Diagnostic research and diagnostic practice frequently do not cohere. Studi
es commonly evaluate whether a single test discriminates between disease pr
esence and absence, whereas in practice a test is always judged in the cont
ext of other information. This study illustrates drawbacks of single-test e
valuation and discusses principles of diagnostic research. We used data on
140 patients suspected of pulmonary embolism who had an inconclusive ventil
ation-perfusion lung scan. We evaluated three tests: partial pressure of ox
ygen in arterial blood (PaO2), x-ray film of the thorax, and leg ultrasound
. On the basis of single-test evaluations, ultrasound was most informative.
Given a prior probability of 0.27, it had a much better combination of pos
itive and negative predictive value (0.71 and 0.21, respectively) relative
to thorax x-ray (0.33 and 0.11) and PaO2 (0.35 and 0.27). The combination o
f positive and negative likelihood ratio was also more promising for ultras
ound (7.3 and 0.7) than for thorax x-ray (1.3 and 0.3) and PaO2 (1.3 and 0.
9). As the tests are always performed after the history and physical, we ju
dged their added. value using multivariable logistic modeling with receiver
operating characteristic (ROC) analyses. The ROC areas of the model, inclu
ding history and physical, with additional PaO2, thorax x-ray, or ultrasoun
d, were 0.75, 0.77, 0.81, and 0.81, respectively, which indicated similar a
dded value of thorax x-ray and ultrasound. Application of the models to pat
ient subgroups also yielded added predictive value for thorax x-ray film. T
hus, the results of single-test evaluations may be very misleading. As no d
iagnosis is based on one test, single-test evaluations have limited value i
n diagnostic research and only have relevance in the context of screening a
nd the initial phase of test development. Diagnostic research should always
apply an approach of constructing, extending, and validating diagnostic mo
dels in agreement with routine clinical work up using logistic regression a
nalyses.