By Beth Harper & Audrey Rossow
As a CEO of a biopharmaceutical company, have you ever found yourself wondering the following:
- Our compound is so compelling, our science is great, so why are we having enrollment problems?
- Why does my staff seem so afraid to let me know about the enrollment issues?
- Why hasn’t anyone ever told me that the likelihood of us having enrollment difficulties will be 80 percent or greater?
- I’m paying the CRO a fortune; why aren’t they managing enrollment better?
If you answered yes to any of the above, you aren’t alone. The fact is — enrollment is difficult. It always has been, and it always will be. There are no silver bullets or quick fixes. It is complex, and there is no “one-size-fits-all” solution to fix it. But you can do something about it. What follows are insights for the simple things you can do to mitigate the most common problem that every study (with very few exceptions) will inevitably face.
BASIC FACTS TO RECOGNIZE REGARDING …
You may have a blind spot about the enrollment issues based on your focus on other issues, your passion for your compound, or your confidence in your team. It’s important to recognize that you can never truly outsource enrollment management. While you may be able to find phenomenal “child care,” ultimately, the study is your “baby.” No enrollment = no data = no answers = no approvals. While you can involve your CRO in the process, don’t expect them to own it. You also need to appreciate that enrollment is expensive; whether you pay now or later, either way you will have a significant investment toward achieving on-time enrollment.
Your Clinical Operations Team
No matter how qualified and experienced they are, they will be hesitant to call your attention to any issues thinking that they have things under control. The team is always thinking, “How do we tell the truth about enrollment in a way that it demonstrates reality without management hitting the roof?” They may want to be protective of the information or will want it to appear on track for fear of getting in trouble of some kind. So, they spend endless hours going through many machinations to vet and position the information, but this won’t hide the overarching reality (also their time could be much better spent on other things). The team will often manage all of this stress surrounding bad news by managing detailed site-activation status trackers and the like, setting up a pattern in which the data is scrutinized for the answers to the problem — the tail is now officially wagging the dog. Meanwhile, the enrollment problem worsens.
"You may have a blind spot about the enrollment issues based on your focus on other issues, your passion for your compound, or your conﬁdence in your team."
Your CRO Partner
Your CRO may have more incentive to add enrollment rescue services (via change orders and more costly interventions) than they do to achieve on-time enrollment, unless you have an air-tight performance-based contract. They also will quickly get paralyzed if they feel all the blame for poor enrollment has been shifted to them; after all, their internal KPIs may differ from the sponsor’s KPIs, a nuance that may create a fissure in the CRO-sponsor relationship, as well as the creation of the “elephant in the room.” Remember, they are not enrollment experts. Enrollment is a mix of art and science and can’t be distilled down to quick fixes. So, the tendency will be to turf the problem on to the sites (even though they supposedly selected the best ones possible through a rigorous site-selection process).
Unfortunately, sites are potentially rewarded for being overly optimistic about enrollment and disincentivized for being truthful about their true enrollment potential. They are hoping to be asked for input about the study design and its executability, and they will be honest about sharing the challenges and their study support and enrollment needs if you just ask them! Be sure to set realistic expectations of them and treat them like a valued study partner.
Now that we have your attention with some of the brutal truths about the enrollment problem, here’s what can be done to address them. While everyone would ultimately like more up-front time and preparation to establish more realistic enrollment timelines, the reality is that competitive landscapes, financial pressures, and an unrelenting determination to bring more meaningful treatments to patients will always drive the need to get enrollment done as quickly as possible. Let’s start with the dreaded rescue situation.
WHAT YOU’LL BE TEMPTED TO DO, AND WHY YOU SHOULDN’T DO THESE THINGS!
When enrollment starts to slip, study teams often default into the following go-to interventions, most of which rarely work.
By now you are getting the sense that we are strong advocates for conducting a thorough root cause analysis of the enrollment issue (Hint: There are over 150 reasons for why sites fail to enroll. Seriously. We have literally mapped this out!). We are also in favor of asking the sites what they need and creating site-specific solutions.
That said, there are times when it makes sense to bring in the expertise of a patient-recruitment services provider. There are currently more than 140 of these kinds of companies. Here are our top three recommended questions to ask when evaluating a potential patient-recruitment services provider:
- Tell me how your methodology or recruitment approach is tailored to the specific nuances of my patient population/disease indication?
- How do you maximize the site’s ability to actually enroll the patients you refer to them?
What is your specific approach to providing site-specific support?
- Explain your payment structure and the milestones upon which you are paid. How will you guarantee success?
METRICS THAT MATTER
As the saying goes, you can’t manage what you don’t measure. The same holds true for enrollment. While study teams track typical metrics (the ubiquitous site activation and enrollment curves and screening/randomization rates), these often prove to be of limited value when it comes to actively managing recruitment and retention. Better leading indicators for managing site-enrollment performance include:
- systematically measuring activity across all aspects of the recruitment funnel
- The number and percent of patients failing at prescreening, consenting, screening, and post randomization drop-outs (including the key reasons for the losses)
- the number and percent of sites actively prescreening, screening, and enrolling on a monthly basis
- the time from site activation to first patient in or first patient visit by site and overall averages
- Hint: Generally speaking, unless it’s a rare disease, if it’s >30 days, you’re in trouble!
- number of days since the last patient screened.
By defining expected thresholds and more systematically tracking these KPIs, you and your teams will get much better visibility into what is happening and areas to target for intervention.
PROACTIVE RECRUITMENT OPTIMIZATION — TIPS FOR SUCCESS
Beyond some of the “rescue interventions” and metrics suggestions that we have already outlined, our top tips for proactive enrollment management are included here.
TOP RECOMMENDATIONS FOR CEOS:
- Anticipate that enrollment will be a challenge. Plan for it to be a problem from the get-go and proactively put all contingencies in place.
- Get educated about the complexities of enrollment.
- Always ask yourself if you would enroll your parent/sibling/spouse/child in the trial your team has designed. If not, why not? Put yourself in the shoes of the patient and challenge every aspect of the trial to ensure it is as enrollable as possible.
- Keep a close connection to the sites. Ask for and be open to their input during the protocol design stage and throughout study execution.
- Don’t nickle and dime site budgets. Enrollment only truly happens at the site; make sure the sites are resourced appropriately to implement your study safely and efficiently.
- Make it easy and comfortable for your team to share the truth with you.
- Help your CRO partners to be more successful by investing in a strong working relationship with them especially when the going gets tough.
- Recognize that your team may not be comfortable with (or experienced in) conducting a true root-cause analysis of the enrollment issues. Facilitate these discussions, bring them together, and go through this process before allowing them to throw everything at the problem.
- Never stop asking your staff, “If time, money, and resources were unlimited, what three things can I be doing to help you be successful in enrolling the study?”
"Unfortunately, sites are potentially rewarded for being overly optimistic about enrollment and disincentivized for being truthful about their true enrollment potential."
TOP RECOMMENDATIONS FOR CLINOPS TEAMS:
- Take off your ClinOps hat when the CEO approaches you. Be composed and succinct with the information you share and avoid “death by trackers” when speaking about enrollment performance.
- Spend less time tracking status, massaging the data, and QC’ing presentations for your CEO. Be transparent with the information and spend more time on understanding the root-cause issues and presenting solutions. Be prepared in 30 seconds or less to explain in a “thumbs up” or “thumbs down” way the current enrollment status. If thumbs down, express the one idea or suggestion that may help move the dial on the enrollment issue
- Truly understand the patient population and the patient care continuum to know who owns the patient relationship, how the patient navigates through the healthcare system, and the type of sites that are best suited to enroll the subjects before you start the site selection process.
- Never stop asking the sites, “If time, money, and resources were unlimited, what three things can we be doing to help you be successful in enrolling the study?”
TOP RECOMMENDATIONS FOR CROs:
- Identify and empower one person on the study team to take an objective bird’s-eye view of the enrollment across the sites and assess the overall picture.
- Mandate that the CRAs specifically ask sites questions around the patient population and the patient care continuum to understand who owns the patient relationship and how the patient navigates through the healthcare system. Develop a script if you must.
- Do not be afraid to ask managers for their help in enrollment issues — also speak to your colleagues in study startup, legal, site payments, and other functional areas to get their take on what they feel is their sphere of influence in the enrollment status at the sites.
- Identify and engage one or more team members at the sponsor with whom you can interact in a transparent and solution-focused way. Become their partner in the solution, not the bottleneck.
- Identify who in your organization is comfortable with (or experienced in) conducting a true root-cause analysis of the enrollment issues. Facilitate these discussions.
- Similarly, identify who at the sponsor is comfortable with (or experienced in) conducting a true root-cause analysis of the enrollment issues. Facilitate these discussions. Be the advocate for your sponsor within your organization. Challenge the status quo and ask every member of the study team to think differently about the true root causes of the enrollment problem and creative solutions.
If there’s one thing to take from this crash course, it would be to appreciate that the science of understanding how to optimize enrollment is just as important as the science behind your compound! While this article just represents the tip of the iceberg, we are always available to share more insights, additional tools, and helpful resources with you.
AUDREY ROSSOW is principal at A. Rossow Consulting. She has over 20 years of experience in pharmaceutical and biotech clinical drug development.
BETH HARPER is president of Clinical Performance Partners, a clinical research consulting firm specializing in enrollment and site performance management and facilitating productive sponsor-site relationships.