Why is my patient retention rate so low? How can I better reach potential participants? What are the bottlenecks in my workflow?
Chances are, these are questions you may have asked yourself at some point about a clinical trial that you have worked on.
As part of WCG’s “Stump the Experts” webinar series, we called upon our industry peers to submit their most burning questions about patient recruitment. Mark Summers, President of Patient Engagement at WCG, and Molly Hair, Director of Site Engagement and Management at WCG ThreeWire, came together to provide their insights, tactics, and strategies for these questions.
Let's start with the way not to do it. I started my career at a site, so I've lived through this. You never want to do an estimate of the number of patients you may end up with. For example, "I've had 50 patients in the last 90 days and surely 10% of them will enroll, so I should have five enrollments 90 days from now." That's not the way to do it. The way to realistically forecast enrollment is to literally develop a flowchart beginning with study candidate identification, how that is going to be done, and following that all the way through to scheduling the initial office visits, attending office visits, all of the site's screening processes.
You would then get into the processes that have to happen at the site, mapping out who's going to do each of those steps. Because identifying patient candidates is often easier than solving the problem of site bandwidth, it’s very important to map that all out. Be sure to map out the associated time, making sure you know who will be assigned to specific tasks. I've very seldom seen that done when that is not an eye-opening exercise. When there are gaps in your processes, ask yourself how are those gaps going to be filled? Make sure that simple things, simple questions are answered.
If you're going to have a screen fail rate of 70%, which is not uncommon, that means for every 10 consents you're going to get three enrollments. That means you're going to have 7 screen fails. If your site is booking appointments four to six weeks out, then that's a built-in delay right there that you're going to have unless you can create additional bandwidth by scheduling a Saturday morning clinic or a Thursday evening clinic just for clinical research patients, which many investigators are willing to do.
My advice would be to extend your hours to a night or weekend or several nights during the week. I think that is a pivotal component to the success of the site. If sites are new to clinical research or they're looking for ways to revamp their model at their site, that would be one of the number one steps that I would suggest.
Additionally, about the overall question, sites really do need to be honest with themselves about what competition is at their site. Not just competition for the patient but competition for their team's time and competition against maybe less obvious sources like the standard of care. Perhaps there's a study where the standard of care tends to be working, so what is the motivation of the of the patient to participate in a new clinical trial? Those motivations can be there. It could be the investigational drug has the potential to provide an adverse reaction that's less significant than the standard of care, something like that. But, you must, again, have the time to explain all of that to the patient and really develop that relationship as part of the recruitment process. There are a lot of different types of competition that could come into play.
Q: "What are your suggestions related to enrollment strategy for Alzheimer's patients and their caregivers for an 18-month study?"
The key word here in this question is “caregiver.” Because for an Alzheimer's population, you are really recruiting the caregiver as much, if not more, than the actual patient. Because you have a caregiver who is going to have to accompany the patient, ensure that they make it in for their visits. They're going to have to help with medication compliance. Typically, this is going to be an adult child. And so, in terms of patient identification, to go back to the last webinar, think about the concentric circle model where you begin with those active patients in the clinic and recruit from that population. That's going to be the best place to start. Begin to work out from there into inactive patients. These are patients that don't necessarily have a clinic visit scheduled but can be identified through chart review. You would then begin to work out into other referral clinicians and community outreach. We've found that community outreach is very, very effective at recruiting patients for AD studies.
The one thing we have found that does not work is media. If you're a sponsor or CRO, it's largely a waste of time and money. And we would strongly recommend against using that. It's not needed and it is going to result in a lot of spending and very little return for it.
As for the 18 month study, this goes back to the caregiver and making it easy for them to be involved in this study with what most likely is an aging parent. Things to consider are that you have a caregiver who is probably working and is going to need to take time off work. Then you get into all the associated costs with that, the transportation logistics, parking, all of those things that could be potential barriers that need to be addressed at the site.
Any time that you're dealing with a caregiver, you also need to think of their larger support network. And unless you are in a situation where it's a single child of a patient, you probably have other voices in the mix. Even in that case, there might be the sibling of the patient or a spouse or someone else that may not be the functional caregiver but has a voice in the process. This again comes back to the theme of “time.” What are the resources at the site that will allow these other participants, these advocates for the patient, to get information to understand the full impact of participating in the study? How can they help support the caregiver in the act of facilitating participation in the study? All of that might require calls at 9:00 PM on a Wednesday night to the sister that lives in Omaha, or something like that. So if you're not prepared to do that type of work on behalf of the caregiver, as a study site, then you have a couple options. One would be to not do the study. But, instead, I would suggest that you think of what alternatives to resources can you have.
This is an interesting question. This has been on everybody's mind for the last four, five, six years. I don't think I've gone to a conference in the industry without hearing a presentation on digital outreach or social media. There have been various recruitment companies who have positioned themselves as the “digital or social media experts.” I think a consistent theme that I have observed is that there is still a significant gap between the promise of digital outreach, what it promises to deliver on the one hand, and on the other hand the reality of what it actually delivers. The reality is, that it consistently comes short of what the promise of it is. It has the allure of broad reach, placing digital ads is low cost, but with any recruitment method, recruitment must be looked at from a return on investment standpoint. What is my recruitment program going to cost? How many patients is it going to produce? How many enrollments? Digital outreach and the digital companies are fond of focusing on every metric except enrollment. They’re fond of focusing on the number of clicks, page views, referrals, and so on. If you're a sponsor or CRO, the only thing that matters is enrollment. You don't get to include data on a patient in your study unless they're enrolled in the study. You must view any recruitment program, and digital is no different, from a standpoint of what you’re going to spend, how many enrollments you will get, and then divide the number of enrollments into what you spend. That will be your cost per enrolled patient.
Most importantly, how much time is that going to save me and what is the value of that time saving on a per-patient basis? It’s possible with a simple spreadsheet to calculate this. That’s the way that it has to be viewed. I would say digital, and we have used digital before at WCG ThreeWire, is a valuable adjunct to recruitment. The idea that you're going to fill up a study with digital enrollment, it's just a fallacy. It's not going to happen. And many of the digital companies will advertise the number of enrollments that they've produced without revealing how much time it took, what the cost was and what the ROI was. Enrollments without context is a meaningless statistic
One of the last things I'll mention about digital, is that patients are going to drop out of the patient recruitment funnel at about double the rate of patients identified through more traditional media channels. It really doesn't matter the therapeutic area. We see that consistently. What that means is an added burden for sites. Many sites will tell you that they've gotten lots of digital patients who have been referred to them who are very, very poorly qualified. Having a means of qualifying those patients and scrubbing those patients really well before sending them over to sites is also crucial.
The first thing I would say is, unless you have a patient population that you're recruiting from where the patients are going to predominate in rural areas, then don't pick sites in rural areas. Because recruiting in a rural area is very difficult. This is more a question than an answer to which entails going upstream into the site selection process. If you must choose patients in rural areas, conduct a very careful site qualification process. You should be picking sites that have patients in their database or have ready access to patients without advertising for the study so that you don't have to rely on advertising in a rural area. As I said, advertising in a rural area is a very difficult challenge. You have a very sparsely distributed patient population, media costs are going to be amortized over those patients, and it's going to be very expensive.
Again, the way to do that is choose sites that have a demonstrated database of patients and ability to access those patients. If you do have to advertise, then local advertising is going to be the way to go, meaning local newspapers. Interestingly, the page per page readership of a small-town newspaper tends to be a lot higher than it is in big cities. That can be a surprisingly good channel.
I agree that there needs to be a reason that you go to a rural site, and there may be very logical reasons depending on what your protocol is. What I would recommend to the sponsors or CROs, in order to set the sites up for success, is that they engage in discussing recruitment earlier on in the process and possibly interact with a recruitment vendor or other places where they can consult with experts about recruitment earlier in the process. The information that they get about strategy may better equip the sponsor for adjusting timelines for recruitment and can give them a more realistic notion of when the timelines can be achieved within a rural setting.
Q: "When a stipend isn’t offered by a sponsor because it is considered standard of care, (due to insurance, extra visits, travel expenses etc.) how do you handle a patient with reservations of being involved in a clinical trial?"
One of the themes that you'll hear me talk about throughout this webinar is “time.” Time at the site and time that the site must dedicate to their patients. The amount of time that site coordinators or other site representatives have regarding the education of patients about the specifics of their participation in the study. Specifics like the number of visits, the requirements that they may have to participate in unexpectedly, such as extra visits. These all must be outlined in advance and in detail with the patients prior to their enrollment. Of course, we all know this, but sometimes sites find that they lack the time to go in and spend maybe a half an hour or more talking about these details.
The first thing that comes to my mind is handling reservations that patients have due to extra expense when no stipend is offered. I would say if you're a sponsor or Contact Research Organization (CRO), don't set yourself up for that. Just because something is considered standard of care, clinical research study is a care pathway that the patient might not otherwise engage in if they weren't in your study. It is costing the patient time and it is costing them in real terms for transportation. Even if it's standard of care, trying to save money in this area for a sponsor or a CRO, is not a wise thing to do. The value of each enrolled patient, when you take the cost of a study as a function of time and you work that out to the value of each patient enrolled in a study, is probably a quarter to a half million dollars or more. It's a big number. Trying to save a couple thousand dollars or a few hundred dollars on expense at the cost of adding and reducing that return on investment just doesn't make sense.
This is a question that really is all about “communication.” The way to decrease no-shows and lost follow-ups is through superb communication. Some of the things that we’ve referred to throughout this Q&A in terms of mapping out process for enrollment, and then for maintaining patients in studies.
You must stay in constant communication. Make calls to patients. Make appointment reminder calls. Get affirmative confirmation from patients that they're going to attend that call. You can make more than one call. Use tools, online tools, online appointment reminders with appointment confirmation buttons that a patient can click. The closer to the appointment that you do that, the more it's going to help you to reduce the no-show rate. Lost follow-ups, again, it's a matter of communication. If you're maintaining ongoing communication with the patient, you're going to greatly reduce the chance of lost follow-ups.
Always remember that this is a human-to-human relationship that is being cultivated between the site staff and the patient. It is much more difficult to no-show when Molly is the one that's calling to remind of your appointment. I say, "Hey Mark, I'm just calling to remind you of your appointment on Tuesday. By the way, how is your grandson doing?" And then you're like, "Oh he’s great!" and you tell me all about him.
That type of interaction is so important because you're creating a relationship, you're creating a bond with the patient. They are feeling committed to you in the same way that you are showing commitment to them.
Q: "Does your approach include recruitment at any cost? Where are the limitations of that approach?"
The short answer is no. It's not recruitment at any cost. It is recruitment at a cost which represents an ROI that is acceptable to the sponsor or CRO, whoever's paying for recruitment. The limitations are really going to be set by that ROI, which will depend on each individual study. As I mentioned, it's possible to calculate the value of each enrolled patient. There's a simple spreadsheet tool we've developed at WCG ThreeWire to do that. You can then build a recruitment funnel, an enrollment funnel, and evaluate the cost.
With this, you can compare the cost of enrolling each patient against the value of that enrolled patient and determine return on investment. We try to do that up front. It could be that for some projects we have a cost per enrolled patient of $4,000 or $5,000, and that's acceptable. On some it's $25,000 or $30,000, and that can be acceptable. But a $25,000 or $30,000 cost per enrolled patient where it should be $5,000 or $6,000, that's not acceptable. In short, it’s not recruitment at any cost. It must be reasonable, and it has to make sense and represent that reasonable return on a study-by-study basis.
With rare disease, oftentimes you're looking at a site that has been identified because of a key opinion leader or other factors that may mean that they're a terrific site, but don't have an extensive database. Because of the rare disease, you may be very limited in media outreach capabilities. That just might not be the sensible solution. What we tend to look at a lot with rare disease is a referral physician networking and expanding that database of the primary site outward. And that can mean a lot of different things.
In a study that isn't rare disease, let's say diabetes, you may go look at a larger institution, you're going to go to General Practices that are attached to the same hospital, you're going to look at other sites in the same community. With rare disease, you often must expand and take a more regional look when you're talking about outreach. The example that I would give here in Minnesota is that if the Mayo Clinic down in Rochester is the primary site, there's only one other hospital in Rochester. The Olmsted Community Hospital has probably already sent all of their patients with this rare condition over to the Mayo Clinic. You’re not going to have a lot of alternatives to find patients. But it would be a true shame if the four patients or five patients that are going through the University of Minnesota, just an hour and a half north of Rochester are not identified. Because those individuals would most likely be more than happy to travel that distance to participate.
When I give a scenario like this, we are now back to the topic that Mark has brought up so often in laying out a plan and identifying the gaps in that plan. Who's going to do the outreach to the sites throughout a reasonable travel range? Who's going to check in with them on a weekly basis or a couple times a week? Who's going to have those conversations with the patients and talk to them about travel and things like that? Those are the primary things that I think about when thinking about rare disease.
With rare disease, the challenge is identifying patient candidates, but travel may be the bigger issue. Sites often know who the patients are, and in some cases with rare diseases, you often have very strong patient advocacy groups. Because of that specific example, identifying patient candidates is less of an issue. It's more of an issue of travel logistics. You must be able to physically put the patient and the site together. That means accounting for getting the patient, and often a family member, a caregiver, to the site. We often come across sponsors who are doing rare disease studies but don't have any funds committed, they don't have any funding available for travel for the patient to get to the site. These are often patient populations that may number only a few thousand in the US. If you're a sponsor or CRO, that's just not realistic.
You have to think, “do you want to get the study done and enrolled or not?” There's a cost to extended enrollment in a study, and is saving a few thousand dollars on travel expense, are you stepping over hundred dollar bills to pick up pennies? it's really an issue of travel logistics and assisting patients with that.
It goes back to a theme we've talked about earlier which is making it easy for the patient to participate in the study. Some of this, by the way, can entail designing a protocol that makes it so that the patient doesn't have to physically come to the site for some of the site visits. Maybe some of those can be conducted remotely. Maybe a local physician can be included as a sub-investigator who can provide some of the testing that's needed in between what would normally be site visits in the protocol. But, again, it all goes back to planning for it and creating that care pathway that Molly mentioned and making sure that it is not a burden on the patient to follow that pathway to be able to participate in the study.
Q: "What are some techniques, monetary motivation, et cetera, to retain subjects over a multi-day protocol?"
So monetary motivation is terrific because it, when appropriately measured, is respectful of the patient and the caregiver that are participating. It's acknowledging that their participation is taking away from their daily life. I think that we err on the side of hubris when we say that “everyone just wants to do my study because it's going to be so awesome and this is such a cool drug.” Oftentimes that may be the case, but the structure of the protocol, the scheduling, the time commitment, the time away from your family, and your job, may prohibit participation. When there's a financial component that can offset that aspect of it, then that for sure should be considered.
Beyond monetary motivation, retaining subjects over extended protocol goes back to what we've repeatedly been saying about relationship building, transparent study education, and laying out the entire process for the patient, while identifying what that patient's other motivations may be besides the monetary component.
Q: "What do you see as the biggest challenge to patient recruitment? And what do you see as the best solution to solve it?"
The biggest challenge to patient recruitment, and I'm going to conflate the words recruitment and enrollment here because recruitment is simply the means to the ultimate end of getting a study enrolled. Far and away, the biggest challenge is site bandwidth. Sites are very busy. They have a busy clinical practice. They have other studies. They're the only ones who can enroll patients in your study. The biggest challenge is ensuring that that study works for your site. Again, helping map out processes so that realistic expectations can be set for sites in terms of what is going to be required from them to participate in a clinical research study.
I think that if we go beyond that, it's getting the word out about what clinical research is and what it means within our society. I’d guess that every single person attending this webinar, that's worked at a site, has sat a dinner party and had to explain what they do for a living. My guess would be that most of the people had no idea that their job even existed. Well that's a problem for recruitment. That’s where, as a site, you may want to consider how you brand clinical research, how you teach your typical population coming through your clinic about clinical research so that when an individual does become a candidate for a study, it's not the first time they've ever heard about it. That helps to reduce stigma and fear and really make that initial conversation about participation, when it is about you specifically, a lot easier to have.