# Section 5: Patient Voice & Patient-Reported Outcome Synthesis *This section centers the people these therapies are for. It synthesizes published patient-reported outcome (PRO) data used in and around these programs, and the documented positions of patient organizations — because the single strongest finding of this landscape is that **programs which understood what patients actually experience designed better trials.** Instruments are catalogued in pro_instruments.csv.* --- ## 5.1 Why patient voice is not optional here Every therapy in this landscape treats a disease where **the patient's lived experience is the efficacy signal**. In celiac disease and EoE the regulatory endpoint *is* a patient-reported symptom measure. The field learned — sometimes the hard way — that you cannot design a credible trial without first understanding, in patients' own words, what the disease feels like and what relief would mean to them. --- ## 5.2 Celiac disease — the richest PRO story, and a cautionary one **What the Nexvax2 program taught the field about patients.** Nexvax2 used the **CeD PRO** (Celiac Disease Patient Reported Outcome), a 0–10 symptom scale whose Total-GI domain was the Phase 2 *primary endpoint*. In building and running it, the program produced a genuinely important patient-experience finding: **nausea and vomiting — not diarrhea — are the most common acute symptoms of gluten exposure**, accompanied by systemic cytokine release specific to celiac patients. This reshaped how the field thinks about what a "gluten reaction" is. **But the PRO also exposed a design trap.** Because a gluten-free diet is the only management option and yet **intestinal injury and acute cytokine-release reactions persist despite it**, patients live with ongoing, unpredictable symptoms. When Nexvax2 (the peptide *is* gluten) was dosed, it could itself provoke the very symptoms the PRO was measuring — and the trial could not separate drug reactogenicity from lack of protection. The lesson, in patients' experiential terms: *a therapy made of the offending antigen must prove it does not simply reproduce the misery patients already know.* **The instrument ecosystem is mature.** Six validated PRO/HRQoL instruments exist for celiac (CeD PRO, CDSD/CDSD 2.1, CD-QOL, CSI, CDAQ, CD-GSRS), several FDA/EMA-reviewed. The CD-QOL was validated in **453 US adults through the iCureCeliac patient-powered research network** — patients literally built the evidence base. A recurring patient-reported theme: **the burden of the gluten-free diet itself** (social limitation, vigilance, anxiety) is a major quality-of-life driver independent of symptoms — captured in dedicated scales like the Impact of Adhering to a Gluten-Free Diet Questionnaire. --- ## 5.3 Type 1 diabetes — patient organizations drove the screening agenda In T1D the pivotal endpoints are biomarker-based (C-peptide) or clinical (time-to-diagnosis), so PRO plays a supporting role — but the **patient-advocacy voice was decisive in a different way**: patient organizations (JDRF, now Breakthrough T1D) built and championed the **autoantibody-screening infrastructure** that makes teplizumab usable at all. Because Tzield can only help someone identified in presymptomatic Stage 2, the entire value of the drug depends on screening programs that advocacy groups pushed into existence. Patient-experience concerns documented around T1D immunotherapy: **anxiety of "knowing but waiting"** (being told you will likely develop a disease years before it arrives), the **burden of 14 daily infusions in an asymptomatic person**, and equity concerns that screening access is uneven. The Canadian reimbursement review explicitly recorded patient-group input on these points. --- ## 5.4 EoE — patient voice is already codified in the regulatory pathway For EoE the patient voice is not aspirational — it is **built into FDA guidance**. FDA's *Eosinophilic Esophagitis: Developing Drugs for Treatment* requires **co-primary endpoints: a patient-reported symptom measure (dysphagia, via a validated COA such as the DSQ) AND histologic response**. Dysphagia is the dominant patient-reported symptom in adolescents and adults and was specifically identified for the COA co-primary. **Patient-organization voice in EoE is active and organized:** - **APFED** (American Partnership for Eosinophilic Disorders) co-authored the **Global EoE Position Paper (May 2025)** and successfully advocated for disease-specific **ICD-10 codes** — concrete infrastructure wins. - APFED + AGA launched a joint **World EoE Day** awareness campaign (2026) framing EoE as a disease where *"something as routine as eating [can] feel difficult, and at times, unsafe."* - **CURED** (Campaign Urging Research for Eosinophilic Disease) and APFED are named as recruitment/awareness partners for EoE trials, alongside the CEGIR (US) and EUREOS (Europe) research consortia. **What EoE patients say matters (from the codified patient-experience record):** food impaction and the fear of choking; the social isolation of not being able to eat normally; the burden and invasiveness of repeated endoscopies; the progression to fibrostenosis (irreversible narrowing) if untreated; and — for the many diagnosed as children — a lifetime of disease management. These are the lived priorities any EoE pMHC vaccine must speak to. --- ## 5.5 Cross-disease patient-priority synthesis Common threads across celiac, T1D, and EoE patient voices — the requirements an antigen-specific therapy must satisfy to be *wanted*, not just approved: 1. **Reduce the daily vigilance burden.** In all three diseases the avoidance/monitoring regimen (gluten-free diet, glucose monitoring, food elimination) is itself a dominant quality-of-life cost. A therapy that *relaxes* that vigilance is worth more than one that only moves a biomarker. 2. **Do not reproduce the disease to treat it.** The Nexvax2 experience is the patient-facing warning: a therapy built from the offending antigen must not deliver the symptoms patients fear (for EoE, this includes anaphylaxis risk with food allergens). 3. **Minimize procedural/administration burden**, especially for people who feel well (early/at-risk) or children. 4. **Make screening/eligibility accessible and equitable** — the companion diagnostic is a patient-access issue, not just a commercial one. 5. **Measure what patients feel, with instruments patients helped build.** The celiac iCureCeliac model and the EoE COA co-primary are the templates. *These five priorities become the backbone of the EoE patient-survey instrument in Section 10.*