Introduction Sanfilippo syndrome (MPS III) is a rare, degenerative condition characterized by symptoms impacting cognitive ability, mobility, behavior, and quality of life. Currently there are no approved therapies for this severe life-limiting disease. Integrating patient and caregiver experience data into drug development and regulatory decision-making has become a priority of the Food and Drug Administration and rare disease patient communities. Methods This study assesses parents’ perceptions of their child’s Sanfilippo syndrome disease-related symptoms using a research approach that is consistent with the Center for Drug Evaluation and Research (CDER) guidance. This study was initiated by the Cure Sanfilippo Foundation, and all steps in the research process were informed by a multidisciplinary advisory committee, with an objective of informing biopharmaceutical companies and regulatory agencies. We explored caregiver burden, symptoms with greatest impact, and meaningful but unmet treatment needs. Data were collected from 25 parents through three focus groups and a questionnaire. Transcripts were coded and analyzed using inductive thematic analysis, and descriptive analysis of quantitative data was conducted. Results Participating parents’ children ranged in age from 4 to 36 years. Participants endorsed high caregiving burden across all stages of the disease. Analysis revealed multiple domains of unmet need that impact child and family quality of life, including cognitive-behavioral challenges in communication, relationships, behavior, anxiety, and child safety; and physical health symptoms including sleep, pain, and mobility. Participants reported placing high value on incremental benefits targeting those symptoms, and on a treatment that would slow or stop symptom progression. Conclusion Even modest treatment benefits for Sanfilippo syndrome were shown to be highly valued. Despite high caregiver burden, most parents expressed a willingness to “try anything,” including treatments with potentially high risk profiles, to maintain their child’s current state. Electronic supplementary material The online version of this article (10.1007/s40120-020-00226-z) contains supplementary material, which is available to authorized users.

Background Newborn screening (NBS) occupies a unique space at the intersection of translational science and public health. As the only truly population-based public health program in the United States, NBS offers the promise of making the successes of translational medicine available to every infant with a rare disorder that is difficult to diagnose clinically, but for which strong evidence indicates that presymptomatic treatment will substantially improve outcomes. Realistic NBS policy requires data, but rare disorders face a special challenge: Screening cannot be done without supportive data, but adequate data cannot be collected in the absence of large-scale screening. The magnitude and scale of research to provide this expanse of data require working with public health programs, but most do not have the resources or mandate to conduct research. Methods To address this gap, we have established Early Check, a research program in partnership with a state NBS program. Early Check provides the infrastructure needed to identify conditions for which there have been significant advances in treatment potential, but require a large-scale, population-based study to test benefits and risks, demonstrate feasibility, and inform NBS policy. Discussion Our goal is to prove the benefits of a program that can, when compared with current models, accelerate understanding of diseases and treatments, reduce the time needed to consider inclusion of appropriate conditions in the standard NBS panel, and accelerate future research on new NBS conditions, including clinical trials for investigational interventions. Trial registration Clinicaltrials.gov registration # NCT03655223 . Registered on August 31, 2018.

Background: Now that severe combined immune deficiency (SCID) has been added to newborn screening panels in all 50 states in the U.S., there is a need to develop and disseminate well-designed educational materials to parents who need information to make informed decisions about treatment and care for identified infants. SCID Compass was designed to address this gap. We summarize the results of two needs assessment activities for parents-a journey mapping exercise and online survey-which will inform the development of a website and new resources.Methods: We conducted in-depth interviews with seven parents of children with SCID identified through newborn screening. Participants were asked to complete a journey map to describe key timepoints related to SCID, starting at diagnosis through present day. This qualitative information informed an online survey that was completed by 76 parents who had a child with SCID. All participants were from the United States.Results: Analysis of journey maps revealed five distinct stages that parents experience: (1) Diagnosis, (2) Pre-Treatment, (3) Treatment, (4) Post-Treatment, and (5) The New Normal. At each stage, parents described unique emotions, challenges, contextual factors that can make a difference in their experience, and information and resource needs. Survey results indicated the highest-rated information needs for parents were understanding available treatment options and what to expect across the SCID lifespan. Emotional support needs included dealing with uncertainty about child's future and additional opportunities to connect with other families. Parents preferred receiving new materials from their healthcare provider or other families, and preferred materials in print, from social media, or online. Several differences were found among subgroups of parents, including those whose child had been identified through newborn screening as well as those considered medically underserved.Conclusions: Findings about unmet parent needs and informational preferences will serve as the foundation for creating a suite of resources for those who have a child Raspa et al.Unmet Parent Needs in SCID with SCID. The materials will be tailored to specific stages of the journey. By using a family-centered approach, we will help to ensure that the materials designed and developed as part of SCID Compass will be understandable, comprehensive, and useful.

IMPORTANCE Novel therapies, including cell and gene therapies, can radically improve outcomes among patients with rare disorders, especially if provided early. Newborn screening (NBS) could support early access to novel therapies, but the speed of new therapy development is a disruptive event for which the public health NBS system and state newborn screening programs are unprepared. OBJECTIVETo identify and evaluate possible solutions for modernizing NBS. DESIGN, SETTING, AND PARTICIPANTS In this survey study, NBS experts representing clinical research, federal or state advisory boards, patient advocacy groups, industry, or state laboratories completed an online survey in which they considered 20 potential solutions for modernizing NBS and rated each. EXPOSURES Participants considered 20 potential solutions in the 5 following domains: (1) timeliness of disorder review, (2) alternative mechanisms to offer screening for new disorders not currently part of NBS, (3) expanded data collection, (4) support for states, and (5) emerging methods of screening and their consequences. MAIN OUTCOMES AND MEASURES Mean ratings for each solution on efficacy, acceptability, feasibility, and sustainability. RESULTS The survey was completed by 40 NBS experts (median [range] age, 54 [37-73] years; 22[55.0%] women). Participants acknowledged that substantial change is needed to prepare the NBS system for rapid expansion of novel therapies; on a scale of 0 (no change) to 10 (extensive change), the median (range) score was 8 (2-10), with 18 respondents (45.0%) believing that the NBS would need many new components or an entirely new system to accommodate the changes. All solutions for modernization were considered potentially efficacious by at least 23 respondents (57.5%). The 2 most strongly endorsed were to establish mechanisms for cross-state data coordination for provisional disorders (38 respondents [95.0%]) and create a network of regional screening laboratories (36 [90.0%]). These were closely followed by aligning programs across federal agencies (35 [87.5%]), expanding funding for research (34 [85.0%]), expanding funding to states (34 [85.0%]), building capacity to identify genetic variants and an associated clinical database (34 [85.0%]), and conducting surveillance to study long-term outcomes (34 [85.0%]). CONCLUSIONS AND RELEVANCEIn this study, there was consensus among experts that NBS needs to change if the system is to be prepared for a rapid increase in transformative therapies. To our knowledge, this is the first systematic inventory of potential solutions for modernizing NBS and expert perceptions of each. The findings suggest that the modernization of NBS will require the (continued) Key Points Question What solutions do subject matter experts recommend to prepare newborn screening for a rapid increase in the number of transformative therapies that must be provided early in life? Findings In this survey study, 40 experts in newborn screening evaluated 20 potential solutions. The highest rated solutions addressed cross-s...

Violence against children, including corporal punishment, remains a global concern. Understanding sources of support for corporal punishment within cultures, and the potential for intergenerational transmission of child maltreatment, is essential for policy-development and community engagement to protect children. In this study, we use data from a cross-section of women in Meru County, Kenya ( n = 1,974) to profile attitudes toward violence against children using the Velicer Attitudes Towards Violence-Child subscale. We find reported histories of sexual abuse, emotional and physical neglect, and witnessing interpersonal violence during childhood predict more violent attitudes toward children in adulthood. The pathway between these forms of child maltreatment and violent attitudes is significantly mediated by family function, perceived stress, and attitudes toward violence against women. Interventions to prevent sexual abuse, intimate partner violence, and promote attachments between parents and children may benefit future generations in this population. Furthermore, secondary prevention of the effects of these childhood adversities may require development of social support, improving family function and challenging violent attitudes against women.