Prognostic biomarkers for malignant progression of oral epithelial dysplasia: an updated systematic review and meta-analysis.

Oral epithelial dysplasia (OED) is a premalignant condition that carries an appreciable risk of malignant progression. The current grading system for severity, as defined by the World Health Organization, is a valuable clinical tool, but further work is required to improve the accuracy of predicting OED malignant progression. This systematic review aimed to assess progress in prognostic biomarker discovery in OED over the past 16 years. The primary objective was to update the latest evidence on prognostic biomarkers that may predict malignant progression of OED, with strict inclusion criteria of studies with a longitudinal design and long-term follow-up data to enhance the robustness and translational clinical potential of the findings. Of 2829 studies identified through the searching of five databases, 20 met our inclusion criteria. These studies investigated a total of 32 biomarkers, 20 of which demonstrated significant potential to predict malignant progression of OED. Meta-analysis demonstrated the significant prognostic value of four biomarkers: podoplanin, EGFR expression, p16 methylation, and DNA aneuploidy. Our review has identified 20 reported biomarkers with prognostic potential to predict malignant progression in OED, but their translation into clinical practice remains elusive. Further research is required, and this should focus on validating the promising biomarkers identified in large cohort studies, with adherence to standardised reporting guidelines.

Human robotic surgery with intraoperative tissue identification using rapid evaporation ionisation mass spectrometry.

Instantaneous, continuous, and reliable information on the molecular biology of surgical target tissue could significantly contribute to the precision, safety, and speed of the intervention. In this work, we introduced a methodology for chemical tissue identification in robotic surgery using rapid evaporative ionisation mass spectrometry. We developed a surgical aerosol evacuation system that is compatible with a robotic platform enabling consistent intraoperative sample collection and assessed the feasibility of this platform during head and neck surgical cases, using two different surgical energy devices. Our data showed specific, characteristic lipid profiles associated with the tissue type including various ceramides, glycerophospholipids, and glycerolipids, as well as different ion formation mechanisms based on the energy device used. This platform allows continuous and accurate intraoperative mass spectrometry-based identification of ablated/resected tissue and in combination with robotic registration of images, time, and anatomical positions can improve the current robot-assisted surgical platforms and guide surgical strategy.

A Survey to Assess the Current Status of Structured Benefit-Risk Assessment in the Global Drug and Medical Device Industry.

BACKGROUND: This industry survey was conducted to gain insight into the ways structured Benefit-Risk assessment (sBRA) of medical products is approached across drug or medical device developing companies, including frameworks and methods that are currently used and areas where future work is being planned. METHODS: A survey containing 28 questions covering five key areas of sBRA was set-up and shared with representatives from the participating companies. Each company was asked to complete a single survey response including inputs across the company's multidisciplinary key representatives involved in benefit-risk assessment. RESULTS: Of the 26 participating companies, 21 (81%) are conducting sBRA. Considering these 21 qualitative frameworks were used by almost every company (19, 90%), while only 12 (57%) have used a quantitative method. Many companies have sBRA training (17, 81%), document templates (16,76%), Standard Operating Procedures (SOPs)/checklists (13, 62%), and /or best practice manuals/examples (12,57%) available. Considering all 26 companies Software tools (15, 58%) and BR planning documents (11,42%) were identified as areas into which many companies intend to put effort. CONCLUSIONS: The industry survey confirmed a wide usage of sBRA by many companies involved in research and development. Nevertheless, sBRA is evolving and several future opportunities like the implementation of visualization tools were identified by the representatives of the pharmaceutical companies. Finally, challenges like the cross-functional comprehension of the added value of sBRA are still seen.

Key Opinion Leaders' Interviews to Inform the Future of Benefit-Risk Planning in the Medical Total Product Life Cycle of Global Pharmaceutical and Medical Device Organizations.

BACKGROUND AND OBJECTIVES: Key opinion leader (KOL) interviews were conducted by the Benefit-Risk Assessment Planning (BRAP) Taskforce to seek expert opinion mainly from industry and regulatory bodies, about the current status and future direction of benefit-risk assessment (BRA) planning in the lifecycle of medical product development. The findings from these interviews are intended to help communication concerning planning for BRA between industry and regulators and shape future guidance. METHODS: Key opinion leader interviews consisted of 5 questions related to BRA planning, which were administered to volunteers (mainly clinicians and statisticians) within a pool of experienced pharmaceutical and medical device professionals representing academia, industry, regulatory agencies and a patient group. The interviewees' responses to the 5 questions were summarized. To analyze the qualitative data, a Coding System was developed to label themes arising from the interviews. The key findings from the interviews were summarized into a Master Template. A quantitative analysis based on descriptive statistics was also conducted. RESULTS: Of the 27 interviewees, there were 11 professionals from regulatory agencies, 11 from industry, 4 from academia and 1 from a patient advocacy group. Key findings based on the comments provided by 48% of the interviewees indicated the need of incorporating BRA into other (e.g., existing) processes with the importance of alignment between processes being stressed in the comments provided by 59% of the interviewees. Commencing BRA early in the product lifecycle was emphasized in comments provided by 44% of the interviewees. Among other needs identified were an appropriate contextualization of benefits and risks (based on comments provided by 41% of interviewees) through adoption of an integrated approach with structured support by regulatory agencies and a need for understanding the audience with better communication of benefit-risk (BR) among all stakeholders (based on comments provided by 44% of the interviewees). Almost all comments provided by interviewees (96%) highlighted the importance of utilizing patient experience/preference to guide new product development and BRA. Comments provided by 74% of the interviewees expressed the need to understand patient tolerance for risk and trade-offs, with a majority (78%) of interviewees highlighting how to gather information, and 59% stressing the need for the selection and development of appropriate methodologies as important considerations for enhancing the quality and relevance of the data collected from patients. CONCLUSIONS: Interviewees indicated that BRA should commence early in the medical product development and inform decision-making throughout the product lifecycle. Better planning and integration of BRA into existing processes within industry would be valuable. The importance of incorporating the patient voice into BRA and medical product development was emphasized. Other key findings from the KOL interviews included a need for improved communication of BR information, and establishment of methodologies for performing BRA and soliciting patient input.