The Burden of the 'False‐Negatives' in Clinical Development: Analyses of Current and Alternative Scenarios and Corrective Measures

Autor: Tal Burt, Howard Thom, Katherine S. Button, Marcus R. Munafò, Robert J. Noveck
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Offset (computer science)
statistical errors
Computer science
clinical development
Treatment outcome
Brain and Behaviour
Type-II error
early-phase clinical development
General Biochemistry
Genetics and Molecular Biology
Statistical power
Profit (economics)
Article
Phase-3
03 medical and health sciences
proof-of-concept
Statistics
late-phase clinical development
Humans
Computer Simulation
General Pharmacology
Toxicology and Pharmaceutics
False Negative Reactions
Phase-2
economic modelling
Economic productivity
statistical power
Probability
Clinical Trials as Topic
General Neuroscience
Research
Tobacco and Alcohol
economic productivity
General Medicine
Limiting
Articles
drug development
030104 developmental biology
Treatment Outcome
Type-I error
Costs and Cost Analysis
simulations
Type I and type II errors
Zdroj: Clinical and Translational Science
Burt, T, Button, K, Thom, H, Noveck, R & Munafo, M 2017, ' The Burden of the “False-Negatives” in Clinical Development : Analyses of Current and Alternative Scenarios and Corrective Measures ', Clinical and Translational Science . https://doi.org/10.1111/cts.12478
ISSN: 1752-8062
1752-8054
DOI: 10.1111/cts.12478
Popis: 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.
Databáze: OpenAIRE
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