medication guides.

BACKGROUND: Med Guides are the only Food and Drug Administration-regulated source of written patient information distributed with prescriptions drugs. Despite their potential value, studies have found them to have limited utility. OBJECTIVE: To evaluate the effectiveness of patient-centered strategies for the design of Med Guides to improve comprehension. DESIGN: A cross-sectional, randomized trial. SETTING: Two primary care clinics in Chicago, Illinois; one based in a public university hospital and the other within a private academic medical center. PATIENTS: A total of 1003 adults aged 18-85 years. INTERVENTION: The format and layout of content from 3 typical Med Guides (by reading difficulty, length, exposure) were modified several ways to promote information accessibility. Working with patients, the 3 most preferred versions were evaluated. The first used 2 columns to organize content (Column), a second mimicked over-the-counter "Drug Facts" labeling (Drug Facts), and the third followed health literacy best practices using a simple table format (Health Literacy prototype). MEASURES: Tailored comprehension assessment of content from 3 representative Med Guides. RESULTS: Comprehension was significantly greater for all 3 prototypes compared with the current standard (all P<0.001). The Health Literacy prototype consistently demonstrated the highest comprehension scores, and in multivariable analyses, outperformed both the Drug Facts [ß=-4.43, 95% confidence interval (CI), -6.21 to -2.66] and Column (ß=-4.04, 95% CI, -5.82 to -2.26) prototypes. Both older age (older than 60 y: ß=-10.54, 95% CI, -15.12 to -5.96), low and marginal literacy skills were independently associated with poorer comprehension (low: ß=-31.92, 95% CI, -35.72 to -28.12; marginal: ß=-12.91, 95% CI, -16.01 to -9.82). CONCLUSIONS: The application of evidence-based practices to the redesign of Med Guides significantly improved patient comprehension. Although some age and literacy disparities were reduced with the Health Literacy format in particular, both older age and low literacy remained independently associated with poorer comprehension. More aggressive strategies will likely be needed to gain assurances that all patients are informed about their prescribed medications. TRIAL REGISTRATION: Clinical Trials.Gov #NCT01731405.

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.

A Mixed-method Approach to Develop an Ambulatory Module of the SMA Independence Scale.

BACKGROUND: Limited qualitative data exist on the symptoms and impacts of spinal muscular atrophy (SMA) experienced by ambulant individuals. An ambulant module of the SMA Independence Scale (SMAIS) was developed to quantify the assistance required to perform everyday mobility-related activities. OBJECTIVE: The objective of this study was to develop a patient-centered module that provides key insights into what constitutes independence for ambulant and near-ambulant individuals with SMA. METHODS: A stepwise, mixed-method approach was used. Semi-structured interviews were conducted in three waves with individuals with SMA and caregivers of children with SMA who were ambulant or near-ambulant (can walk ≥5 steps with support). Wave 1 interviews (n = 20) focused on concept elicitation. Wave 2 and 3 interviews (n = 15, both) involved completion and cognitive debriefing of items generated based on Wave 1 interviews. Therapeutic area experts were consulted throughout all key steps of the study. In particular, feedback was provided for item refinement and response option decisions. A macro-level preliminary, exploratory analysis, using Rasch Measurement Theory (RMT), provided insight on measurement properties. RESULTS: Wave 1 resulted in 42 mobility and 11 instrumental activity of daily living (iADL) items. During Wave 2, participants defined independence as completing a task with supportive aids but without help from another person, leading to item refinement and modifications to the response scale. Lack of conceptual relevance and ceiling effects led to the removal of all iADL items after Wave 2, and 41 mobility items were tested in Wave 3. Final exploratory RMT and item refinement to reduce overlap led to a 27-item set related to mobility tasks. CONCLUSIONS: Our study provides preliminary support for using the 27-item SMAIS-Ambulatory Module for ambulant or near-ambulant individuals with SMA. Larger-scale analyses to further assess the psychometric properties of the scale are warranted.

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.

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.

The Cure SMA Membership Surveys: Highlights of Key Demographic and Clinical Characteristics of Individuals with Spinal Muscular Atrophy.

BACKGROUND: Cure SMA maintains the largest patient-reported database for people affected with spinal muscular atrophy (SMA). In 2017, Cure SMA initiated annual surveys with their membership to collect demographic and disease characteristics, healthcare, and burden of disease information from patients and caregivers. OBJECTIVE: To summarize results from two large-scale Cure SMA surveys in 2017 and 2018. METHODS: Cure SMA database members were invited to complete surveys; these were completed by caregivers for living or deceased individuals with SMA and/or affected adults. RESULTS: In 2017, 726 surveys were completed for 695 individuals with SMA; in 2018, 796 surveys were completed for 760 individuals with SMA. Data from both survey years are available for 313 affected individuals. Age at symptom onset, distribution of SMN2 gene copy number, and representation of each SMA type in the surveys were consistent with that expected in the SMA population. In the 2018 survey, the average age at diagnosis was 5.2 months for SMA type I and the reported mean age at death for this subgroup was 27.8 months. Between survey years, there was consistency in responses for factors that should not change within individuals over time (e.g., reported age at diagnosis). CONCLUSIONS: Results from the Cure SMA surveys advance the understanding of SMA and facilitate advocacy efforts and healthcare services planning. Longitudinal surveys are important for evaluating the impact of effective treatments on changing phenotypes, and burden of disease and care in individuals with SMA.

Quality of life data for individuals affected by spinal muscular atrophy: a baseline dataset from the Cure SMA Community Update Survey.

BACKGROUND: Individuals and/or caregivers of individuals affected by spinal muscular atrophy (SMA) completed the 2019 Cure SMA Community Update Survey, online, assessing health-related quality of life (HRQoL), loss of work productivity, and fatigue using the Health Utilities Index Questionnaire (HUI), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the Patient Reported Outcomes Measurement Information System Fatigue Short Form (PROMIS Fatigue SF), respectively. The purpose was to collect baseline quality of life results among individuals affected by SMA using the above Patient Reported Outcome Measures (PROMs). RESULTS: Of 666 surveys completed between March and May 2019, 478 were included in this analysis, accounting for duplicates, missing data, or deaths. The breakdown across SMA type I, II and III was 25, 47 and 28%, respectively. Responses were characterized by current functional status/milestone, with subsets for "permanent ventilation," "non-sitters," "sitters," "walk with support," and "walk alone." WPAI and HUI respondents included affected adults and caregivers. The PROMIS Fatigue SF was completed by the primary caregiver of affected children. Overall, those affected by a less severe form of SMA and with a higher functional status reported higher HRQoL and lower work productivity and activity impairment. All affected individuals reported higher fatigue levels than the general population. CONCLUSIONS: This study offers useful insights into the burden of SMA among affected individuals and their caregivers. The results provide a baseline picture of the patient and caregiver experience with SMA in a post-treatment era from which to measure year-over-year changes in quality of life scores from new therapies and improved care. The WPAI demonstrates the significant impact of work productivity among SMA populations. Aspects of the HUI seem more appropriate to certain SMA sub-populations than others. Measures from the PROMIS Fatigue SF appear to under-represent the burden of fatigue often reported by SMA individuals and caregivers; this may, perhaps be due to a lack of sensitivity in the questions associated with fatigue in the SMA affected population, when compared with other studies on this topic. Overall, these results suggest the need for SMA-specific quality of life outcome measures to fully capture clinically meaningful change in the SMA population.

Economic burden of spinal muscular atrophy: an analysis of claims data.

Background: Spinal muscular atrophy (SMA) is a rare genetic neuromuscular disease. Objective: Characterize direct costs associated with SMA management. Data source: Truven Health Analytics MarketScan claims data (2012-2016). Patients: Eligible patients had ≥2 SMA-related medical claims ≥30 days apart. Patients were matched (1:1) to controls by birth year, gender, and geographic region. Patients were categorized as having infantile, child, or juvenile SMA based on diagnosis at age <1, 1-3, or 3-18 years, respectively. Main outcome measures: Annual inpatient and outpatient insurance claims and costs (2019 USD) for cases versus controls. Results: Fifty-eight, 56, and 279 cases and controls comprised the infantile, child, and juvenile cohorts, respectively. Cases had more inpatient claims than controls (infantile: 60.3% vs 1.7%; child: 35.7% vs 3.6%; juvenile: 47.0% vs 4.3%; all P ≤ 0.002). Mean net payments for inpatient admissions were higher for cases versus controls (infantile: $118,609.00 vs $58.79; child: $26,940.01 vs $143.56; juvenile: $39,389.91 vs $701.21; all P ≤ 0.01), as were mean net payments for outpatient services (infantile: $55,537.83 vs $2,047.20; child: $73,093.66 vs $1,307.56; juvenile: $49,067.83 vs $1,134.69; all P ≤ 0.0002). Conclusions: Direct costs of SMA are tremendous, often >50-fold higher compared with matched controls. Efforts are needed to reduce costs through improved standards of care.

Spinal Muscular Atrophy (SMA) Subtype Concordance in Siblings: Findings From the Cure SMA Cohort.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous survival of motor neuron 1 (SMN1) gene disruption. Despite a genetic etiology, little is known about subtype concordance among siblings. OBJECTIVE: To investigate subtype concordance among siblings with SMA. METHODS: Cure SMA maintains a database of newly diagnosed patients with SMA, which was utilized for this research. RESULTS: Among 303 sibships identified between 1996 and 2016, 84.8% were subtype concordant. Of concordant sibships, subtype distribution was as follows: Type I, 54.5%; Type II, 31.9%; Type III, 13.2%; Type IV, 0.4%. Subtype and concordance/discordance association was significant (Fisher's exact test; p < 0.0001). Among discordant sibships (chi-square test, p < 0.0001), Types II/III (52.2%) and Types I/II (28.3%) were the most common pairs. No association was found between sibling sex and concordance. Our findings show that most siblings with SMA shared the same subtype concordance (most commonly Type I). CONCLUSIONS: These data are valuable for understanding familial occurrence of SMA subtypes, enabling better individual treatment and management planning in view of new treatment options and newborn screening initiatives.

Evaluating Benefit-risk Decision-making in Spinal Muscular Atrophy: A First-ever Study to Assess Risk Tolerance in the SMA Patient Community.

PURPOSE: Patients' perceptions of benefit-risk are essential to informing the regulatory process and the context in which potential therapies are evaluated. To bring this critical information to regulators, Cure SMA launched a first-ever Benefit-Risk Survey for spinal muscular atrophy (SMA) to characterize decision-making and benefit-risk trade-offs in SMA associated with a potential therapy. We hypothesized that risk tolerance would be correlated with SMA type/severity and disease progression. This article presents the results of a benefit-risk survey to enhance understanding of how patients with SMA and caregivers evaluate specific benefits and risks associated with potential therapies. METHODS: Affected adults, representing all SMA types (I-IV) within the Cure SMA database, and caregivers of affected individuals of all ages/types were invited via e-mail to participate. Best-worst scaling (BWS) was used to assess participants' priorities on benefit-risk trade-offs, as it provides higher discrimination and importance scaling among tested attributes. Twelve potentially clinically meaningful treatment benefits and 11 potential risks (ranging in severity and immediacy) were tested. Multiple factors were correlated with individual responses, including: SMA type/disease severity, stage of disease, respondent type, sex, and quality of life/level of independence (current and expected). Survey respondents were also evaluated for "risk-taking attitudes." FINDINGS: A total of 298 responses were evaluated (28% affected adults and 72% caregivers, mostly parents). Most respondents were diagnosed >5 years ago (67.3%), with 22.1% SMA type I, 45.6% SMA type II, and 27.9% SMA type III. No strong correlation was found between risk tolerance and SMA type, stage of disease progression, respondent type, sex, quality of life assessment, or rated levels of independence. Irrespective of SMA type, respondents consistently rated the following risks, associated with a potential treatment, as "least tolerable": life-threatening allergic reactions; 1 in 1000 risk of life-threatening side effects leading to possible organ failure; or worsening quality of life. Furthermore, all SMA type respondents rated these risks as "most tolerable": invasive mode of treatment administration (including need for general anesthesia); side effect of dizziness; and other common side effects such as nausea, vomiting, loss of appetite, headaches, back pain, or fatigue. IMPLICATIONS: With the approval of the first SMA treatment, these findings offer a unique opportunity to assess and characterize baseline risk-tolerance in SMA against which to evaluate future SMA treatment options. Although differences had been expected in risk tolerance among respondents based on disease baseline and certain patient attributes, this was not observed. Survey results should inform future SMA drug development and benefit-risk assessments.

Newborn Screening and Birth Prevalence for Spinal Muscular Atrophy in the US.

This cross-sectional study describes the collection and use of state-provided data on newborn screening for spinal muscular atrophy.