MASTER trial

The sponsor and investigator, as appropriate, must retain all essential documents relating to the trial for at least 5 years after its completion. Documents should be securely archived, with restricted access to maintain subject confidentiality. Collectively, these constitute the Trial Master File, and facilitate any audit and evaluation of... 

Figure 5.5 Essential documentation for a Trial Master File.

One of the copies should be designated as master. No item should be added to this before being finalized. On the other copies, adding the desired features will be a matter of trial and error on paper, with many copies ending up in the waste paper basket. 

This method is also being used at the Hines VA CSPCC for a number of trials. It appears to be superior to the paper data collection with centralized interactive data entry. It is not time consuming because data are entered with high-speed double-key data entry, which expedites processing of received forms and thus the accumulation of the master database. Another major advantage is that only one person is needed to run the system. 

Ramelteon (Rozerem). Recently approved by the FDA for treatment of insomnia in the US, ramelteon acts via a completely novel mechanism of action, that is, stimulating so-called melatonin Ti and T2 receptors in the brain s suprachiasmatic nucleus (SCN). The SCN is regarded as the body s master clock that regulates the sleep-wake cycle and other circadian rhythms. The effects of ramelteon in some respects mimic those of melatonin. Ramelteon, in clinical trials, administered at bedtime doses of 8 mg, outperformed placebo with respect to several indices of sleep disturbance (see Table 9.4). 

The steps and sequence of events required to carry out a process validation assignment are outlined in Table 8. The objective of prospective validation is to prove or demonstrate that the process will work in accordance with a validation master plan or protocol prepared for pilot-product (100 x size) trials. 

When a protocol is issued, the study is put on the Master Schedule. The Master Schedule is a computer-generated document that can be formatted and sorted to accommodate the needs of various participants in the study as well as the Quality Assurance Section. It contains the protocol number, the trial numbers, the study title, the proposed start and finish dates of field and analytical segments of the study, the proposed reporting date, the names of field participants, the name of the study director, and other information that may be useful to the users of the master schedule. As a study... 

Records are kept of when a sample was collected, the method of collection, who collected the sample, what the elapsed time was between harvest and freezing, the conditions under which it was stored, how it was shipped to the laboratory, and when it was shipped. When a sample arrives at the laboratory, the condition of the sample is checked and recorded. Then the information on the sample bag (sample number, application rate, preharvest interval, etc.) is compared to the trial information sheets which are submitted along with the samples. Any omissions or discrepancies are corrected at that time. If there is an omission or discrepancy that cannot be easily corrected by a telephone call from the sample processing laboratory to the field scientist, the study director is notified. The study director must make the decision about the validity of the sample and put a note in the data file explaining how the problem was corrected or that the problem could not be corrected and the trial is to be abandoned. If the trial is dropped, Quality Assurance is notified, the trial is deleted from the active Master Schedule, and an explanation is put in the study file. 

The major concern with document linking to validation is with master batch records and SOPs. The defined ranges for the operating parameters (as established in development) as defined in the master batch record are confirmed to be satisfactory during the validation effort. There is no requirement, nor should there be, to establish on a commercial scale that success is possible at the extremes of these ranges. That type of confirmation is ordinarily restricted to developmental trials, in which the financial impact is less significant. The only common exception to this practice is in the validation of sterilization processes, in which the performance qualification efforts will oftentimes use worst-case conditions at or below the routine sterilization parameters. 

The standard or color master is the single most important factor involved in any match because is serves as the reference to which all match trials are visually compared. It is absolutely necessary to ensure that the submitted standard or color master is the true standard the customer wants matched. Very often a part piece will be submitted for matching that is not the approved, true standard. Although the submitted piece may be within the color sphere relative to the approved, true standard, the color may lie to one side or the other, making a close match to the approved, true standard impossible. Always attempt to obtain an approved, true standard to use as the reference for future trial matches. 

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