Active control arm

Phase II investigates the compound s efficacy and safety in controlled clinical trials for a specific therapeutic indication. To eliminate as many competing factors as possible, Phase II trials are narrowly controlled. They are characterized as small—several hundred subjects with the indicated disease or symptoms—and are closely monitored. The control may be either a placebo study arm or an active control arm. The endpoint measured may be the clinical outcome of interest or a surrogate. Phase II trials may last for several months or even several years. Early pilot trials to evaluate safety and efficacy are called Phase Ila. Later trials, called Phase lib, are important tests of the compound s efficacy. These trials may constitute the pivotal trials used to establish the drug s safety and efficacy. At least one pivotal trial (most frequently a large, randomized Phase III study) is done. Only about one third of compounds entered into Phase II will begin Phase III studies [61],... 

In the third randomized trial of an MMPI (British Biotech Study 145) (12), patients with locally advanced or metastatic gastric cancer were randomized in a double-blind fashion to a low dose (10 mg bid) of marimastat or matching placebo. Marimastat 10 mg po bid, which had inferior survival compared to the higher dose of marimastat, was presumably selected as the active control arm for this trial based on its superior tolerability compared to high-dose marimastat. Patients randomized to marimastat had a trend to better overall survival (167 d vs 135 d p = 0.07) at the protocol stipulated endpoint of the study, and this statistical trend strengthened with an additional 6 mo of follow up (p = 0.048). Nevertheless, patients randomized to marimastat 10 mg po bid had statistically superior progression-free survival compared to patients randomized to placebo (p = 0.027). Marimastat 25 mg po bid, which was the most efficacious dose in British Biotech Study 128, was not tested in Study 145. 

The one study done to date with venlafaxine used a double-blind continuation design rather than a crossover design used with the SSRIs ( Table 7-21). Responders in the double-blind, placebo- and active-controlled acute efficacy phase could elect to remain on double-blind treatment for a 1-year follow-up phase ( 271). The treatment arms in these studies included venlafaxine, trazodone, imipramine, and placebo. At the end of 1 year, 18% of patients on venlafaxine had relapsed versus 32% on placebo. The difference between the venlafaxine and the placebo groups was smaller than that seen between the SSRIs and their respective placebo groups (Table 7-20), consistent with the difference in the design of these studies. 

These findings prompted the development and evaluation of the currently available form of inhaled tobramycin, which is sterile and free of preservatives. The benefit of maintenance therapy with this inhaled tobramycin is supported by the results from two 24-week, multicenter, randomized, double blind, placebo-controlled clinical trials [6]. In these studies, patients with cystic fibrosis were at least six years of age, with an FEVj between 25% and 75% predicted. All subjects had evidence of colonization with Pseudomonas aeruginosa. Exclusion criteria included an elevated serum creatinine or colonization with Burkholderia cepacia, which is typically resistant to tobramycin. Subjects in the active treatment arm received inhaled tobramycin 300 mg twice daily through... 

These new mode-rich systems increase the need for and difficulty of maintaining mode awareness, which can be defined in STAMP terms as keeping the controlled-system operating mode in the controller s process model consistent with the actual controlled system mode. A large number of modes challenges human ability to maintain awareness of active modes, armed modes, interactions between environmental status and mode behavior, and interactions across modes. It also increases the difficulty of error or failure detection and recovery. 

This study is focused on analysis of a 20-story active controlled structure described in numerical example. Active devices are located at the floors, where their positive effect is maximal. In cases, when the maximum control force value, required at a certain floor, is higher than the peak force that may be produced in a single device, lever arms are used for connection of active dampers. It allows reduction of dampers and increases the efficiency of control. 

Other effective mechanical amplifying systems are also used for connecting semi-active and active dampers in order to reduce the control forces and the energy required for activation of control devices (Gluck, 2000, Ribakov, 2000). In this study efficiency of lever arm amplifiers for connection of active controlled devices is studied. First optimal locations of control devices are obtained. The amplifiers are used for further decreasing the number of control devices at each floor. 

If a viscous device is connected to a lever arm, the lever arm deflection decreases the amplification effect. For active controlled actuators the control force usually does not depend on velocity, but the lever arm deflection increases the energy, required for activation of actuators. Following Ribakov (2003), when the desired amplification is determined from other considerations, the... 

It was assumed that in the frame of this study the number of active floors, m is equal to 8. This number ofactive floors allows an economical solution yielding according to the selected efficiency criteria about 70 - 85% of the effect that may be achieved by an optimal set of active controlled devices located at all floors (see Figure 4). Following Table 1, the optimal solution requires 21 devices connected to Chevron braces or 9 devices connected to lever arms. 

Roof acceleration time histories are shown in Figure 6. As it follows from this figure, using an optimal set of active controlled devices yields a significant reduction in peak roof accelerations of the stmcture under all ground motions that were used in the study. Like in the case of peak displacements, also roof accelerations for cases 3 and 4 were equivalent. It proves that using lever arms as amplifiers for connection of active controlled devices (Case 4) yields the same reduction in stmctural response like an optimal limited set... 

It was demonstrated that using an optimal limited set of active controlled devices yields almost the same reduction in structural displacements and accelerations like an optimal set of devices located at all floors. It was further shown that connecting the control devices to lever arms allows getting the same improvement in structural behavior like by connecting them to Chevron braces, but the first configuration requires less devices and enables... 

The results ofthis study show an attractive way for selection of proper dampers location and configuration, allowing the lowest and most effective control. In the authors opinion, efficiency of lever arm configuration in active controlled structures, designed using non-linear control algorithms, should be further investigated. 

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