Deviations in Medical Device Clinical Studies

Clinical Trial Services

Introduction

During the conduct of a study, there may be instances where the study protocol is not followed as intended. These events are commonly referred to by various terms including deviation, violation, variance, departure, or non-compliance. For this blog, the term “deviation” will be used. Regardless of terminology, deviations in medical device clinical studies need to be processed in accordance with the Sponsor and/or Investigator quality system procedures to not only comply with regulatory requirements, but also to uphold the integrity of the study and ensure patient safety, rights, and welfare. Deviations can occur at the patient, site, or study level and can be isolated incidents or indicative of systemic problems. Rather than being viewed solely as negative events, deviations should be seen as opportunities to improve study conduct and quality systems.

Regulatory context

Deviations in medical device clinical studies are not well-defined in FDA regulations nor ICH GCP E6(R3). However, ISO 14155:20 defines a deviation as an “instance of failure to follow, intentionally or unintentionally, the requirements of the CIP [clinical investigation plan]”. Recently, FDA published a draft guidance on protocol deviations, emphasizing that not all GCP non-compliance should be handled within the protocol deviation framework. Instead, FDA recommends that sponsors distinguish between protocol deviations and broader GCP compliance issues.  Furthermore, GCP assigns responsibility to the sponsor for defining study-specific criteria and to classify  deviations appropriately. As a result, the protocol should proactively include definitions and examples of important and other (e.g., minor, noncritical, and non-significant) deviations to guide consistent classification and management.

Processing and Reporting

When a potential deviation is identified, the sponsor should first confirm whether it qualifies as a protocol deviation and classify it as important or other (e.g., minor, noncritical, or non-significant). . Deviations can be assessed using a Corrective and Preventative Action (CAPA) process. Conducting a root cause analysis allows sponsors and sites to identify the underlying reasons for deviations—whether they stem from unclear protocol instructions, training gaps, or operational challenges. This way, targeted corrective and preventive actions can be implemented.

Deviations should be reported as specified in the protocol and in accordance with IRB and FDA requirements. According to 21 CFR 812.150(a)(4), investigators must notify the sponsor and IRB within 5 working days if a deviation was necessary to protect the life or physical well-being of a patient in an emergency. In contrast, planned deviations (i.e., intentional) that could impact scientific integrity or subject safety require prior written approval from the sponsor, IRB, and potentially the FDA. Other cases of deviations may still require IRB notification, depending on that IRB’s specific policies and reporting timelines.

Reducing deviations

Preventing deviations begins during the protocol development phase. Protocols should be carefully reviewed to confirm that eligibility criteria, visit schedules, and procedural requirements are feasible for both sites and patients. During the study, regular monitoring, site communications, and data review can help identify early warning signs of non-compliance, confusion, or future systemic issues. Additional tools such as protocol training, clarifying memos, and Case Report Form completion guidelines can enhance consistency and reduce ambiguity, further ensuring protocol compliance, especially for complex procedures and/or endpoints.

Conclusion

Deviations in medical device clinical studies are more than just compliance concerns; they offer opportunities to identify gaps and improve study processes. When managed appropriately, discovering and addressing deviations can lead to robust protocols, better site performance, and ultimately, more reliable study outcomes.

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