Cambridge University Press 978-1-108-43671-7 — Evidence-Based Diagnosis 2Nd Edition Index More Information

Cambridge University Press 978-1-108-43671-7 — Evidence-Based Diagnosis 2nd Edition Index More Information

Index

AAA. See abdominal aortic adjustment from anchor, in AUROC. See area under an aneurysm probability estimates, ROC curve ABCD2 Score, 339–40 310–11 AUSTRI trial, 216–17 ® abdominal aortic aneurysm Advair inhaler, 216–17 authors, of randomized trials, (AAA), reliability of age at first birth, college 206 testing for, 338 education and, 349 autism spectrum disorder with screening tests, 350 ALND. See axillary lymph node (ASD), 354–5 absolute risk increase (ARI), dissection autonomy, clinician, 306–7 221–2 α, 281 availability, in probability absolute risk reduction (ARR), Altman, Douglas, 290 estimates, 310 3, 215–17, 221–2 ambiguous test results, average standard deviation, 123 confidence intervals around, spectrum bias from axillary lymph node dissection 292–3 exclusion of, 86–97 (ALND), 79–80, 318–56 black belt, 295 American Cancer Society, blue belt, 294 305–6 B. See cost of failing to treat brown belt, 294–5 amoxicillin bacteremia green belt, 293–4 for bacteremia in newborns, classification trees for, 183, white belt, 293 292–5 185 yellow belt, 293 for OME, 344–5 in newborn, 5, 47–8 accuracy, 8–9, 12, 319–20 amylase, serum, 78–80 confidence intervals in in diagnostic test studies, anchoring bias, 311–12 negative studies of, 292–5 76–80 anticholinergic medication, for posterior probability for reliability in lieu of, 110 enuresis, 345–6 multi-level tests of, 60 of risk predictions antidepressants regret graphs for, 63–4 calibration in, 147–9, prenatal, 354–5 ROC curve and, 48–51, 55 152–67, 338–9 randomized trials with, bacterial meningitis discrimination in, 146, confidence intervals in, bias in diagnostic test studies 150–67, 338–9 353–4 of, 330 NRI and IDI for, 165–6 appendicitis classification trees for, 183, quantification of, 146–67, partial verification bias and, 185 338–9 83 ROC curve and, 51–2 recalibration and, 154 reliability of testing for, 333 base-rate neglect, 309, 311–12 ® acetaminophen (Tylenol ), speed bumps as diagnostic Bayes, Thomas, 3 355–6 tool for, 332 Bayesian statistical analysis. See ACI-TIPI. See Acute Coronary WBC count for, 313 also posterior Ischemia–Time area under an ROC curve probability; prior Insensitive Predictive (AUROC), 51 probability Instrument discrimination in risk of clinical trials, 291–2 acute cardiac ischemia, wall predictions and, 150–67 confidence intervals and, 290 motion abnormalities as Wilcoxon Rank Sum test P-values and, 282–4 test for, 80, 329 and, 54–5 benefit per bad outcome Acute Coronary ARI. See absolute risk increase prevented (BBOP), Ischemia–Time ARR. See absolute risk 218–21 Insensitive Predictive reduction β, 281 Instrument (ACI-TIPI), ASD. See autism spectrum between-group comparisons, in 192–3 disorder randomized trials, 214 acute ligamentous knee injury, 2 as-treated analysis, 211–13 bias ADHD. See attention deficit- attention deficit-hyperactivity anchoring, 311–12 hyperactivity disorder disorder (ADHD), 348 cognitive, 311

357

Index

bias (cont.) blinding, in randomized trials, for ICU Mortality confirmation, 311 208–9, 345 Probability Model, in diagnostic test studies, 78 blue belts, 294 153–67 application of, 100–1 BMD. See bone mineral density for low back pain, 152 differential verification, BNP. See B-type natriuretic mean bias, MAE, and Brier 81–2, 86–8, 329–30 peptide Score for, 147–9, 338–9 double gold standard, body packing, reliability of recalibration and, 154 81–2, 86–8, 329–30 testing for, 333–8 ROC curves compared imperfect gold standard, bone mineral density (BMD), with plots of, 151–67 81–2, 89–91, 330–2 test–retest reliability in, cancer screening tests incorporation, 78–82, 329 127–9 differential verification bias partial verification, 80–5, Bonferroni correction, 287–9 in, 86 330 in antidepressant in EBM, 304–6 spectrum, 81–2, 86–97, randomized trials, overdiagnosis in, 263–5 330 353–4 total v. cause-specific falsification tests for, 236–8, bootstrap aggregation, 196 mortality in, 266–9 348 branch, of classification trees, cannabinoid hyperemesis immortal time, 242, 349 181–2 syndrome, 308 mean, 147–9, 338–9 BRCA testing, referral Cardiac Arrhythmia in post-test probability screening tool for, Suppression Trial, 252 estimates, 311–13 321–39 cardiovascular disease in pre-test probability breast cancer, 5, 269–70 risk predictions for, 341–2 estimates, 309–11 ALND for staging of, 79–80, vitamin E for prevention of, publication, 161–2 318–56 231–2, 237 in randomized trials, 215 BRCA referral screening tool case-control sampling, 12–14, in screening test studies, for, 321–39 321 258–68 EBM and screening of, 304–6 in diagnostic test studies, lead-time, 260–1 likelihood ratios applied to, 75–7 length-time, 261–2 16–17, 21 categorical variables pseudodisease, 263–6 risk prediction studies for, disease definition and, 93–5 slippery linkage, 267–8 163 inter-observer agreement for, stage migration, 261–3, stage migration bias and, 111–21, 332–8 353 262–3 category-free NRI, 165–6 sticky diagnosis, 258–68 2×2 table method applied to, cause-specific mortality, total volunteer effect, 259–60 15–16 mortality v., 266–9 spectrum breast development, reliability CBOP. See cost per bad in bacterial meningitis of staging of, 131 outcome prevented findings, 330 unbalanced disagreement CDC. See US Centers for definition of, 81–2, 91–3 and, 116 Disease Control disease definition v., 93–5 weighted kappa for, 118–20 ceftriaxone, for post Lyme disease prevalence and, Brier Score, 147–9, 338–9 syndrome, randomized 94–5 brown belt, 294–5 trials of, 345 ESR and, 92–3 Browner, Warren, 285 CHD. See congenital heart exclusion of intermediate B-type natriuretic peptide disease test results and, 86–97 (BNP), 58–9, 80 chest pain sensitivity in, 81–2, 91–3 classification trees for, 183–4 specificity in, 81–2, 91–3 C. See cost of treating reliability of testing for, tests nonindependence nondisease 333–4 and, 177–8 CACE. See Complier Average chest wall motion, as test for bilirubin, partial verification Causal Effect acute cardiac ischemia, bias and, 83–5 Calibrated Finger Rub Auditory 80, 329 Bland–Altman plot, 128–9, 338 Screening Test chest x-ray, for lung cancer modified, 127–30 (CALFRAST), 327–8 screening, 350–1 variable types and, for calibration, 127–30 CHF. See congestive heart reliability, 110–11 in risk predictions, 146–9 failure

358

Index

chorionic villus sampling conclusions, in diagnostic test congestive heart failure (CHF), (CVS), 5, 93–5, 178–83, studies, 76–80 BNP test in, 58–9, 80 186, 189–91 conditional independence continuous measurements, chromosomal abnormalities, in imperfect gold standard reliability in, 121 fetal, 5, 93–5, 178–83, bias, 89–90 calibration for, 127–30 186, 188–91 of tests, 175 test–retest, 121 classification trees, 181–5 conditional probability, 10 average standard deviation clinical decision making, confidence intervals, 280 and, 123 probability estimates v., for acetaminophen with correlation coefficient and, 312–13 vaccines, 355–6 123–5 clinical decision rules in antidepressant error by magnitude with, clinician v., 198 randomized trials, 125–7 EBM in future, 314–15 353–4 method comparison for, k-fold cross validation in, 196 around ARR, 292–3 127–9 logistic regression in black belt, 295 within-subject standard development of, 192–5 blue belt, 294 deviation/repeatability, overfitting and, 193–6 brown belt, 294–5 122–3 test selection for, 192–6 green belt, 293–4 continuous outcomes, risk clinical experience, statistical white belt, 293 predictions for, 164 expertise v., 304 yellow belt, 293 continuous test, 47 clinical trials, Bayesian analysis background on dichotomous, 47–8 of, 291–2 classical (frequentist) Grim Reaper walking speed, clinician statistics, 281–2 327 autonomy of, 306–7 stochastic and epistemic in hypothetical trial cases, clinical decision rules v., 198 probability, 280–1 326–7 EBM diagnostic errors and, definition of, 289–90 logistic regression for, 308–13 for epidural analgesia and 189–91 CMV. See cytomegalovirus C-section rates, 355 ROC curves in, 51–2 cognitive bias, 311 for Grim Reaper walking AUROC and, 51, 54–5 colic, testing for, 318 speed, 354 information in, 55 college education, age at first in prenatal antidepressant and likelihood ratio birth and, 349 autism studies, 354–5 relationship to, 57–9, colon cancer, screening tests P-values and, 292–3 325–6 for, 269–70 in sentinel-node biopsy optimal cutoffs and, 62–3 community-acquired v. axillary dissection, in signal detection theory, pneumonia, risk 356 49–50 predictions for, 340 for small numerators, for urinalysis, 323–5 comparison group, in 295–6 walking man approach to, randomized trials, 207 confirmation bias, 311 52–4 Complier Average Causal Effect confounding for WBC count in joint (CACE), 234 falsification tests for, 236–8, fluid, 322–3 composite endpoints, 209–10 348 WBC counts and, 48–51, computed tomography (CT), 4 in observational studies, 55 for AAA, reliability of testing 231–3 Wilcoxon Rank Sum test for, 338 propensity scores for, and, 54–5 for body packing, reliability 238–41, 348–9 WBC count, 47–8 of testing for, 333–8 randomized trials for continuous variables, 110–11 for lung cancer screening, minimization of, 205–6 disease definition and, 93, 350–1 in screening tests, 259–60 330 computed tomography confounding by indication, in randomized trials, 215 angiography (CTA), 231–3 cooling, of newborns, 291–2 spectrum bias in, 93 congenital CMV, screening copper standard. See imperfect computed tomography tests for, 353 gold standard bias pulmonary angiogram congenital heart disease coronary artery aneurysms, (CTPA), for PE, 60–2, (CHD), screening tests multiple tests for, 66, 325–6, 343–4 for, 353 332–42 359

Index

correlation coefficient, ROC curves and, 62–3 individual patient data test–retest reliability ROC curves and, 48–52, meta-analysis of, 99–100 and, 123–5 62–3 for metastatic cost of failing to treat disease CVS. See chorionic villus undifferentiated (B), 23, 34–6 sampling carcinoma, 318 cost of test (T), 23, 34–6 cytomegalovirus (CMV), P-values and, analogy with, cost of treating nondisease (C), screening tests for, 353 282–6 23, 34–6 results of, disease probability cost per bad outcome prevented D+/DÀ. See dichotomous estimation and, 3 (CBOP), 218–21 disease state risk predictions v., 144–6 count outcome variables, in D-Dimer, 60–2, 66, 325–6, for rotavirus, 318 randomized trials, 215 343–4 for sexual abuse, in critical appraisal decision curves, 156–60 prepubertal girls, of diagnostic test studies, decision making, probability 336–7 step-by-step approach estimates v., 312–13 step-by-step appraisal of to, 75–80 decision problems, in studies of, 75–80 of randomized trials, 206 diagnoses, 4–5 studies for design and conduct, decision rules appendicitis diagnosis with 206–11 EBM in future, 314–15 speed bumps, 332 results analysis, 211–15 multivariable, 175, 180–1, bias in, 78–97, 100–1 of screening test studies, 192–5 checklists for, 100–1 257–70 clinician v., 198 conclusions in, 76–80 mortality v. survival in, k-fold cross validation in, design for, 75–7, 79–80 258 196 gold standard test in, 76–7, observational studies, overfitting and, 193–6 79–80 259–66 test selection for, index test in, 76–7, 79–80 randomized trials, 265–9 192–6 outcome variables, 76–7, of studies of prediction, deep vein thrombosis (DVT), 79–80 160–3 ultrasound diagnosis of, predictor variables, 76–7, cross-sectional sampling, 9–14, 96–7 79–80 321 delayed cooling study, Bayesian research questions in, in diagnostic test studies, analysis of, 291–2 79–80 75–7 depression, paroxetine or results in, 76–80 C-section rates, epidural imipramine for, step-by-step appraisal of, analgesia and randomized trials with, 75–80 confidence intervals in, 355 confidence intervals in, subjects in, 75–7, 79–80 observational studies of, 353–4 systematic reviews of, 244–5, 338–47 derivation sets, 195–6 98–100, 332–54 CT. See computed tomography dermoscopy, for melanoma dichotomous disease state CTA. See computed diagnosis, 332–54 (D+/DÀ), 4 tomography diagnosis, in EBM, 2–3 dichotomous tests angiography with CT, 4 accuracy in, 8–9, 12, 319–20 CTPA. See computed D+/DÀ and, 4 benefit/cost quantification in, tomography pulmonary decision problems in, 4–5 23 angiogram errors in, 307–13 continuous, 47–8 custom weights, for weighted purpose of, 1–2 cutoffs in, 8, 47–8 kappa statistic, 120–1 testing in, 4 ROC curves and, 48–52 cutoffs, 8, 47–8 diagnostic tests, 4 definitions of, 8, 31 in classification trees, 183–4 bias in studies of, 78–97, for Grunderschnauzer disease definition and, 93, 100–1, 329–32 disease, 319 330 for breast cancer, 79–80, likelihood ratios for, 319–20 logistic regression and, 189 318–56 derivation of, 19–20, 32 in multilevel testing, 61–2 checklists for, 100–1 posterior probability D-Dimer, 325–6 for colic, 318 calculation with, 16–17, graphical approach to, for ectopic pregnancy, 21 63–4 studies for, 4 slide rule for, 21–2, 25–7 360

Index

multiple discrimination, in risk errors logistic regression for, predictions, 146, 150, conditionally independent, 186–7 338–9 in imperfect gold result combination of, for ICU Mortality Probability standard bias, 89–90 178–81 Model, 153–67 in EBM diagnostic process, negative predictive value and, for low back pain, 152 307 8–11, 319–21 recalibration and, 154 clinician, 308–13 patient information risk ratios, rate ratios, and differential diagnosis, 308 combined with, 14–15 hazard ratios for, 154 oversimplification of positive predictive value in, ROC curves and, 150–67 diagnostic problem, 313 8–11, 319–21 diseases probability, 308–13 post-test probability in, classification systems for, mean absolute, 147–9, 338–9 12–14 1–2 post-test estimate, 311–13 pre-test probability in, 11, definition of, spectrum bias pre-test estimate, 309–11 13–14 v., 93–5 Type 1, 281 prevalence in, 9–11 dichotomous erythrocyte sedimentation rate ROC curve for, 51 oversimplification of, 4 (ESR), likelihood ratios sampling schemes for, 9–14, heterogeneous, 176 for, 92–3 321 latent phase of, 257 evidence-based medicine sensitivity, 8–10, 320–39 probability estimates for, (EBM), 303 specificity, 8–11, 320–39 2–3, 308–13 cancer screening tests in, for streptococcal infection, screening tests for, 251–2 304–6 321–2 double gold standard bias, cognitive errors in diagnostic treatment and testing 81–2, 86–8, 329–30 process of, 307 thresholds for, 22–40, Downsyndrome,5,93–5, clinician, 308–13 321–2 178–83,186,188–91, 344 differential diagnosis, 308 expected cost of, 23–5 CHD screening in, 353 oversimplification of for imperfect and costly dual-energy x-ray diagnostic problem, 313 test, 29–30, 34–6 absorptiometry (DXA), in probability estimates, for imperfect but costless test–retest reliability in, 308–13 test, 25–6, 29, 34–6 127–9 criticisms of, 307 no treat-test, 25–30, 37–40 DVT. See deep vein thrombosis clinical experience for perfect but risky or DXA. See dual-energy x-ray denigration as, 304 expensive test, 28–9, absorptiometry limits to clinician 34–6 autonomy as, 306–7 test-treat, 25–30, 37–40 EBM. See evidence-based nihilism of, as basis for, treatment threshold medicine 304–6 probability and, 23–5 echocardiogram, as test for payment denial as, 306–7 visualization of, 25–7 acute cardiac ischemia, pharmaceutical industry 2×2 table method for 80, 329 influence as, 307–8 updating prior ectopic pregnancy, diagnostic randomized trial probability in, 15–16, testing studies for, 4 overemphasis as, 303–4 19–20 elbow extension test, 329–30 statistical expertise blank, 15 enuresis, randomized trials for, overvaluation as, 304 completed, 16 345–6 definition of, 2–3 dichotomous variables, epidural analgesia, C-section diagnosis in, 2–3 110–11 rates and future of, 314–15 kappa for, 112–13 confidence intervals in, 355 as malpractice, 305–6 differential diagnosis, in EBM, observational studies of, in media, 304–6 308 244–5, 338–47 probability in, 308–9 differential distance epistemic probability, 280–1 post-test estimate errors instrument, 234–5 equivalency trials, 215 in, 311–13 differential verification bias, error, measurement. See pre-test estimate errors in, 81–2, 86–8, 329–30 measurement error, in 309–11 discrete variables, 110–11 testing PSA in, 305–6

361

Index

evidence-based medicine funding source, of randomized ICU Mortality Probability (EBM) (cont.) trials, 206 Model, calibration and reasons for teaching, 313–14 discrimination in, treatment in, 2–3 gastroenteritis, diagnostic 153–67 disease classification testing for, 318 IDI. See integrated systems and, 1–2 genetic tests, 162–4 discrimination ® evolocumab (Repatha ), 210, Glasgow Coma Scale, 110–11 improvement 217, 346–7 weighted kappa statistic for, imipramine, for depression, excessive screening, reasons for, 120–1 randomized trials with, 254–6 gold standard test, 8–9 confidence intervals in, expected agreements, with in diagnostic test studies, 353–4 kappa statistic 76–7, 79–80 immortal time bias, 242, 349 balanced/unbalanced, differential verification imperfect gold standard bias, 115–16, 333–6 bias and, 81–2, 86–8, 81–2, 89–91, 330–2 calculations of, 112 329–30 incorporation bias, 78–82, 329 definition of, 112–14 imperfect gold standard independence, of tests, 175–7 marginals impact on, 115 bias and, 81–2, 89–91, spectrum bias and, 177–8 330–2 index testing, in diagnostic test False Discovery Rate (FDR), incorporation bias and, studies, 76–7, 79–80 288–9 78–82, 329 differential verification bias false negative, 8–9 partial verification bias and, 81–2, 86–8, 329–30 false positive, 8–9 and, 80–5, 330 imperfect gold standard bias false-negative rate, 12–14 nonexistent, 91 and, 81–2, 89–91, 330–2 false-negatives, P-values and, reliability in lieu of, 110 incorporation bias and, 282–4 goodness of fit, in logistic 78–82, 329 false-positive rate, 12–14, regression, 191–2 partial verification bias and, 320–1 green belts, 293–4 80–5, 330 false-positives, P-values and, Grim Reaper walking speed, individual patient data meta- 282–4 327, 354 analysis, 99–100 falsification tests, 236–8, 348 group A streptococcus, RADT influenza testing FDR. See False Discovery Rate for, 5, 342–3 CDC website on rapid, 320–1 fecal occult blood screening, Grunderschnauzer disease, prevalence, pre-test 269–70 dichotomous tests for, probability, post-test fetal chromosomal 319 probability and abnormalities, 5, 93–5, Guyatt, Gordon, 2 accuracy calculations 178–83, 186, 188–91 for, 8–14 Feynman, Richard, 286–7 harms, from screening tests, sensitivity, specificity, fluticasone, randomized trials 252–4 positive predictive value of, 216–17 hazard ratios, 154, 354–5 and negative predictive focal segmental β-HCG, 4 value calculations for, glomerulosclerosis, 1–2 Health Professionals study, 8–11, 320–1 follow-up loss 237, 237 treatment thresholds for, in randomized trials, 210–11 Healy, Bernadine, 304–6 22–30, 34–6 in risk predictions studies, hearing loss, CALFRAST instrumental variables, 232–5, 161 screening for, 327–8 244–5, 338–49 follow-up time, in hepatitis C, 330–2 integrated discrimination observational studies, heterogeneous disease, 176 improvement (IDI), 241–2, 349 heterogeneous nondisease, 165–6 FOURIER trial, 210, 217, 176–7 intentionally ordered tests, 286 346–7 heuristics, in pre-test intention-to-treat analysis, Framingham Risk model, probability estimates, 211–13, 232–4, 347–8 decision curves for, 309–11 interaction terms, in logistic 159–60 hypotheses regression, 191–2 fremanezumab, for migraine advance statement of, 286–7 intermediate test results, headaches, randomized multiple, 287–9 spectrum bias from trials of, 346 null, 281 exclusion of, 86–97 362

Index

inter-observer agreement, for Kawasaki disease, multiple tests LRs. See likelihood ratios categorical variables, for, 332–42 lung cancer, screening tests for, 111–21, 332–8 k-fold cross validation, 196 350–1 inter-rater reliability kidney biopsies, 1–2 for diagnosing sexual abuse knee injury, 2 machine learning, 196–7 in prepubertal girls, MAE. See mean absolute error 336–7 latent phase, of disease, 257 magnetic resonance imaging kappa statistic for, 110–12, lead time bias, 260–1 (MRI), for multiple 333–8 leaf, of classification trees, sclerosis diagnosis, classifications of, 121 181–2 99–100 for dichotomous variables, length time bias, 261–2 malignant pleural effusion, 112–13 leukemia, classification of, 2 testing for, 318 expected agreements with, likelihood ratios (LRs), 319–20 malpractice, EBM as, 305–6 112–16, 333–6 definitions of, 16–17 mammography, 5, 30, 269–70 formula for, 112–15 derivation of, 19–20, 32 in EBM, 304–6 good, 121 for ESR, 92–3 likelihood ratios applied to, sensitivity and specificity interval, 55–9 16–17, 21 v., 116–17 for multilevel tests, 55–9, 325–6 2×2 table method applied to, for three or more D-Dimer, 325–6 15–16 categories, 117–21 urine WBC, 323–5 Mann–Whitney U-test, 54–5 interval likelihood ratios, 55–9 odds ratios v., 187–8 marginals, 112, 115 intervention group, in posterior probability masking, in randomized trials, randomized trials, 207 calculation with, 16–17, 208–9, 345 intuition, anchoring bias and, 21 MASS. See Multicentre 311–12 slide rule for, 21–2, 65–6 Aneurysm Screening intussusception, differential in testing threshold Study verification bias in visualization, 25–7 Mayo Lung Study, 265 ultrasound of, 86–8 test independence and, McIsaac Score, for strep throat, inverse probability of treatment 175–7 342–3 weighting, 239 for trisomy 21, 344 mean absolute error (MAE), iron deficiency anemia, 94–5 for WBC count, 55–9 147–9, 338–9 linear weights, for weighted mean bias, 147–9, 338–9 jaundice, partial verification kappa statistic, 117–19 measurement error, in testing, bias and, 83–5 lipase, serum, 78–80 110 joint fluid, WBC count in, lipid-lowering agents, peri- test–retest reliability and, 322–3 operative use of, 349 125–7 liver biopsy, for hepatitis melanoma, dermoscopy Kahenman, Daniel, 312 C staging, 330–2 v. naked eye for kappa statistic, 110–12, Local Average Treatment diagnosing, 332–54 332–3 Effect, 234 Menger, Fred, 193 classifications of, 121 logarithm of odds, 66 Merenstein, Daniel, 305–6 for dichotomous variables, logarithms, 65–6 meta-analysis, individual 112–13 logistic regression, 185–6 patient data, 99–100 expected agreements with clinical decision rules metastatic undifferentiated balanced/unbalanced, developed with, 192–5 carcinoma, testing for, 115–16, 333–6 dichotomous, 186–7 318 calculations of, 112 interaction terms and migraine headaches, definition of, 112–14 goodness of fit in, 191–2 randomized trials for, marginals impact on, 115 modeling for, 188–9 346 formula for, 112–15 odds ratios and, 186–9 minimal change disease, 1–2 good, 121 for single continuous test, mortality sensitivity and specificity v., 189–90 survival v., 258 116–17 for two continuous tests, total v. cause-specific, for three or more categories 189–91 266–8, 267, 269 unweighted, 117 low back pain, risk predictions walking speed as predictor weighted, 117–21 for, 152 of, 327, 354 363

Index

MRI. See magnetic resonance for single continuous test, white belt, 293 imaging 189–90 yellow belt, 293 MS. See multiple sclerosis for two continuous tests, neonatal pain, 347–8 Multicentre Aneurysm 189–91 nephrotic syndrome, 1–2 Screening Study machine learning in, 196–7 net benefit (NB) (MASS), 350 multiple hypotheses and, calculation of, 155–7 multilevel tests, 47 287–9 decision curves for, 156–60 CALFRAST screening for for pulmonary embolism, net reclassification index (NRI), hearing loss, 327–8 343–4 165–6 Grim Reaper walking speed, for strep throat, 342–3 new user design, 232–42 327 multivariable decision rules, newborn in hypothetical trial cases, 175, 180–1, 192–5 bacteremia in, 5, 47–8 326–7 clinician v., 198 confidence intervals in likelihood ratios for, 55–9, k-fold cross validation in, negative studies of, 325–6 196 292–5 D-Dimer, 325–6 overfitting and, 193–6 continuous/multilevel urine WBC, 323–5 test selection for, 192–6 testing for, 55–7 optimal cutoffs for, 61–2 myocardial infarction posterior probability for D-Dimer, 325–6 classification trees for, 183–4 multi-level tests of, 60 graphical approach to, 63–4 logistic regression for regret graphs for, 63–4 ROC curves and, 62–3 predicting, 192–3 ROC curve and, 48–51, 55 probability for, 59–61 myocardial ischemia, wall cooling of, 291–2 CALFRAST screening, motion abnormalities as jaundice in, partial 327–8 test for, 80, 329 verification bias and, D-Dimer, 325 83–5 urine WBC, 323–5 nasal bone absence, in Down urinalysis in, ROC curves for, multiple hypotheses, multiple syndrome diagnosis, 5, 323–5 tests and, 287–9 93–5, 178–83, 186, NEXUS Rule, 181 multiple sclerosis (MS) 188–91 NICE Framingham Risk model, genetic tests for, 163–4 National Lung Screening Trial decision curves for, systematic review of MRI (NLST), 350–1 159–60 diagnosis of, 99–100 natural logarithms, 65 NIH. See negative in health multiple tests NB. See net benefit NLST. See National Lung classification trees in, 181–5 negative in health (NIH), 9–11 Screening Trial decision rules for, 175, negative predictive value, 8–11, NNH. See number needed to 180–1, 192–5 319–21 harm clinician v., 198 in diagnostic test studies NNT. See number needed to k-fold cross validation in, differential verification treat 196 bias effects on, 81–2, no treat–test threshold, 25–30, overfitting and, 193–6 86–8, 329–30 37–40 test selection for, 192–6 imperfect gold standard nominal variables, 110–11 dichotomous bias effects on, 81–2, nonindependence, of tests, logistic regression for, 186–7 89–91, 330–2 175–7 result combination of, incorporation bias effects spectrum bias and, 177–8 178–81 on, 81–2 NRI. See net reclassification independence in, 175–7 partial verification bias index spectrum bias and, 177–8 effects on, 81–5 nuchal translucency, 178–83, for Kawasaki disease, 332–42 spectrum bias effects on, 188–91 logistic regression in, 185–6 81–2, 91–3 null hypothesis, 281 clinical decision rules negative studies, confidence number needed to harm developed with, 192–5 intervals in reporting of, (NNH), in randomized dichotomous, 186–7 292–3 trials, 221–2 interaction terms and black belt, 295 number needed to treat (NNT), goodness of fit in, 191–2 blue belt, 294 3 modeling for, 188–9 brown belt, 294–5 in randomized trials, 215–18, odds ratios and, 186–9 green belt, 293–4 220–1 364

Index

numeric variables, 110–11 overdiagnosis, 263–6 polymerase chain reaction Nurses' Health study, 237 overfitting (PCR) tests, influenza in risk predictions studies, 161 virus, 8–9 observational studies, 231 in test selection for decision pooled cohort equations, in risk confounding by indication rules, 193–6 predictions for in, 231–3 oversimplification, in EBM cardiovascular events, of epidural analgesia and C- diagnostic errors, 313 341–2 section rates, 244–5, PORT Pneumonia Score, 192–5 338–47 pain sensitivity, 347–8 positive in disease (PID), 9–10 falsification tests in, 236–8, pancreatitis, 78–80 positive predictive value, 8–11, 348 paroxetine, for depression, 319–21 follow-up time in, 241–2, 349 randomized trials with, in diagnostic test studies instrumental variables in, confidence intervals in, differential verification 232–5, 244–5, 338–49 353–4 bias effects on, 81–2, propensity scores in, 238–41, partial verification bias, 80–5, 86–8, 329–30 348–9 330 imperfect gold standard of screening tests, 259 partitioning, recursive, bias effects on, 81–2, lead-time bias in, 260–1 181–5 89–91, 330–2 length-time bias in, 261–2 patent ductus arteriosus (PDA), incorporation bias effects overdiagnosis in, 263–6 screening for, 348–9 on, 81–2 stage migration bias in, patient information, test partial verification bias 261–3, 353 information combined effects on, 81–5 volunteer effect in, 259–60 with, 14–15 spectrum bias effects on, odds patient populations, alternative, 81–2, 91–3 logarithm of, 66 237–8, 348 post Lyme syndrome, probability and, 16–19, 33 payment, EBM in denial of, randomized trials for, odds ratios 306–7 345 confidence intervals for, PCR tests. See polymerase posterior probability, 12–14, 319 293–4 chain reaction tests in clinical trial analysis, likelihood ratios v., 187–8 PDA. See patent ductus 291–2 in logistic regression, for arteriosus confidence intervals and, 290 multiple tests, 186–9 PE. See pulmonary embolus EBM diagnostic errors and, in randomized trials, 217–18 Pediatric Research in Office 308–9, 311–13 OME. See otitis media with Settings (PROS) Febrile likelihood ratios for effusion Infant Study, 183, 185 calculation of, 16–17, 21 ® OncoTypeDX , breast cancer Pediatric Ulcerative Colitis for multilevel tests, 59–61 staging with, 318–56 Activity Index CALFRAST screening, ordinal variables, 110–11 (PUCAI), reliability of 327–8 continuous, 47 testing for, 334–6 D-Dimer, 325 discrete, 47 per-protocol analysis, 211–13 urine WBC, 323–5 in randomized trials, 215 pharmaceutical industry, EBM P-values and, 284, 286 ® oseltamivir (Tamiflu ), 218–21 influence by, 307–8 test independence and, otitis media with effusion photophobia, as diagnostic test 175–6 (OME), 344–5 for bacterial meningitis, 2×2 table method for Ottawa Ankle Rule, 181 330 calculation of, 15–16 outcome variables, 76–7, 79–80 PID. See positive in disease post-test probability, 12–14, additional, 236, 348 PLCO Cancer Screening Trial. 308–9. See also in randomized trials, 209–10 See Prostate, Lung, posterior probability count, 215 Colorectal, and Ovarian estimate errors in, 311–13 dichotomous, 215–18 Cancer Screening Trial prediction, 144–6. See also risk ® in screening tests, 257 plecanatide (Trulance ), 215 predictions ovarian cancer pleural effusion, testing for, predictive value, 8–11, 16 BRCA referral screening tool 318 in diagnostic test studies for, 321–39 pneumonia differential verification screening tests for, 352–3 PORT score for, 192–5 bias effects on, 81–2, overconfidence, 312 risk predictions for, 340 86–8, 329–30 365

Index

predictive value (cont.) pre-test estimate errors in, propensity scores, 238–41, imperfect gold standard 309–11 348–9 bias effects on, 81–2, EBM diagnostic errors and, PROS Febrile Infant Study. See 89–91, 330–2 308–13 Pediatric Research in incorporation bias effects epistemic, 280–1 Office Settings Febrile on, 81–2 likelihood ratios and, Infant Study partial verification bias 319–20 Prostate, Lung, Colorectal, and effects on, 81–5 definitions of, 16–17 Ovarian (PLCO) spectrum bias effects on, derivation of, 19–20, 32 Cancer Screening Trial, 81–2, 91–3 posterior probability 351–3 predictor variables, 76–7, 79–80 calculation with, 16–17, prostate cancer, 4, 256, 265, additional, 237, 347–8 21 305–6, 351–2 in screening tests, 257 slide rule for, 21–2, 25–7 prostate-specific antigen (PSA), premature closure, 311 for multilevel tests, 59–61 4, 256, 265, 352 prenatal antidepressants, 354–5 CALFRAST screening, in EBM, 305–6 prenatal ultrasound, 5, 93–5, 327–8 pseudodisease, 263–6 178–83, 186, 188–91 D-Dimer, 325 in Mayo Lung Study, 265 presymptomatic disease, urine WBC, 323–5 PTT. See treatment threshold screening tests for, odds and, 16–19, 33 probability 251–2 posterior (See posterior publication bias, 161–2 pre-test probability, 11, 13–14, probability) PUCAI. See Pediatric 308–9. See also prior post-test, 12–14, 308–9 Ulcerative Colitis probability estimate errors in, 311–13 Activity Index estimate errors in, 309–11 predictive value, 8–11, 16 pulmonary embolus (PE) prevalence pre-test, 11, 13–14, 308–9 D-Dimer test for, 60–2, 66, in dichotomous tests, 9–11 estimate errors in, 325–6, 343–4 spectrum bias and, 94–5 309–11 multiple tests for, 343–4 priming effect, 310–11 prior (See prior probability) V/Q scans for, 86–97 prior probability, 11, 13–14 propensity scores and, Wells Score for, 343–4 in clinical trial analysis, 238–41, 349 P-values, 280 291–2 P-values and, 282, 284, 286 in antidepressant confidence intervals and, 290 representativeness in, randomized trials, diagnostic test study 309 353–4 conclusions and, 78 stochastic, 280–1 background on EBM diagnostic errors and, test independence and, classical (frequentist) 308–11 175–6 statistics, 281–2 for multilevel tests, 59–61 treatment threshold (See stochastic and epistemic CALFRAST screening, treatment threshold probability, 280–1 327–8 probability) as conditional probability, urine WBC, 323–5 2×2 tables and 284 P-values and, 284, 286 blank, 15 confidence intervals and, test independence and, completed, 16 292–3 175–6 prevalence, pre-test black belt, 295 2×2 table method for probability, post-test blue belt, 294 updating, 15–16, 19–20 probability and brown belt, 294–5 probability accuracy, 8–14, 319–20 green belt, 293–4 adjustment from anchor in, for prior probability white belt, 293 310–11 updating, 15–16, 19–20 yellow belt, 293 availability in, 310 sampling schemes and, definition of, 282 conditional, 10 9–14, 321 diagnostic test analogy with, confidence intervals and, 290 sensitivity, specificity, 282–6 diseases and, estimates for, positive predictive value false-positive/false-negative 2–3, 308–13 and negative predictive confusion with, in EBM, 308–9 value, 8–11, 319–39 282–4 post-test estimate errors probiotics, for colic, 318 hypotheses stated in advance in, 311–13 prognostic tests, 144 and, 286–7 366

Index

intentionally ordered tests follow-up starting point in, likelihood ratio relationship and, 286 241 to, 57–9, 325–6 in multiple hypotheses and FOURIER trial, 210, 217, optimal cutoffs and, 62–3 multiple tests, 287–9 346–7 in signal detection theory, FDR and, 288–9 instrumental variables in, 49–50 232–5, 244–5, 338–49 SROC, 98–100, 332–54 QRISK2 score, decision curves outcomes in, 209–10 for urinalysis, 323–5 for, 159–60 for post Lyme syndrome, 345 walking man approach to, QUADAS. See Quality propensity scores and, 52–4 Assessment of 238–41, 348–9 for WBC count in joint fluid, Diagnostic Accuracy purpose of, 205–6 322–3 Studies of screening tests, 265–9 WBC counts and, 48–51, 55 quadratic weights, for weighted treatment effect Wilcoxon Rank Sum test kappa statistic, 119–20 quantification with, 3, and, 54–5 Quality Assessment of 205 recurrence index, for breast Diagnostic Accuracy alternatives to, 231–43 cancer, 163 Studies (QUADAS), CBOP and BBOP, 218–21 recursive partitioning, 181–5 100–1 continuous, ordinal and reference standard. See gold QuickVue, sensitivity, count outcome variables standard test specificity, positive in, 215 referral bias. See partial predictive value and dichotomous outcome verification bias negative predictive variables in, 215–18 referral screening tool (RST), value calculations for, effect size inflation in, with for BRCA testing, 8–11 odds ratio, 217–18 321–39 for enuresis, 345–6 regret bias, 310 RADT. See rapid antigen for migraine headaches, regret graphs, 23, 63–4 detection test 346 decision curves v., 158–60 random forests™, 196–7 NNH, 221–2 relative risk (RR), 215–17 randomized trials NNT, 215–18, 220–1 relative risk reduction (RRR), analysis of for OME, 344–5 215–17 as-treated, 211–13 relative v. absolute reliability, in testing, 110 bias directions in, 215 measures of, 216–17 for AAA, 338 intention-to-treat, 211–13, treatment cost per good for appendicitis, 333 232–4, 347–8 outcome caused, 221 Bland–Altman plot for, multiple comparisons in, rapid antigen detection test 128–9, 338 214 (RADT), for strep modified, 127–30 per-protocol, 211–13 throat, 5, 342–3 variable types and, subgroup, 213–14 rapid influenza diagnostic tests 110–11 between v. within-group (RIDT), 320–1 for body packing, 333–8 comparisons in, 214 rate ratios, 154 for chest pain, 333–4 binding in, 208–9, 345 recalibration, in risk of continuous measurements, conduct of, 206–11 predictions, 154 121 confidence intervals, with receiver operating average standard antidepressants, 353–4 characteristic (ROC) deviations and, 123 critical appraisal of, curve, 51–2 calibration for, 127–30 206 AUROC and, 51, 54–5 correlation coefficients design and conduct, for CALFRAST screening, and, 123–5 206–11 327–8 error by magnitude with, results analysis, 211–15 discrimination in risk 125–7 design of, 206–11 predictions and, method comparison for, in diagnostic test studies, 150–67 127–9 75–7 for Grim Reaper walking test–retest, 121–9 equivalency trials and, 215 speed, 327 within-subject standard falsification tests in, 236–8, for hypothetical trial cases, deviation/repeatability, 348 326–7 122–3 follow-up losses in, 210–11 information in, 55 inter-rater 367

Index

reliability, in testing (cont.) for community-acquired in EBM, 304–6 for diagnosing sexual pneumonia, 340 overdiagnosis in, 263–5 abuse in prepubertal for continuous outcomes, total v. cause-specific girls, 336–7 164 mortality in, 266–9 kappa statistic for, 110–21, diagnostic tests v., 144–6 Cardiac Arrhythmia 332–8 genetic tests, 162–4 Suppression Trial, 252 literature studies of, 130–1 hazard ratios in, 154 for CHD in Down syndrome, for PUCAI, 334–6 rate ratios in, 154 353 variable types and risk ratios in, 154 for colon cancer, 269–70 Bland–Altman plot and, for stroke after TIA, 339–40 for congenital CMV, 353 110–11 studies of, 160 critical appraisal of studies continuous, 110–11 follow-up loss in, 161 of, 257–70 dichotomous, 110–13 new information mortality v. survival in, discrete, 110–11 quantification in, 162–3 258 kappa statistic and, overfitting in, 161 observational studies, 110–21, 332–8 publication bias in, 161–2 259–66 nominal, 110–11 treatment effects in, 160–1 randomized trials, 265–9 numeric, 110–11 value assessment for, 154–5 definitions of, 250–1 ordinal, 47, 110–11 decision curves, 156–60 differential verification bias ® Repatha . See evolocumab net benefit calculations, in, 86 repeatability, within-subject 155–7 excessive, reasons for, 254–6 standard deviation and, risk ratios, 154 false results from, 256 122–3 in randomized trials, 215–17 fecal occult blood, 269–70 representativeness, in ROC curve. See receiver harms from, 252–4 probability estimates, operating characteristic importance of critical 309 curve approach to, 252–7 reproducibility. See reliability, root, of classification trees, for lung cancer, 350–1 in testing 181–2 for ovarian cancer, 352–3 research questions, in rotavirus testing, for for PDA, 348–9 diagnostic test studies, gastroenteritis, 318 for prostate cancer, 4, 256, 79–80 RR. See relative risk 265, 351–2 results RRR. See relative risk reduction public support for, diagnostic test, disease RST. See referral screening tool 256 probability estimation Rule of Three, 295–6 randomized trials of, 265–9 and, 3 types of in diagnostic test studies, salmeterol, randomized trials for presymptomatic 76–80 of, 216–17 disease, 251–2 spectrum bias from exclusion sampling schemes for risk factors, 251–2 of, 86–97 for diagnostic test studies, for unrecognized review bias, 78–80 75–7 symptomatic disease, RIDT. See rapid influenza for dichotomous tests, 9–14, 251–2 diagnostic tests 321 underutilization of, 257 risk factors, screening tests for, screening tests, 250 SEA. See spinal epidural abscess 251–2 for AAA, 350 sensitivity, 8–10, 320–39 risk predictions, 144 biases in, 258–68 in diagnostic test studies, accuracy of lead-time, 260–1 76–80 calibration in, 147–9, length-time, 261–2 differential verification 152–67, 338–9 pseudodisease, 263–6 bias effects on, 81–2, discrimination in, 146, slippery linkage, 267–8 86–8, 329–30 150–67, 338–9 stage migration, 261–3, imperfect gold standard NRI and IDI for, 165–6 353 bias effects on, 81–2, quantification of, 146–67, sticky diagnosis, 258–68 89–91, 330–2 338–9 volunteer effect, 259–60 incorporation bias effects recalibration and, 154 for cancer on, 81–2, 329 for cardiovascular events, differential verification partial verification bias 341–2 bias in, 86 effects on, 81–4, 330 368

Index

spectrum bias effects on, definition of, 81–2, 91–3 systematic reviews, of 81–2, 91–7, 330 disease definition v., 93–5 diagnostic tests, 98–100, in individual patient data disease prevalence and, 94–5 332–54 meta-analysis, 99–100 ESR and, 92–3 kappa statistic v., 116–17 exclusion of intermediate test T. See cost of test ® ROC curves and, 48–51 results and, 86–97 Tamiflu . See oseltamivir in systematic reviews, 98–100 sensitivity in, 81–2, 91–3 test result-based sampling, 14, sentinel-node biopsy, 356 specificity in, 81–2, 91–3 321 septic arthritis, 322–3 tests nonindependence and, test statistics, 282 serum amylase, 78–80 177–8 testing, statistical significance, serum lipase, 78–80 speed bumps, appendicitis 281–2 severity, disease, 176 diagnosis with, 332 test–retest reliability, 121 sexual abuse in prepubertal spinal epidural abscess (SEA), average standard deviation girls, reliability of accuracy of classic triad and, 123 testing for, 336–7 for, 319–20 correlation coefficient and, sigmoidoscopy, second SpPIN mnemonic, 9–11 123–5 outcomes measured for, SROC. See summary receiver error by magnitude with, 236–8 operating characteristic 125–7 signal detection theory, 49–50 curve method comparison for, significance testing, classical stage migration bias, 261–3, 127–9 (frequentist), 281–2 353 within-subject standard skin conditions, 2 staging, of breast cancer, 79–80, deviation/repeatability, slide rule, for likelihood ratios, 318–56 122–3 65–6 standard deviation, reliability tests in testing threshold and cancer screening, 86, 263–9 visualization, 25–7 average, 123 in EBM, 304–6 slippery linkage bias, 267–8 within-subject, 122–3 continuous, 47 small numerators, confidence statins, peri-operative use of, dichotomous, 47–8 intervals for, 295–6 349 ROC curves in, 48–55, SnNOUT mnemonic, 9–10 statistical learning, 196–7 57–9, 62–3, 322–6 sonographic screening, statistical significance testing, cost, T, 23 prenatal, 5, 93–5, 281–2 diagnostic (See diagnostic 178–83, 186, 188–91 stenosis, CTA diagnosis of, 93 tests) specificity, 8–11, 320–39 sticky diagnosis bias, 258–68 dichotomous (See in diagnostic test studies, stochastic probability, 280–1 dichotomous tests) 76–80 strep throat, 5, 321–2 EBM in critical evaluation of, differential verification multiple tests for, 342–3 314–15 bias effects on, 81–2, stroke, risk predictions for, genetic, 162–4 86–8, 329–30 339–40 index, 76–7, 79–80 imperfect gold standard study design, for diagnostic test influenza bias effects on, 81–2, studies, 75–7, 79–80 prevalence, pre-test 89–91, 330–2 subarachnoid hemorrhage, 4 probability, post-test incorporation bias effects subgroup analysis, 213–14 probability and on, 81–2, 329 subjects accuracy calculations partial verification bias in diagnostic test studies, for, 8–14 effects on, 81–4, 330 75–7, 79–80 sensitivity, specificity, spectrum bias effects on, in randomized trials, 206–7 positive predictive value 81–2, 91–7, 330 in reliability studies, 130–1 and negative predictive in individual patient data summary receiver operating value calculations for, meta-analysis, 99–100 characteristic (SROC) 8–11, 320–1 kappa statistic v., 116–17 curve, 98–100, 332–54 intentionally ordered, 286 ROC curves and, 48–51 suppression, 231 multilevel, 47 in systematic reviews, 98–100 surprise question, systematic likelihood ratios for, 55–9, spectrum bias review of, 98–9 323–6 in bacterial meningitis surrogate outcomes, 209 optimal cutoffs for, 61–4, findings, 330 survival, mortality v., 258 325–6 369

Index

tests (cont.) for migraine headaches, UA. See urinalysis probability for, 59–61, 346 ulcerative colitis, 334–6 323–5, 327–8 NNH, 221–2 ultrasound multiple NNT, 215–18, 220–1 for AAA classification trees in, for OME, 344–5 reliability of testing for, 181–5 relative v. absolute 338 decision rules for, 175, measures of, 216–17 screening tests, 350 180–1, 192–6, 198 treatment cost per good DVT diagnosis with, dichotomous, 178–81, outcome caused, 221 intermediate test results 186–7 in risk predictions studies, in, 96–7 independence in, 175–8 160–1 for intussusception, logistic regression in, treatment threshold probability differential verification – – – – 185 95 (PTT), 22 40, 321 2 bias in, 86 8 machine learning in, 196–7 expected cost of, 23–5 prenatal, 5, 93–5, 178–83, multiple hypotheses and, formulas for, 34–6 186, 188–91 287–9 for influenza, 22–30, 34–6 unbalanced disagreement, result combination of, NNT and, 220–1 115–16, 333–6 178–81 no treat-test, 25–30, 37–40 unrecognized symptomatic prognostic, 144 testing of disease, screening tests reliability and measurement for imperfect and costly for, 251–2 error in, 110 test, 29–30, 34–6 unweighted kappa statistic, 117 screening (See screening for imperfect but costless urinalysis (UA), 13–14 tests) test, 25–6, 29, 34–6 ROC curves for, 323–5 test–treat threshold, 25–30, likelihood ratio slide rule urinary tract infection (UTI) 37–40 in, 25–7 odds ratios and likelihood 3×2 table, for intermediate test for perfect but risky or ratios for, 187–8 results, 86–97 expensive test, 28–9, test nonindependence and TIA. See transient ischemic attack 34–6 spectrum bias in, 177–8 tolterodine, for enuresis, visualization of, 25–7 urine culture, 13–14 randomized trials of, test-treat, 25–30, 37–40 US Centers for Disease 345–6 trial cases, continuous/ Control (CDC), rapid total mortality, cause-specific multilevel tests and, influenza diagnostic mortality v., 266–9 326–7 testing web page of, transient ischemic attack (TIA), trisomy 21. See Down 320–1 risk predictions for, syndrome US News and World Report, 339–40 true negative, 8–9 304–6 treatment, in EBM, 2–3 true positive, 8–9 US Preventative Health ® disease classification systems Trulance . See plecanatide Services Task Force, and, 1–2 2×2 table 256, 304–6, 351–2 treatment cost per good prevalence, pre-test UTI. See urinary tract infection outcome caused, in probability, post-test randomized trials, 221 probability and vaccination, confidence treatment effects accuracy, 8–14, 319–20 intervals and, in studies in EBM, 2–3 sampling schemes and, 9–14, of, 355–6 randomized trials for 321 validation, in test selection for quantification of, 3, 205 sensitivity, specificity, decision rules, 193–6 alternatives to, 231–43 positive predictive value validation sets, 195–6 CBOP and BBOP, 218–21 and negative predictive variables continuous, ordinal and value, 8–11, 319–39 categorical count outcome variables 2×2 table method disease definition and, in, 215 blank, 15 93–5 dichotomous outcome completed, 16 inter-observer agreement variables in, 215–18 for updating prior probability, for, 111–21, 332–8 effect size inflation in, with 15–16, 19–20 continuous, 110–11 ® odds ratio, 217–18 Tylenol . See acetaminophen disease definition and, 93, for enuresis, 345–6 Type 1 error, 281 330 370

Index

in randomized trials, viral gastroenteritis, 318 white blood cell (WBC) count 215 vitamin E, for cardiovascular for appendicitis, dichotomous, 110–11 disease prevention, 313 kappa for, 112–13 231–2, 237 for bacteremia, 5, 47–8, discrete, 110–11 volunteer effect, in screening 60 instrumental, 232–5, 244–5, tests, 259–60 in joint fluid, 322–3 338–49 V/Q scans, intermediate test likelihood ratios for, kappa statistic and, 110–21, results in, 86–97 55–9 332–8 regret graphs for, 63–4 nominal, 110–11 walking man approach, to ROC ROC curve and, 48–51, 55 numeric, 110–11 curves, 52–4 urine, 323–5 ordinal, 110–11 walking speed, as mortality Wilcoxon Rank Sum test, in randomized trials, 215 predictor, 327, 354 54–5 outcome, 76–7, 79–80 wall motion abnormalities, within-group comparisons, in additional, 236, 348 as test for acute randomized trials, in randomized trials, cardiac ischemia, 80, 214 209–10, 215 329 within-subject standard in screening tests, 257 WBC count. See white blood deviation, 122–3 predictor, 76–7, 79–80 cell count work-up bias. See partial additional, 237, 347–8 weighted kappa statistic, verification bias in screening tests, 257 110–11 verification bias for three or more categories, yellow belt, 293 differential, 81–2, 86–8, 117–21 Youden’s Index, 51, 165 329–30 Wells Score, 343–4 partial, 80–5, 330 white belt, 293 zero numerators, 295–6

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