Brandy Lind, Senior Director of Operations, has been in project management at Rho since 2004. During this time, she has led several large programs and individual projects in multiple therapeutic areas. She has worked on observational trials, interventional trials, and Phase I-III clinical trials throughout her career.
According to a 2013 report by the Tufts Center for Drug Development, timelines are typically extended to nearly double their original duration in order to meet enrollment goals which is a significant contributor to increased costs. Hitting the clinical trial enrollment goal is not only important to meeting overall study timelines and budgets, it is critical to the success of the clinical study. If you don't have enough participants, you won't have enough data to support your objectives. That's why it's important to plan for enrollment just as you would plan for collecting and analyzing the data. In this post, we’ll share 5 keys to successful enrollment.
1. Identify sites with the most potential
It all starts by choosing the right sites. Research sites with experience in your therapeutic area. Are there existing site networks that can be leveraged? Check clinicaltrials.gov to see which sites are currently participating in similar studies or have in the past. One of the best ways to find qualified, high performing sites is to reuse sites that have demonstrated both an ability to enroll and produce high quality data. Past performance is one of the best indicators of how sites will perform on future studies.
Put the time in up front to complete a full feasibility. It can be tempting to jump right into site start-up, but time and money spent on feasibility upfront can save you time and money downstream by preventing protocol amendments and enrollment struggles. Ask sites about how they identify subjects, how many patients are already in their database, and how many patients come to their facility each month. Find out what they do when they have exhausted their own database. Competing studies can impact their ability to enroll on your study, so find out if they are currently conducting other studies in the same patient population. If they are, press for information about whether they have access to enough patients for both studies or if inclusion/exclusion criteria are different enough to allow them to support both.
Get feedback from sites on the eligibility criteria and feasibility of operationalizing the protocol. They may have suggestions for changes that can increase the enrollment rate without impacting the scientific integrity of the protocol. The sites also know the patients well and can help you assess patient interest. Consider whether the indication is serious enough that patients will want to participate and also consider existing therapies that are available to patients that may impact enrollment.
Study logistics can also impact patients’ willingness to participate, so consider the burden the schedule of events will place on participants. How long will visits be? Will they have to stay overnight? Does transportation to and from the site present an obstacle for patients? If you have an elderly or pediatric population, consider the impact on caretakers and how they will need to be involved in the process. Sites can help you identify opportunities to ease these burdens for study participants and their caretakers.
Finally, prioritize sites based on start-up timeframe, recruitment potential, and previous research experience. Make sure you also identify some back-up sites that can replace underperforming sites or be added later to boost enrollment. You can achieve some efficiency by getting these sites through start-up along with the main sites you have identified.
2. Set expectations with sites
Make sure you set clear expectations with sites from the beginning rather than waiting until you start to see issues. CRAs should work closely with each site to develop an individualized enrollment plan. Where will they get patients? What recruitment materials will work best for their site? Are there other healthcare providers they can network with to gain additional participants? A one-size-fits-all approach to recruitment rarely works.
Once sites are activated, have routine calls, individually and as a group, to discuss clinical trial enrollment strategies and plans. Have sites share what’s working and what’s not, share ideas, and build relationships. Find out from sites why patients don’t want to enroll. If you do have to adjust the protocol, the earlier the better. During group calls, have your high performing sites share lessons learned, tips, and successes.
Develop a plan for how you will address sites who are not meeting enrollment expectations. Give them all the support you can, but also be prepared to follow through with your mitigation plan if they are not able to turn things around.
3. Start with accurate projections
It is tempting to create timelines based on best case scenarios. Excitement about getting a new product to market, helping patients, and meeting investor expectations can all be strong motivators to be overly optimistic about enrollment projections, but this will just create more delays and increase costs downstream. Be realistic about how many patients each site can enroll each month based on feasibility -- you (and your investors) don't want surprises!
Consider study-specific issues that may affect enrollment like seasonal effects. Create graphics to show expected enrollment over time versus actual enrollment to date. Having this information at your fingertips can help you make informed decisions about whether to add a back-up site, change recruitment methods, and project when actual enrollment is likely to end. Use this information to continually reassess your upfront assumptions, so you can be proactive if enrollment isn’t moving forward as expected.
4. Build relationships with sites
Maintaining strong relationships with sites is critical. They provide key insights into the therapeutic landscape. They are close to patients and can help you understand patient concerns and perspectives, which can help improve recruitment and retention.
Use the investigator meeting as an opportunity to build and strengthen these relationships. Explain the importance of the study and the potential benefits for the patient population. Engage sites and make them a partner in your research. Creating a situation where sites want to work with you again will be of great benefit to future studies!
5. Collaborate with your CRO
Look for a CRO that acts as an extension of your team and sees your study as a collaborative endeavor. During enrollment, it's important to have constant communication between the Sponsor and CRO regarding the status of site activations and enrollment numbers, risks to the clinical trial if we are not on track to hit the goals, and mitigation strategies to get enrollment back on track.