Validation of novel imaging methodologies for use as cancer clinical trial end-points

D. J. Sargent, L. Rubinstein, L. Schwartz, J. E. Dancey, C. Gatsonis, L. E. Dodd, L. K. Shankar

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

The success or failure of a clinical trial, of any phase, depends critically on the choice of an appropriate primary end-point. In the setting of phases II and III cancer clinical trials, imaging end-points have historically, and continue presently to play a major role in determining therapeutic efficacy. The primary goal of this paper is to discuss the validation of imaging-based markers as end-points for phase II clinical trials of cancer therapy. Specifically, we outline the issues that must be considered, and the criteria that would need to be satisfied, for an imaging end-point to supplement or potentially replace RECIST- defined tumour status as a phase II clinical trial end-point. The key criteria proposed to judge the utility of a new end-point primarily relate to its ability to accurately and reproducibly predict the eventual phase III end-point for treatment effect, which is usually assessed by a difference between two arms on progression free or overall survival, both at the patient and more importantly at the trial level. As will be demonstrated, the level of evidence required to formally and fully validate a new imaging marker as an appropriate end-point for phase II trials is substantial. In many cases, this level of evidence will only become available by conducting a series of coordinated prospectively designed multicentre clinical trials culminating in a formal meta-analysis. We also include a discussion of situations where flexibility may be required, relative to the ideal rigorous evaluation, to accommodate inevitable real-world feasibility constraints.

Original languageEnglish (US)
Pages (from-to)290-299
Number of pages10
JournalEuropean Journal of Cancer
Volume45
Issue number2
DOIs
StatePublished - Jan 2009

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Phase II Clinical Trials
Clinical Trials
Neoplasms
Multicenter Studies
Meta-Analysis
Therapeutics
Survival
Response Evaluation Criteria in Solid Tumors

Keywords

  • Imaging endpoint
  • Meta-analysis
  • Phase II clinical trial
  • RECIST
  • Surrogate endpoint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sargent, D. J., Rubinstein, L., Schwartz, L., Dancey, J. E., Gatsonis, C., Dodd, L. E., & Shankar, L. K. (2009). Validation of novel imaging methodologies for use as cancer clinical trial end-points. European Journal of Cancer, 45(2), 290-299. https://doi.org/10.1016/j.ejca.2008.10.030

Validation of novel imaging methodologies for use as cancer clinical trial end-points. / Sargent, D. J.; Rubinstein, L.; Schwartz, L.; Dancey, J. E.; Gatsonis, C.; Dodd, L. E.; Shankar, L. K.

In: European Journal of Cancer, Vol. 45, No. 2, 01.2009, p. 290-299.

Research output: Contribution to journalArticle

Sargent, DJ, Rubinstein, L, Schwartz, L, Dancey, JE, Gatsonis, C, Dodd, LE & Shankar, LK 2009, 'Validation of novel imaging methodologies for use as cancer clinical trial end-points', European Journal of Cancer, vol. 45, no. 2, pp. 290-299. https://doi.org/10.1016/j.ejca.2008.10.030
Sargent DJ, Rubinstein L, Schwartz L, Dancey JE, Gatsonis C, Dodd LE et al. Validation of novel imaging methodologies for use as cancer clinical trial end-points. European Journal of Cancer. 2009 Jan;45(2):290-299. https://doi.org/10.1016/j.ejca.2008.10.030
Sargent, D. J. ; Rubinstein, L. ; Schwartz, L. ; Dancey, J. E. ; Gatsonis, C. ; Dodd, L. E. ; Shankar, L. K. / Validation of novel imaging methodologies for use as cancer clinical trial end-points. In: European Journal of Cancer. 2009 ; Vol. 45, No. 2. pp. 290-299.
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