Spectrum Bias (January 4, 2005)
This page is moving to a new website.
I tried to start a page on diagnostic tests
a while back, but have not had the time to fully develop it. One of the
important issues for diagnostic tests is spectrum bias.
The sensitivity and specificity of a diagnostic test can depend on who
exactly is being tested. Think of disease as a range of possibilities from
slight to moderate to extreme. If only a portion of the disease range is
included, you may get an incorrect impression of how well a diagnostic test
works. This is known as spectrum bias.
The most obvious manifestation of spectrum bias is in the use of a
case-control design in studying diagnostic tests. In the case control design,
a group of patients with disease and a group of patients without disease are
asked to undergo a diagnostic test. They already know that they have the
disease, but they are asked to take the test to see how well it performs. In
a case-control design, though, you get the black (overtly diseased) and the
white (overtly healthy) but often miss out on the gray (subtly diseased). As
a result, the difference in the diagnostic test between healthy and diseased
patients is often overstated leading to overly optimistic values for
sensitivity and/or specificity.
Much better would be to evaluate sensitivity and specificity in a cohort
design. With this design, people who have certain symptoms and who come to a
health care professional for evaluation are given a diagnostic test and that
test is compared to a gold standard (which is often just waiting to see if
the disease fully manifests itself over time). With such a design, you
are likely to get a wide range of disease states and (hopefully) a fairer
depiction of the performance of a diagnostic test.
Spectrum bias is a potential issue whenever there is heterogeneity in the
response of patients to a diagnostic test. For example, in Muhlerin 2002, the
performance of an enzyme immunoassy for Chlamydia trachomatis was shown to
vary by age group. The sensitivity was much better in the patients older than
24 years (76% vs 58%). While the specificity showed less dramatic changes, it
was also significantly higher in the older group (99.5% versus 99.2%).
With such a finding, you should be cautious about extrapolating results of
Spectrum bias can also influence other measures in a diagnostic test, such
as the ROC curve and the likelihood ratios. The way to avoid spectrum bias is
to include a broad range of disease severity in your sample and to try to
identify sources of heterogeneity in that sample.
Spectrum bias is just one of several issues that you face when you make a
critical evaluation of a research article on diagnosis. The STARD initiative
promotes good quality reporting for these type of articles and will help you
evaluate diagnostic tests properly.
STARD Initiative -- Towards Complete and Accurate Reporting of Studies on
Diagnostic Accuracy. STARD Group. Accessed on 2003-07-29.
- We are overinterpreting the predictive value of serum
follicle-stimulating hormone levels. Barnhart K, Osheroff J. Fertil
Steril 1999: 72(1); 8-9.
- "Smart asses"--and spectrum bias. Corson SL. Fertil Steril 1999:
- Body mass index compared to dual-energy x-ray absorptiometry:
evidence for a spectrum bias. Curtin F, Morabia A, Pichard C, Slosman
DO. J Clin Epidemiol 1997: 50(7); 837-43.
- Near-patient tests in primary care: setting the standards for
evaluation. Delaney B, Wilson S, Fitzmaurice D, Hyde C, Hobbs R. J
Health Serv Res Policy 2000: 5(1); 37-41.
- The relationship between the clinical features of pharyngitis and the
sensitivity of a rapid antigen test: evidence of spectrum bias. Dimatteo
LA, Lowenstein SR, Brimhall B, Reiquam W, Gonzales R. Ann Emerg Med 2001:
- Spectrum bias: a quantitative and graphical analysis of the
variability of medical diagnostic test performance. Goehring C, Perrier
A, Morabia A. Stat Med 2004: 23(1); 125-35.
- Spectrum bias of a rapid antigen detection test for group A
beta-hemolytic streptococcal pharyngitis in a pediatric population. Hall
MC, Kieke B, Gonzales R, Belongia EA. Pediatrics 2004: 114(1); 182-6.
- Utility of captopril renal scans for detecting renal artery stenosis.
Huot SJ, Hansson JH, Dey H, Concato J. Arch Intern Med 2002: 162(17);
- Specificity of MR angiography as a confirmatory test of carotid
artery stenosis. Kallmes DF, Omary RA, Dix JE, Evans AJ, Hillman BJ.
AJNR Am J Neuroradiol 1996: 17(8); 1501-6.
- Spectrum bias in the evaluation of diagnostic tests: lessons from the
rapid dipstick test for urinary tract infection. Lachs MS, Nachamkin I,
Edelstein PH, Goldman J, Feinstein AR, Schwartz JS. Ann Intern Med 1992:
- Prevalence of cognitive impairment amongst Singapore's elderly
Chinese: a community-based study using the ECAQ and the IQCODE. Lim HJ,
Lim JP, Anthony P, Yeo DH, Sahadevan S. Int J Geriatr Psychiatry 2003:
- "Smart asses"--and spectrum bias. McDonough PG. Fertil Steril
1999: 72(6); 1147-8.
- Disease based spectrum bias in referred samples and the relationship
between type A behavior and coronary artery disease. Miller TQ, Turner
CW, Tindale RS, Posavac EJ. J Clin Epidemiol 1988: 41(12); 1139-49.
- Spectrum bias or spectrum effect? Subgroup variation in diagnostic
test evaluation. Mulherin SA, Miller WC. Ann Intern Med 2002: 137(7);
- Usefulness of physical examination in detecting the presence or
absence of anemia. Nardone DA, Roth KM, Mazur DJ, McAfee JH. Arch Intern
Med 1990: 150(1); 201-4.
- The effect of spectrum bias on the utility of magnetic resonance
imaging and evoked potentials in the diagnosis of suspected multiple
sclerosis. O'Connor PW, Tansay CM, Detsky AS, Mushlin AI, Kucharczyk W.
Neurology 1996: 47(1); 140-4.
- Integrating stratum-specific likelihood ratios with the analysis of
ROC curves. Peirce JC, Cornell RG. Med Decis Making 1993: 13(2); 141-51.
- Problems of spectrum and bias in evaluating the efficacy of
diagnostic tests. Ransohoff DF, Feinstein AR. N Engl J Med 1978:
- Application of stratum-specific likelihood ratios in mental health
screening. Schmitz N, Kruse J, Tress W. Soc Psychiatry Psychiatr
Epidemiol 2000: 35(8); 375-9.