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National Toxicology Program Position Statement on Informed ("Nonblinded") Analysis in Toxicologic Pathology
Robert C Sills1, Mark F Cesta1, Cynthia J Willson2
1Division of the National Toxicology Program, Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Toxicologic Pathology
|September 17, 2019
Summary
The National Toxicology Program (NTP) uses rigorous histopathological evaluation in toxicity studies. An informed approach, rather than masked analysis, is supported to ensure accurate diagnoses by comparing treated and control groups.
Area of Science:
- Toxicology
- Pathology
- Animal Studies
Background:
- Histopathological evaluation is crucial for the National Toxicology Program's (NTP) toxicity and carcinogenicity studies.
- NTP employs a multi-step peer review process with experienced toxicological pathologists and standardized terminology.
- Ancillary data, including organ weights and clinical pathology, support diagnostic corroboration.
Purpose of the Study:
- To describe the NTP's peer review process for histopathological evaluations.
- To discuss the role and limitations of masked analysis in these studies.
- To advocate for an informed approach to histopathological evaluation.
Main Methods:
- Rigorous peer review by multiple toxicological pathologists.
- Use of standardized terminology in evaluations.
- Corroboration of diagnoses with ancillary data (e.g., organ weights, clinical pathology).
- Limited use of masked analysis for subtle lesions or severity scoring during Pathology Working Groups.
Main Results:
- The NTP's peer review process involves multiple experts and standardized methods.
- Ancillary data are integrated to strengthen diagnostic confidence.
- Masked analysis, while used selectively, can hinder direct comparison with concurrent controls.
Conclusions:
- The NTP's histopathological evaluation process is comprehensive and relies on expert review and supporting data.
- An informed approach, allowing comparison between treated and control groups, is essential for accurate histopathological assessment in toxicity studies.
- The NTP prioritizes an informed evaluation strategy over fully blinded assessments to maintain diagnostic integrity.
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