Validity Generalization Hein Stigum Presentation, data and programs at: http://folk.uio.no/heins/ May-16 H.S. 1 Precision and validity • Measures of populations – precision - random error - statistics – validity - systematic error – epidemiology • Lack of validity = measures are biased – type of bias – direction of the bias Precision Bias True value May-16 H.S. Estimate 2 Type of bias • Selection bias – Are those who answer different? • Information bias – Do they tell the truth? • Confounding – Is the association a cause? May-16 H.S. 3 Selection bias May-16 H.S. 4 Sources of selection bias • Selective response – sexual survey • Self selection – Nevada atom test and leukemia • Loss to follow up connected to disease – air pollution and astma • Healthy worker effect – aluminium workers and lung disease May-16 H.S. 5 Selection bias Population Sample Respons Responders Non-responders Outcome May-16 H.S. 6 Selective survival Selective survival 6 Disease Death 5 4 3 2 1 0 0 May-16 2 4 6 H.S. 8 10 7 Information bias May-16 H.S. 8 Non-differential misclassification Heart disease + + 200 800 Smoke - 100 2 900 RR= True smoking 6.0 Heart disease + + 180 720 Smoke - 120 2 980 RR= 1 000 3 000 4 000 10% of smokers report no smoking 900 3 100 4 000 5.2 Non-differential: May-16 H.S. RR 9 Sources of information bias • Not true – males report more partners than females • Not blinded – passive smoking and astma • Selective recall – alcohol in pregnancy and malformations May-16 H.S. 10 CONFOUNDER DEFINITION May-16 H.S. 11 Confounding • Ideal: Exposed – Same subjects are both exposed and unexposed at the same time, (counterfactual) • Practice: Unexposed – As equal as possible • Comparison bias: – Confounding May-16 H.S. 12 Associations • E and D associated E D – E causes D C – E and D have common cause E D C – Both E May-16 D • Overall E-D association = spurious effect from C + causal E-D effect H.S. 13 Classic confounder C is the confounder RRED is biased RRED|C is unbiased C E D age + + vitamins - birth defects RRED =0.8 positive bias Adjust for age: RRED|C=0.5 is unbiased true biased 0 May-16 1 H.S. 14 Confounding: Downs syndrom by parity Downs syndrom 0.3 0.25 0.2 % 0.15 0.1 0.05 0 0 1 S1 2 Parity May-16 H.S. 3+ 15 Downs by parity and mothers age 0.5 0.4 0.3 % 0.2 0.1 0 0 May-16 1 >32 <32 2 H.S. 3+ 16 Downs syndrom, logistic regression Crude Adjusted Odds Confidence Ratio interval Variable Parity +1 child 1.4 Adjusted Odds Confidence Ratio interval Variable Parity +1 child Mothers age +1 year May-16 (1.2 - 1.6) H.S. 1.0 (0.8 - 1.2) 1.3 (1.2 - 1.3) 17 Generalization May-16 H.S. 18 Generalization • Do the result apply outside the sample? • Statistical generalization • Smoking among males, generalize to females? – Representative sample • Biological generalization • Drug effect on males, generalize to females? – Information from outside the study • Animal studies, generalize to humans? – Homogenous sample May-16 H.S. 19