publication date: Aug. 9, 2019
Trials and Tribulations
Measures to improve clinical trial enrollment: Marshfield Clinic Cancer Care and research approach
Adedayo A. Onitilo, MD, PhD, MSCR, FACP
Oncology/Hematology and Radiation
Oncology Service Line
Department chair, Oncology/Hematology, Marshfield Clinic
Daniel Wall, BSc
Stephanie Engelien, RN, MSN
Oncology research nurse, Marshfield Clinic
Part II of a two-part series
It is estimated that, each year, as few as 2–3% of cancer patients enter clinical trials. In part I of this series, we discussed four key barriers to participation: physician barriers, protocol barriers, research team barriers, and insurance barriers. In part II, we will look at solutions to these barriers and how to implement them in the clinical setting.
The biggest physician barriers to research participation are lack of training and inadequate time and compensation1,2. Since most health care systems measure physician productivity by number of patient appointments, medical procedures, and relative value units (RVUs), the additional time needs for research training and participation are inherently discouraged3,4. There is no additional compensation offered for the increased workload required of physicians who want to enroll patients in clinical trials.
There are multiple engagement strategies that have been implemented by Marshfield Clinic in an effort to improve physician participation and subject enrollment. A citizenship and engagement matrix has been developed at Marshfield Clinic that defines physician expectations in research. The matrix includes research meeting attendance, enrollment of participants in clinical trials, and taking on the role of principal investigator as new trials are opened. Defining these expectations helps oncologists to manage their time and encourages improved communication with clinical research staff5.
Other strategies include hosting a robust biweekly study selection feasibility meeting, sharing the feasibility meeting facilitator role and working with non-oncology service line leadership to ensure ongoing support for clinical trials. At Marshfield Clinic, oncologists take turns presenting potential studies to their colleagues. This rotation promotes engagement and often sparks insightful discussion. The selection process is further enhanced when varying experiences and perspectives are combined in the decision-making process.
In the same spirit, the oncologists are reaching out to the service line leaders to facilitate better working relationships among ancillary departments. This early-stage collaboration is essential when opening trials that require involvement of various specialties.
The majority of practicing physicians have expressed their desire to utilize clinical trials as treatment options3,4. Additionally, these physicians are basing their treatment decisions on evidence gained through clinical trials. Making clinical trial participation accessible in the clinic setting has great potential to improve patient outcomes.
One method of accomplishing this goal is physically relocating research staff in the clinical area of the health system. More frequent face-to-face interaction between oncologists, nurses, and research staff results in increased awareness of available clinical trials and increased patient contact with research staff.
There is a discrepancy between the needs of the writers and administrators of research protocols and those of the physicians who are relied upon to enroll patients to the protocols6,7. Maintaining the integrity of the data results in strict eligibility criteria for many treatment trials makes it difficult, at times, to enroll realistic patient populations. Study chairs must consider the possibility of allowing physicians some discretion when enrolling patients. The data is not truly pragmatic if it is gathered entirely from patients who do not fit the usual profile of the disease being treated.
The selection process utilized by a clinic when deciding which clinical trials to open requires thoughtful consideration and realistic feasibility analysis. Ensuring the clinic has an appropriate patient population that may meet the eligibility criteria is often challenging, yet paramount to the success of the trial.
In addition, sites should consider conducting a formal cost analysis that considers all resources that may be needed and the staff workload to successfully execute the study. It is paramount to not only consider the patient care costs, but to include the administrative costs. It is also important to note that highly complex protocols or protocols that focus on rarer cancers may not enroll many patients, but are often opened for orphan diseases or specific patient population.
To minimize the administrative barriers, health care systems should consider the use of Central Institutional Review Boards (CIRB) whenever possible. The National Cancer Institute’s CIRB is an example of a well-run CIRB and allows for the streamlined review of NCORP studies.
In addition, research sites should have well-documented processes for opening studies. As in many cases in health care, a one-size fits all approach will not work since administrative processes must be scalable to fit the needs of the study. Without proper planning, small obstacles can completely stall the opening of a study.
During all phases of the study opening process, study teams need to be on the vigilant lookout for software and websites that may require I.S. Security Review, unique study training requirements, or special drug or specimen storage requirements. It is important for the oncology research team to have a strong working relationship with IT/IS, Legal, Compliance/Privacy, Lab and Pharmacy.
The importance of regular communication of new protocols cannot be overemphasized and communication methods must go beyond email. Principal Investigators should provide study updates at department and/or service line meetings. Study enrollment progress and goals should be reported along with enrollment challenges.
In addition, health care systems should consider the use of technology to increase clinical trial enrollment. It is common for NCORPs, and other large oncology research centers, to have hundreds of active protocols. Tools must be developed or purchased to streamline the identification of potentially eligible study participants and, likewise, identify protocols that match a patients disease.
Research team solutions
Building the right team model for your health care system is critical to the long-term success of an oncology clinical trials program. In the past, many oncology research groups have chosen to develop disease-specific teams to implement clinical trials. While this method is suitable to large clinics where physicians treat only one type of cancer, it is not cost effective in smaller health systems and most community practices, where provider disease specialization is not possible. Smaller systems frequently require study teams to be based on geographical location. This means that research team members must receive education and training in all types of cancer.
Many oncology clinics have utilized a disease-based model in research, which has resulted in multiple “silos” of staff rather than a cohesive group. Shifting to a team-based model has resulted in increased clinical trial enrollments at Marshfield Clinic. Oncologists are partnered with a research nurse and coordinator who implement and manage any trials that are pertinent to that oncologist’s patients, regardless of diagnosis.
In addition, new research support positions have been created, which allows more time for nurses and coordinators to screen and meet with patients. A key position is a dedicated project manager for clinical trials. This role facilitates the opening of new clinical trials in a timely manner, ensuring that patients have a variety of studies available to them.
Traditionally, education and training of research teams have taken the form of attending conferences hosted by research organizations8. While there is some benefit to attending industry conferences, it may not be the best way to provide education. There may be more benefit to research staff to attend small classes or clinics that focus on a related group of topics. This method allows for greater detail in the information disseminated and encourages peer discussions.
At Marshfield Clinic, research staff are encouraged to attend NCORP research base meetings and to serve on the committees associated with those research bases. These activities expose team members to researchers from many regions of the country and, at times, globally. The insights gained in these relationships assist Marshfield Clinic staff and management in their efforts to develop best practices in the clinical trial program.
Finally, never underestimate the power of positivity. Research staff at Marshfield Clinic were asked to send a group email to the research team and oncologists each time a new patient is enrolled to a clinical trial. All members of the team then have the opportunity to reply with positive reinforcement and encouragement.
This practice has resulted in a change in the culture of the research department to one in which staff is engaged and supportive of one another, as well as invoked a friendly competition among teams.
One of the most frustrating aspects of cancer treatment is the constant battle with insurance companies over treatment reimbursement and clinical trial participation in general. Most federally funded reimbursement programs allow patients to participate in clinical trials, however, there are differences among states in the interpretation of these clauses1, 9. Federally funded programs should be consistent throughout the country.
Private insurance companies have long denied patients participation in clinical trials based on the potential for adverse events with investigational products10. During treatment trials, investigational drugs or devices are typically provided by the research organization. Therefore, the insurance companies are only being asked to pay for standard of care treatment.
Since there is no way to accurately predict which patients will have adverse reactions to any medication, it is unreasonable to assume that adverse events increase in investigational drugs by the time clinical trials reach phase II and III. Perhaps legislation to close this loophole is necessary in order to provide patients with more treatment options.
Marshfield Clinic is constantly reviewing and revising their prior authorization process. After an initial investigation into the desired components and wording of prior authorization submissions, staff were trained on how to submit prior authorizations and follow up, as needed, based on the response from the insurance company.
Providing accurate information and appropriate details concerning the clinical trial, patient condition, and rationale for treatment decisions is key to the approval of the prior authorization. However, even with a well-documented process, the oncology team is relying on the Prior Authorization Team to ensure the request receives the appropriate approvals.
In many cases, insurance companies will broadly deny all requests for participation without looking at the study. The only way to resolve this is through appealing the decision, which unfortunately is costly in staff time and delays the patients’ treatment. It is imperative that health care systems fight for the inclusion of clinical trials in plans they manage or own.
While there are many barriers to enrolling patients in clinical research trials, there are solutions out there. It is imperative that traditional practices at the administrative, physician, and research staff levels be evaluated for their continued effectiveness. It is necessary that insurance practices be standardized so that greater coverage is available to all oncology patients.
As medical advancements continue at a rapid pace, physicians, health systems, and insurance companies must be willing to adapt practices to accommodate patients’ treatment needs.
Corresponding Author: Adedayo A. Onitilo, MD, PhD, MSCR, FACP
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