The Predictive Value of Clinical Laboratory Test Results PHILIP G. ARCHER, Sc.D. Department of Biometrics, University of Colorado Medical School, Denver, Colorado Archer, Philip G.: The predictive value of clinical laboratory test results. Am J Clin Pathol 69: 32-35, 1978. Bayes' formula is being used with increasing frequency to calculate predictive values for positive and negative clinical laboratory test results. Because of its nonlinear form, however, it is difficult to visualize how changes in the test characteristics or disease prevalence will effect predictive values. This paper shows that Bayes' formula is transformed to a linear function through the use of odds, rather than probabilities, thus facilitating conceptualization, understanding, and memory. (Key words: Laboratory tests; Predictive value; Bayes' formula; Probability; Odds ratios.) where*: p+ Se Sp p predictive value of a positive test sensitivity of the test specificity of the test prevalence rate (or prior probability) of the disease In pragmatic terms, the prevalence rate, p, is an index (on a scale of 0 to 1.0) of suspicion that the disease is present before testing, and p + shows the comparable index of suspicion after having received a positive test result for a patient who comes from a population in which the prevalence rate is thought (believed or known) to be p. The experienced geometer can illustrate the effects on p + of varying the individual parameters on the right-hand side of equation 1, but at best, the graphic illustration is somewhat awkward to construct and interpret in this nonlinear form. A similar development in terms of odds in favor of the presence of disease, rather than the probability of its presence, reduces the relationship to a linear one in the odds, thus facilitating both conceptualization and memory. THE PREDICTIVE VALUE of "positive" and "negative" laboratory test results has been receiving increased exposure and discussion in the medical literature in recent years, and a recently published book by Galen and Gambino 2 treats the subject in some detail from the point of view of the potential users of clinical laboratory results. Some efforts have been made to ease the computational aspects of the use of Bayes' formula, 2 ' 3,6 and to provide geometric illustrations of the effects on predictive values when prevalence, sensitivity, and specificity are individually altered. 3 To date, however, there seems to have been no elucidation of a unifying concept that will allow the clinician or research worker easily to grasp the interaction of all of the factors involved. I believe the following argument will provide such a concept. Although none of the ideas is new, 5 they do not seem to have been formulated previously in the context of the interpretation of laboratory results in the practice of clinical medicine. Odds Ratios Although odds are commonly used in reference to betting (racing, poker, football, etc.), with the exception of the literature on relative risk, one doesn't often see them used in medical applications in this country. This is similarly true of the British literature, though there are exceptions in both countries. 1,4 If p is the prevalence rate of the disease, then the odds in favor of the disease (relative to 1.0) are: Bayes' Formula The "predictive value of a positive test result," p + , is defined as the proportion of positive test results that represent persons who have the disease the test being used is supposed to detect. In other words, p + represents the conditional probability of the presence of disease, given that the patient has had a positive test result. Bayes' formula gives this as 2 : PSe P S e + (1 - S„)(l - p) = = = = ci = l - P _P_ q (2) Solving for p in terms of CI, one has: (1) CI 1 + CI Received December 9, 1976; accepted for publication December 27, 1976. Address reprint requests to Dr. Archer: Department of Biometrics, University of Colorado Medical School, 4200 East Ninth Ave., Box B-119, Denver, Colorado 80262. (3) * Sensitivity is the probability of a positive test, given presence of the disease. Specificity is the probability of a negative test, given absence of the disease. Prevalence is the presumed frequency of the disease in the population tested. 0002-9173-78-0100—0032S00.60 © American Society of Clinical Pathologists 32 33 PREDICTIVE VALUE OF TEST RESULTS Vol. 69 • No. I so that the conversion in either direction is a simple one, which can usually be done in one's head.t Table 1 gives a list of probability values and the corresponding odds for values of p between 0.05 and 0.95. Figure 1 100.0 shows a graph of p vs. . For many practical situ1 - p ations, one can take ft = p whenever p < 0.05, and ft = = — when p s 0.95, as can also be seen 1 - p q from Figure 1. If we express the "prior probability," p, in terms P of prior odds, ft = , and the "posterior proba1 -p bility", p + , in terms of posterior odds, we can derive y '°: the following relationship from equation 1: n+ = 1 1 - Sn ft = b+n. (4) This is a straight line through the origin in the odds plane, having slope b + = — .Since both S e and S p 1 — 5»p will generally be greater than 0.5, b + will generally be greater than 1.0, showing that the odds favoring presence of the disease increase by a simple multiplicative factor with the knowledge of a positive test result. (b + = 1.0 whenever S e + S p = 1, which will generally not be true of any laboratory test of use to clinicians.) The "predictive value of a negative test result," q", is defined as the proportion of negative test results that represent persons who do not have the disease the test being used is supposed to detect. (I have used the notation q~ here .since we are using the letter p to represent the probability of the presence of the disease. Similarly, any odds ratio, ft, represents odds favoring presence of the disease.) Bayes' formula can be used to express q~ as: SP(1 - p) S p (l - p) + (1 - Se)p 1 ft = b-a (6) where ft- = 1 -qq- 1 - p- 2:100 1:100 o.or FIG. 1. The odds ratio (fi) as a function of prevalence (p) and two functions that furnish approximations to the odds ratio at the extremes of the prevalence domain. straight line through the origin. The slope of the negative result line, b~, will generally be less than 1.0 for practical values of S e and S p . Discussion (5) In terms of the posterior odds in favor of the presence of the disease following a negative test result, we have: ft- = 5:100 (7) Equation 6, like equation 4, is represented by a t In case the odds are not given relative to 1.0, say in the form a>,:oj2, then p is given by p = coj/Ccu, + ai2). For example, odds of 3:2 in favor of the disease being present correspond to a probability of p = 3/(3 + 2) = 3/5 = 0.60 of its presence. Both lines (equations 4 and 6) are shown in Figure 2. For any particular value of the prior odds, say ft,, Table 1. Relationship between Prevalence (p) and Odds (ft) Prevalence 0.05 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 0.95 Odds 0.05 0.11 0.25 0.43 0.67 1.00 1.50 2.33 4.00 9.00 19.00 = = = = = = = = = = = 5:100 11:100 25:100 43:100 67:100 100:100 = 1:1 1.5:1 2.3:1 4:1 9:1 19.: 1 34 ARCHER Puteni OMt Trior Odds FIG. 2. Linear relationships between prior and posterior odds for positive and negative test results. one can see that the posterior odds will be unchanged whenever Se + Sp = 1.0. Furthermore, one can easily visualize both the direction and magnitude of changes in the posterior odds that would be produced by any combination of changes in sensitivity, specificity, and/or prevalence. In addition, the use of equations 4 and 6, together with equations 2, 3, and 7, makes the calculation of predictive values a very simple matter, easily carried out by hand or with a pocket calculator. The following example illustrates the ease of using Bayes' formula in this form. A prevalence of p = 0.20 would yield (from equation 2) prior odds of D, = 0.25. If the test to be used is presumed to have a sensitivity of Se = 0.90 and specificity of Sp = 0.95, then (from equations 4 and 6) the slopes of the positive and negative result lines would be b + = 18.0 and b" = 0.1053, which yield (again using equations 4 and 6) posterior odds of H+ = 4.5 and il" = 0.0263 for positive and negative test results, respectively. Converting back to probabilities, the predictive value of a positive test (from equation 3) would be p + = 0.82, and the predictive value of a negative test (from equations 3 and 7) would be q- = 1 - p~ = 1 - 0.0256 = 0.97. Thus, under these circumstances, a positive test result should cause us to increase our suspicion of the presence of disease from a prior estimate of p = 0.20 to a posterior estimate of p + = 0.82. On the other hand, the receipt of a negative test result should cause us to view the posterior estimate of the absence of disease as having increased to q" = 0.97 from the prior estimate of q = 1 - p = 0.80. The graphs shown in Figure 3 may still further assist in easing calculation, but are given in order to illustrate the changes in slope of the odds lines pro- A.J.C.P. • January 1978 duced by changes in the characteristics (sensitivity and specificity) of the test employed. From Figure 3A, one can see that substantial changes in sensitivity have relatively little effect on the positive test slope, b + (and therefore on the posterior odds, D + , or the posterior probability, p + ), provided specificity is high. On the other hand, relatively small changes in specificity can produce very large changes in b + when Sp is high to begin with. In a similar vein, Figure 3B illustrates the diminished effect of specificity on changes in the negative test slope, b~, when sensitivity is high. An increase in sensitivity, on the other hand, can produce very large changes in b~ when Se is high to begin with, particularly when specificity is low. A further rule of thumb, which can be derived directly from equation 5, is the fact that whenever Se and Sp are both greater than 0.5 (which will generally be the case), q~ never falls below 0.9 until the prevalence, p, is greater than 0.10. A) b I-S„ Specificity (S.) as 0.6 0.7 o.s Sensitivity ($,) 0.9 B) b --P- i.o •" 0 Specificity ( y O.S 0.6 0.7 O.t 0.9 1.0 Sensitivity (S,) FIG. 3. Linear relationships between sensitivity and specificity for fixed values of the slopes of the odds lines. A, the slope of the positive results line, b + . B, the slope of the negative results line, b". PREDICTIVE VALUE OF TEST RESULTS Vol. 69 • No. 1 While the formulas for the slopes of the odds lines, b and b _ , given by equations 4 and 6, facilitate computation, it is easier to remember the slopes in terms of ratios of conditional probabilities. These are given by: + b+ = P(+|D) P(+|D) (8) and b~ = P(-|D) P(-|D) where: P(+1D) = probability of a positive test given presence of the disease P(+| D) = probability of a positive test given absence of the disease P(-1D) = probability of a negative test given presence of the disease P(-1D) = probability of a negative test given absence of the disease. 35 In each case, the slope is given by the ratio of the probabilities of the test result, conditional on the presence or absence of the disease. Perhaps many will find it a little awkward to reorient their thinking in terms of odds rather than (or in addition to) probabilities, but for a real understanding of predictive values, the benefits should be worth the effort. References 1. Fleiss JL: Statistical Methods for Rates and Proportions. New York, John Wiley and Sons, 1973 2. Galen RS, Gambino SR: Beyond normality: The Predictive Value and Efficiency of Medical Diagnoses. New York, John Wiley and Sons, 1975 3. Katz MA: A probability graph describing the predictive value of a highly sensitive diagnostic test. N Engl J Med 291: 1115-1116, 1974 4. Oldham PD: Measurement in Medicine. The Interpretation of Numerical Data. Philadelphia, J. B. Lippincott, 1968 5. Smith CAB: Biomathematics. Fourth edition. Volume 2, Chapter 19. London, Charles Griffin and Company Limited, 1969 6. Sunderman FW, Van Soestbergen AA: Laboratory suggestion: Probability computations for clinical interpretations of screening tests. Am J Clin Pathol 55:105-111, 1971
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