title: Clinical Endpoints for Respiratory Syncytial Virus Prophylaxis Trials in Infants and Children in High-income and Middle-income Countries.
abstract: Respiratory syncytial virus (RSV) continues to cause significant clinical and economic burden around the world. Historically, RSV-associated hospitalization was used as a primary endpoint for RSV prophylaxis trials in infants. However, because of the changing epidemiology and healthcare system landscape, this endpoint has become a critical bottleneck on the pathway to licensure for new therapeutics. A panel of 7 RSV experts was convened (Chicago, IL, May 22, 2014) to evaluate the challenges of defining RSV prevention endpoints for clinical trials and to develop endpoints that are clinically meaningful while minimizing subjectivity and bias to achieve sufficient consistency of response for regulatory approval. Particular consideration was given to the ability to collect data systematically and consistently in countries with different healthcare practices and systems, while capturing the greatest proportion of disease impact. The group consensus was that a clinically meaningful primary endpoint could include medically attended RSV illness in settings beyond RSV-associated hospitalizations alone, in particular, a composite reduction in hospitalization, emergency room or urgent care center visits because of an RSV respiratory infection. Relevant secondary endpoints included reductions in RSV lower respiratory tract infection, RSV-related intensive care unit rates, subsequent recurrent wheezing or asthma and direct and indirect costs.
authors.affiliation: From the *Department of Pediatrics, Section of Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado; †Department of Epidemiology and Center for Global Health, Colorado School of Public Health, Aurora, Colorado; ‡Neonatology Service, Hospital Clinic, Institut d'Investigacios Biomediques August Pi Suñer (IDIBAPS), Barcelona, Spain; §Division of Pulmonology Medicine, Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio; ¶Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; ‖Department of Microbiology and Immunology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas; **Division of Infectious Diseases, Nationwide Children's Hospital, Ohio State University, Columbus, Ohio; and ††Division of Pediatric Infectious Diseases, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors.forename: Eric A F
authors.initials: EA
authors.lastname: Simões
authors.forename: Xavier
authors.initials: X
authors.lastname: Carbonell-Estrany
authors.forename: Theresa
authors.initials: T
authors.lastname: Guilbert
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Mansbach
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Piedra
authors.forename: Octavio
authors.initials: O
authors.lastname: Ramilo
authors.forename: Robert
authors.initials: R
authors.lastname: Welliver
mesh_terms: D000553:Ambulatory Care / Q000706:statistics & numerical data; D019072:Antibiotic Prophylaxis / Q000706:statistics & numerical data*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D002675:Child, Preschool; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007223:Infant; D012135:Respiratory Sounds; D018357:Respiratory Syncytial Virus Infections / Q000191:economics / Q000453:epidemiology* / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents