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Surrogate endpoints examples

Relevance influences the usefulness of information, in that the more likely the user is to encounter the need for this particular information, the greater the relevance. For example, information about clinical conditions rarely encountered in an individual s practice has low overall relevance to the practitioner. Relevance also has another aspect that of closeness of fit of the information to the user s interest. Patients are primarily interested in outcomes that have personal meaning, such as morbidity, mortality, or quality of life. Information concerning these outcomes has high relevance. Information about the disease state or about surrogate endpoints has lower relevance for the patient. [Pg.785]

Exposure-response data, using short-term biomarkers or surrogate endpoints, can sometimes make further exposure-response studies from clinical endpoints xmnecessary. For example, if it can be shown that the short-term effect does not increase beyond a particular dose or concentration, there may be no reason to explore higher doses or concentrations in the clinical trials. Similarly, short-term exposure-response studies with biomarkers might be used to evaluate early (i.e., first dose) responses seen in clinical trials. [Pg.341]

The result of the Phase II trial is information needed to determine the effective dose and the dosing regimen of frequency and duration. Specihc chnical endpoints or markers are used to assess interaction of drug and disease. There are two types of markers definitive and surrogate. For example, in the case of cancer or hypertension, the definitive markers are mortality and stroke, respectively, and the surrogate markers may be tumor size, or cancer-associated proteins p53, TGF-a in the case of cancer, and blood pressure or cholesterol level in hypertension. Statistical analysis is carried out to evaluate the... [Pg.182]

The statins have been demonstrated to markedly lower plasma LDL levels (and triglyceride levels to a lesser extent). In fact, statins were approved by the US FDA on the basis of a surrogate endpoint reduction in plasma cholesterol levels. Since we know that increased plasma cholesterol levels are correlated with increased risk of coronary artery disease, it seems logical that reducing plasma cholesterol levels would lead to reduced risk. That turns out to be true in this case. However, see the case of hormone replacement therapy (HRT) for women for a more complex example, discussed below. [Pg.269]

The limitations of the use of biomarkers in healthy volunteers must be recognised. For example, although there have been attempts to simulate migraine headache in volunteers, to date none of these models can be considered adequate to serve as a surrogate endpoint. Patients with migraine are not difficult to recruit and are usually healthy apart from their migraine. In this case, it maybe more appropriate to establish tolerability and pharmacokinetics in healthy volunteers and then to select a maximum well-tolerated dose with which to perform a small proof of principle clinical trial in patients. This will need to be followed by larger trials to establish the dose-response relationship. [Pg.164]

The use of biomarkers and surrogate endpoints in patients is well established in virtually all therapeutic areas. After all, blood pressure has been used as a surrogate for cardiovascular risk for many decades. Some other examples are given in Table 4.5. [Pg.172]

There are many examples of biomarkers, which have been used as surrogates in prominent clinical trials that have been subsequently formd to be inadequate, illustrating the difficulty in identifying a surrogate endpoint. One notable scenario is that of a biomarker that responds to therapy and is highly predictive of survival, but does not predict the effect of treatment on survival. The use of CD4-I- counts in HIV trials is an example of such a biomarker. ... [Pg.279]

There are of course practical considerations in clinical research. We may find patient recruitment difficult in single centre studies and this is one of the major drivers to multicentre and multinational trials. Alternatively, we may need to relax the inclusion/exclusion criteria or lengthen the recruitment period. Unfortunately, while each of these may indeed increase the supply of patients they may also lead to increased variability that in turn will require more patients. A second issue is the size of the CRD which, if it is too small, will require a large number of patients. In such circumstances we may need to consider the use of surrogate endpoints (Section S.3.3.2). Finally, the standard deviation may be large and this can have a considerable impact on the sample size - for example, a doubling of the standard deviation leads to a four times increase in the... [Pg.304]

There is limited evidence on the effectiveness of most drugs at the time they are introduced. For example, many drugs are granted marketing authorization based on surrogate endpoints, such as reduction in lipid levels, as the actual effects on health may take a very long time to be measured. The rewards authority would therefore have to make its best estimate as to the risk-benefit profile of the product, and would presumably update the reward level as new information became available. [Pg.280]

Surrogate endpoints are usually used when it is not possible within the timeframe of the trial to measure true clinical benefit. Many examples exist as seen in Table 1.3. [Pg.21]

Instead, less traditional measures called surrogate endpoints are used to evaluate effectiveness. These are laboratory findings or signs that may not be a direct measurement of how a patient feels, functions, or survives, but are considered likely to predict benefit. For example, a surrogate endpoint could be the lowering of HIV blood levels for short periods of time with anti-retroviral drugs. [Pg.246]

Examples of some commonly used biomarkers and surrogate endpoints are listed along with clinical endpoints for several therapeutic classes in Table 17.1. [Pg.275]

The choice of endpoints used in studies of new therapies may evolve over time as knowledge is gained about the natural history of the disease or the reliability of surrogate endpoints. Endpoints used to evaluate the benefits of new drugs are provided in Table 4.1 for a number of diseases. Many diseases are associated with numerous medical conditions of consequence to the patient (for example, pain and disability resulting from rheumatoid arthritis), which may be the target for a particular new therapy. [Pg.42]

All the values allowing an accurate evaluation of the endpoints (toxicity and clinical response biomarkers, surrogate endpoints, or clinical endpoints). Treatment data, for example, dose and actual times of start and end of infusion. [Pg.794]


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