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Statistical Design and Evaluation of Biomarker Studies

  • Kevin K. Dobbin
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1102)

Abstract

We review biostatistical aspects of biomarker studies, including design and analysis issues, covering the range of settings required for translational research—from early exploratory studies through clinical trials.

Key words

Translational research Experimental design Sample size Power 

Notes

Acknowledgment

This work was supported by the Distinguished Cancer Scholars grant program of the Georgia Research Alliance.

References

  1. 1.
    Rothberg BEG, Bracken MB, Rimm DL (2009) Tissue biomarkers for prognosis in cutaneous melanoma: a systematic review and meta-analysis. J Natl Cancer Inst 101:452–474CrossRefGoogle Scholar
  2. 2.
    Simon R (2010) Clinical trial designs evaluating the medical utility of prognostic and predictive biomarkers in oncology. Per Med 7:33–47PubMedCrossRefGoogle Scholar
  3. 3.
    McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2005) Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst 97:1180–1184PubMedCrossRefGoogle Scholar
  4. 4.
    Prentice RL (1989) Surrogate endpoints in clinical trials: discussion, definition and operational criteria. Stat Med 8(4):431–440PubMedCrossRefGoogle Scholar
  5. 5.
    Friedman LM, Furberg CD, DeMets DL (2010) Fundamentals of clinical trials, 4th edn. Springer, New YorkCrossRefGoogle Scholar
  6. 6.
    Cook TD, DeMets DL (2008) Introduction to statistical methods for clinical trials. Chapman and Hall, New YorkGoogle Scholar
  7. 7.
    Fleming TR, DeMets DL (1996) Surrogate end points in clinical trials: are we being misled? Fleming TR and DeMets DL. Ann Intern Med 125(7):605–613PubMedCrossRefGoogle Scholar
  8. 8.
    Buyse M, Sargent DJ, Grothey A, Matheson A, de Gramont A (2010) Biomarkers and surrogate end points: the challenge of statistical validation. Nat Rev Clin Oncol 7:309–317PubMedCrossRefGoogle Scholar
  9. 9.
    Dobbin KK, Beer DG, Meyerson M, Yeatman TJ, Gerald WL, Jacobson JW, Conley B, Buetow KH, Heiskanen M, Simon RM, Minna JD, Girard L, Misek DE, Taylor JMG, Hanash S, Naoki K, Hayes DN, Ladd-Acosta C, Enkemann SA, Viale A, Giordano TJ (2005) Interlaboratory comparability study of cancer gene expression analysis using oligonucleotide microarrays. Clin Cancer Res 11:565–572PubMedGoogle Scholar
  10. 10.
    Shoukri MM (2004) Measures of interobserver agreement. Chapman and Hall, Boca RatonGoogle Scholar
  11. 11.
    Simon RM, Paik S, Hayes DF (2009) Use of archived specimens to evaluate prognostic and predictive biomarkers. J Natl Cancer Inst USA 101(21):1446–1452CrossRefGoogle Scholar
  12. 12.
    Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26:1626–1634PubMedCrossRefGoogle Scholar
  13. 13.
    Karapetis CD, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR (2008) K-RAS mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359:1757–1765PubMedCrossRefGoogle Scholar
  14. 14.
    Dancey JE, Dobbin KK, Groshen S, Jessup JM, Hruszkewicz AH, Koehler M, Parchment R, Ratain MJ, Shankar LK, Stadler WM, True LD, Gravell A, Grever MR, Biomarkers Task Force of the NCI Investigational Drug Steering Committee (2010) Guidelines for the development and incorporation of biomarker studies in early clinical trials of novel agents. Clin Cancer Res 16(6):1745–1755PubMedCrossRefGoogle Scholar
  15. 15.
    McShane LM, Hunsberger S, Adjei AA (2009) Effective incorporation of biomarkers in phase II trials. Clin Cancer Res 15(6):1898–1905PubMedCrossRefGoogle Scholar
  16. 16.
    Freidlin B, McShane LM, Korn EL (2009) Randomized clinical trials with biomarkers: design issues. J Natl Cancer Inst 102:152–160CrossRefGoogle Scholar
  17. 17.
    Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ, Press M (2002) Efficacy and safety of trastuzumumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20(3):716–726CrossRefGoogle Scholar
  18. 18.
    Sparano JA (2006) TAILORx: trial assigning individualized options for treatment (Rx). Clin Breast Cancer 7(4):347–350PubMedCrossRefGoogle Scholar
  19. 19.
    Cardoso F, Van’t Veer L, Rutgers E, Loi S, Mook S, Piccart-Gebhart MJ (2008) Clinical application of the 70-gene profile: the MINDACT trial. J Clin Oncol 26(5):729–735PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, New York 2014

Authors and Affiliations

  • Kevin K. Dobbin
    • 1
  1. 1.Department of Epidemiology and BiostatisticsCollege of Public Health, University of GeorgiaAthensUSA

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