Evidence map›Paper›PMID 27668084›Full record

ReviewEvidence-based preclinical medicine2014

A systematic review and meta-analysis of gene therapy in animal models of cerebral glioma: why did promise not translate to human therapy?

T C Hirst, H M Vesterinen, S Conlin, K J Egan, A Antonic, A Lawson McLean, M R Macleod, R Grant, P M Brennan, E S Sena and 1 more

Open access · hybridAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Evidence-based preclinical medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 4 pooled it
1.0field-weighted citation impact, top 23% 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

14 citing papers in PubMed, 4 syntheses or guidelines pooled it, 19 citations in OpenAlex.

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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

11 authors at 3 institutions in 2 countries.

T C HirstCentre for Clinical Brain Sciences Chancellors Building University of Edinburgh Edinburgh UK.
H M VesterinenCentre for Clinical Brain Sciences Chancellors Building University of Edinburgh Edinburgh UK.
S ConlinCentre for Clinical Brain Sciences Chancellors Building University of Edinburgh Edinburgh UK.
K J EganCentre for Clinical Brain Sciences Chancellors Building University of Edinburgh Edinburgh UK.
A AntonicFlorey Neuroscience and Mental Health Institute University of Melbourne Victoria Australia.
A Lawson McLeanCentre for Clinical Brain Sciences Chancellors Building University of Edinburgh Edinburgh UK.
M R MacleodDivision of Clinical Neurosciences University of Edinburgh Western General Hospital Edinburgh UK.
R GrantDivision of Clinical Neurosciences University of Edinburgh Western General Hospital Edinburgh UK.
P M BrennanDivision of Clinical Neurosciences University of Edinburgh Western General Hospital Edinburgh UK.
E S SenaCentre for Clinical Brain Sciences Chancellors Building University of Edinburgh Edinburgh UK; Florey Neuroscience and Mental Health Institute University of Melbourne Victoria Australia.
I R WhittleDivision of Clinical Neurosciences University of Edinburgh Western General Hospital Edinburgh UK.
University of Edinburgh · GBUniversity of Melbourne · AUWestern General Hospital · GB

Funding

National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/L000970/1
6 · The paper itself

Abstract

backgroundThe development of therapeutics is often characterized by promising animal research that fails to translate into clinical efficacy; this holds for the development of gene therapy in glioma. We tested the hypothesis that this is because of limitations in the internal and external validity of studies reporting the use of gene therapy in experimental glioma.

methodWe systematically identified studies testing gene therapy in rodent glioma models by searching three online databases. The number of animals treated and median survival were extracted and studies graded using a quality checklist. We calculated median survival ratios and used random effects meta-analysis to estimate efficacy. We explored effects of study design and quality and searched for evidence of publication bias.

resultsWe identified 193 publications using gene therapy in experimental glioma, including 6,366 animals. Overall, gene therapy improved median survival by a factor of 1.60 (95% CI 1.53-1.67). Study quality was low and the type of gene therapy did not account for differences in outcome. Study design characteristics accounted for a significant proportion of between-study heterogeneity. We observed similar findings in a data subset limited to the most common gene therapy.

conclusionAs the dysregulation of key molecular pathways is characteristic of gliomas, gene therapy remains a promising treatment for glioma. Nevertheless, we have identified areas for improvement in conduct and reporting of studies, and we provide a basis for sample size calculations. Further work should focus on genes of interest in paradigms recapitulating human disease. This might improve the translation of such therapies into the clinic.

Indexed as

gene therapygliomarodent modelssystematic review

Identifiers

PMID27668084
PMCPMC5020579
OpenAlexW2098993139

What OpenQuestion holds

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LicenceCC BY
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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.