Classifying the unclassifiable—a Delphi study to reach consensus on the fibrotic nature of diseases

BACKGROUND: Traditionally, clinical research has focused on individual fibrotic diseases or fibrosis in a particular organ. However, it is possible for people to have multiple fibrotic diseases. While multi-organ fibrosis may suggest shared pathogenic mechanisms, yet there is no consensus on what constitutes a fibrotic disease and therefore fibrotic multimorbidity. AIM: A Delphi study was performed to reach consensus on which diseases may be described as fibrotic. METHODS: Participants were asked to rate a list of diseases, sub-grouped according to eight body regions, as ‘fibrotic manifestation always present’, ‘can develop fibrotic manifestations’, ‘associated with fibrotic manifestations’ or ‘not fibrotic nor associated’. Classifications of ‘fibrotic manifestation always present’ and ‘can develop fibrotic manifestations’ were merged and termed ‘fibrotic’. Clinical consensus was defined according to the interquartile range, having met a minimum number of responses. Clinical agreement was used for classification where diseases did not meet the minimum number of responses (required for consensus measure), were only classified if there was 100% consensus on disease classification. RESULTS: After consulting experts, searching the literature and coding dictionaries, a total of 323 non-overlapping diseases which might be considered fibrotic were identified; 92 clinical specialists responded to the first round of the survey. Over three survey rounds, 240 diseases were categorized as fibrotic via clinical consensus and 25 additional diseases through clinical agreement. CONCLUSION: Using a robust methodology, an extensive list of diseases was classified. The findings lay the foundations for studies estimating the burden of fibrotic multimorbidity, as well as investigating shared mechanisms and therapies.