Trial duration

Fig. 7.10 (Continued) (b) VN-x inhibits response to female urine by male guinea-pig X-2 sequential trials (duration, sec. x s.e.) (from Beauchamp et al., 1982). (c) Inter-strain (domestic vs. wild) discrimination by male domestic guinea pig of female urines [sequential testing sec/4 min, s.e., Ss above each bar intact/sham-VN-x. above]. WF= wild female, F = domestic female (from Beauchamp et al., 1982). (d) Effects of VN-x on maternal chemoinvestigation ewe responses to lambs, including tongue-manipulation of palate [c.f. Fig. 7.6(d)], procaine = MOE inhibition, a sign, versus control (from Booth and Katz, 2000).

In recent years, several pilot clinical trials, assessing the elfects of GH administration to ageing adults, have been carried out. Typically, trial duration is 4-6 months. A 7% increase in lean body mass and skin thickness, along with a 14% drop in body fat, was observed in one trial, although results recorded in other trials were less striking. More detailed clinical trials and cost benefit analysis must be carried out in order to fully assess the potential of GH to counteract some of the elfects of ageing in the elderly population. 

Q1A(R2) Stability Testing of New Drug Substances and Products Stability testing protocols including temperature, humidity, and trial duration... 

There are several MWT variants with respect to trial duration. This variation stems from the fact that the MWT can be adapted to a variety of situations depending on the degree of sleepiness and motivational characteristics of the population to be studied. As examples, with extremely somnolent subjects such as patients with narcolepsy, a shorter trial duration, say 20 min, can be used with minimal ceiling effects. In individuals who are only moderately sleepy (say, MSLT sleep latencies in the 6-10 min range), as opposed to extremely sleepy (say, MSLT sleep latencies in the 0-5 min range), MWT trial durations of 30 min or 40 min are needed to reduce problems with ceiling effects (15-17). 

It is recognized that various MWT trial durations and rules for termination of trials have been used depending on the setting. Choices among these variations allow the MWT to be adapted to a variety of settings and needs. For example, if there are concerns about sleep accumulation during trials or about sleep inertia after... 

MWT trial duration will be 20 min. The rationales for this decision are that the 20-minute trial MWT has been used in both clinical and research settings and has been validated against longer MWT trials. Moreover, pilot data showed that an MWT with 20-minute trials statistically distinguishes subjects on active CPAP from subjects on sham CPAP. 

Summary statistics for normative MWT data. For 64 healthy volunteers, the average sleep latencies for four 40-min trials are presented as well as the average across the four-trial MWT. Results for 30-min and 20-min trial durations have been estimated by truncation. (See text and Ref. 11 for details.)... 

If, for example, reproductive toxicity studies are required for vaccines, the trial duration and details of clinical and pathological investigations of standard trial procedures may be adopted, whereas the dosing must be chosen individually for each product to be tested and should be justified in the study protocol. Most likely it will be similar to the clinical use of the vaccine. 

EWOC requires only the information currently available at the time of inclusion, whereas in the standard scheme the inclusion of a new patient can only be done after evaluation of all the patients from the previous cohort. This results in shortening the trial duration. 

Following discussion and acceptance of the SA results, including both model-based and trial-based input factor adjustments, the efficacy trial simulations may proceed as planned. For each possible trial design, the appropriate input factors and output responses are simulated and results are compared to determine the most appropriate design. As discussed previously, this final decision likely will not only be based on a specific p-value or trial power, but will also include valuations based on trial duration, monetary cost, or information gained or lost toward continuing development goals (e.g., an overall measure of clinical utility). 

Tlydroxyzine and kava kava are two alternatives. Patients with GAD demonstrated contmned efficacy for 3 months with hydroxyzine or bromazepam (not marketed in the United States), but not with placebo. Efficacy was maintained in 86% of the hydroxyzine group and 88% of the bromazepam group. A meta-analysis of randomized trials comparing the herbal preparation kava kava found it was more effective than placebo for anxiety during trial durations of 1 to 24 weeks. Many patients experienced CNS effects (e.g., tremors, drowsiness, restlessness, and headaches) and abdominal discomfort during short-term treatment. Because of recent reports of hepato-toxicity, kava kava is not recommended as an anxiolytic. ... 

One hundred twenty-five events would provide 90% power, and 95 events would provide 80% power to illustrate the 95% Cl is < 1.8 based on a Cox proportional hazard model. Therefore, in a clinical trial with an expected event rate of 1 event per 100 patient-years and a 5% annual dropout rate, 90% power would be achieved by enrolling 200 patients per month for 24 months and following all enrolled patients for an additional 24 months. The total trial duration would be 48 months. If, however, the true event rate was actually 0.75%, the power would decrease to 80%—a doubling of the type 2 error. Furthermore, if the event rate were actually 0.5%, then the power would drop to 65%, a type 2 error 3.5 times as high. Because it is hard to predict CV event rates in noncardiac populations, such overestimates are not uncommon. Similarly, if the actual event rate... 

All tested magnesia-chromite bricks show macroscopically either no or minimal wear after both rotary kiln tests. The possible explanation for the latter is the trial duration of 20 cycles which is standard testing method at the TC Leoben due to tightened testing methods. Nevertheless the following observations can be summarized comparing both tests ... 

Table 13.2 Impact of sample size and cardiovascular event rate on trial durations at 90 and 80 %...

Esteban A, Alia I, Tobin MJ, et al. Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med 1999 159(2) 512-518. 

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