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In April 2016, PPMD convened a workshop to assess the measures used to evaluate pulmonary strength, air flow and lung volumes. Thanks to the tireless effort of Dr. Jonathan Finder, this summary has now been published.

 

It is our hope that these recommendations will assist in the accurate evaluation of pulmonary status and data collection for all trials utilizing pulmonary outcomes.

 

The goals of this workshop, chaired by Dr. Jonathan Finder (Children’s Hospital of Pittsburgh) were:

 

  • Assess currently utilized pulmonary outcome measures, their clinical meaningfulness, possible limitations, and the need to implement novel pulmonary outcome measures
  • Identify how our current knowledge of pulmonary outcome measures can further drug development
  • Identify gaps in our current knowledge of pulmonary outcome measures
  • Utilize this forum to educate ourselves, the greater Duchenne clinical and research community, and the FDA on the need for reliable, responsive, and meaningful pulmonary outcome measures

 

Recommendations from the workshop included:

 

  1. Clinical evaluator training is needed for consistency of measurements
  2. Standardization of measurements and predicted values is necessary
    • Forced Vital Capacity (FVC) measurements for clinical trials are acceptable if modified ATS (American Thoracic Society) criteria are met (15).
    • Both height and ulna length should be measured when subjects are ambulatory; ulna length when non-ambulatory.
      • Until additional data are available, height should be predicted from ulna length using equations of Gauld et al
      • FVC% predicted should be calculated using predicted equations from the Global Lung Function Initiative
  3. Standardization of respiratory data set
  4. For clinical trials, individual longitudinal data should be tracked individually rather than used in cross-section since pulmonary function will change with disease trajectory. In addition, clinical response to a therapy can be misinterpreted if the stage of decline of the subject’s FVC is not determined and taken into account prior to drug initiation. Alterations in the rate of change of absolute FVC better reflect response to drugs.
  5. Clinical trial endpoints should include skeletal muscle endpoints (e.g., age at loss of ambulation, Brook Upper Extremity Function Scale) and FVC.
  6. Power calculations must be based on rate of change of the primary outcome
  7. Inclusion/Exclusion Criteria may be age and disease-stage based.
  8. Investigators should consider absolute values of lung function measurements rather than solely percent predicted.
  9. Choice of primary outcome should be based on age of subject, effect of drug/mechanism of action.
  10. Duration of clinical (drug) trials should not be less than 52 weeks – and for outcome measures that are primarily pulmonary, not less than 104 weeks

 

Authors:

  • Jonathan Finder, MD (Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA)
  • Oscar Henry Mayer, MD (University of Pennsylvania School of Medicine, Daniel Sheehan, MD (University at Buffalo)
  • Hemant Sawnani, MD (Cincinnati Children’s Hospital Medical Center)
  • R. Ted Abresch, MS (University of California Davis)
  • Joshua Benditt, MD (University of Washington School of Medicine)
  • David J. Birnkrant, MD (MetroHealth Medical Center and Case Western Reserve University)
  • Tina Duong, MPT (Stanford University)
  • Erik Henricson, PhD, MPH (University of California Davis)
  • Kathi Kinnett, MSN, CNP (PPMD)
  • Craig M. McDonald, MD (University of California Davis)
  • Anne M. Connolly, MD (Washington University School of Medicine)

 

Attendees of this workshop:

  • MyMy Buu, MD
  • Cara Carty
  • Avital Cnaan, PhD
  • Linda Cripe, MD
  • Heather Gordish-Dressman, PhD
  • Richard Kravitz, MD
  • Mika Leinonen, MSc
  • Marianne Mann, MD
  • Stefan Matecki, MD, PhD
  • Robert Meyer, MD
  • Richard Shell, MD
  • Lisa Wolfe, MD
  • Brenda Wong, MD

 

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