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Terms

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Bias
systematic error in a study which results in an incorrect estimate of the association between exposure and disease
Types of Bias
Two broad classification of bias: Selection bias Observation (information) bias
Selection Bias
a systematic error in the process of identifying and recruiting members of the study sample related to either outcome or exposure does NOT relate to sample representativeness or generalizability
Sources of Selection Bias
Differential diagnosis, surveillance or referral into the study Differential refusal or non-response rates among subjects by either disease or exposure status
Differential Diag
Particularly a problem for facility-based research persons who have a risk factor may be tested and diagnosed at a faster rate, and be in care at a different rate, than those who do not have the risk
Differential Surveillance
Particularly a problem when using passively reported data persons who are treated by different care providers may have differential rates of disease reporting
Differential Referral
Recruitment of subjects from sources (service providers) that are not accessed equally by those at risk or with disease recruiting cases solely from private physician offices, while controls are from private and public facilities
Differential Refusal or non-response
Subject willingness to participate may be influenced by either their disease or exposure status persons asked to be controls in a case-control study of behavioral risks for HIV may be unwilling to participate because they do not wish to reveal risk factors
Observation (info) Bias
systematic error in the collection or measurement of data related to either exposure or outcome
Misclassification
when the data gathered does not actually reflect the true/real disease or exposure status random (non-differential) is not a serious problem, although it can dilute your measured association non-random (differential) can distort observed relationship and conclusions relative to true situation
Recall (obs) Bias
Recall Bias patient characteristics may influence data gathered - age, lifestyle, attention to detail women who are experiencing uterine CA may, because of the disease, spend more time remembering their past reproductive history (not as much hopefully) than those without disease
Interviewer (obs) Bias
Interviewer Bias interviewer actions may influence data gathered a chart abstractor may be more aggressive in seeking risk information in the chart for cases than controls, or ask probing questions when they get a negative response in an interview
Follow-up (obs) Bias
Follow-up Bias ability to gather data over time varies by exposure and outcome tracking subjects may be influenced by exposure status - workers exposed to asbestos may be more likely to remain in study and be diagnosed than unexposed workers who drop out but still develop disease
Control of Bias
Careful study design and study implementation are the only ways to control for selection bias, and for many forms of observation bias
Methods to Control Bias
Choice of study subjects thinking of as many problems as possible before diving into the process establishing clear inclusion/exclusion criteria for all subjects defining a strict recruitment protocol Choice of study subjects Consistency in sources of disease and exposure information defining if and how multiple sources will be used which source takes precedence if there is a conflict Mechanisms in data collection objective measures and standard protocols training of study personnel “blinding” of researchers and subjects
Specific Designs & Their Impt Bias Threats
Case-control selection and recall bias Retrospective cohort recall and selection bias Prospective cohort interviewer and follow-up bias Randomized controlled trial interviewer and follow-up bias
Confounding
The mixing of the effect of the exposure upon disease with the effect of a second factor that is related to both the exposure and the disease Essentially, real relationships that create “noise” in the study
Confounding details
Confounders are: predictive, but not necessarily causal for disease associated, but not necessarily causally related, with the measured exposure not an intermediate link in the causal chain or web between the disease and exposure
Confounding (ex)
In a study of the contribution of air pollution to occurrence of bronchitis (can be contagious), urban density or crowding acts as a confounder In a New Mexico study of CHD mortality, altitude of residence appeared protective, but was in fact confounded by ethnicity
ID-ing Confounding
Potential confounders are identified: NOT by levels of significance of its relationship to either disease or exposure But rather by: knowledge of the disease previous investigations of similar questions and populations by testing for differences in crude and adjusted rates and RR/OR in the study sample
Confounding effects
The effect of confounding can be either: Positive - enhancing the apparent association observed; e.g. a true RR of 4.5 is estimated as 6.7 Negative - diluting the association and bringing it closer to 1.0 (no effect)
Control of Confounding
Confounding can be controlled at the design phase through: Randomization of subjects in clinical trials Restriction of sample Matching* Confounders are controlled at the analysis phase by: Matched analysis* Stratification Multivariate analysis
Randomization
Not possible in observational studies; Only way to control for unknown confounders; Helps ensure that potential confounders (known and unknown) are evenly distributed in your study sub-groups; Sample size must be sufficiently large for randomization to be effective
Restriction
reduces size of pool of potential study subjects; controls only known confounders; does not allow assessment of the association at varying levels of the confounding variable; reduces generalizability
Matching
Must be addressed at design AND analysis Can control only a limited number of confounders Potentially expensive in $$ and time Matched factor cannot be tested as to its effect on the outcome Useful strategy for environmental / genetic factors Useful when number of cases is small and multiple controls can be matched
Types of Matching
Frequency Proportion of sample in each level of a confounder in one study arm (usually exposure or case) is determined, and then the same frequency distribution is sought for the other study arm Individual each case is matched individually with a specific control on the confounder(s) (charts)
Odds Ratio for matched case-control study
OR = b/c
Stratified analysis
Magnitude of confounding is determined by the difference between crude and adjusted risk measures Calculates unconfounded estimates of risk within each level of potential confounder Evaluates both confounding and effect modification
Adjusted or Standardized OR & RR
There are a number of different formulas and formula choice depends upon: study design whether stratum-specific estimates are uniform or non-uniform whether incidence is in CI or ID format
Effect Modification
A variable is an effect modifier when the association between the exposure of interest and the disease varies with the level of that variable also called an “interaction” Don’t worry about material in text that focuses in depth on effect modification (charts)
Multivariate analysis
Allows for simultaneous control of multiple confounders Choice of model is a complex process, linked to design used and purpose of study Reliance on analysis packages is often detrimental to real understanding of dynamics of relationships

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