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                • EMA 2004 — Guideline on clinical investigation of medicinal products for psoriasis (CHMP/EWP/2454/02)
                • Fink 2018 — Inter- and intra-observer variability of image-based PASI
                • Huang 2023 — AI-based PASI severity assessment: real-world study (SkinTeller)
                • King 2022 — Baricitinib BRAVE-AA1 / BRAVE-AA2 (SALT as FDA / EMA primary endpoint)
                • Mattei 2014 — PASI ↔ DLQI correlation in biologic RCTs (r² = 0.80)
                • Mrowietz 2011 — European treat-to-target consensus for moderate-to-severe psoriasis
                • Olsen 2004 — Alopecia areata investigational assessment guidelines (SALT definition, NAAF)
                • Schaap 2022 — CNN-based automated PASI scoring
                • Schmitt 2014 — HOME IV: EASI as core instrument for clinical signs of atopic eczema
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  • EMA 2004 — Guideline on clinical investigation of medicinal products for psoriasis (CHMP/EWP/2454/02)

EMA 2004 — Guideline on clinical investigation of medicinal products for psoriasis (CHMP/EWP/2454/02)

Citation​

European Medicines Agency, CHMP. Guideline on clinical investigation of medicinal products indicated for the treatment of psoriasis. CHMP/EWP/2454/02 corr., adopted 18 November 2004, in operation June 2005. URL: ema.europa.eu/documents/scientific-guideline/guideline-clinical-investigation-medicinal-products-indicated-treatment-psoriasis_en.pdf

Document type​

Regulatory guideline (not a primary study). Sets EU expectations for clinical development of topical and systemic psoriasis treatments; applies to all EU psoriasis drug approvals.

Key endpoints established​

  • PASI (Psoriasis Area and Severity Index) — recommended primary efficacy variable
  • PGA / IGA (Physician / Investigator Global Assessment) — mandatory co-primary endpoint
  • BSA (Body Surface Area) — supportive measure
  • Response threshold: PASI-75 (historical baseline); PASI-90 acknowledged as high-level therapeutic goal
  • HRQoL co-endpoints (DLQI) required to link severity to patient-relevant outcome

Surrogate-to-outcome linkage​

Formally anchors PASI and PGA/IGA surrogates to clinically relevant patient outcomes (disease control, HRQoL) via regulator-required co-endpoints. Constitutes the strongest possible form of surrogate endorsement: regulatory acceptance of these scores as proxies for treatment benefit in EU drug approvals.

CRIT1–7 appraisal​

CriterionScoreJustification
CRIT1 Relevance3Direct — codifies the EU regulatory surrogate endpoint for the severity-scoring domain.
CRIT2 Methodologyn/aGuideline (derived from systematic evidence and expert consensus).
CRIT3 Reporting3Formal EMA document with stated endpoint definitions and response thresholds.
CRIT4 Applicability3EU regulatory context directly applicable to the MDR Pillar-1 argument.
CRIT5 Evidence weight3Regulatory guideline — strongest precedent form.
CRIT6 Risk of bias2Dates to 2004; pre-dates IL-17 / IL-23 biologics era where PASI-90 / PASI-100 are standard targets.
CRIT7 Contribution3Foundational regulatory anchor — establishes PASI / IGA as EMA-accepted proxies for patient outcome.

Aggregate: very strong.

Limitations and notes​

Pre-dates modern biologic era; threshold generalisability to AI-generated scores requires additional validation (not a weakness of the guideline — a downstream task). Supplement with HOME (Schmitt 2014) for atopic dermatitis, with Simpson 2016 / King 2022 for pivotal-trial endpoint use.

Strength as anchor​

Essential regulatory anchor. The VCA argument for severity scoring as a Pillar-1 surrogate leans on regulator acceptance of PASI / EASI / SCORAD / SALT in drug approvals; this guideline is the formal EU statement for psoriasis. Counterpart for atopic dermatitis is EuroGuiDerm / HOME; for alopecia areata is Olsen 2004 / King 2022; for acne is FDA acne guidance.

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  • Citation
  • Document type
  • Key endpoints established
  • Surrogate-to-outcome linkage
  • CRIT1–7 appraisal
  • Limitations and notes
  • Strength as anchor
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