@article {Milne2021.03.18.434657, author = {Sarah C Milne and Seok Hun Kim and Anna Murphy and Jane Larkindale and Jennifer Farmer and Ritchie Malapira and Mary Danoudis and Jessica Shaw and Tyagi Ramakrishnan and Fatemeh Rasouli and Eppie M Yiu and Nellie Georgiou-Karistianis and Geneieve Tai and Theresa Zesiewicz and Martin B Delatycki and Louise A Corben}, title = {The responsiveness of gait and balance outcomes to disease progression in Friedreich ataxia}, elocation-id = {2021.03.18.434657}, year = {2021}, doi = {10.1101/2021.03.18.434657}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Objective To identify gait and balance measures that are responsive to change during the timeline of a clinical trial in Friedreich ataxia (FRDA) we administered a battery of potential measures three times over a 12-month period.Methods Sixty-one ambulant individuals with FRDA underwent assessment of gait and balance at baseline, six months and 12 months. Outcomes included: GAITRite{\textregistered} spatiotemporal gait parameters; Biodex Balance System Postural Stability Test (PST) and Limits of Stability; Berg Balance Scale (BBS); Timed 25 Foot Walk Test; Dynamic Gait Index (DGI); SenseWear MF Armband step and energy activity; and the Friedreich Ataxia Rating Scale Upright Stability Subscale (FARS USS). The standardised response mean (SRM) or correlation coefficients were reported as effect size indices for comparison of internal responsiveness. Internal responsiveness was also analysed in subgroups.Results SenseWear Armband daily step count had the largest effect size of all the variables over six months (SRM=-0.615), while the PST medial-lateral index had the largest effect size (SRM=0.829) over 12 months. The FARS USS (SRM=0.824) and BBS (SRM=-0.720) were the only outcomes able to detect change over 12 months in all subgroups. The DGI was the most responsive outcome in children, detecting a mean change of -2.59 (95\% CI -3.52 to -1.66, p\<0.001, SRM=-1.429).Conclusions The FARS USS and BBS are highly responsive and can detect change in a wide range of ambulant individuals with FRDA. However, therapeutic effects in children may be best measured by the DGI.Competing Interest StatementThis study was sponsored by the Friedreichs Ataxia Research Alliance (USA); PTC Therapeutics and Voyager Therapeutics as a part of FARAs Biomarker Consortium. S.C. Milne received a National Health and Medical Research Council of Australia Postgraduate Scholarship (APP1093259); J. Larkindale was employed by the Friedreichs Ataxia Research Alliance; J. Farmer is employed by the Friedreichs Ataxia Research Alliance; E.M. Yiu is a National Health and Medical Research Council Early Career Fellow (APP 1073323); L.A. Corben is a Medical Research Futures Fund Career Development Fellow (APP1143098).}, URL = {https://www.biorxiv.org/content/early/2021/03/20/2021.03.18.434657}, eprint = {https://www.biorxiv.org/content/early/2021/03/20/2021.03.18.434657.full.pdf}, journal = {bioRxiv} }