From a clinical operations perspective at a US-based pharma/biotech company, conducting international clinical trials can be a bit more challenging than conducting a domestic clinical trial, but with appropriate planning and organization it can be an exciting experience while being effective at the same time.
Once you have a study design and protocol in place, there are many things to consider. You must look at your company’s internal resources and determine what expertise you have versus what expertise you need. That will be vital in determining which tasks you can take on and which tasks require outsourcing. The majority of US-based companies that conduct international clinical trials require some sort of outsourcing, and determining the appropriate outsourcing model is extremely important. There is the ‘full-service model’ (all-inclusive CRO), the ‘functional model’ (a specific vendor for each service need and function), the ‘hybrid model’ (company control with access to SOPs and expertise of a full-service CRO), and the ‘risk-sharing model’ (strategic partnerships with shared risk and shared reward).
Whichever outsourcing model is chosen, it is extremely helpful to actively engage the CRO (or multiple CROs) in the clinical trial development and start-up phase as early as possible. From the perspective of a US-based pharma/biotech company, it is important to choose a CRO that can properly inform you about the national regulatory requirements to ensure compliance and meet the timelines associated with various international submissions. There are often substantial differences when managing an international clinical trial versus a domestic one (e.g., patient reimbursement policies); therefore, capitalizing on their expertise is invaluable. It is important to be able to answer the question “Do you do want a CRO from the Unites States to manage your sites in Europe?” Sometimes the uniqueness of the CRO can offer valuable advantages that should not be overlooked but the most important thing to remember is that candid communication up front regarding strategy and expectations is vital to the selection of the appropriate CRO for your international trial needs.
Once the CRO is chosen, the real teamwork effort begins. Teamwork is critical in building a collaborative relationship and I believe that is vital for effective trial management. In an international clinical trial, this can be the most challenging component because of geography, cultural differences, and even language barriers. You can’t necessarily control the successful outcome of your clinical trial but you can control the success of your relationship with your CRO.
The best way to start building a relationship with your CRO is to make the CRO an extension of your internal team. Begin with a face-to-face kick-off meeting and build a rapport to create structure with flexibility. Set mutual expectations and areas of responsibility but be willing to shift them as needed during the course of the trial. And don’t forget the power of laughter in developing a positive relationship!
While managing the ongoing clinical trial, it is important to create an environment that is open to suggestions and creative thinking not only from the CRO, but also from the clinical sites and the site monitors. Collaboration is a skill set and the art of ‘listening’ is a powerful tool. When a Sponsor maintains total power and control, they leave little room for learning and progress. Sometimes a simple question from a site, a monitor, or a CRO can lead to a productive discussion that leads to improvement in the conduct of a clinical trial. Always remember to be open to suggestions.
While it isn’t always logistically possible to schedule multiple face-to-face meetings between the Sponsor and the CRO or sites in a clinical trial that is conducted internationally, regular teleconferences with your CRO and site investigators are critical to effective communication. Even occasional Sponsor visits to the sites can be extremely effective in the successful conduct of a clinical trial and should be factored into the overall study budget whenever possible.
Managing international clinical trials can present challenges, but by focusing on good communication and the development of positive relationships with your sites, your vendors, and your monitors, can mean the difference between success and failure. When sites are happy and feel as though they are an important part of the team, they focus on study recruitment and are eager to enter data and resolve queries in a timely manner. When monitors are happy and feel as though they are an important part of the team, they are more willing to step up to help meet critical data monitoring deadlines throughout the study. When CROs are happy and feel as though they are an important part of the team, they make themselves available to meet the needs of the study and are more likely to adopt the ‘whatever it takes’ attitude.
Data cuts for interim analyses and database lock can be especially challenging in any clinical trial. They often become even more challenging in an international trial because of time zone differences and various country holidays that interrupt work flow. Every effort in the beginning that is devoted to developing a collaborative team and positive relationships (as well as maintaining them) will be well worth it in the end.
If CROs can continue to deliver dependable, quality service at a competitive cost, US-based biotech companies can expect to see increased reliance on outsourcing models to support global clinical development. If we nurture and value the relationships with our CROs and vendors, we can maximize the benefits of the services they provide. And if Sponsors can maintain positive and collaborative relationships with sites and site monitors in spite of geographical distances, the conduct and overall management of international clinical studies will be far more efficient. Remember that true synergy increases effectiveness and equals success!