• Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer.

      Kennedy, Sean P; Han, Jeremy Z R; Portman, Neil; Nobis, Max; Hastings, Jordan F; Murphy, Kendelle J; Latham, Sharissa L; Cadell, Antonia L; Miladinovic, Dushan; Marriott, Gabriella R; et al. (2019-03-21)
    • Using administrative health data for palliative and end of life care research in Ireland: potential and challenges.

      Kelly, Maria; O'Brien, Katie M; Hannigan, Ailish (2021-05-26)
      Background: This study aims to examine the potential of currently available administrative health and social care data for palliative and end-of-life care (PEoLC) research in Ireland. Objectives include to i) identify data sources for PEoLC research ii) describe the challenges and opportunities of using these and iii) evaluate the impact of recent health system reforms and changes to data protection laws. Methods: The 2017 Health Information and Quality Authority catalogue of health and social care datasets was cross-referenced with a recognised list of diseases with associated palliative care needs. Criteria to assess the datasets included population coverage, data collected, data dictionary and data model availability, and mechanisms for data access. Results: Nine datasets with potential for PEoLC research were identified, including death certificate data, hospital episode data, pharmacy claims data,  one national survey, four disease registries (cancer, cystic fibrosis, motor neurone and interstitial lung disease) and a national renal transplant registry.  The ad hoc development of the health system in Ireland has resulted in i) a fragmented information infrastructure resulting in gaps in data collections particularly in the primary and community care sector where much palliative care is delivered, ii) ill-defined data governance arrangements across service providers, many of whom are not part of the publically funded health service and iii) systemic and temporal issues that affect data quality. Initiatives to improve data collections include introduction of i) patient unique identifiers, ii) health entity identifiers and iii) integration of the Eircode postcodes. Recently enacted general data protection and health research regulations will clarify legal and ethical requirements for data use. Conclusions: Ongoing reform initiatives and recent changes to data privacy laws combined with detailed knowledge of the datasets, appropriate permissions, and good study design will facilitate future use of administrative health and social care data for PEoLC research in Ireland.
    • Weekly platinum-based chemotherapy versus 3-weekly platinum-based chemotherapy for newly diagnosed ovarian cancer (ICON8): quality-of-life results of a phase 3, randomised, controlled trial.

      Blagden, Sarah P; Cook, Adrian D; Poole, Christopher; Howells, Lesley; McNeish, Ian A; Dean, Andrew; Kim, Jae-Weon; O'Donnell, Dearbhaile M; Hook, Jane; James, Elizabeth C; et al. (2020-07-01)
      In this open-label, randomised, controlled, phase 3, three-arm, Gynecologic Cancer Intergroup (GCIG) trial done at 117 hospital sites in the UK, Australia, New Zealand, Mexico, South Korea, and Republic of Ireland, women (aged at least 18 years) with newly diagnosed, histologically confirmed International Federation of Gynecology and Obstetrics stage IC-IV ovarian cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were randomly assigned (1:1:1) centrally using minimisation to group 1 (intravenous carboplatin area under the curve [AUC]5 or AUC6 and 175 mg/m2 intravenous paclitaxel every 3 weeks), group 2 (carboplatin AUC5 or AUC6 every 3 weeks and 80 mg/m2 paclitaxel weekly), or group 3 (carboplatin AUC2 weekly and 80 mg/m2 paclitaxel weekly). Randomisation was stratified by GCIG group, disease stage, and outcome and timing of surgery. Patients and clinicians were not masked to treatment assignment. Patients underwent immediate or delayed primary surgery according to clinicians' choice. Patients were asked to complete European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-OV28 questionnaires at enrolment, before each chemotherapy cycle, then 6-weekly up to 9 months, 3-monthly up to 2 years, and 6-monthly up to 5 years. Quality of life was a prespecified secondary outcome of the ICON8 study. Within the quality-of-life study, the co-primary endpoints were QLQ-C30 global health score at 9 months (cross-sectional analysis) and mean QLQ-C30 global health score from randomisation to 9 months (longitudinal analysis). Data analyses were done on an intention-to-treat basis. The trial is registered on ClinicalTrials.gov, NCT01654146 and ISRCTN Registry, ISRCTN10356387, and is currently in long-term follow up.