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@ARTICLE{Reetz:157803,
      author       = {Reetz, Kathrin and Dogan, Imis and Hilgers, Ralf-Dieter and
                      Giunti, Paola and Parkinson, Michael H and Mariotti,
                      Caterina and Nanetti, Lorenzo and Dürr, Alexandra and
                      Ewenczyk, Claire and Boesch, Sylvia and Nachbauer, Wolfgang
                      and Klopstock, Thomas and Stendel, Claudia and Rodríguez de
                      Rivera Garrido, Francisco Javier and Rummey, Christian and
                      Schöls, Ludger and Hayer, Stefanie and Klockgether, Thomas
                      and Giordano, Ilaria and Didszun, Claire and Rai, Myriam and
                      Pandolfo, Massimo and Schulz, Jörg B and Labrum, Robyn and
                      Thomas-Black, Gilbert and Manso, Katarina and Solanky, Nita
                      and Gellera, Cinzia and Mongelli, Alessia and Castaldo, Anna
                      and Fichera, Mario and Palau, Francesc and O'Callaghan, Mar
                      and Biet, Marie and Monin, Marie Lorraine and Eigentler,
                      Andreas and Indelicato, Elisabetta and Amprosi, Matthias and
                      Radelfahr, Florentine and Bischoff, Almut T. and Holtbernd,
                      Florian and Brcina, Nikolina and Hohenfeld, Christian and
                      Koutsis, Georgios and Breza, Marianthi and Bertini, Enrico
                      and Vasco, Gessica},
      title        = {{P}rogression characteristics of the {E}uropean
                      {F}riedreich's {A}taxia {C}onsortium for {T}ranslational
                      {S}tudies ({EFACTS}): a 4-year cohort study},
      journal      = {The lancet / Neurology},
      volume       = {20},
      number       = {5},
      issn         = {1474-4422},
      address      = {London},
      publisher    = {Lancet Publ. Group},
      reportid     = {DZNE-2021-01260},
      pages        = {362 - 372},
      year         = {2021},
      abstract     = {Background: The European Friedreich's Ataxia Consortium for
                      Translational Studies (EFACTS) investigates the natural
                      history of Friedreich's ataxia. We aimed to assess
                      progression characteristics and to identify patient groups
                      with differential progression rates based on longitudinal
                      4-year data to inform upcoming clinical trials in
                      Friedreich's ataxia.Methods: EFACTS is a prospective,
                      observational cohort study based on an ongoing and
                      open-ended registry. Patients with genetically confirmed
                      Friedreich's ataxia were seen annually at 11 clinical
                      centres in seven European countries (Austria, Belgium,
                      France, Germany, Italy, Spain, and the UK). Data from
                      baseline to 4-year follow-up were included in the current
                      analysis. Our primary endpoints were the Scale for the
                      Assessment and Rating of Ataxia (SARA) and the activities of
                      daily living (ADL). Linear mixed-effect models were used to
                      analyse annual disease progression for the entire cohort and
                      subgroups defined by age of onset and ambulatory abilities.
                      Power calculations were done for potential trial designs.
                      This study is registered with ClinicalTrials.gov,
                      NCT02069509.Findings: Between Sept 15, 2010, and Nov 20,
                      2018, of 914 individuals assessed for eligibility, 602
                      patients were included. Of these, 552 $(92\%)$ patients
                      contributed data with at least one follow-up visit. Annual
                      progression rate for SARA was 0·82 points (SE 0·05) in the
                      overall cohort, and higher in patients who were ambulatory
                      (1·12 [0·07]) than non-ambulatory (0·50 [0·07]). ADL
                      worsened by 0·93 (SE 0·05) points per year in the entire
                      cohort, with similar progression rates in patients who were
                      ambulatory (0·94 [0·07]) and non-ambulatory (0·91
                      [0·08]). Although both SARA and ADL showed slightly greater
                      worsening in patients with typical onset (symptom onset at
                      ≤24 years) than those with late onset (symptom onset ≥25
                      years), differences in progression slopes were not
                      significant. For a 2-year parallel-group trial, 230 (115 per
                      group) patients would be required to detect a $50\%$
                      reduction in SARA progression at $80\%$ power: 118 (59 per
                      group) if only individuals who are ambulatory are included.
                      With ADL as the primary outcome, 190 (95 per group) patients
                      with Friedreich's ataxia would be needed, and fewer patients
                      would be required if only individuals with early-onset are
                      included.Interpretation: Our findings for stage-dependent
                      progression rates have important implications for clinicians
                      and researchers, as they provide reliable outcome measures
                      to monitor disease progression, and enable tailored sample
                      size calculation to guide upcoming clinical trial designs in
                      Friedreich's ataxia.},
      keywords     = {Activities of Daily Living / Adult / Cohort Studies /
                      Disease Progression / Europe / Female / Friedreich Ataxia:
                      complications / Friedreich Ataxia: pathology / Friedreich
                      Ataxia: physiopathology / Humans / Male / Middle Aged /
                      Mobility Limitation / Registries / Time Factors / Young
                      Adult},
      cin          = {U Clinical Researchers - München / Patient Studies Bonn /
                      AG Jucker / AG Gasser / AG Höglinger 1 / AG Klockgether},
      ddc          = {610},
      cid          = {I:(DE-2719)7000003 / I:(DE-2719)1011101 /
                      I:(DE-2719)1210001 / I:(DE-2719)1210000 / I:(DE-2719)1110002
                      / I:(DE-2719)1011001},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 352 -
                      Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33770527},
      pubmed       = {33770527},
      doi          = {10.1016/S1474-4422(21)00027-2},
      url          = {https://pub.dzne.de/record/157803},
}