If you’ve ever had to manage a trial with underperforming enrollment levels (chances are, you have!), you know firsthand the headaches this can cause. Teams often feel overwhelmed and helpless.
I first blogged about this subject in 2015. In general, clinical trial sponsors are much more proactive when it comes to planning their study enrollment strategies and tactics than they were back then. In fact, the number of enrollment rescue projects we support here at Imperial has continuously declined for more than a decade. These rescue projects are being made obsolete by proactive, well-planned enrollment enhancement programs. The COVID pandemic has shifted that trend into high gear. Without proactive planning for how to find individuals who qualify, and also how to bring the study to them, the study is dead in the water at site initiation visit.
Technology to the rescue?
We have seen the introduction of amazing new technologies, yet they haven’t caused a seismic shift away from the old ways of educating, enrolling, and retaining participants in clinical trials.
But the availability of these technologies, combined with a raging global pandemic, has created a true catalyst for change. Where does that leave us now? Well, it leaves us with a hybrid approach, in terms of how trials will need to be conducted, and also in terms of what tactics can be employed for turning around a slow enrolling trial. The fact is, some of the tried and true ways remain. These have been supplemented by new approaches that leverage technology and the realities of today’s world in terms of decentralized approaches to study conduct, patient centricity, urgency, and more.
Addressing enrollment up front
The proactive sponsor that focuses on enrollment up front will not make these once common mistakes:
- Over-reliance on brick and mortar study sites for all elements of enrollment and study conduct. Decentralized approaches will likely need consideration for at least some study visits. This includes:
- Mobile health vehicles
- Screening camps
- At-home study visits
- Virtual visits
- Lack of planning around logistical hurdles: how to get study materials and equipment where it needs to go in time for site visits and initiations. Common hurdles include Brexit, Importer of Record requirements, EORI numbers, and COVID-driven supply chain issues.
- Lack of stakeholder input during protocol development.
- No study and site feasibility analysis.
- Investigator grants, contracts, and relations not competitive or included in planning. Sites will prioritize enrollment for trials they are being better compensated for. They will also prioritize work for sponsors who care, who check on them to ensure they have what they need, and are interested in building long term relationships.
- Lack of availability of patient recruitment expertise and support at study sites.
- Not fully understanding patient volumes, catchment area, and sources.
- Not considering patient mobility and transportation access.
- No contingency planning.
- Lack of real-world data elements to determine pockets of disease prevalence, clinicians treating highest volume of eligible individuals, epidemiology data.
- Incomplete diversity strategies.
- Misalignment of information with health literacy levels in target population.
Addressing enrollment after the fact
Yes, it’s nice to hear that slow-enrolling trials aren’t as common as they used to be. But how does that help you when you have a trial with slow enrollment? Here are some tips.
For many sponsors, too often, the approach to addressing slow enrollment is to add sites and extend enrollment timelines. While that approach might ultimately be needed, there are other approaches that can be made first to rally the troops and right the ship.
In order to combat low enrollment, you need a solid plan of attack. This plan needs to be proactive, thoughtful, and aggressive.
Make the medical community your ally
Sponsors may be tempted to conduct an aggressive and expensive direct-to-patient marketing campaign. For highly prevalent, chronic conditions, such an approach might work. In today’s research environment, protocol complexity is increasing, and FDA burden of proof on clinical trials and drug approvals is much more stringent. Thus, finding patients for today’s study protocols often requires a different approach – one that leverages the expertise of the medical community to properly identify the correctly diagnosed patient and initiate a referral to study sites.
A hidden benefit of this methodology is that approaching the medical community about your trial does not require IRB approval. In a rescue situation, time is of the essence – a medical community outreach initiative can be executed quickly and begin paying dividends while you ramp up other initiatives.
Some CROs and sites have developed medical advisory panels for this very reason. Being able to translate study protocol requirements and targets to the real-world care and treatment regimen is critical. Does this patient exist as defined in the protocol? What is the standard of care? What is the treatment pathway they most often follow? Are they mobile, and can they visit the study site? Are they more likely to be found in urban or rural communities? Do they have concerns or skepticism about clinical trials? Medical advisory panels can answer these questions.
You might have attended one or many investigator meetings where the investigators hypothetically tear about the study protocol because the patient described doesn’t exist in that form, or the requirements to get that patient study qualified are too stringent. The medical perspective helps, and study coordinators can offer real-life operational and logistical perspectives. Where are these patients locally? What transportation methods are available? What issues might we face with retention? Study coordinators will help.
Plan, plan, plan
So much of the above is far from magical. It’s like anything else in life – planning plays a critical role in the probability of success. Sites and medical advisors can give you a leg up. Get them involved EARLY!
Thankfully, over the course of my career and a lot of trial and error, I’ve learned a few golden nuggets with regards to turning around slow-enrolling trials. This blog post comes from years of experience supporting sponsors facing enrollment challenges.
I’d love to hear from you. What approaches have you found to be successful?