Learning Objectives When you have completed this session you will be able to: Understand the basis and use of Kochs Postulates Define the issues relevant to causality Describe the impact of bias Define types of bias Describe methods of reducing bias
2 Causality What do we mean by 'cause'?
"Money is the root of all evil. Smoking causes lung cancer. Drinking cold soda can give you flue 3 Causal Association A change in the frequency or quality of an exposure or characteristic results in a corresponding change in the frequency of the disease of outcome of interest. 4 Three Types of Causality 1. Sufficient cause 'X Y' (X implies Y; if X occurs then Y will follow) This means that if X happens, then Y will also happen. Medical example: Iron deficiency causes anaemia. (However, the reverse is not true: all cases of anaemia are not caused by iron deficiency - bleeding, vitamin B 12 -deficiency, leukaemia.) 5 Types of Causality 2. Necessary cause 'X Y' (Y implies X; if Y occurs then it must have been preceded by X) Medical example: Exposure to the tubercle bacillus causes tuberculosis. (Yes, you cannot get TB without being exposed to the bacillus. However, most people exposed will never develop disease.) 6 Types of Causality 3. Additive cause Several risk factors are needed to cause disease. Medical example: Coronary infarction (heart attack) Smoking High blood pressure Diet Lack of exercise 7 Types of causation A1 A2 A3 A4
B
C
A1 + A2 + A3 B C A1, A2, A3 (2 of 3) B C 8 Seldom as simple as one risk factor being at the same time a necessary and a sufficient cause of a disease. Example? 9
How do you determine that a factor causes disease (in either of the three ways above)?
One of the first attempts: Lffler's postulates (1883):
"The fulfilment of these postulates is necessary in order to demonstrate strictly the parasitic nature of a disease:
1. The organism must be shown to be constantly present in characteristic form and arrangement in the diseased tissue.
2. The organism which, from its behaviour appears to be responsible for the disease, must be isolated and grown in pure culture.
3. The pure culture must be shown to induce the disease experimentally."
(Sometimes called Koch's postulates.)
What type of cause do these describe? 10 How do these postulates work in public health?
Best way to prove Kochs is experimentation.
However, in most situations in public health, we cannot perform experiments.
Instead, we look at associations between a risk factor and a disease.
Such as smoking and lung cancer or high fat intake and cardiovascular disease.
(or - an economic system and living standard)
(or - a legal system and crime rate)
(or - a health care system and general health)
11 Causality in Public Health Strength of association Consistency of association Specificity of the association Temporal relationship Dose-Response Biologic plausibility Experimental confirmation 12 We can never be 100% certain. However, Bradford Hill also pointed out (1965): "All scientific work is incomplete - whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action it appears to demand at a given time." In everyday life - beware of regarding temporal associations as causal! 13 Validity External validity Does sample represent the population Measure the phenomena of interest Can we generalize our findings Can we generalize the status of HIV infection in Rwanda from a study in the East Province? 14 Validity Internal Validity How well was the study done? Are the measurements accurate? Are the groups comparable?
Example: Study of circumcision preventing HIV infection that takes volunteers for the circumcision group 15 Error The difference between the true value and the recorded value Random Error Role of chance Sample size, measurement accuracy Systematic error Related to study design Bias and confounding 16 Chance Chance may influence the resultsdue to random variation from sample to sample 17 Chance ExampleObesity Study Weigh 5 people 40, 60, 70, 90, 110 Kilogram Great variability
Kilograms 40 60 70 90 110 18 Chance ExampleObesity Study Weigh 100 people 40-110 pounds Less variability, more reliability
Kilograms 19 Random error valid but not precise x x x x x x x x x x x 20 Systematic error may be precise, but not valid x x x x x x x x x x x 21 Bias Any systematic error in an epidemiologic study that results in an incorrect estimate of the association between exposure and risk of disease Hennekens and Buring, 1986
Not even, unbalanced, preferred Miss the target every time in the same way 22 Stages of study at which bias occurs Reading literature Selecting sample Execution of study Measuring exposures or outcomes Analyzing data Interpreting analysis Publishing results EVERYWHERE 23 Selection Bias Systematic error in the specification of the study sample(s) or in the enrollment of study participants that results in a mistaken estimate of an exposures effect on the risk of disease. OR A problem with who gets into your study. 24 Selection Bias Enrolment criteria differs between groups of comparison AND is related to exposure and outcome Exposure + -- Disease status Controls Cases A B C D a c b d 25 Selection Bias Comparison group must had the opportunity to have been exposed to the causative factors(s) as were the cases.
26 Selection Bias Diagnostic Bias How define a case Knowledge of exposure Is it a real non-case
Example: Selecting controls for a measles vaccine study: Controlsnever had measles, but could have had subclinical measles 27 Selection Bias Comparison group Hospitalized patients Friends Neighbors Random selection from community from which cases come 28 Selection Bias Self-selection Soldiers to be part of a study of Gulf War syndrome Diagnostic bias Often use hospitalized patients to make conclusions Many studies made on hospital patients Case fatality rate Vaccination status Cases more thoroughly investigated than controls. 29 Selection Bias Non-response bias Low response rate Bias introduced if response less than approximately 80% of those selected to be in study. Ex: Study of sexual practices Non-participation bias People who volunteer may be very different from those who don't. modern sexual behaviour studies any postal questionnaire Survivorship bias More likely to study people with less severe disease Study of men with prostate cancer in general medicine clinic 30 Selection Bias Big problem in case control studies Control group not representing the true background population. Controls are different from cases Every control, if he had been sick, should have been eligible as a case. 31 70% of women married more than five years are having sex outside of marriage. - The New Hite Report Based on 4,500 responses 32 Information Bias Systematic error in the collection of exposure or disease data that results in a mistaken estimate of an exposures effect on the risk of disease. OR A problem with the information you get from the people in your study. 33 Information Bias Questionnaire Design Unclear questions Inappropriate questions
Interviewer Bias Asks questions differently 34 Information Bias Respondent Bias The respondent may give false answer in order to please the interviewer or withhold data
Recall Bias Influenced by time between cause and effect
Reporting or Ascertainment Bias Results from publicity 35 Misclassification or Information Bias
Exposure + -- Disease status Controls Cases A B C D a c b d 36 Information bias Differential misclassification Misclassification in one direction related to exposure or outcome status Controls for cholera cc study claim to treat water more than cases Bias OR/RR in one direction Nondifferential misclassification Misclassification in both directions, not related to exposure or outcome, random Cases and controls equally likely to forget exposure Bias OR/RR towards null 37 Information bias Recall bias Mothers of babies with birth defect remember drugs they took during pregnancy better Cases of aflatoxin remember eating rotten maize more than controls Interviewer bias Interviewer tries harder to find exposure in cases than controls 38 Control of Bias Bias cannot always be controlled in the analysis Prevention of bias in the design phase of an investigation is crucial to the validity of the study results. Choice of study population Comparability (hospital controls) Reduce loss to follow-up Methods of data collection Data collection instruments Administration of those instruments, Training important No prompting for responses Give prompts to help recall (calendars, sample of pill)
39 Recap Now that you have completed this session you should be able to: Understand the basis and use of Kochs Postulates Define the issues relevant to causality Describe the impact of bias Define types of bias Describe methods of reducing bias
40 Information Bias Even with a perfect sample a subjects, we may not be getting the information we think. (Relates mostly to interview situations.) Questionnaire faults Do others mean what we mean? pre-test reverse translation cut down Questionnaire design is a science in itself. Interviewer bias Is everyone asked the same questions in the same way? hepatitis C in blood donors different interviewer for cases and controls 41 Recall Bias Cases may be able to (want to) remember exposures much better than controls food items at an outbreak abortion and risk of breast cancer Greatest problem when hypothesis tested is already known Creutfeldt-Jakob and beef consumption When there may be economic compensation involved. 42 Biases can give rise both to apparent associations when there aren't any, and also hide true associations. Impossible to say which.
A bias introduced into a study can never be removed by clever manipulation in the analysis of data.
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