Study initiation date

The FDA has indicated that study initiation date (defined in 58.3(e)) and study completion date (defined in 58.3(p)) are administrative dates and should not be used to determine whether or not a study is of more than 4 weeks duration. Instead, terms-of-the-art (e.g., 14-day acute study, 28-day repeated dose study, etc.) will determine whether reserve samples are required under 58.105(d). 

Many of you have expressed an interest in a format for your master schedule. Figure 1 depicts the format Mobay Chemical Corp. uses. It is self explanatory and covers the items required in the GLP regulations (test substance test system nature of study study initiation date current status sponsor identity, if explicable and name of study director). For a contract laboratory, the sponsor s identity must appear on the master schedule sheet for each study listed. There are several terms that require definition. In... 

The study initiation date, which is the date that is entered on the master schedule, is defined as the date the protocol is signed by the study director. The study completion date will refer to the date that the final report is signed fcy the study director. 

Study initiation date" means the date the protocol is signed by the study director. 

Prepare an Operational Qualification Report. This should include date study initiated date completed observations made problems encountered completeness of information collected summary of deviation report results of control/alarm tests sample data if appropriate location of original data other information relevant to the study and conclusions on the validity of the equipment/system operations. 

Study plan amendment means an intended change to the study plan after the study initiation date. 

Study initiation date means the date the Study Director signs the study plan. 

Study Protocol signed (Study Initiation Date)... 

Only one study to date has been conducted on the treatment of acute pancreatitis with antioxidants. Clemens et al. (1991) were unable to show any difference in the incidence or severity of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in a prospective, randomized, double-blind, placebo-controlled trial of allopurinol. However, Salim (1991) performed a similar trial of the effect of allopurinol and DMSO in patients with pain from recurrent pancreatitis, and found significant benefit. On the basis that depletion of antioxidants is important in the pathogenesis of chronic pancreatitis, the administration of a cocktail of antioxidants was assessed for its effect on pain in this disease. Treatment with a combination of organic selenium, d-carotene, vitamins C and E, and methionine was of benefit in the initial pilot study, and in a placebo-controlled trial (San-dilands etal., 1990 Uden et al., 1990). 

An accurate and complete history of pesticide use for the test site, including material applied, rate and date of application (if possible), for 3 years prior to study initiation, and also during the study, should be documented. 

Most FPA studies to date on DNA have lacked sufficient time resolution to observe directly the relaxation of the internal correlation functions. Instead, the initial anisotropy r0 is taken as an adjustable parameter. Equations (4.30) show that such a procedure is completely valid for anisotropic diffusors (i.e., (A ft)2 = (dx(t)2)), provided the rapid internal motion of the transition dipole is isotropic. It has not yet been ascertained whether the internal motion actually is isotropic, so this must be assumed.(83) A recent claim(86) that large amplitudes of polar wobble are required to fit both the small amplitude of initial FPA relaxation 87 and the linear dichroism88 has been refuted. 83j... 

Pharmaceutical Comparison. At least 8 studies to date have examined the effectiveness of hypericum compared to the pharmaceutical antidepressants imipramine, amitriptyline, and maprotiline. Preliminary results indicate that hypericum is equivalent to standard antidepressants in effectiveness (Linde et al. 1996 Vorbach 1997). Similar to the pharmaceutical antidepressants, there is a 10-14 day lag for therapeutic effects of hypericum (Harrer et al. 1994). Indeed, the differences seen between hypericum and placebo groups becomes apparent between 2 and 4 weeks (Sommer and Harrer 1994). Hypericum has been reported to have a more favorable side-effect profile than several pharmaceutical antidepressants as well (Vorbach et al. 1994 Harrer et al. 1994). In double-blind studies, subjects have reported fewer and less-severe side effects. Although these initial results are promising, Linde and colleagues (1996) have concluded that the present evidence is inadequate to establish... 

FDA on or after June 20, 1979. For studies in progress on June 20, 1979, only those portions of the study done on or after June 20 were required to be done in compliance with the regulations. Of course, those studies initiated on or after the effective date were to be done in full compliance with the GLPs. 

In the only study to date of the mechanism of PFS initiation, Sims (40) could conclude only that polymerization of THF with PF5 as catalyst is a very complex system. He found that there appears to be a slow initiation reaction which does not reach completion until at least half of the polymerization is over. Sims also studied the effect of water on the polymerization, but could not fully explain the complex results. He... 

Although the novelty of observing chemically produced vibrational excitation provided an initial impetus, the main purpose of the studies to date has been to determine in detail the relative proportions of excited molecules in the various energy states, the fraction of the reaction energy that goes into internal excitation, which products are excited, and the fate of the excited molecules. Such data are used as aids in the construction of potential energy surfaces to be used, in turn, to describe the dynamics of the reactions. In short, the studies have been in the hands of kineticists. As interest in the subject has spread, more attention has been paid to applications laser action and the reactions of the excited molecules. 

In one of the most extensive studies to date, Tomita (5) found that phosphate buffer more effectively enhanced the yield of antioxidative activity produced from tryptophan and glucose than either veronal or borate buffer. The optimum concentration of phosphate buffer was 0.1 M and the optimum initial pH was 9. He also reported that an increase in antioxidative activity was directly associated with an increase in the molar ratio of sugar to amino acid and was... 

Is the master schedule adequate with contents (viz., test substance initiation date name of the sponsor study director name) ... 

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