Establishing Data-Derived Adjustment Factors from Published Pharmaceutical Clinical Trial Data

Silverman, Keith C.; Naumann, Bruce D.; Holder, Daniel; Dixit, Rakesh; Faria, Ellen C.; Sargent, Edward V.; Gallo, Michael A.

doi:10.1080/10807039991289347

Cited by 43 publications

(17 citation statements)

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“…95th) to its central tendency (e.g. median) in the population (Meek et al 2002;Silverman et al 1999), such as illustrated for benzene, chloroform, and other solvents by Valcke and Krishnan (2014). Alternatively, they are calculated as the ratio between the values for an upper percentile in a presumed susceptible subpopulation and the central tendency in the general healthy population.…”

Section: Hazard Assessmentmentioning

confidence: 99%

“…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%

“…grouping of compounds based on specific knowledge that they have similar toxicological action (e.g. Silverman et al 1999) or common elimination pathways (e.g. Dorne et al 2005;Dorne 2007).…”

Section: Hazard Assessmentmentioning

confidence: 99%

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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

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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

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Section: Hazard Assessmentmentioning

confidence: 99%

Section: Terminology/definitionsmentioning

confidence: 99%

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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

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show abstract

“…For instance, the U.S. EPA (2002) recommends using "half log" (i.e., 10 0.5 or approximately 3) factors where uncertainty is reduced by the availability of multispecies pharmacokinetic or pharmacodynamic data. Others have advocated uncertainty factors that are derived on a compound-speciWc basis from supporting data ("data-derived factors"; Naumann and Weideman, 1995;Renwick, 1993;Silverman et al, 1999 or "chemical-speciWc adjustment factors"; IPCS, 2001). Table 2 describes our implementation of these concepts, incorporating the considerable amount of human and laboratory data available for APIs.…”

Section: Development Of Adismentioning

confidence: 99%

Human pharmaceuticals in US surface waters: A human health risk assessment

Schwab

Hayes

Fiori

et al. 2005

Regulatory Toxicology and Pharmacology

358

182

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“…Renwick and Lazarus (1998) supported the even split of the 10X factor based on the database which covered 60 compounds for kinetics and 49 effect measures. Silverman et al (1999) showed that the majority of the kinetic adjust factors from published pharmaceutical clinical trial data did not exceed a value of 3.2. Further, Suh et al (1999) demonstrated that most of the subfactors for kinetics and dynamics of therapeutic drugs were less than proposed default factors and all composite factors in human sensitivity were lower than 10.…”

Section: Introductionmentioning

confidence: 97%

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

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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.

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Establishing Data-Derived Adjustment Factors from Published Pharmaceutical Clinical Trial Data

Cited by 43 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

Human pharmaceuticals in US surface waters: A human health risk assessment

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

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