*This information was originally published as part of an abstract for Rare Disease Day at NIH 2026*
Understanding Rett Syndrome and the Unmet Patient Need
Rapid therapeutic advances in Rett syndrome (RTT), including the availability of novel therapies, have expanded opportunities to meaningfully improve symptom management and quality of life. However, the introduction of novel therapies has also introduced new complexity into clinical practice, from early and atypical diagnosis to treatment selection, adverse event (AE) mitigation, and caregiver counseling.
Despite these advances, significant gaps persist in real-world integration. Providers report challenges differentiating early RTT from nonspecific developmental delay or autism, interpreting subtle presentations without classic regression, and navigating limited exposure to RTT during training. Treatment-related uncertainty, particularly around trofinetide efficacy, safety monitoring, and multidisciplinary coordination further contributes to variability in care delivery.
These persistent barriers underscore the need for practical, case-informed education designed to translate emerging evidence into confident, routine clinical practice.
The Medlive Approach
To address these real-world challenges, Medlive partnered with the National Organization for Rare Disorders (NORD) and the International Rett Syndrome Foundation (IRSF) to develop a national, case-based CME initiative grounded in clinician-reported patient scenarios. In collaboration with multidisciplinary experts and patient advocacy leadership, the curriculum was designed to bridge diagnostic uncertainty and therapeutic implementation gaps in RTT care.
The initiative included:
- A 60-minute foundational module: “Personalizing Care for Rett Syndrome: From Early Detection to Shared Decision-Making in the Era of New Therapies” (launched August 20, 2025)
- A three-part case-based multidisciplinary series (launched October 8, 2025; data collection ongoing)
- A national survey of clinicians managing RTT
- A micro-learning video campaign (1–5 minutes each), targeted to NPI-verified neurologists and pediatricians via LinkedIn
Educational content focused on:
- Early and atypical RTT recognition
- Evidence-based use of trofinetide
- Proactive AE management through multidisciplinary collaboration
- Integration of rehabilitation services
- Caregiver counseling and individualized goal-setting
Impact was assessed using pre- and post-activity knowledge and competence questions developed in accordance with National Board of Medical Examiner guidelines, along with post-activity evaluations capturing intended practice changes. Statistical testing and effect size analysis (Cohen’s d) were applied.
Key Findings
- Strong clinician engagement in rare disease education:
The initiative reached 6,362 participants nationwide, including 4,218 NPI-verified neurologists and 1,646 pediatricians. Among CME learners, 95% were MD/DOs and 86% reported actively managing patients with RTT, reflecting strong alignment with frontline providers.
- Baseline diagnostic and therapeutic gaps identified:
Pre-activity data revealed persistent challenges in differentiating RTT from global developmental delay or autism (35%), recognizing early or atypical presentations (28%), and limited exposure to RTT during training (22%). When considering trofinetide initiation, decisions were primarily driven by symptom severity (36%) and caregiver goals (30%), underscoring the importance of shared decision-making.
- Transitional adoption patterns with real-world barriers:
Trofinetide was widely referenced across severity levels, with reported benefits including improvements in communication and behavior. However, GI adverse events were common and affected adherence in approximately one-quarter of cases. Two-thirds of clinicians cited access barriers such as insurance delays and prior authorization challenges, and more than half expressed a need for additional long-term efficacy and safety data.
- Significant gains in knowledge and clinical competence:
Learners demonstrated statistically significant improvements across all four assessed domains, including early recognition of RTT signs (+27%), knowledge of trofinetide efficacy (+31%), awareness of adverse-event management (+34%), and caregiver counseling strategies (+25%). The overall educational effect size was large (Cohen’s d = 1.2), exceeding established CME benchmarks. - Practice intentions aligned with multidisciplinary care models:
Seventy-five percent of learners reported an intended practice change, most commonly increasing collaboration with multidisciplinary team members (55%), followed by modifying treatment approach (23%), adjusting supportive therapies (12%), and refining diagnostic strategy (10%).
Are you an HCP?
Medlive has joined forces with the National Organization of Rare Disorders (NORD) to host our first ever Rare Disease CME Challenge. Now through March 31st, sign up to get started and earn your stripes!
Conclusion – Supporting Confident Integration of Novel RTT Therapies
This national, case-based CME initiative demonstrated broad engagement and measurable improvements in clinician knowledge, competence, and intended practice behaviors related to diagnostic recognition, therapeutic adoption, and multidisciplinary management in Rett syndrome.
Findings reveal an evolving practice landscape marked by increased uptake of trofinetide, despite persistent diagnostic uncertainty, adverse-event management challenges, and access barriers. Outcomes-driven, real-world–grounded education remains essential to bridging evidence-to-practice gaps and supporting consistent, high-quality care for individuals with RTT.
To learn more about partnering with Medlive to develop impactful CME programs, reach out via our Contact Us page.
This activity was supported by an independent medical education grant from Acadia Pharmaceuticals, Inc.
