1. Principals of Biomedical Research Guri Tzivion, PhD tzivion@windsor.edu Extension 506 PBMR 611: Winter 2016 Windsor University School of Medicine

2. PBMR 611 MDII: Principals of Biomedical Research Class 2 Introduction to Biomedical Research PBMR 611 MDII: Principals of Biomedical Research Class 2 Introduction to Biomedical Research 2. Biomedical research types: basic, clinical and epidemiological research

3. Biomedical Sciences Biomedical sciences are a set of applied sciences, applying portions of natural science or formal science, or both, to developing knowledge, interventions, or technologies of use in healthcare or in public health

4. Biomedical Research Biomedical research, or experimental medicine, includes basic, applied, translational and clinical research aimed at developing and enhancing our knowledge in the field of medicine

5. Biomedical Research Biomedical research types: Basic and Preclinical Research Basic and Preclinical Research Clinical Research and Applied or Translational Research Clinical Research and Applied or Translational Research

6. Basic Biomedical Research Basic biomedical research is defined as research that tackles the most fundamental areas of medical research including, but not limited to: Cellular and Molecular Biology Cellular and Molecular Biology Medical Genetics Medical Genetics Immunology Immunology Medical Biochemistry Medical Biochemistry Physiology Physiology

7. Basic Biomedical Research Aims to establish an understanding of the cellular, molecular and physiological mechanisms underpinning human health and disease. Since many organisms share a common evolutionary history with humans and hence common features and systems, the basic end of medical research shades into basic biology and vice versa.

8. Basic Biomedical Research: Preclinical Research Pre-clinical research covers research that prepares the ground for clinical research with patients. Typically the work requires no ethical approval (though some work with animals does), is supervised by people with PhDs rather than medical doctors, and is carried out in a university or company rather than a hospital. It includes also the preclinical phase of drug testing.

9. Clinical Research Clinical research is carried out with patients. It is generally supervised by doctors in a medical setting such as a hospital and requires ethical approval and IRB (Institutional Review Board). The clinical phase of drug testing is covered by Clinical Trials.

10. Clinical Research Clinical studies include the formulation of trials and experiments, as well as observational studies in medical, clinical and other types of research (e.g., epidemiological) involving human beings. The goal of a clinical study is to assess the safety, efficacy, and/or the mechanism of action of an investigational medicinal product, or new drug or device that is in development, but not yet approved by a health authority (e.g. FDA).

11. Clinical Research Outline of types of designs for clinical studies: Treatment studies: randomized controlled trials: includes blinded and non-blinded trials. Treatment studies: randomized controlled trials: includes blinded and non-blinded trials. Observational studies: includes prospective and retrospective cohort studies Observational studies: includes prospective and retrospective cohort studies Epidemiological studies Epidemiological studies

12. Journal Club 1 st theme: longevity research and sirtuin activators 1.Howitz KT, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003 Sep 11;425(6954):191-6. 2.Baur JA, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16;444(7117):337-42. 3.Hubbard BP and Sinclair DA. Small molecule SIRT1 activators for the treatment of aging and age-related diseases. Trends Pharmacol Sci. 2014 Mar;35(3):146- 54.

13. Journal Club 1 st theme: longevity research and sirtuin activators 1.Howitz KT, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003 Sep 11;425(6954):191-6. 2.Baur JA, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16;444(7117):337-42. 3.Hubbard BP and Sinclair DA. Small molecule SIRT1 activators for the treatment of aging and age-related diseases. Trends Pharmacol Sci. 2014 Mar;35(3):146- 54.

14. Journal Club 2 nd theme: B-Raf mutations and their targeting in Melanoma 4.Davies H, et al. Mutations of the BRAF gene in human cancer. Nature. 2002 Jun 27;417(6892):949-54. 5.Tsai J, et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3041-6. 6.Bollag G, et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature. 2010 Sep 30;467(7315):596-9. 7.Sosman JA et al. Survival in BRAF V600–Mutant Advanced Melanoma Treated with Vemurafenib. N Engl J Med 2012; 366:707-714. Full text link: http://www.nejm.org/doi/full/10.1056/NEJMoa1112302

15. Journal Club 3 rd theme: Diabetes and high cholesterol management 8.Knowler WC, et al. "Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin". The New England Journal of Medicine. 2002. 346(6):393-403 Full text link: http://www.nejm.org/doi/full/10.1056/NEJMoa012512 9.Patel A, et al. "Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes". The New England Journal of Medicine. 2008. 358(24):2560- 2572. Full text link: http://www.nejm.org/doi/full/10.1056/NEJMoa0802987 10. Kastelein JJ, et al. "Simvastatin with or without ezetimibe in familial hypercholesterolemia". The New England Journal of Medicine. 2008. 358(14):1431-1443. Full text link: http://www.nejm.org/doi/full/10.1056/NEJMoa0800742

16. Course Description Journal Club: 10 research papers will be assigned, covering all aspects of biomedical research, including basic, clinical and epidemiological research 10 research papers will be assigned, covering all aspects of biomedical research, including basic, clinical and epidemiological research Each student will present one paper Each student will present one paper All students are required to read the weekly papers and are expected to actively participate in group discussions All students are required to read the weekly papers and are expected to actively participate in group discussions

17. Journal Club Presentation format: Introduction to the subject area: Introduction to the subject area:  General review of the subject  What was known before the authors started their work The declared hypothesis and objectives of the study The declared hypothesis and objectives of the study Methodologies used in the study Methodologies used in the study Results: Results:  Present the actual results of the study  Discuss each of the figures in detail

18. Journal Club Presentation format: Discuss the significance of the study and its contributions to advancing the subject area/field (as presented by the authors) Discuss the significance of the study and its contributions to advancing the subject area/field (as presented by the authors) Your critical analysis of the study: Your critical analysis of the study:  Strengths and weaknesses  If you were the reviewer of the paper, what would be your critique?

19. Journal Club Other points to consider in preparing your presentation: Have a simple title for each slide Have a simple title for each slide Fonts should be large enough to be seen clearly from the back of the room Fonts should be large enough to be seen clearly from the back of the room Figures: for multi-panel figures, enlarge and show each panel separately Figures: for multi-panel figures, enlarge and show each panel separately

20. Journal Club Presentation skills: Be familiar with the presentation content Be familiar with the presentation content Speak loudly and clear Speak loudly and clear Speak with excitement, don’t be monotone Speak with excitement, don’t be monotone Do not read the slides – use the text as reference Do not read the slides – use the text as reference Face the audience, make eye contacts Face the audience, make eye contacts Use body language (facial expression, gesture) Use body language (facial expression, gesture) Do not abuse the pointer Do not abuse the pointer

21. Journal Club Presentation evaluation grid: Familiarity with the subject (20%): Familiarity with the subject (20%): Presentation skills (20%): Presentation skills (20%): Stimulation of group discussion (20%): Stimulation of group discussion (20%): Preparedness (20): Preparedness (20): Overall presentation quality (20): Overall presentation quality (20): Final evaluation: Final evaluation: Comments for the student: Comments for the student:

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