Epidemiology Kept Simple Chapter 12 Error in Epidemiologic Research 7/28/2016 1 §12.1 Introduction • View analytic studies as exercises in measuring association between exposure & disease • All such measurements are prone to error • We must understand the nature of measurement error if we are to avoid train wrecks* * a disaster or failure, especially one that is unstoppable or unavoidable 7/28/2016 2 Parameters and Estimates Understanding measurement error begins by distinguishing between parameters and estimates Parameters – Error-free – Hypothetical – Measure effect Statistical estimates – Error-prone – Calculated – Measure association Epidemiologic statistics are mere estimates of the parameters they wish to estimate. 7/28/2016 3 Target Analogy Let Φ represent the true relative risk for an exposure and disease in a population Replicate the study many times Let ˆi represent the RR estimate from study i How closely does an estimate from a given study reflect the true relative risk (parameter)? 7/28/2016 4 Target Analogy 7/28/2016 5 Random Error (Imprecision) • Balanced “scattering” • To address random error, use – confidence intervals – hypothesis tests of statistical significance 7/28/2016 6 Confidence Intervals (CI) • Surround estimate with margin of error • Locates parameter with given level of confidence (e.g., 95% confidence) • CI width quantifies precision of the estimate (narrow CI precise estimate) 7/28/2016 7 Mammagraphic Screening and Breast Cancer Mortality • Exposure ≡ mammographic screening • Disease ≡ Breast cancer mortality • First series (studies 1 – 10): women in their 40s • Second series (studies 11 – 15): women in their 50s 7/28/2016 8 Hypothesis Tests • Start with this null hypothesis H0: RR = 1 (no association) • Use data to calculate a test statistic • Use the test statistic to derive a Pvalue • Definition: P-value ≡ probability of the data, or data more extreme, assuming H0 is true • Interpret P-value as a measure of evidence against H0 (small P gives one reason to doubt H0) R.A. Fisher 7/28/2016 9 Conventions for Interpretation • Small P-value provide strong evidence against H0 (with respect to random error explanations only!) • By convention – P ≤ .10 is considered marginally significant evidence against H0 – P ≤ .01 is considered highly significant evidence against H0 • Do NOT use arbitrary cutoffs (“surely, god loves P = .06”) R.A. Fisher 7/28/2016 10 Childhood SES and Stroke Factor RR P-value Crowding < 1.5 = 0.4 1.5 – 2.49 = 1.0 (ref.) 2.5 – 3.49 = 0.6 3.5 = 1.0 trend P = 0.53 Tap water 0.73 P = 0.53 Toilet type flush/not shared = 1.3 flush/shared = 1.0 (referent) no flush = 1.0 trend P = 0.67 Ventilation good = 1.0 (ref.) fair = 1.7 poor = 1.7 trend P = 0.08 Cleanliness good= 1.1 fair = 1.0 (ref.) poor = 0.5 trend P = 0.07 (persons/room) 7/28/2016 Source: Galobardes et al., Epidemiologic Reviews, 2004, p. 14 Nonsignif. evidence against H0 Marginally significant evidence against H0 11 Systematic Error (Bias) • Bias = systematic error in inference (not an imputation of prejudice) • Amount of bias • Direction of bias –Toward the null (under-estimates risks or benefits) –Away from null (overestimates risks or benefits) 7/28/2016 12 Categories of Bias • Selection bias: participants selected in a such a way as to favor a certain outcome • Information bias: misinformation favoring a particular outcome • Confounding: extraneous factors unbalanced in groups, favoring a certain outcome 7/28/2016 13 Examples of Selection Bias • • • • • • Berkson’s bias Prevalence-incidence bias Publicity bias Healthy worker effect Convenience sample bias Read about it: pp. 229 – 231 7/28/2016 14 Examples of Information Bias • Recall bias • Diagnostic suspicion bias • Obsequiousness bias • Clever Hans effect • Read about it on page 231 7/28/2016 16 Memory Bias • Memory is constructed rather than played back • Example of a memory bias is The Misinformation Effect ≡ a memory bias that occurs when misinformation affects people's reports of their own memory • False presuppositions, such as "Did the car stop at the stop sign?" when in fact it was a yield sign, will cause people to misreport actually happended Loftus, E. F. & Palmer, J. C. (1974). Reconstruction of automobile destruction. Journal of Verbal Learning and Verbal Behaviour, 13, 585-589. 7/28/2016 17 Recall Bias in CaseControl Studies 7/28/2016 18 Differential & Nondifferential Misclassification • Non-differential misclassification: groups equally misclassified • Differential misclassification: groups misclassified unequally 7/28/2016 19 Nondifferential and Differential Misclassification Illustrations 7/28/2016 20 Confounding • A distortion brought about by extraneous variables • From the Latin meaning “to mix together” • The effects of the exposure gets mixed with the effects of extraneous determinants 7/28/2016 22 Properties of a Confounding Variable • Associated with the exposure • An independent risk factor • Not in causal pathway 7/28/2016 23 Example of Confounding E ≡ Evacuation Died Survived Total method Helicopter 64 136 200 Road 260 840 1100 D ≡ Death following auto • R1 = 64 / 200 = .3200 • R0 = 260 / 1100 = .2364 accident • RR = .3200 / .2364 = 1.35 • Does helicopter evacuation really increase the risk of death by 35%? Surely you’re joking! • Or is the RR of 1.35 confounded? 7/28/2016 25 Serious Accidents Only (Stratum 1) • • • • Died Survived Total Helicopter 48 52 100 Road 60 40 100 R1 = 48 / 100 = .4800 R0 = 60 / 100 = .6000 RR1 = .48 / .60 = 0.80 Helicopter evacuation cut down on risk of death by 20% among serious accidents 7/28/2016 26 Minor Accidents Only (Stratum 2) Helicopter Road • • • • Died Survived Total 16 84 100 200 800 1000 R1 = 16 / 100 = .16 R0 = 200 / 1000 = .20 RR2 =.16 / .20 = 0.80 Helicopter evacuation cut down on risk of death by 20% among minor accidents 7/28/2016 27 Accident Evacuation Properties of Confounding • Seriousness of accident (Confounder) associated with method of evacuation (Exposure) • Seriousness of accident (Confounder) is an independent risk factor for death (Disease) • Seriousness of accident (Confounder) not in causal pathway between helicopter evaluation (Exposure) and death (Disease) 7/28/2016 28