Evidence map›Paper›PMID 38357386›Full record

ArticleBrazilian journal of biometrics2022

Modeling synergism in early phase cancer trials with drug combination with continuous dose levels: is there an added value?

Mourad Tighiouart, José L Jiménez, Marcio A Diniz, André Rogatko

Abstract read
In one paragraph

Article in Brazilian journal of biometrics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

4 authors.

Mourad TighiouartBiostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, California, USA.ORCID https://orcid.org/0000-0001-8021-5690
José L JiménezNovartis Pharma A.G., Basel, Switzerland.ORCID https://orcid.org/0000-0002-8809-2717
Marcio A DinizBiostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, California, USA.ORCID https://orcid.org/0000-0002-2427-7843
André RogatkoBiostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, California, USA.ORCID https://orcid.org/0000-0001-8935-8890

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
The paradoxical roles of beta hydroxy butyrate in the liver pro-metastatic nicheP01CA233452 · NCI · CEDARS-SINAI MEDICAL CENTER · PI BHOWMICK, NEIL A., LU, SHELLY CHI-LOO · 2020 to 2024
$9.5M
Advancing Analysis and Interpretation ofAdverse Events and PROs in Cancer Clinical TrialsU01CA232859 · NCI · CEDARS-SINAI MEDICAL CENTER · PI GANZ, PATRICIA A., TIGHIOUART, MOURAD · 2018 to 2023
$3.7M
NCATS NIH HHS UL1 TR001881NCI NIH HHS P01 CA233452NCI NIH HHS U01 CA232859
6 · The paper itself

Abstract

In parametric Bayesian designs of early phase cancer clinical trials with drug combinations exploring a discrete set of partially ordered doses, several authors claimed that there is no added value in including an interaction term to model synergism between the two drugs. In this paper, we investigate these claims in the setting of continuous dose levels of the two agents. Parametric models will be used to describe the relationship between the doses of the two agents and the probability of dose limiting toxicity and efficacy. Trial design proceeds by treating cohorts of two patients simultaneously receiving different dose combinations and response adaptive randomization. We compare trial safety and efficiency of the estimated maximum tolerated dose (MTD) curve between models that include an interaction term with models without the synergism parameter with extensive simulations. Under a selected class of dose-toxicity models and dose escalation algorithm, we found that not including an interaction term in the model can compromise the safety of the trial and reduce the pointwise reliability of the estimated MTD curve.

Indexed as

Cancer phase I trialsDose limiting toxicityDrug combinationEscalation with overdose controlMaximum tolerated doseSynergism

Identifiers

PMID38357386
PMCPMC10865897

What OpenQuestion holds

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Registered trials

None linked

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.