Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany
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Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany. / Isbary, Georg; Staab, Thomas R; Amelung, Volker E; Dintsios, Charalabos-Markos; Iking-Konert, Christof; Nesurini, Sonja Mariotti; Walter, Miriam; Ruof, Jörg.
in: VALUE HEALTH, Jahrgang 21, Nr. 6, 06.2018, S. 698-706.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany
AU - Isbary, Georg
AU - Staab, Thomas R
AU - Amelung, Volker E
AU - Dintsios, Charalabos-Markos
AU - Iking-Konert, Christof
AU - Nesurini, Sonja Mariotti
AU - Walter, Miriam
AU - Ruof, Jörg
N1 - Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
PY - 2018/6
Y1 - 2018/6
N2 - BACKGROUND: In oncology clinical trials, crossover is used frequently but may lead to uncertainties regarding treatment effects.OBJECTIVE: To investigate the handling of evidence from crossover trials by the European Medicines Agency (EMA) and the German Federal Joint Committee (G-BA).METHODS: For oncology medicines with early benefit assessments before January 2015, presence of crossover, clinical data, EMA requests for additional data, and G-BA benefit ratings/evidence levels were analyzed from manufacturers' dossiers, G-BA appraisals, European Public Assessment Reports, and original publications.RESULTS: Eleven of 21 benefit assessments included crossover trials. Significant intergroup differences (P < 0.05) in overall survival (OS) were noted in 7 of 11 trials with and 7 of 10 without crossover. For 6 of 11 medicines with crossover, these were demonstrated before crossover. Treatment effects generally worsened with increasing proportions of crossover. The EMA requested additional data more frequently if crossover was performed, particularly if no OS data were available before crossover. The G-BA granted a considerable benefit to 73% of medicines with crossover and 40% of those without. Evidence levels were intermediate for 50% and 75%, respectively. None of the medicines received the highest evidence level.CONCLUSIONS: In G-BA appraisals, oncology medicines with crossover received better additional benefit ratings, but were assigned lower evidence levels, than those without. The five medicines with crossover after progression were assigned lower evidence levels than the six medicines with crossover after demonstration of superior OS, indicating that the way in which crossover is implemented may be one factor influencing the assignment of evidence levels by the G-BA.
AB - BACKGROUND: In oncology clinical trials, crossover is used frequently but may lead to uncertainties regarding treatment effects.OBJECTIVE: To investigate the handling of evidence from crossover trials by the European Medicines Agency (EMA) and the German Federal Joint Committee (G-BA).METHODS: For oncology medicines with early benefit assessments before January 2015, presence of crossover, clinical data, EMA requests for additional data, and G-BA benefit ratings/evidence levels were analyzed from manufacturers' dossiers, G-BA appraisals, European Public Assessment Reports, and original publications.RESULTS: Eleven of 21 benefit assessments included crossover trials. Significant intergroup differences (P < 0.05) in overall survival (OS) were noted in 7 of 11 trials with and 7 of 10 without crossover. For 6 of 11 medicines with crossover, these were demonstrated before crossover. Treatment effects generally worsened with increasing proportions of crossover. The EMA requested additional data more frequently if crossover was performed, particularly if no OS data were available before crossover. The G-BA granted a considerable benefit to 73% of medicines with crossover and 40% of those without. Evidence levels were intermediate for 50% and 75%, respectively. None of the medicines received the highest evidence level.CONCLUSIONS: In G-BA appraisals, oncology medicines with crossover received better additional benefit ratings, but were assigned lower evidence levels, than those without. The five medicines with crossover after progression were assigned lower evidence levels than the six medicines with crossover after demonstration of superior OS, indicating that the way in which crossover is implemented may be one factor influencing the assignment of evidence levels by the G-BA.
KW - Antineoplastic Agents
KW - Clinical Trials as Topic
KW - Cost-Benefit Analysis
KW - Cross-Over Studies
KW - Drug Approval
KW - Evidence-Based Medicine
KW - Germany
KW - Humans
KW - Medical Oncology
KW - Neoplasms
KW - Outcome Assessment (Health Care)
KW - Research Design
KW - Technology Assessment, Biomedical
KW - Treatment Outcome
KW - Journal Article
U2 - 10.1016/j.jval.2017.09.010
DO - 10.1016/j.jval.2017.09.010
M3 - SCORING: Journal article
C2 - 29909875
VL - 21
SP - 698
EP - 706
JO - VALUE HEALTH
JF - VALUE HEALTH
SN - 1098-3015
IS - 6
ER -