Role of the Study Pathologist

Abstract

Toxicologic pathology relies on many disciplines of toxicology and basic sciences and often requires other fields and skills such as biostatistics, study design, guidelines, and knowledge of Good Laboratory Practices (GLP) regulations. Pathology is an integrative discipline where specific training and experience are required in order to integrate chemical or biological structures, molecular biology, physiology, and morphology for candidate selection and early development of a test article and to help in the design of appropriate preclinical/toxicology studies. Experience does matter and successful learning is determined by personal behavior; pathologists who not only read slides but research their topics and keep current with the literature are apt to be successful.

Pathology is the study and diagnosis of diseases and hence deals with the cause/etiology, pathogenesis, morphological changes and clinical manifestations of a disease. General pathology investigates the mechanisms of injury to cells, tissues, and organisms and applies the obtained knowledge to diagnose diseases in humans and animals. Toxicologic pathology studies the structural and functional changes in cells, tissues and organs that are induced by toxicants. This includes mechanistic studies. The results from these toxicologic studies are the basis for risk assessment and risk management. Toxicologic pathology relies on other disciplines of toxicology, i.e., biochemistry, pharmacodynamics, and pharmacokinetics, as well as basic sciences (e.g. physiology, anatomy, molecular biology, immunology, pharmacology, organic and inorganic chemistry, etc.) and often requires other fields and skills such as biostatistics, study design, guidelines, and knowledge of Good Laboratory Practices (GLP) regulations. Thus, pathology is an integrative discipline.

The main difference between diagnostic and toxicologic pathology is that diagnostic pathology considers all available data obtained from a single individual whereas toxicologic pathology evaluates a group of animals. Specific training and experience are required in order to integrate chemical or biological structures, molecular biology, physiology and morphology for candidate selection and early development of a test article and to design appropriate preclinical/toxicology studies

Nevertheless, the majority of human and veterinary pathologists are by training not focused on pre-clinical toxicologic pathology. A board certified pathologist may not be the better pathologist considering the limited education provided in toxicologic pathology. Experience does matter and is achieved through interactions with other pathologists in the discipline of toxicologic pathology, by undergoing training periods in other institutions, by participating in national and international special courses, by taking part in slide seminars, and by participation in pathology working groups. Successful learning is determined by personal behavior; pathologists who not only read slides, but research their topics and keep current with the literature are apt to be successful.

To function as a study pathologist, the individual needs to understand the underlying mechanisms of induced lesions. For this reason, the cooperation of the study director is essential in order to obtain background information on the test article. The study pathologist should be involved in the design of the protocol before the study starts. Detailed discussions with the sponsor on test article structure or the composition of a medical device, intended indications (medicinal, chemical, agrochemical), results of previously performed studies with the test item under investigation or with similar compounds, and collaborations with experts in other fields (pharmacologists, metabolism experts, animal care staff) may be necessary to later allow the best possible interpretation of study results. A study pathologist should be able to seek contact with another reliable and experienced pathologist to discuss doubtful cases. In any case, the credibility of the results increases with a peer review.

Often, the study pathologist coordinates all studies (where pathology is involved) in a package that will be submitted to regulatory authorities. At these times, the pathologist functions as a study monitor due to the fact that all important test article information is controlled by one individual. This enables the study pathologist to discuss deeply all substance-related issues, and hence, she/he is an excellent partner for a sponsor in making next-step decisions or to include in discussions with the regulatory authorities.

In summary, a study pathologist needs to not only be trained in general pathology but to also have a sound knowledge in the basic sciences Diagnostic pathology is instrumental in understanding possible background lesions. Professional ethics cannot be neglected since the study pathologist should always be mindful of the possible harm of a wrong interpretation or assessment of a test article, not only with respect to the use of the test article on an individual but also for any loss that may be incurred by the sponsor of the test article.