Preclinical systematic review and meta-analysis

Preclinical systematic review and meta-analysis are meta-research tools that we use to investigate some of the challenges of translational biomedical research. They provide a summary of research findings in a field and allow judgement of both the range and quality of available evidence, including the likelihood that findings are at risk of bias. The results can help us identify areas for improvement in preclinical research and inform the development of strategies to address these challenges.

Further, preclinical systematic review can help to:

  • Identify gaps in a field
  • Assess for publication bias
  • Explain discrepancies between preclinical and clinical trial results
  • Inform clinical trial design
  • Inform 3Rs (Replacement, Reduction, and Refinement of animal use in research) decisions

We focus primarily on the review of data from studies involving animal models of stroke and other neurological diseases and have a range of ongoing projects:

Docosahexaenoic acid as a treatment for acute stroke: a systematic literature review and meta-analysis

Currently, dissolving or removing a blood clot are the only approved therapies for ischaemic stroke. However, many patients are ineligible or don’t benefit from these therapies, so researchers are focussed on finding novel treatments. DHA, an omega-3 fatty acid, is one of the major building blocks of the brain. It is essential for normal brain growth and function, and dietary sources (e.g. fish, fish oils) are required to maintain necessary levels throughout life. Animal studies suggest that acute DHA administration may be able to protect the brain after stroke. This project investigates whether there is sufficient preclinical evidence to support a clinical trial of DHA administration for the treatment of ischaemic stroke.

The protocol for this project can be found here.

Effectiveness of biomaterial-based combinational strategies for spinal cord repair – a systematic review and meta-analysis of preclinical literature

Traumatic spinal cord injury (SCI) is a debilitating condition with no treatment available to date. To address the complex damage that occurs following injury, it is now well recognised that a combination strategy involving novel therapies is required. Biomaterials can be used as part of a combination therapy to bridge the injured site in the spine, provide structural support, and act as a depot for cells, molecules, and drugs. This project investigates the most promising characteristics of biomaterials tested in models of SCI, to inform future research on biomaterial-based therapies.

The protocol for this project can be found here.

Preclinical systematic review and meta-analysis of the effects of age and comorbidities on ischaemic stroke outcome and treatment efficacy

In stroke research, the results from animal models often fail to translate to clinical benefit in humans. Our ability to generalise results beyond the laboratory may be affected by a number of factors, including how well we model relevant patient characteristics. Stroke affects women and men, who are usually elderly, and often suffer from comorbidities such as hypertension and diabetes. The most commonly used models of stroke, in contrast, are young, healthy, male rodents. In vitro stroke experiments that use ischaemia-like conditions are also used to investigate stroke pathophysiology and treatments. These experiments often inform animal and human studies, however their external validity has also not been systematically studied to date.

This project investigates the impact of modelling advanced age and comorbidities on stroke outcome and treatment efficacy in animal and in vitro models of ischaemic stroke. An important feature of this project will be the use of new automation tools including machine learning and text mining to improve the accuracy and speed of the review, and to contribute to the development and validation of these tools.

This project is supported by the Federal Ministry of Education and Research (BMBF) under the Confirmatory Preclinical Studies and Systematic Reviews Initiative.

Identifying stroke therapeutics from preclinical models: a novel application of network meta-analysis

Over 1,000 potential neuroprotective therapeutics have been evaluated in preclinical ischaemic stroke models. It is important to use robust evidence synthesis methods to assess appropriately which therapies should be translated to the clinical setting for evaluation in human studies. This study uses systematic review to identify and appraise eligible studies and network meta-analysis to synthesize available evidence to investigate the relative benefits of competing therapies tested in combination with the gold standard treatment, alteplase, in improving stroke outcome in preclinical in vivo models of focal ischemic stroke.

The protocol for this project can be found here.

Network meta-analysis (NMA) of anaesthetic neuroprotection in preclinical stroke in rodents

Our ability to translate promising animal studies to clinical treatments for ischaemic stroke may be affected by experimental design. Often stroke is modelled in anaesthetised animals, however human patients are rarely under the influence of anaesthetics when they suffer a stroke. Because they may have intrinsic neuroprotective properties, anaesthetics have the potential to contribute to translational failure by confounding the results of animal studies testing new treatments. A systematic review has estimated the neuroprotective effects of anaesthetics in animals to be approximately 30%. Network meta-analysis is a relatively new analysis technique that offers the opportunity to compare the neuroprotective efficacy of different anaesthetics and inform future experimental design.

The protocol for this project can be found here.