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


Journal Article

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 underpowered 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 three developmental scenarios. Scenario 1, representing the current status quo, assumed 50% statistical power at phase II and 90% at phase III. Scenario 2 assumed increased power (80%), and Scenario 3, increased stringency of alpha (1%) at phase II. Scenario 2 led, on average, to a 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 II studies are offset by the increase in productivity. We discuss the implications of our results and propose corrective measures.

Full Text

Cited Authors

  • Burt, T; Button, KS; Thom, H; Noveck, RJ; Munafò, MR

Published Date

  • November 2017

Published In

Volume / Issue

  • 10 / 6

Start / End Page

  • 470 - 479

PubMed ID

  • 28675646

Pubmed Central ID

  • 28675646

Electronic International Standard Serial Number (EISSN)

  • 1752-8062

International Standard Serial Number (ISSN)

  • 1752-8054

Digital Object Identifier (DOI)

  • 10.1111/cts.12478


  • eng