Because of the importance of clinical pharmacology to drug development, it is essential to consider the expertise of your product development team early and to determine whether additional clinical pharmacology support is required. If it is, you may be wondering how best to fill this need. For some companies, this means recruiting and directly hiring individuals to fill whatever roles are needed, such as a pharmacokineticist or pharmacometrician. For others, outsourcing a consultant makes more strategic and financial sense. The decision of whether to hire a clinical pharmacologist or to outsource work to a consultant is difficult, and several crucial questions must be asked. For example, does your company have enough work to support an in-house, full-time pharmacokineticist? What about a pharmacometrician? If not now, then as your business grows, where is the inflection point for building up your internal team versus outsourcing?
Why is Clinical Pharmacology Important?
Clinical pharmacology is the study of how a drug interacts with the human body. This includes the body’s effect on the drug (pharmacokinetics [PK]) and the drug’s effect on the body (pharmacodynamics [PD]). Clinical pharmacologists seek to define:
- the drug’s absorption, distribution, metabolism, and excretion (ADME)
- the drug’s mechanism of action
- how the body’s cells, tissues, organs, and organ systems respond to the drug
- how an individual’s race, sex, and genetic make-up influence drug concentrations and response
- how the drug interacts with other drugs and with food or alcohol
- other sources of variability (intrinsic and extrinsic factors) that impact these interactions
Using this information, clinical pharmacologists are uniquely positioned to identify safe and effective doses for clinical development and subsequently, for patients. Because both safety and efficacy are closely intertwined with pharmacology, it comes as no surprise that clinical pharmacology drives much of the decision-making from early development through Phase 3 clinical trials. Pharmacology is an important component of the target product profile (TPP) and influences the types of studies that are conducted and how these studies are designed and analyzed. Clinical pharmacology also has an enormous impact on the marketing application (NDA/BLA), and a significant portion of a drug’s product label/package insert is directly influenced by the pharmacological properties of the drug.
The Role of Clinical Pharmacology During Drug Development
Clinical pharmacology impacts every stage of drug development. Even before a drug enters the clinic, sponsors should be thinking critically about formulation development, an appropriate route of administration, effective dose regimens, possible off-target effects, and the potential for dose-related or concentration-related toxicities. Each of these will impact how the drug is used in humans and whether the drug satisfies the “safe and effective” requirement for approval. Once sufficient nonclinical data have been acquired from pharmacological models and IND-enabling toxicology studies, early clinical dose selection can begin. The goal at this stage is to ensure a safe initial dose for the first-in-human (FIH) study and to devise an appropriate dose-escalation strategy to ensure that potentially effective doses are studied. Decisions about the initial doses in an FIH trial are made according to health authority guidances and should be based upon available information regarding the drug’s pharmacologically active dose, toxicity profile, and PK. During the FIH trial, the first human PK and safety data are generated, and these data are used to make real-time decisions about how to proceed with the trial. Should a higher dose be tested? Should additional subjects be dosed at the current dose level? Is there a need to return to a lower dose due to the emergence of safety signals? Answering these important questions falls to the data review committee, and clinical pharmacologists are a crucial part of this team. In this role, a clinical pharmacologist is uniquely suited to weigh in on the emerging PK and PD data, spot trends, and make predictions about the behavior of the drug at higher doses. As the clinical program progresses, the clinical pharmacologist’s role remains vitally important. This includes key input into clinical trial design, sampling strategies, and data analysis. In phase 2, clinical pharmacologists are responsible for helping to choose an appropriate range of doses based on safety, PK, and PD/biomarker data from phase 1 studies and potentially an understanding of nonclinical or other data supporting the predicted effective dose. Based upon the data gathered in phase 2, clinical pharmacologists begin to make important connections between drug exposure (i.e., the concentration of the drug in blood or another appropriate matrix) and the efficacy and safety of the drug in a relevant patient population. With this information and the valuable insights from phase 1, clinical pharmacologists help identify the best dose regimen and patient population for the phase 3 trial(s), all the while keeping an eye on the intended use of the drug once approved. During development, clinical pharmacologists also advise on the need for additional studies such as drug-drug interaction, food effect, organ impairment (e.g., kidneys and liver), and cardiodynamics (QT studies), and provide input on modeling and simulation activities to provide a deeper understanding of the relationships and sources of variability within the drug’s PK, PD, safety, and efficacy profiles. In addition to input on clinical trial design, performing various analyses of PK and PD data, and defining critical exposure-response relationships for efficacy and safety endpoints, clinical pharmacologists also help prepare and review the marketing application, including the biopharmaceutics and clinical pharmacology sections of Module 2. Clinical pharmacologists provide key input on the draft product label, which is one of the most important components of the marketing application and, once finalized, conveys critical information about the approved use of the drug.
Challenges of Insourcing Clinical Pharmacology
Under the appropriate circumstances, having in-house clinical pharmacology expertise can be highly beneficial. The clinical pharmacologists on staff will be solely dedicated to your program(s) and can be deployed as desired within and across project teams and refocused as needed to meet program goals and deadlines. However, along with these positives, there are also challenges. Among these challenges, clinical pharmacology is a broad field with many subdisciplines, including noncompartmental analysis (NCA), pharmacometrics (i.e., modeling and simulation, including PBPK and QSP), and many specialized roles, including assisting with formulation development, providing input on special patient populations, and helping to make critical strategic planning decisions on both the study-level and program-level. To accommodate these diverse and vital areas of expertise, companies will often need to recruit, train, and place multiple individuals within their clinical pharmacology team. Additionally, there is often a need to hire additional staff to perform supporting roles for the clinical pharmacologists, including programmers, medical writers, and others. However, building out a team in this way poses several potential issues, including financial challenges (i.e., salary and benefits) and logistical challenges (i.e., ensuring appropriate training and a consistent level of work throughout the year regardless of the program stage and without extended periods of overwork or underwork). These challenges can be significant and may prove insurmountable for all but the largest companies. Even when a company can hire its own clinical pharmacologists, there may still be times when the amount of work will outpace capacity, and the work will need to be outsourced anyway because of bandwidth issues.
Benefits of Outsourcing Clinical Pharmacology
Outsourcing your clinical pharmacology program (or even parts of it) to a clinical pharmacology consultant or consulting team can help fill expertise gaps and add efficiencies. For companies with an established clinical pharmacology team, engaging outside experts can free up internal resources and can provide the independent insights, niche expertise, and diverse scientific and regulatory experience to propel your program forward. For companies without existing in-house clinical pharmacology expertise, outsourcing can mean the difference between an inefficient or stalled clinical program and a smooth road to approval. While there are many consulting options available, they are not all the same. Before deciding on a consultant or consulting firm, it is vital to ensure that you choose a partner that not only has the requisite experience, expertise, and resources to get the job done but one who will also be as dedicated to your program’s success as you are.
Conclusions
Allucent has a large team of experts who have extensive experience in clinical pharmacology, PK, and pharmacometrics. Our team provides hands-on expertise, which ensures a high level of support for ongoing development activities and interactions with global health authorities. Allucent’s scientists translate complex data into actionable insights across the entire drug development spectrum. With our background in clinical pharmacology and PK/PD, we enable our clients to make better strategic decisions and improve their clinical and nonclinical studies. Our specialized focus helps our clients avoid costly missteps and decrease the possibility of regulatory rejection. In addition to our senior clinical pharmacology experts, Allucent is proud to provide our clients with exceptional support from skilled medical writing, data management, programming, project management, and quality assurance professionals. No matter what your program needs, we pride ourselves on being not only a trusted partner for clinical pharmacology services but a true extension of your drug development team. Contact us to learn how Allucent can help support your clinical pharmacology and other drug development needs.