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Causation and Causality BMA Medical College and Vajira Hospital Cause A B Result BMA Medical College and Vajira Hospital Enabling factor Precipitating factor Predisposing factor Reinforcing factor Causation BMA Medical College and Vajira Hospital OBSERVED ASSOCIATION Could it be due to selection or measurement bias? NO Assessing the relationship between a possible cause and an outcome Could it be due to confounding? NO Could it be a result of chance? PROBABLY NOT Could it be causal? Apply guidelines and make judgment BMA Medical College and Vajira Hospital Association of causation (Bradford Hill Criteria) Temporal relation Does the cause precede the effect? Plausibility Is the association consistent with other knowledge? (mechanism of action; evidence from experimental animals) Consistency Have similar results been shown in other studies? Strength What is the strength of the association between the cause and the effect? (relative risk) Dose-response relationship Is increased exposure to the possible cause associated with increased effect? Reversibility Does the removal of a possible cause lead to reduction of disease risk? Study design Is the evidence based on a strong study design? Judging the evidence How many lines of evidence lead to the conclusion? BMA Medical College and Vajira Hospital Causation in social determinant • • • • Individualism Reductionism Mono-causality Legitimacy of social inequalities Armstrong 1999 BMA Medical College and Vajira Hospital Causality method Individual inductive deductive refer infer Population BMA Medical College and Vajira Hospital A number of factors probably affect the likelihood that a notifiable disease will be reported: 1. The clinical severity of the condition 2. Whether the affected individual consults a physician 3. The type of physician consulted (eg, private vs public provider, generalist vs specialist) 4. Any social stigma associated with the condition 5. Level of interest in the condition among clinicians 6. The physician's knowledge of reporting requirements 7. Existence of an adequate definition of the condition for surveillance purposes 8. Availability and utilization of appropriate diagnostic laboratories 9. Availability of effective disease control measures 10. Interests and priorities of local and state health officials BMA Medical College and Vajira Hospital "Causal inference in epidemiology is better viewed as an exercise in measurement of an effect rather than as criterion-guided process for deciding whether an effect is present or not.“ Rothman & Greenland 2005 BMA Medical College and Vajira Hospital OR = 2.25 34/40 36/60 24/60 6/40 18/20 OR = .6 2/20 OR = .6 BMA Medical College and Vajira Hospital Bias BMA Medical College and Vajira Hospital Bias • Deviation from the truth • Arises from some aspect(s) of study design or conduct • Can serve to incorrectly estimate – Occurrence of disease – Existence (or absence) of an association – Strength of an association • Can be random / non-random BMA Medical College and Vajira Hospital RANDOM BIAS BMA Medical College and Vajira Hospital Random Bias • Random deviation from the truth • Incorrect assessment of exposure / outcome – Continuous: Incorrect measurement – Binary / Categorical: Incorrect categorisation • May result from – Poor instruments / tests – Data-entry error – Subject error BMA Medical College and Vajira Hospital Random Bias • Is misclassification a problem? – Example 1 Schoolbag weight (kg) LBP No LBP RR (95%CI) Light 37 (16.2%) 192 1.0 Medium 51 (20.0%) 204 1.2 (0.8-1.9) Heavy 45 (18.4%) 199 1.1 (0.7-1.8) BMA Medical College and Vajira Hospital Random Bias • Is misclassification a problem? – Example 2 Conduct problems LBP No LBP RR (95%CI) Low 60 (15.9%) 317 1.0 Medium 58 (17.6%) 271 1.1 (0.8-1.6) High 50 (25.5%) 146 1.6 (1.1-2.3) BMA Medical College and Vajira Hospital Random Bias (Summary) • Random misclassification <50% – Decreases likelihood of observing an effect – Bias findings towards the null • Increases likelihood of Type II error (falsely accepting H0) – Serves to underestimate any association • Random misclassification >50% – Mathematically possible to model the effect – Improves the accuracy of the magnitude of your effect estimate • But not the direction! BMA Medical College and Vajira Hospital Random Bias (Summary) • Cannot be controlled for in the analysis • Can be minimised (at the design stage) by use of accurate, effective, and efficient instruments – Sensitivity / Specificity – Validity / Reliability BMA Medical College and Vajira Hospital NON-RANDOM BIAS BMA Medical College and Vajira Hospital Non-Random Bias • Systematic deviation from the truth • Can increase or decrease an effect estimate • Study design can (help to) eliminate • Can be a problem, but may be useful – Can be investigated – Size of increase or decrease can be estimated BMA Medical College and Vajira Hospital Non-Random Bias • Selection bias – Concerned about who is in your study • Information bias – Concerned about the information you elicit from your subjects BMA Medical College and Vajira Hospital Selection Bias • How is the study population selected? • Concern – Selected subjects are systematically different to subjects not selected . . . with respect to the relationship under examination • Sources – Volunteer bias – Referral bias – Healthy-worker effect – Non-response (follow-up) BMA Medical College and Vajira Hospital Selection Bias – Volunteer Bias • To estimate the prevalence of dementia in the UK population, in persons aged 70-80yrs – Study 1 • Newspaper advertisement. Respondents to attend research unit • Prevalence: 1.5% – Study 2 • Subjects selected from GP age/sex register. Postal questionnaire • Prevalence: 3.5% • Potential effect of volunteer bias – Underestimate of disease prevalence – Might the effect be an overestimate? BMA Medical College and Vajira Hospital Selection Bias – Referral Bias • To examine the association between smoking and duodenal ulcer – Cases: Selected from specialist GE clinic – Controls: Selected from general population – Conclusion (1) • Smoking increases the odds of duodenal ulcer – Conclusion (2) In persons with duodenal ulcers, smoking increases symptom severity . . . and therefore likelihood of attending GE clinic • Potential effect of referral bias (here) – To increase the strength of the observed association BMA Medical College and Vajira Hospital “Healthy Worker” Effect • Typically, but not exclusively, in occupational environments • Example: – Case-control study LBP No LBP Builders 23 154 Chi2: 4.59; p=0.03 Site Offices 14 42 OR: 0.4 (0.2-0.9) • Conclusions – Builders experience protection? – Healthy worker effect? BMA Medical College and Vajira Hospital Non-Participation Bias • Most frequent cause for concern in large-scale epidemiological surveys – Non-participation – Loss to follow-up • Systematic differences between participants and non-participants – With respect to the relationship under examination • Typical non-participants – Young / Male / Ethnic minorities BMA Medical College and Vajira Hospital Selection Bias – What to Do • If possible – Prevent it • At the very least – Take steps to minimise it • And perhaps – Estimate its effect • What effect(s) might it have had on your study? • How might this change the results? • Does this change the conclusions? BMA Medical College and Vajira Hospital Minimising Selection Bias • Be aware – Potential sources of selection bias • Equal opportunity for participation and follow-up – Cases / Controls – Exposed / Unexposed groups – Intervention / Control groups • Tactics for high participation / follow-up rates – Reminders / Postcards / Phone calls BMA Medical College and Vajira Hospital Questionnaire plus language choice Language request Response Non-response Questionnaire Questionnaire Questionnaire plus language choice plus language choice plus language choice New questionnaire Response Non-response Language request Response Non-response Language Language New request questionnaire request Response Response Response Non-response Non-response Questionnaire Non-response plus language choice Language request Response New New questionnaire questionnaire Response New questionnaire Response Response Not at home Refusal Non-response Phone call Not at home Response Response Visit Non-response Non-response Non-response Refusal BMA Medical College and Vajira Hospital Assessing Selection Bias • Demographic approach / Alternative data – What information is available on your non-responders? – Where did you get sample from? – Can you examine response by age / sex / occupation / etc? • Examine “reluctant” responders Prevalence Wave 1 15% 15% Wave 2 14% 12% Wave 3 15% 10% BMA Medical College and Vajira Hospital Potential Effect of Non-response • Study: to estimate the prevalence of Raynauds Phenomenon in schoolchildren – Subjects: – Response rate: 903 children aged 12-15yrs 80% (183 non-responders) • What is potential effect of non-response bias? RP No RP Prevalence 95%CI Original 107 613 14.9% 12.3-17.5% - 107 796 11.8% 9.7-14.0% Over: ~25% 290 613 32.1% 29.1-35.2% Under: ~50% BMA Medical College and Vajira Hospital Non-Random Bias • Selection bias – Concerned about who is in your study • Information bias – Concerned about the information you elicit from your subjects BMA Medical College and Vajira Hospital Information Bias • What information are you getting from subjects? • Concern – Are there systematic differences in what is being collected, between study groups? – Does each subject have an equal chance of providing the same information? • Sources – Observer bias – Attention bias – Surveillance bias – Recall bias BMA Medical College and Vajira Hospital Information Bias – Observer Bias • Interviewer knowledge may influence structure of questions • Preconceived expectations of study outcome • Study methods may change over time • Different investigators may examine different subjects • Times / locations of interviews may vary BMA Medical College and Vajira Hospital Minimising Observer Bias • Standardised techniques / instruments / etc – Thorough training of data collection staff – Test agreement between interviewers / instruments • Use objective measurements where possible • Where possible, researchers should be – Randomly allocated to subjects – Blind to study question – Blind to case / control status BMA Medical College and Vajira Hospital Information Bias – Attention Bias • “Hawthorn” Effect – Western Electric Co., Illinois • People may respond differently if they think they know what is being studied • Potential effect: – ↑↓ prevalence of disease – ↑↓ relationship under examination BMA Medical College and Vajira Hospital Minimising Attention Bias • Mask true study question from participants – Ethics – Informed consent – “Health” study • Collect information about several outcomes – Difficult in a case-control study • Collect information about several exposures BMA Medical College and Vajira Hospital Information Bias – Surveillance • Tendency to examine more closely those with outcome of interest – Case-control study to examine the association between occupational asbestos exposure and lung cancer – Temptation to follow cases • Tendency to follow more closely (or for longer) those with exposure of interest – Randomised controlled trial to examine CBT for low back pain – Temptation to follow treatment group BMA Medical College and Vajira Hospital Minimising Surveillance Bias • Ensure identical methodological procedures for all study participants • Where possible, blind researchers – To study question – To case / control status – To exposure / non-exposure status – To treatment / non-treatment group BMA Medical College and Vajira Hospital Information Bias – Recall Bias • Major concern where exposure data measured retrospectively – Cross-sectional study – Case-control studies • Concern – Differential recall between cases and controls BMA Medical College and Vajira Hospital Information Bias – Recall Bias Odds Ratio: Chronic Widespread Pain 20 Hospitalisation Operation 10 8 6 4 2 1 .8 .6 .4 .2 N Y Y N Y Y Self-report GP records BMA Medical College and Vajira Hospital Minimising Recall Bias • Minimise period of recall (if possible) • Measure exposure data objectively – Medical notes – Third-party verification of exposure information – Triangulation of measurements • Do you have to conduct a retrospective study? – Prospective (e.g. National Childhood Development Study) – Retrospective (e.g. Pre-eclampsia and Hypertension) BMA Medical College and Vajira Hospital Bias – Summary • Concerned with the internal validity of a study – i.e. the extent to which, within the subjects studied, the results are true • Deviation of results, or inferences, from the truth – Or, processes leading to such deviation • Results from some aspect(s) of study design or conduct BMA Medical College and Vajira Hospital Bias – Summary • Can serve to incorrectly estimate – Occurrence of disease – Existence (or absence) of an association – Strength of an association • Random bias – Random misclassification – Biases results towards null hypothesis (until >50%) • Non-random bias – Can bias results towards, or away, from null hypothesis BMA Medical College and Vajira Hospital Bias – Summary • Can be prevented by design – Use of accurate instruments – Volunteer bias e.g. pre-select potential participants – Recall bias e.g. prospective design – Non-response bias e.g. high response rate – Loss to follow-up e.g. high response rate – Observer bias e.g. blinding of researchers • Equal importance (equal treatment) – Cases / Controls – Exposed / Unexposed individuals – Treatment / Non-treatment groups BMA Medical College and Vajira Hospital Bias – Summary • Can be estimated • Cannot be overcome by analysis • May be useful BMA Medical College and Vajira Hospital Any Questions? • Random bias – Random misclassification • Non random bias – Selection • • • • Volunteer bias Referral bias Healthy-worker effect Non-response (follow-up) – Information bias Observer bias Attention bias Surveillance bias Recall bias – Note: this lists are not exhaustive! BMA Medical College and Vajira Hospital Confounding BMA Medical College and Vajira Hospital What is Confounding? • Confusing, or mixing, of effects • Two (or more) different explanations for trends in the data cannot be differentiated • You observe a relationship Exposure Outcome – Could this be due to another exposure? BMA Medical College and Vajira Hospital Down’s Syndrome 18 Cases per 1000 live births 16 14 12 10 8 6 4 2 0 1 2 3 4 5+ Birth order BMA Medical College and Vajira Hospital Down’s Syndrome 90 Cases per 1000 live births 80 70 60 50 40 30 20 10 0 <20 20-24 25-29 30-34 35-39 40+ Maternal age (yrs) BMA Medical College and Vajira Hospital Down’s Syndrome 100 Cases per 1000 live births 90 80 70 60 50 40 30 20 Birth order 3 4 5+ 40+ 2 35-39 1 <20 20-24 0 25-29 30-34 10 Maternal age (yrs) BMA Medical College and Vajira Hospital Association between A and B X • They are unrelated A • A causes B A B • B causes A B A • 3rd Variable C A C B B BMA Medical College and Vajira Hospital Is “C” a Confounder? • C is only associated with A X • C is only associated with B X • C is associated with both A and B ? • C is on the path between A and B X Exposure (A) Variable C Outcome (B) Variable C Variable C Variable C BMA Medical College and Vajira Hospital Coffee and Myocardial Infarction • Hypothesis – Drinking coffee causes an increase in the risk of myocardial infarction Coffee ? ? M.I. ? Smoking • Conclusion Step 6 1 2 3 4 5 – What Smoking Is Could there the happens potential cigarette smoking an is association? a confounding to be confounder smoking the a path association confound variable? variable associated between the relationship? withcoffee the outcome? exposure? drinking and if we for smoking? – MI Effect of adjust non-adjustment: over-estimation of effect BMA Medical College and Vajira Hospital Obesity and Myocardial Infarction • Hypothesis – Obesity causes in increase in the risk of myocardial infarction Obesity M.I. Cholesterol • However Query6 Step – What Cholesterol Could happens cholesterol is ato path the confound variable, association this notassociation? between a confounding obesity variable and MI if we – adjust Shouldfor notcholesterol? adjust for cholesterol BMA Medical College and Vajira Hospital Smoking and Low Birth Weight • Hypothesis – Smoking increases the risk of having a baby of low birth weight Smoking Low weight Maternal age • Conclusion Query6 Step – Maternal Could happens What maternal age isto age a confounding theconfound association this variable between association? smoking and low if we adjust for maternal age? of effect – birth Effectweight of non-adjustment: under-estimation BMA Medical College and Vajira Hospital Properties of a Confounder • A confounder must be – Associated with the exposure – Associated with the outcome • A confounder must not be – A path variable • A confounder may – Increase any observed effect – Decrease any observed effect BMA Medical College and Vajira Hospital Properties of a Path Variable • Must be on the same “path” as exposure and outcome Obesity M.I. Cholesterol • But needn’t be between them Obesity M.I. Cholesterol BMA Medical College and Vajira Hospital How to Control for Confounding • Prevent it – Restriction – Randomisation – Matching • Assess it – Stratification – Standardisation – Adjustment BMA Medical College and Vajira Hospital Preventing Confounding • Restriction – Specify restricted inclusion criteria – Study will be homogeneous for the potential confounder • Randomisation – Randomise participants based on the exposure of interest – Potential confounders evenly distributed between groups • Matching – Match subjects based on (potential) confounding variable – Potential confounder evenly distributed between groups BMA Medical College and Vajira Hospital Preventing Confounding • Hypothesis Aspirin ↓DVT • Potential confounder – Smoking status • Methods to prevent confounding – Restriction – Randomisation – Matching BMA Medical College and Vajira Hospital Preventing Confounding • Hypothesis Aspirin ↓DVT • Restriction – Include only non-smokers • Advantages • Disadvantages – Any observed effect should not be confounded by smoking – Smoking Error in measurement Misclassification – Residual confounding BMA Medical College and Vajira Hospital Preventing Confounding • Hypothesis Aspirin ↓DVT • Randomisation – Randomise subjects • Advantages • Disadvantages – Any observed effect should not be confounded by smoking – Nor any other variable – Errors in randomisation – Smoking Error in measurement Misclassification – Residual confounding BMA Medical College and Vajira Hospital Preventing Confounding • Hypothesis Aspirin ↓DVT • Matching – If cases smoke, match to a smoker; likewise nonsmokers • Advantages • Disadvantages – Any observed effect should not be confounded by smoking – Smoking Error in measurement Misclassification – Residual confounding BMA Medical College and Vajira Hospital Disadvantages of Prevention • Restriction – Harder to achieve desired sample size – Limits generalisability – Increasingly difficult with >1 potential confounder • Randomisation – Limited use outside RCTs • Matching – Limited use outside case-control studies – Increasingly difficult with >1 potential confounder – Effects of matched variables cannot be examined BMA Medical College and Vajira Hospital How to Control for Confounding • Prevent it – Restriction – Randomisation – Matching • Assess it – Stratification – Standardisation – Adjustment BMA Medical College and Vajira Hospital Assessing Confounding • Stratification – Assess exposure-outcome relationship independently for different confounder strata • Standardisation – Model exposure-outcome relationship weighted by the potential confounder • Statistical adjustment – Model exposure-outcome relationship while controlling for potential confounders BMA Medical College and Vajira Hospital Stratification • Separate (stratify) analysis into sub-groups – Choose sub-groups (strata) based on value of potential confounding variables • Analogy – Conducting several restricted studies within the same sample population BMA Medical College and Vajira Hospital Stratification – Example • Study: to examine whether breast feeding decreases the risk of infant gastroenteritis Breast feeding Gastroenteritis • We know that ↑ Soc-Ec group ↑ Breast-feeding ↑ Soc-Ec group ↑ Hygiene ↓ Over-crowding ↑ Hygiene ↓ Over-crowding ↓ Gastroenteritis BMA Medical College and Vajira Hospital Stratification – Example • Is breast feeding is protective of gastroenteritis? – Cohort Study Breast-fed Hospital admission for gastroenteritis Yes No No 77 (22%) 274 RR: 1.3 Yes 89 (17%) 443 (1.0-1.8) • Query: relationship with socio-economic group S-Ec group Low 82 (24%) 254 RR: 1.6 High 85 (15%) 472 (1.2-2.2) BMA Medical College and Vajira Hospital Stratification – Example • Stratify analysis by socio-economic group Hospital admission for gastroenteritis Breast-fed (High S-Ec) Breast-fed (Low S-Ec) Yes No No 24 (17%) 118 RR: 1.1 Yes 60 (15%) 344 (0.7-1.8) No 53 (26%) 152 RR: 1.1 Yes 28 (23%) 95 (0.8-1.6) • Risk the same in both groups – Association is confounded by socio-economic group BMA Medical College and Vajira Hospital Stratification – Presenting Results • Presenting crude results = misleading – (Non) breast-feeding and gastroenteritis – RRcrude 1.3 (1.0-1.8) • Present stratified results – RRHigh S-Ec group – RRLow S-Ec group 1.1 (0.7-1.8) 1.1 (0.8-1.6) • Present summary result – Mantel-Haenszel method – RRM-H 1.1 (0.8-1.5) – See: Silman and Macfarlane – Chapter 18 BMA Medical College and Vajira Hospital Stratification – Pros and Cons • Advantages – Can compute summary estimate of effect – Flexible and reversible – Can choose which potential confounders to examine after data collection • Disadvantages – Number of strata is limited by the sample size needed for each stratum – Increasingly difficult with >1 potential confounder – Difficult to incorporate confounders as continuous variables BMA Medical College and Vajira Hospital Assessing Confounding • Stratification – Assess exposure-outcome relationship independently for different confounder strata • Standardisation – Model exposure-outcome relationship weighted by the potential confounder • Statistical adjustment – Model exposure-outcome relationship while controlling for potential confounders BMA Medical College and Vajira Hospital Standardisation • Adjust risk in exposed group to that which would have been observed had they had the same confounder distribution as the unexposed group • Compute effect measure using conventional methods – Relative risk – Odds ratio – Etc BMA Medical College and Vajira Hospital Standardisation – Example • Conduct crude analysis Exposure Disease Person years Incidence Yes 15 500 3% No 38 2500 1.5% • Crude Risk Ratio – Ratio of crude incidence Incidenceexposed Incidencenon-exposed = 3.0 1.5 = 2.0 BMA Medical College and Vajira Hospital Standardisation – Example • Could this relationship be confounded by age? Exposed Group Age Non-exposed Group Number Proportion Number Proportion 25-44 100 0.20 900 0.36 45-64 180 0.36 820 0.33 65+ 220 0.44 780 0.31 Total 500 1.0 2500 1.0 Age Disease Person years Incidence 25-44 6 994 0.6% 45-64 14 986 1.4% 65+ 33 967 3.3% BMA Medical College and Vajira Hospital Standardisation – Example • Crude Risk Ratio – Ratio of crude incidence Incidenceexposed Incidencenon-exposed = 3.0 1.5 = 2.0 • Standardised Risk Ratio – Ratio of age-standardised incidence Age-adjusted Incidenceexposed Incidencenon-exposed = ?? 1.5 = ?? BMA Medical College and Vajira Hospital Standardisation – Example • Standardisation – Examine the age-specific incidence in the exposed group – Examine age profile in the non-exposed group – Multiply, to produce age-specific values for exposed group – Sum, to produce weighted incidence for exposed group Exposed Group Unexposed Group Disease Person years Inc. (%) Number Proportion Weighted incidence (IncW) 24-44 1 100 1.0 900 0.36 0.36 45-64 4 180 2.2 820 0.33 0.73 65+ 10 220 4.5 780 0.31 1.40 [Crude incidence = 3.0%] Total 1.0 ΣIncW=2.5% BMA Medical College and Vajira Hospital Standardisation – Example • Crude Risk Ratio – Ratio of crude incidence Incidenceexposed Incidencenon-exposed = 3.0 1.5 = 2.0 • Standardised Risk Ratio – Ratio of age-standardised incidence Age-adjusted Incidenceexposed Incidencenon-exposed = 2.5 1.5 = 1.7 • Conclusion – Exposure associated with a 70% increase in risk, not 100% BMA Medical College and Vajira Hospital Standardisation • Advantages – Can compute summary estimate of effect – Flexible and reversible – Can choose which potential confounders to examine after data collection • Disadvantages – Increasingly difficult with >1 potential confounder – Difficult to incorporate confounders as continuous variables BMA Medical College and Vajira Hospital Assessing Confounding • Stratification – Assess exposure-outcome relationship independently for different confounder strata • Standardisation – Model exposure-outcome relationship weighted by the potential confounder • Statistical adjustment – Model exposure-outcome relationship while controlling for potential confounders BMA Medical College and Vajira Hospital Statistical Adjustment • Model the relationship of interest, mathematically – Adjust for variance in the potential confounding variable(s) • Simple relationship – Analysis of relationship – Statistically adjusted analysis of relationship Variation in Exposure Exposure Variation Outcome in Outcome Variation in potential confounder BMA Medical College and Vajira Hospital Statistical Adjustment • Study – To examine association between breast-feeding and infant gastroenteritis – Crude (unadjusted) model Poisson regression Log likelihood = -441.94016 Number of obs LR chi2(1) Prob > chi2 Pseudo R2 = = = = 883 3.00 0.0831 0.0034 -----------------------------------------------------------------------------gastro | IRR Std. Err. z P>|z| [95% Conf. Interval] -------------+---------------------------------------------------------------breast | 1.31131 .2040887 1.74 0.082 .9665549 1.779033 ------------------------------------------------------------------------------ BMA Medical College and Vajira Hospital Statistical Adjustment • Study – To examine association between breast-feeding and infant gastroenteritis – Adjusting for socio-economic group Poisson regression Log likelihood = -435.22429 Number of obs LR chi2(2) Prob > chi2 Pseudo R2 = = = = 874 9.71 0.0078 0.0110 -----------------------------------------------------------------------------gastro | IRR Std. Err. z P>|z| [95% Conf. Interval] -------------+---------------------------------------------------------------breast | 1.136832 .1909347 0.76 0.445 .8179641 1.580005 socec | 1.531345 .2566646 2.54 0.011 1.102568 2.126868 ------------------------------------------------------------------------------ BMA Medical College and Vajira Hospital Statistical Adjustment • Study – To examine association between breast-feeding and infant gastroenteritis – Adjusting for socio-economic group and over-crowding Poisson regression Log likelihood = -430.45422 Number of obs LR chi2(5) Prob > chi2 Pseudo R2 = = = = 874 19.25 0.0017 0.0219 -----------------------------------------------------------------------------gastro | IRR Std. Err. z P>|z| [95% Conf. Interval] -------------+---------------------------------------------------------------breast | 1.159983 .1952895 0.88 0.378 .8339633 1.613452 socec | 1.517063 .2544418 2.48 0.013 1.092044 2.107498 crowding_2 | 1.267779 .3345957 0.90 0.369 .755774 2.126645 crowding_3 | 1.880479 .4896574 2.43 0.015 1.128819 3.132656 crowding_4 | 1.903118 .6026854 2.03 0.042 1.023068 3.540193 ------------------------------------------------------------------------------ BMA Medical College and Vajira Hospital Statistical Adjustment • Advantages – Can choose which potential confounders to examine after data collection – Easy to incorporate >1 potential confounder – Continuous variables can be fully used (with care) – Flexible and reversible • Disadvantages – Relevant co-variables must have been measured – Results may be hard to understand – Will produce the best mathematical model BMA Medical College and Vajira Hospital CONFOUNDING – SUMMARY BMA Medical College and Vajira Hospital Confounding – Summary • Describes an association that is true but is misleading • To be a confounder a variable must – Be associated with the outcome of interest; and – Be associated with the exposure of interest • To be a confounder a variable must not – Be on the path • Upstream or downstream from the exposure BMA Medical College and Vajira Hospital Confounding – Summary • Confounding – May increase or decrease the magnitude of any observed effect – Can be prevented in design • Restriction • Randomisation • Matching – Can be overcome in analysis • Stratification • Standardisation • Statistical adjustment (multivariable models) – Is not black and white! BMA Medical College and Vajira Hospital Confounding – Extra • A potential confounder may be – More than one variable – But it’s only possible to adjust for variables you have measured! • Residual confounding: potential effect of – All unexamined variables – All unmeasured variables – All extra variance in poorly measured variables • Very important to measure all potential confounders BMA Medical College and Vajira Hospital Any Questions? • Confounding • Path variables • Preventing confounding – Restriction – Randomisation – Matching • Assessing confounding – Stratification – Standardisation – Multivariable analysis BMA Medical College and Vajira Hospital