Overcoming Obstacles to Clinical Trial Recruitment and Retention
Laura S. Wood, MSN, RN, OCN, spoke to Physician's Education Resource regarding resources to increase clinical trial awareness and participation.
Clinical trials, a cornerstone of drug development, link groundbreaking discoveries in cancer research with the general patient population. Enrolling adequate numbers of participants with characteristics that represent all patients with a particular cancer remains a daunting challenge.1 As many as 20% of clinical trials fail due to insufficient enrollment.2 Patient awareness of clinical trials is the first hurdle to clear, although financial and geographic constraints may also limit patients’ involvement in this research. Stringent trial eligibility requirements may exclude up to 25% of patients attempting to enroll in a study.3 Further, patient misperceptions of clinical trials may create reluctance to participate in research.4 Despite the rarity of placebo-only use in oncology clinical trials, many patients fear receiving a placebo or substandard care. In this article, Laura S. Wood, MSN, RN, OCN, describes the obstacles to clinical trial recruitment, enrollment, and retention as well as opportunities to overcome these deterrents.
Q: What is involved in the clinical trial recruitment and enrollment process?
Wood: Recruitment and enrollment are 2 very distinct processes.5 Recruitment involves informing people about the clinical trial. Recruitment is done either by networking with colleagues—we have a lot of community physicians who have referred patients to us—or through the national organizations, such as the Oncology Nursing Society (ONS), the American Society of Clinical Oncology (ASCO), or the American Society of Hematology.6-8 It can also involve radio, social media, or other internet sources to help patients identify available clinical trials.9 Knowing which centers do clinical trials and which centers focus on specific diseases is certainly helpful.
The enrollment process, then, is what a patient goes through to determine whether or not they are appropriate and eligible for a clinical trial.5 Clinical trials have very defined inclusion and exclusion criteria.3 If the objective of this study is to look at how a drug, drug combination, or procedure works, who is the patient population who can meet that objective? What are the patient characteristics? There are typically 20 to 40 inclusion and exclusion criteria in a given protocol. We want to make sure that the potential benefits outweigh the potential risks. Early clinical trials and new drug clinical trials have laboratory parameters that are representative of the patient population.5
Q: Why is it important to have a representative or balanced patient population in trials?
Wood: So much time, effort, and money go into developing new drugs and new drug combinations that drug companies want to be sure that the results are going to be generalizable.10 So we are broad in our general clinical trials to be equitable for all individuals. We want to take all comers for whom the risk-benefit ratio is reasonable, recognizing that there is more that we do not know about the safety of a drug or drug combination than what we do know. That is why we are doing the clinical trial. Then there may be some smaller substudies that follow, looking at more specific patient populations, such as individuals who have poor kidney function or poor liver function, be it because of liver comorbidities or liver metastasis. The trials are looking, then, at extending the safety profile in a more high-risk patient population.
Q: What are the major barriers to clinical trial enrollment for patients in underrepresented populations?
Wood: The biggest barrier is knowledge. The patient, the caregiver, and sometimes the local oncologist are not aware of the potential for clinical trials.4 It is a specialized group of individuals who do clinical trials, and they are not always in your backyard.
One of the other significant barriers is location.4 Patients may know about a clinical trial and may be ideal for the clinical trial, but can they get there? Is it feasible both location and transportation-wise? Is it feasible financially? Is it feasible logistically? Will the patient need a caregiver? Can the caregiver get time off from work? There is the Family Medical Leave Act (FMLA), but that is not always sufficient for the frequency of visits required to participate in clinical trials.
A lot of work has been done by the Clinical Trials Network, the Association of Community Cancer Centers (ACCC), and national organizations trying to make access easier.11,12 Pharmaceutical companies may allow stipends to be provided to help with accessibility costs. Can laboratory testing be done at a local facility? Can certain parts of the clinical trial be done closer to home? Do you have to come to the main institution for everything, or can you go to one of our family health centers or one of our satellite locations that might be more feasible to you? I will always ask a patient, “Do you have a family member who lives in 1 of these 2 cities where this trial is being conducted that is
probably closer to you or within your insurance network?”
There are a lot of nuances that the oncology team can help with. I would absolutely encourage patients to be referred for clinical trials and go with the premise that they are eligible and it is feasible until proven otherwise. There are a lot of resources out there. The whole research team—the oncologist, potentially a navigator, the research nurse, a social worker—can help with finding resources that might be available to minimize those barriers.7
Q: What are some options for patients who do not live near clinical trial sites?
Wood: One of the things that I had to do for a patient was to find out where they could park their camper, because they basically did road trips. Every time they needed to come, they came in their camper, and they stayed in their camper. We just needed to find where on our campus was appropriate for them to park it.
We have long-term-stay hotels in our area that will work with us for patients with cancer needing extended stays due to clinical trial participation. They will discount the stay, because they know that patient will keep coming back, whether it is every 2 weeks, every 4 weeks, or every 8 weeks. There’s that comfort level of continuity for the patient as well—knowing where they are going to be. They get to know the front desk staff, and it is another whole support group for them as they go through treatment. It is peace of mind, and it takes away a stressor for the patient and the caregiver. It’s huge.
Q: In your experience, what are some key patient concerns when they are contemplating enrolling in a clinical trial?
Wood: The key concerns are, “Is it feasible, and can I afford it?”2 There are a lot of disease-specific groups, such as the Kidney Cancer Association (KCA), with members who can help look at what resources are available to address those concerns.13 The institution’s social worker, navigator, or research nurse also knows what resources may be available to help with the concerns of financial costs, time off work, filling out FMLA papers, and working with the co-pay assistance foundations to try to help cover the co-pay.6
One of the groups that I worked with extensively for clinical trial enrollment was the Lazarex Cancer Foundation.14 It is a foundation that supports both pediatric and adult financial challenges with clinical trial participation. The foundation has a form for the clinical trial team to fill out, and they then identify needs with the patient and caregiver and see what financial resources, such as a gas card, are available to help them during the duration of their clinical trial participation.
Also, managers at the cancer center that is doing the clinical trial are going to develop a research budget to identify those things that are standard-of-care tests and procedures that are covered by insurance and those things that are not. The clinical trial sponsor will cover those as research-related costs.15 So patients need to know which costs are their responsibility and which are covered by their insurance, as well as which tests and procedures are research related and covered by the clinical trial. This information is included in the informed consent for clinical trial participation.
Q: How would you counsel patients who are concerned that clinical trial participation will interfere with their work or family obligations?
Wood: The technical term is shared decision-making, but most of that is listening.5 What are the patient’s goals? We have patients who refuse to participate in clinical trials, because they don’t want any chance of extra costs to challenge the financial status of the family. That is their right. I can try to support them, but the best support I can give them is to say, “I totally value what you are saying and what your goals are, and we are happy to continue with the standard plan.” Clinical trials are not the ideal thing for everybody, and they are not even a potential consideration for some people. We need to respect that.
There are also some individuals who have a higher risk associated with participating from a safety perspective.5 We need to know, are they able to take an oral medication? Can they keep track of it? Are they aware enough and able enough to communicate with us as frequently as needed about the potential adverse effects so we can identify and intervene early, or are they going to be at risk? In which case, it may be more appropriate for them to come into the clinic to get an infusion. Again, that is where that whole shared decision-making is important.
Q: How can patient navigators address the challenges facing clinical trial recruitment?
Wood: The most important thing for any provider to do, especially a navigator or care coordinator, is to be aware of what the clinical trials are and what the time frames are.16 They need to network with the research staff so that they are aware of frequency of visits, and they need to help facilitate the conversation between the patient and the research site. Perhaps the patient can do a virtual visit to go through the primary checklist and see if there are any red flags that can be identified before they pack a suitcase. The navigator can say, “Yes, it seems reasonable to pursue this,” or “No, we are very sorry, but there’s a red flag. You’re not eligible. I recommend going back to your treating physician and resuming the discussion of local treatment options.”
Q: What role can community oncologists and nurses play in supporting clinical trial enrollment and retention?
Wood: Being a facilitator is the most important aspect. If you know a bit about the clinical trial and the patient already has some specific questions, you can make a quick phone call to the research site.7 I get a lot of phone calls from community offices from oncology nurses saying, “Hey, we have a potential patient. Can we see if he is eligible or not? Walk me through what the frequency of visits are. What can we do by phone before we refer the patient over to you?”
It is also important to know what resources are available so you can find out the most pertinent information.4 The ClinicalTrials.gov website can help facilitate awareness.17 Look to your network and community, maybe the Leukemia & Lymphoma Society, etc.18 There are a lot of different disease-specific groups that may cross-network with some of these other resources. Is there an organization that is geared toward your cancer, such as the KCA or the American Bladder Cancer Society? What groups are out there, and what are the reputable websites where you can get good, sound information and contact information, such as a phone number for you to be able to ask some of those questions? One of the resources that the KCA has, which I’m sure others do as well, is a clinical trial matching network through the KCA navigator.13 The network can help patients identify available options for open clinical trials and help them navigate and understand what clinical trials are.
Patients and caregivers need to know what it means to participate in a clinical trial.5 What are the terminologies? Is it randomized? Is it placebo controlled? Is the drug brand-new and early in clinical trial development? Giving patients information sheets from cancer.net or ASCO is an important step oncologists and nurses can take to help patients understand what clinical trials are. Our role is to be the link in the chain between the community, the center doing the research, and ACCC, which is a nationwide network.
Key References
2. Barriers to Patient Enrollment in Therapeutic Clinical Trials for Cancer: A Landscape Report. American Cancer Society Cancer Action Network; 2018. Accessed October 12, 2023. https://www.fightcancer.org/sites/default/files/National%20Documents/Clinical-Trials-Landscape-Report.pdf
5. AACR Cancer Progress Report. American Association for Cancer Research. Accessed October 12, 2023. https://cancerprogressreport.aacr.org/progress/
7. Flocke SA, Antognoli E, Daly BJ, et al. The role of oncology nurses in discussing clinical trials. Oncol Nurs Forum. 2017;44(5):547-552. doi:10.1188/17.Onf.547-552
To view the full reference list, and to receive CME credits, visit: https://www.gotoper.com/learn/course/overcoming-obstacles-to-clinical-trial-recruitment-and-retention/journal-credit/activity-outline
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