When PSI published a blog post on the current state of radiopharmaceutical clinical trials in 2019, we had no way of knowing of the changes that would transform the clinical trial industry – along with every other one on earth – just a few months later.
Of course, managing global nuclear medicine trials has never been easy due to the complexity of regulatory requirements in each country and the necessity for experienced, highly trained sites either within close proximity to the material’s manufacturing site or with the ability to provide at the site level. However, travel restrictions and supply chain challenges have only exacerbated these obstacles. While some of these issues are starting to ease, the need for an experienced, global perspective toward managing these studies has only increased.
Success starts with understanding the risk factors that can impact your radiopharmaceutical trial from startup through the clinical phase. Drawing on our experience as we continue to run radiopharm studies in multiple oncology indications, we’ve highlighted some of the most common challenges to consider below – and how to overcome them.
1. Country-specific Regulatory Requirements for Radiopharmaceutical Agents
As development interest in this new class of agents has continued to grow, so has the complexity of the regulatory landscape. Additional approvals should be considered for studies in both the United States and the United Kingdom, as outlined in the table below:
|USA||Radiation Safety Committees approvals typically obtained before submissions to IRBs|
|UK||HRA radiology review prior to submission is needed, as well as approval of Administration of Radioactive Substances Advisory Committee (ARSAC). ARSAC review goes in parallel to the ethics/regulatory review|
The European Union’s Clinical Trial Regulation has streamlined the process for submitting clinical trial applications in the EU, but many countries still encourage or require additional approvals. An in-depth understanding of each specific country’s requirements in your trial is essential to proactively anticipate requirements and potential questions that can delay approvals. Drawing on our experience with these studies, PSI maintains a library of country-specific radiopharmaceutical requirements and regulations within VISIONAL™, our machine-learning-powered system for data-driven feasibility and enrollment forecast. This pairing of regulatory expertise and technology allows us to accurately predict timelines and model hundreds of country and site combinations, their budgets, and probability of success within minutes.
2. Site Imaging Qualifications and Other Common Delays in Site Activation
Site qualification can be time-consuming for sites, so sponsors should confirm timelines during the feasibility process and ensure that sites are well-trained and supported with any study-specific calibration or camera requirements. PSI created the role of Site Support Specialist to help support sites in the qualification and camera process as well as during the study, saving them time and frustration. An example of the site imaging qualification process is shown below.
This is a simplified example, and the process can be much lengthier if dosimetry is included as part of the study. We have found having a dedicated Site Support Specialist assigned to work one-on-one with each site during the qualification process significantly decreases delays in site activation due to camera qualification.
Issues with technical transfer, or IND amendments (if the drug will be manufactured on-site), can also lead to delays. In some instances, choosing a central procurement facility may be effective, allowing one facility to execute the contract and technical transfer independent of site startup and activation.
3. Logistical Issues During Clinical Phase
As noted in our previous article, cooperation and coordination are imperative every step of the way for the successful delivery of radiopharmaceutical trials: from the facilities and procedures that produce the nuclear material to their handling and storage to the transportation of the drug and dispensation. Understanding the patient journey and which procedures must be completed at each step, including when the investigational product should be ordered, is recommended as a proactive foundational tool. At PSI, we have developed a detailed and unique visual patient journey utilized at the site and project levels.
In addition, other tools for clinical staff, such as a patient visit and MRI/whole brain PET scan tracker calendar, biopsy procedure schedule, source template, and automatic calculator for time-dependent procedures, will help provide additional clarity and compliance. We also recommend tracking key steps via Interactive Response Technology.
4. Central Radiology Review and Delays in Submitting Scans
It is critical to manage and track all steps in the imaging process at each site, including navigating the technical dialogue between nuclear medicine technologists, nuclear physicians/radiologists, investigators, and other stakeholders. Sponsors should ensure clear communication and receipts from the central reader for all scans received and that the appropriate project team members are copied on any queries to the site. PSI’s Site Support Specialist is key in ensuring every stage is performed accurately and on time, including monitoring site submissions in real time and assisting sites with submissions when needed. This role has also proven beneficial in managing and providing oversight of all site queries, cutting the site team’s time spent on imaging queries in half.
5. Development and Implementation of Site-Specific Enrollment Plans
Solid tumor oncology trials represent one of the most competitive markets in clinical research, with over 3,000 trials ongoing or planned, according to data from clinicaltrials.gov, Citeline, and GlobalData. With additional obstacles presented by sites’ limited proximity to manufacturing centers, sponsors and their partners should have detailed site-specific enrollment plans that consider the patient journey at each site, from identifying prospective patients to scheduling the needed imaging assessments and surgeries or biopsies. Walking through this patient journey helps both the site and the CRA to identify all the involved team members so that potential risk factors can be mitigated. PSI’s dedicated Site Support Specialists may meet with sites as soon as they’re selected by clients to understand this patient journey and put together a tailored site enrollment strategy based on site referral patterns, facilities, capabilities, and other key factors.
Meet the challenge of your radiopharmaceutical pivotal trial with PSI
Every study is different, and there is no one-size-fits-all solution for ensuring success. With an established and proven database of more than 1,000 global radiopharmaceutical sites, PSI specializes in delivering radiopharm studies on time and with quality data. Seventy-nine percent of PSI CRAs have oncology experience, and PSI has developed therapeutic-specific training and resources for radiopharmaceutical trials to achieve the highest level of quality for your study. In addition, PSI’s Site Support Specialist role has led to a dramatic improvement in site activation and enrollment.
Contact us here to learn more about running your pivotal Phase 2 and 3 radiopharmaceutical trials with PSI.