The role of clinical suspicion in evaluating a new diagnostic test for active tuberculosis - Results of a multicenter prospective trial

Context In laboratory trials, nucleic acid amplification tests for the diagnosis of tuberculosis (TB) are more accurate than acid-fast bacilli (AFB) smear microscopy and are faster than culture. The impact of these tests on clinical diagnosis is not known. Objective To assess the performance of a nucleic acid amplification test, the enhanced Mycobacterium tuberculosis Direct (E-MTD) test, against a uniform clinical standard stratified by level of clinical suspicion. Design Prospective multicenter trial conducted between February and December 1996, documenting the clinical suspicion of TB at enrollment and using final comprehensive diagnosis as the criterion standard. Setting Six urban medical centers and 1 public health TB clinic. Patients A total of 338 patients with symptoms and signs consistent with active pulmonary TB and complete clinical diagnosis were stratified by the clinical investigators to be at low (less than or equal to 25%), intermediate (26%-75%), or high (>75%) relative risk of having TB. Main Outcome Measures Sensitivity, specificity, and positive and negative predictive values of the E-MTD test in clinical suspicion of groups with low (n = 224); intermediate (n = 68); and high (n = 46) clinical suspicion of TB. Results Based on comprehensive clinical diagnosis, sensitivity of the E-MTD test. was 83%, 75%, and 87% for low, intermediate, and high clinical suspicion of TB, respectively, and corresponding specificity was 97%, 100%, and 100% (P = .25). Positive predictive value of the E-MTD test was 59% (low), 100% (intermediate), and 100% (high) compared with 36% (low), 30% (intermediate), and 94% (high) for AFB smear. Corresponding negative predictive values were 99%, 91%,and 91% (E-MTD test) vs 96%, 71%, and 37% (AFB smear). Conclusions For complex diagnostic problems like TB, clinical risk assessments can provide important information regarding predictive values more likely to be experienced in clinical practice. For this series, a clincial suspicion of TB was helpful in targeting areas of the clinical spectrum in which nucleic acid amplification tests can make an important contribution.