Basic concept of clinical study

1. Basic concept of clinical study Vuthiphan Vongmongkol WeranuchWongwatanakul

2. Epidemiology Basic science of public health “The study of the distribution and determinants of health-related states or events in specified population and the application of this study to control of health problems” Last JM:A dictionary of Epidemiology,ed 2. New York, Oxford University Press,1988 Distribution (Prevalence, Incidence) Determinants (Risk factors, Causes of diseases) *Ram Ragsin, MD MPH DrPH Department of Military & Community Medicine Phramongkutklao College of Medicine

3. Research question in Epidemiology • Size of the problems • Prevalence of DM in the population • How many people don’t have adequate health care? • Association of the problems • Did the DM in this population related to education level? • Did those Whose do not have adequate health care relate to geographic region of residences? *Ram Ragsin, MD MPH DrPH Department of Military & Community Medicine Phramongkutklao College of Medicine

4. Measurements in Epidemiology • Size of the problems (Measuring the occurrence) • Prevalence • Incidence • Association of the Problems (Measuring the association) • Prevalence Rate Ratio ===> Cross-Sectional Study • Odds Ratio ===> Case-Control study • Relative Risk ===> Cohort study *Ram Ragsin, MD MPH DrPH Department of Military & Community Medicine Phramongkutklao College of Medicine

5. Rate • The central tool of Epidemiology is the comparison of RATES - Mortality Rate - Prevalence - Incidence

6. Prevalence “The number of existing case of disease at a particular point in time.”

7. Incidence (1) There are two ways of measuring • Cumulative incidence

8. Measuring the incidence (2) 2) Incidence density or Incidence rate • Adding “Time Dimension” into the denominator “Person-time” • person-month, person-year • 1 person-year = Following 1 person for 1 year period • 10 person-year = Following 1 person for 10 year period • or Following 10 persons for 1 year period *Ram Ragsin, MD MPH DrPH Department of Military & Community Medicine Phramongkutklao College of Medicine

9. Measuring the incidence (3) 2) Incidence density or Incidence rate If 100 subjects are followed for 1 year and 20 develop disease, the incidence density is 20 cases/ 100 person-years of observation = 20/100 person-years

10. ความสัมพันธ์ระหว่างการสูบบุหรี่กับอุบัติการการเกิดอัมพาต ของประชากร 118,539 คนในเวลา 8 ปี Smoking No. of stroke Person-years Incidence rate of observation /100,000 person-years Never 70 395,594 17.7 Ex-smoker 65 232,712 27.9 Smoker 139 280,141 49.6 Total 274 908,477 30.2 Cumulative incidence = 274 / 118,539 = 2.31 / 1,000

11. Cross-sectional Case control Cohort Classification of Clinical Study Design Observation (natural exposure) Experiment (exposure given by researcher) Randomized controlled trials

12. Ability to prove causation

13. Cohort Study !!!! We are dealing with “INCIDENCE” *Ram Ragsin, MD MPH DrPH Department of Military & Community Medicine Phramongkutklao College of Medicine

14. Cohort Study (1) • The most powerful observational study for identifying an association between risk factors and a disease • The most time consuming • The most expensive *Ram Ragsin, MD MPH DrPH Department of Military & Community Medicine Phramongkutklao College of Medicine

15. Cohort Study (2) • Start with a group of people without the disease • Then divide people based on the basis of the exposure to a suspected risk factor • Follow the “whole group” for a period of time • Then assess the disease occurrence outcome *Ram Ragsin, MD MPH DrPH Department of Military & Community Medicine Phramongkutklao College of Medicine

16. Cause Effect • Lung Cancer • Disease • Death • Intermediate outcomes • - CD4+count • - Increased Creatinine • Cigarette • Exposure • Risk factor • Covariate • - Age • - Gender • - Income *Ram Ragsin, MD MPH DrPH Department of Military & Community Medicine Phramongkutklao College of Medicine

17. disease Peoplewithout The disease Exposed no disease Population disease Not Exposed no disease Design of a cohort study Time Direction of inquiry

18. Risk “ The probability of disease incidence” Risk = number of cases of disease number of people at risk

19. CA Lung No CA A B Smoke A+B C D Not Smoke C+D Relative Risk Relative Risk = A / A+B C / C+D

20. CA Lung No CA 45 445 Smoke 500 1 499 Not Smoke 500 Interpretation of Relative Risk (RR) Incidence of smoker who develop Lung Cancer = 45/500 Incidence of Non-smoker who develop Lung Cancer = 1/500 Relative Risk of smoking for Lung Cancer = 45/500 = 45 1/500 “Those who smoked were 45 times more likely to develop lung cancer than those who did not smoke” *Ram Ragsin, MD MPH DrPH Department of Military & Community Medicine Phramongkutklao College of Medicine

21. Population Exposed Controls (People without disease) Not Exposed Design of case-control study Exposed Cases (People with disease) Not Exposed Time Direction of inquiry

22. Cause Effect Factors Disease Case-Control Factors Disease Cohort Case-control VS Cohort *Ram Ragsin, MD MPH DrPH Department of Military & Community Medicine Phramongkutklao College of Medicine

23. Case-Control Study • Strengths • Uniquely suited to diseases with long incubation periods • More efficient in terms of time and money • Good for study of rare disease • Can look at multiple exposures for a single disease • Case-control studies usually require much smaller sample sizes than do equivalent cohort studies • Case-control studies are generally able to evaluate confounding and interaction rather more precisely for the same overall sample size than are cohort studies. *Janit Kaewkungwal Faculty of Tropical Medicine Mahidol University

24. Case-Control Study • Limitation • Inefficient for evaluation of rare exposures • Cannot directly compute incidence rates of disease • Temporal relationship between E and D may be hard to establish. Case-control studies often do not involve a time sequence, and so are limited in their ability to demonstrate causality. • Particularly prone to bias (selection and recall in particular) • Being identified as a case might reflect survival rather than morbidity. • Case-control studies can investigate only one disease outcome. • May be confounded by unknown exposures • Appropriate control group often difficult to find *Janit Kaewkungwal Faculty of Tropical Medicine Mahidol University

25. Odds “The number of times the outcome occurs relative to the number of times its does not.” Odds = number of cases of disease number of non-cases of disease

26. a b a+b c+d d c a+c b+d N Odds Ratio Disease CA lung (case) No CA (control) smoke Exposure Not smoke Odds of exposure if case = [a/(a+c)] / [c/(a+c)] = a/c Odds of exposure if control = [b/(b+d)] / [d/(b+d)] = b/d OR = Odds of exposure if case = a/c Odds of exposure if controlb/d

27. Relative risk VS Odds ratio (1) If disease is rare relative risk  Odds ratio Relative Risk = A / A+B = 0.75%/0.25% = 3.0 C / C+D

28. Relative risk VS Odds ratio (2) Odds ratio = 75X50 = 3.0 25x50 relative risk  Odds ratio

29. Cross-sectional studies • Measure the prevalence of disease and often called prevalence studies • The easiest step to find an association (Factor & Disease) by comparing exposed and non-exposed population • Assess both EXPOSURE and DISEASE at the SAME TIME (simultaneously) • Analyze results from a survey *Ram Ragsin, MD MPH DrPH Department of Military & Community Medicine Phramongkutklao College of Medicine

30. Design of a Cross-sectional study +Exposure +Disease Gather data on Exposure and disease (simultaneously) +Exposure -Disease Defined population -Exposure +Disease -Exposure -Disease

31. Prevalence Rate Ratio • Estimate the “Relative Risk” from a cross-sectional study • Prevalence Rate Ratio = 10% / 5% = 2 • “Those who had high cholesterol were 2 times more likely to develop HT than those who did not” *Ram Ragsin, MD MPH DrPH Department of Military & Community Medicine Phramongkutklao College of Medicine

32. Thank you