5.1 The assessment consisted of a systematic review of the evidence on clinical effectiveness for new generation cardiac CT scanners in people with known and suspected coronary artery disease in whom imaging is difficult.
5.2 All studies included in the systematic review reported test accuracy data for people in whom imaging is difficult. Results were summarised by patient group (obese, high heart rate, high coronary calcium score and so on) and further stratified by unit of analysis (patient, artery, or arterial segment). For all included studies, the absolute numbers of true positive, false negative, false positive and true negative test results, as well as sensitivity and specificity values, with 95% confidence intervals (CIs), were presented.
5.3 Modelling was undertaken to assess final patient outcomes and cost effectiveness. Diagnostic strategies themselves do not have direct implications for health-related quality of life. Therefore, a linked evidence approach to modelling was used to link intermediate outcomes (diagnostic accuracy of the tests) to treatment outcomes and hence quality-adjusted life year (QALY) gains.
5.4 Based on the data from the included studies, the External Assessment Group was able to deduce true positive, true negative, false positive and false negative rates for new generation cardiac CT scanners compared with invasive coronary angiography. Sensitivities and specificities were computed from meta-analysis (a bivariate summary receiver operating curve [SROC] model). When the bivariate model could not be fitted because of the small number of relatively homogenous studies involved, the DerSimonian and Laird method for meta-analysis was used. Per-patient summary estimates were also used when possible. A summary of the data on the test performance of the scanners among the patient groups in whom imaging is difficult is given below. In all cases the studies were quite consistent and inter-study heterogeneity was low to moderate.
5.5 One study involving 125 participants reported 543 per segment data on the performance of new generation cardiac CT scanners in detecting coronary artery disease in people with obesity. Obesity was defined as having a body mass index (BMI) of 30 kg/m2 or above. The index test was Somatom Definition (a model predating the Somatom Definition Flash) and the reference test was invasive coronary angiography. The sensitivity was 90.4% (95% CI 83.8 to 94.9) and the specificity was found to be 92.1% (95% CI 89.1 to 94.5).
5.6 Four studies reported on the performance of new generation cardiac CT scanners in detecting coronary artery disease in people with high levels of coronary calcium. The high calcium score threshold was set to above 400. Data were derived from 1304 segments in 91 participants. The index test was Somatom Definition and the reference test was invasive coronary angiography. The sensitivity was 92.7% (95% CI 88.3 to 95.6) and the specificity was 90.6% (95% CI 80.6 to 95.8%).
5.7 Five studies reported on the performance of new generation cardiac CT scanners in detecting coronary artery disease in people with arrhythmia. Data for 126 patients and 1526 segments were obtained from the studies. For the patient data, sensitivity was 97.7% (95% CI 88.0 to 99.9) and specificity was 81.7% (95% CI 71.6 to 89.4). For the segment data, sensitivity was 87.4% (95% CI 68.3 to 95.7) and specificity was 96.0% (95% CI 91.2 to 98.2).
5.8 Eight studies in total reported 24 data sets on the performance of new generation cardiac CT scanners in detecting coronary artery disease in people with a high heart rate. Five studies with 462 participants reported per-patient data. The pooled estimates of sensitivity and specificity, derived from these data using a bivariate model, were 97.7% (95% CI 93.2 to 99.3) and 86.3% (95% CI 80.2 to 90.7) respectively. Four studies reported data for 664 arteries. The pooled estimates of sensitivity and specificity, derived from these data using a bivariate model, were 93.7% (95% CI 87.8 to 96.9) and 92.4% (95% CI 83.3 to 96.8) respectively. All eight studies reported accuracy data by arterial segment (8133 segments). The pooled estimates of sensitivity and specificity, derived from these data using a bivariate model, were 92.7% (95% CI 89.3 to 95.1) and 95.7% (95% CI 92.8 to 97.4) respectively. All eight studies used a threshold of vessel narrowing of at least 50% to define significant stenosis.
5.9 Beta-blockers are normally prescribed to slow the heart rate for people with heart rates too high for scanning. Some people with high heart rates are intolerant to beta-blockers, which makes it difficult to image them with earlier generation CT scanners. However, no studies were identified on the accuracy of new generation cardiac CT scanners for the detection of coronary artery disease in people who are intolerant to beta-blockers.
5.10 Seven studies reported ten data sets describing the accuracy of new generation cardiac CT scanners for the detection of coronary artery disease in people with previous stent implantation. Four studies reported per-patient data for 233 participants. The pooled estimates of sensitivity and specificity were 96.0% (95% CI 88.8 to 99.2) and 81.6% (95% CI 74.7 to 87.3) respectively. Six studies reported accuracy data by stent or stented lesion (n = 582). The pooled estimates of sensitivity and specificity were 93.6% (95% CI 86.1 to 97.2) and 91.0% (95% CI 87.3 to 93.7) respectively.
5.11 The modelling comprised five sub-models based on existing models to estimate the clinical outcomes of using new generation cardiac CT scanners. QALYs and costs in all five models were calculated and discounted at a rate of 3.5% for benefits and costs. These models are described below.
5.12 A diagnostic model was used to estimate the initial outcomes of treatment and initial diagnosis. This model was created through extending and linking the five sub-models. The primary measures of benefit used in this analysis were:
the complication rate for invasive coronary angiography and revascularisation (myocardial infarction and stroke)
the benefits associated with reduction in the incidence of cancer as a result of reduction in radiation dose
morbidity and mortality from coronary artery disease.
5.13 Using invasive coronary angiography as a comparator, three diagnostic strategies were evaluated. These strategies were:
Invasive coronary angiography only: people in whom imaging is difficult had invasive coronary angiography only, which was assumed to be perfectly accurate.
New generation cardiac CT scanner only: people in whom imaging is difficult had a new generation cardiac CT scan only; the accuracy of the scan was based on invasive coronary angiography as the reference standard.
New generation cardiac CT scan plus invasive coronary angiography: cardiac CT was performed on everyone in whom imaging is difficult, and those with a positive scan then had invasive coronary angiography. No false positives could occur with this strategy because invasive coronary angiography was assumed to have perfect specificity.
5.14 The clinical outcomes assessed for people with coronary artery disease were mortality, morbidity and the percentage of correct diagnostic classifications (true positives, false positives, true negatives, false negatives) associated with each of the three strategies.
5.15 Using life tables, a healthy population model that only applied to people without coronary artery disease (true negatives and false positives) was used to predict mortality on the assumption that people with true negative and false positive test results do not differ from the average UK population.
5.16 The EUROPA model modelled the progression of stable coronary artery disease by predicting cardiovascular events and mortality. Health-related quality of life estimates were assigned to each Markov state based on age, gender, baseline Canadian Cardiovascular Society classification and whether the person had undergone treatment.
5.17 The costs and outcomes of people who experienced a stroke because of initial invasive coronary angiography or revascularisation were modelled with a mortality model. Mortality rates were based on UK life tables and a relative risk of 2.5 to reflect the increased risk of mortality after a stroke.
5.19 The models described above were also used to estimate the costs of the diagnostic tests and treatments people received for their initial conditions, and any subsequent related conditions that developed. Although there is some variation in the costs of the new generation cardiac CT scanners, the models assumed that each scanner cost £1 million.
5.20 The comparator, invasive coronary angiography, was presumed to be perfectly accurate (a gold standard) and, despite a known increase in complication rate compared with CT, generated more QALY gains than CT. It was also more expensive than imaging with a new generation cardiac CT scanner. The incremental cost-effectiveness ratio (ICER) of invasive angiography when compared with new generation cardiac CT is significantly greater than the NICE cost-effectiveness threshold.
5.21 In people with suspected coronary artery disease in whom imaging is difficult, the health economic analysis showed that, given a threshold of £20,000 per QALY gained, using new generation cardiac CT scanners instead of invasive coronary angiography is cost effective. The 'new generation CT scanner only' strategy was the most cost-effective strategy. The 'new generation CT scan plus invasive coronary angiography for those with positive CT scans' strategy delivered very small additional QALYS per patient (0.002) at a cost of £142. The ICER was £71,000 per QALY gained compared to the 'new generation CT scanner only' strategy. Similarly, relative to the 'new generation CT scanner only' strategy, 'invasive coronary angiography alone' also delivered a very small number of additional QALYS per patient (0.009) at a cost of £726 (ICER of £80,667 per QALY gained).
5.22 In people with known coronary artery disease who are difficult to image, the most cost-effective strategy was 'new generation cardiac CT scan plus invasive coronary angiography' for those with positive CT scans. This strategy dominated (more effective and less costly) the 'invasive coronary angiography only' strategy, generating more QALYs per patient (0.022) at reduced cost. The 'new generation cardiac CT scan plus invasive coronary angiography' strategy was the most preferred strategy for this cohort. Although it generated a very small reduction in QALYs per patient (0.001), it yielded a relatively large reduction in cost (£443) (ICER £726,230 per QALY) relative to the 'new generation cardiac CT scan only'.