Patient Benefit and Risk in Anticancer Drug Development: A Systematic Review of the Ixabepilone Trial Portfolio

摘要: Abstract OBJECTIVE To describe the patient burden and benefit, dynamics of trial success in development ixabepilone—a drug that was approved US but not Europe. DATA SOURCES Trials were captured by searching Embase MEDLINE on July 27, 2015. STUDY SELECTION Inclusion: 1) primary reports, 2) interventional trials, 3) human subjects, 4) phase 1 to 3, 5) trials ixabepilone monotherapy or combination therapy 6) pre-licensure cancer indications. Exclusion: secondary interim results, meta-analyses, retrospective/observational studies, laboratory analyses (ex vivo tissues), reviews, 7) letters, editorials, guidelines, interviews, abstract-only poster presentations. EXTRACTION AND SYNTHESIS Data independently double-extracted differences between coders reconciled discussion. MAIN OUTCOMES MEASURES We measured risk using number drug-related adverse events grade 3 higher, benefit objective response rate outcomes whether studies met their endpoint with acceptable safety. RESULTS identified 39 publications 23 therapy, representing 5615 patients 1598 patient-years involvement over 11 years involving 17 different malignancies. In total, 830 receiving experienced tumour (16%, 95% CI 12.5%–20.1%), 74 died from toxicites (2.2%, 1.6%–2.9%). Responding indications combinations very quickly; thereafter, search for additional responding did lead labelling additions. A total “uninformative” found, 27% testing efficacy, 208 3–4 226 (21% 26% portfolio respectively). After European Medicines Agency rejected licensing, all further activity pursued outside DISCUSSION Risk/benefit who enrolled non-approved improve course drug’s development. Clinical value discovered however, a large fraction uninformative.