Evaluation of historical control data in carcinogenicity studies

Abstract

<jats:p> Results obtained in long-term carcinogenicity studies with animals should be evaluated, first and foremost, by statistical comparisons of the data obtained from the treated group with that from the concurrent control group. Often the results are compared with data from so-called historical control groups in order to take variations in the incidences of spontaneous tumours into account. Because historical control data change in the course of time and for a variety of reasons, certain requirements must be met before they may be used in the evaluation of the results of long-term studies. </jats:p><jats:p> The present paper discusses potential sources of variability of tumour incidences in untreated animals, presents databanks for historical control data, mentions the factors that affect tumour incidences in untreated animals and describes biostatistical data evaluation. Finally, details are given of the criteria used by the DFG Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area to decide whether historical control data may be applied. These include the requirement that the historical control data were obtained with animals of the same species and strain and from the same breeder. The data were obtained in the same laboratory, the study design, experimental methods and assessment criteria were the same, and the studies used for the comparison were carried out within a limited time window. Historical control data that have not been published may be used provided they fulfil the above criteria and have been made available in sufficient detail to be comprehensible. </jats:p>

Carcinogenicity Evaluation: Comparison of Tumor Data from Dual Control Groups in the Sprague–Dawley Rat

“…It has been highlighted that historical control data has a role in the evaluation of rare neoplasms, high-incidence tumors, marginal increases in incidence and in the assessment of the quality of a study (Greim et al, 2003). However, it is known that variation of incidence of tumor types within the same strain and sex and, within the same laboratory, occur due to the progression of time (Gopinath, 1994).…”

Incorporating Historical Control Data When Comparing Tumor Incidence Rates

“…The need for a formal method of incorporating historical control data in the analysis of the current experiment has long been recognized (Haseman et al, 1984;Haseman 1995), but no procedure has emerged as the clear favorite (Greim et al, 2003). The Technical Reports Review Subcommittee of the NTP Board of Scientific Counselors, which includes two statisticians, has not endorsed any of the current methods and recommended a new procedure be developed for this important problem (http://ntp.niehs.nih.gov/files/TRRSMins0905.pdf).…”

Glyphosate toxicity and carcinogenicity: a review of the scientific basis of the European Union assessment and its differences with IARC

“…Spontaneous incidences and use of historical control data(Dinse and Peddada 2011; Greim et al 2003; Keenan et al 2008; Ma et al 2002; Massarelli et al 2013)Relevance for humans, e.g. species-specific mechanism that does not operate in humansThe use of historical data is mentionedAll valid studies are considered negative.…”

“…In addition to best practices (Greim et al 2003; Keenan et al 2009), graphical visualisations (Elmore and Peddada 2009) and statistical approaches (Dinse and Peddada 2011; Peddada et al 2007) have been developed, although direct comparison with the historical control range in the test laboratory around the time of the study is the approach mostly used in the regulatory context, and preferred in the EU assessment. This approach was considered for malignant lymphomas and haemangiosarcomas in mice when the studies reported the historical range for the test laboratory.…”