Multiple-comparison issue studies

Hypothesis-driven study and the results are easy to interpret small sample size requirement simple analysis no multiple comparison issue low cost easy to validate... 

Multiple confounding issues make interpretation and comparison of these results difficult. Differences in MTX dose and schedule clearly may limit the reproducibility of studies. Furthermore, incomplete ascertainment of toxicity, particularly when performed retrospectively, may impact on study validity. Finally, modest and heteregenous sample sizes clearly limit the available statistical power to detect clinically meaningful differences in treatment response. 

In Chapter 11 we discussed the issue of multiple comparisons and multiplicity in the context of pairwise treatment comparisons following a significant omnibus F test. When we adopt the 5% significance level (a = 0.05), by definition it is likely that a type 1 error will occur when 20 separate comparisons are made. That is, a statistically significant result will be "found" by chance alone. The greater the number of objectives presented in a study protocol, the greater the number of comparisons that will be... 

This approach reduces the number of study participants necessary to achieve the required statistical power in two ways. If the three individual components of the MACE composite endpoint (or the higher number of individual components in a MACE-plus composite endpoint) were compared separately between treatment groups, the numbers of events in each case would be lower than the total number of composite endpoint events. Moreover, a statistical correction would need to be made to address the issue of multiplicity as more comparisons are made, the chances of finding a statistically significant difference that does not in fact exist, i.e., committing a type I error, increase (recall discussions in Chap. 4). To counter this possibility, the alpha level (typically 0.05 for a single comparison) used for each of the multiple comparisons must be lowered. 

A critical methodological issue for a proper meta-analysis is the choice of studies. It is important that all studies meet reasonable criteria otherwise, a potential bias is introduced. We chose only those studies that had an appropriate control group, which provided a standard by which a drug s effects could be measured. By contrast, there have been meta-analyses of multiple studies on psychotherapy, all done without comparison groups or with invalid comparison groups. Combining the... 

Classical trajectory studies of the association reactions M+ + H20 and M+ + D20 with M = Li, Na, K (Hase et al. 1992 Hase and Feng 1981 Swamy and Hase 1982,1984), Li+(H20) + H20 (Swamy and Hase 1984), Li+ + (CH3)20 (Swamy and Hase 1984 Vande Linde and Hase 1988), and Cl- + CH3C1 (Vande Linde and Hase 1990a,b) are particularly relevant to cluster dynamics. In these studies, the occurrence of multiple inner turning points in the time dependence of the association radial coordinate was taken as the criterion for complex formation. A critical issue (Herbst 1982) is whether the collisions transfer enough energy from translation to internal motions to result in association. Comparison of association probabilities from various studies leads to the conclusion that softer and/or floppier ions and molecules that have low frequency vibrations typically recombine the most efficiently. Thus, it has been found that Li+ + (CH3)20 association is more likely than Li+ + H20 association, and similarly H20 association with Li(H20)+ is more likely than with the bare cation Li+. The authors found a nonmonotonic dependence of association probability on the assumed HaO bend frequency and also a dependence on the impact parameter, the rotational temperature, and the orientation of the H20 dipole during the collision. 

The IND differs in a number of ways from its European counterparts. First, it is much longer a typical IND is of at least 1000 pages, and for dmgs with foreign human experience, often many multiples of this number. The UK Clinical Trials Certificate, used very rarely for this reason, and not the Clinical Trials Exemption ( CTX ), would be the nearer comparison. Second, an IND is required for all human exposure to INDs, and this includes normal volunteer studies. Third, all being well, there is only a 30-day wait between filing and commencement of the clinical study no news from FDA after this time period has elapsed is presumptive evidence that the study may proceed (most FDA divisions will, in fact, issue affirmative letters that this is the case, within 30 days). Fourth, once an IND has become active, there is no subsequent 30-day wait when further clinical protocols are submitted. 

Despite the reasonable predictivity of the TDAR, especially if conducted at the optimal time and using multiple isotype assessment, it is still considered that this assay needs to be combined with other functional and/or structural assessments to give the best overall assessment of true DIT risk. Limitation in the TDAR as a single-parameter predictor for immunotoxicity in rodents is not a new issue. Furthermore, no other single functional measure appears adequate for a DIT determination either. Table 9.1-1 summarizes results of a recent comparison of 16 DIT studies employing different combinations of assessment parameters (Dietert and Holsapple, 2007). 

Although the accurate computation of liquid-phase reactions remains difficult due to numerical issues, Aold et al. [82] performed simulations of various model reaction systems, allowing relative comparisons. In particular, they studied the effects of the width of the fluid lamellae and the rate constants on reactant conversion and product selectivity. Qualitatively, the results reveal a strong dependence of the product selectivity on the lamellar width. From these CFD simulations, a model was developed that relates lamellar width, rate constants and product selectivity for various multiple reactions and reaction conditions. 

The preceding discussion illustrates the versatility of electroactive SAMs for addressing fundamental issues in electron-transfer kinetics. So far, an extended kinetic analysis with comparison to theory has been applied only to simple one-electron-transfer redox molecules. Clearly, there is an opportunity to study more complex redox systems. For example, a triruthenium cluster bound to a SAM exhibits multiple oxidation states and the reversible binding and release of CO [240]. Another area deserving more quantitative work is electrocatalysis in which the attached redox molecule mediates the electron transfer between a solution redox molecule and the electrode. 

Because of the hydrophobic character of the side chain, these amino acids are usually involved in protein or enzyme constmction but rarely in protein fimction [86-88]. The main issues in the study of such aliphatic a-amino acids are the increase of conformational possibiUties from the multiple configurations associated to torsion about single bond in the lateral chain. Two conformers of types I and II shown in Fig. 13 were ultimately detected in the supersonic jet for valine, isoleucine, and leucine, and conclusively identified through comparison of the experimental rotational and " N nuclear quadrupole coupling constants with the predicted values ab initio, as described in Sect. 3. 

Despite the fact that filler dispersion has been identified as one of the major factors affecting the properties of polymer nanocomposites, there is currently no consensus in the fidd on how best to quantify this property. Currently, the quality of dispersion is most commonly chararterized qualitativdy using optical and dectron miaoscopy techniques. The qualitative nature of imaging methods can limit the usefulness of comparisons made aaoss multiple studies owing to the lack of a standard metric or benchmark. To address this issue, several spatial statistical analyses for various images have been proposed from which quantitative measures of dispersion can be obtained. Kashiwagi et al. proposed two dispersion metrics. 

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