Conduct↦Safety↦Safety Assessment↦Medical Device
Was betrifft es? Warum ist das wichtig?
Safety assessment (SA) of Investigational Medical Devices (IMD) is a standardised procedure used to evaluate the occurrence of Adverse Events (AEs) and other reportable events, such as Device Deficiency (DD) during study conduct.
In IMD studies, SA of AEs is based on 4 main criteria:
- Severity: the SP-INV grades the intensity of an AE based on severity definitions defined in a particular study
- Seriousness: grades the effective harm of an AE to study participants, MD users, or other persons. The grading is based on clear regulatory definitions (e.g. serious / non-serious)
- Causality: suspected relationship with
- IMD exposure
- Study procedures, or
- Comparator (e.g. a licensed MD used as a control)
- Anticipation / Expectedness: assess AE occurrence based on previously observed events in current risk assessment documents (e.g. risk analysis report and/or CIP, the “instruction for use” for licensed MDs, the IB for non-licenced MDs (IMD))
IMD safety assessment also includes the evaluation whether the AE was due to a device deficiency (DD), namely any inadequacy of the IMD itself.
Mehr
A DD assessment includes:
- The nature of the DD (i.e. malfunction, using error, inadequate labelling, or other)
- The inadequacy type (i.e. related to the IMD identity, quality, durability, reliability, safety or performance)
- If the DD has led to an AE, could it have led to an SAE?
Seriousness
For IMD serious is defined as any adverse event that led to any of the following (MDCG and MDR):
- Death
- Serious deterioration in the health of the subject, that resulted 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
- Foetal distress, foetal death or a congenital physical or mental impairment or birth defect
Causality
The following grading system is required:
- Not related: Relationship can be excluded
- Possible: Weak relationship but cannot be ruled out completely. Alternative causes are also possible
- Probable: Relationship with device or comparator relevant and/or AE cannot reasonably be explained by another cause
- Causal relationship: Relationship with device, comparator or procedures beyond reasonable doubt
Expectedness
Refers to the previous occurrence of serious AE similar in nature and severity, based on RSI (e.g. in the “instruction for use” for licensed MDs, the IB for non-licenced MDs (IMD))
DD with an SAE potential
Is defined as a DD that might have led to an SAE if:
- Appropriate action had not been taken
- Intervention had not occurred, or
- Circumstances had been less fortunate
Was muss ich befolgen?
As a Site-INV, assess each AE and:
- Determine its severity (e.g. intensity) as defined in the Clinical Investigation Plan
- Determine whether the AE qualifies as serious. A serious AE is named a Serious Adverse Event (SAE)
- Determine whether there is reason for causality. In the event of a possible causal relationship, the event is named an Adverse Device Effect (ADE)
- An AE that is both serious and related is named Serious Adverse Device Effect (SADE)
- Record and assess any DDs
- Report DDs and AEs to the SP-INV
As a SP-INV:
- Re-assess each AE reported by the Site-INV(s) on severity, seriousness, and causality (relatedness)
- Determine expectedness (in nature, intensity or frequency) based on current risk assessments
- Events that are serious, related and not expected are named Unanticipated Serious Adverse Device Effect (USADE)
- Inform the Site-INV
- Re-assess each DD reported by the Site-INV and determine whether it could have led to an SAE (DD with SAE potential)
- Report safety events as required by applicable laws (e.g. to EC/RA such as Swissmedic and manufacturer if applicable)
- If applicable, re-evaluate the risk-benefit of the study
Mehr
For all AEs, Site-INV and SP-INV both assess intensity, seriousness, and causality. The SP-INV assesses expectedness based on previous occurrence of the same AE.
In the event the SP-INV and Site-INV disagree on the assessment, they should try to find a consensus. If not possible, the opinion of both the Site-INV and the SP-INV should be included in the safety report.
Wo kann ich Hilfe anfordern?
Your local CTU↧ can support you with experienced staff regarding this topic
Basel, Departement Klinische Forschung, CTU, dkf.unibas.ch
Lugano, Clinical Trials Unit, CTU-EOC, www.ctueoc.ch
Bern, Clinical Trials Unit, CTU, www.ctu.unibe.ch
Geneva, Clinical Research Center, CRC, crc.hug.ch
Lausanne, Clinical Research Center, CRC, www.chuv.ch
St. Gallen, Clinical Trials Unit, CTU, www.kssg.ch
Zürich, Clinical Trials Center, CTC, www.usz.ch
External Links
Swissmedic – see in particular information sheets
- BW600_00_015e Clinical trials of medical devices
- MU680_20_004e_MB Medical devices FAQs Patients
References
ISO 14155:2020 Medical device (access liable to cost) – see in particular sections and annex
- 3.1 ADE definition
- 3.2 AE definition
- 3.19 DD definition
- 3.33 Malfunction definition
- 3.44 SADE definition
- 3.45 SAE definition
- 3.46 Serious health threat
- 3.51 USADE definition
- 3.52 Use error
- 7.4 AE and DD
- Annex F Adverse event categorization
MDCG 2020-10/1 – see in particular articles
- 3.2 AE definition
- 3.5 DD definition
- 3.8 SAE definition
- 9. Causality Assessment
MDR 2017-745 – see in particular articles
- Art. 2 (57) AE definition
- Art. 2 (58) SAE definition
- Art. 2 (59) DD definition
- Art. 80 (1) Recording and reporting of AE that occur during clinical investigations
Swiss Law
ClinO-MD – see in particular articles
- Art. 32 Documentation of AE
- Art. 33 Reporting of SAE
- Art. 34 Reporting of safety and protective measures