The Burden of the “False-Negatives” in Clinical Development: Analyses of Current and Alternative Scenarios and Corrective Measures

Tal Burt, Katherine Button, Howard Thom, Robert Noveck, Marcus Munafo

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)
449 Downloads (Pure)

Abstract

The ‘false-negatives’ of clinical development are the effective treatments wrongly determined ineffective. Statistical errors leading to ‘false-negatives’ are larger than those leading to ‘false-positives’ especially in typically under-powered early-phase trials. In addition, ‘false-negatives’ are usually eliminated from further testing, thereby limiting the information available on them. We simulated the impact of early-phase power on economic productivity in 3 developmental scenarios. Scenario 1, representing the current status-quo, assumed 50% statistical power at Phase-2 and 90% at Phase-3. Scenario 2 assumed increased power (80%), and Scenario 3, increased stringency of alpha (1%) at Phase-2. Scenario 2 led, on average, to 60.4% increase in productivity and 52.4% increase in profit. Scenario 3 had no meaningful advantages. Our results suggest that additional costs incurred by increasing the power of Phase-2 studies are offset by the increase in productivity. We discuss the implications of our results and propose corrective measures.
Original languageEnglish
Number of pages10
JournalClinical and Translational Science
Early online date4 Jul 2017
DOIs
Publication statusE-pub ahead of print - 4 Jul 2017

Structured keywords

  • Brain and Behaviour
  • Tobacco and Alcohol

Keywords

  • clinical development
  • drug development
  • statistical power
  • statistical errors
  • Type-I error
  • Type-II error
  • Phase-2
  • Phase-3
  • early-phase clinical development
  • late-phase clinical development
  • proof-of-concept
  • economic productivity
  • economic modelling
  • simulations

Fingerprint Dive into the research topics of 'The Burden of the “False-Negatives” in Clinical Development: Analyses of Current and Alternative Scenarios and Corrective Measures'. Together they form a unique fingerprint.

Cite this