IOM Report Calls for Sweeping Changes in Cancer Clinical Trials
The National Cancer Institute's (NCI) Clinical Trials Cooperative Group program is “approaching a state of crisis,” according to a new report. In the report, a committee from the Institute of Medicine of the National Academies recommends 12 sweeping changes in how federally funded cancer clinical trials are conducted and financially supported—changes that are likely to affect a broad swath of researchers, including those involved with translational science.
One of the recommendations, for example, calls for the increased use of predictive markers that could enable testing of more homogenous populations that are more likely to benefit from new drugs. The report also supports the increased use and standardization of biorepositories that store and process biospecimens for future scientific research. In addition, the authors call for more adaptive trial designs, in which researchers hone in on the populations most likely to benefit from a therapy and drop those arms of a study that are not likely to help patients.
“The result of adaptive trial designs is that trials can become smarter and more informative. Biostatisticians truly believe that the data from such trials are more robust,” said Michael Carducci, MD, a member of the IOM committee and AEGON professor in prostate cancer research at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine in Baltimore, Maryland.
The committee also hopes the use of biomarkers will make clinical trials more efficient and provide larger gains in understanding how to treat different cancers. “If we can use biomarkers to more precisely define the population of patients being treated we might be able to demonstrate a larger treatment effect,” said Richard Schilsky, MD, a member of the IOM committee and professor of medicine and chief of the hematology/oncology section at the University of Chicago in Illinois. “The use of biomarkers would also require many fewer patients and trials could get completed more quickly.”
Dr. Schilsky also notes that while biorepositories already exist, there's a need to preserve and expand them, and to ensure the specimens are of high quality. “These are very valuable specimens if they are all obtained from patients who are participating in clinical trials where the treatments are standardized and the outcomes are known. So they’re very well annotated specimens and could be very informative if made available widely to the research community,” he said.
In the report, the IOM committee also concludes that it takes far too long—an average of more than 2 years—to get Cooperative Group clinical trials up and running, often because of multiple approval procedures that must be shouldered by investigators. The system is underfunded, according to the committee, since only $2,000 of the $6,000 per‐case costs of running a trial are reimbursed by the NCI. The report recommended changes that would streamline approval processes and reward innovative and efficient disease site committees and prioritize research at each Cooperative Group program.
If the IOM committee's recommended changes are put into effect, the result could be that more translational researchers would seek out Cooperative Group support for their investigations, Dr. Carducci said. “Right now, there's an element of bureaucracy to the Cooperative Group programs and funding for correlative science (which includes better patient selection and use of predictive markers) is poor. That has meant that translational researchers feel that the questions being asked by the Cooperative Groups are not the most pressing or interesting,” he said.
To read the report, “A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Program,” visit http://www.nap.edu.
Cleveland Clinic to Expand Its Translational Research Capabilities
The Taussig Cancer Institute of the Cleveland Clinic in Ohio plans to spend $2 million in government stimulus money to upgrade research facilities, a move that will allow it to attract translational researchers, according to offi cials with the institute.
The renovation will remodel 3,600 square feet of laboratory bench space dating from the 1920s and last renovated in the 1950s, enabling the institute to hire 4 new researchers and 12 technical support staffers, according to John Pellecchia, MS, administrator in the department of translational hematology and oncology research at the Taussig Cancer Institute.
The current cancer institute is housed in a building built in 2000, but the space devoted to research there has reached capacity. “The added space will give us the capability to attract and house translational scientists in areas such as cancer genomics, stem cell biology, epigenetics, drug development, and cancer pharmacology,” Mr. Pellecchia said.
Aside from individual laboratories, the renovated building will have a shared instrumentation room with novel imaging equipment that can detect circulating tumor cells in the blood stream, as well as fl ow cytometry equipment. “With these capabilities, we hope to attract individuals interested in these cuttingedge technologies,” Mr. Pellecchia said.
He noted that construction should be completed by the end of 2011.
NIH Funding 30 Research Projects on Molecular Probes
The National Institutes of Health (NIH) is planning to spend $6 million in 2011 to fund 30 projects meant to develop new molecular probes, or research assays for novel targets that can be automated, miniaturized, and used to screen small molecules against more than 300,000 active compounds.
The program, part of the Molecular Libraries and Imaging Roadmap Initiative, will award up to $100,000 per project. This initiative is meant to expand knowledge and public access to small molecule chemical structures and tools for pharmacological and biological research available in PubChem (http://pubchem.ncbi.nlm.nih.gov/), a database of molecules that is maintained by the National Center for Biotechnology Information. In addition, the molecular probes developed through the grants will be used by the Molecular Libraries Probe Production Center Network, funded by the NIH, to run a high throughput screen of groups of compounds that might interact with a probe's target. Often the most challenging aspect of pharmaceutical research is finding out whether scientists can change the disease process by modifying a biological target with a small molecule or drug, according to Mark Scheideler, PhD, senior scientific officer with the National Institute of Neurological Disorders and Stroke, who spearheads the development of the assay program. “But the intent of the molecular library initiative is not to develop drugs, but to develop toolsets that will de‐risk novel targets,” Dr. Scheideler said. The assays developed could also be used to understand the function of genes, proteins, and biological chemical pathways, specifically to measure protein interactions important in biological signaling, how gene expression is modulated, and other basic research questions, he said. The deadline for the next round of grant applications is October 29, and applications will be judged not only on the novelty of the assay technology described in the proposal, but also on the novelty of the proposed targets, he said.
NIH Aims to Increase Number of Minority Scientists
Only 6% of scientists and engineers in the U.S. are African‐American or Hispanic.
Only 6% of scientists and engineers in the U.S. are African‐American or Hispanic and only 7% have a disability, according to the National Science Foundation (NSF). In addition, male scientific doctoral faculty outnumber female faculty members 2 to 1, the NSF reports on its website. It's statistics like these that are the impetus behind a new grant program from the National Institutes of Health (NIH).
The Director's Pathfinder Award to Promote Diversity in the Workforce program will use funding provided by the American Recovery and Reinvestment Act to award $10 million over 3 years to up to 5 projects that employ innovative approaches to encouraging minority representation in the scientific workforce. “Having a scientific workforce that is a representative of society is important for increasing the diversity of the research that NIH does, and to increase the ability of scientists to work with people with different perspectives in scientific endeavors that have become increasingly team based,” said Clifton Poodry, PhD, director of the Division of Minority Opportunities in Research at the National Institute of General Medical Sciences.
As of May, 95 research groups across the U.S. have applied for the Pathfinder grant for which NIH director Francis Collins, MD, PhD, will be awarding selections in the fall. The researchers selected are expected to take novel approaches to increasing diversity in the scientific workforce that couldn't be funded with existing mechanisms, Dr. Poodry said. “There's a hope that we can invest in people with proven track records of creativity who may provide new insights that others have overlooked,” he added. Dr. Poodry noted that a number of programs already exist to fund research that seeks to understand the sociology of minority underrepresentation in the sciences or to increase levels of participation among minority science students at educational levels from high school through postdoctoral programs. These types of research projects, therefore, are unlikely to receive awards. Rather, the projects are expected to tackle the problem of minority underrepresentation from a different perspective, for instance, to focus on the institutional problems that keep minorities out of scientific education and employment.
The emphasis on meritocracy in the sciences, and the emphasis placed on judging applications for graduate school through objective criteria such as standardized tests and GPA may have kept minorities out of the pipeline that supplies future scientists, Dr. Poodry said. “Some of the tools for objective measurement that came into use in the 1950s may disadvantage students who don't have the life experience to do well on standardized tests,” he added.