It’s common for “standard” oncology studies to encounter delays, which are typically caused by challenges with enrolling the right patients according to their study timeline. The main reason for these delays is site selection. Determining the right investigator mix that matches your protocol criteria and enrollment timelines is absolutely critical, and many sponsors underestimate the time required to onboard and train the site to start the patient enrollment process.
For immuno-oncology studies, there are an entirely different set of complexities that cause additional delays. Immuno-oncology is a promising area of research, with thousands of new studies launching each year. Medelis has been pioneering immunotherapy studies since 2008, running many CAR T-cell therapy studies, checkpoint inhibitor studies and bispecific antibody treatment studies. This experience has allowed us to understand the most common causes of delays in immuno-oncology studies, which we will discuss below with recommendations on how to mitigate.
The RAC process is triggered by recommendation by an Institutional Review Board (IRB) or Institutional Biosafety Committee and it been determined to meet one or more of the following criteria:
It’s natural for sponsors to want a study to initiate quickly, but it is important to thoroughly examine the critical fine points of a study to mitigate increased trial costs and extension of timelines. The rule of thumb is the more complex the study, the more layers of approval that are required. Medelis, as a specialty oncology CRO, is comfortable to help you navigate this complex process, preventing delays by providing advice on which committees to engage. We understand the submission process at the site level and can help you best understand the timelines required to support your study and use our vast experience to guide you through the approval process, no matter how complex your study is.
Because many immuno-oncology therapy studies are new, it’s common for sites to have limited (or even no) experience in complex immuno-oncology trials. Immuno-oncology studies have a steep learning curve, so selecting a site with prior clinical trial experience in immunotherapies relieves the burden of training the site from scratch. Turnover is common at sites, so comprehensive training, even for experienced sites, is critical. If a site is new to clinical research, additional time for start-up, comprehensive training, and constant communication and support are essential to success. Even the most experienced sites may not fully understand how to budget for these types of new immunotherapy trials. Here’s more detail about how Medelis trains and manages sites for a CAR T-cell therapy study.
Additionally, if your treatment is BSL-2 or higher, it will affect site selection because not all sites have the processes or infrastructure to handle these types of agents, which require the use of surgical gowns, gloves, goggles, safety glasses and possibly a Class II biological safety cabinet.
Delivering new immunotherapies can create new challenges that extend timelines. Export of a drug is not a simple task. It is imperative to take the time to qualify and choose the right vendor as shortcuts can cause many study problems downstream. Medelis can help you develop a checklist and help qualify vendors in the RFP phase. When dealing with U.S. or European sites, there are manufacturer and export challenges to consider. After purchase of your drug, the drug needs to be stocked, labeled and stored. What are the risks to your drug if there is a temperature excursion? Take the time and incorporate the costs and to qualify a central lab. This information is key to document in the laboratory manual as well as the site procedural manual when getting ready to execute your study. Medelis is experienced to help you understand the drug-delivery challenges that may arise and offer solutions to mitigate unexpected challenges.
If your study is on multiple countries or continents, you may encounter delays or issues with transportation or delivery of drug and equipment. For example, some device companies will not export their pumps overseas. There are also risks to consider in delivering the immunotherapy drug. Will the drug product clog the filters at different concentrations? Can drug smell, viscosity or color cause unintentional bias in a blinded study?
The pump tubing may require validation, and use of an infusion pump in the US may differ from pumps being used in European countries. This may necessitate further unanticipated validation.
Several of the immunotherapy studies we’ve managed have required us to follow the NIH BioSafety Level 2 (BSL-2) Guidelines for the handling of therapies utilizing microorganisms associated with human diseases. As a reminder, Level 2 studies work with agents that are associated with human disease, Level 3 studies work with indigenous or exotic agents that cause serious or lethal disease via aerosol transmission, and Level 4 studies work with extremely dangerous agents that pose risk of life-threatening diseases for which there are no vaccines or cures can create shipping challenges. Make sure your vendor is well-aware of anticipating problems and managing the strict export control laws governing your study.
In addition to the export challenges, manufacturing of these new therapies, delivery devices and drug safety and storage tools can cause delays. Medelis can evaluate transfer of the manufacturing process, monitor expiration dates, conduct stability testing, validation and ensure proper labeling.
Understanding all of the above is necessary to properly evaluate the timelines of a complex I/O study. It’s common for sponsors launching their first immuno-oncology study to pushback at these extended timelines, but they’re necessary to conduct the study properly. It is imperative to have complete understanding of realistic timelines and cost and be sure it is built into the study. As an example of this, a client came to Medelis but did not factor in the cost and time to identify a central lab that was necessary to ship a drug on their behalf and prepare the necessary drug kits. One of the sites involved placed a hold on the study because the lab manual was considered incomplete. The study site would not submit to the IRB until this step was complete and placed the study on hold causing the sponsor an unexpected 8-week delay. There is time involved to perform due diligence in obtaining quotes and approving vendors. Once qualified, the details need to be incorporated into the lab manual. Cutting corners leads to the sticker shock of unforeseen costs and delays on the back end of a study. Even worse, delays can lead to potential patient safety issues.
Understanding these six causes of delays can help you prevent the unexpected and allow your trial to progress closer to the initial timeline. The Medelis team is highly experienced at managing the CRO, site and the sponsor levels. Our team offers the diversity and depth of experience to understand any roadblocks in study design and execution to mitigate potential risks or delays to timeline and ensure your study has the best chance of success. The expert team you meet during consult will be the same team to close out your clinical study report.
Connect with us if you’d like to discuss your upcoming immuno-oncology study.