Optimize Clinical Trial Site Selection in 4 Steps

What is site selection in clinical trials?

In clinical trials, patients interface with the trial and the study team (for enrollment, study visits, administration of interventions, follow-up) at independent sites - which are typically medical facilities such as hospitals, university research centers, and doctors’ offices.[¹] Site selection in clinical trials describes the process that sponsors undertake to identify, evaluate, and select suitable facilities for conducting the clinical trial effectively.

Clinical trial sites are independent institutions which are tasked with the responsibilities of patient recruitment, administering the study interventions, performing procedures and/or assessments, capturing patient data, and acting as the direct point-of-contact for medical assistance or resolving concerns related to the trial. Sites have a significant impact on the rate at which patients are screened and enrolled in a clinical trial, and further influence patient retention and experience, data quality, and adherence to regulations and the study protocol. Ultimately, each clinical trial site affects the overall timeline and quality of the study.[¹]

It’s relevant to note that many studies are shifting toward different trial models; in a fully decentralized, direct-to-patient trial, there might not be any sites involved at all. In this article, we are discussing site selection in the context of traditional site-based clinical trials. Site-based trials remain important, as it is simply not feasible for certain types of trials to be conducted without sites - for example those involving tests that are performed with specialized medical equipment or interventions that require supervision or guidance.

Why is site selection important in clinical trials?

A whopping 80% of clinical trials worldwide fail to reach enrollment targets, leading to monetary losses, extension of the trial timeline, and potentially the need to add new sites.[²] That statistics exemplifies why site selection plays such a crucial role in clinical trials. Each site will have its own unique patient database, outreach capacities, physician network, and local population demographic. Besides recruitment abilities, site performance directly influences many trial quality metrics, including treatment adherence rate, data quality, and follow-up completion.[³]

Thus, a critical element for running successful clinical trials is selecting high-performing clinical trial sites. Such sites will have the resources and capability to:

• Enroll patients swiftly
• Keep patients continuously engaged to prevent attrition
• Conduct the trial strictly in line with the clinical protocol and in compliance with regulations
• Maximize the quality and availability of data
• Navigate software tools being used by the sponsor and integrate them into workflows
• Increase the probability of the trial results demonstrating a statistically significant therapeutic effect[¹]

High-quality trial sites minimize delays and errors, ultimately extending the sponsor’s ROI, the effective lifespan of the novel drug’s patent, and the potential therapeutic benefit for patients in need.[¹]

On the flip side, underperforming or low-quality sites can result in delays, increased costs, low recruitment rates, and bad data quality, and could necessitate protocol amendments, addition of study sites, and even increases the risk to patients due to errors by the site team.[⁴],[⁵] In the worst case, poor site selection can lead to failure of the study.

What to look for: Considerations for assessing site characteristics and feasibility

When selecting sites, there are a few main considerations to keep in mind to increase the certainty that a study site will perform adequately. Here’s an overview of what to look for when engaging in site selection for clinical trials:

• Experience in related studies/fields of research
• Location and access to patient demographic
• Ethics and regulatory compliance
• Capacities: Facilities, staff, and equipment

Many factors that play into site selection are study specific, so it is not always possible to predict how a site will perform; nonetheless, these considerations will help you assess each site comprehensively and make informed decisions.[⁴]

Experience in related studies/fields of research

The strongest predictor of a trial site’s future performance is its past performance record. Sites that have performed well in the past tend to continue to do well.[¹]

However, it’s important for the clinical site to have a demonstrated track record of success in trials that are similar to your current trial, whether that be in regards to therapeutic area, trial phase, trial design, or target demographic (or ideally a combination of all these factors). Studies vary widely between fields of research and across phases and different designs, and patient groups can differ even more widely..

Sites with insufficient experience are more likely to commit protocol violations or provide low-quality data, which will ultimately require more on-site visits, training, and query resolutions.[⁵]

A 2019 survey of CROs and biotech firms revealed that these sponsors identified prior experience in conducting clinical trials as being a more important factor in site selection for early-phase trials than for phase III trials, since the former are operationally complex and demand a high level of expertise.[⁶]

Location and access to patient demographic

According to an online survey among decision makers for site selection in Nordic countries, 75% of respondents agreed that their company would cooperate with an inexperienced site if it had access to a large patient population.[⁶] In general, sponsors prefer to work with trial sites that have demonstrable access to the target population.[⁴]

Moreover, proper trial site selection in terms of geographical location can reduce long travel times for patients.[⁴] So, the location of the site is important in terms of both access to a local patient population and accessibility for that population. Sites with a strong database of patients with characteristics that are relevant to the study and a network of physicians and patient advocacy groups will generally have better enrollment capacities, and obviously prior patient recruitment expertise plays into that as well..

A 2016 overview looking at site performance in heart-failure intervention studies noted that rates of withdrawal of consent and loss to follow-up tended to be higher (worse) at smaller sites, and that high-volume recruiting centers appeared to have lower rates of rehospitalization and death than centers with fewer patients.[3] Care should be taken in generalizing these conclusions as they were drawn from a specific field of study, but they serve to illustrate that site size and enrollment influence more than just enrollment numbers.

Ethics and regulatory compliance

Sites that are closely familiar with ethical and regulatory standards, with strong experience in aspects such as informed consent and submissions to ethics boards and regulatory authorities, have an excellent advantage in terms of optimizing the overall regulatory compliance of the study and minimizing protocol deviations and non-compliance.[⁵]

You might ask to see staff certifications and training records that demonstrate their understanding of regulations, good clinical practice, ethical treatment of research subjects, and other aspects of operations pertaining to the specific study protocol.

Capacities: Facilities, staff, and equipment

A site may demonstrate all of the above qualities, but if they are lacking staff, equipment, or have poorly maintained facilities, they are likely to run into problems. The operational aspects of a clinical trial site should be taken into consideration, including the availability of staff who are adequately trained and experienced, clean and well-maintained facilities, medical equipment/devices required for the study, general medical supplies, standard operating protocols (SOPs), and established quality management/control systems or processes. Staff demeanor and their enthusiasm is also important for providing patients with a positive experience.[⁵] Once the site is tasked with executing the trial, it is up to them to gather high-quality data according to protocol, maintain records, communicate to the sponsor, and above all, treat participants safely, ethically, and help them feel valued. Thus, the site’s capacity for operational efficiency and professionalism should be a major factor in site selection.

Optimize clinical trial site selection in 4 steps

Now that we’ve gone over some of the main factors to keep in mind, we will discuss practical steps sponsors and CROs can take to go about actually assessing sites and selecting those best suited for their trial.

Step 1. Establish clear preliminary site selection criteria

First, determine the factors that are most important for your specific trial. Making a list of priorities will help you progressively narrow down the list of prospective sites. For instance, consider which of the factors mentioned above are most important for the sites to exhibit in order to conduct your trial optimally. Then, establish a site selection criteria checklist that reflects these priorities.[⁶]

As an example, your checklist could include the following in descending order of priority:

1. Access to a large population of patients with diabetes

2. High level of interest and commitment

3. Record of reaching enrollment targets

4. Strong protocols for data entry, documentation, and reporting

5. Easily reachable site personnel and backup

6. Having a key opinion leader associated with the site

7. Up-to-date equipment and facilities

Using this checklist, sites can be assessed in a way that prioritizes your most important needs. Such a list will also help in organizing and tracking the assessment process, as discussed next.

Step 2. Use tools to streamline site identification and selection

Sponsors and CROs can use various tools to facilitate their site selection process, such as site feasibility questionnaires or study feasibility questionnaires (SFQ) or a financial feasibility analysis tool. A site feasibility questionnaire tailored to your distinct study can help you ask various sites the same questions in a systematic way, tailored to your priorities and needs as identified in the preceding step. This standardized form should be clear and concise, and ideally digital to capture data more coherently. You can use field validation rules to collect responses in a way that makes the data easy to assess quickly.[⁵] Even simple forms can be integrated with basic automated data analysis functions, such as Excel sheets, to allow for streamlined preliminary identification of the sites that best match your trial’s needs and priorities.

A well-designed SFQ (consider mirroring best practices for eCRF design to optimize clarity and data consistency) will give you an overview to help you quickly understand a prospective site’s capabilities, experience, enrollment rate, equipment, staff resources, and other aspects that factor into your site selection decisions.

Step 3. Establish open, clear communication

While site feasibility questionnaires are often the standard for gathering basic information about potentially matching sites, it is beneficial to follow up with dialogue with the prospective sites identified in the last step. Not everything can be captured in the SFQ, and establishing communication with the site may be more effective for gaining insights into aspects such as staff enthusiasm and compassion, commitment and drive, and can give the site a chance to share more about its specific protocols, strengths, and what it can offer you. This also represents an opportunity to clarify any doubts remaining after collecting the SFQ, and to get a glimpse of how it will be to actually work with the site in practice.

Step 4. Clinical site visits

Finally, sponsors (or monitors) should visit sites in-person before formalizing the contract. These site selection visits are important as they represent the opportunity to verify information the site shared in the SFQ. The monitor can inspect facilities to ensure they are presentable, well-maintained, and comfortable for patients, check that that equipment is in working order, inspect training records and SOPs, and meet staff to get a feel for their demeanor.[⁵]

When visiting the site, check that the information entered in the questionnaire aligns with reality; any attempt at deception would be a bad sign as it could indicate distrust or potential problems down the line with compliance.

Conclusion

Site selection for clinical trials plays a crucial role in many aspects of the trial’s success: patient enrollment, engagement, retention, and satisfaction; treatment adherence rates; data quality; regulatory compliance; ethical treatment of participants; and adherence to protocol and target timelines. High-performing and well-matched sites increase the probability of the trial being a success, both for the sponsor and in the eyes of the patients.

When undertaking site selection, look for sites with experience in similar studies, access to the target patient demographic, solid operational practices and protocols, qualified and professional staff, adequate and well-maintained facilities and equipment, and a track record of success. Identify the factors that are most important for your study, and then streamline the site identification process using well-designed, online SFQs focusing on those priorities. After analyzing the SFQs to identify the most-promising sites, clinical trial agreements (CTAs) with sites should not be finalized until you have visited the site or otherwise confirmed its capacities. Following these steps will help ensure that the execution of your trial is in good hands and maximize the likelihood of successful outcomes.