Treatment benefit

The activities described in this section intend to minimize or avoid the release of chemicals into the stream wastewater by substitution, optimization, reuse, and recycling. Besides a lowering of the costs for following up general wastewater treatment, benefits due to minimization of chemical consumption are intended. As there are various specific problems arising from the particular treatment steps applied for different fibers, this section concentrates on the most important problems. Table 2 gives an overview of the annual production of textile fibers [10]. 

One potential difficulty of cost-benefit analysis is that it requires researchers to express an intervention s costs and outcomes in the same units. Thus, monetary values must be associated with years of life lost and morbidity due to disease and with years of life gained and morbidity avoided due to intervention. Expressing costs in this way is obviously difficult in health care analyses. Outcomes (treatment benefits) may be difficult to measure in units of currency. Translating disease and treatment outcomes into monetary measures may be more difficult than translating them into clinical outcome measures, such as years of life saved or years of life saved adjusted for quality. 

The importance of this effort is illustrated in the following hypothetical example. A new therapy is under development that reduces the absolute risk of dying from a chronic disease by 50% as measured in a one-year trial. However, this therapy is not curative. A four-year trial was initiated at the same time as the one-year trial. The first-year results were the same in both the four-year trial and the one-year trial. However, there was an increased risk of death for treatment patients in the second and third year of the four-year trial, and by the end of the third year of the trial the survival rate was identical in the treatment and control arms of the four-year trial. While there was a clear benefit to the new therapy in terms of postponing events from the first year of treatment to later years, the economic assessment of the therapy would suggest a greatly reduced treatment benefit from the four-year trial as compared with the one-year trial. 

In projecting results of short-term trials over patients lifetimes, it is typical to present at least two of the many potential projections of lifetime treatment benefit. A one-time effect model assumes that the clinical benefit observed in the trial is the only clinical benefit received by patients. Under this model, after the trial has ended, the conditional probability of disease progression for patients is the same in both arms of the trial. Given that it is unlikely that a therapy will lose all benefits as soon as one stops measuring them, this projection method generally is pessimistic compared to the actual outcome. A continuous-benefit effect model assumes that the clinical benefit observed in the trial is continued throughout the patients lifetimes. Under this model, the conditional probability of disease progression for treatment and control patients continues at the same rate as that measured in the clinical trial. In contrast to the one-time model, this projection of treatment benefit most likely is optimistic compared to the treatment outcome. 

Measures of treatment benefit for categorical and ordinal data... 

Questions relating to those interaction terms are addressed through the d coefficient as before. In the above example, looking for treatment-by-covariate interactions would be asking whether the treatment benefit, in terms of a reduction in the likelihood of the baby suffering respiratory distress, was the same for babies delivered at 37, 38 and 39 weeks. 

Clinical relevance. The estimated size of the treatment benefit must be large enough to be clinically valuable... 

Physicians need improved tools for selecting treatments for individual patients. For example, many cancer treatments benefit only a minority of the patients to whom they are administered. Being able to predict which patients are most likely to benefit would not only save patients from uimecessary toxicity and inconvenience, but might facilitate their receiving drugs that are more likely to help them. In addition, the current over-treatment of patients results in major expense for individuals and society, an expense that may not be indefinitely sustainable. In this discussion we will address some key issues in the validation of pharmacogenomic classifiers. 

Freidlin and Simon (10) have shown, however, how one pivotal trial can be used potentially for both purposes—if the set of patients used to develop the classifier is kept distinct from the set of patients used to evaluate treatment benefit. Generally, however, the studies should be kept separate. Developmental studies are exploratory, though they should result in completely specified binary classifiers. Studies on which claims of drug benefit are based should be non-exploratory, but should instead test prospectively defined hypotheses about treatment effect in a pre-defined patient population. 

To support approval as a nonbotanical drug, adequate and well-controlled clinical studies are required. Not only must the treatment be shown to be effective, with real patient benefits in morbidity and/or mortality to justify the safety risk of adverse reactions as observed, but the clinical data must also provide practical instructions for use, which can be reasonably followed by health care professionals. There is no reason why these requirements should be different for botanical drugs, because patient suffering and treatment benefits are independent of medical theory or practice. Regardless of medical systems and terminology used, courses of diseases/conditions should be established and treatment effects must be clinically meaningful. Incorporation of alternative medical practice into the clinical studies will be acceptable if the new set of instructions derived from such studies will be practical. 

Total neutral sterol excretion by mice (male, C57BL/6) fed a chow diet is typically 80 15 nmol per day per gram body weight and bile acid excretion is 50 10 nmol per day per g body weight. On semi-purified diets, which are low in fiber and reduce gut motility, neutral sterol excretion is reduced as much as 50% and bile acid excretion can be reduced as much as 5-fold or more (unpublished results). Thus, the diet used in a given study must be chosen carefully. Since human diets have a tendency to be low in fiber, a chow diet may partially mask potential treatment benefits because sterol excretion is already quite high. 

Lorain, O., B. Hersant, F. Persin, A. Grasmick, N. Brunard, and J. M. Espenan. 2007. Ultrafiltration membrane pre-treatment benefits for reverse osmosis process in seawater desalting. Quantification in terms of capital investment cost and operating cost reduction. Desalination 203 277-285. 

Table 3 summarizes the primary results of these trials. Overall the use of GPIIb/llla inhibitors was associated with a modest, but significant reduction in the primary endpoint in PRISM, PRISM-PLUS, and PURSUIT Treatment benefit was confined to early time points in PRISM (48 hours) and PRISM-PLUS (seven days), but not sustained at 30 days (17,18). In contrast, treatment with eptifibatide reduced the incidence of composite endpoint by 1.5% absolute risk difference (ARD) in PURSUIT which was observed within four days and maintained for 30 days without attenuation or amplification (19). 

From these lines of evidence, it is apparent that the most likely reason for variability between interventional and medical management trials appears to be related to the frequency of early revascularization (100% in the former vs, <20% in the latter) and the utilization of periprocedural biomarker elevation criterion for Ml. Thus, treatment benefit associated with GPIIb/llla inhibitor is observed very early and is primarily driven by reduction in postprocedural biomarker elevation, the least robust but the most prevalent component of the composite endpoint with little benefit on death or Q-wave Ml. 

Is it likely that this unfavorable trend might reverse itself If the trial is stopped and the trend would have reversed itself, evidence of treatment benefit that would have been obtained will not be obtained, and that treatment will not reach patients who might have benefited from it. 

In 2004, Draelos and coworkers reported the effect of a petrolatum-containing body wash on the treatment of xerotic eczema. In this study, the researchers found that the patients who used a petrolatum-containing body wash in addition to moderate corticosteroid therapy had improved significantly more than the patients who used a more potent topical corticosteroid and a typical synthetic detergent cleansing bar. Thus, the petrolatum s skin treatment benefits were clearly evident, even when it was contained in a wash-off product.86... 

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