Converging or Crossing Curves: Untie the Gordian Knot or Cut it? Appropriate Statistics for Non-Proportional Hazards in Decitabine DACO-016 Study (AML)

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dc.identifier.uri http://dx.doi.org/10.15488/858
dc.identifier.uri http://www.repo.uni-hannover.de/handle/123456789/882
dc.contributor.author Tomeczkowski, Jörg
dc.contributor.author Lange, Ansgar
dc.contributor.author Güntert, Andreas
dc.contributor.author Thilakarathne, Pushpike
dc.contributor.author Diels, Joris
dc.contributor.author Xiu, Liang
dc.contributor.author De Porre, Peter
dc.contributor.author Tapprich, Christoph
dc.date.accessioned 2016-12-16T09:39:05Z
dc.date.available 2016-12-16T09:39:05Z
dc.date.issued 2015
dc.identifier.citation Tomeczkowski, J.; Lange, A.; Güntert, A.; Thilakarathne, P.; Diels, J. et al.: Converging or Crossing Curves: Untie the Gordian Knot or Cut it? Appropriate Statistics for Non-Proportional Hazards in Decitabine DACO-016 Study (AML). In: Advances in Therapy 32 (2015), Nr. 9, S. 854-862. DOI: https://doi.org/10.1007/s12325-015-0238-9
dc.description.abstract Introduction: Among patients with acute myeloid leukemia (AML), the DACO-016 randomized study showed reduction in mortality for decitabine [Dacogen® (DAC), Eisai Inc., Woodcliff Lake, NJ, USA] compared with treatment choice (TC): at primary analysis the hazard ratio (HR) was 0.85 (95% confidence interval 0.69-1.04; stratified log-rank P=0.108). With two interim analyses, two-sided alpha was adjusted to 0.0462. With 1-year additional follow-up the HR reached 0.82 (nominal P=0.0373). These data resulted in approval of DAC in the European Union, though not in the United States. Though pre-specified, the log-rank test could be considered not optimal to assess the observed survival difference because of the non-proportional hazard nature of the survival curves. Methods: We applied the Wilcoxon test as a sensitivity analysis. Patients were randomized to DAC (N=242) or TC (N=243). One-hundred and eight (44.4%) patients in the TC arm and 91 (37.6%) patients in the DAC arm selectively crossed over to subsequent disease modifying therapies at progression, which might impact the survival beyond the median with resultant converging curves (and disproportional hazards). Results: The stratified Wilcoxon test showed a significant improvement in median (CI 95%) overall survival with DAC [7.7 (6.2; 9.2) months] versus TC [5.0 (4.3; 6.3) months; P=0.0458]. Conclusion: Wilcoxon test indicated significant increase in survival for DAC versus TC compared to log-rank test. Funding: Janssen-Cilag GmbH. eng
dc.language.iso eng
dc.publisher New York : Springer Healthcare
dc.relation.ispartofseries Advances in Therapy 32 (2015), Nr. 9
dc.rights CC BY-NC-ND 4.0
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject Acute myeloid leukemia eng
dc.subject Dacogen® eng
dc.subject Decitabine eng
dc.subject Log-rank test eng
dc.subject Non-proportional hazards eng
dc.subject Oncology eng
dc.subject Wilcoxon test eng
dc.subject decitabine eng
dc.subject acute myeloblastic leukemia eng
dc.subject adult eng
dc.subject cancer chemotherapy eng
dc.subject cancer patient eng
dc.subject cancer regression eng
dc.subject cancer statistics eng
dc.subject cancer survival eng
dc.subject comparative study eng
dc.subject controlled study eng
dc.subject follow up eng
dc.subject human eng
dc.subject major clinical study eng
dc.subject nonproportional hazard eng
dc.subject overall survival eng
dc.subject randomized controlled trial eng
dc.subject rank sum test eng
dc.subject sensitivity analysis eng
dc.subject statistical concepts eng
dc.subject survival rate eng
dc.subject.ddc 610 | Medizin, Gesundheit ger
dc.title Converging or Crossing Curves: Untie the Gordian Knot or Cut it? Appropriate Statistics for Non-Proportional Hazards in Decitabine DACO-016 Study (AML)
dc.type article
dc.type Text
dc.relation.issn 0741238X
dc.relation.doi https://doi.org/10.1007/s12325-015-0238-9
dc.bibliographicCitation.issue 9
dc.bibliographicCitation.volume 32
dc.bibliographicCitation.firstPage 854
dc.bibliographicCitation.lastPage 862
dc.description.version publishedVersion
tib.accessRights frei zug�nglich


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