Early indicators of disease progression in Fabry disease that may indicate the need for disease-specific treatment initiation: findings from the opinion-based PREDICT-FD modified Delphi consensus initiative.

Abstract

OBJECTIVES:

The PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease (PREDICT-FD) initiative aimed to reach consensus among a panel of global experts on early indicators of disease progression that may justify FD-specific treatment initiation.

DESIGN AND SETTING:

Anonymous feedback from panellists via online questionnaires was analysed using a modified Delphi consensus technique. Questionnaires and data were managed by an independent administrator directed by two non-voting cochairs. First, possible early indicators of renal, cardiac and central/peripheral nervous system (CNS/PNS) damage, and other disease and patient-reported indicators assessable in routine clinical practice were compiled by the cochairs and administrator from panellists' free-text responses. Second, the panel scored indicators for importance (5-point scale: 1=not important; 5=extremely important); indicators scoring ≥3 among >75% of panellists were then rated for agreement (5-point scale: 1=strongly disagree; 5=strongly agree). Indicators awarded an agreement score ≥4 by >67% of panellists achieved consensus. Finally, any panel-proposed refinements to consensus indicator definitions were adopted if >75% of panellists agreed.

RESULTS:

A panel of 21 expert clinicians from 15 countries provided information from which 83 possible current indicators of damage (kidney, 15; cardiac, 15; CNS/PNS, 13; other, 16; patient reported, 24) were compiled. Of 45 indicators meeting the importance criteria, consensus was reached for 29 and consolidated as 27 indicators (kidney, 6; cardiac, 10; CNS/PNS, 2; other, 6; patient reported, 3) including: (kidney) elevated albumin:creatinine ratio, histological damage, microalbuminuria; (cardiac) markers of early systolic/diastolic dysfunction, elevated serum cardiac troponin; (CNS/PNS) neuropathic pain, gastrointestinal symptoms suggestive of gastrointestinal neuropathy; (other) pain in extremities/neuropathy, angiokeratoma; (patient-reported) febrile crises, progression of symptoms/signs. Panellists revised and approved proposed chronologies of when the consensus indicators manifest. The panel response rate was >95% at all stages.

CONCLUSIONS:

PREDICT-FD captured global opinion regarding current clinical indicators that could prompt FD-specific treatment initiation earlier than is currently practised.

• Authors: Derralynn A Hughes, Patricio Aguiar, Patrick B Deegan, Fatih Ezgu, Andrea Frustaci, Olivier Lidove, Aleš Linhart, Jean-Claude Lubanda, James C Moon, Kathleen Nicholls, Dau-Ming Niu, Albina Nowak, Uma Ramaswami, Ricardo Reisin, Paula Rozenfeld, Raphael Schiffmann, Einar Svarstad, Mark Thomas, Roser Torra, Bojan Vujkovac, David G Warnock, Michael L West, Jack Johnson, Mark J Rolfe, Sandro Feriozzi
• Journal: BMJ open (BMJ Open) Vol. 10 Issue 10 Pg. e035182 (10 10 2020) ISSN: 2044-6055 [Electronic] England
• PMID: 33039984 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Topics

• Consensus
• Delphi Technique
• Disease Progression
• Fabry Disease (diagnosis, drug therapy)
• Humans
• Surveys and Questionnaires