Accruing patients depends greatly on engaged, enthusiastic PIs, as they are the gatekeepers in helping patients decide to participate in clinical trials. Building staff awareness and enthusiasm are also essential for retaining participants.
Global clinical trial performance and efficiency are being plagued by high turnover and noncompliance among principal investigators (PIs) and patients. According to the Tufts Center for the Study of Drug Development, while the highest turnover is observed among the least active investigators, turnover rates have been getting progressively worse among more active investigators. Moreover, despite thousands of trials and millions of cancer patients, less than 3% of U.S. adults with cancer enter into a clinical trial.
Engaging physicians, sites, staff and patients in the clinical trial process is crucial in moving forward with new and effective oncology therapies. Accruing patients depends greatly on engaged, enthusiastic PIs, as they are the gatekeepers in helping patients decide to participate in clinical trials. Building staff awareness and enthusiasm are also essential for retaining participants. To improve identifying, enrolling and retaining patients, sponsors need to prepare and engage those administering the trial through a thoughtful and prudent resource approach. This can be achieved through a variety of strategies, which are outlined in this article.
Planning for patients
Several factors are critical to the process of finding patients. First and foremost, sponsors should plan patient accrual and retention as part of a study’s initiation activities as this information allows sponsors to better understand the realities of patient selection and enrollment patterns. Recruitment strategies must define the overarching plans to announce and generate interest in the trial as well as accrual and slot assignment processes for sites, so synergies can be maximized and adjustments made as the trial progresses. Similarly, plans must include strategies for fielding enrollment queries from out-of-region patients or healthcare professionals as may happen with online trial registries.
With about one-third of trial costs stemming from patient enrollment across all therapeutic areas, understanding cancer prevalence within each geography and site is critical to successful site enrollment for oncology trials. A site’s patient population and trial experience take on even more significance if the targeted cancer is rare or patient access is limited. Furthermore, a site’s experience and capabilities relevant to a specific protocol may be difficult to discern, as not all countries or even regions within countries treat patients with the same cancer in the same way.
For example, variations exist between and within European nations in the diagnosis and surgical treatment for colorectal cancer patients and in the staging at diagnosis and subsequent treatment for breast cancer patients, according to the International Cancer Benchmarking Partnership. And while these medical differences were examined as part of an analysis of cancer survival, it is reasonable to extrapolate how such differences also impact the availability of cancer patients as potential trial participants.
Specialty oncology CROs can address these challenges through an experienced feasibility group. With access to local, country-specific medical experts who routinely treat cancer prevalence and are familiar with standards of care, feasibility experts can accurately assess the type and size of patient populations a potential study site can realistically target.
Planning how to accrue oncology trial patients will inevitably raise several site feasibility questions such as:
Because trial protocols increasingly apply the latest in technology to bring greater specificity to the research process, a site’s ability to test for things such as patient-specific biomarkers as part of enrollment or trial monitoring can be as important as considering the site’s experience with a particular type of therapy. Having in-depth, site-specific knowledge helps to efficiently manage within each site’s standard operating procedures, including institutional contracting processes, scientific review board practices, ethics committees and data collection practices.
Accruing patients is also dependent upon engaged, enthusiastic PIs who understand and can champion the science of the candidate treatment to truly support a sponsor’s trial and patient enrollment. However, the biggest hurdles physicians report for not participating in trials are perceived lack of time, responsibilities related to participation and compensation for work involved with screening, scheduling and managing patients. Also often cited is the intensity of paper work collection and filing as well as staff documentation training. Physician peer-to-peer communications cannot be underestimated in its importance in influencing physicians to join trials, as physicians are more likely to accrue patients if they are discussing treatment options with other physicians.
A study presented at a past American Society of Clinical Oncology (ASCO) annual meeting found the use of direct physician-to-physician communications improved monthly accruals and increased enrollment 27.7 percent per site per month during a 15-month engagement and 16.3 percent during an 18-month engagement, respectively.
To facilitate these physician conversations, sponsors or CROs should prepare PIs both on trial specifics and likely questions from clinicians, staff and patients. Because of the dynamic nature of cancer science, ensuring PIs receive the peer-reviewed science supporting the candidate treatment helps to facilitate their understanding of the underlying scientific rationale of the investigational compound. This knowledge boosts PI interest, making the research more compelling and increasing the likelihood a PI will engage in trial discussions with their patients.
Because more than half of patient accruals in U.S. trials are drawn from community-based practices, PIs must proactively address concerns referring physicians may have about a trial. The greater the understanding referring physicians have of a trial and the ease with which they can follow the patient’s progress, the more motivated they are to enroll patients. Understanding the referral physician network of sites is key to enabling sponsors to partner effectively to assure access to the broadest patient population.
For sponsors outsourcing their trials, arranging for Clinical Research Associates (CRAs) to be on location for first-patient enrollment provides additional support and reassurance while building staff awareness and enthusiasm for the trial. As the trial unfolds, CRAs routinely communicate and visit with site staff, help manage screening and enrollment logs, check patients’ case reports, note the patients’ calendars of events, facilitate enrollment and identify potential competing studies or responsibilities at the site. Trial managers can track site-specific patient flow and accrual, identify changes or trends and adjust the enrollment plans or accrual methods, either at individual sites or trial-wide through good trial management and a robust clinical trial management system.
Some organizations are implementing new technologies such as document exchange portals to support PIs and staff managing multi-site trials. Ideally, a CRA acts as an extension of the site staff team – someone with whom they can freely discuss any barriers to enrollment so together they can develop solutions.
Talking with patients
Physicians who “open the gate” to trials for patients need to do more than talk at a patient, they need to have a two-way conversation to achieve enrollment. Patients and their caregivers have many questions about research in general and the trial in particular and their first and most trusted source is their physician. Since many patients will not easily understand medical jargon, providing patient materials in lay terms fosters good communication and enrollment. Patient-focused trial materials may include posters, fact sheets and brochures.
Many oncology trials will require the accrual of women, underserved and minority populations and geriatric patients. For these groups, sponsors must recognize hurdles to trial enrollment, which include language, ethnic perceptions of illness and healing or cultural barriers of age or race. Notably, language and literacy are significant issues not just in initial physician-led conversations but also when acquiring patients’ informed consent – extensive legal language in consent forms is known to decrease the desire to enroll.
Retaining enrolled patients
A variety of reasons exist to explain why patients stay for the duration of a clinical trial. Motivation can be a big factor for patients and site staff alike. When site staff use a variety of tactics to encourage patients, they have better results. The connections afforded by the Internet and social media appear to be ready made to help with trial communications; both to staff and to patients, yet many sponsors are still working on the most effective means to apply these tools beyond the use of trial registries.
Sending text messages to remind patients to take medications, make diary entries or get ready for a visit are other great ways to make patients feel more involved. For “science fan” patients, research updates have great appeal. Altruistic patients may appreciate recognition of their contributions to creating future treatments and standards of care. In more advanced trials where a new treatment may lead to significant delays in disease progression or regression, personal health updates take on even more significance to encourage patients.
To aid in peer-to-peer trial communications, password-protected web portals, separate from the formal trial operational and data management infrastructure could create seamless virtual peer communities where staff informally share recruitment tips, case studies, updates and experiences.
In addition to peer-to-peer staff communications, regular CRA communications build encouraging relationships with staff and help convey the importance of follow-up with patients before dropouts happen. CRAs can convey the encouragement and critical updates needed to keep a sponsor’s trial top-of-mind, as competing trials and routine patient care also demand site staff attention. Regular onsite meetings permit a CRA to give site staff the trial progress as a big picture as well as site-specific activity. These connections also allow the CRA to acknowledge the staff’s hard work and continue to foster positive relationships.
Regardless of the tactic, engaging sites, physicians, staff and patients in the clinical trial process are essential in moving forward with new and effective oncology therapies.
Cathy White, Vice President, Operations, Novella Clinical