Registration reference study

In the actual practice of exposure assessment for registration purposes, one would like to start with a representative well-designed field study with the compound under consideration for the requested use scenario. When such a study is not available, one might look for a reference study carried out with another compound for the relevant use scenario. Such a reference study may be more appropriate than predictive models, considering that a model contains all types of studies, which by themselves may be less comparable with the considered use scenario. The reference study must also be well designed and of appreciable size to be appropriate. Such a reference study will preferably be a biological monitoring study (EUROPOEM, 1996). 

May be tested as part of registration stability studies only also refer to Section 16.9. 

The MDL and practical quantitation limit (PQL) should be appropriate for the objectives of the analysis. MDL refers to the minimum concentration of the compound of interest that can be measured and reported with a specified confidence (99% probability) that the concentration is above zero. The registrants must provide or develop an analytical method for water for the parent pesticide and its degradates that has an MDL of 0.01% of the label application rate (calculated as the average concentration in the top six inches of soil), or 0.05 pgL , whichever is lower. PQL refers to the lowest concentration at which the laboratory can confidently quantify the concentration of the compound of interest. The study authors must report all samples with concentrations above the MDL as detections, including those below the PQL in which the concentration cannot be quantified. In addition, the study authors must provide sample equations to demonstrate how the PQL was calculated. 

One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.5 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. 

A registration application is initially examined for completeness and compliance with the formal requirements, before the technical and scientific examination by specialized groups commences. The first official response from an authority may be a notification of the deficiencies of the dossier. Partly the objections may address only formal faults, other problems may be clarified by reference to the existing data, in other cases additional studies may have to be conducted to provide the required information. 

Recommendations for Improvements in the Design of Guideline Studies 36 Population Selection 36 Sampling Location 36 Sampling Season 36 Duration of Measurements 37 Post-Registration Studies 37 CONCLUSIONS AND RECOMMENDATIONS 37 ACKNOWLEDGEMENTS 38 REFERENCES 38... 

Official reference may not be available until registration studies... 

The manufacturer must carry out on-going real-time stability studies to substantiate the expiry date and the storage conditions previously projected. The data needed to confirm a tentative shelf-life must be submitted to the registration body. Other results of ongoing stability studies are verified in the course of GMP inspections. To ensure the quality and safety of products with particular reference to degradation, national health authorities should monitor the stability and quality of preparations on the market by means of a follow-up inspection and testing programme. 

In Austria, the incidence of different subtypes of hyperthyroidism was registered before (retrospective) and after (both retrospective and prospective) the iodization of table salt was increased in the mid-1990s (Mostbeck et aL, 1998). In Austria, thyroid examinations were mostly carried out in nuclear medicine centers, and the registration was based on all patients with newly diagnosed hyperthyroidism referred to one of 19 nuclear medicine departments in the study area. No linkage to other hospital records or contact with GPs was made, to ensure that all patients were referred to hospital and thereby registered in the study. 

So, if there is a place for sequential analysis of drug-development trials, monitoring and so forth, it is either for safety and/or lack of efficacy reasons, or for economic reasons. The latter can be important for some indications. There may be cases where the sponsor realizes that the number of patients needed to prove efficacy may, for a fixed trial, exceed those which need to be studied for registration. Under such circumstance, the possibility of early stopping, either for proven efficacy or lack of efficacy (what was referred to in section 19.1 as futility), may be attractive. The expected run length will be less than the fixed sample size required, the costs of the trial may be less, and the time to registration if the trial is successful will probably be reduced. 

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