SpringerLink
Log in

Exact Inference for Adaptive Group Sequential Designs

  • Conference paper
  • First Online:
Pharmaceutical Statistics (MBSW 2016)

Part of the book series: Springer Proceedings in Mathematics & Statistics ((PROMS,volume 218))

Included in the following conference series:

Abstract

In this paper we present a method for estimating the treatment effect in a two-arm adaptive group sequential clinical trial that permits sample size re-estimation, alterations to the number and spacing of the interim looks, and changes to the error spending function based on an unblinded look at the accruing data. The method produces a median unbiased point estimate and a confidence interval having exact coverage of the parameter of interest. The procedure is based on map** the final test statistic obtained in the modified trial into a corresponding backward image in the original trial. Methods that were developed for classical (non-adaptive) group sequential inference can then be applied to the backward image.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Brannath, W., Mehta, C., Posch, M.: Exact confidence intervals following adaptive sequential tests. Biometrics 64, 1–22 (2009)

    MATH  Google Scholar 

  2. Cui, L., Hung, M.J., Wang, S.-J.: Modification of sample size in group sequential clinical trial. Biometrics 55, 853–857 (1999)

    Article  Google Scholar 

  3. Gao, P., Liu, L., Mehta, C.R.: Exact inference for adaptive group sequential designs. Stat. Med. 32, 3991–4005 (2013)

    Article  MathSciNet  Google Scholar 

  4. Jennison, C., Turnbull, B.W.: Interim analyses: the repeated confidence interval approach (with discussion). J. R. Stat. Soc. B 51(3), 305–61 (1989)

    MATH  Google Scholar 

  5. Lan, K.K.G., DeMets, D.L.: Discrete sequential boundaries for clinical trials. Biometrika 70, 659–663 (1983)

    Article  MathSciNet  Google Scholar 

  6. Lehmacher, W., Wassmer, G.: Adaptive sample size calculations in group sequential trials. Biometrics 55, 1286–1290 (1999)

    Article  Google Scholar 

  7. Mehta, C.R., Pocock, S.J.: Adaptive increase in sample size when interim results are promising: a practical guide with examples. Stat. Med. 30(28), 3267–3284 (2011)

    Article  MathSciNet  Google Scholar 

  8. Mehta, C.R.: Sample size re-estimation for confirmatory clinical trials. In: Harrington, D. (ed.) Designs for Clinical Trials: Perspectives on Current Issues, Chapter 4. Springer, New York (2012)

    Google Scholar 

  9. Mehta, C.R., Bauer, P., Posch, M., Brannath, W.: Repeated confidence intervals for adaptive group sequential trials. Stat. Med. 26(30), 5422–5433 (2007)

    Article  MathSciNet  Google Scholar 

  10. Müller, H.H., Schäfer, H.: Adaptive group sequential designs for clinical trials: combining the advantage of adaptive and of classical group sequential approaches. Biometrics 57, 886–891 (2001)

    Article  MathSciNet  Google Scholar 

  11. Tsiatis, A.A., Rosner, G.L., Mehta, C.: Exact confidence intervals following a group sequential test. Biometrics 40, 797–803 (1984)

    Article  MathSciNet  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cytel Corporation, Cambridge, MA, USA

    Cyrus Mehta, Lingyun Liu & Pranab Ghosh

  2. Harvard School of Public Health, Boston, MA, USA

    Cyrus Mehta

  3. Brightech-International, 285 Davidson Ave, Somerset, NJ, 08873, USA

    ** Gao

Authors
  1. Cyrus Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lingyun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pranab Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. ** Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cyrus Mehta .

Editor information

Editors and Affiliations

  1. Statistical Innovation and Consultation group, Takeda Pharmaceuticals, Cambridge, MA, USA

    Ray Liu

  2. Division of Biometrics VI, CDER, U.S. Food and Drug Administration , Silver Spring, MD, USA

    Yi Tsong

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Mehta, C., Liu, L., Ghosh, P., Gao, P. (2019). Exact Inference for Adaptive Group Sequential Designs. In: Liu, R., Tsong, Y. (eds) Pharmaceutical Statistics. MBSW 2016. Springer Proceedings in Mathematics & Statistics, vol 218. Springer, Cham. https://doi.org/10.1007/978-3-319-67386-8_10

Download citation

Publish with us

Policies and ethics

Search

Navigation