Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany

Georg Isbary; Thomas R Staab; Volker E Amelung; Charalabos-Markos Dintsios; Christof Iking-Konert; Sonja Mariotti Nesurini; Miriam Walter; Jörg Ruof

doi:10.1016/j.jval.2017.09.010

Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany

Standard

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, Vol. 21, No. 6, 06.2018, p. 698-706.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Isbary, G, Staab, TR, Amelung, VE, Dintsios, C-M, Iking-Konert, C, Nesurini, SM, Walter, M & Ruof, J 2018, 'Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany', VALUE HEALTH, vol. 21, no. 6, pp. 698-706. https://doi.org/10.1016/j.jval.2017.09.010

APA

Isbary, G., Staab, T. R., Amelung, V. E., Dintsios, C-M., Iking-Konert, C., Nesurini, S. M., Walter, M., & Ruof, J. (2018). Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany. VALUE HEALTH, 21(6), 698-706. https://doi.org/10.1016/j.jval.2017.09.010

Vancouver

Isbary G, Staab TR, Amelung VE, Dintsios C-M, Iking-Konert C, Nesurini SM et al. Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany. VALUE HEALTH. 2018 Jun;21(6):698-706. https://doi.org/10.1016/j.jval.2017.09.010

Bibtex

@article{19cb9913c9a94ce487985802c9f5f0cf,

title = "Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany",

abstract = "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.",

keywords = "Antineoplastic Agents, Clinical Trials as Topic, Cost-Benefit Analysis, Cross-Over Studies, Drug Approval, Evidence-Based Medicine, Germany, Humans, Medical Oncology, Neoplasms, Outcome Assessment (Health Care), Research Design, Technology Assessment, Biomedical, Treatment Outcome, Journal Article",

author = "Georg Isbary and Staab, {Thomas R} and Amelung, {Volker E} and Charalabos-Markos Dintsios and Christof Iking-Konert and Nesurini, {Sonja Mariotti} and Miriam Walter and J{\"o}rg Ruof",

year = "2018",

month = jun,

doi = "10.1016/j.jval.2017.09.010",

language = "English",

volume = "21",

pages = "698--706",

journal = "VALUE HEALTH",

issn = "1098-3015",

publisher = "Elsevier Limited",

number = "6",

}

RIS

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

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 -