Name: Radiopharmaceutical Clinical Trials: Key Challenges and Practical Solutions
Uploaded: 2025-12-11T16:05:18.449Z
Duration: 22 min 52 s
Description: Radiopharmaceutical Clinical Trials: Key Challenges and Practical Solutions

Transcript for "Radiopharmaceutical Clinical Trials: Key Challenges and Practical Solutions": My name is Lucy Knight. I am director of project management at PSI, and I'm part of a dedicated team of people delivering ready pharmaceutical trials. I want to share with you today a little bit about how we're overcoming some of the additional complexities that these studies are bringing to us. We are part of a community that's working in this space, and I think it's really important for us to talk about how we operationalize these types of studies and what makes RLT trials different from studies with nonradioactive IP. To get a drug to the point of approval, global expertise is, of course, essential. PSI is a CRO with a track record of delivering phase three and pivotal radiopharmaceutical trials with different targets and different indications and with different isotopes. But what's really important to us is how we take the experience we've gained and feed this expertise back into our operational processes and plans. For example, we've developed a radiopharmaceutical training program, and all of our monitors must pass an exam before they can go and monitor at the radiopharmaceutical site. We deliver workshops, and we hold regular lessons learned meetings. And we have also developed a guide for project managers on how to deliver, RLT trials. And this is our agenda for today, and there are five key areas where I think radiopharm trials are different from drugs with non radioactive IP. The first is in radioactive drug management. The second is having specialists who can support with imaging and dosimetry who are part of the COA project team. The third is how we facilitate site logistics and also how we're supporting our investigators. And all of that is helping to deliver enrollment either ahead of time or on time. And the last pillar to talk about today then is how we monitor radiopharmaceutical sites because this is different with unique aspects to it. So the first, aspect then that we are going to discuss today is radioactive drug management. Drug is not at site prior to initiation in these studies. It must be ordered, delivered, and dosed on a per patient basis. And for theranostics to these, this means timing the delivery of both the imaging and the therapeutic agents. And often, actually, we also have to maintain a window between administration of the radioactive IP and the standard of care drugs or the procedures. The half life of isotopes can vary quite a lot, but what's really important for us is understanding the shelf life. So that is the man maximum time then from manufacture to dosing, and that includes, of course, the decay that will occur during the shipment. If we're going to use airports to transport our IP, then we have to check there's no embargo on radioactive goods. And if the imaging agent has a short half life, then it may be necessary to have a cold kit manufactured, and that would then be radio labeled by central radio pharmacies who would then ship the product kind of ready to use to the sites. And if we're going to go down that route, then we need to qualify those radio pharmacies, and we need to factor in the time to do that as part of our start up timelines. We also need to think about the stock level of those cold kits at the central radio pharmacies. We have to monitor that, and we have to make sure we've set the right threshold to trigger reordering. And we have studies where sites are doing their own radio labeling. And if that's the case, then it's really important for us to understand how the isotope is going to be sourced. And on some studies, we have a combination of different manufacturing processes that are allowed. And in a scenario like that, you need to have dedicated drug managers in every region. Site selection is driven by logistics, for example, by proximity to airports or to central ready pharmacies. And we need to factor in the lead time for, the different IP. We need to place orders in advance, a specified number of days before dosing. And once the dose then arrives at the site and its, receipt is acknowledged, then a QA release process needs to be completed before, the drug can be administered. And something that's, interesting and can vary between studies is that due to the nature of the disease, we need to be prepared that for some indications, we may need to be rescheduling or canceling a certain percentage of doses as well. So here are some of the steps then that we have to think about when it comes to radioactive IP management. What's most important actually is that all the key aspects of the drug supply process are very clearly described in the IB, in the drug management plan, in the pharmacy manual, and in the IRT guidelines. And it's really important because of the complexity of the processes that we don't rely on self study of these documents and that we provide, instructor led training from experts. And we always discuss with the sites if they have restrictions regarding the time between receipt and dosing and when dosing is performed. A lot of hospitals will only dose patients, for example, on specific days of the week. And we are supporting sites with scan and treatment scheduling by providing them tools such as a participant visit calendar, which would have automatic calculators built into it for these time dependent procedures. We are thinking about we're asking the sites about the availability of the administration rooms and the radiation limits. We need to check these to make sure that there is capacity for the study. And depending on the size and the countries involved in the trial, we need to consider using IRT for drug management. It needs to be set up very carefully to reflect the patient visit schedule and the ordering requirements specific to the protocol. It means then that we have an audit trail with all the orders placed, that we have visibility on expected cycle dates, and we know in real time when orders have been placed. We would receive alerts if orders have not been placed as expected. And in many cases, there is a only a certain number of doses that can be produced each week. And in that in that scenario, it's critical to keep track of the patient's schedules and making sure that doses can be delivered on time, and IRT is doing this automatically for us. So the second pillar for success then is providing specialist support as part of the project team for imaging and dosimetry requirements. If the CRO has those specialists on staff, then they can support the project team and support the sites and reduce the burden on the sponsor. So radiopharm trials are really relying on the expertise of qualified nuclear medicine technologists, dosimetrists, and radiopharmacists. Their goal, when they're part of the project team is to support the sites and the vendors, to ensure that the time required to qualify the different pieces of equipment, such as the dose calibrators, the specs, the pet cameras, is not rate limiting to site activation. They are providing comprehensive tracking for all the steps that's tailored to the needs of the study. They are providing a technical review of the RAM licenses early in the process. That's to make sure that the right, isotopes are included with the right capacity, and they are local specialists. So they are checking country specific requirements. Maybe they need to the areas where the dosimetry and the imaging are going to be performed, or maybe a daily maximum use permit is required in addition to the license as well. And the imaging and dosimetry endpoints are crucial for these kinds of trials. So ensuring timely submission of scans to the imaging vendor is really important. Imaging specialists can check and discuss with the sites in real time if the sites have been done according to the schedule, and they can check that the CRF's been updated. And we need to ensure very regular reconciliation of the CRF with the imaging database as well. We all know that different isotopes have different challenges. An example here would be actinium two two five. It decays into multiple daughters, and those daughters are producing alpha and beta emissions until it re reaches stability. And what this means is that there are multiple photo peaks on the scans, so energy windows have to be set then for each spec acquisition. And the imaging manual needs to include this information, and the imaging specialist can support the sites then in exactly how to do this. And this is just showing you some of the typical challenges that sites are having with imaging a dosimetry dosimetry for this type of clinical trial and how those can be avoided or solved. Our aim is to support the sites to complete all the necessary trial qualification steps within a maximum of four months from the date the sites receive the imaging questionnaire to complete. And on a recent study, our global average was forty five days. And we're doing this by providing a live tracker for questionnaires, for queries, imaging qualification, and for waivers. We are also supporting with dry runs and mock shipments if those are needed to make sure that all the aspects of the drug supply process are working together with the setup of each individual hospital. Those orders have to be placed upfront. We are providing calendars with dose availabilities weekly or biweekly to ensure that the site's orders can be accommodated. And even though the IP is then not for human use, in some countries, import permits are required and have to be organized, and we support with that. And what's really important to say is that having local technology specialists always on standby is, really important to support the sites, with everything that they need to complete these qualifications timely. So the third pillar then would be facilitating site logistics and supporting investigators. It's really key to understand the setup of each and every hospital as part of the selection process. Sites in radiopharmaceutical trials need the right balance of therapeutic experience, access to a relevant participant pool, and technical capabilities, And CRAs need to coordinate interactions between PIs, subIs, radiologists, nuclear medicine technicians, medical physicists, and a biometric department or the off-site imaging facility. And this is even more important in multi indication radiopharm studies such as all solid tumor or basket trials. We need to avoid logistical issues by checking equipment availability early in the process. It's really important for us to know if sites plan to change or upgrade any of the qualified equipment. For example, a dose calibrator or a gamma counter because in this case, re qualification would be needed. We need to know if a phantom is available at the site and if it can actually be used for the trial because it will need time time to decay after normal use. So purchasing or loaning of phantoms is is expensive, and therefore, we really need to assess this upfront. And generators are also expensive, so we need to look at local solutions. Maybe one of the hospitals can act as a supplier for other sites, so then this is good for the patient because they can go to their, to the hospital that's most local to them. And if the study requires PK, we need to check the local radiation limits to make sure that, the sites can store the samples for the required amount of time. We also need to think about those countries where an IATA certificate is needed to transport samples with a certain, amount of radioactivity. And you may know that to get this certification, sites sites have to undergo a four hour training, and they have to pass an assessment. This also has a cost, associated with it, and we need to check with sites upfront if their staff already have this qualification. And if not, we need to arrange this. Sometimes people are asking the question, well, what support do we need from investigators on a radiopharm study compared to a study with nonradioactive IP? Radiopharm studies tend to have stricter enrollment criteria with limitations around IP availability. And this means then that investigators have to take, strategic decisions about treatment and trial enrollment. For example, they may want to put a patient on a bridging therapy. We need to make sure that that bridging therapy then isn't exclusionary. So having a collaborative research team is really important to the PI because it's a more dynamic process to manage eligibility and to schedule, dosing. The fourth pillar is ensuring on time enrollment. It's so important to understand the prescreening funnel and how patients are going to come on to the study and then to track the potential start dates for screening, for the imaging scan, and for dosing. And this means that monitors need to very regularly contact the sites to collect information. We also need to very carefully analyze the reasons why participants might not progress to dosing. We need to support investigators to carefully manage the expectations of participants if their eligibility for treatment is going to depend on the result of the PET CT scan. In some studies, there are high percentage of imaging scan failures. This may be the case of those different indications or those different stages of patient treatment being tested, and some protocols require a quantitative approach or maybe they have a threshold for positivity. So patients are having to visit different locations within the hospital, and we need to make it straightforward for them as we possibly can. And to support the consenting process, we can provide a study discussion guide. We can use this to serve as the referring physician letter. And if the indication is still quite new for radiopharm, then we would always recommend providing educational materials to the patients as well. I can't emphasize enough. It's it's the case on on many types of study, but especially radiopharm that detailed planning for successful investigator meeting is really important, especially having live training for imaging and dosimetry. And what's also important is scheduling regular teleconferences with investigators in different regions so that we can provide updates, for example, on dosimetry and safety data or on response rates because this can be very motivating to, encourage enrollment. This slide is showing, the patient pathway for a non radiopharm study, just for screening up to the end of cycle one. And you can see that it's relatively straight forward even though PK is involved, even though the eligibility is being checked by a medical monitor. But what you can see on this next slide is a typical, patient pathway for screening through cycle one for a radiopharm trial, and you can immediately see how much more complicated it is, and how many more steps there are to complete. It's really important in radiopharm studies that we map out the patient flow in relation to the timing of the imaging scan, the dosing, and considering the lead time for the IP ordering. And for some studies, there is a actually a two step eligibility confirmation so that each patient only receives the radioactive imaging scan if they are already confirmed eligible based on all other criteria. And if it's a diagnostic study, we may need to adhere to very specific gaps between imaging scans and standard of care imaging. And we have to confirm the subsequent dosing cycle ahead of time to preorder the IP. So for RLT trials, then the pathway needs to be customized for every individual site to align the product ordering and the delivery with the site procedures and time points for the receipt, the scanning, and the dosing. And we can then use this pathway to run a mock patient through each site before they are activated, and we can attach an inclusion exclusion criteria card to this so that the sites have everything very conveniently in one place for them. And the last aspect that I wanted to discuss today is about how monitoring of a radiopharmaceutical trial differs from a traditional nonradioactive IP trial. There is additional complexity, and there are unique risks and considerations. So the monitoring plan needs to be specific for this type of study with its own template. No IP will be stored at sites, so we're going to use those preparation records, IRT printout, shipment documents, IP logs for drug accountability. The monitors on radiopharm studies have to visit, additional facilities, and that means that they need extra time. And we need to clarify and confirm the what the expectations are for those departments that we can't visit in person, for example, radiopharmacies or hot laboratories. We might need to have separate ICFs, for example, for dosimetry and PK assessments if they're not mandatory for all the patients. And our central monitoring also considers different criteria as well. So here we are proactively identifying and addressing risks, setting up key risk indicators with thresholds to then track those risks across the sites. For example, we might be looking at the rate of missed PK samples or the number of not done spec CT CT scans because we know that this could impact the endpoints of the trial. We also need to, monitor the amount of radioactivity that's delivered to the patient. We need to confirm this with an appropriately calibrated dose calibrator before and after the administration of the study drug. And if there are cases when the results are indicating that the dose is too low or too high, then it's really important that we conduct an investigation then with the manufacturer and the site. And in terms of data entry, it's even more important to provide clear guidance, because for radiopharm trials, we are collecting data from many different departments at sites. And some of these procedures and some of the assessments might have country or site specific aspects to them as well. So to summarize then, there are five key areas that are distinguishing delivery of a radiopharm trial from those with different classes of IP. Drug supply, manufacturing, transport, delivery, and administration must be very clearly described in study documents with instructor led training providers. Imaging and dosimetry experts should be part of the CRI project team, supporting the sites and liaising between the vendors and the sponsors. We need to identify and coordinate all the trial requirements and the stakeholders at the sites. To enroll the studies on time, we have to educate and support the trial participants. And there is additional complexity when monitoring radiopharm studies. So this means then that a comprehensive and RLT specific monitoring plan is absolutely essential. And in summary, what I would say then is that collaboration between the CRO, the hospital sites, the trial sponsor, and all the vendors, including imaging and dosimetry is is critical for efficient trial execution. And as the CRO, we need to essentially coordinate and proactively manage aligning all the activities. Thank you very much for listening today.