Evidence map›Paper›PMID 36176591›Full record

ArticleImmunotherapy advances2022

De-risking clinical trial failure through mechanistic simulation.

Liam V Brown, Jonathan Wagg, Rachel Darley, Andy van Hateren, Tim Elliott, Eamonn A Gaffney, Mark C Coles

Open access · goldAbstract read
In one paragraph

Article in Immunotherapy advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 36% of its field
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

2 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. 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 at 3 institutions in 2 countries.

Liam V BrownWolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, UK.ORCID https://orcid.org/0000-0001-9870-8418
Jonathan WaggPharmaceutical Sciences-Clinical Pharmacology, Roche Innovation Center Basel, Basel, Switzerland.
Rachel DarleyCentre for Cancer Immunology, Institute for Life Sciences, University of Southampton, Southampton, UK.
Andy van HaterenCentre for Cancer Immunology, Institute for Life Sciences, University of Southampton, Southampton, UK.
Tim ElliottCentre for Immuno-oncology, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Eamonn A GaffneyWolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, UK.
Mark C ColesKennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
University of Oxford · GBUniversity of Southampton · GBRoche (Switzerland) · CH

Funding

Cancer Research UK 28279
6 · The paper itself

Abstract

Drug development typically comprises a combination of pre-clinical experimentation, clinical trials, and statistical data-driven analyses. Therapeutic failure in late-stage clinical development costs the pharmaceutical industry billions of USD per year. Clinical trial simulation represents a key derisking strategy and combining them with mechanistic models allows one to test hypotheses for mechanisms of failure and to improve trial designs. This is illustrated with a T-cell activation model, used to simulate the clinical trials of IMA901, a short-peptide cancer vaccine. Simulation results were consistent with observed outcomes and predicted that responses are limited by peptide off-rates, peptide competition for dendritic cell (DC) binding, and DC migration times. These insights were used to hypothesise alternate trial designs predicted to improve efficacy outcomes. This framework illustrates how mechanistic models can complement clinical, experimental, and data-driven studies to understand, test, and improve trial designs, and how results may differ between humans and mice.

Indexed as

late-phase trialmathematical modellingoncologypeptidevaccines

Identifiers

PMID36176591
PMCPMC9514113
OpenAlexW4292488042

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.