Why Sponsors Must Check For Site GCP Adherence During Feasibility Studies

By Donatella Ballerini, GCP consultant

In the complex world of clinical research, GCP stands as a critical framework ensuring trial participants' safety and data integrity. While GCP’s role in the operational conduct of clinical trials is well recognized, its impact during site feasibility is equally vital yet often under-discussed. This article explores how adherence to GCP influences these early and crucial stages of clinical trials, shaping their success and credibility.

Site feasibility determines whether a particular clinical site is suitable for conducting a specific clinical trial. Site selection criteria typically include the availability of the target patient population, investigator qualifications, site resources (e.g., equipment, staff), and the site's previous performance in similar trials. A thorough feasibility assessment ensures that the selected sites can meet the study's demands and recruit and retain participants effectively.

So, if site feasibility assesses the suitability of specific research sites to conduct a clinical study, then why are audit and inspection issues so frequent? (If you’re privy to internal information, you likely understand the breadth of this issue. If you aren’t, you need only review regulatory reports, such as FDA Warning Letters, to understand that GCP gaps still exist.) In some cases, these issues arise because sponsors have not investigated or established sites’ GCP knowledge and expertise before starting a clinical study.

Redefining Site Feasibility With A GCP Perspective To Mitigate Risk

As we know, GCP is a cornerstone of ethical and scientific quality standards in the design, conduct, and reporting of clinical trials. However, GCP compliance is not only a regulatory requirement but a critical factor that can significantly influence the outcome of site feasibility assessments. The assessment of whether a site is suitable to conduct a clinical trial depends on different dimensions but heavily on its adherence to GCP guidelines, which ultimately ensures that the rights, safety, and well-being of trial subjects are protected and that the data generated are credible and accurate.

When evaluating a site, one of a sponsor’s first considerations is the patient population: Does the site possess access to enough patients who meet the study’s inclusion/exclusion criteria? If the answer is yes, the site lands on the “good” list and will probably be selected. But what about the site’s history of GCP compliance? Does the site have the knowledge, expertise, process, and staff to manage patients and data properly according to GCP? Even if a site is a top recruiter for a clinical trial but it’s failing to adhere to GCP, there is a high probability the sponsor is wasting its time and money. The capacity and ability to recruit lots of patients is not the only element to be considered during site feasibility; if a site lacks GCP compliance, its data (and patients) are at risk.

Let’s think about a site that failed to ensure data integrity and control or that didn’t treat the patient according to GCP. Is that (top recruiter) site still a “good” site? Probably not, and a good GCP site feasibility conducted in the planning phase could have saved resources and time. A GCP site feasibility includes reviewing past audits, inspections, and any regulatory actions taken against the site. A site that consistently adheres to GCP is more likely to have robust standard operating procedures (SOPs), well-trained staff, and a clear understanding of the regulatory environment. This reduces the risk of non-compliance during the trial, which can lead to delays, increased costs, or even the invalidation of trial data.

Incorporating GCP compliance into site feasibility assessments helps sponsors mitigate various risks associated with clinical trials. Noncompliance with GCP can result in regulatory penalties, critical findings, trial delays, negative public perception, and, in extreme cases, the termination of the trial or the disqualification of data. By selecting sites with a proven record of GCP adherence, sponsors can reduce these risks and increase the likelihood of a successful trial outcome.

GCP For Quality And Reliability Of Data

One of the primary reasons why GCP adherence is crucial for ensuring the reliability of clinical trial data is its emphasis on data integrity (especially in the new ICH R3 with the concept of data governance). GCP guidelines mandate that clinical trial data must be accurate, complete, and verifiable. During a GCP site feasibility, sponsors should assess the site’s data management practices, including the accuracy of data recording, the security of data storage, and the traceability of data changes. Sites that demonstrate strong data management practices in compliance with GCP should be preferred over those that don’t to avoid critical issues during the active trial.

A frequent finding during site audits is data and source documentation mismanagement. Too often the site processes are weak or absent, and that leads to serious risks in data reliability. That is the reason why during site feasibility, sponsors should assess whether a site has the necessary processes and controls in place to maintain source documents and data control. This includes evaluating the site’s data collection methods, data storage systems, and the procedures for handling data discrepancies.

Another critical aspect of GCP adherence is its role in protecting against bias in clinical trial data. GCP guidelines emphasize the importance of maintaining objectivity in data collection and reporting. During site feasibility, sponsors should assess whether the site has measures in place to prevent bias, such as blinding and randomization procedures, as well as the independent oversight of data. Sites that adhere to GCP are less likely to produce biased data, which is crucial for drawing accurate conclusions about the efficacy and safety of the investigational product.

Adherence to GCP not only ensures the reliability of data but also enhances the credibility and trustworthiness of the clinical trial and the sponsor itself. Patients, healthcare providers, regulatory agencies, and others are more likely to trust the results of a trial that adheres to GCP. During site feasibility, sponsors should evaluate the site’s commitment to GCP as an indicator of its overall reliability and professionalism. Sites that adhere to GCP are more likely to be trusted partners in clinical research, contributing to the successful conduct and completion of the trial.

7 Practical Tips For Conducting GCP Site Feasibility

1. Assess GCP Compliance History

• Request and review the site’s past performance and compliance history with GCP guidelines. Check for any regulatory findings, audit reports, or previous clinical trial deviations. Sites with a strong GCP track record are more likely to conduct trials efficiently and ethically.

2. Evaluate Investigator And Staff Experience

• Ensure that the principal investigator (PI) and key staff have sufficient experience and training in GCP by inquiring during an interview and/or verifying their training certificates. Their familiarity with regulatory requirements and clinical trial protocols is crucial for the successful conduct of the study.

3. Examine Site Infrastructure And Resources

• Verify that the site has the necessary infrastructure, such as equipment, facilities, and technological resources, to conduct the study per GCP standards. The availability of these resources ensures that the site can maintain data integrity and participant safety.

4. Check Patient Recruitment Capabilities

• Assess the site's ability to recruit and retain the target patient population. Consider their access to a diverse patient pool and their strategies for meeting enrollment targets without compromising GCP requirements.

5. Review Standard Operating Procedures (SOPs)

• Ensure that the site’s SOPs are aligned with GCP guidelines. SOPs should cover key areas such as informed consent, data management, and adverse event reporting, and be regularly updated to reflect the latest regulatory standards.

6. Assess Data Management Systems

• Ensure that the site has a robust data management system in place, such as data governance and an audit trail review process, that comply with GCP standards. The systems should be capable of maintaining accurate, complete, and secure data throughout the trial.

7. Evaluate Communication And Reporting Practices

• Check the site’s practices for communication and reporting to ensure they align with GCP requirements. Effective communication between the site, sponsor, and regulatory bodies is essential for timely reporting of any issues.

Challenges To Conducting A GCP Site Feasibility

Despite all its benefits, implementing a GCP perspective into the site feasibility process can have some challenges. GCP knowledge and expertise are expected by regulatory authorities but how to meet this expectation is unclear.

Complexity Of Regulatory Requirements

In multinational trials, the regulatory landscape can differ significantly from country to country. Sites may have varying levels of familiarity with GCP, and their adherence to local regulations may not fully align with international GCP standards. This requires a thorough understanding of both local and international regulations during the feasibility assessment.

Diverse Levels Of Experience Among Sites

Sites often vary in their experience with clinical trials, especially regarding GCP adherence. Some sites may have extensive experience, while others, particularly in emerging markets, may have limited exposure to GCP. Sites with less experience may need additional training or support to meet GCP standards, which can complicate the feasibility assessment process. Moreover, identifying and quantifying the level of training needed can be challenging.

Investigator And Staff Training And Compliance

GCP compliance depends heavily on the training and competence of the investigators and study staff. Inadequate training can lead to deviations from the protocol, improper handling of adverse events, and noncompliance with documentation standards. Ensuring that all personnel involved in the trial are adequately trained in GCP is critical. The feasibility assessment should include a review of the training programs in place at the site, as well as an evaluation of the staff’s understanding and adherence to GCP principles, which can be challenging. Is the completion of GCP training sufficient to ensure GCP adherence by site staff?

Study Design

Sometimes, the site feasibility criteria are strictly linked to the population availability. Some diseases are concentrated in certain countries, for example, and sometimes only a few sites can treat a disease adequately. In this scenario of constraints, it is important to implement preventive actions at the site to ensure a good level of GCP compliance.

Time Constraints

Finally, another challenge is balancing the need to expedite the site feasibility processes with the requirement to maintain rigorous GCP standards. Rushing these assessments can lead to oversights, increasing the risk of noncompliance later in the trial. Sponsors must strike a balance between speed and quality to ensure that the selected sites are both compliant and capable. Spending more time at the very beginning of site feasibility with a GCP assessment can save time later when an audit and/or monitoring can lead to critical and major findings, compromising the entire clinical trial.

Final Thoughts

GCP plays a critical role in site feasibility processes, ensuring that clinical trials are conducted with the highest standards of quality, ethics, and regulatory compliance. Adherence to GCP during these early stages can mitigate risks, enhance credibility, and contribute to the overall success of the trial. It plays a key role in maintaining data integrity, standardizing processes, protecting against bias, facilitating regulatory approval, and enhancing the credibility of the trial. By selecting sites that adhere to GCP, sponsors can ensure that the data generated is reliable, credible, and acceptable to regulators, ultimately contributing to the success of the clinical trial. Integrating GCP into site feasibility is a strategic approach that can significantly impact the outcome of a clinical trial. Sponsors, CROs, and sites that prioritize GCP compliance from the outset are better positioned to conduct successful, credible, and ethically sound trials.

About The Author:

With 16 years of experience in the pharma industry, Donatella Ballerini first gained expertise at Chiesi Farmaceutici in the global clinical development department, focusing on clinical studies in rare disease and neonatology. Later, in global rare disease, Donatella served as a document and training manager, where she developed and implemented documentation management processes, leading the transition from paper to eTMF. In 2020, she became the Head of the GCP Compliance and Clinical Trial Administration Unit at Chiesi, ensuring all clinical operations processes complied with ICH-GCP standards and maintained inspection readiness. In 2021, she joined Montrium as the Head of eTMF Services, where she helps pharmaceutical companies in eTMF implementation and process improvement, and also works as an independent GCP consultant. Donatella has been a member of the CDISC TMF Reference Model Education Governance Committee since 2023 and the CDISC Risk White Paper Initiative since 2024.