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Special Communication
December 13, 2018

Development of a Retinopathy of Prematurity Activity Scale and Clinical Outcome Measures for Use in Clinical Trials

Author Affiliations
  • 1Department of Ophthalmology, Harvard Medical School, Boston Children’s Hospital, Boston, Massachusetts
  • 2Department of Clinical Neuroscience at Institute of Neuroscience and Physiology, University of Göteborg, Göteborg, Sweden
  • 3Department of Ophthalmology, University of Freiburg, Freiburg, Germany
  • 4Department of Optometry & Visual Science, City University of London, London, United Kingdom
  • 5Division of Transplant and Ophthalmology Products, US Food and Drug Administration, Bethesda, Maryland
  • 6Human Medicines Research and Development Support Division, European Medicines Agency, London, United Kingdom
  • 7Department of Ophthalmology, Duke University, Durham, North Carolina
  • 8Department of Ophthalmology, Indiana University, Indianapolis
  • 9Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand
  • 10Department of Ophthalmology, State University of New York Downstate Medical Center, Brooklyn
  • 11Division of Paediatrics, Karolinska University Hospital, Stockholm, Sweden
  • 12The Floating Hospital for Children, Tufts Medical Center, Boston, Massachusetts
  • 13Department of Pediatrics, Tufts University School of Medicine, Boston, Massachusetts
JAMA Ophthalmol. 2019;137(3):305-311. doi:10.1001/jamaophthalmol.2018.5984

Importance  To facilitate drug and device development for neonates, the International Neonatal Consortium brings together key stakeholders, including pharmaceutical companies, practitioners, regulators, funding agencies, scientists, and families, to address the need for objective, standardized clinical trial outcome measurements to fulfill regulatory requirements. Retinopathy of prematurity (ROP) is a disease that affects preterm neonates. The current International Classification of Retinopathy of Prematurity does not take into account all of the characteristics of ROP and does not adequately discriminate small changes in disease after treatment. These factors are critical for evaluating outcomes in clinical trials.

Observations  There is need for an updated ROP acute disease activity and structure scale as well as end-stage structure and ophthalmologic outcome measures designed for use at different ages. The scale and measures, based on current diagnostic methods and treatments, could be used as a guideline for clinical intervention trials. The scale is intended to be validated against retrospective data and revised for use in future trials. An iterative revision process can be accomplished if new measures are added to clinical trials and evaluated at the end of each trial for prognostic value. The new measures would then be incorporated into a new version of the activity scale and the outcome measures revised.

Conclusions and Relevance  An ROP activity scale and outcome measures to obtain the most robust and discriminatory data for clinical trials are needed. The scales should be dynamic and modified as knowledge and imaging modalities improve and then validated using data from well-documented clinical trials. This approach is relevant to improving clinical trial data quality.