# Section 10: EoE pMHC-Vaccine Patient Survey — Design Plan & Instrument Blueprint

## Purpose and guiding principles (patient-partnership-first)

This section commits the working group to a concrete next step: fielding a patient survey to ground pMHC (peptide-MHC) tolerance vaccine development for eosinophilic esophagitis (EoE) in the lived experience of the people it is meant to serve, rather than in assumptions made on their behalf. The lead investigator's own standing as an EoE patient is not incidental to this plan — it is the organizing principle. Every design choice below follows from a single conviction: instruments and development pathways built without patients at the table tend to measure what is convenient to measure, not what patients experience as burden, risk, or benefit.

Four principles govern this design:

1. **Nothing about us without us.** Patients and caregivers co-design the instrument, not merely respond to it. Draft items in this document are a starting point for patient-advisor revision, not a final survey.
2. **Anchor to lessons already paid for.** The Nexvax2 experience (a celiac gliadin-peptide immunotherapy halted after triggering allergic-type reactions in trials) and the Tzield post-market adoption problem (14 daily IV infusions proving a hard sell to asymptomatic at-risk individuals) are treated as empirical priors, not hypotheticals. This survey is designed to detect analogous failure modes for EoE — especially anaphylaxis risk from food-antigen-derived peptides and schedule/route burden — before they are designed into a program.
3. **Measure what patients feel, using tools patients helped build.** Wherever validated instruments exist (DSQ, EEsAI, PROMIS), we anchor to them for comparability and regulatory relevance. Where they do not — patient willingness to accept anaphylaxis risk in exchange for reduced avoidance burden, for instance — we build new items transparently and iteratively.
4. **This is a companion, not a replacement, for a formal Patient-Focused Drug Development (PFDD) meeting.** No dedicated EoE PFDD currently exists. This survey generates the quantitative and qualitative substrate that can seed one, convened jointly with APFED and CURED.

Nothing in this document constitutes medical advice, and no item here is final; all items require review by the patient advisory panel and IRB approval before fielding.

## Research questions

1. What is the current burden of EoE and its management (dietary, endoscopic, pharmacologic) as patients themselves rank it?
2. How well do patients understand the concept of a pMHC/antigen-based tolerance vaccine, and what explanatory framing is needed for informed response?
3. What efficacy profile (symptom relief vs. histologic remission vs. diet liberalization) would patients consider worth pursuing, and what is the minimum acceptable benefit?
4. What routes, schedules, and administration burdens are patients willing to tolerate, and how does this vary by symptom severity and life stage (child, adolescent, adult)?
5. What level of risk — particularly anaphylaxis and other immune-mediated reactions — are patients willing to accept, and how does this trade off against potential benefit?
6. How does prior treatment history (biologics, steroids, diet elimination, dilation) shape fatigue, trust, and willingness to enroll in novel trials?
7. What information, consent processes, and trust-building steps do patients need before considering participation?
8. Is HLA-typing or other companion-diagnostic screening acceptable, and what equity barriers might it introduce?
9. What forms of ongoing involvement do patients want in the development pipeline itself?

## Target population and sampling (incl. pediatric/caregiver considerations)

**Target population:** Individuals with a clinician-confirmed diagnosis of EoE (self-reported diagnosis acceptable with a confirmatory screening question), age 8 and up, across the disease spectrum — newly diagnosed, well-controlled, and refractory/fibrostenotic. Given that a large share of EoE patients are diagnosed in childhood, the sample must include both pediatric patients (via caregiver-assisted or caregiver-proxy response) and adults who were diagnosed as children, whose retrospective perspective on years of dietary and procedural burden is distinct and valuable.

**Sampling strata:**
- Age at survey: child (8–12, caregiver-assisted), adolescent (13–17, assent + caregiver), adult (18+)
- Age at diagnosis: pediatric-onset vs. adult-onset
- Current disease control status: active symptoms vs. histologic/clinical remission
- Current management: elimination diet only, topical steroids, biologic therapy, dilation history, combination
- Geographic and sociodemographic diversity, with deliberate oversampling outreach to underrepresented racial/ethnic groups and lower-income/rural respondents, given known disparities in specialist access

**Target sample size:** Minimum n=400 adults and n=150 caregiver-proxy pediatric responses to support subgroup analysis (informed by prior EoE registry survey response patterns); powered as a descriptive/exploratory study, not a hypothesis-testing trial.

**Caregiver considerations:** For children under 13, caregivers complete the survey with the child; for adolescents 13–17, a dual instrument (adolescent self-report + caregiver report) captures both the patient's own risk tolerance and the caregiver's, since these may diverge meaningfully on questions like anaphylaxis risk acceptance.

## Recruitment strategy (patient organizations: APFED, CURED; clinical networks: CEGIR)

Recruitment will be led by trusted patient-community channels rather than cold clinical outreach, consistent with the patient-partnership principle:

- **APFED (American Partnership for Eosinophilic Disorders):** primary distribution partner via newsletter, member portal, and social channels; APFED's existing patient registry (if consented for research contact) as a sampling frame.
- **CURED Foundation:** parallel distribution, particularly valuable for reaching pediatric-diagnosed and caregiver populations given CURED's family-support focus.
- **CEGIR (Consortium of Eosinophilic Gastrointestinal Disease Researchers):** clinical-site recruitment through participating academic centers, providing a clinically-verified (vs. self-reported) diagnosis subgroup and access to patients with more severe/refractory disease who may be underrepresented in patient-organization-driven samples.
- **Snowball and social recruitment:** shareable survey link with plain-language explainer video, encouraging forwarding within patient communities.
- **Incentive design:** modest, equitable incentive (e.g., gift card) to reduce participation burden without being coercive, reviewed by IRB for appropriateness across income levels.

All recruitment materials will be drafted with patient advisors and will disclose the survey's purpose, sponsor, voluntary nature, and data use plainly before consent.

## Survey domains and sample items

*All items below are illustrative drafts for patient-advisor and IRB revision — not a final instrument.*

**Domain 1: Disease and treatment burden / current experience**
1. In the past month, how often did swallowing difficulty (dysphagia) affect what or how you ate? (Never / Rarely / Sometimes / Often / Every day)
2. How much does fear of a food getting stuck (impaction) affect your food choices? (Not at all — A great deal, 5-point Likert)
3. Rank the following burdens from most to least disruptive to your daily life: dietary restriction, fear of food impaction, endoscopy frequency, medication routine, symptom unpredictability.
4. In the past year, approximately how many upper endoscopies have you had? (0 / 1 / 2 / 3 / 4+ )
5. Open text: "Describe, in your own words, what living with EoE costs you day to day."

**Domain 2: Understanding of the pMHC/tolerance vaccine concept**
1. Before today, had you heard of a "tolerance vaccine" or antigen-based immunotherapy approach for allergic or immune conditions? (Yes / No / Not sure)
2. After reading the plain-language explanation provided, how clear is your understanding of how this approach is intended to work? (1=Not at all clear – 5=Very clear)
3. What questions do you still have about how this type of treatment would work? (open text)

**Domain 3: Efficacy expectations and acceptable outcomes**
1. If a treatment reduced your swallowing symptoms but did not fully normalize esophageal tissue (histology), would you consider that worthwhile? (Yes / No / Depends on degree of symptom relief)
2. Which outcome matters most to you personally? (Choose one: fewer swallowing symptoms / ability to eat previously avoided foods / fewer endoscopies / reduced medication use / normal biopsy results)
3. What is the minimum symptom improvement that would make ongoing treatment worth it to you? (0–25% / 25–50% / 50–75% / 75–100% improvement)

**Domain 4: Route and schedule tolerance**
1. Which administration route would you find most acceptable? (Oral pill / Under-the-skin injection / IV infusion in a clinic / Patch or skin-based / No preference)
2. If effective, how many clinic visits per year would you be willing to accept for treatment administration? (1–2 / 3–6 / 7–12 / more than 12 / none — would require self-administration only)
3. Would a multi-dose induction schedule (e.g., several visits in the first month) affect your willingness to start treatment? (Yes, less willing / No effect / Yes, more willing) with open-text follow-up on why.

**Domain 5: Risk tolerance, including anaphylaxis and immune-related risk**
1. How concerned would you be about a treatment made from the same food-protein fragments that trigger your EoE causing an allergic reaction, including anaphylaxis? (Not at all concerned – Extremely concerned, 5-point)
2. What is the highest level of risk of a serious allergic reaction you would accept in exchange for a meaningful reduction in your EoE symptoms? (No added risk / Small risk, e.g., similar to routine allergy shots / Moderate risk, requiring in-clinic monitoring / Would accept regardless of risk level / Not sure)
3. Would you want treatment administered only in a setting equipped to treat anaphylaxis (e.g., clinic with emergency equipment), even if less convenient? (Yes / No / Depends)
4. Open text: "What would make you feel a new treatment was being tested safely?"

**Domain 6: Prior-treatment history and fatigue**
1. Which treatments have you tried for EoE? (checklist: elimination diet, topical/swallowed steroids, biologic injection, dilation procedure, other)
2. How many different treatment approaches have you tried in total? (1 / 2–3 / 4–5 / 6+)
3. How "burned out" do you feel by ongoing EoE management and trying new treatments? (1=Not at all – 5=Extremely)
4. Has treatment fatigue ever led you to stop or delay a recommended treatment or trial participation? (Yes / No / Prefer not to say)

**Domain 7: Trust, consent, and information needs**
1. How much do you trust that a new EoE treatment developed from research would be tested thoroughly for safety before being offered to patients? (1–5 scale)
2. What information would you want before agreeing to try an experimental tolerance vaccine? (checklist: how it was tested in animals/early trials, specific risks including allergic reaction, what monitoring would occur, who developed it and funding source, other — specify)
3. Would knowing that EoE patients helped design the trial increase your trust in participating? (Yes, a lot / Somewhat / No difference / Not sure)

**Domain 8: Screening/HLA-typing acceptability**
1. Would you be willing to undergo a blood test (e.g., genetic/HLA typing) to determine if this treatment might work for you or carries elevated risk? (Yes / Yes, with concerns / No / Not sure)
2. What concerns, if any, would you have about genetic or immune-marker testing as an eligibility requirement? (open text)
3. Would cost or travel required for this testing affect your willingness to participate? (Yes, significantly / Somewhat / No)

**Domain 9: Desire for involvement in development; Demographics**
1. How interested are you in being involved in future stages of this treatment's development (e.g., advisory panels, reviewing trial materials, giving feedback on study design)? (Not interested – Very interested, 5-point)
2. Which forms of involvement appeal to you? (checklist: joining a patient advisory board, reviewing plain-language study materials, participating in a PFDD-style meeting, being contacted for future surveys, none at this time)
3. Demographics: age, age at diagnosis, sex, race/ethnicity, geographic region, insurance status, household income bracket (optional/skippable), caregiver-vs-self-report indicator.

## Validated-instrument anchors (map domains to DSQ/EEsAI/PROMIS)

- **Domain 1 (burden/current experience)** anchors to the **Dysphagia Symptom Questionnaire (DSQ)**, the FDA-recognized symptom COA for EoE trials, and the **EEsAI (EoE Symptom Activity Index)** for composite symptom/impact scoring. Using DSQ-consistent recall periods and phrasing allows direct comparability to regulatory-grade endpoints.
- **Domain 3 (efficacy expectations)** cross-references EEsAI domains (dysphagia frequency, avoidance/modification behaviors, associated symptoms) so that patient-defined "meaningful improvement" can eventually be benchmarked against EEsAI score changes used in trials.
- **Domain 6 (fatigue, burden of prior treatment)** and general quality-of-life items draw on **PROMIS** short forms (Fatigue, Global Health, Anxiety) to allow comparison with broader chronic-disease populations and existing PROMIS normative data.
- Domains 2, 4, 5, 7, 8, and 9 (concept understanding, route/schedule, risk tolerance, trust, screening, engagement) have no existing validated instrument in EoE — these are the novel contribution of this survey, and a priority candidate set for future psychometric validation, potentially through a formal EoE PFDD process.

## Analysis plan (quantitative + qualitative/thematic; segmentation)

**Quantitative:** Descriptive statistics (frequencies, means, medians) for all closed-ended items; comparison across pre-specified segments (pediatric-onset vs. adult-onset, active vs. controlled disease, treatment-naive vs. treatment-experienced, biologic-exposed vs. not) using chi-square/Fisher's exact tests for categorical items and Kruskal-Wallis for ordinal Likert items given expected non-normality. Composite burden and risk-tolerance scores will be constructed and correlated with DSQ/EEsAI-anchored items to test convergent validity. Where sample size allows, latent class or cluster analysis will be used to identify patient segments (e.g., "risk-averse/high-vigilance," "high-burden/high-risk-tolerance," "diet-fatigued/procedure-averse") to inform differentiated trial-design and communication strategies.

**Qualitative:** Open-text responses will undergo inductive thematic coding by at least two coders (including a patient co-analyst) with a reconciled codebook, focused especially on Domains 1, 2, 5, and 7 where nuance is expected to exceed closed-ended capture. Illustrative de-identified quotes will be retained for the eventual PFDD briefing document.

**Segmentation reporting:** All findings will be reported by pediatric/caregiver vs. adult, and by disease severity strata, to avoid masking divergent needs within an averaged "EoE patient" profile.

## Ethical considerations & health-literacy/plain-language design

All survey materials will be written at a 6th–8th grade reading level, reviewed with a health-literacy checklist, and piloted with a small patient-advisor group (including at least one adolescent and one caregiver) for comprehension before full fielding. The pMHC/tolerance-vaccine explainer (Domain 2) requires particular care: it must convey mechanism honestly, including the Nexvax2-informed anaphylaxis-risk context, without inducing undue alarm or, conversely, false reassurance. Consent language will be layered (short summary plus expandable detail), translated into languages reflecting the recruitment population, and reviewed for accessibility (screen-reader compatibility, plain visual design). Pediatric assent will use age-appropriate language distinct from the adult/caregiver instrument. The full instrument, recruitment materials, and consent forms require IRB approval prior to fielding, and no data collection will begin without it. Nothing in this survey or its resulting report is intended as individual medical advice; respondents will be reminded of this, and directed to their own clinicians for treatment decisions.

## Patient-engagement model — embedding patients at each development stage

Patient involvement is not a single survey event but a standing structure:

- **Advisory board (ongoing):** A standing EoE Patient Advisory Board (recruited via APFED/CURED, including pediatric-diagnosed adults and caregivers) reviews and approves all survey instruments, recruitment materials, and consent language before fielding, and reconvenes at each subsequent development milestone.
- **Co-design (pre-fielding):** Draft items in this document go through at least two rounds of patient-advisor revision and cognitive-interview pilot testing (5–10 respondents) before the survey is