Abstract
Translational medicine (TM) components of prospective clinical trials provide an invaluable opportunity to test hypotheses that contribute to our knowledge of human disease biology and/or the mechanism of action of a given therapeutic intervention. Our ability to sample tumors and their microenvironment, and the depth and breadth of biological information that can be extracted from them, has increased exponentially in recent years. This information is critical to guide the next steps clinical research if we are to accelerate the pace of progress in cancer treatment. Thus, TM studies should be considered key components of any clinical trial. However, TM studies are costly and biologic sampling can impose significant morbidity on our patients. Therefore, TM investigators should be engaged early in the design process (similar to a statistician) to ensure that the most imperative research questions are rigourosly defined, that the obtained specimens can be used to answer them and that the results will serve as the foundation for additional studies. In this review, we focus on TM studies in the context of the National Cancer Institute's National Clinical Trials Network trials and offer a description of the genesis of TM components, methods in sample acquisition and biomarker research, and a guide to funding mechanisms, in order to provide a blueprint for future TM research protocols. While TM studies can take many forms, the research discussed primarily focusses on basic and translational research involving molecular, cellular, and immunobiology.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 313-317 |
| Number of pages | 5 |
| Journal | Urologic Oncology: Seminars and Original Investigations |
| Volume | 37 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2019 |
Funding
Funding: JM is supported by a SEED grant from the HOPE Foundation, BX003692-01 from the VHA and the John P. Hanson Foundation. Foundation support (from organizations like the HOPE Foundation) offers an unprecedented opportunity for funding support of TM research [7] . The HOPE foundation supports research through the Southwest Oncology Group (SWOG) and provides multiple funding mechanisms through the year including SEED and Impact grants that are similar to R03 and R21 mechanisms from the NIH. These grants are competitive, and even an Impact award is not sufficient to complete a TM project but would be sufficient to submit a high-quality grant with preliminary data. Funding of TM research is one of the most important challenges in clinical research and the responsibility of the TM team. While the clinical trial is often funded by a combination of standard-of-care (insurance) and NCI/CTEP, the TM component usually receives little to no funding through the NCI. Once approved by CTEP, most trials have a minimum budget that includes funding for obtaining slides for banking and resources for one tube of blood. The pharmaceutical industry is sometimes able to support TM research, especially for the development or validation of biomarkers that can support the application of their drugs. These relationships, once thought to negatively influence a trial, should be evaluated on an individual basis depending on the trial and company. With pharma involvement, the science should still be performed in an unbiased manner with unlimited access to the data for all involved from the TM team. The cooperative group contracting and legal services can ensure that the research will be performed and reported regardless of the trial outcome. A more challenging situation occurs when no funding is provided. Therefore, these TM projects require competitive applications and grant support. For NCTN trials, an NCI BIQSFP (Biomarker, Imaging and Quality of Life Studies Funding Program) application is an outstanding mechanism that can fund integrated or integral biomarker research [6] . The goal of BIQ funding is to identify biomarkers that could shape clinical practice and these assays should be reliable and validated, with locked down cut points. BIQ funding applications are required within three months of review of the CTEP concept proposal. Important factors in BIQ review are (1) validation of the biomarker, (2) applicability to the trial, and (3) platform rigor with possible commercialization. Given the demand for funding dollars, predictive biomarkers are prioritized over prognostic biomarkers. The BIQ application is reviewed by NCI Clinical and Translational Research Operations Committee (CTROC). In 2016, over . The goal of BIQ funding is to identify biomarkers that could shape clinical practice and these assays should be reliable and validated, with locked down cut points. BIQ funding applications are required within three months of review of the CTEP concept proposal. Important factors in BIQ review are (1) validation of the biomarker, (2) applicability to the trial, and (3) platform rigor with possible commercialization. Given the demand for funding dollars, predictive biomarkers are prioritized over prognostic biomarkers. The BIQ application is reviewed by NCI Clinical and Translational Research Operations Committee (CTROC). In 2016, over $10 million was approved for funding. Most of the challenge of the BIQ is developing a fundable concept within the short-time from clinical trial submission. If the BIQ application is unfunded, many will not be funded on resubmission. BIQ applications that are descriptive or propose discovery research have a very low likelihood for success.0 million was approved for funding. Most of the challenge of the BIQ is developing a fundable concept within the short-time from clinical trial submission. If the BIQ application is unfunded, many will not be funded on resubmission. BIQ applications that are descriptive or propose discovery research have a very low likelihood for success.
Keywords
- Translational medicine
ASJC Scopus subject areas
- Urology
- Oncology
