Biomarkers evaluation
This call is now closed for applications and is only available for reference purposes.
The MRC launched a call for proposals for the evaluation of biomarkers on 12 July 2006. For the purposes of the call a biomarker is defined as an objective measurement that acts as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to therapeutic intervention (eg cholesterol, troponin T and I and FDG-PET) and qualification should be taken to mean demonstrating the utility of the marker(s) for use in clinical or public health studies.
Background
A recent MRC-sponsored international symposium on biomarkers highlighted the considerable interest in this area from academics, regulators and the pharmaceutical industry. Biomarkers are seen as valuable tools for: diagnosing disease; risk stratification and informing the mechanism of action of therapeutic agents; and, investigating the safety profile of an intervention and the response of patients to treatment. For example, in drug development an appropriate biomarker can help reduce the number of participants needed for a study and enable critical decisions on the efficacy and safety of a new therapy to be made more quickly, reducing patient exposure and cost.
The symposium highlighted the shortage of biomarkers that have been evaluated or ‘qualified’ for use in clinical studies. The process of biomarker evaluation is similar to that used for drug development in that the performance of a potential biomarker needs to be tested in an appropriate human population, using a robust study design with sufficient power to judge its value with confidence. This requires a cross-discipline approach involving laboratory scientists, clinicians, trial methodologists and epidemiologists and in many cases will benefit from collaboration between Academia and Industry.
It was recognised that the qualification of biomarkers is under-resourced, in part because it is seen as a major undertaking and is high-risk. However, the risk in exploring a putative biomarker for clinical studies is reduced if the biomarker is biologically plausible, that is, it can be linked closely to the pathology of the disease or is on a pathway that is closely linked to the effect of a treatment.
Focus of the call
In this call proposals were invited to evaluate potential biomarkers in diagnosis of disease, disease heterogeneity and underlying mechanisms, susceptibility, exposure or response to interventions. Studies that evaluate safety biomarkers, which was the focus of a recent DTI initiative, will also be considered. Applications were invited across a range of technological approaches that focus on the measurement of pathological or biological processes or the response to interventions. Studies centred on screening methodologies for biomarker discovery (e.g. anonymous genome, proteome, metabolome screens) are excluded. The primary objective should be to select, develop and qualify a biomarker (or discrete panel of biomarkers) as an indicator of a normal biological process, pathogenic process, or pharmacologic response to therapeutic intervention. Applications capitalising on existing well-characterised cohorts are particularly encouraged.
Specifically, proposals were invited to investigate the performance of a putative biomarker or group of biomarkers in studies on patients or population samples using a robust clinical study design. The following elements should be addressed in the proposal:
- A key feature of this initiative is the promotion of new academic-industry partnerships. It is expected that most applications will include a substantial contribution (scientific or financial) from the industrial partner (including small- and medium-sized enterprises; SMEs); the commitment should represent a real partnership and, typically, will amount to 50 per cent of the value of proposal.
- The proposal should address an area of unmet clinical need and propose clinically plausible marker(s).
- The biomarker(s) should be of demonstrable mechanistic relevance; for instance, clear evidence of a relationship to the pathogenesis of a disease, disease subtype(s), underlying mechanisms/pathways or mechanism of action of an intervention should be presented.
- The investigators should have established access to the relevant well-characterised population or suitably stored patient samples to avoid problems with recruitment.
- Applicants should demonstrate that they have the range of skills required to conduct the study or that appropriate collaborations are in place.
- It is envisaged that proposals would normally seek funding over three years in the range £300k to £1M (inclusive of industry funding). Awards may be higher if justified by the question to be addressed.
It will be a condition of all awards that any data originating from the study will be made publicly available.
Funding Available
The minimum of £10m of MRC funding was available to spend under this call and it is anticipated that we will fund a broad range of proposals. Opportunities to work with other funders (research councils and charities) are being actively investigated.
Funding Decisions
The MRC announces the awarded applications following the Biomarkers Call for Proposals – March 2007. The decision of the Panel is not open to appeal.