By Roger Tell, M.D., Ph.D.
In recent years, global clinical trials have become standard, and for a good reason. In broad terms, expanding clinical trials across the world gives the investigational drug better opportunity to demonstrate its true impact.
Global clinical trials offer key advantages to patients and industry; however, smaller companies may be hesitant to partake, wondering if the inevitable challenges outweigh the benefits. Companies with limited resources may struggle to handle relationships among necessary external contacts, including CROs, investigators, and regulatory agencies. Throughout my career as an oncologist and in my role as the chief medical officer at Isofol Medical, a Swedish biotech company running a global Phase 3 clinical trial in advanced colorectal cancer, I’ve become familiar with several best practices to overcome many of these issues.
In this article, we’ll look at three key considerations when designing a global clinical trial: selecting the most appropriate trial sites with a representative patient population, choosing to work with the right partners, and ensuring you are up to speed with local regulatory and clinical requirements.
SELECTING THE RIGHT LOCATIONS FOR THE TRIAL
When planning for a global clinical trial, the site selection process is one of the most challenging tasks. Multiple elements must be taken into consideration. First, it’s important to strategically select trial sites in different geographic locations with a representative patient population and a proper market for the investigational drug. This varies based on the drug’s intended indication and the disease epidemiology. For example, the selection process can be limited for an indication that is more common in particular regions or population demographics. The selection process tends to be broader for indications that have an international public health impact or generally affect people broadly, such as cancers.
Isofol currently has sites up and running for its Phase 3 clinical trials in the U.S., Canada, Australia, Japan, and Europe. What is their common ground? Each region has a high incidence of, and an unmet need for treating, advanced colorectal cancer. In addition, regulatory agencies in each region want to see locally sourced data, requiring trials to be performed there for possible approval.
SELECTING THE CROS AND EXTERNAL PARTNERS
In addition to reaching the patients most in need in the appropriate global regions, it’s important to carefully evaluate all external partners who will be involved, including CROs, advisors, and principal investigators specific to each region. Their influence and commitment to the trial is a crucial success factor. Ensuring that you have open lines of communication will help streamline what could be years of mission-critical discussions.
Selecting the right CRO is one of the most important decisions a company will make, especially for a company with limited resources. CROs provide access to virtually everything needed to fully execute a clinical trial. They improve efficiency and increase productivity, allowing the company to focus on overall strategy and goals. From personal experience, I know that it is crucial to choose a CRO with a management team, experience, capabilities, and relationships that best align with the trial’s design. A CRO with a proven track record and experienced team in the given therapeutic area in a specific region is also a plus. This ensures that they are up to speed with rapidly changing standards of care and regulatory updates. Take time to fully evaluate their patient statistics and assessment of timelines. Know the organization inside and out before making a decision. Their ability to execute is critical to a trial’s success.
"Companies often make the mistake of working with a different CRO in each region, making the entire process more difficult to oversee."
When working with CROs in a global clinical trial, the phrase “less is more” comes to mind. Companies often make the mistake of working with a different CRO in each region, making the entire process more difficult to oversee. Ideally, companies should work with one CRO that is capable of working in multiple regions; otherwise, they should use as few as possible. This may be challenging, as conducting trials in some regions requires working with a local CRO that is knowledgeable about its specific market and regulatory guidelines. One key factor is finding balance between streamlining the CRO relationships and having the best local talents. Once companies have the right CROs on board, they must make sure there is constant communication among CROs and between the CROs and the trial sponsor.
Collaborating with the top physicians who can serve as local principal investigators for each region is another success factor. Their expertise, guidance, and face time with patients greatly impact many aspects of the trial. A global clinical trial requires building relationships with leading physicians in the spaces specific to each region. The time investment is invaluable. All effort spent during the planning process will have a significant impact down the road if you can ensure that a trial runs smoothly by selecting the right people.
Appointing investigators with top-notch medical experience specific to a trial’s indication is important, but the selection process runs deeper than that. Taking on the responsibility of a lead investigator of a trial is a heavy lift. Some large trials can last up to four years. Investigators need to be flexible; they must have the time and willingness to participate in all required tests, visits, training, and conversations specific to the trial throughout this extended time period. The more experience an investigator has with the clinical trial process from previous work, the easier it is to ensure that they will be ready for the commitment on your trial.
REGULATIONS: AN ONGOING CHALLENGE TO A GLOBAL TRIAL
Once the trial site, CRO, and investigator selection are completed and the global clinical trial is running, constantly making sure you are abiding by changing regulatory and clinical guidelines is an enduring and ongoing challenge. In a perfect world, a universal protocol would be the answer, but this can be difficult to create and maintain in the current climate where regulatory standards among countries often differ significantly. Standards of care and ethical practices are different in every country, and language and cultural barriers are inevitable. There isn’t a “one-answer-fits-all” for such challenges, but there are ways to prevent the problems they tend to cause.
Preparing a strategy that best fits the different local regulatory requirements will result in a practical trial protocol. Partnership-oriented approaches where local partners are familiar with local requirements, as well as up-front dialogues between CROs and investigators, are crucial for avoiding miscommunication. Overall, constant and effective communication among all internal and external parties is key to keeping everyone on the same page at all times. How is this accomplished?
Use your time wisely. Time is even more precious when working with partners across the world.
Communicate with external parties often and have a plan. Despite the timing, language, and cultural barriers, don’t leave a meeting with anything unresolved.
Make sure everyone is in agreement at all times.
Running a global clinical trial can seem like an insurmountable challenge, but paying attention to important factors such as selecting the most appropriate trial sites, choosing the best partners, and always being aware of changing regulatory landscapes can help you stay ahead of roadblocks along the way. Taking time to plan ahead, especially for a process that could last for several years, will have major payouts.
DR. ROGER TELL is the chief medical officer, chief scientific officer, and senior vice president at Isofol Medical in Gothenburg, Sweden. He has extensive experience as an oncologist and as an advisor to a number of biopharma companies, including Eli Lilly, AstraZeneca, and Merck Serono.