Error & Bias in Epidemiological Studies Flashcards

1
Q

How are the 2 types of error related to precision and accuracy?

A
  1. RANDOM ERROR due to chance has low precision but is accurate
  2. SYSTEMATIC ERROR not due to chance has low accuracy but is consistent (has a bias)
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2
Q

What is accuracy? Bias?

A

ACCURACY = whether there is agreement between a measurement made on an object and its true value

BIAS = difference between the average measurements made on the same object and its true value (not accurate = bias)

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3
Q

What are the 3 major types of bias?

A
  1. SELECTION BIAS - related to procedures used to selec units for the study —> study groups differed from source population
  2. INFORMATION BIAS - misclassification related to the information recorded for the study where units are incorrectly assigned positive/negative exposure or disease
  3. CONFOUNDING BIAS - some other factor changes or distorts the effect of exposure on the outcome (diseased vs. non-diseased)
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4
Q

What are the consequences of bias like in descriptive and explanatory studies?

A

DESCRIPTIVE = outcome only affected —> higher or lower estimates of disease frequency

EXPLANATORY = outcome and explanatory variables taken into account —> altered disease frequency moves effect estimate towards or away from the null (no statistical difference)

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5
Q

What does it mean to move toward or away from the null? Which is better?

A

TOWARD = bias causes the study to observe no real effect of exposure/risk factor on disease status

AWAY = bias causes the study to observe that exposure/risk factors have more effect on disease status than they actually do

TOWARD NULL - better to underestimate and do further studies

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6
Q

How is magnitude of bias calculated?

A

difficult —> sensitivity simulations can help

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7
Q

What is surveillance bias?

A

selection bias where mild/subclinical disease is more likely to be detected in animals under frequent medical surveillance and/or enrolled in surveillance programs

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8
Q

What is referral bias (admission risk bias/Berkson’s fallacy)?

A

selection bias where differential referral patterns are a source of bias in hospital-based case-control studies

  • is the hospital population representative of the whole population?
  • socioeconomic representation in hospital population
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9
Q

What is non-response bias?

A

selection bias where >20-30% of non-responses or refusal to participate in a study may contribute a bias

  • only accounts for passionate people in the study
  • high overall response = less bias
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10
Q

What is missing data bias?

A

selection bias where >20-30% of data is missing and an accurate result cannot be attained

  • not enough serum from blood draw to run a test
  • missing data does not confirm non-diseased state
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11
Q

What is loss to follow-up bias?

A

participants are dropping out of a study, which can alter the new group, making them less representative of the actual population

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12
Q

What is selective sentry (survival) bias?

A

traits are naturally selected when choosing a group of subjects and treatments that prolong lifespan increase prevalence of disease

  • “healthy worker” effect in occupational health studies - those working tend to be more healthy than unemployed
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13
Q

In what 4 ways can selection bias be reduced? How can it NOT be corrected?

A
  1. random sampling - assesses probability of bias by distributing risk factors equally between groups
  2. maximize response rates - questionnaires are enticing to get more participants to respond
  3. minimize withdrawal rates - keep participants in study
  4. ensure equal responses/withdrawals from exposed/non-exposed and diseased/non-diseased

analytical techniques

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14
Q

How can selection bias be reduced in observational studies?

A

consider the forces at play with selecting individuals

  • case-control: use incidental cases and get controls from the same source population as the cases
  • cohort: persistent follow-up with creative strategies for maintaining full participation
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15
Q

How can selection bias be reduced in controlled trials?

A

RANDOMIZE allocation to intervention and comparison groups and BLIND recruiters and participants to allocation (exposed vs non-exposed), while minimizing withdrawals and maximizing retention

(randomize and blind…everything should be fine)

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16
Q

What is recall bias?

A

information bias where cases are better at recalling past exposure compared with non-cases

  • Salmonella + cases are likely to remember what they last ate compared to Salmonella - cases
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17
Q

What is interview bias?

A

information bias where interviewers are privy to the hypothesis under investigation

  • more likely to ask leading questions to support hypothesis
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18
Q

What is obsequiousness bias (Clever Hans effect)?

A

information bias where subjects systematically alter responses toward perceived desirable answers

  • people commonly change answers based on welfare and hygiene/sanitation based on what should be
  • Hans was a trained horse who could supposedly perform arithmetic, but it was found tat he was getting non-verbal cues from his trainer on when to stop stomping his hoof
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19
Q

What is the non-differential consequence of information bias (misclassification) like? How does it compare to null?

A

systematic errors in one group are independent of the other group where there are equal amounts of systemic error in E regardless of D status and systemic error in D regardless of E —> best possible bias

errs toward null —> decreased power and ability to find an effect

20
Q

What is the differential consequence of information bias (misclassification) like? How does it compare to null?

A

systematic error occurs to a greater extent in one group than another —> unequal amount of systemic error in E and D DEPENDING on D and E status —> worst bias, throws off RR and OR

err in any direction (toward or away from null) —> unbalanced link to disease status

21
Q

What are 4 ways to reduce information bias (misclassification)?

A
  1. E and D status should be assessed independently - should be blind to the status of cohorts, cases, and controls
  2. use rigorous and valid methods for determining D and E - explicit case definitions, best available test + confirmatory test, measure specific exposures (not general)
  3. use complete and detailed sources of information - complete exposure histories with as much info as possible
  4. use objective measures when available - no leading questions, clear cut answers
22
Q

How can interviews and questionnaires be used to reduce information bias (misclassification)?

A
  • minimize time between diagnosis and questioning
  • use validated survey instruments (pilot study to test question clarity and detail level)
  • standardized interview protocols with clear guidelines
  • well-trained qualified interviewers vs. mail/phone
  • state/demonstrate clear confidentiality of information
23
Q

How can information bias (misclassification) be corrected after the study? Why should this be done carefully? What way cannot be used?

A

validation study where a sub-sample from the study is used to verify classification of E and D and post-hoc adjustments

very sensitive to changes in estimates —> much better to prevent information bias than to correct it

analytical techniques

24
Q

How can information bias (misclassification) be reduced in observational studies?

A

CASE-CONTROL: explicit definitions for cases, determining E status independent from D status, interview as soon as possible

COHORT: determining D status independent from E status, valid method and objective measures for determining D status

25
Q

How can information bias (misclassification) be reduced in controlled trials?

A
  • blind to intervention allocation (E+ vs E-) to prevent D status from being influenced by E status by interviewers and participants
  • valid method and objective measures for determining outcome (D status)
26
Q

Selection and information bias re-cap:

A
27
Q

What are confounders?

A

a third factor that distorts the true underlying relationship between an exposure and an outcome of interest

28
Q

How do confounders compare to outcome and exposure?

A

causally associated with the outcome in non-exposed animals

non-causally associated with exposure and both are on 2 separate causal pathways to the outcome

29
Q

What are classical confounders? How do they affect the exposure and outcome?

A

age, sex, breed/species, weight/BCS, location, herd size

will not be affected by either - being raised on grass will not make cows younger

30
Q

Age-specific comparison of death from all cases for Tolbutamide and Placebo treatment groups:

  • OUTCOME: survival during follow-up period = 409
  • EXPOSURE: treatment (Tolb. [204] vs Placebo [205])
  • CONFOUNDER: age (< 55y = 226; >55y = 183)

How can it be confirmed that age is a confounder?

A
  • must be associated with the outcome in the non-exposed: 18.8 > 4.2 RR in placebo groups
  • must be associated with exposure: despite randomization, there was still a difference of age by treatment (<55y on Tolb = 52%; <55y Placebo = 59%)
  • must be on separate causal pathways: drug doesn’t change age of participants
31
Q

How can you decide what RR to report on studies with confounders?

A

compare difference between Mantel-Haenszel combined OR of strata of confounders and the crude OR

  • > 20-30% = significant confounder, should report combined OR
  • <20-30% not significant and can report the RR of all participants
32
Q

Tolbutamide and death study, Mantel-Haenszel vs crude OR:

A
33
Q

How can confounding bias be controlled before the study begins?

A
  • restriction (exclusion): purposefully restrict study to a specific group of individuals (loses generalizability, or external validity, since only one group is being studied/reported)
  • randomization: randomize allocation to E+ and E- groups in a controlled trial to produce very similar groups
34
Q

How can matching be used in cohort and case-control studies to decreased confounding bias? What are disadvantages of each?

A

COHORT - match confounders by E (E+ individual is male, find a E- male) —> unable to estimate the effect of the matched factor (male) and may affect global surrogate factors and match-out multiple factors

CASE-CONTROL - match confounders by D (D+ individual is male, find a D- male) —> matching WILL NOT control confounding in these studies since exposure is unknown, but it can increase power

35
Q

What is the best way to control confounding bias? What are 3 examples?

A

ANALYTICAL MODELS

  1. standardization (human) - adjustment to an external standard
  2. STRATIFICATION - analysis within each strata separately and use Mantel-Haenszel to make a summary across strata
  3. MULTIVARIABLE - control for multiple factors using linear (continuous) and logistic (dichotomous) regressions
36
Q

How can analytical (statistical) control for confounding be detected in studies?

A
  • UNIVARIABLE = univariate, unconditional associations, raw, crude, bivariate logistic regression = no control for confounding
  • STRATIFICATION: M-H OR, adjusted OR, multivariable, = confounding accounted for
  • MULTIVARIABLE REGRESSION: multivariable, conditional regression, confounders/factors are included in the same model (already built-in, not reported)
37
Q

How does confounding compare to interaction?

A

CONFOUNDING = third factor distorts the true underlying relationship between an exposure and an outcome

INTERACTION = third factor is necessary to explain the relationship between exposure and outcome - outcome DEPENDS on both exposure and interaction factor

38
Q

What are the 2 types of interactions?

A
  1. synergistic (positive) - joint effect is greater than the sum of independent (factor) effects (E + I = greater O compared to no I)
  2. antagonistic (negative) - joint effect is less than the sum of independent factor (E + I = less O compared to no I)
39
Q

What is the test of homogeneity? What is the consequence of heterogeneity?

A

formal statistical test to see if interaction exists between strata depending on the participants within them

  • P > 0.05 = homogeneity = no difference among strata
  • P < 0.05 = heterogeneity = difference among strata

need to use strata-specific estimates (RR or OR for each stratum)

40
Q

Interaction of Neomycin (G-) and Cloxacillin (G+) usage on Nocardia infection (G+):

A
41
Q

How a decision to report confounding and interactions be made?

A

Does the factor interact with the exposure?
- YES = test homogeneity p < 0.05 (M-H) and report separate measures of associated for each level of the factor
- NO = test homogeneity p > 0.05 (M-H)….

Does the factor confound the relationship between exposure and outcome?
- YES = >20-30% change between crude and M-H estimates = report summary measure of association, adjusting for the presence of the factor
- NO = ignore the factor

42
Q

Interactions vs. Confounding:

A
43
Q

What results should be reported?

A

p > 0.05 —> HOMOGENOUS = no interaction, may be confounding

crude vs. M-H = (1.56 - 2.32)/1.56 = 0.487 = 48.7%
- > 20% = confirmed confounder, report summary measure of association adjusting for the presence of the factor - 2.32

44
Q

What results should be reported?

A

p < 0.05 —> HETEROGENOUS = interaction

report separate measures of association for each level of the factor - 0.67 for puppy, 2.22 for adult —> age interacts with food to cause obesity

45
Q

What results should be reported?

A

p > 0.05 —> HOMOGENOUS = no interaction, may be confounding

crude vs. M-H = (1.56 - 1.63)/1.56 = 0.045 = 4.5%
- < 20% = factor is not a confounder and can be ignored to report the crude OR - 1.56 (no significant difference compared to 1.63)