Endpoint analysis

Endpoint analysis uses the last observation made on a subject. Patients often gradually improve or worsen. Some drop from the study when they get so much better that they are discharged or it seems pointless to continue in the study. Some can deteriorate to a dangerous state, so that they must be dropped for clinical reasons. 

Adler, I.-D. Pacchierotti, F., eds (1998) Multi-endpoint analysis of genetic damage induced by... 

Yoko yama M, Origasa H, Matsuzaki M, et al. Effects of eicos-apentaenoic acid (EPA) on major coronary events in hyperc-holesterolemic patients (JELIS) a randomized open-label blinded 170. endpoint analysis. Lancet 2007 369 1090-1098. 

Methods for homogeneous SNP analysis in a closed-tube system differ greatly in their level of complexity (Figure 37-32). The number of oligonucleotides required varies from 2 to 8. The simpler techniques do not require probes at aU, although some of the more complex techniques require up to three labels or modifications on each probe. All of these methods use fluorescence and solution hybridization. Some of the methods that use melting analysis will detect more than two alleles if present those based on aHele-specific amplification or endpoint analysis are limited to two. 

A difiSculty frequently arises in clinical trials because not all patients allocated to a treatment will complete the designated period of treatment or follow up. Non-completion may be a function of the particular treatment allocated, in that the reason for discontinuation of therapy may be inadequate efficacy or an adverse effect. If non-completing patients are omitted from fhe treatment comparison, bias may be introduced. Simply, if a treatment s failures are omitted from further consideration, the treatment will appear to be better than it really is. Thus, the primary efficacy analysis for the comparison of treatments must include all patients allocated to each treatment, whatever their ultimate fate. This is known as intention-to-treat (ITT) analysis. The implementation of an ITT analysis is not always easy, but usually either an endpoint analysis (in which the final assessment, whenever it was made, is used for fhe treatment comparison) or one of the strategies based on ranking the patients (from the best to the worst in the study) proposed by Gould. ... 

Stratta RJ, Alloway RR, Lo A, Hodge E. Two-dose daclizumab regimen in simultaneous kidney-pancreas transplant recipients Primary endpoint analysis of a multicenter, randomized sffidy. Transplanation 2003 75 1260-1266. 

Multi-Endpoint Analysis. Until recently, in vitro evaluations were typically done using primary cell cultures and a limited number of doses to monitor changes in one or two endpoints. The new paradigm is to evaluate toxicity much earlier in the discovery process. To be useful to discovery teams, these evaluations must be done with a small amount of compound, require no more than 1 or 2 weeks to turn data around, provide information on a new compound s toxicity relative to other chemicals in class, enable the prioritization of new leads based on some parameter of toxicity (e.g., the concentration that produces a half-... 

Figure 16.6. Multiple endpoint analysis (tox-cluster) for determining toxicity.

The field of gene expression analysis has only recently become of broader interest to users of mass spectrometry. The reason for this lag in interest was simply the lack of methods allowing the absolute quantification of NAs in general, or mRNA in particular. Mass spectrometry only allows an endpoint analysis, and even then a standard for normahzation (such as a second allele) is required. Hence, the approaches used have focused on the semi-quantitative analysis of allelic expression which, as described above, is a rather narrow-albeit expanding-field of research. 

Gold, M.R., et al., T-Wave Altemans SCD HeFT Study Primary Endpoint Analysis. Circulation, 2006.114 p. II-428-9. 

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