Surrogate marker

Doses should be titrated as tolerated with the goal of decreasing heart rate by 25% or to approximately 55 to 60 beats/minute.11,36 Heart rate is not an accurate marker for portal pressure reduction, but it is the accepted surrogate marker for effectiveness because there are no other acceptable alternatives. 

Pyrazinamide Adults Based on IBW 40-55 kg 1000 mg 56-75 kg 1500 mg 76-90 kg 2000 mg Children 15-30 mg/kg Hepatotoxicity, gastrointestinal symptoms (nausea, vomiting), non-gouty polyarthralgia, asymptomatic hyperuricemia, acute gouty arthritis, transient morbilliform rash, dermatitis Serum uric acid can serve as a surrogate marker for compliance FFTs in patients with underlying liver disease... 

The information requirements for products such as prolonged-release oral dosage forms will depend on whether or not it has been possible, during the development of the product, to establish an in vivo-in vitro correlation between clinical data and dissolution studies. In vivo-in vitro correlations should be attempted using product at different stages of development, but bioavailability and pharmacokinetics data from pivotal clinical studies using at least pilot-scale production materials and possibly routine production material are particularly important. Where it is not possible to establish an in vivo-in vitro correlation, additional data will be required to compare the bioavailability of product developed at laboratory scale, pilot scale, and production scale. In the absence of an in vivo-in vitro correlation, the dissolution test will be a quality control tool rather than a surrogate marker for in vivo performance of the product. 

Rininger JA et al. Differential gene expression technologies for identifying surrogate markers of dmg efficacy and toxicity. DDT 2000 5 560-568. 

The number of CD4 lymphocytes in the blood is a surrogate marker of disease progression. The normal adult CD4 lymphocyte count ranges between 500 and 1,600 cclls/pb, or 40% to 70% of all lymphocytes. 

Andersson et al. (2002) have shown in a randomized clinical trial that raloxifene does not affect insulin sensitivity or glycemic control in postmenopausal women with type-2 diabetes mellitus. It has favorable or neutral effects on selected surrogate markers of cardiovascular risk while decreasing hyperan-drogenicity in these patients. 

Healthy lifestyle is mandatory for all postmenopausal women together with adequate correction of detected risk factors. That is why this intervention is in the center of the diagram and concerns 100% of the women in this period. Then a decision must be made as to whether the woman s risk profile calls for any intervention beyond lifestyle improvement. The use of surrogate markers or risk scores can be useful in evaluating individual patients. 

QT prolongation is a surrogate marker used in cardiac safety studies, but several lines of experimental evidence indicate that it is a poor surrogate of TdP a number of drugs, because of their complex pharmacological profile, can prolong the QTc with a relatively low proarrhythmic risk (e.g. amiodarone). 

The predictive value of an integrated evaluation of nondinical studies should be acknowledged, all the more so because the thorough QT/QTc clinical study is not an infallible tool and relies on a surrogate marker of toxidty. 

Further, there is an increased reliance on use of in vitro dissolution as a surrogate marker for in vivo blood level data. When dissolution is used as a QC test for IR products, it is generally a single-point dissolution test and is represented... 

Isepamicin Population PK and Bayesian estimates of individual PK parameters were used to calculate various surrogate markers of isepamicin exposure to be tentatively correlated with clinical outcome and nephrotoxicity. No correlation was found between peak, AUC, or their ratio with MIC and clinical efficacy suggesting the drug should not be monitored using PK parameters... 

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... 

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