Table 1.
Factors impacting accrual and potential solutions
| Challenges | Potential Solutions |
|---|---|
| A: Patient and Community Factors | |
| Hindrances to patient’s decision-making ability, including low level of education, limited understanding of clinical trials, and impact of disease on neurocognitive function | • Provider education to improve communication with patients regarding clinical trials (including written and online materials and videos) |
| • Engagement of patients and providers with advocacy groups | |
| • Use of clinical trial patient navigator | |
| Patient’s limited awareness of clinical trial opportunities | • Patient education campaigns focused on reducing barriers to trial participation |
| • Brain tumor registry to help providers identify trial eligible patients and to provide an opportunity for outreach to those patients | |
| • Simplify the ability to identify local and national trials through improved online search tools, smart phone apps, or clinical trial patient navigators | |
| • Engagement with patient advocacy groups, brain tumor support groups, and use of patient navigators | |
| Patient misconceptions about research study involvement including negative personal and family attitudes about clinical trials and perceived lack of personal benefit | • Patient education campaigns focused on demystifying clinical trials and dispelling rumors about them |
| • Engagement with patient advocacy groups which can promote the existence and benefits/ risks of joining a clinical trial | |
| Suboptimal (ie, poorly timed or rushed) discussion of clinical trial opportunities with overwhelmed patients/caregivers | • Heighten empathy for patients/caregivers |
| • Incorporate multimedia materials to effectively describe in layman’s terms the study rationale, potential benefits/risks and logistics | |
| • Improve informed consent documents and processes to facilitate greater understanding of the issues involved in clinical trial participation | |
| • Provide enough time for patient/caregivers concerns to be addressed; incorporate additional research team input from nurses, mid-levels, and navigators | |
| • Refer patients to brain tumor patient advocacy organizations for additional support and access to patient navigators | |
| Concerns about the complexity and difficulty of complying with protocols, cost, and time/convenience | • Design trials that are more patient friendly by obtaining their input |
| • Resources to facilitate travel and reduce costs of trial participation such as parking, housing, and absence from work | |
| • Ensure coverage of routine patient care costs in clinical trials by both federal and private payers | |
| • Open larger number of trials at smaller centers (a role especially for the National Clinical Trials Network in the United States) | |
| • Use novel technologies such as telemedicine to minimize trips for clinical trial assessments | |
| • Trial-design changes aimed at reducing the number of clinical trial visits | |
| B: Disparities | |
| Access and referral patterns | • Establish standard paradigm for referral of patients to neuro/medical oncology |
| • Implementation of patient navigators dedicated to support of URM/vulnerable patients | |
| • Establish partnerships with community-based organizations serving URM | |
| Unconscious bias | • Unconscious bias training with regular evaluation of its efficacy and relevance |
| Lack of diversity in oncology workforce | • Strengthen pipeline of URM candidates into neurology, oncology, neurosurgery, and radiation oncology |
| C: Physician and Provider Factors | |
| Failure to discuss clinical trials as an option with patients | Change standard practice to one where clinical trials are always discussed as an option in addition to existing standard therapies, particularly at two timepoints: |
| • When formulating the initial plan of care. | |
| • At the time of disease progression or disease recurrence. | |
| • Early on, dispel potential patient and caregiver attitudes that clinical trials are only for a time when all other options have run out, especially since patients who are heavily pre- treated are less likely to qualify for trials | |
| Time and inconvenience | • Trial navigators and/or electronic tools (eg, apps) to allow for rapid, real-time trial matching |
| • Brief trial summaries pitched at physicians and at patients to provide a high-level overview of the trial rationale, design, risks/benefits, and visit schedule can distill complex information into some of the key elements | |
| • Optimizing and streamlining referral processes on both the referring and receiving ends to reduce the barriers to referring patients to outside institutions for trials. | |
| Lack of knowledge | • For complex cases scheduled in advance, care team members could prepare ahead of the encounter to gather information on the best course of action |
| • If preparing ahead of the encounter is not possible, an alternative could be to acknowledge the complexity of the patient’s case, and explain that further discussion with colleagues will take place (ie, multidisciplinary tumor board) to identify the best course of action | |
| Lack of information about available clinical trials including eligibility criteria | • Take advantage of resources such as a clinical research navigator and on-line matching tools (eg, apps), who can help identify clinical trials available at the institution that may be appropriate for each patient |
| • When a patient is a good candidate for clinical trials and there is not a trial available at the provider’s institution, consider searching for studies available at referring center(s) | |
| • Efforts to develop trial search engines which can provide accurate and appropriate potential trial matches while minimizing manual data input from the provider, and which can filter for key factors (geography, stage, disease status, lines of therapy, relevant biomarkers) are underway and should continue | |
| Lack of willingness to refer a patient to another center for study (including financial incentives) | • Encourage a change in culture to always consider referring patients to centers with trials if one is not available locally, if practically feasible. |
| • Allow patients to receive some of their evaluations and treatments with the referring physician to reduce the sense that the physician is “losing” their patients; to validate the importance of a continued connection between the referring physician and the patient; to reduce the financial disincentive to refer patients; and to support stronger collaborations between oncology teams at the referring and trial sites | |
| Lack of Incentive | • Consider a research RVU system that compensates for clinical trial related activities |
| • Increase possibility of authorship for physicians who enroll patients into clinical trials | |
| Concerns regarding a patient’s interest and ability to participate | • A candid discussion with the patient and the research staff, ideally during the encounter to discuss treatment options, should be conducted to address any source of concerns for participation |
| Concern about the interference in the physician-patient relationship | • Discussions about goals of care, patient’s preferences and expectations should be done during the clinical trial in the same manner as they are done during routine clinical care |
| Conflict between the physician’s role as caregiver versus scientist | There are at least three strategies to help mitigate this concern: |
| • To place the patient’s needs and preferences first | |
| • To enroll or refer to trials which are scientifically valid and designed in a clinically justifiable manner | |
| • To explain the differences between the role of the primary oncologist and the role of the clinical investigator, particularly when they are embodied in the same person | |
| • Ask patients for any source of concerns about conflicts between the roles, and address them | |
| Physician burnout | • Understand and acknowledge the effect that clinical trials can have on physician burnout |
| • Work with institutional leadership to emphasize the value of access to clinical trials and the need for resources to facilitate clinical research. | |
| • Work with the research staff, research nurses, clinical research coordinators and other personnel to address challenges to distribute the burden across the trial team. • Future platforms, such as artificial intelligence may assist with curating clinical trial options. • Shared electronic medical records across institutions may improve access. |
|
| D: Clinical Trial Factors | |
| Patient/caregiver hardships due to frequent study center visits limit enthusiasm for trial participation | • Incorporate patient/caregiver/advocate feedback into early drafts of clinical trial during development |
| • Allow study assessments and treatments, especially those considered “standard of care” to be done locally; | |
| • Require study center visits only when critically relevant to the study therapy; | |
| • Proactively incorporate patient/caregiver considerations into need for regulatory requirements for source documentation | |
| Inefficient clinical trial design features | • Incorporate multi-stage, multi-arm trials with adaptive randomization |
| • Incorporate careful toxicity and efficacy stopping rules | |
| • Consider lower statistical power thresholds for non-registration efficacy trials | |
| • Involve at an early stage of clinical trial design patient advocacy organizations, patients and caregivers | |
| Excessively stringent eligibility criteria limit trial participation | • Limit inclusion/exclusion to criteria critically relevant to study primary endpoint |
| • Ensure eligibility criteria do not preferentially exclude a demographic or racial group, eg, upper or lower age limits, or excluding comorbidities more highly associated with demographic or socioeconomic subgroup unless specific rationale for exclusion exists. | |
| • Include patients with primary and metastatic brain tumors in early phase oncology clinical trials | |
| Technology trials ignore clinical equipoise challenges and incorporate traditional trial endpoints | • Allow non-traditional primary endpoint/s that addresses key clinically meaningful objective of technology being assessed |
| E: Site and Organizational Factors | |
| Clinical research requires specialized personnel, training, infrastructure, resources | • Effective leadership of a multidisciplinary team and organization culture to promote accrual |
| • Adequate infrastructure to allow clinical research | |
| • Cancer care accreditation to incentivize trial enrollment | |
| • Hire physicians and research staff committed to clinical research | |
| Slow activation of trials due to IRB issues, contracting issues, etc. | • Centralize IRB operations with harmonization across countries |
| Limited resources at community centers to support clinical research | • Greater partnership between academic and community oncology centers |
| • Enhanced incentives for patient enrollment in clinical trials or referrals to academic centers for clinical trials | |
| • Education programs for community physicians emphasizing the importance of clinical trials |
Abbreviations: IRB institutional review board, RVU relative value unit, URM underrepresented minority