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Editorials |
1 From the Cancer Imaging Program, National Cancer Institute, 6130 Executive Blvd, Suite 3007, MSC 7319, Rockville, MD 20892-7319. Received April 16, 2006; final version accepted April 24. Address correspondence to the author (e-mail: becker{at}rsna.org).
In an editorial in this issue of Radiology (1), Dr Subramaniam, congratulates the Radiological Society of North America (RSNA) for having delivered its first Clinical Trials Methodology Workshop in Phoenix, Ariz, from January 7 to 13, 2006. As one of the organizers and faculty and as Science Liaison of the RSNA Board of Directors, I have been asked to provide a perspective on the workshop. I shall do so first by focusing more broadly on the state of clinical trials in the United States and then by returning to a discussion of the workshop.
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BACKGROUND |
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The report, which was based on analysis of an FDA database of more than 100 000 clinicians registered as PIs between 1977 and 2004, cites the following among the most important causes of the disturbing trends: (a) insufficient remuneration (per-procedure, per-patient compensation for physicians declined 27% between 1998 and 2003); (b) onerous regulation; (c) inadequate supply of properly trained investigators; and (d) increased acceptability to the Food and Drug Administration of data from trials conducted outside the United States, owing to efforts aimed at international harmonization among regulatory agencies (2). In the report, Getz correctly pointed out that these multifactorial problems threatening U.S. clinical trials must be addressed by multiple stakeholders, including industry, academia, insurers, medical professional organizations, government, ethicists, and the public (2).
The concerns and sentiments expressed in the report by Getz (2) are widely shared and have been expressed previously. They extend well beyond the bounds of FDA-regulated research. Indeed it was in response to the 1999 Statement by David Korn, MD, of the Association of American Medical Colleges, entitled, "Clinical Research: A National Call to Action" (3), as well as in response to requests from other organizations, that the Institute of Medicine and the Commission on Life Sciences of the National Academies convened the Clinical Research Roundtable from 2000 until 2005 (4). The roundtable aimed to improve understanding of clinical research among the scientific community and the public and to enhance the public's participation in clinical studies. Stakeholders participating in the roundtable and its workshops included federal agencies, clinical research sponsors, insurers, foundations, health care purchasers, patient interest groups, ethicists, and others.
Korn's statement (3) summarized the findings of Graylyn Consensus Development Conference convened at Wake Forest University (Winston-Salem, NC) in November of 1998 by 50 select representatives from 10 groups with a major stake in the future of clinical research (5). Most of the content of Korn's statement and the subsequent workshops and reports of the Clinical Research Roundtable are beyond the scope of this editorial, but two aspects are not. First is the definition of clinical research agreed upon by the conference participants as
a continuum of studies involving interactions with patients, diagnostic clinical materials or data, or populations in and of the following categories: (1) disease mechanisms (etiopathogenesis); (2) bi-directional integrative (translational) research; (3) clinical knowledge, detection; diagnosis and natural history of disease; (4) therapeutic interventions including clinical trials of drugs, biologics, devices and instruments; (5) prevention (primary and secondary) and health promotion; (6) behavioral research; (7) health services research, including outcomes, and cost-effectiveness; (8) epidemiology; and (9) community-based trials (5).
Second, and most germane to the RSNA Clinical Trials Methodology Workshop, is the recognition of our current pressing need to expand the number of our nation's physician-investigators. Korn (3) commended the National Institutes of Health (NIH) for offering K awards as one effort to deal with the shortage but went on to make clear that physician-investigator workforce development is everyone's problem.
Throughout the 14 Clinical Research Roundtable symposia and workshops held from June 2000 to September 2004, several common threads emerged, one of the most important among them being that the various stakeholder groups can each play a role in systematically addressing the challenges in American clinical research. In a report by Sung and colleagues entitled "Central Challenges Facing the National Clinical Research Enterprise" (6), authors and roundtable participants described the two great translational blocks: translation of basic science discoveries into clinical studies and translation of clinical study results into medical practice and health policy. The four central challenges the authors said must be addressed to overcome these translational blocks are (a) enhancement of public participation in clinical research, (b) development of information systems, (c) an adequately trained workforce, and (d) funding. A description of each challenge was followed by recommendations to specific stakeholder groups.
Concerning the main challenge of the four that is most germane to the present perspective, that of ensuring an adequately trained workforce, the authors cited the alarming statistics that only 8% of PIs conducting industry-sponsored clinical trials are under 40 years of age and that fewer than 4% of competing research grants awarded by NIH are awarded to investigators aged 35 years or younger. They went on to cite evidence that the number of physician-investigators is declining and listed several contributory factors, including debt borne by recent medical school graduates, length of clinical training, difficulty in securing research grants, uncertainty about promotion in academic health centers where basic science investigation may be more highly valued, and scarcity of experienced mentors. The authors did credit the NIH for demonstrating an impressive commitment to clinical research with its K23 (new investigators in patient-oriented research), K24 (midcareer investigators in patient-oriented research), and K30 awards for clinical research curriculum development in institutions across the United States but underscored the need for salary support for most trainees in the K30 programs.
Finally with respect to the challenge of ensuring an adequately trained workforce, Sung and colleagues (6) issued specific recommendations, including (a) expand educational loan repayment programs and eligibility (federal government); (b) increase opportunities for training in all areas of clinical research (academic health centers and research sponsors); (c) develop mentor-training systems for senior investigators, assign mentors to junior investigators, and reward effective mentors (academic health centers, professional societies); (d) develop criteria for excellence in clinical research and apply them in appointment and promotion (academic health centers, professional societies); and (e) ensure that providers apply clinical evidence to clinical practice and decision making (academic health centers, professional societies, health care delivery systems).
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THE RSNA CLINICAL TRIALS METHODOLOGY WORKSHOP |
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The idea for the workshop was first suggested more than 2 years ago to C. Leon Partain, MD, PhD, then chairman of the RSNA Research Development Committee (RDC), G. Scott Gazelle, MD, PhD, vice-chairman of the committee, and me by Daniel C. Sullivan, MD, RDC member and associate director of the Cancer Imaging Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute. Dr Sullivan's suggestion came from his participation several years in a row as a faculty member of a similarly conceived, highly successful workshop sponsored by the American Association for Cancer Research and the American Society of Clinical Oncology (AACR-ASCO), entitled "Methods in Clinical Cancer Research." He had been impressed that the intense week-long experience provided by the faculty of approximately 60 for a group of more than 100 "students" (finishing fellows and junior faculty) was indeed extraordinary and that the students did in fact manage to produce full protocols by the end of the week, complete with informed consent, biostatistical design, et cetera. The AACR-ASCO workshop, which has now completed its 11th year, is supported by educational grants from industry, as well as by a generous training grant from the National Cancer Institute.
The RSNA RDC quickly accepted Dr Sullivan's suggestion and proposed a radiology-oriented version of the workshop to the RSNA Board of Directors. The Board of Directors approved the concept and the appointments of Dr Sullivan and Constantine A. Gatsonis, PhD, of Brown University (Providence, RI) as workshop cochairmen. The cochairmen were asked to work with Linda B. Bresolin, PhD, MBA, CAE, RSNA Assistant Executive Director for Research and Education; with Dr Gazelle, the new RDC chairman; and with me on development of a specific proposal, complete with budget, to present to the RSNA Board of Directors for approval. A planning group was appointed and RSNA board approval of a more mature proposal was accomplished within a few months.
Detailed planning involved a year-and-a-half–long series of monthly conference calls of the planning committee, with frequent attention to lessons learned through participation in the AACR-ASCO workshop. Today I can say with certainty that my role as a faculty member at the AACR-ASCO workshop in 2005 gave me added perspective that proved valuable in planning the RSNA workshop. Others on the RSNA Clinical Trials Methodology Workshop planning committee with added perspective from the AACR-ASCO workshop included Dr Sullivan, C. Carl Jaffe, MD, of the NCI Cancer Imaging Program, and Bruce J. Hillman, MD, Chairman of the American College of Radiology Imaging Network. Other planning committee members who contributed to workshop development were Nancy Obuchowski, PhD, Elizabeth G. McFarland, MD, Diane Mitchell, James H. Thrall, MD, Anthony Shields, MD, PhD, Craig C. Beam, PhD, Etta D. Pisano, MD, Jeffrey G. Jarvik, MD, MPH, Curtis P. Langlotz, MD, PhD, Mitchell D. Schnall, MD PhD, Susan Clayton, Wendy Hayes, MD, Robert M. Califf, MD, and Bill Freeberg. Other RSNA staff who provided invaluable help and support in planning and conducting the workshop included Tracy Schmidt, Fiona Miller, Janet Cooper, and Lynn Beresoff.
Importantly, the RSNA set its sights on a smaller experience, with 25–30 students in the first workshop and a similar number of faculty. The period January 7–13, 2006, was chosen because it followed the RSNA Scientific Assembly and Annual Meeting and the holidays but preceded the February start of Spring semester course responsibilities of a number of our faculty. It was thought by the planning group that most faculty would not commit a week in the summer to such an intense workshop. It was also believed that mid-Spring courses are doomed to failure because of the many competing radiology meetings that occur at that time of year.
To participate, prospective students were required to compete by means of an online application process. Applications included an abstract of the proposed clinical research, an abbreviated curriculum vitae, and letter of support from the prospective student's department chair. Successful applicants were required to commit a full week to the workshop in Phoenix, and their departments were required to fund their travel and accommodations. There were no fees for course registration or materials. Meals were included with the workshop.
In the final planning stages, a small subcommittee divided the 25 accepted abstracts by topic into five protocol development groups (PDGs), which would each have five students and three to four faculty members, all of whom would work closely together in the afternoons throughout the week of the workshop. The principal aim of the PDGs was to help the students develop their complete protocols. PDG topics for the 2006 workshop included image-guided intervention, vascular imaging, oncology, musculoskeletal imaging, and miscellaneous. Faculty had the contact information for students and the opportunity to communicate with them in advance of the workshop to suggest specific preparations that could be made to enhance the upcoming weeklong experience. PDG faculty were nonuniform in their approach to this opportunity for the first workshop.
The workshop began on the afternoon and early evening of January 7, 2006, with the students taking a 40-question pretest compiled from the material to be presented in the didactic sessions throughout the week. A keynote address by Dr Hillman followed, and the first meetings of the PDGs then capped off the evening. In these first meetings, faculty listened to the students present their clinical research protocol ideas and were able to ascertain a great deal about the depth and type of assistance each student would need, as well as which students were likely to require a substantial change in direction.
Throughout the week, morning sessions consisted of didactic presentations on topics including study design, diagnostic technology assessment, evidence-based diagnosis, clinical studies of therapy, cost-effectiveness, regulatory issues, biostatistics, receiver operating characteristics analysis, biases, FDA regulatory matters, outcomes analysis in diagnostic studies, reader studies, predictive value of tests, medical ethics, quality-of-life studies, imaging as a measure of therapeutic response, image-guided interventions, screening studies, sponsorship and economics of clinical trials, and more. Afternoons included PDG sessions, as well as break-out group discussions and prearranged one-on-one mentoring ("the doctor is in") sessions, for which students could sign up as the week progressed and their specific needs began to crystallize. In addition, Dr Jaffe conducted some special sessions on informatics tools for protocol development. Evenings were devoted to protocol development by individual students. The resource room at the workshop, which was in physical proximity to the main lecture hall, offered computer stations, Internet access, printing, and RSNA staff support.
The milestones (due dates) for the students throughout the week were as follows: final concept sheets due on Sunday night (January 8), draft protocols due Tuesday night (January 10), draft informed consent due Wednesday evening (January 11), posttest taken Thursday evening (January 12), and completed protocols due and workshop adjourns Friday morning (January 13). At each stage throughout the week, the faculty were each required to review the work product of each student and to make specific suggestions for improvement of the protocols (eg, background, specific aims, hypotheses, research methods, biostatistical design, informed consent). This was accomplished on paper and in conversation at the PDG sessions. Each faculty member and student had a mail slot outside of the resource room to facilitate the exchange of information throughout the week. Almost every student produced a protocol by week's end that could be fine-tuned into a document for submission to a local institutional review board. Many of these were well suited for later transition to a multi-institutional phase, with possibilities for funding through the American College of Radiology Imaging Network or other mechanisms.
By the end of the workshop, faculty and students alike were convinced of the uniqueness and power of the experience to which they had been treated. After all, where else could one possibly go for a week to take full advantage of a wide range of clinical research expertise and concentrated time to succeed in producing an implementable clinical research protocol?
Early each morning throughout the week, planned faculty breakfast meetings were held in advance of the didactic sessions to discuss problems that surfaced during the workshop and to suggest solutions and ideas for future workshop planning. A final faculty meeting at the end of the week was used to collect final overall impressions of the workshop and additional specific suggestions from the faculty. Not surprisingly, important ideas emerged concerning (a) enhancing the awareness of the workshop among radiologists through a variety of media, (b) standardizing the preworkshop experience of the students (preparatory materials, mentorship questions and suggestions, familiarization with local institutional review board processes, and specific contacts and discussions with colleagues in related or referring disciplines on accrual and related clinical issues), (c) shortening or lengthening certain parts of the program and eliminating and adding others, and (d) postworkshop follow-up metrics.
Under Dr Gazelle's chairmanship of the RDC and with the assistance of RSNA staff, Drs Sullivan and Gatsonis are already well along in planning the 2007 RSNA Clinical Trials Methodology Workshop. More information can be found at http://www.rsna.org/CT2007. Through these workshops, the RSNA is addressing head-on the challenge of ensuring an adequately trained workforce of clinical investigators to overcome the translational blocks identified by the Clinical Research Roundtable. I am proud to have been a part of the development and implementation of this new, exciting, and extraordinary RSNA activity.
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FOOTNOTES |
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