The clinical impact of rapid sample-to-answer "syndromic" multiplex polymerase chain reaction (PCR) testing for respiratory viruses is not clearly established. We performed a systematic literature review and meta-analysis to evaluate this impact for patients with possible acute respiratory tract infection in the hospital setting. We searched EMBASE, MEDLINE, and Cochrane databases from 2012 to present and conference proceedings from 2021 for studies comparing clinical impact outcomes between multiplex PCR testing and standard testing. Twenty-seven studies with 17,321 patient encounters were included in this review. Rapid multiplex PCR testing was associated with a reduction of - 24.22 h (95% CI -28.70 to -19.74 h) in the time to results. Hospital length of stay was decreased by -0.82 days (95% CI -1.52 to -0.11 days). Among influenza positive patients, antivirals were more likely to be given (RR 1.25, 95% CI 1.06-1.48) and appropriate infection control facility use was more common with rapid multiplex PCR testing (RR 1.55, 95% CI 1.16-2.07). Our systematic review and meta-analysis demonstrates a reduction in time to results and length of stay for patients overall along with improvements in appropriate antiviral and infection control management among influenza-positive patients. This evidence supports the routine use of rapid sample-to-answer multiplex PCR testing for respiratory viruses in the hospital setting.

The present study aimed at systematically reviewing the role and extent of patient-reported outcomes (PROs) usage within the package of scientific evidence considered for marketing authorization (MA). All regulatory information published by the European Medicines Agency (EMA) for products authorized between January 2008 and December 2012 and appearing in the European Public Assessment Report (EPAR) database was examined for efficacy endpoints. The endpoints here considered included: PROs, clinician reported outcomes (CROs), and laboratory reported outcomes (LROs). LROs were the most frequently reported endpoints. Out of the 180 products here selected, 99 (55%), 67 (37%), and 30 (17%), respectively, used LROs, CROs and PROs as primary endpoints (PEs). PROs as any endpoints were used in 82 (46%) products. Out of these, PROs were documented as PE in 30 (37%), with 27 (33%) products having used PROs both as primary and non-PEs. PRO usage was most frequently identified with nervous system and antineoplastic agents. During the study period, the use of all the three types of endpoints appeared to be static. Both the regulatory bodies and the industry should ensure complete and clear reporting of all endpoints used, including PROs, to improve transparency.

Treatment resistance due to gene alterations remains a challenge for patients with EGFR-mutated advanced or metastatic non-small-cell lung cancer (a/mNSCLC). A systematic literature review (SLR) was conducted to describe resistance mutation profiles and their impact on clinical outcomes in adults with a/mNSCLC in the United States (US). A comprehensive search of MEDLINE and Embase (2018–August 2022) identified 2986 records. Among 45 included studies, osimertinib was the most commonly reported treatment (osimertinib alone: 15 studies; as one of the treatment options: 18 studies), followed by other tyrosine kinase inhibitors (TKIs; 5 studies) and non-TKIs (1 study). For first-line (1L) and second-line (2L) osimertinib, the most frequent EGFR-dependent resistance mechanisms were T790M loss (1L: 15.4%; 2L: 20.5–49%) and C797X mutation (1L: 2.9–12.5%; 2L: 1.4–22%). EGFR-independent mechanisms included MET amplification (1L: 0.6–66%; 2L: 7.2–19%), TP53 mutation (1L: 29.2–33.3%), and CCNE1 amplification (1L: 7.9%; 2L: 10.3%). For patients receiving osimertinib, EGFR T790M mutation loss, EGFR/MET/HER2 amplification, RET fusion, and PIK3CA mutation were associated with worse progression-free survival. Resistance mechanisms resulting from current NSCLC treatments in the US are complex, underscoring the need to address such heterogeneous resistance profiles and improve outcomes for patients with EGFR-mutated a/mNSCLC.