The guidance addresses aspects related to the safety measures to be developed and introduced by the parties responsible for performance trials in order to ensure the safety of study participants while maintaining the accuracy and reliability of the study results.
Table of Contents
The Swiss regulating authority in the sphere of healthcare products (Swissmedic) has published a guidance document dedicated to performance studies involving in vitro diagnostic (IVD) medical devices. The document provides an overview of the applicable regulatory requirements as well as additional recommendations and clarifications to be taken into consideration by medical device manufacturers and study sponsors in order to ensure compliance. At the same time, provisions of the guidance are non-binding in their legal nature and are not intended to introduce new rules or impose new obligations. The authority also reserves the right to make changes to the guidance, should such changes be reasonably necessary to reflect corresponding amendments to the underlying legislation.
In particular, the guidance contains appendices that provide a detailed description of the information the authority expects to be included in the respective submission.
Risk Mitigation Measures
Under the general rule, a party responsible for the performance study shall duly develop and implement efficient risk mitigation measures, taking into consideration the stage of clinical development, innovation, and risk potential. In order to assist the parties involved in following the above requirement, the document provides an overview of the safety measures to be considered and, when necessary, incorporated into a study plan. The main goal is to identify potential issues as early as possible, preventing the study subjects from being exposed to unnecessary risk. However, the overview provided by the authority is non-exhaustive and merely illustrates the approach to be applied, while the specific scope of measures should be determined on a case-by-case basis.
According to the guidance, safety measures for pre-market interventional performance studies should include:
- Procedures for the installation of devices and instructions or training of users This also includes the procedures to be followed when taking samples, especially if the procedure is surgically invasive. The description should also include details about the necessary qualifications.
- Risk-adapted recruitment and intern analysis As explained by the authority, the number of study subjects should not be unnecessarily large, and study phases should be clearly defined. Furthermore, an interim analysis is required before the commencement of each new phase. In terms of the interim analysis, the authority mentions that (i) the data needed should be properly defined, including the number of follow-ups, and (ii) source data verification is required.
- Considerations related to the timeframes for submissions of safety-related data The authority mentions that in cases of repetitive errors, the respective investigation sites should be subject to retraining. In the event of any unexpected problems identified, risk-mitigation measures applied should be duly re-evaluated, and suspension should be applied if reasonably necessary.
- Considerations related to the involvement of safety committees, including data monitoring committees, data safety monitoring boards, or data safety monitoring committees As further explained by the authority, in the case of a double-blinded randomized study, unblinded data should be subject to periodic assessment on a regular basis and also in case of unexpected events.
- Criteria to be applied to stop the study (the type and number of incidents due to which the study will be suspended)
- The procedure for systematic return and examination of medical devices is subject to investigation in the event of problems.
- The procedures for follow-up are necessary in order to ensure the achievement of study goals as well as the safety of patients.
- Details of contact persons and relevant procedures in case of serious incidents.
Endpoint-Related Considerations
As further stated by the authority, performance studies should be planned in a way that ensures the endpoints foreseen by the sponsor are recorded correctly, while any deficiencies related to the study planning or misses could impact the accuracy and reliability of the results.
In this respect, the following aspects are to be considered:
- The informed consent form used should include consent for the sharing of medical information with a contact person, allowing an investigator to request additional information about the patient’s state and disease from a general practitioner.
- The clinical performance study plan should address, inter alia, the following matters:
- Procedures for follow-up visits (if a subject can no longer be traced, his or her address and state of health should quickly be clarified by the investigator with the contact person);
- Monitoring plan (if a subject can no longer be traced, the monitor should check with the center on the appropriateness of attempts made to contact the subject and the relevant contact person);
- Missing data and statistical considerations (if the occurrence of adverse endpoints cannot be established, sensitivity analysis should usually be provided for the analysis of the effect of the missing data on the results).
- Details on reports, e.g., the number of patients lost to follow-up, as well as the results of sensitivity analysis.
The document also provides examples of potential issues related to inadequate study planning in the context of endpoints, namely:
- Failure to include the measures for the lost patients’ follow-up in a clinical performance study plan.
- Failure to address the sensitivity analysis (i.e., failure to take into consideration that subjects lost to follow-up might have incurred severe adverse effects).
Inclusion and Exclusion Criteria
Under the general rule, vulnerable persons could be included as study subjects only in case the equivalent findings could not be obtained in any other way. For the purpose of guidance, vulnerable persons are minors, adults lacking the capacity to provide their consent, patients that are in an emergency situation, or pregnant women. At the same time, the authority also mentions that the involvement of own employees is questionable due to the certain level of dependence.
Thus, a party responsible for a performance study should pay special attention to the inclusion and exclusion criteria to be applied when involving study subjects.
In summary, the present document provides additional clarifications to be followed when developing and implementing additional safety measures. The document also covers the aspects related to the follow-up procedures and practices to be employed by study sponsors.
How Can RegDesk Help?
RegDesk is a next-generation web-based software for medical device and IVD companies. Our cutting-edge platform uses machine learning to provide regulatory intelligence, application preparation, submission, and approvals management globally. Our clients also have access to our network of over 4000 compliance experts worldwide to obtain verification on critical questions. Applications that normally take 6 months to prepare can now be prepared within 6 days using RegDesk Dash(TM). Global expansion has never been this simple.
