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Related Experiment Videos

On changing a long-term clinical trial midstream.

Janet Wittes1

  • 1Statistics Collaborative Inc., 1710 Rhode Island Avenue, NW, Suite 200, Washington DC 20036, USA. janet@statcollab.com

Statistics in Medicine
|September 27, 2002
PubMed
Summary
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Modifying clinical trial designs, especially sample size, is crucial when new data or medical changes arise. This paper advocates for flexible trial designs to maintain integrity while adapting to evolving research landscapes.

Area of Science:

  • Clinical trial methodology
  • Biostatistics
  • Medical research integrity

Background:

  • Clinical trialists often avoid altering ongoing study protocols due to concerns about compromising study integrity.
  • Changes in the medical environment or accumulating trial data can challenge original study design assumptions.

Purpose of the Study:

  • To encourage the consideration of protocol and design modifications in long-term clinical trials.
  • To advocate for methods that allow for study adaptation without undermining trial integrity.
  • To discuss the role of sample size recalculation in maintaining study power and validity.

Main Methods:

  • Review of mature methodologies for sample size recalculation for various endpoint types (continuous, discrete, time-to-failure, longitudinal analysis).

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  • Discussion of variance estimation, testing approaches, and timing of recalculations.
  • Analysis of the responsibilities of sponsors, Data Safety Monitoring Boards (DSMBs), and Executive Committees in sample size adjustments.

    • Main Results:

    • Methodologies for sample size recalculation have advanced, offering robust techniques for diverse data types.
    • The choice of variance estimation and the timing of recalculation are critical for maintaining study integrity.
    • The responsibility for recommending sample size increases often falls to a sponsor, DSMB, or Executive Committee.

    Conclusions:

    • Adapting clinical trial designs, including sample size, is feasible and necessary under specific circumstances.
    • Careful implementation of modifications is essential to preserve the integrity and validity of trial results.
    • Data Safety Monitoring Boards may not be the ideal body for recommending sample size increases due to potential conflicts of interest related to treatment effect knowledge.