The new article highlights the aspects related to serious adverse events, how they should be documented and reported, and the annual reporting requirements and procedures.
The Swiss regulating authority in healthcare products (Swissmedic) has published an information sheet dedicated to performance studies with in vitro diagnostic (IVD) medical devices. The document provides an overview of the applicable regulatory requirements set forth under the existing framework, as well as additional clarifications and recommendations to be taken into consideration by medical device manufacturers and other parties involved in order to ensure compliance thereto. At the same time, provisions of the guidance are non-binding in their legal nature, nor are they intended to introduce new rules or impose new obligations. The authority also reserves the right to change the guidance and recommendations provided therein, should such changes be reasonably necessary to reflect corresponding changes to the underlying legislation.
Reporting: Specific Aspects
The scope of the guidance covers, inter alia, the aspects related to reporting adverse events during the investigation. For instance, the document outlines the seriousness criteria to be applied, including, inter alia, the following:
- Serious deterioration in the health of the individual being tested or the recipient of tested donations or materials that results in any of the following:
- Life-threatening illness or injury;
- Permanent impairment of a body structure or a body function;
- Hospitalisation or prolongation of patient hospitalisation;
- Medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function;
- Chronic disease.
At the same time, planned hospitalization related to the condition existing before the investigation will not be considered a serious adverse event. However, even though the mere continuation of the said condition will not be considered a serious adverse event, the increase in its severity should be duly documented as an adverse event.
According to the guidance, the causal relationship of an adverse event with all the elements of the study, including the medical device in question, should be subject to a rigorous assessment by both the party responsible for the study (study sponsor) and the investigator. In this respect, the study sponsor should consider all the available data. Based on the said assessment, one of the four determinations regarding causal relationship should be made:
- Not related,
- Causal relationship.
With respect to causal attribution, the document also refers to the relevant guidance document issued by the MDCG.
The authority additionally emphasizes that the study sponsor should not rule out entirely the causal relationship in the following cases:
- There is insufficient information for causality assessment;
- No other clear cause can be identified, and there is a correlation in time or with the bodily part concerned;
- The investigational device or a procedure could affect the bodily part concerned;
- Similar events have already been recorded as side effects or complications with other, similar devices and procedures; or
- User errors are involved, e.g., in case of an injury due to an operating error.
Under the general rule, serious adverse events during a multi-center study should be reported to the authority within 7 days. In particular, a party responsible for a clinical trial should submit a filled-in table containing the main information regarding the case necessary for the authority to assess the risks associated thereto. Should the reportable event take place in a Swiss center, additional information should be provided.
Annual Safety Report
The document issued by Swissmedic also provides additional clarifications regarding the annual safety report to be submitted to the authority and the cantonal ethics committee with respect to an approved study. According to the guidance, such a report should contain the following information:
- Data cut-off date up to which study data has been considered in the report and the reporting period;
- Status of recruitments: current number of subjects worldwide and in Switzerland, duration of the currently existing follow-up observations;
- Status of the performance study abroad (countries involved, any study interruptions or early terminations);
- Anticipated serious adverse events: description, occurrence in the trial arm versus control arm and medical literature, evaluation by the sponsor;
- Unanticipated serious adverse events and any device deficiencies: causality of the SAE with the IVD for performance study or a procedure, possible causes, problems related to the use of the investigational devices at the centers;
- Safety-related measures taken by the sponsor or imposed by ethics committees or authorities anywhere in the world;
- Results from other performance studies with the IVD (if applicable);
- Sponsor’s conclusions regarding the safety of the subjects and the continuation of the investigation;
- Annex with the cumulative list of reportable serious adverse events and device deficiencies per cut-off date.
The authority additionally emphasizes the importance of ensuring the report is up to date – a cut-off date older than 2 months from the report date is unacceptable. It is also allowed to submit the annual report to Swissmedic before the expected reporting date in case the study in question is multinational, and a joint annual report is to be submitted to all the regulating authorities and ethics committees involved.
In summary, the present information sheet issued by Swissmedic addresses certain aspects related to adverse event reporting, outlining the applicable criteria and providing additional clarifications and recommendations to be considered. The scope of the guidance also covers annual safety reports to be submitted by the parties responsible for clinical investigations regularly.
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