11 viii. Develop capacity for signal detection and causality assessment Multi-partner training package on active TB drug safety monitoring and management (aDSM) July 2016

Key steps in aDSM implementation Create a national coordinating mechanism for aDSM Develop a plan for aDSM Define management and supervision roles and responsibilities Create standard data collection materials Train staff on the collection of data Define schedules and routes for data collection and reporting Consolidate aDSM data electronically Develop capacity for signal detection and causality assessment

Learning objective By the end of this presentation, the participant is expected to … Understand how to build capacity in-country to undertake causality assessment and contribute to signal detection

Introduction Building capacity will need a dual investment in human resource development, and facilities (location, equipment, consumables, infrastructure…) needed to undertake causality assessment and signal detection within the health care services The aDSM plan needs to make provision for these coordinated activities and budget for them

Human resource development (1) training staff Based on the roles and responsibilities of the staff who will be carrying out the aDSM (see module 11.iii), a training plan is drawn up with objectives and training material. Appropriate experts will be needed to prepare for and undertake the training. These experts may be present in the country (e.g. pharmacovigilance centre); if not the expertise may be accessed through technical partners

Human resource development (2) overall learning objectives (1) After the training, the participant is expected to be able to: Identify key concepts and definitions of aDSM Describe how to implement and manage aDSM within a TB programme Detect adverse events through clinical monitoring during TB treatment Manage adverse events clinically Record adverse events and ensure quality of data records Understand key concepts of causality assessment, signal detection and safety risk management

Human resource development (3) overall learning objectives (2) In addition the training should allow for the following discussions: How to implement aDSM at national level? What should be the flow of safety data including reporting route?

Human resource development (4) aDSM training curriculum (sample) Modular structure: Background, overview and objectives Introduction, rationale for aDSM, learning (pedagogical) objectives. The basics of aDSM Key definitions and concepts around aDSM activities. Implementing aDSM Essential elements to the implementation of aDSM Causality assessment and signal detection “deep dive” into the specifics of the two aspects of aDSM

Human resource development (5) training as a trainer Familiarize yourself with the content of all modules Delegate the technical modules if not your specialty e.g. AE clinical management can be delegated to a medical doctor, key definitions to a specialist from the national pharmacovigilance structure Select commonplace examples from your context, for instance it is better to use scenarios of TB cases with HIV co-infection if you work in southern Africa Leave space for questions and discussions, 2 important activities in the frame of the curriculum concern the initiation of discussions

Facilities (1) conducive environment In order to undertake causality assessment and signal detection, the environment - (location, equipment, consumables, infrastructure… - needs to be conducive for the workers to undertake the required tests (clinical and special tests) among target patients and to report the associated data appropriately If staff are trained to undertake causality assessment they need to be able to access special diagnostic facilities (e.g. have ECGs and calculation of the corrected QT interval) Beyond the first training, the staff need to have mentoring and access to specialist opinion to resolve any difficulties which they may have

Facilities (2) support to signal detection While causality assessment is primarily an activity which needs to happen at local level, for signal detection the pooling of data across different cohorts is expected given that new signals may be relatively uncommon. This is the primary rationale underpinning the creation of a global aDSM database, to unite safety reports from TB patients on treatment in different countries. For staff from an individual country or subnational centre to participate effectively in the global database they will need to adhere to the reporting specifications and also to receive feedback on the relevance of their contribution to global knowledge

Conclusion Developing capacity for signal detection and causality assessment requires investment in the training and support of national staff The skills needed for staff to be able to establish causal links and determine the probability of an association are rooted in epidemiology and in drug safety In addition to training, the staff would need to count upon support from expert staff to answer to any difficulties which they may experience The facilities available - including equipment, consumables, and infrastructure - also need to be conducive to the required practice