Study types

In summary, solvents can influence Diels-Alder reactions through a multitude of different interactions, of which the contributions to fire overall rate uniquely depend on the particular solvent-diene-dienophile combination. Scientists usually feel uncomfortable about such a situation and try to extract generalities. When limited to the most extensively studied type A Diels-Alder reactions this approach seems feasible. These Diels-Alder reactions are dominated by hydrogen bonding interactions in combination with solvophobic interactions. This observation predicts a very special role of water as a solvent for type A Diels-Alder reactions, which is described in Section 1.4. 

Generalizations are not as easy for structured packings as for random packings. See the following subsection, Comparison to Trays, for study type structured packing data. 

This is the most extensively, as well as intensively, studied type of the decarbonylation. Nevertheless, kinetic data are scarce. Conversion of metal acyls to their respective alkyls has been investigated for two systems RCOMn(CO), 37, 50, 51) and XCH2COIr(PPh3)2Cl2 (X = Ph or a substituted Ph group) 160). 

Study type Required pre- or post-registration Use of radiolabel Identification of unknowns Need for mass balance Importance of low detection limits Importance of adjustable sampling frequency... 

OPP scientists are identifying the data elements (or fields) of interest for each study type where the reviewers felt that supplemental files would be useful, are identifying other information for each study type, which would be useful to have as electronic files, and are developing guidance for submission of supplemental files. This guidance is not ready to be published, but the scientists will work with the data submitters to ensure that the supplemental files for the particular study will be useful to the science reviewers. Even when guidance becomes available, OPP intends to be fiexible about the format of the supplemental files and will modify the guidance as needed. 

Because of this length dependence, IR and VCD of -turns may provide a means of discriminating and detecting them in a protein structure. Short Aib peptide results provide examples of type III /3-turn VCD (Yasui et al., 1986b), while cyclic peptides have been used to study type I and II turns, which are implied to have unique VCD band shapes (Wyssbrod and Diem, 1992 Xie et al., 1995). We have identified distinct turn modes... 

The bacterial bioluminescent reaction is also catalyzed by a luciferase (EC 1.14.14.3) isolated from marine bacteria. The four most studied types are Vibrio harveyi, Vibrio fischeri, Photobacterium phosphoreum and Photobacterium leiognathi18, 19. In these different luminescent bacteria the... 

Recently, a new polyketide biosynthetic pathway in bacteria that parallels the well studied plant PKSs has been discovered that can assemble small aromatic metabolites.8,9 These type III PKSs10 are members of the chalcone synthase (CHS) and stilbene synthase (STS) family of PKSs previously thought to be restricted to plants.11 The best studied type III PKS is CHS. Physiologically, CHS catalyzes the biosynthesis of 4,2, 4, 6 -tetrahydroxychalcone (chalcone). Moreover, in some organisms CHS works in concert with chalcone reductase (CHR) to produce 4,2 ,4 -trihydroxychalcone (deoxychalcone) (Fig. 12.1). Both natural products constitute plant secondary metabolites that are used as precursors for the biosynthesis of anthocyanin pigments, anti-microbial phytoalexins, and chemical inducers of Rhizobium nodulation genes.12... 

SP Indicator test species Study type Endpoint Toxicity... 

Prospective Study—Type of cohort study in which the pertinent observations are made on events occurring after the start of the study. A group is followed over time. 

Many of the studies done in safety assessment are multiple endpoint screens. Such study types as a 90-day toxicity study or immunotox or neurotox screens are designed to measure multiple endpoints with the desire of increasing both sensitivity and reliability (by correspondence-correlation checks between multiple data sets). 

TABLE 8.2. Comparison of ICH Stages and Study Types with Similar Regulatory Protocols... 

Study Type. Metabolic and pharmacokinetic data from a rodent species and a nonrodent species (usually the dog) used for repeat dose safety assessments (14 days, 28 days, 90 days or six months) are recommended. If a dose dependency is observed in metabolic and pharmacokinetic or toxicity studies with one species, the same range of doses should be used in metabolic and pharmacokinetic studies with other species. If human metabolism and pharmacokinetic data also are available, this information should be used to help select test species for the full range of toxicity tests, and may help to justify using data from a particular species as a human surrogate in safety assessment and risk assessment. 

Study title Key study findings Study type Species/strain... 

FIGURE 1.9 Selection of cinchonan carbamate CSPs that have been prepared in the course of selector optimization studies (type I prototype type II, O-9-linked thiol-silica supported prototype type III, C-ll-linked thiol-silica supported CSPs type IV, dimeric selectors). (Adapted from M. Lammerhofer and W. Lindner, J. Chromatogr. A, 741 33 (1996) W. Lindner et al., PCT/EP97/02888, US 6,313,247 B1 (1997) P. Franco et ah, J. Chromatogr. A, 869 111 (2000) C. Czerwenka et ah. Anal. Chem., 74 5658 (2002).)... 

Drug Type Genotype Study type Result Outcome measure Comment... 

Cohort Study—type of epidemiological study of a specific group or groups of people who have had a common insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are followed forward from exposure to outcome. At least one exposed group is compared to one unexposed group. 

Study type Species No. of animals Cost ( thousands) Test material (Factor Q ) Report (weeks)... 

Since the S5(R2) document is relatively short (24 pages in PDF version available for download at http //www.ich.org) readers, especially those who are directly impacted by this guideline, are encouraged to take the time to thoroughly read the document. The present chapter outlines the essential points and highlights methods that are often utilized. Readers interested in the practical implementation of S5(R2) and adequate study designs are referred to a series of papers on each study type published in Birth Defects Research (Part B) volume 86, number 6, 2009, and other reviews (2). 

In this study type the test substance is administered in graduated doses to several groups of males and females. Males should be dosed for a minimum of4 weeks females should be dosed throughout the study (approximately 54 days). Normally, matings one male to one female should be used in this study. 

---