Exposure–Effects Analysis Service

Study on the relationship between drug exposure and effects is a key part of the drug discovery process. This study provides important evidence for effectiveness and safety, supporting preliminary efficacy studies. Through this study, Creative Biolabs can help customers initially explore suitable target population, and adjust the dose and medication regimen according to internal and external factors.

We provide but are not limited to:

1. Parallel dose-effect study. Parallel dose-effect study can yield a population-mean dose-effect relationship, rather than a volume-effect curve distribution or shape.
• The research objects are randomly divided into several experimental groups with fixed dose respectively, that is random parallel dose-effect study. This study is simple, widely used and effective. Fixed dose refers to the final or sustained dose. The research objects can be administered immediately or titrated gradually to the dose. In both cases, the final dose should be maintained long enough to allow a dose-response comparison.
• By including both the placebo and the active drug control group, sensitivity evaluations can be made to distinguish between ineffective drugs and incorrect research methods. Comparing the dose-response curve of the tested drug with that of the control drug can provide better efficacy and comparability of efficacy and safety studies than comparing single dose of two drugs.
• Factorial experiment is a special method used in parallel dose- effect study to evaluate combination therapy, and is especially suitable for drugs that have an impact on the same response variable. This study can also be applied in this case that the effect of one drug will mitigate the adverse effect of the other. This study can show the effects of various ingredients when they are combined and provide dosage information of the drug when used alone or in combination.
2. Multiple comparison. The main objective of dose- effect study is to determine the appropriate dose, such as the minimum effective dose. Creative Biolabs can help customers determine the minimum effective dose through multiple comparison study. The commonly used methods are Dunnett test and stepwise multiple comparison.
• Dunnett test. Dunnett test is applicable to multiple comparisons of effect differences between K-1 dose group and a control group. This test can directly calculate the lower limit of unilateral confidence interval of effect differences between each dose group and the control group. By comparing the value of the lower limit with corresponding parameters, the minimum effective dose can be determined.
• Stepwise multiple comparison. Stepwise multiple comparison is used to compare the difference in effect between the K-1 dose group and a control group. Unlike the Dunnett test, this method does not require correction. By controlling the family wise error rate (FWE) within a specified α, stepwise multiple comparison ensures the robustness of the relationship curve. The estimation of the minimum effective dose is only limited to the dose range used in the experiment, and the effects of other doses cannot be inferred by extrapolation.
3. Model approach. The model approach takes the dose as a continuous quantitative variable. According to the pre-specified parameter model, Creative Biolabs constructs the functional relationship between the dose and clinical effect. The model is used to test whether there is a dose-effect relationship. An inverse regression method is used to estimate the dose to achieve the target effect.

References

1. Koenig F, et al. Adaptive Dunnett tests for treatment selection. Stat Med. 2008, 27(10):1612-1625.
2. Lee S, et al. What is the proper way to apply the multiple comparison test? Korean J Anesthesiol. 2018, 71(5):353-360.

*For Research Use Only. Not for use in diagnostic procedures.