Most sponsors prefer to conduct clinical trials of new cancer treatments at major academic research centers with a long track record, well-published principal investigators (PIs), good infrastructure, and a recognizable “brand.” However, large academic centers have many competing studies and must limit the number of trials they run due to staffing and asset constraints. At Parexel, we see institutional disease and resourcing review groups increasingly reject labor-intensive studies, particularly as cancer trials become increasingly complex.
The traditional approach to site selection in oncology has created bottlenecks and fatigue at major centers. It has restricted patient access to potentially life-saving therapies by enrolling only those with the means and ability to travel to major urban areas where most academic centers are located. This has limited the geographic, socioeconomic, and racial diversity of studies.1
To solve this growing problem, at Parexel, we are increasing our engagement with regional and community sites while upholding the quality standards typical of major academic centers. We follow five best practices to position regional and community sites for success and mitigate risks for sponsors:
1. Collect and curate site data precisely
At Parexel, we maintain a comprehensive profile of oncology sites’ interests, geographies, capabilities, patient populations, and principal investigators (PIs) in our Site Alliance Oncology Network. This enables us to match the right sites with the trials that meet their patients' needs. If a site does not fit the protocol, we don’t burden them with unproductive feasibility requests.
Up-to-date data gathered directly from sites speeds enrollment. For example, we recently selected sites for a first-line solid tumor treatment trial. The trial enrolled a subset of patients with a specific backbone chemotherapy regimen. While the regimen is considered standard of care, many major academic centers use different approaches to treat newly diagnosed patients. Using our data, we selected community sites that utilized the protocol-specified regimen and exceeded the sponsor’s patient enrollment expectations.
Study design, phase, and complexity determine whether community sites are appropriate for a precision oncology trial. And as protocols are amended, the answers change. Last month, we finalized the site plan for a cancer trial that did not require overnight hospital stays. Many suitable community sites were on the list. However, a last-minute change to the protocol required four overnight hospitalizations, which most community sites in the United States cannot provide. Experience and a well-curated database allowed us to revise our site selection quickly.
Study design, phase, and complexity determine whether community sites are appropriate for a precision oncology trial.
To enhance site selection further, a senior assessor visits every site within our oncology network and compiles a comprehensive structured document specific to conducting cancer trials. This contains an extraordinary level of detail. It captures a site’s investigational product storage capabilities by temperature (controlled room temperature, refrigerator, freezer, nitrogen freezer, etc.) and the storage temperature monitoring systems, including the hardware and software used. It records the make and model of radiology equipment such as CT scanners, MRIs, PET/CT, and bone scanners and how often they are calibrated. It outlines a site’s pharmacokinetics and pharmacodynamics capabilities, the standard of care used to treat specific cancers and tumors, and the research priorities of its oncology PIs. It also details contract requirements, patient reimbursement systems, average timelines for a fully executed contract, previous FDA Form 483s (and how they were resolved), monitoring visit processes, electronic medical records software, and more.
Recently, a sponsor came to us concerned that they might be unable to get their on-site monitors timely access to trial data for an upcoming visit. We consulted the site assessment document and explained the facility’s process and timing for accessing and monitoring trial data. The sponsor was relieved, and the on-site monitoring went without incident. We resolved the situation without having to take site personnel’s time to explain or defend their longstanding practices.
2. Partner with sites
At Parexel, we invest time and resources in listening to sites and understanding the burdens and obstacles of clinical trials. We treat them with respect as partners. For example, one common complaint is the introduction of multiple handheld data entry devices and databases. Too many new passwords and cumbersome user interfaces to remember and learn mean study staff spend time managing systems instead of treating patients. As a result, we scrutinize the number of new tools and technologies utilized in any given protocol.
If a site enters our network, we have already determined that it has the skill sets, expertise, support, and infrastructure to be considered for a trial: we do not increase the administrative burden with unnecessary and duplicative requests.
Sponsors depend on sites to meet tight deadlines. Recently, a sponsor requested a site turn around a signed contract in 24 hours. The timeline was not feasible, as the study was a complex cancer trial. Acting as the go-between, we explained the constraints to the sponsor and worked with the site to smooth the process. We provided the sponsor with additional options, the contract was signed before the forecast site initiation visit (SIV) date, and the site met its start-up target.
Early oncology dose escalation trials are driven by the first patient in (FPI), which depends on the site start-up cycle. Therefore, at Parexel, we focus on streamlining study start-ups. Our site profiling document speeds decision-making because we don’t need to revisit a site or request more information—we already have the answer.
3. Strive to reduce the burden of training
Training sites to conduct a clinical trial in compliance with regulatory, clinical, data, and ethical requirements is critical, but it’s still an imperfect science. Many sites find that portions of the mandatory training are repetitive, irrelevant, and time-consuming. That’s because the traditional approach to site training covers every topic, from the purpose of clinical research to a primer on data collection. Only after that does it delve into study-specific training. Every protocol is treated as though it is the site’s first ever.
CROs and sponsors should provide tailored site training that considers seniority, experience, context, and qualifications. For example, registered nurses and doctors can skip training for medical procedures such as electrocardiographs. Instead, site staff can be asked to sign a statement of knowledge for a procedure instead of attending redundant training modules. Soliciting input from site staff while developing training materials will result in a more thoughtful plan.
Many sites find that portions of the mandatory training are repetitive, irrelevant, and time-consuming. CROs and sponsors should provide tailored site training that considers seniority, experience, context, and qualifications.
4. Advocate for sites
Due to the complexity of oncology trials and the fraught patient experience, Parexel takes a white-glove approach to site support. All our clinical trial professionals have an oncology background and are passionate about the field. Many have lost loved ones to cancer or are cancer survivors. We advise our team members to ask themselves: Would you ask a relative to do this study? If the answer is no, explore ways to lessen the patient’s burden.
We do everything we can to ensure that sites are assigned to studies that align with their patients’ needs and provide them with more treatment options. We rely on our in-depth data to help sites avoid the disappointment of not being selected. Parexel is available to sites 24 hours a day, seven days a week, in every time zone worldwide. We are the point of escalation for sponsors and provide uninterrupted site support.
Sponsors will always have the final say on where they conduct their trials and whether they will consider community sites. However, where sponsors and CROs manage the risks through due diligence, continuous support, and fast and effective troubleshooting, community sites can accelerate recruitment and enrollment and increase patient access.
Sponsors will always have the final say on where they conduct their trials and whether they will consider community sites. However, where sponsors and CROs manage the risks through due diligence, continuous support, and fast and effective troubleshooting, community sites can accelerate recruitment and enrollment and increase patient access.
5. Compensate fairly and on time
One of the greatest challenges for sites in clinical research today is getting paid on time. According to a recent survey, 82% of sites are negatively affected by late payments.2
The problem is especially acute in oncology. Cancer studies are long-term commitments for sites: the active phase of the trial may last three to five years, while safety follow-up visits could extend to a decade or more. Complex seamless trial protocols that morph from dose escalation to the pivotal efficacy phase are resource- and labor-intensive, upfront and later. They often require safety data collection after the study ends and even after a drug reaches the market.
Late payments can breed discontent at sites. At Parexel, we have a team dedicated to handling contracts and payments. The liaison assigned to each trial handles delinquent payments and resolves the sites’ financial issues.
Sponsors should consider the complexity of a protocol to ensure adequate payment for the work sites do. For example, many are eager to utilize remote source document verification. However, we advise them that this is initially more expensive and time-consuming for sites than preparing for on-site visits because it entails learning new software, obtaining licenses, and ensuring data privacy, among other things. Remote monitoring may be well worth this investment, but sponsors must understand the upfront costs. We advocate for sites by characterizing the burden of each protocol precisely.
Inflation, remote monitoring, next-generation sequencing tests, and managing sensors and wearables are just a few factors driving up the cost of trials for sites. For advanced cancer indications, site staff often must describe and document multiple prior treatment regimens (up to four or five) to determine a patient’s eligibility. Site payments must adequately reflect the effort and resources required for trials to ensure sites can sustainably participate in clinical research.
Expanding trials to community sites accelerates precision oncology
The increasing number and complexity of oncology clinical trials—many replete with exploratory endpoints, radiographic assessments, and genetic testing—is straining the traditional clinical research infrastructure.3 Community sites are eager to conduct precision cancer trials because they want their patients to access potentially life-altering and life-saving treatments. By bringing trials closer to patients, we give them access to cutting-edge treatments. Sponsors also benefit from faster enrollment times, more diverse patient populations, and the same high-quality trial data.
Contributing Experts
