Clinical endpoint intermediate

In CEA, the total cost and the total benefits, measured in terms of an efficacy parameter, associated with two or more treatment pathways are added, and the increment is calculated. The incremental costs are then compared (in a ratio) with incremental outcomes (as measured in physical or natural emits). Physical and natural units can include both intermediate (surrogate) clinical endpoints (e.g. millimetres of mercury blood pressure reduction, changes in FEVi) or final endpoints (e.g. deaths averted or life-years gained). In a study that assessed the cost per deaths due to pulmonary embolism averted, Hull and associates reported that subcutaneous administration of... 

The types of data available at the end of a clinical trial will depend upon the trial s sample size, duration, and clinical endpoint. There are two categories of clinical endpoints considered in pharmacoeco-nomic analysis intermediate endpoints and final endpoints. An intermediate endpoint is a clinical parameter, such as systolic blood pressure, which varies as a result of therapy. A final endpoint is an outcome variable, such as change in survival, or quality-adjusted survival, that is common to several economic trials, which allows for comparisons of economic data across clinical studies and is of relevance to policy makers. 

An intermediate endpoint is a clinical endpoint assessed at some stage of a study but not at its very raid. Ultimate outcome is a clinical endpoint such as survival, onset of serious morbidity or symptomatic response that captures the benefits and risks of a treatment. Admission to a nursing home could serve as an ultimate outcome in the case of a drug intended to treat outpatients with Alzheimer s disease. 

Intermediate A clinical endpoint that is not the ultimate endpoint outcome but is nonetheless of real clinical... 

One frequent point of confusion is whether a clinical rating scale/ such as the Hamilton Depression scale/ is a biomarker or a clinical endpoint. As these scales attempt to capture the multifaceted dimensions of a complex clinical condition/ they are in fact clinical endpoints. However/ they are like intermediate endpoints because they do not encompass all dimensions of the disease being evaluated or the therapeutic response in all patients. 

The use of intermediate endpoints to demonstrate clinical efficacy is common in clinical trials, because it reduces both the cost of the clinical development process and the time needed to demonstrate the efficacy of the therapy. Intermediate endpoints are most appropriate in clinical research if they have been shown to be related to the clinical outcome of interest, as in the following ... 

Although an intermediate endpoint is associated with clinical benefit/ this benefit may be more than offset by the adverse effects of drug therapy when the ultimate outcome is considered. For example/ ventricular fibrillation is associated with increased mortality in the setting of acute myocardial infarction. The demonstration that lidocaine effectively prevents ventricular fibrillation in myocardial infarction patients at first provided a rationale for treating these patients prophylactically with this drug (7). However/ subsequent meta-analyses of several studies by MacMahon (8) and Hine (9) indicated that this use of lidocaine therapy actually worsens patient... 

A large number of clinical intervention studies have examined the effect of supplemental p-carotene on intermediate cancer endpoints, as shown in Table 1. The results of these trials indicate that supplemental p-carotene consistently results in regression of oral precancerous lesions (oral leukoplakia, oral dysplasia), and a decreased frequency of micronucleated buccal mucosal cells. While many of the trials of oral precancerous endpoints were not placebo-controlled, and thus somewhat difficult to interpret because spontaneous regression can occur, those that were placebo-controlled nonetheless demonstrated significant benefit to p-carotene relative to placebo. From Table 1 it appears that the chemopreventive efficacy of p-carotene varies by site, with evidence for efficacy in the oral cavity and possibly esophagus, mixed evidence in cervix and lung, and convincing evidence of a lack of efficacy in the prevention of recurrent colorectal polyps. 

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