Feasibility/Site Selection Process Ripe For Improvement

By Life Science Connect Editorial Staff

Twenty years ago, the vast majority of clinical trials — about 80% — had not enrolled sufficient patients by their target start dates. This figure is not much lower today, despite the existence of specialized patient recruitment companies, sponsors with patient recruitment departments, and numerous ways to improve the site feasibility process.

The abundance of recruitment tools and strategies has done little to alleviate tension among sponsors and CROs, which tend to believe sites inflate recruitment numbers. PIs and site staff also get frustrated when asked to make a recruitment assessment before the study protocol is final or even before a draft synopsis exists.

According to panelists during a Clinical Leader Live titled “How Can We Improve Clinical Trial Feasibility Processes?” one of the keys to a more effective feasibility process is simply more transparent communications and collaboration between sponsors, CROs, and sites. Sponsors must provide clear information to each site to enable a more accurate recruitment assessment, and the sites must properly digest the information to give an accurate projection. Then, follow-up discussions between investigators and sponsors are critical in clarifying perspective among all parties and moving everyone toward a more accurate understanding of each site’s feasibility.

Use Data-Driven Solutions for Patient Recruitment

Advancements in technologies like data analytics, AI, machine learning (ML), and real-time monitoring are helping sponsors and sites find agreement in recruitment figures. For example, AI and ML have streamlined a site feasibility process that was traditionally labor-intensive, involving manual collection and analysis of site data. Modern CTMS platforms now can integrate data from multiple sources to provide a comprehensive view of each site in terms of performance, capability, and historical track record — metrics used by AI and ML to rank those sites.

Further, technologies like EHR and patient-recruitment systems make it easier to manage and analyze site-related information for a feasibility assessment. The data these tools generate enables more accurate and timely insights about sites and their performance, helping sponsors be more proactive in adjusting recruitment strategy and encouraging sites to provide more realistic recruitment forecasts.

Sponsors and CROs can leverage historical data and some predictive models to validate how each site estimates its recruitment numbers. If the sponsor or CRO identifies an outlier and asks the investigator why they projected that amount, something could be revealed that helps inform a more accurate feasibility assessment (e.g., have both parties considered all possible exclusion criteria?). Additionally, integrating clinical ops historical data with real-world data helps investigators and sponsors to better understand the diversity within patient pools and work toward a more representative trial.

It's also important to remember that research-naive sites do not show up on historical data sets. Therefore, the more sponsors and CROs rely on data sets to inform their site list, the more difficult it is for such sites to gain traction. The industry must be open minded and not blindly relying on what that data output is saying, particularly when considering the clinical value of enrolling diverse populations.

Ask the Right Questions

To ensure the site feasibility process goes smoothly, the sponsor needs to provide all applicable data to the site, with clear direction and appropriate expectations. By narrowing the focus to key elements that impact enrollment, the site can respond more accurately. For example, with the questionnaire,  try to distinguish between qualitative/strategic questions and operational questions. Do not waste time with questions that can be asked during pre-study visits (PSVs).

The questionnaire should contain the basics, such as:

• Is the site interested in participating in this specific study?
• Is it capable of executing this study?
• Does the site have access to the target patient population?
• Can the site complete enrollment?

Usually, a CRO partner is working on a condensed timeline to kick off the study from the moment it is hired/contracted, because it costs the sponsor money every day the CRO is active. So, the more the sponsor can accomplish ahead of time to engage sites or to connect with investigators — informing study design, learning the patient population, planning for a high standard of care, etc. — the more profound the impact on the pace of site selection and enrollment.

Data-Informed Site Feasibility

In January 2021, the American Society of Clinical Oncology (ASCO) released recommendations to improve the site feasibility assessment process for oncology clinical trials, and the principles involved are widely applicable.ⁱ Among the group’s recommendations was streamlining the feasibility assessment process. To achieve this goal, a combination of quantitative and qualitative methods exist to measure a feasibility study’s effectiveness.

A key measure of success is how accurately sites are selected; a quantitative assessment can track the number of sites selected that are successfully enrolling patients, as well as how many patients are enrolled at each site versus the target number. A qualitative method also can review how those sites were chosen based on the aforementioned criteria of demonstrating interest, capability, and access to the appropriate patient population. Emphasizing high-quality data and completeness in data reporting from sites minimizes data queries and discrepancies. Good performance under these metrics also can indicate strong site training and protocol adherence.

This is because site feasibility includes protocol feasibility: reviewing the protocol design and discovering challenges to patient enrollment or even investigator recruitment. If sponsors discover too late that their eligibility criteria or schedule assessment are not aligned with the sites, the timeline and cost impacts are significant. Some protocol amendments cannot be avoided, so the sponsor’s ability to understand and circumvent the avoidable ones is another qualitative metric of site feasibility success.

Some CROs build site lists that are triple or quadruple the targeted number of sites. Even though they are leveraging useful data to build their lists, they are not executing quality control (QC) well, or they are lumping people together based on a loose association with a given indication or a past study. Using data from past enrollment performance and regulatory startup performance at the site level can help the sponsor’s efforts to be more structured.

Clinical quality assurance (QA) can be a great ally to sponsors during site selection, but in-depth collaboration is important to find out what value they can bring to the feasibility process, since it might vary from company to company. This goes back to creating targeted site lists: by exploring options up front and accessing the right data sets, sponsors can create a profile describing the types of investigators and sites they want to include in the study.

The list can be narrowed via country feasibility based on regulatory environments, logistics, or other factors relevant to a given study. Once this is planned, sponsors can be more targeted in building a viable site list and beginning outreach. By having a better-informed protocol and considering country feasibility, the number of sites a sponsor needs to contact is much less and the response rate from site outreach tends to be significantly higher.

Some industry experts have suggested the creation of a central repository of site capability/feasibility that focuses on general infrastructure and non-protocol-specific questions about site capability. While the idea has promise, such a repository faces numerous obstacles — the inherent nature of competition between sponsors to work with well-regarded sites among them — and would have to result from a combined, industrywide collaboration.

Think Outside the List

Whether a clinical trial is studying rare disease therapies or large-volume vaccines, three Ps define the approach to site feasibility: patients, product, and procedures. Advanced technological and methodological tools can assist sponsors, CROs, and sites in identifying fruitful collaborations, but person-to-person discussion and communication — understanding your partners’ challenges and helping them work toward positive outcomes — must drive those collaborations.