Evidence map›Paper›PMID 30309262›Full record

ArticleClinical trials (London, England)2019

Shift models for dose-finding in partially ordered groups.

Bethany Jablonski Horton, Nolan A Wages, Mark R Conaway

Abstract read
In one paragraph

Article in Clinical trials (London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Concurrent dose-finding of a novel cancer drug with and without a second agent.Journal of clinical and translational science · 2023
    Article
  6. Article
  7. Article
  8. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Bethany Jablonski HortonDivision of Translational Research & Applied Statistics, Department of Public Health Sciences, The University of Virginia Health System, Charlottesville, VA, USA.ORCID 0000-0002-6866-4626
Nolan A WagesDivision of Translational Research & Applied Statistics, Department of Public Health Sciences, The University of Virginia Health System, Charlottesville, VA, USA.
Mark R ConawayDivision of Translational Research & Applied Statistics, Department of Public Health Sciences, The University of Virginia Health System, Charlottesville, VA, USA.

Funding

Designs for phase I trials of combinations of agentsR01CA142859 · NCI · UNIVERSITY OF VIRGINIA · PI CONAWAY, MARK R · 2010 to 2017
$2.1M
Phase I Designs for Combined Immunotherapies in CancerK25CA181638 · NCI · UNIVERSITY OF VIRGINIA · PI WAGES, NOLAN · 2014 to 2018
$780k
NCI NIH HHS K25 CA181638NCI NIH HHS R01 CA142859
6 · The paper itself

Abstract

backgroundLimited options are available for dose-finding clinical trials requiring group-specific dose selection. While conducting parallel trials for groups is an accessible approach to group-specific dose selection, this approach allows for maximum tolerated dose selection that does not align with clinically meaningful group order information.

methodsThe two-stage continual reassessment method is developed for dose-finding in studies involving three or more groups where group frailty order is known between some but not all groups, creating a partial order. This is an extension of the existing continual reassessment method shift model for two ordered groups. This method allows for dose selection by group, where maximum tolerated dose selection follows the known frailty order among groups. For example, if a group is known to be the most frail, the recommended maximum tolerated dose for this group should not exceed the maximum tolerated dose recommended for any other group.

resultsWith limited alternatives for dose-finding in partially ordered groups, this method is compared to two alternatives: (1) an existing method for dose-finding in partially ordered groups which is less computationally accessible and (2) independent trials for each group using the two-stage continual reassessment method. Simulation studies show that when ignoring information on group frailty, using independent continual reassessment method trials by group, 30% of simulations would result in maximum tolerated dose selection that is out of order between groups. In addition, the two-stage continual reassessment method for partially ordered groups selects the maximum tolerated dose more often and assigns more patients to the maximum tolerated dose compared to using independent continual reassessment method trials within each group. Simulation results for the proposed method and the less computationally accessible approach are similar.

conclusionThe proposed continual reassessment method for partially ordered groups ensures appropriate maximum tolerated dose order and improves accuracy of maximum tolerated dose selection, while allowing for trial implementation that is computationally accessible.

Indexed as

Maximum Tolerated DoseAgedClinical Trials, Phase I as TopicDose-Response Relationship, DrugFrail ElderlyHumansIrinotecanResearch DesignIrinotecanClinical trialscontinual reassessment methoddose-finding studiesmaximum tolerated dosepartially ordered groupsphase I designs

Identifiers

PMID30309262
PMCPMC6684162

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.