Background: EarlyCDT Lung (Oncimmune Holdings plc, Nottingham, UK) is a blood test to assess malignancy risk in people with solid pulmonary nodules. It measures the presence of seven lung cancer-associated autoantibodies. Elevated levels of these autoantibodies may indicate malignant disease. The results of the test might be used to modify the risk of malignancy estimated by existing risk calculators, including the Brock and Herder models.
Objectives: The objectives were to determine the diagnostic accuracy, clinical effectiveness and cost-effectiveness of EarlyCDT Lung; and to develop a conceptual model and identify evidence requirements for a robust cost-effectiveness analysis.
Data sources: MEDLINE (including Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE), EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index, EconLit, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment database, NHS Economic Evaluation Database ( NHS EED ) and the international Health Technology Assessment database were searched on 8 March 2021.
Review methods: A systematic review was performed of evidence on EarlyCDT Lung, including diagnostic accuracy, clinical effectiveness and cost-effectiveness. Study quality was assessed with the quality assessment of diagnostic accuracy studies-2 tool. Evidence on other components of the pulmonary nodule diagnostic pathway (computerised tomography surveillance, Brock risk, Herder risk, positron emission tomography-computerised tomography and biopsy) was also reviewed. When feasible, bivariate meta-analyses of diagnostic accuracy were performed. Clinical outcomes were synthesised narratively. A simulation study investigated the clinical impact of using EarlyCDT Lung. Additional reviews of cost-effectiveness studies evaluated (1) other diagnostic strategies for lung cancer and (2) screening approaches for lung cancer. A conceptual model was developed.
Results: A total of 47 clinical publications on EarlyCDT Lung were identified, but only five cohorts (695 patients) reported diagnostic accuracy data on patients with pulmonary nodules. All cohorts were small or at high risk of bias. EarlyCDT Lung on its own was found to have poor diagnostic accuracy, with a summary sensitivity of 20.2% (95% confidence interval 10.5% to 35.5%) and specificity of 92.2% (95% confidence interval 86.2% to 95.8%). This sensitivity was substantially lower than that estimated by the manufacturer (41.3%). No evidence on the clinical impact of EarlyCDT Lung was identified. The simulation study suggested that EarlyCDT Lung might potentially have some benefit when considering intermediate risk nodules (10-70% risk) after Herder risk analysis. Two cost-effectiveness studies on EarlyCDT Lung for pulmonary nodules were identified; none was considered suitable to inform the current decision problem. The conceptualisation process identified three core components for a future cost-effectiveness assessment of EarlyCDT Lung: (1) the features of the subpopulations and relevant heterogeneity, (2) the way EarlyCDT Lung test results affect subsequent clinical management decisions and (3) how changes in these decisions can affect outcomes. All reviewed studies linked earlier diagnosis to stage progression and stage shift to final outcomes, but evidence on these components was sparse.
Limitations: The evidence on EarlyCDT Lung among patients with pulmonary nodules was very limited, preventing meta-analyses and economic analyses.
Conclusions: The evidence on EarlyCDT Lung among patients with pulmonary nodules is insufficient to draw any firm conclusions as to its diagnostic accuracy or clinical or economic value.
Future work: Prospective cohort studies, in which EarlyCDT Lung is used among patients with identified pulmonary nodules, are required to support a future assessment of the clinical and economic value of this test. Studies should investigate the diagnostic accuracy and clinical impact of EarlyCDT Lung in combination with Brock and Herder risk assessments. A well-designed cost-effectiveness study is also required, integrating emerging relevant evidence with the recommendations in this report.
Study registration: This study is registered as PROSPERO CRD42021242248.
Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 49. See the NIHR Journals Library website for further project information.
Keywords: DIAGNOSTIC ACCURACY; ECONOMIC ANALYSIS; EarlyCDT LUNG; LUNG CANCER; PULMONARY NODULES; SYSTEMATIC REVIEW.
People at risk of lung cancer sometimes undergo computerised tomography ( CT ) scans of their lungs. These scans may identify lung nodules that could be cancerous. Currently, CT scans of the lung nodules, or sometimes further positron emission tomography–computerised tomography ( PET-CT ) scans, are used to predict the risk that a nodule is cancerous. EarlyCDT Lung is a blood test that detects substances, called autoantibodies, associated with having cancer. If the autoantibodies are detected, the chance of a lung nodule being cancerous may be substantially increased. This test could help doctors make decisions about whether to treat immediately, carry out further tests or monitor the nodule over time to see if it grows or changes shape. This project examined the evidence on the clinical value of the EarlyCDT Lung test. We reviewed all published studies of EarlyCDT Lung and reanalysed the reported data. We found that there has been little research on EarlyCDT Lung among people with lung nodules (only five studies comprising 695 patients). This makes it difficult to draw any firm conclusions. The evidence suggests that EarlyCDT Lung may not be particularly effective at determining which lung nodules are cancerous, and may not improve diagnosis when compared with using CT and PET - CT scans. However, this is uncertain because the evidence is so limited. This project also looked for evidence on the value for money of the EarlyCDT Lung test in detecting lung cancer, and found no relevant evidence. This means that the value for money of EarlyCDT Lung is largely unknown, and there is currently no good evidence to support further analyses on this. We therefore sought to summarise the information and analyses that would be needed to support a future assessment of the value for money of EarlyCDT Lung.