Introduction Autoinflammatory diseases can cause irreversible tissue damage due to systemic inflammation. Recently, the Autoinflammatory Disease Damage Index (ADDI) was developed. The ADDI is the first instrument to quantify damage in familial Mediterranean fever, cryopyrin-associated periodic syndromes, mevalonate kinase deficiency and tumour necrosis factor receptor-associated periodic syndrome. The aim of this study was to validate this tool for its intended use in a clinical/research setting.
Methods The ADDI was scored on paper clinical cases by at least three physicians per case, independently of each other. Face and content validity were assessed by requesting comments on the ADDI. Reliability was tested by calculating the intraclass correlation coefficient (ICC) using an ‘observer-nested-within-subject’ design. Construct validity was determined by correlating the ADDI score to the Physician Global Assessment (PGA) of damage and disease activity. Redundancy of individual items was determined with Cronbach’s alpha.
Results The ADDI was validated on a total of 110 paper clinical cases by 37 experts in autoinflammatory diseases. This yielded an ICC of 0.84 (95% CI 0.78 to 0.89). The ADDI score correlated strongly with PGA-damage (r=0.92, 95% CI 0.88 to 0.95) and was not strongly influenced by disease activity (r=0.395, 95% CI 0.21 to 0.55). After comments from disease experts, some item definitions were refined. The interitem correlation in all different categories was lower than 0.7, indicating that there was no redundancy between individual damage items.
Conclusion The ADDI is a reliable and valid instrument to quantify damage in individual patients and can be used to compare disease outcomes in clinical studies.
- fever syndromes
- familial Mediterranean fever
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Handling editor Josef S Smolen
Contributors NMtH, ALJvD, KVA and JF designed the study, created the patient cases and wrote the manuscript. HvS contributed to the study design and analysis. KLD represented the patient’s perspective. SMAM, GA, JA, KSB, SB, PAB, LC, MC, AVC, FdB, FD, AAdJ, ED, PD, KLD, GF, RG, RGM, EH, VH, TH, MH, HMH, AI, AFJ, TK, IKP, AK, JBKD, HJL, RML, AM, SN, IN, AKO, SO, EPA, PQ, DR, RR, AS, MT, YU, AR, GS, MG and JF provided patient cases and (except for JF) scored the ADDI on the rewritten case scenarios. All authors have read and approved the manuscript.
Funding The project was supported by ERANET-PRIOMEDCHILD RaDiCEA Project No 40-41800-98-007. The Eurofever Registry was funded by the Executive Agency for Health and Consumers (EAHC, Project No 2007332). The consensus meeting was supported by an unrestricted grant by Novartis Pharma.
Disclaimer Novartis Pharma did not have any influence on the selection of participants or on the content of the ADDI/consensus meeting or the reporting of the findings.
Competing interests Novartis Pharma financially supported meetings with the methodologist. PAB: consultancy/speaking fees from Novartis, Roche, SOBI, UCB. FdB: Novartis, Novimmune, Hoffmann-La Roche, SOBI, AbbVie. LC: speaker’s fee from Novartis and SOBI. MC: consultancy fees for Novartis, SOBI and Abbvie. KLD: consultancy work for SOBI and Novartis; donations, honorariums and unrestricted grants have been received by the Autoinflammatory Alliance from SOBI, Novartis and Regeneron. RG: consultant for Abbvie. RGM: study support from SOBI, Novartis, Regeneron. VH: honorariums and educational grants from Novartis; honorariums from SOBI. MH: consultant for Novartis. HMH: consultant for Novartis and SOBI; speaker for Novartis. TK: research grant by Novartis; speaker’s bureau by Roche, BMS, Novartis and SOBI. JKD: consultant/speaker for Novartis and SOBI, and has received grant support from SOBI and Novartis. RML: ad board and consultant for Abbvie and Novartis. PQ: investigator, consultant and speaker’s bureau for Novartis and SOBI. MG: consultant for and unrestricted grants to Eurofever and speaker’s fee from SOBI and Novartis. YU: grant/research support from Novartis; consultant for Novartis; speaker’s bureau of Abbvie, Neopharm, Novartis, Roche. JF: consultant for Novartis. GS: consulting fees for Novartis. FD: attended to Novartis advisory board meeting.
Patient consent Not required.
Ethics approval Local IRB of each participating centre granted approval to enter patient data in the Eurofever Registry. The present study is a validation of the ADDI; development of the ADDI was approved by the IRB of UMC Utrecht.
Provenance and peer review Not commissioned; externally peer reviewed.
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