A Structured Approach to Optimizing Animal Model Selection for Human Translation: The Animal Model Quality Assessment.

Animal studies in pharmaceutical drug discovery are common in preclinical research for compound evaluation before progression into human clinical trials. However, high rates of drug development attrition have prompted concerns regarding animal models and their predictive translatability to the clinic. To improve the characterization and evaluation of animal models for their translational relevance, the authors developed a tool to transparently reflect key features of a model that may be considered in both the application of the model but also the likelihood of successful translation of the outcomes to human patients. In this publication, we describe the rationale for the development of the Animal Model Quality Assessment tool, the questions used for the animal model assessment, and a high-level scoring system for the purpose of defining predictive translatability. Finally, we provide an example of a completed Animal Model Quality Assessment for the adoptive T-cell transfer model of colitis as a mouse model to mimic inflammatory bowel disease in humans.

Recommended Guidelines for Developing, Qualifying, and Implementing Complex In Vitro Models (CIVMs) for Drug Discovery.

The pharmaceutical industry is continuing to face high research and development (R&D) costs and low overall success rates of clinical compounds during drug development. There is an increasing demand for development and validation of healthy or disease-relevant and physiological human cellular models that can be implemented in early-stage discovery, thereby shifting attrition of future therapeutics to a point in discovery at which the costs are significantly lower. There needs to be a paradigm shift in the early drug discovery phase (which is lengthy and costly), away from simplistic cellular models that show an inability to effectively and efficiently reproduce healthy or human disease-relevant states to steer target and compound selection for safety, pharmacology, and efficacy questions. This perspective article covers the various stages of early drug discovery from target identification (ID) and validation to the hit/lead discovery phase, lead optimization, and preclinical safety. We outline key aspects that should be considered when developing, qualifying, and implementing complex in vitro models (CIVMs) during these phases, because criteria such as cell types (e.g., cell lines, primary cells, stem cells, and tissue), platform (e.g., spheroids, scaffolds or hydrogels, organoids, microphysiological systems, and bioprinting), throughput, automation, and single and multiplexing endpoints will vary. The article emphasizes the need to adequately qualify these CIVMs such that they are suitable for various applications (e.g., context of use) of drug discovery and translational research. The article ends looking to the future, in which there is an increase in combining computational modeling, artificial intelligence and machine learning (AI/ML), and CIVMs.

Experiential learning of systems-based practice: a hands-on experience for first-year medical residents.

Systems-based practice, a domain of expertise mandated for all residencies by the Accreditation Council for Graduate Medical Education, requires an interdisciplinary approach that involves communicating with the other members of the health care team as well as utilizing the many components of health care delivery. The Mercy Catholic Medical Center internal medicine residency leadership developed a two-week supervised experience in systems-based practice for first-year medical residents to give them firsthand experience with nonphysician providers' delivery of health care. The disciplines in the experience were home care services, hospice care, pharmacy services, laboratory services, utilization services, and nutrition services. Nonphysician health care providers willingly made themselves available for this educational activity because they felt that such face-to-face interaction fosters an improved understanding of their discipline and its services in the participating physicians. Surveys of resident knowledge pre- and postworkshop suggested that the residents' rudimentary understanding of these disciplines developed into both a deeper theoretical understanding and a greater knowledge of specific policies regarding these health care services. This type of experience is likely a necessary first step toward developing physicians who can provide interdisciplinary medical care that integrates the many other health care disciplines into a comprehensive plan to maximize health outcomes. As physicians become leaders of multidisciplinary teams in the 21st century, firsthand knowledge of the other health services enhances their capacity to maximize the services of these other disciplines for the benefit of patient care.