Analysis populations safety

Module IV Presents the detailed safety findings including the intent-to-treat analysis population and the safety data listings. 

Both the ITT and the safety populations can be used in the analysis of safety data. The ITT and per-protocol population are typically used in the analysis of efficacy data. 

Therefore, an algorithm has to be developed to precisely define how each analysis population of the dataset is defined. For example, there are at least four analysis population datasets, e.g. the intent-to-treat (ITT) population, the per-protocol (PP) population, the safety population, and the microbiological population, as indicated in the diagram (Figure 22.2). During the derivation of various analysis populations, it may be necessary to issue new... 

Kalmeteva, Z.A. Moldobekov, B.D. 2011. The analysis of landslide activity in seismic regions. Abstracts of International Conference. "Environmental Geosciences and Engineering Survey for Territory Protection and Population Safety". EngeoPro—2011. Moscow. 

Derrig, R. A., Segui-Gomez, M., Abtahi, A., and Liu, L.L. 2002. The effect of population safety belt usage rates on motor-vehicle-related fatalities. Accident Analysis and Prevention,... 

The results from the consequence analysis step are estimates of the statistically expected exposure of the target population to the hazard of interest and the safety/health effects related to that level of exposure. For example ... 

Historically, the so-called safety factor approach was introduced in the United States in the mid-1950s in response to the legislative needs in the area of the safety of chemical food additives (Lehman and Fitzhugh 1954). This approach proposed that a safe level of chemical food additives could be derived from a chronic NOAEL from animal studies divided by a 100-fold safety factor. The 100-fold safety factor as proposed by Lehman and Fitzhugh was based on a limited analysis of subchronic/chronic data on fluorine and arsenic in rats, dogs, and humans, and also on the assumption that the human population as a whole is heterogeneous. Initially, Lehman and Fitzhugh reasoned that the safety factor of 100 accounted for several areas of uncertainty ... 

The ADI is usually derived from a detailed analysis of the toxicology of the chemical being examined. The no observed adverse effect level (NOAEL) is determined for the most sensitive adverse effect in the test system (usually animals but occasionally humans), and a safety or uncertainty factor is applied to the NOAEL dose to derive the safe level for the general human population. 

The most recent USEPA dietary assessment for atrazine used 1.8mg/kg (chronic NOAEL from a 6-month rat study) with a 1000-fold safety factor (cRfD = 0.0018mg/kg/day). This analysis also confirmed that potential dietary exposure for all exposed population subgroups was less than 1% of the cRfD (USEPA, 2003). 

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