Laboratory Biomarker Expertise
A biomarker is a measurable component within an organism in which its presence or absence can be correlated to a particular medical issue such as disease or infection. Biomarker assays are often a critical component of preclinical or clinical testing because they are used to provide researchers with information on the effects of the drug within the organism being studied. That pharmacodynamic (PD) information helps researchers determine the drug’s mechanism of action (MOA) and the correct dose for the patient.
The effects that the drug has can be physiological, biochemical, or molecular. For example, one of the pharmacodynamic effects that insulin has on the body is the decrease of glucose in the blood stream. In most cases, pharmacodynamic biomarkers can be determined and then used to examine the dose-response relationship of the drug candidate. The expert bioanalytical chemists at Medpace Bioanalytical Laboratories can assist with the assays of your biomarker PD study.
Biomarkers – Bioanalytical Validation
If a biomarker is chosen as a surrogate endpoint instead of a clinical endpoint, it could greatly increase the speed at which the drug can be approved. In order for a biomarker to be used as a surrogate endpoint, the biomarker should be well validated. If the biomarker is not validated, it is possible that the correlation of the surrogate endpoint and the clinical endpoint is causal. The validation of a biomarker as a surrogate endpoint is very extensive and often requires multiple studies using different drugs. However, the validation of a PD biomarker assay following a bioanalytical method is very straightforward and follows the ICH M10 guidance document, Bioanalytical Method Validation.
Exposure Response – PK-PD Studies
Comparing drug exposure to the pharmacodynamic response provides critical efficacy information. PK-PD studies examine the relationship between drug exposure concentrations detected in blood and effects that the drug has on the body, thereby allowing one to examine the dose-concentration-response relationships. In the insulin example above, as the dose of insulin increases, the amount of glucose in the blood stream will decrease. This PK/PD relationship is often graphically depicted in a dose response curve.
A strong understanding of the dose-concentration-response relationships aid in determining the correct dosing of the patient and which dosage form might be most appropriate.
Pharmacodynamics and Safety Pharmacology Studies
ICH S7A, Safety Pharmacology Studies for Human Pharmaceuticals, defines safety pharmacology studies as those studies that investigate the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above. The main objects of safety pharmacology studies are to:
- Identify undesirable pharmacodynamic properties
- Evaluate adverse pharmacodynamic and pathophysiological effects of a drug candidate in toxicology or clinical trials
- Investigate the mechanism of the adverse pharmacodynamic effects
Biomarker Studies at Medpace
Medpace specializes in both small and large molecule biomarker bioanalysis. The bioanalytical lab at Medpace has 21 mass spec instruments which forms the backbone of Medpace’s small molecule bioanalytical capabilities. For large molecules, Medpace’s state-of-the-art MSD instruments and flow cytometers are often used. However, more important than the instrumentation are the people. Approximately half the staff within the bioanalytical group have PhD degrees ensuring that experts will be working on your biomarker projects.