Clinical pharmacogenomics and transcriptional profiling in early phase oncology clinical trials.

Microarray-based expression profiling studies in the field of oncology have demonstrated encouraging correlations between tumor transcriptional profiles and eventual patient outcomes. These findings have fueled great interest in the application of transcriptional profiling to samples available from real-time clinical trials, and clinical pharmacogenomic objectives utilizing transcriptional profiling strategies are becoming increasingly incorporated into clinical trial study designs. Over the last few years several retrospective studies based on the profiling of archival tumor tissues suggest that transcriptional analysis of oncology samples may provide general prognosis measures, and in some cases may even predict response to specific therapies. Recently the FDA released a voluntary genomic data guidance meant to assist both regulatory agencies and pharmaceutical companies alike in evaluating the potential benefit of implementing expression profiling studies during the preclinical and clinical phases of drug development. Despite the great promise afforded by this technology, the ultimate benefit of applying transcriptional profiling in prospective clinical trials has yet to be realized because a number of practical impediments to this process exist. The multi-fold purpose of the current review is to highlight the increasing evidence from studies that have identified transcriptional signatures in archived tumors prognostic of patient outcome, to describe some of the drivers for the implementation of transcriptional profiling strategies in real-time drug development, to discuss the use of transcriptional profiling in the context of increasingly complex translational medicine strategies, and to highlight the practical issues and potential approaches involved in the successful application of clinical pharmacogenomic objectives during real-time clinical trials. Strategic implementation of transcriptional profiling in early oncology clinical trials can provide an opportunity to identify predictive markers of clinical response and eventually provide a substantial step forward towards the era of personalized medicine.

Recommendations from the Investigational New Drug/Investigational Device Exemption Task Force of the clInical and Translational Science Award Consortium: developing and implementing a sponsor-investigators training program.

OBJECTIVE: The objective of this study was to provide recommendations for provision of training for sponsor and investigators at Academic Health Centers. BACKGROUND: A subgroup of the Investigational New Drug/Investigational Device Exemption (IND/IDE) Task Force of the Clinical and Translational Science Award (CTSA) program Regulatory Knowledge Key Function Committee was assembled to specifically address how clinical investigators who hold an IND/IDE and thus assume the role of sponsor-investigators are adequately trained to meet the additional regulatory requirements of this role. METHODS: The participants who developed the recommendations were representatives of institutions with IND/IDE support programs. Through an informal survey, the task force determined that a variety and mix of models are used to provide support for IND/IDE holders within CTSA institutions. In addition, a CTSA consortium-wide resources survey was used. The participants worked from the models and survey results to develop consensus recommendations to address institutional support, training content, and implementation. RECOMMENDATIONS: The CTSA IND/IDE Task Force recommendations are as follows: (1) Institutions should assess the scope of Food and Drug Administration-regulated research, perform a needs analysis, and provide resources to implement a suitable training program; (2) The model of training program should be tailored to each institution; (3) The training should specifically address the unique role of sponsor-investigators, and the effectiveness of training should be evaluated regularly by methods that fit the model adopted by the institution; and (4) Institutional leadership should mandate sponsor-investigator training and effectively communicate the necessity and availability of training.

The critical need for academic health centers to assess the training, support, and career development requirements of clinical research coordinators: recommendations from the Clinical and Translational Science Award Research Coordinator Taskforce.

Clinical Research Coordinators (CRCs) are a vital component of the clinical research enterprise providing a pivotal role in human subject protection through the numerous activities and responsibilities assigned to them. In 2006, the National Institutes of Health's National Center for Research resources (NCRR) implemented the Clinical and Translational Science Awards program (CTSA) to advance biomedical research. As a part of this endeavor, many workgroups were formed among the Consortium to support translational research. The Research Coordinator Taskforce was created as part of the Regulatory Knowledge group of the Clinical Research Innovation Key Function Committee, and focuses on enhancing CTSA capabilities to provide support and training for CRCs. In the spring of 2008, this taskforce conducted two surveys of the then 24 CTSA Consortium members to better understand the current expectations and responsibilities of research coordinators in addition to the mechanism for providing education, training, and support in order for CRCs to successfully meet the study responsibilities placed upon them. The results of these surveys are summarized in this article and provide context to the recommendations of the Research Coordinator Taskforce for institutional considerations, approaches, and best practices for providing education, training, and support the expanding role of CRCs in fulfilling their responsibilities delegated to them by investigators.

Support for investigator-initiated clinical research involving investigational drugs or devices: the Clinical and Translational Science Award experience.

PURPOSE: Investigator-initiated research involving investigational drugs and devices is key to improving health. However, this requires the investigator to serve as a "sponsor-investigator," which can be complex and overwhelming. The Investigational New Drug/Investigational Device Exemption (IND/IDE) Taskforce of the Clinical and Translational Science Award (CTSA) consortium carried out a survey to examine how academic health centers (AHCs) assist sponsor-investigators with regulatory responsibilities. METHOD: The 24 CTSA centers existing in 2008 were surveyed regarding regulatory oversight and support for sponsor-investigators. Responses were analyzed by descriptive statistics. The evaluation of survey responses yielded three models of institutional support/oversight. RESULTS: Nineteen centers and one affiliate responded. Eleven (55%) reported having an IND/IDE support office, increased from five (25%) prior to their CTSA award. The volume of investigator-initiated IND/IDE research was highly variable (measured by numbers of investigators, IND/IDE applications, and studies). Oversight, if done, was provided by either the IND/IDE office or elsewhere in the institution. Most IND/IDE offices assisted with IND/IDE submissions and preparation for external audits. Half reported advanced training for sponsor-investigators. Almost all reported a goal to increase IND/IDE research. Important issues include the need for robust training of investigator/staff, appropriate determination of IND-exempt research, and sufficient support for preparing IND/IDE applications. CONCLUSIONS: Investigator-initiated research involving IND/IDEs is essential, but complex. AHCs should examine how they support sponsor-investigators in meeting the complex requirements. A model of either expert consultation/support or full service will minimize risks to participants and institutions, and regulatory noncompliance.