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  1. 1. Types of Research Studies Architecture of Clinical Research Rani Gereige, M.D., MPH, FAAP Associate Professor of Pediatrics Associate Director, Residency Program University of South Florida
  2. 2. Learning Objectives <ul><li>Be familiar with the types of research study designs </li></ul><ul><li>Be aware of the advantages, disadvantages, and uses of the various research design types </li></ul><ul><li>Recognize a study design from published study abstracts used as a class exercise </li></ul>
  3. 3. Studies in Medical Literature <ul><li>Two main categories: </li></ul><ul><ul><li>Observational: </li></ul></ul><ul><ul><ul><li>Studies in which subjects are observed </li></ul></ul></ul><ul><ul><li>Experimental: </li></ul></ul><ul><ul><ul><li>Studies in which the effect of an intervention is observed </li></ul></ul></ul>
  4. 4. Observational Studies <ul><li>Case Series </li></ul><ul><li>Case-Control </li></ul><ul><li>Cross Sectional </li></ul><ul><li>Cohort </li></ul>
  5. 5. Observational Studies <ul><li>Case Series </li></ul><ul><ul><li>What are they? </li></ul></ul><ul><ul><ul><li>Author describes some interesting or intriguing observations that occurred to a small number of patients </li></ul></ul></ul><ul><ul><li>Characteristics: </li></ul></ul><ul><ul><ul><li>The simplest design </li></ul></ul></ul><ul><ul><ul><li>Descriptive </li></ul></ul></ul><ul><ul><ul><li>Lead to hypotheses subsequently investigated by other types (Case-Control, Cross-Sectional or Cohort study) </li></ul></ul></ul><ul><ul><ul><li>Generally over short period of time </li></ul></ul></ul><ul><ul><ul><li>Generally no controls </li></ul></ul></ul>
  6. 6. Case Series & Case Reports
  7. 7. Observational Studies <ul><li>Case-Control </li></ul><ul><ul><li>Retrospective </li></ul></ul><ul><ul><li>Question answered: “What happened?” </li></ul></ul><ul><ul><li>Matching needed for controls </li></ul></ul><ul><ul><li>Might be difficult to differentiate from Case Series (Both are after the fact) </li></ul></ul><ul><ul><ul><li>Ask if the goal was to describe a phenomenon, if description is the goal  Case Series </li></ul></ul></ul>
  8. 8. Case Control Studies
  9. 9. Case-control Studies: research in reverse Example: association between smoking and lung cancer. People with lung cancer are enrolled to form the case group, and people without lung cancer are identified as controls . Researchers then look back in time to ascertain each person's exposure status (smoking history), (retrospective design). Investigators compare the frequency of smoking exposure in the case group with that in the control group, and calculate a measure of association.
  10. 10. Observational Studies <ul><li>Cross Sectional </li></ul><ul><ul><li>AKA Surveys, epidemiologic or prevalence studies </li></ul></ul><ul><ul><li>What are they? </li></ul></ul><ul><ul><ul><li>Analyzes data collected on a group of subjects at one time </li></ul></ul></ul><ul><ul><li>Question answered: “What is happening now?” </li></ul></ul><ul><ul><li>Short time </li></ul></ul>
  11. 11. Cross Sectional (cont’ed) <ul><li>Possible uses of Cross Sectional studies: </li></ul><ul><ul><li>Diagnosing or staging a disease </li></ul></ul><ul><ul><li>Evaluating different methods of doing the same thing </li></ul></ul><ul><ul><ul><li>e.g. Examining the relationship between histology slides and MRI findings of diseased carotid arteries </li></ul></ul></ul><ul><ul><li>Establishing norms </li></ul></ul><ul><ul><ul><li>e.g. Establishing normal lab values from normal subjects </li></ul></ul></ul><ul><ul><li>Surveys </li></ul></ul><ul><ul><ul><li>May use preexisting validated surveys </li></ul></ul></ul><ul><ul><ul><li>To learn what people think </li></ul></ul></ul><ul><ul><ul><li>Sometimes combined with interviews </li></ul></ul></ul>
  12. 12. Observational Studies <ul><li>Cohort </li></ul><ul><ul><li>Question answered: “what will happen?” </li></ul></ul><ul><ul><li>Prospective/forward </li></ul></ul><ul><ul><li>e.g. Framingham study of cardiovascular disease: Started in 1948, 6000 citizens participated, followed for 20 years (study in 1970 by Gordon and Kannel) </li></ul></ul><ul><ul><li>Possible uses: </li></ul></ul><ul><ul><ul><li>Typical cohort study </li></ul></ul></ul><ul><ul><ul><li>Outcome assessment (patient outcomes: economic, functional, satisfaction, QOL, ..) </li></ul></ul></ul><ul><ul><ul><li>Historical Cohort studies/AKA Retrospective cohort: Relies on prospective records collected (If accurate) – still forward in time in the past </li></ul></ul></ul>
  13. 13. Cohort Studies
  14. 14. Cohort studies: marching towards outcomes Lancet 2002; 359: 341-45 The defining characteristic of all cohort studies is that they track people forward in time from exposure to outcome . Data collection may be prospective or retrospective. Ex. Contraceptives and DVT .
  15. 15. Both Cohort and Case-Control studies are called “Longitudinal Studies” Notion of time
  16. 16. Observational Studies Case Series Case-Control Cross Sectional Cohort Longitudinal Studies
  17. 17. Experimental Studies <ul><li>AKA Clinical Trials (Involve humans) </li></ul><ul><li>Easier to identify (usually explicitly stated in the abstract) </li></ul><ul><li>Two main categories of clinical trials: </li></ul><ul><ul><ul><li>Controlled trials </li></ul></ul></ul><ul><ul><ul><li>Uncontrolled trials </li></ul></ul></ul>
  18. 18. Experimental Studies <ul><li>Controlled trials </li></ul><ul><li>Experimental drug or procedure compared with another, with a placebo, or with the standard procedure </li></ul><ul><li>Greater validity </li></ul>
  19. 19. Experimental Studies Controlled Trials <ul><li>Trials with independent concurrent controls </li></ul><ul><ul><li>Double or single blind </li></ul></ul><ul><ul><li>Best is randomized assignment </li></ul></ul><ul><ul><li>Same point in time </li></ul></ul><ul><ul><li>These include: </li></ul></ul><ul><ul><ul><li>RCT: </li></ul></ul></ul><ul><ul><ul><ul><li>The epitome of all research designs </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Provides the strongest evidence of concluding causation </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Best insurance that results are due to the intervention </li></ul></ul></ul></ul><ul><ul><ul><li>Nonrandomized trials: </li></ul></ul></ul><ul><ul><ul><ul><li>Assignment not randomized </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Opened to biases </li></ul></ul></ul></ul><ul><li>Trials with self controls </li></ul><ul><ul><li>Subject to bias (Hawthorne effect) </li></ul></ul><ul><ul><li>Can do crossover study (with washout period in between) </li></ul></ul><ul><li>Trials with external control </li></ul><ul><ul><li>Uses the results of another investigator’s research as a comparison </li></ul></ul><ul><ul><li>Historical controls can also be used: for disease with no cures yet </li></ul></ul>
  20. 20. Randomized Controlled Studies
  21. 21. The Double Blind Method
  22. 22. Experimental Studies <ul><li>Uncontrolled trials </li></ul><ul><li>Investigator’s experience with the new drug or procedure is described but not formally compared with another one </li></ul><ul><li>More likely to be used for interventions that are procedures rather than drug </li></ul>
  23. 23. Experimental Studies Controlled trials Uncontrolled trials Self controls Independent concurrent controls External controls RCT Non-randomized
  24. 24. Systematic Reviews &Meta-analyses
  25. 25. Study Pyramid Best Worst
  26. 26. Classification of types of clinical research Lancet 2002; 359: 57-61
  27. 27. Temporal direction of study designs Lancet 2002; 359: 57-61
  28. 28. Advantages & Disadvantages
  29. 29. Clinical Trials <ul><li>Advantages: </li></ul><ul><ul><li>RCT is the gold standard or reference </li></ul></ul><ul><li>Disadvantages: </li></ul><ul><ul><li>Expensive </li></ul></ul><ul><ul><li>Long duration </li></ul></ul>
  30. 30. Cohort Studies <ul><li>Advantages: </li></ul><ul><ul><li>Design of choice for studying cause of a disease, course, risk factors </li></ul></ul><ul><li>Disadvantages: </li></ul><ul><ul><li>Cannot be used to prove causation </li></ul></ul><ul><ul><li>Long studies can be costly </li></ul></ul><ul><ul><li>Vulnerable to patient attrition, migration </li></ul></ul>
  31. 31. Case-Control Studies <ul><li>Advantages: </li></ul><ul><ul><li>Quickest </li></ul></ul><ul><ul><li>Least expensive </li></ul></ul><ul><ul><li>Good for rare diseases and diseases that take long time </li></ul></ul><ul><ul><li>Good for investigation of a preliminary hypothesis </li></ul></ul><ul><ul><li>Time factor research </li></ul></ul><ul><li>Disadvantages: </li></ul><ul><ul><li>Large biases </li></ul></ul><ul><ul><li>Difficult to find matching controls </li></ul></ul>
  32. 32. Cross Sectional Studies <ul><li>Advantages: </li></ul><ul><ul><li>Best for: </li></ul></ul><ul><ul><ul><li>Determining status quo of a disease </li></ul></ul></ul><ul><ul><ul><li>Prevalence of disease </li></ul></ul></ul><ul><ul><ul><li>Evaluation of diagnostic procedures </li></ul></ul></ul><ul><ul><li>Relatively quick and inexpensive </li></ul></ul><ul><li>Disadvantages: </li></ul><ul><ul><li>Provide only a snapshot in time </li></ul></ul>
  33. 33. Case Series <ul><li>Advantages: </li></ul><ul><ul><li>Easy to write </li></ul></ul><ul><ul><li>May be extremely useful to investigators looking for causes of the observation </li></ul></ul><ul><li>Disadvantages: </li></ul><ul><ul><li>Subject to many biases in patient selection </li></ul></ul><ul><ul><li>Should be viewed as hypothesis generating, not conclusive </li></ul></ul>
  34. 34. Class Exercises What Type of Research Design?
  35. 35. Exercise #1 <ul><li>Cryptosporidiosis is an enteric illness that is frequently waterborne. Khalakdina and colleagues (2003) could find no published studies of the risk factors for cryptosporidiosis in immunocompetent adults. Patients with cryptosporidiosis were recruited from a surveillance system, and age-matched controls were recruited by random-digit dialing. Subjects in both groups were interviewed by telephone to obtain information about previous exposures </li></ul>
  36. 36. What is the Study Design?
  37. 37. Drossman DA, Li Z, Leserman J, Toomey TC, Hu YJ. Health status by gastrointestinal diagnosis and abuse history. Gastroenterology 1996;110:999-1007. <ul><li>BACKGROUND & AIMS: Standardized assessment of health status by diagnosis (functional vs. organic) and the relative influence of abuse history on health status have not been studied previously. The aim of this study was to estimate the health status and abuse history for gastrointestinal diagnoses among patients seen in a tertiary-care gastroenterology clinic and to evaluate the relative predictive effects of diagnosis and abuse history on health status. METHODS: Standardized measures of sexual and physical abuse history and six health status measures were estimated for the patients by diagnosis. Analysis of covariance was performed to determine the relative contributions of diagnosis type and abuse history on the health status measures… </li></ul>
  38. 38. What is the Study Design?
  39. 39. Calvert EL, Houghton LA, Cooper P, et al. Long-term improvement in functional dyspepsia using hypnotherapy. Gastroenterology 2002; 123: 1778-85. <ul><li>BACKGROUND & AIMS: We have shown hypnotherapy (HT) to be effective in irritable bowel syndrome, with long-term improvements in symptomatology and quality of life (QOL). This study aimed to assess the efficacy of HT in functional dyspepsia (FD). METHODS: A total of 126 FD patients were randomized to HT, supportive therapy plus placebo medication, or medical treatment for 16 weeks. Percentage change in symptomatology from baseline was assessed after the 16-week treatment phase (short-term) and after 56 weeks (long-term) with 26 HT, 24 supportive therapy, and 29 medical treatment patients completing all phases of the study. QOL was measured as a secondary outcome. </li></ul>
  40. 40. What is the Study Design?
  41. 41. Thomas SH, Silen W. Effect on diagnostic efficiency of analgesia for undifferentiated abdominal pain. Br J Surg 2003; 90:5-9. <ul><li>BACKGROUND: The question of whether it is safe to provide analgesia for patients with undifferentiated acute abdominal pain is marked by longstanding controversy over the possible masking of physical findings. The goal of this review is to assess the pertinent studies. METHOD: A Medline search was performed in April 2002, using the terms 'analgesia', 'abdominal pain', 'acute abdomen' and 'morphine'. Other articles were identified using the bibliographies of papers found through Medline. All articles reporting clinical trials of analgesia and its effects on diagnosis or physical examination were reviewed. </li></ul>
  42. 42. What is the Study Design?