Proportionality assessment

Fig. 13.3 D ose proportionality assessment. The solid line is the predicted exposure based on a linear mixed effects power model having a reference subject. For the tasidotin plots, the predicted line is for a reference patient having a BSA of 1.83 m2.

Teo SK, Scheffler MR, Kook KA, Tracewell WG, Colburn WA, Stirling DI, Thomas SD. Thalidomide dose proportionality assessment following single doses to healthy subjects. J CUn Pharmacol 2001 41(6) 662-7. 

Oxford English Dictionary. However, see Boivin and Sandoz 2006, p. 21 (where it is acknowledged the term definite is similar to the concrete and direct wording used in relation to military advantage in the proportionality assessment, but still suggests the latter wording appears to introduce an additional element of specificity ). 

In the first approach, a vapor cloud s potential explosive power is proportionally related to the total quantity of fuel present in the cloud, whether or not it is within flammable limits. This approach is the basis of conventional TNT-equivalency methods, in which the explosive power of a vapor cloud is expressed as an energetically equivalent charge of TNT located in the cloud s center. The value of the proportionality factor, that is, TNT equivalency, is deduced from damage patterns observed in a large number of vapor cloud explosion incidents. Consequently, vapor cloud explosion-blast hazard assessment on the basis of TNT equivalency may have limited utility. 

Candidates must be in excellent health and have no conditions that would restrict their ability to safely do fire suppression and rescue work. Weight (body fat content) must be proportionate to height for men and women. Uncorrected distance visual acuity of at least 20/100 in the poorer eye and 20/40 in the better eye, correctable to at least 20/40 in one eye and 20/20 in the other eye, is required. Regarding refractive surgery, most persons who have had these procedures will be passed. However, some may be deferred for several months or disqualified based on an individualized assessment of the surgical outcome. Color vision Candidates must be able to accurately and quickly name colors and must be free of other visual impairments that would restrict the ability to perform firefighter duties. 

Yao, M., Swaminathan, A., and Srinivas, N. (2007). Assessment of dose proportionality of muraglitazar after repeated oral dosing in rats via a sparse sampling methodology. Biopharm. Drug Dispos. 28 35-42. 

In recent years it has become increasingly apparent that for chemical contaminants that are abundant in the environment a more sophisticated approach to dose-response characterisation is required. There is increasing evidence that small but significant sub-populations are exposed to intakes that exceed PTWIs and most people are exposed to potential carcinogens through their diet. In such cases the PTWI concept is redundant because it is necessary to assess the actual levels of risk to which individuals are exposed in order to introduce proportionate control measures. Simply knowing that the hazard exists is not sufficient. 

The use of quarks in atomic shell theory provides an alternative basis to the traditional one. The transformations between these bases can be complicated, but there are many special cases where our quarks can account for unusual selection rules and proportionalities between sets of matrix elements that, when calculated by traditional methods, go beyond what would be predicted from the Wigner-Eckart theorem [4,5], This is particularly true of the atomic f shell. An additional advantage is that fewer phase choices have to be made if the quarks are coupled by the standard methods of angular-momentum theory, for which the phase convention is well established. This is a strong point in favor of quark models when icosahedral systems are considered. A number of different sets of icosahedral Clebsch-Gordan (CG) coefficients have been introduced [6,7], and the implications of the different phases have to be assessed when the CG coefficients are put to use. 

Dose proportionality was assessed using the power model. AUC0 24 and Cmax did not change over day of administration, but did increase with increasing dose (p <0.0001 see Fig. 13.3). For AUC0 24, the 90% Cl for the slope related to dose was 0.96, 1.18 with a point estimate of 1.07. The 90% Cl for the slope related to Cmax was 1-02, with a 90% Cl of 0.92, 1.13. Hence, the 90% Cl for both AUC0 24 and Cmax contained the value 1.0 and both parameters were dose-proportional. The between-subject variability for AUC0 24 and Cmax was 32% and 40%, respectively. 

J. McKellar. 1995. Assessment of dose proportionality Report from the Statisticians in the Pharmaceutical Industry/Pharma-cokinetics UK Joint Working Party. Drug Information J. 29 1039-1048. 

The normal method of calculation for company funds is to use the capital asset pricing model (CAPM). This was developed by share analysts keen to have a defence against accusations of negligence in selecting shares for clients as a means of assessing the real value of any share, in the form of risk and desirability. It essentially demonstrates one version of the direct proportionality between risk and return. 

The first tolerability studies in early clinical development always provide pharmacokinetic (PK) data over a considerable dose range. Especially the explorative first-in-man study with escalating single doses, or an explorative proof of principle study with escalating multiple doses provides a valuable basis for an exploratory assessment of dose linearity/ proportionality of drugs in humans. In addition such an assessment can directly help within the same study to optimize the dose selection and dose progression. Already in this early phase of the development, these data are going to support exposure-response relationships, and thus a potential submission (US FDA 2003, ICH E4 1994). 

DoseLinearity/Proportionality typically is assessed, based on exposure-related PK-parameters measured... 

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