J. Evan Sadler, MD, PhD
Recent advances in basic and translational research have set the stage for tremendous progress in clinical hematology research, but trials to pursue these opportunities run afoul of many obstacles. For example, David Dilts, Director of Clinical Research of the Knight Cancer Institute, reported last year that opening a phase III cooperative oncology group trial requires an average of 2.5 years to accommodate 118 decision points, complete more than 769 process steps, and receive approval by up to 36 separate groups or individuals. Whether many of these steps improve trial quality or patient safety is doubtful. Many approved trials never enroll a single patient and barely half are ever completed, which is a terrible waste of human and financial capital. Small wonder that Garret FitzGerald, MD, Director of the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania, has described our current system as “spreading dysfunction that undermines progress for the sake of managing risk.” Not surprisingly, the cost of conducting trials has grown much faster than federal funding, and clinical research is fleeing for more hospitable shores. According to Kenneth A. Getz, a Senior Research Fellow at the Tufts Center for the Study of Drug Development, the number of active FDA-regulated investigators outside of the United States grew 15 percent annually between 2002 and 2007, whereas the number in the United States declined 5.5 percent annually over the same period.
The National Institutes of Health (NIH) clearly recognizes the scope of these problems, and two recent announcements describe major initiatives to reinvigorate clinical trials.
On December 23, the National Cancer Institute (NCI) publicized plans to restructure the nine groups that currently conduct adult cancer trials to make them more efficient. The proposed changes are based upon an NCI-requested April 2010 report from the Institute of Medicine, which recommended total reorganization to reduce redundancy and shift the primary focus of the NCI from oversight to facilitation of clinical trials. The protocol approval process would be streamlined through parallel, concurrent, or joint reviews. Additional measures would standardize data collection and analysis and enhance the sharing of banked specimens. These changes are expected to reduce by half the time needed to initiate new studies. In addition, trials that do not begin within two years of concept approval would be terminated, providing a strong incentive to accelerate enrollment and completion.
Of course the problems besetting clinical trials are not unique to cancer, and the NIH is poised to launch a more comprehensive countermeasure. On December 7, the Scientific Management Review Board (SMRB), which advises the NIH, voted to recommend establishing a new center to focus on translational medicine, provisionally named the National Center for Advancing Translational Sciences (NCATS). NIH Director Francis Collins has outlined plans to integrate several existing translational research programs and their educational infrastructure into this new center. For example, it would absorb the Clinical and Translational Science Awards (CTSAs), which now provide an academic home to train and mentor clinical researchers and manage clinical trials at 55 medical research institutions across the country. The proposed NCATS would have a budget of at least $650 million and could be operational as soon as October 2011.
These developments attempt to address a burning need, but the broader consequences for biomedical research, intended or otherwise, are not yet known. For example, concerns have been raised that the new translational research center could divert funds from basic research. However, Francis Collins has signaled that he will not allow such an outcome. As Garret FitzGerald puts it, this is not necessarily “a zero-sum game: the success of translation requires investment in basic science.”1 Conversely, we cannot shortchange basic research without also crippling clinical research.
These NIH proposals have started a lively discussion about the best way forward, and alternatives surely will be proposed. However these initiatives evolve, reforming the conduct of patient-oriented research should help reestablish the implicit bargain between investigators and their patients, who enroll in trials with the understanding that participation will lead to better medical care, if not for them then at least for future patients. This shared goal is frustrated when clinical trials are conceived but never approved, approved but never accrue, or accrue but never see publication. If changes underway do succeed in restoring the vitality of clinical research, they will translate directly into better, longer lives for more people.
- FitzGerald G. Drug development needs a new brand of science. Nature. 2010;468:869.
To read more about the NIH's plans to restructure visit www.hematology.org/Publications/Hematologist/2011/6469.aspx