Objective: This paper introduces the objectives, methods and results of ontology development in the EU co-funded project Advancing Clinico-genomic Trials on Cancer – Open Grid Services for Improving Medical Knowledge Discovery (ACGT).
The EORTC Board has allocated support for this initiative to promote clinico-genomic trials that cannot be adequately supported by the pharmaceutical industry.
This work has been partially financed by the National Institute for Bioinformatics (www.inab.org), a platform of Genoma España and the EC project 'Advancing Clinico-Genomic Trials on Cancer' (contract no. 026996).
Our results indicate that the current system of providing genomic test results as in the MINDACT trial works well.
The design of genomic-based trials requires consideration of the target population, whether the intervention is equally effective across different populations, potential adjustments to the significance level based on multiple analyses, the use of adaptive trial designs, and, in the case of pragmatic trials, alternative options for the unit of randomization.
The goal of the ACGT project is to contribute to the resolution of these problems by developing an ontology-driven, semantic grid services infrastructure that will enable efficient execution of discovery-driven scientific workflows in the context of multi-centric, post-genomic clinical trials.
We conducted a prospective genomic screening trial with high throughput sequencing and copy number variation (CNV) assay, and immunohistochemistry array in metastatic solid cancer patients.
Furthermore, combining clinical, radiological, pathological and genomic data in trial populations with innovative trial designs (such as in the MINDACT trial [ 84]) will allow us to relate, compare and combine established markers to, and with, new technologies in a range of settings.
National Cancer Institute-Molecular Profiling-based Assignment of Cancer Therapy and National Cancer Institute-Molecular Analysis for Therapy Choice are 2 genomic to phenotypic trials under this National Cancer Institute initiative, where treatment is selected according to predetermined genetic alterations detected using next-generation sequencing technology across a broad range of tumor types.
In genomic medicine, randomized trials are positioned along a spectrum from "explanatory" (e.g., to test whether the use of genomic information, when used under optimal, ideal settings, will improve patient outcomes) to "pragmatic" (e.g., to test whether the use of genomic information improves outcomes under usual clinical practice settings).
The two highly venture-backed oncology startups are creating a database of genomic information, clinical trials, and drug treatment results that will vastly accelerate the development of new cancer drugs.
