Patient-recorded outcome to assess therapeutic efficacy in protoporphyria-induced dermal phototoxicity: a proposal

BACKGROUND: Protoporphyria (PP) resulting from two rare, inherited diseases of heme biosynthesis leads to dermal phototoxicity by accumulation of the heme precursor protoporphyrin IX. No standardized tools to quantify the degree of PP-related phototoxicity and its change by medical intervention have been published. METHODS: Results from a questionnaire completed by 17 affected individuals were used to determine the relative importance of two main components of PP-related phototoxicity, skin pain and sunlight exposure time, with respect to the effectiveness of any particular medical treatment. RESULTS: Inter-rater reliability was 0.71 (n = 490), repeated estimates by four identical individuals showed high reproducibility (Slope = 1, intercept = 0, n = 136, Passing-Bablock). Six different models were developed, three of them showed good correlation with effectiveness estimates. Data from an unpublished trial indicated that the model with highest potential of responsiveness was the so called "Exposure times [multiplied by] Freedom from Pain" (ETFP). The minimal clinically important difference (MID) was 15 (10.2-20.4) ETFP scores, representing 28% of the standard deviation of the clinical trial data and 2.9% of its total range. CONCLUSIONS: Among the six models proposed to assess the effectiveness of therapeutic interventions in PP the ETFP model demonstrates the highest sensitivity using the existing data from a clinical trial of afamelanotide in PP. The results of this study have provided sufficient validation of the ETFP model that is likely to prove useful in future clinical trials.