Study Performance and Reporting

One important aspect of the study plan has already been discussed in section 2.8 (see page 88), namely the fact that even the best conceived plan may be in need of alterations as dictated by study events, and that therefore mechanisms have to be defined by which such changes can be introduced. While the definitions of the terms amendment and deviation have been treated in the above mentioned section, it remains at this point to draw the attention to a small but nevertheless important difference between the ways the study plan and any amendments to it are to be treated with regard to their approval. While the study plan has to be approved not only by the Study Director, but, as described above, ( if required by national regulation or legislation ) also by the test facility management and/or the sponsor, an amendment has only to be approved by the Study Director, since the GLP Principles require only that they should be justified and approved by dated signature of the Study Director and maintained with the study plan . 

In this regard, a small problem, which may lie more on the psychological side, could be posed by the reluctance of sponsors to have to acknowledge large numbers of amendments. The sponsors may prefer, or actually request from the Study Director, that amendments would be bundled, so that e.g. the Amendment No. 1 would be the only one, and would document all the single deviations, precisions or additional informations, and changes that have 

This question of how to handle deviations and amendments with regard to the information of the sponsor is, however, different from the way these deviations and amendments have to be handled within the study itself. Since an amendment is a planned and permanent change in the study plan, it needs to be maintained with the study plan which means that it has to be distributed in the same way as the study plan itself to be immediately accessible to study personnel. This has been stated briefly already at the end of section 2.8 (see page 92), and the issue will be discussed in more detail also at the end of the present section. 

The format of the study plan is laid out in a more or less definitive manner by the GLP Principles, while its contents cannot be conclusively described, since they will depend on the nature of the study to be reported. Therefore, the GLP Principles state that the study plan should contain, but not be limited to the following information , whereupon the main points to be addressed in the study plan are listed. Generally speaking, two parts may be distinguished The study plan should deal in its first part with the more administrative information, while in its second, and main, part the chronology and the scientific conduct of the study have to be described. 

The first, administrative part of the study plan can be considered as a simple listing of information necessary to identify the study and the various individuals and entities connected with its conduct. Every study needs a descriptive title, so that it may easily be recognised and identified in a list of studies conducted at a test facility. This requirement will be evident to anybody who has tried to search for a specific document in a list of computer files all of which are bearing similar and not very illuminating names like memo-xx or document-yy . Such a search can become a very tedious task, and thus the necessity of having a descriptive title, further on accompanied by a state- 

---

Sasich, L., Lurie, P, and Wolfe, S.M., The drug industry s performance in finishing postmarketing research (phase IV) studies, letter and report from Public Citizen, Health Research Group Publication 1520, Washington, DC, April 13,2000. 

What is the quality of the smdies, e.g., study design, performance, and reporting What are the data gaps ... 

It is very important to assess the qualifications and availability of the subinvestigators conducting the study with the principal investigator, who is a field expert, as the subinvestigators will be responsible for performing the majority of study procedures and reporting serious adverse events. 

More recently, comprehensive studies of typical areas of exposure of samples from synthesis, through manufacturing, packaging and in-use have been performed and reported by McGreer (39), Reed et al. (40) and Baertschi et al. (41). The results of these studies show the variety of sources samples are exposed to during their lifetime. A source that is broadband and continuous from about 300 to 700 nm will cover the spectrum of all natural light except for the infrared, and meet the guidelines objectives. 

Khan et al. (2005) performed and reported tyrosinase inhibition studies of a combinatorial library of 2,5-disubstituted-l,3.4-oxadiazoles (25-43) [47]. The library of oxadiazoles was synthesized under microwave irradiation [47]. The synthetic steps involved for these compounds are shown in Scheme 2. Among the compounds from the library, 29 (30-[5-(40-bromophenyl)-1,3,4-oxadiazol-2-yl]pyridine, for structure see Fig. 6) exhibited the most potent (ICso = 2.18 xM) inhibition against tyrosinase, which has found to be more potent than the standard potent inhibitor L-mimosine (IC50 = 3.68 [xM, for structure see Fig. 1) [47]. 

Shaheen et al. (2005) reported lycoctonine-type norditerpenoid alkaloids isolated from the aerial parts of Aconitum laeve Royle, swatinine, delphatine, lappaconitine, puberanine, and N-acetylsepaconitine [48]. They performed and reported the anti-inflammatory, antioxidant, and tyrosinase inhibition studies of all these compounds, in which lappaconitine (IC50 = 93.33 p,M) and puberanine (IC50 = 205.21 xM) were found to be active against the enzyme tyrosinase [48]. 

Heat-transfer aspects and performance were studied and reported on by Depew and Farbar (ASME Pap. 62-HT-14, September 1962). Heat-transfer coefficient characteristics are similar to those shown in Sec. 11 for the indirectly heated fluid bed. Another frequent application on plastics is a sm, rather incidental but necessary amount of drying required for plastic pellets and powders on receipt when shipped in bulk to the users. Pneumatic conveyors modifiea for heat transfer can handle this readily. 

All testing to support notification must be performed by methods specified in Annex V to Directive 79/831/EEC and in accordance with the principles of good laboratory practice (GLP). GLP is concerned with the organizational processes and conditions under which laboratory studies are planned, performed, monitored, recorded and reported. 

The aforementioned reviews and assessments were assimilated to characterize the effect of dielectric, rotational, and mechanical hazards on motor performance and operational readiness. Functional indicators were identified that can be monitored to assess motor component deterioration caused by aging or other accidental stressors. The study also includes a preliminary discussion of current standards and guides, maintenance programs, and research activities pertaining to nuclear power plant safety-related electric motors. Included are motor manufacturer recommendations, responses from repair facilities to a questionnaire, in-service inspection data, expert knowledge, USNRC-IE audit reports, and standards and guides published by the Institute of Electrical and Electronics Engineers (IEEE). 

The study performed by Burns and Roe (BSR) shows that valve failures constitute the component category most responsible for the shutdown of PWR and BWR plants. This Investigation, contracted with SNL for DOE, identified the principal types and causes of valve failures that led to plant trips for the period from 12/72 to 12/78. The primary sources of data for the report were searches of the data base, the monthly Gray Books, Nuclear Power Experience publications, as well as discussions with utilities, valve manufacturers, and suppliers. 

Monobromobenzene 1, 1,2-dibromobenzene 2, 1,3 dibromobenzene 2, 1,4-dibromobenzene 4, hexabromobenzene 5 and tetrabromobisphenol A 6 are used as plasticizers, flame retardants or intermediates for various syntheses. Except for 1, a limited number of studies regarding the toxicity and metabolism of above compounds has been performed. This report presents some studies on the hepatotoxic action (necrotic and porphyrogenic effects) of these compounds. 

---