Rare As One Network 2023 Community Meeting

When a generic PROM won't do, it's time to create your own (spoiler alert – it's neither fast nor cheap). This poster steps through the process of creating the CCM Health Index, including experiences recruiting a diverse patient participant cohort.

Connie Lee <clee@alliancetocure.org>

Alliance to Cure Cavernous Malformation

Background: Congenital hyperinsulinism (HI) is the most frequent cause of severe, persistent hypoglycemia in newborn babies and children. Congenital Hyperinsulinism International (CHI) sponsors HIGR, which consists of thirteen surveys made up of questions about the patient's experience with HI over their lifetime.  Methods: We completed a retrospective review of patient and caregiver-reported HIGR data collected from 2018-2022 on the self-reported variables from the birth and pregnancy surveys to categorize the experience to the known risk factors of hypoglycemia outlined in the PES and AAP guidelines. Results: Of 197 participants in HIGR, 66.0% (n=130) self-reported one or more of the factors that put them at increased risk of hypoglycemia when applying the PES guidelines retrospectively. A total of 232 women completed the pregnancy survey, of whom 43% reported a health problem during pregnancy, including preeclampsia/ eclampsia/ hypertension (15%), gestational diabetes (13%), preterm labor (7%), and diabetes (2%). 78% of women had a glucose tolerance test, of whom 22% reported the test was abnormal. Of these, 65% reported having diabetes (p<.0001, chi2). 31.5% of individuals with a known risk factor of hypoglycemia and 10.8% of individuals who could not maintain blood glucose above 60mg/dL after 48 hours were not identified as being at risk before leaving the birth facility. Discussion: It is critical to identify and manage hypoglycemia from HI in neonates to avert preventable brain damage. Outreach needs to be conducted at birthing facilities to increase awareness of the hypoglycemia guidelines. More widespread screening, such as recognizing glucose as a vital sign, could help identify individuals who do not have an identified risk of hypoglycemia.

Tai Pasquini

Congenital Hyperinsulinism International

Rationale: SCN2A-associated developmental and epileptic encephalopathy (DEE) is a condition with highly variable phenotype and extremely low prevalence. Outcomes targeting patient-important, core, common features of SCN2A-DEE are needed for future precision medicine trials (e.g., gene-targeted) to ensure eligibility of a maximum number of patients (FDA guidance's 2009, 2019, 2022).

Methods: The SCN2A Clinical Trials Readiness Study (CTRS) recruited 66 families of children with pathogenic/likely pathogenic SCN2A variants for longitudinal assessment with validated parent-reported instruments, including the Vineland-3, and other measures of key functional abilities. In July 2022, as part of the Inchstone pilot study,10 of the families also participated in a Goal Attainment Scaling (GAS) process in which parents identified 3 critically important goals of their choice for their child.

Results: SCN2A-affected children had a median age of 6.4 years (Interquartile Range, 4.0 to 10.5, max=29), and 36 (44%) were female. Although substantial impairments were evident in all functional domains, communication was severely to profoundly affected for almost all subjects. Vineland V-scores for expressive (mean=2.5, SD=3) and receptive (mean=2.0, SD=2.7) communication indicated function 4-5 standard deviations below the population mean (population mean=15, SD=3). The median scores for both were 1.0, the floor of the measures. A score of 1 was obtained by >75% on the expressive scale. The primary form of communication was speech (11, 17%), sign language (2, 3%), gestures (12, 18%), sounds (22, 33%), communication devices (10, 15%), gaze/eye-pointing (6, 9%), and other (5, 8%, mostly involuntary behaviors). Based on the mCHAT, only 5 (8%) used pointing with one finger to indicate something of interest. Of 56 subjects ≥2 years-old assessed on the Communication Function Classification System, 4 (7%) were considered “effective” communicators, 5 (8%) communicated only with very familiar people, and 47 (84%) did not communicate effectively even with familiar people. In the GAS pilot study, 9/10 parents identified 10 expressive communication goals, including rudimentary use of communication devices (N=5), making yes/no choices through eye gaze (N=1) or by hand with a yes/no button (N=2), and effective use of one single word (N=2).

Conclusions: Expressive communication is severely to profoundly impaired in almost all people affected by SCN2A-DEE and was identified by 9/10 parents in the GAS pilot as a critically important goal for improvement. As such, per FDA guidance's, expressive communication should be considered a construct of interest for a clinical trial outcome. Use of Clinical Outcome Assessments (COA) standardized to the general population (e.g., Vineland) are inappropriate for SCN2A-DEE because of the severe floor effects. Robust, valid COAs appropriate for measuring expressive communication in the extremely low range of functioning that is typical of this disorder will be required to facilitate robust clinical trials for SCN2A-DEE.

Funding: FamilieSCN2A Foundation, GAS pilot work funded by The Inchstone Project

Shawn Egan PhD

The FamilieSCN2A Foundation, Northwestern University Feinberg School of Medicine, Ardea Outcomes, Mercy Children's Hospital, CLIRINX,

When the LGS Foundation started building its research network three years ago, research was flat, innovation was absent, the patient voice was not present, and no discussions of disease-modifying therapies were taking place. Today that has changed because of the work of the Foundation. The power of patients to bring their voice to research, incentivize innovation, help researchers prioritize what matters, convene key conversations, and fund new projects has the power to change a field. Ask us! We've seen it happen!

Tracy Dixon-Salazar

Lennox-Gastaut Syndrome Foundation

Lola Rahib

Mission: Cure

Necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality of premature infants in the neonatal intensive care unit. This devastating intestinal disease affects approximately 7% of preterm infants born weighing <1500 grams. The pathogenesis of NEC is multifactorial, and diagnosis relies on clinical signs, radiologic findings, and laboratory data that overlap with other clinical conditions common to premature infants. In order to enhance further understanding of clinical markers, prevention and treatment strategies, and the true burden placed on patient-families, a patient-centered outcomes research (PCOR) team was established to develop a prioritized research agenda. An open-ended survey was created and disseminated through social media and partner organizations, seeking input regarding questions and topics related to NEC. The project leadership team reviewed responses and performed thematic analysis. A Delphi-based prioritization process involved determination of patient-centered, comparative-effectiveness research questions and a ranking that narrowed the breadth of topics to 20. The goals, process, and outcomes of the project were shared via a NEC Society webinar https://www.youtube.com/watch?v=1-gincyd380. The NEC Society launched the Research Incubator to foster collaboration and drive these research topics to the forefront and the 2023 NEC Symposium will be centered around transforming these priorities into action. As a result, patient-families will be engaged and empowered to participate in research that is meaningful, relevant, and impactful. Clinician-researchers will be motivated to lead research using the prioritized research agenda with skills to effectively engage patient-families and seek funding.

Erin Pryor <erinpryor@necsociety.org>

NEC Society

Emory University, University of North Carolina Chapel Hill, Cincinnati Children's Hospital

In 2022, PFIC Network relaunched our patient registry in the Redcap Platform. The original registry was created and housed in partnership with CoRDs and was invaluable in providing patient-reported outcome data to support advocacy efforts during an FDA Listening Session. As our community grew, we recognized the need to have more autonomy over the data and improved compatibility with research. We relaunched the registry using the REDcap platform at our Scientific Conference in April 2022, and have 70 participants enrolled to date. We are now collecting longitudinal data and using validated measures to assess patient reported outcomes, such as PROMIS scales, in our surveys. Since the launch, we have begun a major translation project that will allow us to offer the registry in Italian, Polish and Spanish. Recruitment is an ongoing challenge, especially for longitudinal survey completion, but we hope that our registry will be a valuable tool to help prepare the international PFIC community to be active and engaged participants in future research.

Emily Ventura

Progressive Familial Intrahepatic Cholestasis Advocacy and Resource Network Inc.

The Global Genes Grant project, Spanish Language Resources for Hypothalamic-Pituitary Brain Tumor Survivors & Caregivers, aimed to create and disseminate resources both online and in print to Spanish speakers to empower them to make better informed medical decisions, and to introduce them to the Raymond A. Wood Foundation and the supports we can provide them. Additionally, the project aimed to strengthen outreach to Spanish speaking survivors and caregivers and to doctors treating patients in areas with high hispanic populations. The project created a social media campaign during Hispanic Heritage Month, as well as a website with resources in Spanish that included transcribed resource videos, caregiver interviews, and a pamphlet. Physical pamphlets were mailed to thirty medical facilities in five states with the highest hispanic populations (California, Texas, Arizona, Florida, and New York).

Amy Wood, Jamie Ping

Raymond A. Wood Foundation

Global Genes

Start-up mode for a foundation can be overwhelming - especially when you are dealing with a relatively newly-discovered condition and a small patient population. There's so much to do and so many possible paths to take!!

This is the story of our three year journey since starting the Smith-Kingsmore Syndrome Foundation, the relationships we built and decisions we've made, and what we've learned from those experiences.

Key search words: - experts - family conference - natural history - patient registry - Michael Raymond - tough conversations - eggs in a basket - post-doc - dancing mice - leaps of faith - NIH

Susan Dando <susan.dando@smithkingsmore.org>

Smith-Kingsmore Syndrome Foundation

Saad Ehsan

Baylor College School of Medicine, Houston, TX USA

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX USA; Department of Pediatrics, Division of Neurology, Texas Children’s Hospital and Baylor College of Medicine, Houston, TX USA; Department of Pediatrics, Division of Endocrinology, Texas Children’s Hospital and Baylor College of Medicine, Houston, TX USA; Department of Pediatrics, Division of Pediatric Cardiology, Texas Children’s Hospital and Baylor College of Medicine, Houston, TX USA; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX USA; TANGO2 Research Foundation

In 2021, the TBRS Community launched the TBRS Community Patient Registry in affiliation with NORD. This registry acts as a natural history study for Tatton Brown Rahman Syndrome, to ascertain how TBRS evolves over the lifetime of a patient. The TBRS Community also launched our own Biorepository in conjunction with CombinedBRAIN in 2022. This presentation describes the method through which we have connected the registry and the biorepository. Through use of the Clinical Research ID, or CRID, patients can choose to link their information to decrease the burden on patients and advance research on TBRS.

Kit Church

Tatton Brown Rahman Syndrome Community

COMBINEDBrain, NORD

Driving patient-centered research by expanding the SLC13A5 toolkit, growing our network, and supporting early and established investigators.

Tanya L Brown

TESS Research Foundation

Objective: As a grantee of the Chan Zuckerberg Initiative’s Rare as One Project, Cure HHT created a research network (CHRN) to develop a research roadmap for the next 3-5 years. CHRN is led by HHT patients working in collaboration with researchers and clinicians to prioritize research initiatives by order of feasibility, impact, importance, and logical sequence.

Methods: Comprehensive surveys were sent to the HHT patient and professional community to identify perceived gaps in research and treatments. 1,204 patients answered a 49 questions, 42 HHT scientists answered 17 questions, and 96 HHT clinicians answered 25 questions. Based on the analyzed results of patient needs, broad-topic work streams were established which included patients, clinicians, and researchers. Work streams performed a comprehensive literature review on their respective topic, discussed gaps in research, and proposed recommendations to fill each knowledge gap. Finally, a 2-day convening was held with all working groups to present recommendations and vote on a consensus for a final research roadmap to meet patient needs over the next 3-5 years.

Results: 8 work streams identified 31 recommendations to address patient needs. Recommendations were selected by anonymous vote after their presentation to the group and ranked by feasibility, impact, and importance. Additionally, resources and tools were identified to achieve all recommendations. Conclusion: CHRN is poised with specific, actionable goals to address patient priorities. The research roadmap will serve as a guide for next steps, research funding opportunities, and collaboration between patients, clinicians, and researchers at an unprecedented level for the HHT community.

Marianne Clancy

Cure HHT, Monkton Maryland, USA

University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA