Regulatory requirements statistics

Unlike quality assurance plans, which address primarily regulatory requirements involving comprehensive documentation, quality control programs are science based, the components of which may be defined statistically. The two most important components of quality control are (1) determination of the precision of analysis and (2) determination of the accuracy of measurement. 

Apart from compliance with SOPs for biostatistics and report writing, the statistical analysis plan, the trial protocol, regulatory requirements and guidelines (ICH E3, 1995 ICH E9, 1998 ISO 9000 2005, 2005), QA auditors check the internal consistency of the trial report and appendices and between data in tables, figures and graphs and numbers cited in the text. All numbers and percentages must be substantiated by attached tables and listings. In summary, the trial report should be an accurate representation of the clinical data. Allocation of trial... 

Fig. 3 Pharmaceutical development cost Development cost denoted for various mainly chemical pharmaceuticals, including vaccine projects. Correlation with rising regulatory requirements as indicated by the counts of existing guidelines at the indicated point of time. Average consumer cost index for a household of four persons taken from figures released by the Feral German Statistics Office (Statistisches Bundesamt). Graphs show relative figures adjusted to a uniform scale.

To prepare appropriate protocols, staff must understand research design and statistical inferences for clinical research state-of-the-art research designs and trials therapeutic area guidelines GCP regulatory requirements, guidelines and country-specific issues national and international medical practices sponsor protocol review and approval procedures and possess in-depth investigational product-disease knowledge. 

Such a definition of LLOQ is obviously directed at ensuring that quantitative analytical methods developed for bioanalytical purposes are properly vahdated, rather than at describing a definition of LLOQ as a statistically defensible estimate of the minimum concentration that can be measured rehably . In practice bioanalytical laboratories are therefore not necessarily interested in the ultimate performance of their quantitative methods, but rather in ensuring that the method meets the regulatory requirements over the concentration range pertinent to their study in other words, provided that the method satisfies the 20 % demands on accuracy and precision at the lowest concentration relevant to that particular study, that concentration is taken to be the LLOQ. The FDA allows no interpolation or extrapolation of data on accuracy and precision to concentration values other than those at which the experimental determinations were made. 

The Health and Safety Executive web pages provide a useful range of material including health and safety statistics, guidance on regulatory requirements and consultation documents http //www.open.gov.uk/hse/hsehome.htm... 

Statistical analysis is essential In order to gain an overview of the very extensive data collected during such studies and to highlight any underlying trends. This analysis also aids in determining the non-toxic effect level required by regulatory authorities. 

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