CoChat
Sign Up
Cited by 35Statistical Methods in Clinical TrialsMeta-analysis and systematic reviewsStatistical Methods in Epidemiology

Implications of clinical trial design on sample size requirements

Open access
Leon, A. C.·2007·Schizophrenia Bulletin
DOI 10.1093/schbul/sbn035PMC PMC2632464
Open this paper in CoChat — free accountOpen PDF

Abstract

The primary goal in designing a randomized controlled clinical trial (RCT) is to minimize bias in the estimate of treatment effect. Randomized group assignment, double-blinded assessments, and control or comparison groups reduce the risk of bias. The design must also provide sufficient statistical power to detect a clinically meaningful treatment effect and maintain a nominal level of type I error. An attempt to integrate neurocognitive science into an RCT poses additional challenges. Two particularly relevant aspects of such a design often receive insufficient attention in an RCT. Multiple outcomes inflate type I error, and an unreliable assessment process introduces bias and reduces statistical power. Here we describe how both unreliability and multiple outcomes can increase the study costs and duration and reduce the feasibility of the study. The objective of this article is to consider strategies that overcome the problems of unreliability and multiplicity.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/schbul/sbn035

Cites

17 of 17 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The low power of completed trials increases the likelihood of a type II statistical error of concluding that a drug with true efficacy did not have beneficial effect.

    “Our analysis shows that only one in 17 completed trials with available results had sufficient power to detect a medium (d = 0.5) effect size, thus increasing the likelihood of a type II statistical error of concluding that a drug with true efficacy did not have beneficial effect.54,55”

    From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [54]

  • Large samples imply multi-site trials, which present investigators and sponsors with specific challenges.

    “Such large samples imply multi-site trials, which present investigators and sponsors with specific challenges (for review, see ref.54).”

    From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [54]

  • Only one in 17 completed trials with available results had sufficient power to detect a medium (d = 0.5) effect size.

    “Our analysis shows that only one in 17 completed trials with available results had sufficient power to detect a medium (d = 0.5) effect size, thus increasing the likelihood of a type II statistical error of concluding that a drug with true efficacy did not have beneficial effect.54,55”

    From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [54]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Fleiss JL. The Design & Analysis of Clinical Experiments. New York, NY: John Wiley and Sons; 1986.

Cited by

Sorted by citations

Related

Authors
Leon, A. C.
Affiliations
Cornell University (US)
Corresponding author
Leon, A. C.
ORCID
Leon, A. C.
Venue
Schizophrenia Bulletin
Publisher
Oxford University Press (OUP)
Published
2007-11-21
Volume
34
Issue
4
Pages
664-669
ISSN
  • 0586-7614 (ISSN-L)
  • 1745-1701
DOI
10.1093/schbul/sbn035
PMC
PMC2632464
OpenAlex
W2170636614
Cited by
35
References
17
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2022: 1 · 2021: 4 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 3
FWCI
1.87
Type
journal article
Language
en
Open access
Locations
  • Schizophrenia Bulletin (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (MH068638, MH 060447, P30MH068638, R01MH060447)
Topics
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
  • Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
Keywords
clinical trial design, sample size
MeSH terms
Cognition Disorders, Double-Blind Method, Humans, Neuropsychological Tests, Pilot Projects, Psychometrics, Reaction Time, Research Design, Schizophrenia, Statistics as Topic, Reproducibility of Results, Randomized Controlled Trials as Topic, Treatment Outcome, Outcome Assessment, Health Care, Sample Size, Ethics, Research, Control Groups

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review