As the Clinical Pharmacology Operations Team Lead at Shire, Robert Homolka works on
Phase I and Clinical Pharmacology studies across the company’s (drug) pipeline. Homolka has been working in the pharmaceutical industry for more than 30 years. For the last 20 years, he has been employed by Shire and AstraZeneca in Clinical Pharmacology/Experimental Medicine Operations. Currently, he is the Director of Clinical Pharmacology Operations at Shire.
Homolka feels the support the Clinical Pharmacology group provides to the clinical development programs is one of the more important aspects of his job. Clinical pharmacology is the study of drug interactions in humans. Generally, these types of studies have an endpoint that is directly or indirectly related to safety. Studying and ensuring the safety of a drug is of primary importance to the sponsor, and clinical pharmacology is front-and-center in leading that effort.
Within the small molecule arena, one could identify clinical pharmacology’s contribution in the prescribing information. Homolka feels, “if a colleague had read the prescribing information, for a small molecule, he/she could have identified clinical pharmacology’s contribution. An argument could have been made that the majority of the safety information for small molecules comes from clinical pharmacology studies.”
It’s also a discipline that is undergoing significant evolution due to the variety of biopharmaceuticals currently being studied.
These new advances have allowed the industry to become more focused on the development of biopharmaceuticals. This enhanced understanding may ultimately add value in accelerating the time from the first-in-human stage to submission of a Marketing Application.
Don’t Wait Until It Is Too Late
Homolka notes the biggest challenge facing any clinical pharmacology team will arise from teams planning later phase studies, where the importance of clinical pharmacology may not be as well understood. Involving clinical pharmacology early during a drug’s development, where the team can make the biggest impact, is recommended. Collaborative efforts can help in identifying a safety or critical endpoint signal that can drive objectives of later studies.
“It’s not uncommon for teams to not fully appreciate the importance of conducting clinically important clinical pharmacology studies (i.e., special populations, dosing times, administration systems) until it is too late,” he says. “For example, with an orally taken drug, the later phase teams may not appreciate how food, and what type of food, may affect a drug’s pharmacokinetics.” Knowing this information early on may save the development team from trying to parse a large amount of inconsistent and confusing data in later studies.
For that reason, many clinical pharmacology teams and experts make substantial efforts to inform development programs about the importance of engaging clinical pharmacology experts early in the drug development process and especially in key decision-making efforts. Teams need to know that the clinical pharmacology team is available to support their efforts and offer critical insights in development.
When the clinical pharmacology team is notified of a need, the request often comes from one of its own members, such as the pharmacokineticist. The pharmacokineticist is often part of the development team and is able to identify the need to start working on a new study that will add value to the later phases. As a part of clinical development programs, those clinical pharmacology team members bring their particular skill set to the development effort, and are able to sort out what Homolka calls “the differences between noise and the need for a program-supporting study.”
There are other times when an unexpected event may occur concerning a certain class of drugs. This may result in a regulatory body asking for sponsors to further investigate the event regarding their “in-class” drugs before allowing it to proceed to other phases. For example, if there are safety concerns that are not understood within a class of drugs, the agency may request additional assessments to ensure patient safety before allowing the drug in that class to proceed to later phases. Because of the dynamic resourcing within the team, clinical pharmacology is uniquely situated to provide this support, once again illustrating its important role and how clinical pharmacology can make significant contributions to the drug development process.
The Clinical Pharmacology Workforce Fills a Need
Clinical pharmacology studies come in many shapes and sizes. Because of this, the ability to use the operating model that best supports a given study is required. These studies can be outsourced to highly skilled vendors or supported in-house using highly skilled full-time equivalent (FTE) staff or skilled consultants. Several factors, including risk assessment, prioritization of the program, and complexity of the study design, are used to determine the right operating model. Due to the dynamic approach of the operating model, groups that primarily use a specific method of operations may need guidance in understanding the “fit for purpose” clinical pharmacology operating model.
Today, many companies fully outsource clinical pharmacology studies, or they may only outsource studies that have both a low risk and low complexity. They may also internally manage those studies that have a high risk and complexity level by in-house FTEs and/or consultants. In a resource-constrained world where FTEs may be limited, consultants are often used to bring in the needed expertise and meet the dynamic resourcing needs of the study. The use of “as needed” consultants is another way that clinical pharmacology can work within a company’s virtual working environment policy but still make significant contributions and support the clinical pharmacology needs of a program.
For example, some studies require complex preparation and administration of a study drug. The ability to have a consulting pharmacist who can help the team develop the pharmacy manual and consult with the site’s pharmacist such that he/she understands the goal of the study can be helpful. The pharmacist can also observe dosing to ensure that the drug is being prepared and administered as envisioned, which can add significant value to the successful conduct of the study.
As mentioned above, the workload in clinical pharmacology is dynamic and can be unpredictable. Unplanned studies can arise anytime and at a moment’s notice. “If the company needs a study to start right away, we can reprioritize the workload and have the synopsis or protocol started as early as the next day,” says Homolka. “I rely on FTEs and consultants for the clinical part of a study. There are other functions that can be outsourced to a highly skilled vendor. Those functions can include data management, biostatistics, and medical writing.”
For example, a regulatory body once asked a company Homolka worked at to conduct a drug-drug-interaction study. A drug in that class was encountering unanticipated serious adverse events. The marketing application for that drug had been recently submitted. The regulatory body asked for a Clinical Study Report (CSR) 18 weeks from the date of notification.
If the company had not been able to deliver the CSR, it may have jeopardized the ability of that regulatory body to review the marketing application on the original timelines. The clinical pharmacology team worked tirelessly, including on weekends and holidays, to ensure that the protocol was developed, the study was conducted, data were analyzed, and the CSR was delivered on time. In the end, Homolka’s team was able to deliver the CSR a week early.
“If you look at the business implications of the above example, the compound was expected to be successful in the marketplace, and it was hoped that the total revenue from sales would be at least a million dollars, day-after-day,” states Homolka. “Any delay could have resulted in an unrealized loss of future revenues and reinvestment. Once again, this is an example where clinical pharmacology can make a substantial impact on a drug’s development.”
To be able to navigate the fit-for-purpose operating model, Homolka adds, it takes highly trained vendors and staff. Unfortunately, the use of highly skilled vendors, staff, and consultants to meet acute needs is another area where confusion may occur. The clinical pharmacology operations personnel are highly skilled with a broad set of backgrounds that combine the skills of a clinical scientist with the skills found in clinical operations. Due to the compressed timelines, personnel need to be able to contribute to all aspects of a study, whether writing a synopsis or protocol, observing assessments in real time, or monitoring key data.
This article reflects the personal views of Mr. Homolka. They should not be construed to represent the official views or policies of Shire.