Case Studies of Categorical Data-Derived Adjustment Factors

Naumann, Bruce D.; Silverman, Keith C.; Dixit, Rakesh; Faria, Ellen C.; Sargent, Edward V.

doi:10.1080/20018091094213

Cited by 35 publications

(24 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These "categorical factors" (see, for example, Silverman et al 1999;Naumann et al 2001) are intermediates in the continuum of data-derived approaches ( Figure 5). Categorical approaches illustrate the welcomed evolution away from "10-fold default" uncertainty factors toward more refined "default" approaches, but they do not necessarily apply empirical, chemical-specific TK or TD data for the compound of interest, possibly due to the lack thereof.…”

Section: Terminology/definitionsmentioning

confidence: 99%

Evolution of chemical-specific adjustment factors (CSAF) based on recent international experience; increasing utility and facilitating regulatory acceptance

Bhat

Meek

Valcke

et al. 2017

Critical Reviews in Toxicology

View full text Add to dashboard Cite

Brown (2017): Evolution of chemical-specific adjustment factors (CSAF) based on recent international experience; increasing utility and facilitating regulatory acceptance, Critical Reviews in Toxicology, DOI: 10.1080DOI: 10. /10408444.2017 The application of chemical-specific toxicokinetic or toxicodynamic data to address interspecies differences and human variability in the quantification of hazard has potential to reduce uncertainty and better characterize variability compared with the use of traditional default or categorically-based uncertainty factors. The present review summarizes the state-of-the-science since the introduction of the World Health Organization/International Programme on Chemical Safety (WHO/IPCS) guidance on chemical-specific adjustment factors (CSAF) in 2005 and the availability of recent applicable guidance including the WHO/IPCS guidance on physiologically-based pharmacokinetic (PBPK) modeling in 2010 as well as the U.S. EPA guidance on data-derived extrapolation factors in 2014. A summary of lessons learned from an analysis of more than 100 case studies from global regulators or published literature illustrates the utility and evolution of CSAF in regulatory decisions. Challenges in CSAF development related to the adequacy of, or confidence in, the supporting data, including verification or validation of PBPK models. The analysis also identified issues related to adequacy of CSAF documentation, such as inconsistent terminology and often limited and/or inconsistent reporting, of both supporting data and/or risk assessment context. Based on this analysis, recommendations for standardized terminology, documentation and relevant interdisciplinary research and engagement are included to facilitate the continuing evolution of CSAF development and guidance.ARTICLE HISTORY

show abstract

Section: Terminology/definitionsmentioning

confidence: 99%

Evolution of chemical-specific adjustment factors (CSAF) based on recent international experience; increasing utility and facilitating regulatory acceptance

Bhat

Meek

Valcke

et al. 2017

Critical Reviews in Toxicology

View full text Add to dashboard Cite

show abstract

“…The study indicated that kinetic subfactors were higher than dynamic subfactors in children. Naumann et al (2001) suggested that C max and AUC were considered the best indicators of body burden and systemic exposure. Since the C max and AUC values of NMBA examined here were sparse in the literature, other available kinetic parameters (t 1/2 , CL, Vd) were considered in this study, which may represent the high ratios.…”

Section: Discussionmentioning

confidence: 99%

“…Kinetic and dynamic behavior of NMBA may change with different anesthesia, therefore, the paper was carefully selected after examining many parameters especially anesthetic agents. Peak plasma concentration (C max ) and area under the plasma concentration curve (AUC) are considered the best indicators of body burden and systemic exposure as they are direct measures of the amount of compound in the blood (Naumann et al 2001). Because the literature of NMBA examined in this study did not provide enough C max and AUC values, other kinetic parameters considered were elimination half-life (t 1/2 ), clearance (CL) and volume of distribution (Vd).…”

Section: Approachmentioning

confidence: 99%

“…Once relevant kinetic and dynamic parameters were collected, ratios were calculated by dividing the mean plus two standard deviations of sensitive individuals by the mean from the general population (Naumann et al 2001). For the CL and Vd, ratios were obtained by dividing the mean value of data from the general population by the mean minus two standard derivation of the sensitive subpopulation, because CL and Vd values are generally lower in sensitive individuals than in the general population.…”

Section: Approachmentioning

confidence: 99%

See 1 more Smart Citation

Evaluating the 10X Uncertainty Factor for Children and Elderly with Data-Derived Values for Neuromuscular Blocking Agents

Suh

Abdel‐Rahman

2002

Human and Ecological Risk Assessment: An International Journal

View full text Add to dashboard Cite

Conventional risk assessment process utilizes a 10-fold uncertainty factor (UF) to extrapolate from the general human population to sensitive subgroups, such as children and elderly. The purpose of this investigation was to evaluate whether the magnitude of the 10X-UF can be reduced when pharmacokinetic and pharmacodynamic data are incorporated to characterize human sensitivity. An extensive literature search was conducted on seven neuromuscular blocking agents (mivacurium, atracurium, rocuronium, vecuronium, doxacurium, pancuronium, pipecuronium). Composite factors (kinetics × dynamics) were calculated using the highest dataderived kinetic and dynamic values. For the drugs examined, all of the composite factors for the sensitivity of children were lower than 5. In the elderly, all of the composite factors were lower than 10, and five of seven composite factors were less than 5. From this study, it was concluded that relevant compound-specific kinetic and dynamic data can reduce the uncertainties associated with sensitive subgroups.

show abstract

“…A further analysis of a much larger database supported the IPCS conclusions (Renwick and Lazarus 1998;Renwick 2000). Several other investigators (Hattis et al 1987;Silverman et al 1999;Suh et al 1999;Abdel-Megeed et al 2001;Naumann et al 2001;Skowronski et al 2001) have also utilized kinetic and dynamic data to characterize the variability between sensitive groups and the general population or the variability within the general population. The majority of those studies provided support for the use of data-derived adjustment factors to replace the default subfactors.…”

Section: Introductionmentioning

confidence: 94%

Application of Kinetic and Dynamic Data for Antihistamines to Risk Characterization in Sensitive Populations

Skowronski

Abdel‐Rahman

Turkall

2002

Human and Ecological Risk Assessment: An International Journal

View full text Add to dashboard Cite

A major goal of risk assessment is to protect the health of individuals who may be more sensitive than the general population. This study compared human pharmacokinetic and pharmacodynamic data in sensitive groups (i.e., children, the elderly, diseased states, and poor metabolizers) versus young, healthy adults for the antihistamines cetirizine, fexofenadine, loratadine, azelastine, ebastine, chlorpheniramine, and diphenhydramine.The default components (3.16 each for kinetic and dynamic aspects) of the intraspecies uncertainty factor were adjusted with compound specific data for the antihistamines. The majority (16 of 18) of the composite factors (kinetics × dynamics) for the sensitive groups were less than 10. Children had the lowest composite factors for antihistamines, ranging from 1.1 to 6.3. Application of kinetic and dynamic data for antihistamines to the Renwick/International Programme on Chemical Safety (IPCS) scheme can aid in characterizing the extent of variability in sensitive populations, thereby reducing the uncertainty associated with the risk assessment of sensitive populations.

show abstract

Case Studies of Categorical Data-Derived Adjustment Factors

Cited by 35 publications

References 0 publications

Evolution of chemical-specific adjustment factors (CSAF) based on recent international experience; increasing utility and facilitating regulatory acceptance

Evolution of chemical-specific adjustment factors (CSAF) based on recent international experience; increasing utility and facilitating regulatory acceptance

Evaluating the 10X Uncertainty Factor for Children and Elderly with Data-Derived Values for Neuromuscular Blocking Agents

Application of Kinetic and Dynamic Data for Antihistamines to Risk Characterization in Sensitive Populations

Contact Info

Product

Resources

About