NIH workshop on clinical translation of molecular imaging probes and technology--meeting report.

A workshop on "Clinical Translation of Molecular Imaging Probes and Technology" was held August 2, 2013 in Bethesda, Maryland, organized and supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB). This workshop brought together researchers, clinicians, representatives from pharmaceutical companies, molecular probe developers, and regulatory science experts. Attendees met to talk over current challenges in the discovery, validation, and translation of molecular imaging (MI) probes for key clinical applications. Participants also discussed potential strategies to address these challenges. The workshop consisted of 4 sessions, with 14 presentations and 2 panel discussions. Topics of discussion included (1) challenges and opportunities for clinical research and patient care, (2) advances in molecular probe design, (3) current approaches used by industry and pharmaceutical companies, and (4) clinical translation of MI probes. In the presentations and discussions, there were general agreement that while the barriers for validation and translation of MI probes remain high, there are pressing clinical needs and development opportunities for targets in cardiovascular, cancer, endocrine, neurological, and inflammatory diseases. The strengths of different imaging modalities, and the synergy of multimodality imaging, were highlighted. Participants also underscored the continuing need for close interactions and collaborations between academic and industrial partners, and federal agencies in the imaging probe development process.

Workshop on using natural language processing applications for enhancing clinical decision making: an executive summary.

In April 2012, the National Institutes of Health organized a two-day workshop entitled 'Natural Language Processing: State of the Art, Future Directions and Applications for Enhancing Clinical Decision-Making' (NLP-CDS). This report is a summary of the discussions during the second day of the workshop. Collectively, the workshop presenters and participants emphasized the need for unstructured clinical notes to be included in the decision making workflow and the need for individualized longitudinal data tracking. The workshop also discussed the need to: (1) combine evidence-based literature and patient records with machine-learning and prediction models; (2) provide trusted and reproducible clinical advice; (3) prioritize evidence and test results; and (4) engage healthcare professionals, caregivers, and patients. The overall consensus of the NLP-CDS workshop was that there are promising opportunities for NLP and CDS to deliver cognitive support for healthcare professionals, caregivers, and patients.

Moving toward multimedia electronic health records: how do we get there?

This report, based on a workshop jointly sponsored the National Institute of Biomedical Imaging and Biomedical Engineering and the Office of the National Coordinator for Health Information Technology, examines the role and value of images as multimedia data in electronic health records (EHRs). The workshop, attended by a wide range of stakeholders, was motivated in part by the absence of image data from discussions of meaningful use of health information technology. Collectively, the workshop presenters and participants argued that images are not ancillary data and should be central to health information systems to facilitate clinical decisions and higher quality, efficiency, and safety of care. They emphasized that the imaging community has already developed standards that form the basis of interoperability. Despite the apparent value of images, workshop participants also identified challenges and barriers to their implementation within EHRs. Weighing the opportunities and challenges, workshop participants provided their perspectives on possible paths forward toward fully multimedia EHRs.

Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer.

Rapamycin was discovered more than thirty years ago from a soil sample from the island of Rapa Nui. It was isolated from Streptomyces hygroscopicus and initial characterization focused on its antifungal activities. Subsequent characterization showed that it has immunosuppressive properties and has been used successfully to reduce organ rejection with kidney transplantation. Rapamycin has proven to be a versatile compound with several seemingly unrelated properties, including antifungal, immunosuppressive, and anticancer. The National Cancer Institute (NCI) Developmental Therapeutics Program demonstrated that rapamycin inhibited cell growth in tumor cell lines. These observations stimulated research to explore the underlying mechanism of anti-tumor activities. Cell growth inhibition involves binding to the mammalian Target of Rapamycin (mTOR). The mTOR signaling pathway is critical to cell growth, proliferation, and survival and rapamycin inhibits these hallmark processes of cancer. Binding of growth factors activates mTOR signaling, which in turn leads to downstream phosphorylation of protein kinases, e.g., p70S6 kinase and lipid kinases in the phosphorylation of phosphoinositides. Understanding of mTOR signaling provided the biological basis for targeted chemotherapeutics development, including several rapamycin analogues for treating breast and other cancers.

Issues in regulatory guidelines for data monitoring committees.

As clinical trials have emerged as the major research method for evaluating new interventions, the process for monitoring intervention safety and benefit has also evolved. The Data Monitoring Committee (DMC) has become the standard approach to implement this responsibility for many Phase III trials. Recent draft guidelines on the operation of DMCs by the Food and Drug Administration (FDA) have raised issues that need further clarification or discussion, especially for industry sponsored trials. These include, the time when DMCs are needed, the role of the independent statistician to support the DMC, and sponsor participation at DMC meetings. This paper provides an overview of these issues, based on the discussions at the January, 2003 workshop sponsored by Duke Clinical Research Institute.