1. Medical Research and Clinical Trials Rels 300 / Nurs 330 14 October 2015

2. What is a clinical trial? A research study designed to evaluate a new drug or medical therapy; e.g.,  compare a new drug or treatment with a commonly used (older) drug or treatment;  compare [a combination of a new drug + an older drug] with [the older drug alone]  compare different doses of a common drug, or different doses of a newly developed drug 300/330 - appleby 2

3. What else do I need to know?  Interventional study – participants receive specific interventions  Observational study – assess health outcomes in groups of participants  Adverse event – An unfavorable change in the health of a participant  Serious adverse event – An adverse event that results in death, is life-threatening, or incapacitating, or causes a congenital anomaly or birth defect  Placebo – A substance (or intervention) that does not contain active ingredients  Arm (or cohort) – A group or subgroup of participants  Masking (or blinding) – Whether none, or one, or both parties involved with the trial (such as the investigator or participant) know to which arm a person has been assigned. 300/330 - appleby 3

4. 4 Phases of clinical trials Phase 1 Trials Studies designed to assess safety and tolerability – Is this drug safe?  a small group of healthy volunteers are given the drug to see if there are safety issues or common side effects of a drug;  the healthy volunteers may be given various doses of the drug to see what dosages seem most tolerable;  different drug delivery methods may be tested;  sometimes, phase 1 trials are conducted on people for whom no standard treatment would be effective (can you think of an example of this?) 300/330 - appleby 4

5. 4 Phases of clinical trials Phase 2 Trials Studies designed to test the clinical efficacy of the drug – Does this drug work?  people who have the relevant condition or disease take the new drug;  some healthy volunteers also participate in this phase;  larger groups are tested;  continued testing for safety at different doses;  initial assessments of efficacy are made. 300/330 - appleby 5

6. 4 Phases of clinical trials Phase 3 Trials Studies designed to test the effectiveness of the new drug – Is the new drug more effective than existing treatments?  much larger numbers of patients and healthy volunteers are involved in studies;  tests efficacy of the new drug to:  prolong life or improve quality of life;  reduce the risk of disease recurrence;  be effective with fewer or milder side effects.  test safety of the new drug 300/330 - appleby 6

7. 4 Phases of clinical trials Phase 4 Trials Studies conducted after both safety and efficacy have been established Can this drug be used more effectively? Can this drug be used more effectively?  Very large group of study participants;  long-term adverse effects are studied;  dosage adjustments may be done to increase effectiveness or reduce side effects;  Can you think of a phase 4 study that resulted in the removal of a drug from the market? 300/330 - appleby 7

8. Let’s design a study The research question for this study will be: Do students who drink caffeinated beverages perform better on final exams? 1.Design a phase 1 study for this research; what will a phase 1 study be able to establish? 2.Design a phase 2 study ; what will a phase 2 study be designed to test? 3.Design a phase 3 study ; what do you want to accomplish with a phase 3 study? 4.If caffeine has passed in phase 3 studies, how would you design a phase 4 study of caffeine? 300/330 - appleby 8

9. Refine your research on caffeinated beverages Is this drug safe? Phase 1 : Is this drug safe? Does this drug work? Phase 2 : Does this drug work? Is the new drug more effective than existing treatments? Phase 3 : Is the new drug more effective than existing treatments? Can this drug be used more effectively? Is it useful for other conditions or purposes? Phase 4 : Can this drug be used more effectively? Is it useful for other conditions or purposes? 300/330 - appleby 9

10. Ethical analysis of placebo controlled studies Why do researchers use placebo controlled studies? What benefit do they provide for the clinical trial results? What concerns do ethicists have about placebo controlled studies? Are there potential patient risks in placebo studies? 300/330 - appleby 10

11. Tri-Council Policy Statement : TCPS Tri-Council Policy Statement : Ethical Conduct for Research Involving Humans 2 nd Edition, 2014 300/330 - appleby 11 http://www.pre.ethics.gc.ca/pdf/eng/tcps2- 2014/TCPS_2_FINAL_Web.pdf

12.  Canadian Institutes Of Health Research (CIHR)  The Natural Sciences And Engineering Research Council (NSERC)  The Social Sciences And Humanities Research Council (SSHRC) Panel on Research Ethics www.pre.ethics.gc.ca 300/330 - appleby 12

13. Respect for Human Dignity CORE ETHICAL PRINCIPLES “Respect for human dignity requires that research involving humans be conducted in a manner that is sensitive to the inherent worth of all human beings and the respect and consideration that they are due.” In this Policy, respect for human dignity is expressed through three core principles: 1.Respect for Persons 2.Concern for Welfare 3.Justice 300/330 - appleby 13

14. Ethical issues with Placebos “A clinical trial in which one or more intervention arms are compared with a placebo control group raises specific ethical issues. Where there is an established effective treatment, use of a placebo may deprive participants of needed therapy... [use] only in situations that do not compromise the safety and welfare of participants.” 300/330 - appleby 14

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16. Ch. 4, p.149: Clinical Equipoise is present when there is “a state of honest, professional disagreement in the community of expert clinicians as to the preferred treatment.” Does your research ethics case study involve withholding an effective remedy? Or giving one group an inactive substance or intervention? 300/330 - appleby 16 CLINICAL EQUIPOISE