Tolerability data

Figure 2.11 Employment of the tolerance data In the generation of a process capability maps...

Methods for handling the safety and tolerability data the safety data will usually be coded using the MedDRA (Medical Dictionary for Regulatory Activities, www.meddramsso.com) coding system in order to aid summary and presentation... 

Membership organization sponsored by the Office of Pesticide Programs of the U.S. Environmental Protection Agency that maintains the National Pesticide Information Retrieval Service (NPIRS), which provides current information on products registered with the EPA and tolerance data for pesticides and hazardous chemicals. It also provides state registration information, registration guideline information, and descriptions of studies on pesticides and hazardous chemicals. 

After acceptable safety and pharmacokinetic data are observed in phase I trials, phase II studies are initiated with the goal of establishing efficacy, determining the effective dose range, and obtaining safety and tolerability data. In phase II, the dose and dosing interval to be employed in the patient population and the estimated noeffect dose are defined. Phase II studies may require 1-1.5 years to complete and may involve several hundred patients. 

The remaining chapters of the book introduce some of the advanced topics of chemometrics. The coverage is fairly comprehensive, in that these chapters cover some of the most important advanced topics. Chapter 6 presents the concept of robust multivariate methods. Robust methods are insensitive to the presence of outliers. Most of the methods described in Chapter 6 can tolerate data sets contaminated with up to 50% outliers without detrimental effects. Descriptions of algorithms and examples are provided for robust estimators of the multivariate normal distribution, robust PC A, and robust multivariate calibration, including robust PLS. As such, Chapter 6 provides an excellent follow-up to Chapters 3, 4, and 5. 

The information originating from preceding studies is needed for the proper design of a food interaction study safety and tolerance data has to be considered as well as the PK results including a food screen. The terminal half-life of the drug or its active metabolite(s) will provide the basis for the washout periods. Single dose linearity/proportionality will help to define the dose. Safety and tolerance data will justify the dose. The PK comparison in a food screen (FIM study, see below) will influence the sample size. 

Szegedi A, Anghelescu I, Wiesner J, Schlegel S, Weigmann H, Harder S, Hiemke C, Wetzel H. Addition of low-dose fluvoxamine to low-dose clozapine monotherapy in schizophrenia drug monitoring and tolerability data from a prospective clinical trial. Pharmacopsychiatry 1999 32(4) 148-53. 

The separate listing of tolerance tests in the target species in EEC guidelines does not necessarily mean that separate studies have to be performed. Local and general tolerance data to establish the tolerated dose range with an acceptable safety margin can be obtained from other pharmacological, safety and clinical studies. This should be kept in mind when those trial protocols are drafted. 

At doses of 20 mg/m liposomal doxorubicin, combined tolerability data from 705 patients with AIDS-related Kaposi s sarcoma showed that neutropenia (below 1 X 10 /1) and anemia were the most common adverse events, affecting 50 and 19% of patients respectively (14). 

Kopcke W, Sauerland MC. Meta-analysis of efficacy and tolerability data on iron proteinsuccinylate in patients with iron deficiency anemia of different severity. Arzneimittelforschung 1995 45(11) 1211-16. 

In this way, a predictive model is developed for pharmacokinetic parameters of individuals within the population. Compared with the traditional approach, there is some important additional information that can be obtained from this technique. Firstly, the factors contributing to pharmacokinetic variability in the target population can be identified and quantitated. Secondly, the eflFects of many variables can be screened, in fact as many variables as are collected on the case report form. This may enable identification of important drug interactions, or of other patient factors affecting pharmacokinetics that may not have been suspected. Thirdly, as efficacy and tolerability data have been collected in the same patients, this analysis might help to establish a range for therapeutic concentrations. 

Cholinesterase inhibitors should be used throughout the course of illness because of the cognitive benefits, possible treatment of behavioral symptoms, and economic factors. Additionally, vitamin E should be used adjunctively with the chohnesterase inhibitors throughout treatment. Vitamin E is recommended solely based on the results of one smdy that showed no cognitive benefit, but a delayed requirement for nursing home placement with vitamin E. Figure 63-3 shows pharmacotherapeutic treatment algorithms for AD. These recommendations are made based on available efficacy, safety, and tolerability data. 

Numbers in parentheses denote the concentration of element in leaf tissue (/ig/g dry weight or ppm) that shows toxicity in plants that are neither highly senstive or tolerant (data from Kabata Pendias and Pendias, 1984). Source Adapted from J. E. Huheey. 1972. Inorganic Chemistry. New York Harper Row. 

TOLERANCES TOLl, T0L2, XMIN, XSTART, BARMIN and SLACKS are set to values on TOLERANCES data card. 

ALMAN, D. H., BERNS, R. s., SNYDER, G.D. and LARSEN, w. A. (1989) Performance testing of color-difference metrics using a color tolerance data set. Color Research and Application, 14, 139-151. 

To calculate the leaching requirement one needs an estimate of the allowable EC of die saturation extract, such as can he obtained from existing salt tolerance data... 

Explain how the salt tolerance data of Table 11.2 might be related to real-world salinity distributions, such as shown in Figs. 11.2,11.3, and 11.5. 

Tolerability data. Any data collected with an eye on potential side-effects, and in order to profile the safety of a treatment, rather than to measure anticipated benefits of the drug. Measures which the trialist hopes will be irrelevant but fears may not be. They are context dependent, so that blood pressures are not tolerability data in a trial of hypertension (they are efficacy data) but might be in a trial in asthma. 

FDA considers Treatment IND proposals on the basis of a preponderance of evidence of effectiveness, such as may be available at the time of submission, but which has, obviously, not been definitively decided in an NDA review. There will be close attention paid to all tolerability data that can be marshaled in favour of the Treatment IND, but taken in context of the serious nature of the... 

Anghelescu I, Szegedi A, Schlegel S, WeigmannH, Hiemke C, Wetzel H. Ctreatment with clozapine and paroxetine in schizophrenia safety and tolerability data from a prospective open clinical hial. EurNeuropsychopharmacol 1998) 8,315-320. 

Sz edi A, Wetzel H, Leal M, Hmtter S, Hiemke C. Combination treatment with clomipramine and fluvoxamine drug monitcring, safety, and tolerability data. J Clin P duatry 1996) 57,257-64. 

Tolerance analysis extracting tolerance data from the design. 

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