Clinical management guidelines for Friedreich ataxia: best practice in rare diseases
Authors: Corben Louise A. , Collins Veronica , Milne Sarah , Farmer Jennifer , Musheno Ann , Lynch David , Subramony Sub , Pandolfo Massimo , Schulz Jörg B. , Lin Kim , Delatycki Martin B. ,   the Clinical Management Guidelines Writing Group, Akhlaghi Hamed , Bidichandani Sanjay I. , Boesch Sylvia , Cnop Miriam , Corti Manuela , Duquette Antoine , Durr Alexandra , Eigentler Andreas , Emmanuel Anton , Flynn John M. , Foroush Noushin Chini , Fournier Anne , França Marcondes C. , Giunti Paola , Goh Ellen W. , Graf Lisa , Hadjivassiliou Marios , Huckabee Maggie-Lee , Kearney Mary G. , Koeppen Arnulf H. , Lie Yenni , Lin Kimberly Y. , Lowit Anja , Mariotti Caterina , Mathews Katherine , McCormack Shana E. , Montenegro Lisa , Morlet Thierry , Naeije Gilles , Panicker Jalesh N. , Parkinson Michael H. , Patel Aarti , Payne Ronald Mark , Perlman Susan , Peverill Roger E. , Pousset Francoise , Puccio Hélène , Rai Myriam , Rance Gary , Reetz Kathrin , Rowland Tennille J. , Sansom Phoebe , Savvatis Konstantinos , Schalling Ellika T. , Schöls Ludger , Smith Barbara , Soragni Elisabetta , Spencer Caroline , Synofzik Matthis , Szmulewicz David J. , Tai Geneieve , Tamaroff Jaclyn , Treat Lauren , Carpentier Ariane Veilleux , Vogel Adam P. , Walther Susan E. , Weber David R. , Weisbrod Neal J. , Wilmot George , Wilson Robert B. , Yoon Grace , Zesiewicz Theresa 
Published: November 2022

Background

Individuals with Friedreich ataxia (FRDA) can find it difficult to access specialized clinical care. To facilitate best practice in delivering healthcare for FRDA, clinical management guidelines (CMGs) were developed in 2014. However, the lack of high-certainty evidence and the inadequacy of accepted metrics to measure health status continues to present challenges in FRDA and other rare diseases. To overcome these challenges, the Grading of Recommendations Assessment and Evaluation (GRADE) framework for rare diseases developed by the RARE-Bestpractices Working Group was adopted to update the clinical guidelines for FRDA. This approach incorporates additional strategies to the GRADE framework to support the strength of recommendations, such as review of literature in similar conditions, the systematic collection of expert opinion and patient perceptions, and use of natural history data.

Methods

A panel representing international clinical experts, stakeholders and consumer groups provided oversight to guideline development within the GRADE framework. Invited expert authors generated the Patient, Intervention, Comparison, Outcome (PICO) questions to guide the literature search (2014 to June 2020). Evidence profiles in tandem with feedback from individuals living with FRDA, natural history registry data and expert clinical observations contributed to the final recommendations. Authors also developed best practice statements for clinical care points that were considered self-evident or were not amenable to the GRADE process.

Results

Seventy clinical experts contributed to fifteen topic-specific chapters with clinical recommendations and/or best practice statements. New topics since 2014 include emergency medicine, digital and assistive technologies and a stand-alone section on mental health. Evidence was evaluated according to GRADE criteria and 130 new recommendations and 95 best practice statements were generated.

Discussion and conclusion

Evidence-based CMGs are required to ensure the best clinical care for people with FRDA. Adopting the GRADE rare-disease framework enabled the development of higher quality CMGs for FRDA and allows individual topics to be updated as new evidence emerges. While the primary goal of these guidelines is better outcomes for people living with FRDA, the process of developing the guidelines may also help inform the development of clinical guidelines in other rare diseases.