1. CHP400: Community Health Program - lI Research Methodology STUDY DESIGNS Observational / Analytical Studies Present: Disease Past: Exposure Cross - section Cohort Case - control Present: Disease & Exposure Present: Exposure Future: Disease nbmmb Time is Key Clinical trial 

2. STUDY DESIGNS Research Methodology Clinical trials Experimental studies  Definition &rationale  Types of Trials  Phases of Clinical Trials  Steps of clinical trial Develop the study concept Prepare a protocol for the study Protect participants Conduct and Monitor the study Analyze study data and interpret the results Communicate the results Content

3. STUDY DESIGNS Experimental Observational Animal Experiment Human Intervention Clinical trial Analytical Case control Descriptive Case report Case series Cross section Ecological Cohort Research Methodology Clinical trial

4. History Perhaps the first ever clinical trial was James Lind’s demonstration in 1753 that citrus fruits cured scurvy. He compared the effects of various different acidic substances ranging from vinegar to cider, on groups of sailors, and found that the group who were given oranges and lemons had largely recovered from scurvy after 6 days. Clinical trials

5. A planned experiment on humans. The setting is usually a health institutions and it usually involves patients. Rationale: Before a new treatment method is made available to the public it must be studied and tested for safety and effectiveness. Clinical trials Definition

6. Clinical trials Treatment Prevention Diagnostic Screening Quality of Life Types of Trials

7. Treatment Trials New treatments for that disease? Most effective treatment for that disease?

8. Phases of Clinical Trials Most trials that involve new drugs go through a series of steps: 1: Experiments in the laboratory 2: Once deemed safe, go through 1-4 phases

9. N 20 –100 Up to several 100s Phase II 100s – several 1000s Phase III Phase I Length Several months Several months- 2 yrs. 1-4 yrs. Safety, dosage & effectiveness Short term safety; mainly effectiveness Mainly Safety Purpose % Drugs SuccessfullyTested 70% 33% 25-30% Phases of Clinical Trials

10. Prepare a protocol for the study Protect participants Conduct and Monitor the study Analyze study data and interpret the results Communicate the results Develop the study concept Steps of clinical trial

11.  Develop the study concept Review current research Formulate hypothesis Providing the evidence Review of the concept and feedback. Steps of clinical trial

12. Purpose, value and methods Eligibility and exclusion criteria Data to be gathered Study endpoints  Prepare a protocol for the study Steps of clinical trial Details of the therapy

13. Sample Intervention Control OUTCOMEOUTCOME  Prepare a protocol for the study Steps of clinical trial Follow up Reference Population Defining the study design

14.  Prepare a protocol for the study Randomized Controlled Trial (RCT) Difficulties with blinding Steps of clinical trial Single -Blind vs Double-Blind Studies

15. Clinical trials Investigational Group  Prepare a protocol for the study Steps of clinical trial Randomization

16.  Protect participants Informed consent Institutional Review Board Procedures and treatments/duration Tests Possible risks and benefits Steps of clinical trial Good Clinical Practice guidelines

17. Steps of clinical trial Benefits of participation in Clinical Trials: Early access to new treatments. Carefully and regularly monitor the patient’s progress by the medical team. Patients have a chance to help others. Active role in own health care.

18. Steps of clinical trial Risks of participation in Clinical Trials : Unpleasant, serious or even life threatening side effects. New treatments are not always better than, or even as good as, standard care. New treatments may not work for every patient

19. Steps of clinical trial  Conduct and Monitor the study Follows the study protocol Study team Detailed schedule for participant (what each visit involves) Ongoing monitoring to report adverse events

20.  Analyze data and interpret the results Type of analysis is dictated by goals and objectives Minimize bias and uncertainty Steps of clinical trial incomplete data terminology attrition specified analyses statistical analytic plan Analysis follows study protocol

21.  Analyze data and interpret the results Steps of clinical trial Relative Risk(RR): -------------------------------- RR= Total outcome Group NegativePositive a+bbaIntervention c+ddcControl Total Experimental Event Rate (EER) Control Event Rate (CER )

22.  Analyze study data and interpret the results Steps of clinical trial Relative Risk(RR): Total outcome Group SurvivalDeath 644618Ligation 653332Sclerotherapy Total -------------------------------- RR= Experimental Event Rate (EER) Control Event Rate (CER )

23.  Analyze data and interpret the results Steps of clinical trial Relative Risk(RR): ---------- RR= Experimental Event Rate (EER) Control Event Rate (CER ) Statistical power EER =a/(a+b) 18/64 CER = c/(c+d) 32/65 RR= = 0.57 -------------------------------- Total Outcome Group Surv ival Dea th 644618Ligation 653332Scleroth erapy =18/64 =32/65

24.  Communicate the results Steps of clinical trial with participants with the medical community with other researchers with the general public Sharing information

25.  Communicate the results Steps of clinical trial publishing a report community newsletter issuing a news release holding a news conference presenting at a meeting or conference publishing an abstract creating a brochure. Communicating study findings

26. Follow-up RQ: Does diet and exercise reduce risk of developing type 2 diabetes in persons with glucose intolerance? Design: Randomized trial Subjects: 2500 with glucose intolerance Intervention: low fat diet and moderate intensity aerobic exercise outcome = development of frank diabetes

27. Research Methodology Diet and Exercise to Prevent Diabetes in Persons with Glucose Intolerance DM No DM D&E No D& E 65560 125 500 625 625 1060190 1250 RR = 0.5; p = 0.001

28. Case reports Case series Case-control studies Randomized controlled studies Ecological studies Cross-sectional studies Cohort studies Generate hypotheses Establish causality Experimental studies STUDY DESIGNS Research Methodology Clinical trials

29. Conclusions & Take Home Message Clinical trials often yield important results that affect health and well being Must follow guidelines & protocol Must ensure well-being of participant Clinical trials are susceptible to human error either on part of investigator or patient Rank high in the ladder of causality