title: The use of surrogate endpoints in regulating medicines for cardio-renal disease: opinions of stakeholders.
abstract: OBJECTIVE
  There is discussion whether medicines can be authorized on the market based on evidence from surrogate endpoints. We assessed opinions of different stakeholders on this topic.
  
  
  METHODS
  We conducted an online questionnaire that targeted various stakeholder groups (regulatory agencies, pharmaceutical industry, academia, relevant public sector organisations) and medical specialties (cardiology or nephrology vs. other). Participants were enrolled through purposeful sampling. We inquired for conditions under which surrogate endpoints can be used, the validity of various cardio-renal biomarkers and new approaches for biomarker use.
  
  
  RESULTS
  Participants agreed that surrogate endpoints can be used when the surrogate is scientifically valid (5-point Likert response format, mean score: 4.3, SD: 0.9) or when there is an unmet clinical need (mean score: 3.8, SD: 1.2). Industry participants agreed to a greater extent than regulators and academics. However, out of four proposed surrogates (blood pressure (BP), HbA1c, albuminuria, CRP) for cardiovascular outcomes or end-stage renal disease, only use of BP for cardiovascular outcomes was deemed moderately accurate (mean: 3.6, SD: 1.1). Specialists in cardiology or nephrology tended to be more positive about the use of surrogate endpoints.
  
  
  CONCLUSIONS
  Stakeholders in drug development do not oppose to the use of surrogate endpoints in drug marketing authorization, but most surrogates are not considered valid. To solve this impasse, increased efforts are required to validate surrogate endpoints and to explore alternative ways to use them.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Bauke
authors.initials: B
authors.lastname: Schievink
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Hiddo
authors.initials: H
authors.lastname: Lambers Heerspink
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands; Medicines Evaluation Board, Utrecht, The Netherlands.
authors.forename: Hubert
authors.initials: H
authors.lastname: Leufkens
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: De Zeeuw
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Jarno
authors.initials: J
authors.lastname: Hoekman
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000175:diagnosis; D015415:Biomarkers / Q000032:analysis; D035843:Biomedical Research / Q000331:legislation & jurisprudence; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D017277:Drug Approval / Q000331:legislation & jurisprudence / Q000379:methods*; D004345:Drug Industry / Q000331:legislation & jurisprudence; D015507:Drugs, Investigational / Q000627:therapeutic use*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006307:Health Systems Agencies / Q000331:legislation & jurisprudence; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D017410:Practice Guidelines as Topic; D017150:Public Sector / Q000331:legislation & jurisprudence; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D015507:Drugs, Investigational; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human