Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Nov 12;17(1):415.
doi: 10.1186/s13023-022-02568-3.

Clinical management guidelines for Friedreich ataxia: best practice in rare diseases

Louise A Corben  1   2   3 , Veronica Collins  4 , Sarah Milne  4   5   6   7 , Jennifer Farmer  8 , Ann Musheno  8 , David Lynch  9 , Sub Subramony  10 , Massimo Pandolfo  11 , Jörg B Schulz  12   13 , Kim Lin  14 , Martin B Delatycki  4   5   15 ; Clinical Management Guidelines Writing Group
Collaborators, Affiliations

Clinical management guidelines for Friedreich ataxia: best practice in rare diseases

Louise A Corben et al. Orphanet J Rare Dis. .

Abstract

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.

Keywords: Evidence; Friedreich ataxia; GRADE; Guidelines; Recommendations.

PubMed Disclaimer

Conflict of interest statement

VC, SM, KL, JBS, SS, DL and LAC have no competing interests to report. MBD has research funding from the Friedreich's Ataxia Research Alliance, National Health and Medical Research Council (Australia) and Medical Research Future Fund (Australia). MP has research funding from the Friedreich's Ataxia Research Alliance and is a consultant with Design Therapeutics, Aavantibio, Larimar, Minoryx for the development of FRDA therapeutics. JF and AM are employees of the Friedreich’s Ataxia Research Alliance.

Figures

Fig. 1
Fig. 1
Flow chart of the stages of the guidelines development and stakeholder involvement. Red arrows indicate process for obtaining indirect evidence. CMG = Clinical Management Guidelines; PICO = Patient, Intervention, Comparator, Outcome; FACOMS = Friedreich’s Ataxia Clinical Outcomes Measures; EFACTS = European Friedreich’s Ataxia Consortium for Translational Studies; FRDA = Friedreich ataxia
See this image and copyright information in PMC

References

    1. Cossee M, Schmitt M, Campuzano V, Reutenauer L, Moutou C, Mandel JL, et al. Evolution of the Friedreich's ataxia trinucleotide repeat expansion: founder effect and premutations. Proc Natl Acad Sci USA. 1997;94(14):7452–7457. doi: 10.1073/pnas.94.14.7452. - DOI - PMC - PubMed
    1. Delatycki MB, Bidichandani SI. Friedreich ataxia-pathogenesis and implications for therapies. Neurobiol Dis. 2019;132:104606. doi: 10.1016/j.nbd.2019.104606. - DOI - PubMed
    1. Reetz K, Dogan I, Hohenfeld C, Didszun C, Giunti P, Mariotti C, et al. Nonataxia symptoms in Friedreich Ataxia: report from the Registry of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) Neurology. 2018;91(10):e917–e930. doi: 10.1212/WNL.0000000000006121. - DOI - PubMed
    1. Dürr A, Cossee M, Agid Y, Campuzano V, Mignard C, Penet C, et al. Clinical and genetic abnormalities in patients with Friedreich's ataxia. N Engl J Med. 1996;335(16):1169–1175. doi: 10.1056/NEJM199610173351601. - DOI - PubMed
    1. Rummey C, Farmer JM, Lynch DR. Predictors of loss of ambulation in Friedreich's ataxia. EClinicalMedicine. 2020;18:100213. doi: 10.1016/j.eclinm.2019.11.006. - DOI - PMC - PubMed

Publication types