This systematic review assesses the current status of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) tests in the diagnosis and prognosis of rheumatoid arthritis (RA). We reviewed publications on tests and biomarkers for early diagnosis of RA from English-language MEDLINE-indexed journals and non-MEDLINE-indexed sources. 85 publications were identified and reviewed, including 68 studies from MEDLINE and 17 non-MEDLINE sources. Anti-CCP2 assays provide improved sensitivity over anti-CCP assays and RF, but anti-CCP2 and RF assays in combination demonstrate a positive predictive value (PPV) nearing 100%, greater than the PPV of either of the tests alone. The combination also appears to be able to distinguish between patients whose disease course is expected to be more severe and both tests are incorporated in the 2010 ACR Rheumatoid Arthritis Classification Criteria. While the clinical value of anti-CCP tests has been established, differences in cut-off values, sensitivities and specificities exist between first-, second- and third-generation tests and harmonization efforts are under way. Anti-CCP and RF are clinically valuable biomarkers for the diagnosis and prognosis of RA patients. The combination of the two biomarkers in conjunction with other clinical measures is an important tool for the diagnosis and management of RA patients.

FoundationOne®CDx (F1CDx) is a United States (US) Food and Drug Administration (FDA)-approved companion diagnostic test to identify patients who may benefit from treatment in accordance with the approved therapeutic product labeling for 28 drug therapies. F1CDx utilizes next-generation sequencing (NGS)-based comprehensive genomic profiling (CGP) technology to examine 324 cancer genes in solid tumors. F1CDx reports known and likely pathogenic short variants (SVs), copy number alterations (CNAs), and select rearrangements, as well as complex biomarkers including tumor mutational burden (TMB) and microsatellite instability (MSI), in addition to genomic loss of heterozygosity (gLOH) in ovarian cancer. CGP services can reduce the complexity of biomarker testing, enabling precision medicine to improve treatment decision-making and outcomes for cancer patients, but only if test results are reliable, accurate, and validated clinically and analytically to the highest standard available. The analyses presented herein demonstrate the extensive analytical and clinical validation supporting the F1CDx initial and subsequent FDA approvals to ensure high sensitivity, specificity, and reliability of the data reported. The analytical validation included several in-depth evaluations of F1CDx assay performance including limit of detection (LoD), limit of blank (LoB), precision, and orthogonal concordance for SVs (including base substitutions [SUBs] and insertions/deletions [INDELs]), CNAs (including amplifications and homozygous deletions), genomic rearrangements, and select complex biomarkers. The assay validation of >30,000 test results comprises a considerable and increasing body of evidence that supports the clinical utility of F1CDx to match patients with solid tumors to targeted therapies or immunotherapies based on their tumor’s genomic alterations and biomarkers. F1CDx meets the clinical needs of providers and patients to receive guideline-based biomarker testing, helping them keep pace with a rapidly evolving field of medicine.

The novel test has the potential to provide substantial cost savings for NHS. Even when the novel test's cost is added to the current cost of care, the benefits exceed the additional cost, driven by the test's ability to reduce the rates of false-positive and false-negative diagnoses compared to current standard of care. Potential study limitations include the use of a pooled average of the individual sensitivities and specificities of currently used tests since no data were available on combination testing, the reliance on clinical trial data versus actual practice, and the use of clinical expert opinion when published data were unavailable.

This study was designed to assess the cost-effectiveness of erlotinib compared with docetaxel in the second-line management of advanced non-small-cell lung cancer (NSCLC) within the UK National Health Service (NHS). A health-state transition model, based on two randomized phase III studies of erlotinib or docetaxel versus best supportive care, was used to estimate total direct costs, quality-adjusted life years (QALYs) and the subsequent net monetary benefit. Erlotinib was associated with a reduction in total costs ( pound13 730 versus pound13 956) and improved outcomes (total QALYs of 0.238 versus 0.206) compared with docetaxel. Sensitivity analyses demonstrated the robustness of this analysis. In summary, erlotinib appeared to generate similar overall survival, an increase in QALYs and a small reduction in total NHS costs compared with docetaxel, due to lower adverse event and drug administration costs. Consequently, from a health economics perspective for the treatment of relapsed stage III - IV NSCLC patients in the UK, erlotinib has advantages over docetaxel.

Key Points Question What is the comparative effectiveness of single-agent immune checkpoint inhibitors (ICIs) vs taxane chemotherapy in populations of patients with metastatic castration-resistant prostate cancer (mCRPC) defined by levels of tumor mutational burden (TMB)? Findings In this comparative effectiveness study of 741 patients with mCRPC, patients with TMB of 10 mutations per megabase (mt/Mb) or greater had significantly longer time to next treatment and overall survival with ICIs vs taxanes. Meaning These findings suggest that in scenarios where taxane use is considered, ICIs are a viable alternate treatment option for patients with mCRPC and TMB of 10 mt/Mb or greater.