By Neha Bhise, PhD, Sr. Clinical Pharmacologist
Clinical pharmacology is a translational scientific discipline which strives to understand the actions and behaviors of drugs in humans by combining it with the knowledge of human pharmacology. The study of clinical pharmacology is fundamental to our understanding of how drugs are processed by our bodies and how they affect human physiology.
Clinical pharmacology also helps us understand the relationship between a drug’s dose and its effect, the variability in response to a drug or therapy, why some patients experience adverse effects (AEs), how AEs can be minimized, and more. Understanding these aspects of a drug’s action (pharmacodynamics) and disposition (pharmacokinetics), helps drug developers achieve safe, effective, and optimal therapeutic outcomes for patients.
The discipline of clinical pharmacology helps healthcare professionals develop a deep understanding around numerous topics that are essential to the drug development process such as biochemistry, drug metabolism, pharmacokinetics (PK), pharmacodynamics (PD), pharmacometrics (modeling and simulation), pharmacogenomics, human toxicology, drug interactions, and more.
The Roles of Clinical Pharmacologists
Clinical pharmacologists can be physicians, pharmacists, and/or scientists whose primary focus is researching and developing drugs or therapies with the goal of delivering the right drug to the right patient(s), at the right dose, at the right time. A clinical pharmacologist can work in an academic/research, clinical, industry, and/or regulatory setting.
In an academic or research setting, a clinical pharmacologist may be involved with the study of biomarkers, PK, drug metabolism, and/or pharmacogenomics from a cellular level to a population level. Clinical pharmacologists at the academic level are also typically involved in collaborative research with different drug development companies.
Clinical pharmacologists in a clinical setting work with actual patients. They can help design clinical trials, observe adverse reactions to drugs or therapeutics (also known as pharmacovigilance), or they can be involved in teaching, framing policies, and giving advice/recommendations about the proper use of medicines.
In the pharmaceutical industry, clinical pharmacology impacts every stage of drug development. Clinical pharmacologists contribute to decision making at critical milestones such as in early human and/or proof-of-concept phases (preclinical through Phase IIa) or in the later stages where more robust risk and efficacy profiles are established (Phase IIb through Phase III). A significant portion of a drug’s product label/package insert is directly influenced by clinical pharmacology and has an enormous impact on marketing applications (NDA/BLA).
Clinical pharmacologists are also an integral part of various regulatory authorities and they play an important role in developing policies/guidances pertaining to drug regulation, prescribing policies, and best practices etc.
Why is Clinical Pharmacology Important?
Clinical pharmacology is essential for developing safe and effective drugs/therapies and to achieving regulatory approval. One of the most common mistakes in drug development is simply not taking full advantage of what the field of clinical pharmacology has to offer. If utilized appropriately, clinical pharmacology data can be used as a road map to guide the overall clinical development program, saving valuable time and resources.
Clinical pharmacology studies aim to evaluate and understand a drug’s absorption, distribution, metabolism, and excretion (ADME) properties, its pharmacodynamics including both desired effects and adverse effects, and the impact of intrinsic factors (such as age, gender, weight, race/ethnicity, genetics/genomics, organ dysfunction etc.) and extrinsic factors (such as food effect, drug-drug interaction etc.). Clinical pharmacology can also benefit drug development programs by:
- Optimizing dosing regimens for patients to obtain an optimum benefit/risk profile
- Creating a better understanding of the safety and efficacy of drugs in special populations (racial/ethnic minorities, pregnant women, elderly, pediatrics and in patients with organ impairments)
- Evaluating the appropriateness of administering the drug with or without food
- Determining the dosing schedules and body-weight dosing strategies based on the drug’s PK and safety profile
- Mitigating the risk to patients by better understanding the possible drug-drug interactions (DDI)
- Determining the likelihood of a drug prolonging the QTc interval at therapeutic doses or under worst-case scenarios
Drug development involves sequential planned studies that include the initial preclinical phase followed by clinical studies in humans. A clinical pharmacologist can help determine which clinical studies are required to be conducted throughout the drug development process. Depending on the drug, some additional clinical pharmacology studies may be required, or some studies may be avoided with the help of pre-existing data and modeling tools.
Clinical Pharmacology Modeling Tools
In recent years, Model Informed Drug Development (MIDD) has become an integral tool used in clinical pharmacology to optimize the drug development process overall. The use of MIDD is beneficial because it helps facilitate optimal decision-making for drug developers by leveraging all the available data for a drug candidate, from in vitro, preclinical, and clinical studies.
Different types of modeling tools such as, exposure-based models, biological models, and statistical models, can ultimately help predict the likelihood of success of a drug candidate. Some important MIDD tools include:
- Translational PK/PD Modeling
- Pharmacometrics / Population Pharmacokinetics (popPK)
- Physiologically Based Pharmacokinetics (PBPK)
- Quantitative Systems Pharmacology (QSP)
- Quantitative Systems Toxicology (QST)
- Model-Based Meta-Analysis (MBMA)
MIDD can help streamline and accelerate the drug development process by facilitating more informed decision-making and by reducing or eliminating the need for additional studies. Drug developers use MIDD strategies to optimize and reduce the number of patients enrolled in a trial, and to increase the likelihood of trial success by aiding in the selection of the correct dose, duration, and patient population. MIDD approaches can also provide insights into certain unstudied subpopulations or scenarios that help bridge efficacy and safety in such instances.
Applying the knowledge gained through MIDD-based approaches helps us better understand the relationship between a drug’s concentration in the body and its pharmacological response. One critical application of MIDD is to inform pediatric drug development, especially the extrapolation of dose, exposures, and efficacy from adults to pediatric populations based on strong understanding of the disease pathology, pharmacology of the drug, and the response to therapy. MIDD-based approaches are also used to:
- inform clinical trial designs
- predict clinical outcomes
- support evidence of effectiveness
- characterize the variability of drugs
- understand the factors contributing to variability
Conclusions
The role of clinical pharmacology is of utmost importance in rational and efficient drug development. A thorough understanding of the principles, guidances and the tools used in clinical pharmacology are crucial for the successful approval of the drugs by regulatory authorities.
Allucent’s team of experienced clinical pharmacologists can help address gaps in clinical development plans, design clinical studies, analyze the gathered data, and prepare regulatory data packages for submission to relevant regulatory agencies. Browse Allucent’s website to know more about the clinical pharmacology services provided by Allucent.