Browsing by Author "Clayburgh, Daniel"

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    Early, precise, and safe clinical evaluation of the pharmacodynamic effects of novel agents in the intact human tumor microenvironment
    (Frontiers Media, 2024-04-12) Gundle, Kenneth R.; Rajasekaran, Karthik; Houlton, Jeffrey; Deutsch, Gary B.; Ow, Thomas J.; Maki, Robert G.; Pang, John; Nathan, Cherie-Ann O.; Clayburgh, Daniel; Newman, Jason G.; Brinkmann, Elyse; Wagner, Michael J.; Pollack, Seth M.; Thompson, Matthew J.; Li, Ryan J.; Mehta, Vikas; Schiff, Bradley A.; Wenig, Barry I.; Swiecicki, Paul L.; Tang, Alice L.; Davis, Jessica L.; van Zante, Annemieke; Bertout, Jessica A.; Jenkins, Wendy; Turner, Atticus; Grenley, Marc; Burns, Connor; Frazier, Jason P.; Merrell, Angela; Sottero, Kimberly H. W.; Derry, Jonathan M. J.; Gillespie, Kate C.; Mills, Bre; Klinghoffer, Richard A.; Pathology and Laboratory Medicine, School of Medicine
    Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit). Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4–96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure. Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment. Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.
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    Safety Recommendations for Evaluation and Surgery of the Head and Neck During the COVID-19 Pandemic
    (AMA, 2020-03) Givi, Babak; Schiff, Bradley A.; Chinn, Steven B.; Clayburgh, Daniel; Iyer, N. Gopalakrishna; Jalisi, Scharukh; Moore, Michael G.; Nathan, Cherie-Ann; Orloff, Lisa A.; O'Neill, James P.; Parker, Noah; Zender, Chad; Morris, Luc G. T.; Davies, Louise; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Importance The rapidly expanding novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has challenged the medical community to an unprecedented degree. Physicians and health care workers are at added risk of exposure and infection during the course of patient care. Because of the rapid spread of this disease through respiratory droplets, health care workers who come in close contact with the upper aerodigestive tract during diagnostic and therapeutic procedures, such as otolaryngologists–head and neck surgeons, are particularly at risk. A set of safety recommendations was created based on a review of the literature and communications with physicians with firsthand knowledge of safety procedures during the COVID-19 pandemic. Observations A high number of health care workers were infected during the first phase of the pandemic in the city of Wuhan, China. Subsequently, by adopting strict safety precautions, other regions were able to achieve high levels of safety for health care workers without jeopardizing the care of patients. The most common procedures related to the examination and treatment of upper aerodigestive tract diseases were reviewed. Each category was reviewed based on the potential risk imposed to health care workers. Specific recommendations were made based on the literature, when available, or consensus best practices. Specific safety recommendations were made for performing tracheostomy in patients with COVID-19. Conclusions and Relevance Preserving a highly skilled health care workforce is a top priority for any community and health care system. Based on the experience of health care systems in Asia and Europe, by following strict safety guidelines, the risk of exposure and infection of health care workers could be greatly reduced while providing high levels of care. The provided recommendations, which may evolve over time, could be used as broad guidance for all health care workers who are involved in the care of patients with COVID-19.