Journal Article

DZNE-2020-00359

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Enrichment designs using placebo nonresponders.

Benda, N. (Corresponding author) ; Hänisch, B. (Last author)DZNE*

2020
Wiley New York, NY

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Please use a persistent id in citations: doi:10.1002/pst.1992

Abstract: Enrichment designs that select placebo nonresponders have gained much attention during the last years in areas with high placebo response rates, eg, in depression. Proposals were made that re-randomize patients who did not respond to placebo during a first study phase as the sequential parallel design (SPD). This design uses in a second phase an enriched patient population where the treatment effect is expected to be more pronounced. This may be problematic if an effect in the overall population is claimed. Proposals were made to combine the treatment effects in the overall population from study phase 1 and the enriched population from study phase 2, alleviating but not solving the issue of a potential selection bias. This paper shows how this bias corresponding to the effect difference between the overall population and the enriched population depends on the variability of a potential subject-by-treatment interaction. Sample sizes are given, which lead to a significant result in the combining test with a given probability if actually the average effect in the overall population is zero. If, on the other hand, no subject-by-treatment interaction is given, the enrichment is shown to be inefficient. We conclude that enrichment designs using placebo nonresponders are not able to claim a positive average effect in the overall population if a subject-by-treatment interaction cannot be excluded. It cannot be used to demonstrate positive efficacy in the overall population in a pivotal phase III trial but may be used in early phases to demonstrate varying treatment effects between patients.

Keyword(s): Data Interpretation, Statistical (MeSH) ; Double-Blind Method (MeSH) ; Humans (MeSH) ; Models, Statistical (MeSH) ; Placebo Effect (MeSH) ; Randomized Controlled Trials as Topic: statistics & numerical data (MeSH) ; Research Design: statistics & numerical data (MeSH) ; Treatment Outcome (MeSH)

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Contributing Institute(s):

1. Pharmacoepidemiology in Neurodegenerative Disorders (AG Hänisch ; AG Hänisch)

Research Program(s):

1. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2020

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Web of Science Core Collection

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