Safety assessments numbers needed

The PRO ACT-11 trial was designed to assess the clinical efficacy and safety of lA r-pro-UK. In this study, 180 patients were enrolled in a 2 1 randomization scheme to receive either 9 mg lA r-pro-UK plus 4 hours of low-dose IV heparin, or low-dose IV heparin alone. The primary clinical outcome, the proportion of patients with slight or no disability at 90 days (mRS of < 2), was achieved in 40% of the 121 patients in the r-pro-UK treatment group, compared to 25% of the 59 patients in the control group (absolute benefit 15%, relative benefit 58%, number need to treat = 7 p = 0.04). The recanalization rate (TlMl 2 and 3) was 66% for the r-pro-UK group and 18% for the control group (p < 0.001). Symptomatic ICH within 24 hours occurred in 10% of r-pro-UK patients and 2% of control patients (p = 0.06). All symptomatic ICHs occurred in patients with a baseline NIHSS... 

Compared to efficacy, safety is typically more multifactorial, as it is dependent on homeostasis of virtually all cellular processes. A wider number and diversity of potential molecular and cellular effects of compound interactions may affect safety than may affect efficacy or bioavailability. Accordingly, cytotoxicity assessment is less specific, more multi parametric and extrapolatable with less certainty, unless there are specific safety signals indicated by the chemical structure or by its precedents. Extrapolation of safety biomarker data needs a greater foundation of mechanistic understanding of both in vitro and in vivo pathogenesis of toxicities, as well as rigorous, empirical validation of models. 

To be effective, a safety training program needs to be characterized by a number of features. First, a needs assessment or analysis should be undertaken to identify the content of the training program. Content should be both specific to the new employee s job and guided by research findings in the safety literature. The presentation of the content should follow a systematic training model and adopt best practice methods, which should also allow for a consideration of new employee... 

In subgroup analysis, it may become necessary to examine multiple, often numerous, subgroups based on baseline characteristics. This is in addition to a potentially large number of types of adverse events (e.g., MedDRA Preferred Term [PT] level. Standardized MedDRA Queries) that need to be evaluated for safety assessment. 

From the above review, it is clear that some of the centralised applications have more extensive animal safety documentation than needed. This could reflect the state-of-the-art a number of years ago. There are also a few areas in which the documentation is less than what would be advisable, primarily from a clinical trial perspective. However, since the CPMP is normally engaged in pre-clinical safety assessment when there is already substantial clinical experience, many of the concerns that may arise from animal experiments, or sometimes lack thereof, can be discarded. 

Reactive System Screening Tool (RSST) The RSST is a calorimeter that quickly and safely determines reactive chemical hazards. It approaches the ease of use of the DSC with the accuracy of the VSP. The apparatus measures sample temperature and pressure within a sample containment vessel. Tne RSST determines the potential for runaway reactions and measures the rate of temperature and pressure rise (for gassy reactions) to allow determinations of the energy and gas release rates. This information can be combined with simplified methods to assess reac tor safety system relief vent reqiiire-ments. It is especially useful when there is a need to screen a large number of different chemicals and processes. 

You will need to involve a number of different people, including your safety representatives and employees, to do the risk assessments. 

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