- Email: [email protected]
Will 2008 Mark the Start of A New Clinical Trial Era in Gastroenterology?
Comment From the Editors Will 2008 Mark the Start of A New Clinical Trial Era in Gastroenterology?
T
he randomized trial is the “gold standard” design for most clinical research questions related to efficacy of clinical interventions. However, there are numerous barriers to the conduct of such studies. Clinical trials typically require a complex infrastructure to ensure data quality and patient safety. Additionally, there are many regulatory hurdles. Clinical trials also consume huge amounts of resources, both in terms of absolute dollar costs and time commitments. Recruitment of a sufficient number of patients is often among the greatest challenges faced by investigators. To help achieve sufficient sample sizes, many clinical trials are conducted across multiple centers. However, this serves to further increase the intrinsic complexity and expense of these trials. Despite the large number of diseases encompassed by Gastroenterology, the field lags behind others in terms of conduct of clinical trials. A recent search of www.clinicaltrials. gov (December 22, 2007) identified 65 open clinical trials targeting patients with Crohn’s diseases, 44 with ulcerative colitis, 130 with hepatitis C, 89 with hepatitis B, 16 with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis, 69 with cirrhosis, 23 with peptic ulcer disease, 24 with colon polyps, and 2 with celiac disease. By contrast, there were 135 open studies targeting patients with rheumatoid arthritis, 155 with heart attacks, 239 with congestive heart failure, 515 with AIDS, and 1,075 with lymphoma. Recently, several important strategies have been implemented at the National Institutes of Health (NIH) that will impact the potential for future clinical trials in Gastroenterology. The Clinical and Translational Science Awards (CTSA) are designed to facilitate the translation of research find-
ings from the bench to the bedside and from the bedside to populations. Currently, there are 24 funded centers within 18 states. By 2012, it is anticipated that 60 centers will be funded. The funded centers are expected to ultimately function as a consortium that will redefine how collaborative translational research is conducted. The goals are to “encourage the development of new methods and approaches to clinical and translational research, improve training and mentoring to ensure that new investigators can navigate the increasingly complex research system, design new and improved clinical research informatics tools, assemble interdisciplinary teams that cover the complete spectrum of medical research, and forge new partnerships with private and public health care organizations” (http:// www.ctsaweb.org/index.cfm). An obvious byproduct of the CTSA program will be the identification and testing of new therapeutics. However, the CTSA alone are not sufficient to ensure the execution of high-quality clinical trials that define new effective therapies and optimal treatment strategies. Rather, such studies require large-scale grants from the NIH that are specific to the study. Competition for such grants is highly challenging. An investigator is expected to convince the review committee that a proposed study is novel, well designed, and able to be accomplished in the timeline supported by the grant. Even with a novel idea, emerging investigators can struggle to convince reviewers that the study is well designed and able to be accomplished. Supporting evidence may include completion of appropriate preliminary studies and development of a complete research protocol, manual of procedures, data and safety monitoring plan, data management system, case report forms, training materials, and other materials. In my personal experience, developing such materials for a complicated, multicenter clinical trial requires a year or more of
part-time work by the principal investigator and full-time work by support staff. This substantial burden of proof demanded by review committees may serve as a disincentive for potential grantees to pursue such funding. Understanding this predicament, the NIH recently announced the new NIDDK Multi-Center Clinical Study Implementation Planning Grants (U34) (PAR-08-057). The U34 grant mechanism will provide up to 2 years of funding of up to $250,000 per year in direct costs to fund such activities in preparation for a clinical trial. As stated in the announcement (http://grants.nih. gov/grants/guide/pa-files/PAR-08057.html), this funding mechanism will: 1. permit early peer review of the rationale for the proposed clinical study; 2. permit assessment of the design/ protocol of the proposed study; 3. provide support for the development of a complete study protocol and associated documents including a manual of operations; and 4. support the development of other essential elements required for the conduct of a clinical study. Completion of the required products of a U34 grant is a prerequisite for submission of a multicenter clinical study cooperative agreement (U01) application, which will support the actual conduct of the study. Identification of optimal treatment strategies should be a top priority of our profession. To accomplish this mission, collaborations will be imperative at all levels. The CTSA program and the new U34 grant mechanism were created specifically to facilitate such collaborations. Hopefully, these new programs will herald a new order of clinical trials in gastrointestinal diseases. JAMES D. LEWIS, MD, MSCE doi:10.1053/j.gastro.2008.03.030
GASTROENTEROLOGY 2008;134:1289
T
he randomized trial is the “gold standard” design for most clinical research questions related to efficacy of clinical interventions. However, there are numerous barriers to the conduct of such studies. Clinical trials typically require a complex infrastructure to ensure data quality and patient safety. Additionally, there are many regulatory hurdles. Clinical trials also consume huge amounts of resources, both in terms of absolute dollar costs and time commitments. Recruitment of a sufficient number of patients is often among the greatest challenges faced by investigators. To help achieve sufficient sample sizes, many clinical trials are conducted across multiple centers. However, this serves to further increase the intrinsic complexity and expense of these trials. Despite the large number of diseases encompassed by Gastroenterology, the field lags behind others in terms of conduct of clinical trials. A recent search of www.clinicaltrials. gov (December 22, 2007) identified 65 open clinical trials targeting patients with Crohn’s diseases, 44 with ulcerative colitis, 130 with hepatitis C, 89 with hepatitis B, 16 with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis, 69 with cirrhosis, 23 with peptic ulcer disease, 24 with colon polyps, and 2 with celiac disease. By contrast, there were 135 open studies targeting patients with rheumatoid arthritis, 155 with heart attacks, 239 with congestive heart failure, 515 with AIDS, and 1,075 with lymphoma. Recently, several important strategies have been implemented at the National Institutes of Health (NIH) that will impact the potential for future clinical trials in Gastroenterology. The Clinical and Translational Science Awards (CTSA) are designed to facilitate the translation of research find-
ings from the bench to the bedside and from the bedside to populations. Currently, there are 24 funded centers within 18 states. By 2012, it is anticipated that 60 centers will be funded. The funded centers are expected to ultimately function as a consortium that will redefine how collaborative translational research is conducted. The goals are to “encourage the development of new methods and approaches to clinical and translational research, improve training and mentoring to ensure that new investigators can navigate the increasingly complex research system, design new and improved clinical research informatics tools, assemble interdisciplinary teams that cover the complete spectrum of medical research, and forge new partnerships with private and public health care organizations” (http:// www.ctsaweb.org/index.cfm). An obvious byproduct of the CTSA program will be the identification and testing of new therapeutics. However, the CTSA alone are not sufficient to ensure the execution of high-quality clinical trials that define new effective therapies and optimal treatment strategies. Rather, such studies require large-scale grants from the NIH that are specific to the study. Competition for such grants is highly challenging. An investigator is expected to convince the review committee that a proposed study is novel, well designed, and able to be accomplished in the timeline supported by the grant. Even with a novel idea, emerging investigators can struggle to convince reviewers that the study is well designed and able to be accomplished. Supporting evidence may include completion of appropriate preliminary studies and development of a complete research protocol, manual of procedures, data and safety monitoring plan, data management system, case report forms, training materials, and other materials. In my personal experience, developing such materials for a complicated, multicenter clinical trial requires a year or more of
part-time work by the principal investigator and full-time work by support staff. This substantial burden of proof demanded by review committees may serve as a disincentive for potential grantees to pursue such funding. Understanding this predicament, the NIH recently announced the new NIDDK Multi-Center Clinical Study Implementation Planning Grants (U34) (PAR-08-057). The U34 grant mechanism will provide up to 2 years of funding of up to $250,000 per year in direct costs to fund such activities in preparation for a clinical trial. As stated in the announcement (http://grants.nih. gov/grants/guide/pa-files/PAR-08057.html), this funding mechanism will: 1. permit early peer review of the rationale for the proposed clinical study; 2. permit assessment of the design/ protocol of the proposed study; 3. provide support for the development of a complete study protocol and associated documents including a manual of operations; and 4. support the development of other essential elements required for the conduct of a clinical study. Completion of the required products of a U34 grant is a prerequisite for submission of a multicenter clinical study cooperative agreement (U01) application, which will support the actual conduct of the study. Identification of optimal treatment strategies should be a top priority of our profession. To accomplish this mission, collaborations will be imperative at all levels. The CTSA program and the new U34 grant mechanism were created specifically to facilitate such collaborations. Hopefully, these new programs will herald a new order of clinical trials in gastrointestinal diseases. JAMES D. LEWIS, MD, MSCE doi:10.1053/j.gastro.2008.03.030
GASTROENTEROLOGY 2008;134:1289