Basic↦Safety↦Safety Information↦Investigator Brochure
What is it? Why is it important?
The Investigator Brochure (IB):
- Contains a compilation of an investigational product’s safety data
- Provides up to date safety data obtained during product development
- Enables the Site-INV to make an unbiased risk-benefit assessment of a study
In certain circumstances, when the IMP or IMD is a marketed product the IB can be replaced by:
- The Summary of Product Characteristics (SmPC) for marketed MPs:
- Describes relevant properties of the MP (including safety data)
- Describes the approved conditions of use
- Enable healthcare professionals to safely and effectively use the medicine
- Is also named “Product Information” in Switzerland
- The Instruction for Use (IFU) for marketed MD:
- Is provided to users by the MD manufacturer to safely and effectively use the MD
- Provides information on MD intended purpose, proper use, including any required precautionary measures
- Contains (among others) a summary of available safety data
More
The IMP/IMD manufacturer performs yearly IB updates. More frequent updates are triggered if new safety relevant information become available from ongoing clinical studies. The IB:
- Is used for IMPs with no marketing authorisation, or marketed (I)MPs not used in accordance with the terms of its authorisation (e.g. a new route / new dosage / new indication, etc.), or
- Provides a description regarding the nature, seriousness, and frequency of AEs (e.g. IMP=AE; IMD=AE/ADE)
- Provides a cumulative list of expected SARs for IMP (included in the RSI chapter), and foreseeable SAEs and IMD potential risks
The Reference Safety Information (RSI) is a cumulative list of IMPs expected SA(D)R. RSI can be found:
- In a separate section of the IB
- In section 4.8 of the SmPC / Product Information (e.g. for marketed MPs used in accordance with its authorisation)
RSI is used by the study SP-INV in order to determine the expectedness of SARs during study conduct (i.e. not used for investigator decision-making during study conduct).
In the event of a SAR occurrence that is not listed in the RSI, then it is classified as unexpected and is thus a SUSAR (e.g. requiring expedited reporting to EC/RA (e.g. Swissmedic).
Prior to study start, the study relevant RSI is approved by RA (e.g. Swissmedic).
For IMDs, expectedness of SADE occurring in the study is determined by the SP-INV of the study, based on the list of foreseeable SAEs and potential risks mentioned in:
- Risk Analysis Report
- Clinical Investigation Plan (CIP), or
- IB
What do I need to do?
As a Site-INV:
- Read the IB, Product information or IFU provided by the SP-INV to familiarize yourself with the safety concerns regarding the product under investigation
As a SP-INV:
- Ensure to distribute a current and updated IB in due time to participating Site-INV(s) and EC/RA (e.g. Swissmedic).
- Identify the RSI applicable to your IMP study
- Use the RSI to assess SARs expectedness, if potentially occurring during study conduct
As a SP-INV manufacturing the product under investigation:
- Ensure product IB is updated on a yearly basis
- Initiate more frequent updates in the event any relevant preclinical or clinical safety data become available. The inclusion of a new expected SA(D)R in the RSI, must be accompanied by a risk-benefit assessment of the IMP (e.g. whether its risk is still acceptable). The updated RSI (including the new SA(D)R) should be submitted to RA for approval
Where can I get help?
Your local Research Support Centre↧ can assist you with experienced staff regarding this topic
Basel, Departement Klinische Forschung (DKF), dkf.unibas.ch
Lugano, Clinical Trials Unit (CTU-EOC), ctueoc.ch
Bern, Department of Clinical Research (DCR), dcr.unibe.ch
Geneva, Clinical Research Center (CRC), crc.hug.ch
Lausanne, Clinical Research Center (CRC), chuv.ch
St. Gallen, Clinical Trials Unit (CTU), h-och.ch
Zürich, Clinical Trials Center (CTC), usz.ch
Reference
ICH GCP E6(R2) – see in particular guideline
- 7 Investigator’s Brochure
ISO 14155:2020 –Medical device (access liable to costs) – see in particular section
- 6.5 Investigator’s brochure
MDCG 2020-10 / 1Safety reporting in clinical investigations of medical device under the Regulation (EU)
Swiss Law
ClinO – see in particular annex
- Annex 4 Application dossier and investigator brochure