Ethical Concerns if Researchers Fail to Meet Recruitment Targets

By Stacey Kusterbeck

For researchers, failure to meet clinical trial recruitment targets raises not only logistical problems, but also significant ethical concerns. “The study may become scientifically underpowered, producing inconclusive or potentially misleading results,” says Teresa Boitano, MD, a gynecologic oncologist at UAB Medicine’s O’Neal Comprehensive Cancer Center.

For future patients, slow progress delays access to promising therapies. For participants already enrolled, there may be loss of anticipated benefits or reduced monitoring if the study halts early. “Persistent under-enrollment of certain groups can worsen existing disparities,” adds Boitano.

The recruitment target for a clinical trial often is based on a statistical analysis, determining the numbers needed to achieve statistical significance to answer the trial’s question, observes Emerson A. Lim, MD, MS, a clinical investigator at START-Midwest. If the target number is not met, the answer to the question the trial is trying to resolve may not be conclusive. “One ethical concern is that the patients who volunteered to participate in the study would have been subject to the risks of the clinical trial, but their altruistic efforts would not have helped to conclusively answer the question being posed,” says Lim.

Another ethical concern is that if the important question being investigated does not have a conclusive answer, it leaves the medical community with ongoing questions. “One specific example of this occurred around the question of whether adjuvant chemotherapy should be used to treat muscle-invasive bladder cancer. Multiple clinical trials unfortunately did not meet their enrollment targets and were unable to determine whether those patients would benefit from adjuvant chemotherapy,” says Lim.¹

The field was left without a definitive answer until more recent clinical trials were able to reach their target enrollment and provide clear answers that changed clinical practice. “Incomplete enrollment had left physicians and patients trying to navigate this serious clinical question with limited guidance for many years,” says Lim. For Phase I clinical trials evaluating the safety and preliminary efficacy of a new drug in people for the first time, poor recruitment could result in a promising drug not proceeding with further development. “This, in turn, could leave a medical field without the potential benefits of that particular drug,” says Lim.

For patients who are participating in a trial that closes, the ethical concern is whether patients receiving the experimental therapy and benefiting from the drug can continue with their treatment. Pharmaceutical companies might continue to supply existing patients with the experimental drug. “But sometimes drug development and production cease, leaving patients to seek other treatment options,” Lim explains.

Sometimes, the design of a clinical trial hampers enrollment. If a clinical trial is too restrictive in the patient population it is seeking, there may not be enough patients within that population interested in participating, says Lim. If researchers loosen the inclusion and exclusion criteria, it could allow for more robust enrollment.

Many people face logistical, financial, or informational barriers that keep them from participating in research. “Common barriers include limited awareness or understanding of trials, mistrust of the healthcare system, transportation constraints, complex eligibility criteria, time burdens, cultural or language mismatches, and limited time for clinicians to discuss trial options,” says Boitano.

Boitano and colleagues evaluated whether research navigators could increase enrollment and reduce disparities.² “Our goal was to understand whether patient navigators could improve access, communication, and trust in the trial process, particularly for groups that have historically been underrepresented in cancer research,” says Boitano.

A research navigator team approached all 224 patients with gynecologic malignancies who were potentially eligible for a clinical trial from 2018-2022. The control group consisted of 187 patients who had been enrolled in the study before the research navigator team was implemented. Enrollment more than doubled (from 15% to 36.9%) after the research navigation team was initiated, with a high rate of minority inclusion (27.3% of enrolled patients were Black). “We were encouraged to see a clear improvement in trial opportunities for our patients. Even relatively modest navigation efforts meaningfully increased comprehension of trial options and boosted enrollment,” says Boitano.

In some cases, an eligible patient would have wanted to participate in a research study, but there is no one available to enroll the patient. “For critical care trials, researchers don’t know when patients are coming in. Enrollment is especially challenging if we are only recruiting during business hours, however you define those,” says John Lee, MD, PhD, an emergency physician and attending physician at Beth Israel Deaconess Medical Center.

Research staff often are available only during business hours, typically defined as starting at 9 a.m. and ending at 5 p.m. or 6 p.m. Patients presenting outside of those hours cannot be enrolled in the research study. At Beth Israel Deaconess, critical care researchers have made it a priority to have research staff available to enroll patients 24 hours per day, seven days per week. Shift-based research assistants are not always onsite but can be paged if someone presents who meets the study criteria.

Lee and colleagues conducted a study to compare the actual enrollment of five critical care clinical trials against what the enrollment would have been if research staff had been available only during business hours.³ Of the five studies, 352 patients were enrolled in total, and 242 (almost 70%) of those patients were enrolled outside of business hours. More than one-quarter of the patients were enrolled during weekends. More than half of the enrollments occurred from 2 p.m. to 10 p.m. For one trial in particular, recruiting patients only during business hours would have resulted in a prohibitively long time (an additional 15 years) to complete the study. “We thought it was good to publish this so other trialists can think about it when designing studies and requesting grants. This is actually a big issue that we need to budget for,” says Lee.

Not all sites have the resources to do around-the-clock recruitment. “We prioritized this and set aside funding to do it. It definitely takes an intentional commitment to be able to do this. Our argument is that it’s important to at least think about this in the design stage for all trials, but especially for critical care trials when we don’t know when patients are coming in,” says Lee.

When researchers are applying for funding, they can refer to data showing that around-the-clock recruitment can be important for a trial to be successful. For some studies, off-hours recruitment may turn out to be a major factor. For other studies, business hours may be appropriate. “If you cannot do 24/7 enrollment, it may be helpful to see what the enrollment data look like. Look at when patients are coming in and strategically cover those hours,” recommends Lee. Ideally, researchers evaluate this when designing study protocols by looking at data showing what time and day of the week patients with the condition being studied are presenting. For instance, if the study is recruiting middle-aged females with children, those patients may present at different times than older males.

If the trial already has started and researchers are seeing low enrollment, changes may be needed. Researchers may realize that at the current rate of enrollment, they will not meet recruitment targets. It may be necessary to cover certain periods of time, such as weekends or evenings. “Getting additional funding at that point is probably difficult, but moving around the budget can make this work,” suggests Lee.

Given what is at stake, it is worthwhile for researchers to put in the effort to ensure that lack of coverage is not hindering recruitment. “Trials cost so much money, a lot of which comes from federal funding — our tax dollars. There is an ethical obligation for trialists to make sure, to the best of their ability, to get successful enrollment for trials,” says Lee.

Larger academic medical centers should recruit every patient for some sort of study, according to Susan E. Morgan, PhD, a professor in the department of communication studies and former associate provost for research at the University of Miami. ”A menu of possible options can be presented to each patient, preferably before their appointment,” suggests Morgan. Patients can decide on participation based on level of commitment (from one-time quality-of-life surveys to long-term interventional trials), number of visits required, level of risk, invasiveness or discomfort, or incentives offered. “There should be a goal of introducing patients to a culture of research. By giving them an opportunity to have positive experiences with low-risk observational studies, they will be more likely to say ‘yes’ to other opportunities,” says Morgan. Morgan offers these strategies to increase recruitment:

• Do not make it mandatory for prospective research coordinators to have an advanced degree. This is particularly important for observational studies or studies that involve minimal risk. “There are a lot of really smart people out there with great people skills who can be trained in what they need to know in order to effectively recruit for studies,” says Morgan.
• Provide more effective, systematic training for all staff who recruit for clinical trials and research studies. “I have video recordings of professional staff recruiting standardized patients that would make your hair stand on end,” says Morgan.
• Require principal investigators (PIs) to run in-person training and question-and-answer sessions for everyone recruiting for a study. “This is not common practice, so even if a patient is presented with the study, the person presenting it has little in-depth knowledge. If a patient has a glimmer of interest, they are told that someone from the PI’s office will get in contact with them. Frankly, this often does not happen -- or follow-up consists of leaving one voicemail for a patient,” says Morgan.
• Train staff (research coordinators, research assistants, physicians, nurses, and PIs) in skills related to communication about clinical trials. “These include both verbal and nonverbal communication, focusing on clarity, credibility, and empathy,” says Morgan.

Stacey Kusterbeck is an award-winning contributing author for Relias. She has more than 20 years of medical journalism experience and greatly enjoys keeping on top of constant changes in the healthcare field.

References

1. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Adjuvant chemotherapy in invasive bladder cancer: A systematic review and meta-analysis of individual patient data. Eur Urol. 2005;48(2):189-199.

2. Boitano TKL, Wall JA, Bos L, et al. Dedicated research navigators: A tool to decrease disparities in clinical trial enrollment? Int J Gynecol Cancer. 2025;35(2):100066.

3. Lee JH, Vine J, Meier M, et al. The impact of extended-hours patient recruitment on critical care clinical trial enrollment. Crit Care Explor. 2025;7(4):e1239.