Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial

Talimogene laherparepvec is the first oncolytic immunotherapy to receive approval in Europe, the USA and Australia. In the randomized, open-label Phase III OPTiM trial (NCT00769704), talimogene laherparepvec significantly improved durable response rate (DRR) versus granulocyte-macrophage colony-stimulating factor (GM-CSF) in 436 patients with unresectable stage IIIB-IVM1c melanoma. The median overall survival (OS) was longer versus GM-CSF in patients with earlier-stage melanoma (IIIB-IVM1a). Here, we report a detailed subgroup analysis of the OPTiM study in patients with IIIB-IVM1a disease.The patients were randomized (2:1 ratio) to intralesional talimogene laherparepvec or subcutaneous GM-CSF and were evaluated for DRR, overall response rate (ORR), OS, safety, benefit-risk and numbers needed to treat. Descriptive statistics were used for subgroup comparisons.Among 249 evaluated patients with stage IIIB-IVM1a melanoma, DRR was higher with talimogene laherparepvec compared with GM-CSF (25.2% versus 1.2%; P<0.0001). ORR was also higher in the talimogene laherparepvec arm (40.5% versus 2.3%; P<0.0001), and 27 patients in the talimogene laherparepvec arm had a complete response, compared with none in GM-CSF-treated patients. The incidence rates of exposure-adjusted adverse events (AE) and serious AEs were similar with both treatments.The subgroup of patients with stage IIIB, IIIC and IVM1a melanoma (57.1% of the OPTiM intent-to-treat population) derived greater benefit in DRR and ORR from talimogene laherparepvec compared with GM-CSF. Talimogene laherparepvec was well tolerated

Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial

Talimogene laherparepvec is the first oncolytic immunotherapy to receive approval in Europe, the USA and Australia. In the randomized, open-label Phase III OPTiM trial ({"type":"clinical-trial","attrs":{"text":"NCT00769704","term_id":"NCT00769704"}}NCT00769704), talimogene laherparepvec significantly improved durable response rate (DRR) versus granulocyte-macrophage colony-stimulating factor (GM-CSF) in 436 patients with unresectable stage IIIB–IVM1c melanoma. The median overall survival (OS) was longer versus GM-CSF in patients with earlier-stage melanoma (IIIB–IVM1a). Here, we report a detailed subgroup analysis of the OPTiM study in patients with IIIB–IVM1a disease

Building Strong for Tomorrow: Recommendations for the Organizational Design of the NOAA Climate Service

The U.S. Congress asked an expert panel of the National Academy of Public Administration to assist NOAA with a study and analysis of organizational options for a Climate Service within NOAA. Further, NOAA formally asked the Panel to provide an independent assessment of how NOAA should organize its climate capabilities and make recommendations for a Climate Service line office structure that would integrate NOAA's climate science and research with service delivery.Main FindingsThe Panel strongly supports the creation of a Climate Service to be established as a line office within NOAA.The Panel concluded that a NOAA Climate Service, properly configured and implemented, would be uniquely qualified to serve the public and private sectors as a lead federal agency for climate research and services, and to provide an ongoing accessible, authoritative clearinghouse for all federal science and services related to climate.The report also includes the Panel's observations and recommendations regarding the larger federal climate enterprise, key elements of support needed by the NOAA Climate Service and the importance to the new organization of a clear strategic plan and a comprehensive implementation plan. Additionally, the Panel offered observations about institutional change management in the federal sector, identified several management recommendations for implementation and addressed operational priorities and budget challenges

Literature review of visual representation of the results of benefit–risk assessments of medicinal products

Background The PROTECT Benefit–Risk group is dedicated to research in methods for continuous benefit–risk monitoring of medicines, including the presentation of the results, with a particular emphasis on graphical methods. Methods A comprehensive review was performed to identify visuals used for medical risk and benefit–risk communication. The identified visual displays were grouped into visual types, and each visual type was appraised based on five criteria: intended audience, intended message, knowledge required to understand the visual, unintentional messages that may be derived from the visual and missing information that may be needed to understand the visual. Results Sixty-six examples of visual formats were identified from the literature and classified into 14 visual types. We found that there is not one single visual format that is consistently superior to others for the communication of benefit–risk information. In addition, we found that most of the drawbacks found in the visual formats could be considered general to visual communication, although some appear more relevant to specific formats and should be considered when creating visuals for different audiences depending on the exact message to be communicated. Conclusion We have arrived at recommendations for the use of visual displays for benefit–risk communication. The recommendation refers to the creation of visuals. We outline four criteria to determine audience–visual compatibility and consider these to be a key task in creating any visual. Next we propose specific visual formats of interest, to be explored further for their ability to address nine different types of benefit–risk analysis information

Recommendations for benefit–risk assessment methodologies and visual representations

Purpose The purpose of this study is to draw on the practical experience from the PROTECT BR case studies and make recommendations regarding the application of a number of methodologies and visual representations for benefit–risk assessment. Methods Eight case studies based on the benefit–risk balance of real medicines were used to test various methodologies that had been identified from the literature as having potential applications in benefit–risk assessment. Recommendations were drawn up based on the results of the case studies. Results A general pathway through the case studies was evident, with various classes of methodologies having roles to play at different stages. Descriptive and quantitative frameworks were widely used throughout to structure problems, with other methods such as metrics, estimation techniques and elicitation techniques providing ways to incorporate technical or numerical data from various sources. Similarly, tree diagrams and effects tables were universally adopted, with other visualisations available to suit specific methodologies or tasks as required. Every assessment was found to follow five broad stages: (i) Planning, (ii) Evidence gathering and data preparation, (iii) Analysis, (iv) Exploration and (v) Conclusion and dissemination. Conclusions Adopting formal, structured approaches to benefit–risk assessment was feasible in real-world problems and facilitated clear, transparent decision-making. Prior to this work, no extensive practical application and appraisal of methodologies had been conducted using real-world case examples, leaving users with limited knowledge of their usefulness in the real world. The practical guidance provided here takes us one step closer to a harmonised approach to benefit–risk assessment from multiple perspectives

Computerized characterization of breast masses on threeâ dimensional ultrasound volumes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134860/1/mp9531.pd

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries