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Case control study


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Seminar on Case control Study

Published in: Health & Medicine
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Case control study

  1. 1. Presented by: Dr. Adrija Roy Moderator: Dr. (Prof) R.N. Rout(Professor & H.O.D) Dr. Ipsa Mohapatra(Assistant Professor) Dr. Shalini Ray(3rd year P.G.)
  2. 2.  Epidemiology  Types of Studies  Hierarchy of Study Design  Analytical Study  Case-Control Study  Study design  Basic Steps  Selection of cases and controls  Matching  Measurement of exposure  Analysis and outcomes  Bias in Case control Study  Important historical examples  Summary.
  3. 3. DEFINITION: "The study of the distribution and determinants of health- related states or events in specified populations, and the application of this study to control health problems.“ ( John M.Last,1988)
  4. 4. Experimental Observational RCT Field Trials Community Trials Analytical Descriptive Ecological Cross-sectional Case-control Cohort Difference in study groups is CREATED EXPERIMENTALLY and outcomes observed Difference in study groups is ONLY observed & analyzed, NOT created experimentally
  5. 5. Quality of evidence
  6. 6.  In analytical studies , the subject of interest is the individual within the population.  The object is not to formulate but to test the hypothesis.  To evaluate an association between exposure and disease.  Analytical studies focuses on the magnitude of the association between the exposure and the health problem under the study.
  7. 7.  A case–control study is an observational study in which subjects are sampled based upon presence or absence of disease and then their prior exposure status is determined.  A case control study involves two populations – cases and controls and has three distinct features :  Both exposure and outcome have occurred before the start of the study.  The study proceeds backwards from effect to cause.  It uses a control or comparison group to support or refute an inference.
  8. 8.  Unit of Study: Cases/Control(Individuals)  Study Question : What had happened   Direction of Inquiry: Exposure Outcome Study Design:
  9. 9.  Hallmark of Case Control Study: Starts from cases and controls and searches for exposure. Disease No Disease “CASES” “CONTROLS” Not ExposedExposed Exposed Not Exposed POPULATION T I M E D I R E C T I O N O F I N Q U I R Y
  10. 10. FIRST: Select CASES CONTROLS (With Disease) (Without Disease) THEN: Were exposed a b Measure Exposure Were not exposed c d TOTALS a + c b + d Proportions a b Exposed a + c b + d
  11. 11.  Selection of cases and controls.  Matching.  Measurement of exposure  Analysis and interpretation.
  12. 12.  Case : A person in the population or study group identified as having the particular disease, health disorder or condition under investigation. (Dictionary of Epidemiology: 3rd ed; John M Last. 2000)  Control: Person or persons in a comparison group that differs, in disease experience (or other health related outcome) in not having the outcome being studied. (Dictionary of Epidemiology: 3rd ed; John M Last. 2000)
  13. 13. Definition of case: it involve two specifications- (i) Diagnostic criteria :  Enunciate clear cut diagnostic criteria for the disease of interest.  must be specified before the study is undertaken.  Once established, it should not be altered or changed till the study is over.  . (ii) Eligibility criteria : It is always advisable to take the incident cases (new cases) since the prevalent cases (old cases in advanced stages)might have changed their exposure status due to medical advice etc
  14. 14.  Hospitals: • Convenient • Can be chosen from one hospital or a network of hospitals. • Admitted during a specified period of time • Entire case series or random sample is selected.  General population • All cases of the study disease occurring within the same geographical area during a specified period of time. • Through survey, disease registry or hospital network. • Entire case series or random sample. • should be fairly representative of all cases in the community.
  15. 15. (i) Should the controls be similar to the cases in all respects other than having the disease? i.e. COMPARABLE (ii) (ii) Should the controls be representative of all non- diseased people in the population from which the cases are selected? i.e. REPRESENTATIVE
  16. 16.  Selection of CONTROLS: ◦ Comparability vs Representativeness ◦ The control group should be representative of the general population in terms of probability of exposure to the risk factor ◦ AND they should also have had the same opportunity to be exposed as the cases have.  Not that both cases and controls are equally exposed; but only that they have had the same opportunity for exposure.
  17. 17.  Selection of CONTROLS: Criteria ◦ Comparability is more important than representativeness in the selection of controls ◦ The control should resemble the case in all respects except for the presence of disease (and any as yet undiscovered risk factors for disease)
  18. 18.  Selection of CONTROLS: Sources Source Advantage Disadvantage Hospital based Easily identified. Available for interview. More willing to cooperate. Tend to give complete and accurate information (recall bias). Not typical of general population. Possess more risk factors for disease. Some diseases may share risk factors with disease under study. (whom to exclude???) Berkesonian bias Population based (registry cases) Most representative of the general population. Generally healthy. Time, money, energy. Opportunity of exposure may not be same as that of cases. (location, occurance,) Neighbourhood controls/ Telephone exchange random dialing Controls and cases similar in residence. Easier than sampling the population. Non cooperation. Security issues. Not representative of general population. Best friend control/ Sibling control Accessible, Cooperative. Similar to cases in most aspects. Overmatching.
  19. 19.  Selection of Controls : Number o Large study: Cases: Control :: 1:1 o Small study: Cases: Control :: 1:2, 1:3, 1:4. o Use of multiple controls Multiple controls of different types: controls- 1 hospital, 1 neighborhood e.g. case- Children with brain tumor, control- children with other cancer, normal children, risk factor- h/o radiation exposure.
  20. 20.  Multiple controls of different types are valuable for exploring alternate hypothesis & for taking into account possible potential recall bias.  (From Gold EB, Gordis L, Tonascia J, Szklo M; Risk factors for brain tumors in children. Am J Epidemiol 1979) Children with brain tumors Children with other cancers Children without cancer Radiation causes cancers Radiation causes brain cancers only
  21. 21.  Process by which we select controls in such a way that they are similar to cases with regards to certain pertinent selected variables (e g. age, sex, occupation, social status etc. ) which are known to influence the outcome of the disease and if not adequately matched for comparability can distort or confound the results.
  22. 22.  Matching: ◦ Matching variables (e.g. age), and matching criteria (e.g. within the same 5 year age group) must be set up in advance. ◦ Controls can be individually matched (most common) or Frequency matched.  Individual matching (Matched pairs): search for one (or more) controls who have the required matching criteria, paired (triplet) matching is when there is one (two) control (s) individually matched to each cases.  Group matching (Frequency matching): select a population of controls such that the overall characteristics of the case, e.g. if 15% cases are under age 20, 15% of the controls are also.
  23. 23.  Matching: ◦ Avoid over-matching, match only on factors KNOWN to be cause of the disease. ◦ Obtain POWER by matching MORE THAN ONE CONTROL per case. In general, N of controls should be ≤ 4, because there is no further gain of power above that. ◦ Obtain Generalizability by matching more than one type of control.
  24. 24.  Matching: Problems – ◦ Overmatching: Matching on variables other than those that are risk factors for the disease under study, either in a planned manner or inadvertently.  Example: If we use neighborhood controls in a study on nutrition and tuberculosis, we would be inadvertently matching for socioeconomic status and thus nutrition.
  25. 25.  Information about the exposure should be obtained in precisely the same manner for both cases and controls.  This may be obtained by the interviews, by questionnaires, or by studying past records of cases such as hospital records, employment records.
  26. 26.  On analysis of case control study we find out ◦ Exposure rates: the frequency of exposure to suspected risk factor in cases and in controls. ◦ Estimation of Risk: ◦ Relative Risk or Risk Ratio. ◦ Strength of association between risk factor and outcome: (Odds ratio)
  27. 27.  Exposure rates: ◦ A case control study provides a direct estimation of the exposure rates (frequency of exposure) to the suspected factor in disease and non-disease groups. Doll R. and Hill AB. (1950) Brit. Med. J. ◦ Exposure rates  Cases = a/ (a + c) = 33/ 35 = 94.2%  Controls = b/ (b + d) = 55/82 = 67.0% Cases (lung cancer) Controls (without lung cancer) Smokers 33 (a) 55 (b) Non Smokers 2 (c) 27 (d) TOTAL 35 (a + c) 82 (b+d)
  28. 28.  Relative Risk or Risk Ratio (RR): RR = Incidence among exposed Incidence among non- exposed = a/(a+b) ÷c/(c+d). A typical Case Control Study does not provide incidence rates from which RR can be calculated directly. There is no appropriate population or denominator at risk. In general RR can be exactly calculated from a cohort study.
  29. 29.  Odds Ratio. ◦ Odds: Odds of an event is defined as the ratio of the number of ways an event can occur to the number of ways an event cannot occur. (Epidemiology; Leon Gordis. 2004)  If the probability of event X occurring is P, then odds of it occurring is = P/ 1-P. ◦ Odds ratio: Ratio of the odds that the cases were exposed to the odds that the controls were exposed.
  30. 30.  Odds ratio: ◦ Using the four-fold table – Odds that case was exposed ◦ Odds ratio = Odds that control was exposed = (a/b)/ (c/d) = ad / bc Diseased/ Cases Not diseased/ Controls Exposed a b Not exposed c d
  31. 31.  Odds ratio ( = cross products ratio) can also be viewed as the ratio of the product of the two cells that support the hypothesis of an association (cells a & d – diseased people who were exposed and non diseased people who were not exposed), to the product of the two cells which negate the hypothesis of an association (cells b & c – non diseased people who were exposed and diseased people who were not exposed).
  32. 32.  Definition: Any systematic error in the design, conduct, or analysis of a study that results in mistaken estimates of the effect of the exposure on disease.  Types of bias in case control studies: ◦ Bias due to Confounding: ◦ Memory or Recall bias ◦ Selection bias ◦ Berkesonian bias ◦ Interviewer bias
  33. 33.  Confounding: When a measure of the effect of an exposure on risk is distorted because of the association of exposure with other factors that influence the outcome. Not possible to separate the contribution that any single causal factor has made ◦ Confounding Factor: is one which is associated with both exposure & disease , and is distributed unequally in study & control groups. ◦ E.g.: Alcohol & Esophageal Ca ; confounding factor- smoking ◦ Solution: Study design : Matching Analysis: Stratification & Regression
  34. 34.  Information Bias: ◦ Occurs due to - 1. Imperfect definitions of study variables OR 2. Flawed data collection procedures. ◦ Leads to – Misclassification of disease and exposure. ◦ Types of Information bias –  Recall bias  Interviewer bias
  35. 35. Recall bias (usually in case-control studies): Cases who are aware of their disease status may be more likely to recall exposures than controls e.g. congenital malformation with prenatal infections Results in misclassification Solution • Achieving similarity in the procedures used to obtain information from cases and controls • Verify exposure with existing records •Use of information recorded prior to the time of diagnosis.
  36. 36.  Some of the cases or controls who were actually exposed will be erroneously classified as unexposed, and some who were actually not exposed will be erroneously classified as exposed.—this generally results in an underestimate of the true risk of the disease associated with the exposure. e.g. cervical cancer with sexual intercourse with uncircumcised men Comparison of patients’ statements with examination findings concerning circumcision status, Roswell Park Memorial Istitute, New York Patients statement regarding circumcision Examination finding Yes (no.) Yes(%) No (no.) No(%) circumcised 37 66.1 47 34.6 not- circumcised 19 33.9 89 65.4 Total 56 100.0 136 100.0
  37. 37.  Interviewer bias: When interviewer is not blinded (knows) case status of subjects there is potential for interviewer bias. ◦ Leads to –  If interviewer knows case status – differential misclassification likely.  If interviewer does not know case status – non differential misclassification is still possible. ◦ Solution –  Blinding of interviewer as to case status  Equal interview time for all participants
  38. 38.  Selection bias: Arises when cases and control do not represent the general population. Prevention is the cure for this bias!!  Berkesonian bias: Arises due to different rates of admission to hospitals for patients with different diseases, i.E cases and controls.
  39. 39.  Relatively easy to conduct.  Completed in less time and is inexpensive  Suitable for investigating rare diseases .  No risk to the subject as exposure and disease both have occurred before the study.  Possible to study different causative factors.  (therefore their prevention and control strategy can be planned)  No attrition problem as follow up is not required.  Minimal ethical problems.
  40. 40.  Depends on records or memory, accuracy uncertain.  Validation of information difficult or impossible.  Difficult to get perfect control group.  Not possible to measure incidence or relative risk directly  Cannot distinguish between causes and associated factors.  Not appropriate for evaluation of a therapy or prophylaxis of a disease.
  41. 41.  OCP and Thromboembolic Disease  By Aug 1965, BRITISH COMMITTEE ON SAFETY OF DRUGS received 249 reports of adverse reactions and 16 deaths in women taking OCP’s .  Thus there was a need to conduct and epidemiological study.  A case control Study was conducted by Vassey and Doll in 1968.  Controls were matched for age, marital status, parity.  RR of users to non users were 6.3:1  Confirmation was established. No. % who used OCP Cases ( venous thrombosis and pulmonary embolism) 84 50 Controls 168 14
  42. 42.  Thalidomide Tragedy:  Thalidomide was first marketed as a safe, non-barbiturate hypnotic in Britain in 1958.  In 1961 at a Gynaecological congress, it was discussed that a large number of babies with congenital abnormalities were being born (phocomelia) which was associated with thalidomide.  Case control study was carried out,  Confirmed that thalidomide was Teratogenic. No. % who took thalidomide Cases( with congenital defects) 46 41 Controls 300 0
  43. 43.  Useful as a first step when searching for a cause of an adverse health outcome.  Valuable when the disease being investigated is rare.  They have provided much of the current base of knowledge in epidemiology.
  44. 44.  Park’s Textbook of Preventive and Social Medicine – 23rd ed; Park JE. 2015.  Principles and Practice of Medical research- 2nd ed; J.V. Dixit. 2015  A Dictionary of Epidemiology – 3rd ed; Last JM. 2000.  Epidemiology – 5th ed; Gordis L.