Target Safety Assessment: Strategies and Resources.

An in-depth evaluation of target safety is an invaluable resource throughout drug discovery and development. The goal of a target safety evaluation is to identify potential unintended adverse consequences of target modulation, and to propose a risk evaluation and mitigation strategy to shepherd compounds through the discovery and development pipeline, to confirm and characterize unavoidable on-target toxicities in a timely manner to assist in early program advancement decisions, and to anticipate, monitor, and manage potential clinical adverse events. The role of an experienced discovery toxicologist in synthesizing the available information into an actionable set of recommendations for a safety evaluation strategy is critical to its successful application in early discovery programs. This chapter presents a summary of some of the information types and sources that should be investigated, and approaches that can be taken to generate an early assessment of potential safety liabilities.

Rapid health assessment in Aceh Jaya District, Indonesia, following the December 26 tsunami.

OBJECTIVES: To rapidly determine the public health impact of the Asian tsunami on the population of three communities in Aceh Jaya District, Indonesia, and to prioritize health interventions. METHODS: Rapid health assessment, utilizing direct observations, interviews with key informants, a single focus group discussion, town mapping, a review of medical records and a systematic random sample of the entire town of Calang, capital of Aceh Jaya District, Indonesia. RESULTS: Almost 100% of dwellings were destroyed in all three communities. For the town of Calang: only 18.2% of the pre-tsunami population remained 2 weeks following the disaster, with an estimated 70% of the population having died at the time of impact; government estimates of the remaining population were inflated by approximately 250%; mortality rates were not elevated post-tsunami; 100% of the population lacked access to sanitation and clean water; 85% of children under 5 years reported diarrhoea over the preceding 2 week period; 95% of individuals with a medical complaint reported satisfactory access to clinical care; acute malnutrition was not a significant problem; and over one-fifth of households were hosting an orphan. For the villages of Rigah and Sayeung: approximately 46.2 and 86.0% of the population survived the tsunami impact, respectively; mortality rates were not elevated post tsunami; 100% of the population lacked access to sanitation and clean water; diarrhoea was the main cause of morbidity; primary care services were available only in Rigah; and only Rigah had received external assistance. CONCLUSIONS: Almost two-thirds of the population of the three communities died as a result of the tsunami's impact. Although mortality rates were not elevated post tsunami, significant threats to public health persisted, especially water-borne diseases. Priority activities included emergent environmental health interventions, mobile clinics to the two villages and a more detailed assessment of the needs of orphans. Data were shared with agencies better placed to address needs in the areas of shelter and food aid.