Advertisement

Trial Design: Overview of Study Designs

  • Puneet Singh
  • Yu Shen
  • Kelly K. HuntEmail author
Chapter
  • 46 Downloads
Part of the Success in Academic Surgery book series (SIAS)

Abstract

Clinical trials are fundamentally the investigation of human subjects under experimental conditions. For these trials to be successful, they must be well planned in the design phase to evaluate the prespecified outcomes. Thus, it is imperative for the investigators to understand clinical trial design which follows a typical progression from preclinical studies in animals to phase I–IV trials as described in this chapter (Fig. 4.1).

References

  1. 1.
    Umscheid CA, Margolis DJ, Grossman CE. Key concepts of clinical trials: a narrative review. Postgrad Med. 2011;123(5):194–204.CrossRefGoogle Scholar
  2. 2.
    Le Tourneau C, Lee JJ, Siu LL. Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009;101(10):708–20.CrossRefGoogle Scholar
  3. 3.
    Bekele BN, Shen YA. Bayesian approach to jointly modeling toxicity and biomarker expression in a phase I/II dose-finding trial. Biometrics. 2005;61(2):343–54.CrossRefGoogle Scholar
  4. 4.
    Wong KM, Capasso A, Eckhardt SG. The changing landscape of phase I trials in oncology. Nat Rev Clin Oncol. 2016;13(2):106–17.CrossRefGoogle Scholar
  5. 5.
    Ananthakrishnan R, Menon S. Design of oncology clinical trials: a review. Crit Rev Oncol Hematol. 2013;88(1):144–53.CrossRefGoogle Scholar
  6. 6.
    Yuan Y, Hess KR, Hilsenbeck SG, Gilbert MR. Bayesian optimal interval design: a simple and well-performing design for phase I oncology trials. Clin Cancer Res. 2016;22(17):4291–301.CrossRefGoogle Scholar
  7. 7.
    Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361(2):123–34.CrossRefGoogle Scholar
  8. 8.
    Tutt A, Robson M, Garber JE, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010;376(9737):235–44.CrossRefGoogle Scholar
  9. 9.
    Audeh MW, Carmichael J, Penson RT, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010;376(9737):245–51.CrossRefGoogle Scholar
  10. 10.
    Brown SR, Gregory WM, Twelves CJ, et al. Designing phase II trials in cancer: a systematic review and guidance. Br J Cancer. 2011;105(2):194–9.CrossRefGoogle Scholar
  11. 11.
    El-Maraghi RH, Eisenhauer EA. Review of phase II trial designs used in studies of molecular targeted agents: outcomes and predictors of success in phase III. J Clin Oncol. 2008;26(8):1346–54.CrossRefGoogle Scholar
  12. 12.
    Buzdar AU, Ibrahim NK, Francis D, et al. Significantly higher pathologic complete remission rate after Neoadjuvant therapy with Trastuzumab, paclitaxel, and Epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2–positive operable breast Cancer. J Clin Oncol. 2005;23(16):3676–85.CrossRefGoogle Scholar
  13. 13.
    Buzdar AU, Suman VJ, Meric-Bernstam F, et al. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. Lancet Oncol. 2013;14(13):1317–25.CrossRefGoogle Scholar
  14. 14.
    Buzdar AU, Suman VJ, Meric-Bernstam F, et al. Disease-free and overall survival among patients with operable HER2-positive breast cancer treated with sequential vs concurrent chemotherapy: the ACOSOG Z1041 (Alliance) randomized clinical trial. JAMA Oncol. 2019;5(1):45–50.CrossRefGoogle Scholar
  15. 15.
    Jaki T, Vasileiou D. Factorial versus multi-arm multi-stage designs for clinical trials with multiple treatments. Stat Med. 2017;36(4):563–80.CrossRefGoogle Scholar
  16. 16.
    Inoue LY, Thall PF, Berry DA. Seamlessly expanding a randomized phase II trial to phase III. Biometrics. 2002;58(4):823–31.CrossRefGoogle Scholar
  17. 17.
    Fisher B, Montague E, Redmond C, et al. Comparison of radical mastectomy with alternative treatments for primary breast cancer. A first report of results from a prospective randomized clinical trial. Cancer. 1977;39(6 Suppl):2827–39.CrossRefGoogle Scholar
  18. 18.
    Wickerham DL, Costantino JP, Mamounas EP, Julian TB. The landmark surgical trials of the National Surgical Adjuvant Breast and Bowel Project. World J Surg. 2006;30(7):1138–46.CrossRefGoogle Scholar
  19. 19.
    Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305(6):569–75.CrossRefGoogle Scholar
  20. 20.
    Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons oncology group Z0011 randomized trial. Ann Surg. 2010;252(3):426–32.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Neugebauer EAM, Rath A, Antoine SL, et al. Specific barriers to the conduct of randomised clinical trials on medical devices. Trials. 2017;18(1):427.CrossRefGoogle Scholar
  22. 22.
    Mouw TJ, Hong SW, Sarwar S, et al. Discontinuation of surgical versus nonsurgical clinical trials: an analysis of 88,498 trials. J Surg Res. 2018;227:151–7.CrossRefGoogle Scholar
  23. 23.
    Zhang X, Zhang Y, Ye X, Guo X, Zhang T, He J. Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry. BMJ Open. 2016;6(11):e010643.CrossRefGoogle Scholar
  24. 24.
    Singh P, Scoggins M, Sahin AA, et al. Effectiveness and safety of Magseed-localization for excision of breast lesions: a prospective trial. Poster presented at: SSO 2019 annual cancer symposium, March 29, 2019; San Diego, CA.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Division of Surgery, Department of Breast Surgical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of BiostatisticsThe University of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations