Flexible designs

Re-evaluating sample size is one example of adapting the design of the trial based on accumulating data from the trial. There is currently substantial interest in the potential of allowing flexibility in this way. These considerations come under the heading of adaptive or flexible designs. 

Undertaking interim analyses for either efficacy or futility or both, together with sample size re-evaluation already provides a range of flexibility in the design and planned correctly these approaches may cover many situations of practical interest. What more could be done Phillips and Keene (2006) list a range of potential adaptations including the following  

Dropping treatment arms is already done for safety reasons. Outside of that, this could be built into a formal interim look based on futility. Van Leth et al. (2004) provide an example (the 2NN Study) of adding a treatment arm based upon external considerations following the publication of results from a related trial. Analyses of the resulting data involved consideration of all of the data and secondly only those data from the trial following the change. We will discuss further aspects of this trial later in this section. 

The primary endpoint is that endpoint which provides the best measure of treatment response/success and such choices are based on clinical arguments rather than statistical ones. It seems unlikely that a change in this could be justified. 

Finally, it is, in principal, possible to increase the sample size based on the observed treatment difference at an interim stage without affecting the type I error, but great care needs to be taken with regard to dealing with this statistically. Evidence to date suggests that such procedures offer no real advantages over and above a standard interim analysis plan. 

---

Flowever, motor manufacturers may adopt more flexible designs with more reserve capacity and better speed-torque characteristics to suit the requirements of a particular sector. These are particularly for installations where the distribution system may have wider voltage fluctuations or the load itself may have varying load demands. It is possible that the same motor may have to drive more than one type of loads at different times. An agricultural pump motor may be one such application where it may also have to drive a thrasher or a winnower at different times. A motor with higher flexibility would be more desirable for such applications. 

The shaft is a forging and may he designed as a stiff shaft or flexible shaft. A stiff shaft design means that the shaft will operate helow any of its critical speeds. Usual practice limits design operation to 60% of the first critical speed. This requires a heavier shaft than the flexible design that allows the shaft to pass through its first critical speed at 40-60% of normal and maximum operating speeds. 

In contrast with continuous plants, batch plants are intrinsically flexible. Designed properly, they meet changes in product demand and characteristics of processes in the plant. These changes originate from uncertainties in variables determining the performance of the batch plant. There are two different types of uncertainties in the design of batch plants (1) short-term, and (2) long-term variations. 

A lot of marketing hype surrounds the terms component and component-based development. It includes radical pronouncements suggesting that object technology is dead and components are the next salvation. Separation of concerns, encapsulation, and pluggable parts continue to distinguish good, flexible designs from bad. 

N Xi t) + N2X2 t) such that N C = 0, N = [A a NbY This allows w t) to be fully independent of the original state (which is possible because of the exact cancellation of the matrix X t) in (19)). Then, N may be used to cancel the non-linear terms in the w t) dynamics and N may be used to rebuilding the unmeasured state exactly as in (4). Furthermore, in such a case, a matrix A i only left invertible is sufficient. Of course, this allows a more flexible design of the asymptotic observer. Nevertheless, in a more general case, when A t) is not proportional to the identity matrix, any... 

A recent European regulatory document (CHMP (2006) Reflection Paper on Methodological Issues in Confirmatory Clinical Trials with Flexible Design and Analysis Plan ) has given more thought to what is acceptable and what is not, in terms of flexible design. Several common themes are seen to run through this paper ... 

Currently we have little experience with flexible designs more experience is needed before these designs can be used. 

CHMP (2006) Reflection Paper on Methodological Issues in Confirmatory Clinical Trials with Flexible Design and Analysis Plan... 

Figure 14.4 is the three-dimensional view of the process. The figure illustrates the relative water head at different stages. Because of flexible design, Ultrox UV/oxidation treatment systems have a number of advantages (1) very few moving parts (2) operation at low pressure (3) minimum maintenance (4) full-time or intermittent operation in either a continuous or batch treatment mode (5) use of efficient, low-temperature, and long-life UV lamps and (6) use of a microprocessor to control and automate the treatment process (Zeff and Barich, 1992). 

Separation equipment tends to have less flexible design limits and can be costly to modify. For example, the C02 absorber and solvent regenerator towers in a wet scrubbing unit are difficult to replace. Fortunately, it is often possible to make changes to tower internals, or to change the solvent composition, to provide more capacity86. 

Key words receptor binding site, molecular diversity, ligand flexibility, design strategies... 

ARCO Chemical Co. Ethyl tertiary butyl ether (ETBE) Mixed C5s streams and ethanol Reliable, flexible design with high conversion and long-life catalyst 7 1995... 

Contrary to the groups of Lambert, Sakurai, and Suzuki [1] we chose a synthetic route to dendritic polysilanes which makes use only of monosilanes. The reason for this strategy lies on the one hand in an improved accessibility of starting materials and on the other it allows a more flexible design of the desired structure. 

In general, a multi-purpose plant should be able to treat many kinds of different feedstocks. In order to achieve this requirement, a flexible design of the mechanical and electrical parts is required. Nevertheless it is not possible to run every feedstock with a fixed arrangement of apparatus and control units. Thwefore a modular... 

One type of flexible design is the group sequential design (23). Such a design typically includes one or more preplanned interim analyses. Based on the results of the interim analysis, a preplanned action is taken. Most commonly these actions include ... 

---