The Benefits and Risks of Receiving Investigational Solid Tumor Drugs in Randomized Trials : A Systematic Review and Meta-analysis.

BACKGROUND: Many patients participate in cancer trials to access new therapies. The extent to which new treatments produce clinical benefit for trial participants is unclear. PURPOSE: To estimate the progression-free survival (PFS) and overall survival (OS) advantage of assignment to experimental groups in randomized trials for 6 solid tumors. DATA SOURCES: ClinicalTrials.gov was searched for trials of investigational drugs with results posted between 2017 and 2021. STUDY SELECTION: Investigational drugs were defined as those not yet having full approval from the U.S. Food and Drug Administration for the study indication. Trials were included if they were randomized and tested drugs or biologics. DATA EXTRACTION: Data extraction was completed by 2 independent reviewers. Data were pooled using a random-effects model. DATA SYNTHESIS: The sample included 128 trials comprising 141 comparisons of a new drug and a comparator. These comparisons included 47 050 patients. The pooled hazard ratio for PFS was 0.80 (95% CI, 0.75 to 0.85), indicating statistically significant benefit for patients in experimental groups. This corresponded to a median PFS advantage of 1.25 months (CI, 0.80 to 1.68 months). The pooled hazard ratio for OS was 0.92 (CI, 0.88 to 0.95), corresponding to a survival gain of 1.18 months (CI, 0.72 to 1.71 months). The absolute risk for a serious adverse event for comparator group patients was 29.56% (CI, 26.64% to 32.65%), with an increase in risk of 7.40% (CI, 5.66% to 9.14%) for patients in experimental groups. LIMITATIONS: Trials in this sample were heterogeneous. Comparator group interventions were assumed to reflect standard of care. CONCLUSION: Assignment to experimental groups produces statistically significant survival gains. However, the absolute survival gain is small, and toxicity is statistically significantly greater. The findings of this review provide reassuring evidence that patients are not meaningfully disadvantaged by assignment to comparator groups. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Identification of difficult laryngoscopy using an optimized hybrid architecture.

BACKGROUND: Identification of difficult laryngoscopy is a frequent demand in cervical spondylosis clinical surgery. This work aims to develop a hybrid architecture for identifying difficult laryngoscopy based on new indexes. METHODS: Initially, two new indexes for identifying difficult laryngoscopy are proposed, and their efficacy for predicting difficult laryngoscopy is compared to that of two conventional indexes. Second, a hybrid adaptive architecture with convolutional layers, spatial extraction, and a vision transformer is proposed for predicting difficult laryngoscopy. The proposed adaptive hybrid architecture is then optimized by determining the optimal location for extracting spatial information. RESULTS: The test accuracy of four indexes using simple model is 0.8320. The test accuracy of optimized hybrid architecture using four indexes is 0.8482. CONCLUSION: The newly proposed two indexes, the angle between the lower margins of the second and sixth cervical spines and the vertical direction, are validated to be effective for recognizing difficult laryngoscopy. In addition, the optimized hybrid architecture employing four indexes demonstrates improved efficacy in detecting difficult laryngoscopy. TRIAL REGISTRATION: Ethics permission for this research was obtained from the Medical Scientific Research Ethics Committee of Peking University Third Hospital (IRB00006761-2015021) on 30 March 2015. A well-informed agreement has been received from all participants. Patients were enrolled in this research at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn , identifier: ChiCTR-ROC-16008598) on 6 June 2016.