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I. The Role of Clinical Pathology in the Drug Development Process |
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Clinical pathology encompasses the two major disciplines of hematology (with coagulation) and clinical chemistry; the latter often being subdivided into blood chemistry, urine chemistry, and hormone determination. Traditionally, these two disciplines have often been supported in separate laboratories with their own complement of staff and responding to separate line management. Integration of the disciplines is rare, often leading to a lack of overall appreciation of the total clinical pathology picture. A similar situation exists in the Health Service where separate departments receive and analyse samples and invariably report separately the patient's clinical chemistry or hematology results to their investigating physician. In clinical practice this approach is usually satisfactory since it is more common for a physician to be investigating or monitoring a single illness, e.g., anaemia, and rarely requires results for both hematology and clinical chemistry simultaneously. |
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The safety assessment of drugs, both preclinically and during the initial phases of clinical development, requires a totally different approach. In toxicology the studies are designed to screen for adverse changes in clinical pathology in healthy animals following the administration of a novel drug entity. Animals are rarely clinically ill and detection of subclinical target organ toxicity is required. Both clinical chemistry and hematology are routinely monitored and blood samples are often taken from the animals for both disciplines at the same time. Similarly, Phase I clinical trials are usually performed in healthy volunteers and, although they are not intended as human toxicology studies, both clinical chemistry and hematology are monitored at frequent intervals. An integrated clinical pathology report, encompassing the results from both disciplines, is clearly the most appropriate approach for these safety assessment studies. |
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A. Clinical Pathology and Preclinical Studies |
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Invariably, the role of a clinical pathology laboratory in the pharmaceutical environment is seen as principally to support toxicology studies. With a few notable exceptions, most regulatory authorities simply state the need for appropriate clinical pathology testing in toxicology studies without specifying exact requirements. It is not our intention in this chapter to discuss the merits of various tests and procedures for use in preclinical safety assessment and the reader is directed to Evans [1] where animal clinical pathology testing is discussed at length. Suffice to say that, before most new drugs are marketed, extensive animal toxicology studies will have to be completed. |
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A standard general toxicology package will include one or more short-term studies of 7 to 28 day's duration in both a rodent and nonrodent species; a 3- or |
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