Pharmacokinetics in clinical trials is conducted to assess the absorption, distribution, metabolism, and excretion properties of a drug product in healthy volunteers and patients. Pharmacokinetic (PK) data is crucial for designing and conducting subsequent studies. Besides, they can evaluate the efficacy and safety profiles of a new drug product during clinical studies and post-marketing analysis. However, researchers must combine early preclinical data with observed clinical PK assessments while developing a reliable, safe, and effective drug product.
Pharmacokinetics data is intertwined with the bioavailability of a drug product. But what does bioavailability mean? Bioavailability is the fraction of drug components that become available at the site of drug action. Clinical PK data is beneficial for determining the application of a drug according to its patient’s characteristics, such as genotype and disease-specific drug-metabolizing enzymes, and assessing the impact of PK drug interactions. Moreover, pharmacokinetic data also provides information regarding therapeutic drug monitoring. Therapeutic drug monitoring evaluates the pharmacokinetics parameters of study subjects in close association with the efficacy and safety observed in individual subjects. The current article focuses on understanding the role of pharmacokinetics clinical trials in understanding drug efficacy and safety.
Understanding drug efficacy and safety
Treatment or medicinal drug is only used when it has therapeutic benefits for a patient. However, therapeutic benefits include both efficacy and safety of the candidate drug product. Besides pharmacokinetics data, pharmacodynamics assessments are crucial for developing a drug product. A combination of PK and PD analysis in clinical trials is necessary for deciphering the ability of a drug to produce the desired therapeutic result and the likelihood of generating unwanted adverse effects.
Efficacy can be defined as the capacity of a drug product to produce a therapeutic effect. However, assessing efficacy requires ideal conditions, for example, selecting ideal study patients and strict adherence to the dosing schedule. Besides, measuring efficacy requires expert supervision, such as during controlled clinical trials.
On the other hand, effectiveness is concerned with the drug’s therapeutic effects in real-world use. A drug may prove efficacious during clinical trials but not be as effective during actual use. For example, the drug may demonstrate efficacy in lowering blood pressure but may have several adverse effects. Besides, a drug may be less effective if physicians prescribe it for a different therapeutic use. In such cases, effectiveness will be lower than efficacy. Hence, researchers should assess patient-oriented outcomes and not surrogate markers to judge drug efficacy and effectiveness.
Patient-oriented outcomes are the ones that impact the well-being of patients. Patient-oriented outcomes include relief of symptoms, prolonging life, and improved functioning, such as preventing disability.
On the other hand, surrogate outcomes may not necessarily correlate with the well-being of a patient. Therefore, parameters such as physiological features, such as blood pressure, or test data, for example, cholesterol and glucose levels, are surrogate markers and may not help treat disease. For example, lowering blood pressure may lower and control hypertension. However, the drug may lower blood pressure but not reduce the chance of death as it may have fatal adverse effects. Moreover, surrogate markers that are nearly an indicator of a disease and not a cause of disease may not treat the underlying disorders. Hence, surrogate outcomes should not be preferred over efficacy and effectiveness measures.