Evidence map›Paper›PMID 34107029›Full record

ArticleNeuro-oncology2021

Experimental design of preclinical experiments: number of PDX lines vs subsampling within PDX lines.

Jeanette E Eckel-Passow, Gaspar J Kitange, Paul A Decker, Matthew L Kosel, Danielle M Burgenske, Ann L Oberg, Jann N Sarkaria

Abstract read
In one paragraph

Article in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
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

7 authors.

Jeanette E Eckel-PassowDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
Gaspar J KitangeDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Paul A DeckerDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
Matthew L KoselDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
Danielle M BurgenskeDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Ann L ObergDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
Jann N SarkariaDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0001-7489-4885

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI Zhenkun Lou · 2009 to 2026
$37.0M
Pre-Clinical Novel Radiosensitizer Evaluation Program for Brain TumorsU01CA227954 · NCI · MAYO CLINIC ROCHESTER · PI SARKARIA, JANN N. · 2018 to 2022
$3.0M
Role of RBBP4/p300 Complex in Recovery from therapy induced DNA damage in glioblastomaR01CA233522 · NCI · UNIVERSITY OF MINNESOTA · PI KITANGE, GASPAR JULIUS · 2020 to 2024
$1.8M
NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA136393NCI NIH HHS R01 CA233522NCI NIH HHS U01 CA227954
6 · The paper itself

Abstract

backgroundAppropriately designed preclinical patient-derived xenograft (PDX) experiments are important to accurately inform human clinical trials. There is little experimental design guidance regarding choosing the number of PDX lines to study, and the number of mice within each PDX line.

methodsRetrospective data from IDH-wildtype glioblastoma preclinical experiments evaluating a uniform regimen of fractionated radiation (RT), temozolomide (TMZ) chemotherapy, and concurrent RT/TMZ across 27 PDX lines were used to evaluate experimental designs and empirically estimate statistical power for ANOVA and Cox regression.

resultsIncreasing the number of PDX lines resulted in more precise and reproducible estimates of effect size. To achieve 80% statistical power using ANOVA, experiments using a single PDX line required subsampling of 6 mice per PDX for each treatment group to detect a difference in survival of 135 days, and 9 mice per PDX to detect a difference of 100 days. Alternatively, a design that used 10 PDX lines had greater than 80% power to detect a difference of 135 days with a single mouse per PDX per treatment group, a difference of 100 days with 2 mice per PDX per treatment, and 35 days with more than 10 mice per PDX per treatment. Power for Cox regression was slightly smaller than ANOVA for very small experiments regardless of effect size and slightly higher than ANOVA for detecting a smaller effect size of 35 days difference in survival for moderate-to-large experiments.

conclusionsExperimental designs using few mice across many PDX lines can provide robust results and account for inter-tumor variability.

Indexed as

Brain NeoplasmsGlioblastomaAnimalsCell Line, TumorMiceResearch DesignRetrospective StudiesTemozolomideXenograft Model Antitumor AssaysTemozolomideexperimental designGBMglioblastomaPDXpreclinical trial

Identifiers

PMID34107029
PMCPMC8643474

What OpenQuestion holds

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Registered trials

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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.