Structured frameworks to increase the transparency of the assessment of benefits and risks of medicines: current status and possible future directions

Structured frameworks for benefit-risk analysis in drug licensing decisions are being implemented across a number of regulatory agencies worldwide. The aim of these frameworks is to aid the analysis and communication of the benefit-risk assessment throughout the development, evaluation, and supervision of medicines. In this review, authors from regulatory agencies, pharmaceutical companies, and academia share their views on the different frameworks and discuss future directions

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

The complex emplacement dynamics and tsunami genesis of the 1888 Ritter Island sector collapse from 3D seismic data

On March 13 1888, a large sector of the subaerial and submarine edifice of Ritter Island (Papua New Guinea) collapsed and slid into the Bismarck Sea, triggering a tsunami with a run-up height of more than 25 m on the neighboring islands. The tsunami traveled for more than 600 km and caused destruction in several settlements. German colonists described in detail the timing of the arriving waves. During research cruise SO252 onboard RV Sonne, we collected a comprehensive set of multibeam and sediment echosounder data, seafloor video footage, rock samples, 2D seismic profiles, and a 60 km2 high-resolution Pcable 3D seismic cube. This dataset, combined with the historic eyewitness accounts, allows detailed reconstruction of the large-scale volcanic sector collapse and the associated tsunami genesis. The 3D seismic cube shows a change of emplacement dynamics between the initial phase of mass movement and the final collapse of the volcanic edifice.that failure occurred in at least in two steps. The initial failure occurred along a deep slide plane extending from the volcanic cone up to 300 m deep into the seafloor sediments adjacent to the volcanic edifice. Movement of large, intact sediment blocks and shortening characterize this deep-rooted mass-movement. In contrast to the well-preserved mobilization structures in the deep part of the volcanic edifice related to the first phase, there are hardly any proximal deposits of the 2 km3 of the upper part of the volcanic edifice, comprising bedded volcaniclastic stratigraphy, including the subaerial island, which were mobilized in the second phase, indicating that this phase was highly energetic. Instead, the moving mass of the second phase eroded deeply into the deposits of the first slide phase. The fast moving mass was channelized between two volcanic ridges, transported into the basin west of Sakar Island, and then deposited more than 30 km away from its source. We interpret the separation into two phases as the result of gravitational acceleration of the sliding mass leading to a decoupling of the cone from the deeper edifice or a phreatomagmatic explosion due to the contact of the magmatic conduit with seawater