AccelerateRARE Working Groups

Monday, September 14, 2026

Attendance: Requires full Summit registration and organizer approval. To request participation, please email jenny@raretrialssummit.com.  Attendance is limited to 40 participants per group, with priority given to senior leadership.

Objectives:

Develop stakeholder consensus on rare disease clinical development topics.

Create briefing documents and community guidelines to meaningfully accelerate rare disease clinical development.

2025 Report:

37 experts from biopharma and patient advocacy convened at the 2025 Summit to draft the priorities of the rare disease clinical development community ahead of the upcoming PDUFA VIII reauthorization.

Download the Report

2026 Working Group A:

Plausible Mechanism Evidence Playbook

Purpose:

Develop the "interpretation layer" for the upcoming final guidance for the Plausible Mechanism Pathway.

What the February 2026 FDA draft guidance states:

  • “Use mechanistic understanding + limited clinical data”

  • “Natural history matters”

  • “Show the effect is unlikely due to chance”

  • “CMC and manufacturing consistency are critical”

  • “Plan for post-market follow-up”

What remains to be defined/ interpreted:

  • What level of mechanistic evidence is enough (in vitro? animal? human biomarker?)

  • How robust a natural history dataset must be (n=5 vs n=50 vs registry quality)

  • What constitutes a clinically meaningful change vs. noise

  • What statistical standard replaces “adequate and well-controlled”

  • How to handle heterogeneity across n-of-1 or tiny cohorts

  • What minimum CMC maturity is acceptable for individualized therapies

  • What post-market commitments are “reasonable”?

Proposed Output:

A Plausible Mechanism Evidence Playbook, including

  • Evidence tier framework

  • Natural history standards checklist

  • Trial design decision tree

  • Endpoint acceptability matrix

  • CMC readiness checklist

  • Post-market evidence framework

Suggested participant profile

  • Regulatory science leaders with rare disease experience

  • Sponsor clinical-development, translational, and regulatory leads

  • Biostatisticians and trial-methodology experts

  • Natural history, biomarker, and endpoint experts

  • Selected payer, HTA, or access strategists with rare disease experience

2026 Working Group B:

Minimum Readiness Standards for Pediatric Rare Disease Trials

Purpose:

To define the minimum scientific, operational, and caregiver-centered conditions that should be in place before a rare disease trial involving pediatric patients, including infants, very young children, or non-verbal pediatric populations, is considered ready to launch.

This working group exists because:

  • pediatric rare disease trials often struggle not because of scientific intent, but because protocols are launched before assessment strategy, visit burden, and caregiver realities are adequately aligned to the target population.

Core questions this WG will answer:

  • What minimum criteria should define trial readiness for pediatric rare disease studies?

  • What makes an endpoint, ObsRO, biomarker, or digital assessment fit for purpose in non-verbal or developmentally limited populations?

  • What level of visit burden and procedural complexity is realistic across site, home, and local-care settings?

  • How should caregiver burden be evaluated and addressed before trial launch?

  • What pre-launch gaps most reliably predict poor enrollment, weak data quality, or avoidable dropout?

Scope:

  • pediatric and non-verbal pediatric rare disease populations

  • Fit-for-purpose measurement selection

  • Trial burden and visit-model feasibility

  • Caregiver-centered protocol design

  • Practical pre-launch readiness criteria

Output:

Draft Minimum Readiness Checklist for Pediatric Rare Disease Trials, including

  • minimum readiness criteria

  • common pre-launch failure points

  • a sponsor checklist for protocol and feasibility planning

Suggested participant profile:

  • pediatric clinicians with rare disease trial experience

  • pediatric endpoint and outcome-assessment experts

  • sponsor clinical-development and medical leads for pediatric programs

  • caregiver and advocacy leaders with direct trial-design experience

  • operational leaders with experience in pediatric site and home-based execution