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Registration of Pharmaceuticals for Human Use that have come into effect in Europe, the United States, and Japan. In principle the duration of the animal toxicology studies conducted in 2 species should equal or exceed the duration of treatment intended in the clinical trial. Phase I studies of up to 2 weeks require the support of a repeated-dose toxicity study in 2 species for a duration of at least 2 weeks. For subsequent phases and the marketing approval stage, two 1-month toxicity studies would support clinical trials of up to 2 weeks duration. Three-month toxicity studies would support clinical trials of up to 1-month duration and 6-month studies would support the extended clinical trial and fulfill marketing approval requirement if chronic toxicity or carcinogenicity studies are on-going. Completed oncogenicity studies are required only for marketing approval where prolonged use of the drug is anticipated or where there is reasonable cause for concern. In the case of drugs intended to treat life-threatening or severely debilitating disease the oncogenicity studies can be completed postapproval. The evaluation of clinical pathology parameters is an integral and essential part of every clinical trial. The monitoring of volunteers and patients is particularly intense during Phase I and Phase II trials with due note being taken of any clinical pathology changes observed in the toxicology studies. As confidence in the safety of the drug increases the frequency and scope of the clinical pathology testing will reduce such that, for Phase III/IIIb trials, there may be a need only to monitor a few key safety parameters (see Figure 1). |
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The conduct of clinical trials is a complex process requiring the integration of various key components to produce data suitable for regulatory submission. One of these key components is the clinical pathology safety or efficacy data that often represents between 40 and 60 % of the final submission document. The quality of the clinical pathology data must be of the highest standard, principally in order to provide a reliable and valued service to the patient and physician. However, clinical trial objectives require us to look beyond local quality standards to those standards that can be achieved on a much broader scale in order to provide consistency across multicenter clinical trials. There are a number of variables that can influence the production of laboratory data: methodology, instrumentation, reagents standardization, and assay temperature, to name a few. Standardizing the way in which the laboratory data is produced will have a significant impact on the overall quality of the clinical pathology contribution to clinical drug evaluation. |
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C. Integration of Preclinical and Clinical Support |
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The vast majority of Pharmaceutical Companies see the clinical pathology support of preclinical and clinical studies, with the possible exception of some Phase I trials, as being entirely separate. If toxicology studies are performed in house then it is impractical, for reasons of sample volume, to out-source |
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