As most medications are primarily excreted through the kidneys or liver, most drugs in development will require a renal and/or hepatic insufficiency trial to assess the impact of organ impairment on the pharmacokinetic (PK) parameters of the investigational product. The data obtained from these trials will support the development of safe and effective dosing regimens for the affected patient populations. However, due to patient recruitment-related challenges, these trials present a unique challenge not typically found in standard clinical pharmacology studies.
To successfully manage organ impairment studies, clinical research organizations (CROs) must implement a model for study management that promotes communication, transparency and the alignment of overall objectives with sites and subject matter experts who have direct access to the patient population. When the CRO shows flexibility and adaptability to the real-world challenges of these studies, sites feel supported.
Therefore, the CRO should do all they can to remove unnecessary burdens on the sites and should be willing to leverage sites’ medical and operational expertise early and often. Organ impairment studies require this expertise; sites’ contributions to trial design, inclusion and exclusion criteria and patient care should be routine and welcomed.
A deep understanding of this special population is pivotal to developing a protocol that addresses the reality of the patient’s disease state (baseline), laboratory values, co-morbidities and medications. Once the study begins enrolling, investigators may encounter significant laboratory abnormalities, especially when impairment levels increase across the patient arms. Monitoring for significant parameter changes is a critical task across study management and patient oversight. Therefore, assigning investigators who can effectively interpret the laboratory values is crucial to ensure the appropriate patient management in the trial and accurate data reporting.
Lastly, when designing these trials, sponsors and CROs should consider how they can utilize clinical pharmacology tools such as population pharmacokinetic (PopPK) modeling and/or physiologically based PK (PBPK) modeling can in combination with adaptive trial design to decrease the burden on patients with renal and/or hepatic impairment. Furthermore, by using PopPK modeling of data from Phase II and III studies, it may be possible to gain insight into the impact of other impairment levels, potentially reducing the number of patients required for these clinical trials.
Watch this webinar to learn how to effectively manage renal and hepatic impairment trials by leveraging site expertise, enhancing communication and utilizing advanced clinical pharmacology tools.
