What is it? Why is it important?

The study protocol is the document that describes the set-up and implementation of a study. The protocol should include:

  • When and how (serious) adverse events are collected, assessed, documented, reported and managed
  • Safety outcomes, representing variables that are collected and monitored in order to assess the safety of the study, based on its intervention and/or procedures

The objective of collecting safety data during study conduct, and if applicable study follow-up, is to:

  • Ensure study participants are protected from harm
  • Maintain safety outcome oversight
  • Detect the occurrence of new (serious) safety events (e.g. to be added to the product’s safety profile (e.g. IB for IMP/IMD, SmPC / PI for marketed MP, IFU for marketed MDs)
  • Enable risk-benefit assessments on an ongoing basis

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Safety outcomes should be clearly described in the protocol. They should:

  • Cover study relevant safety events (e.g. laboratory parameters, vital signs)
  • Have defined thresholds for abnormal values (e.g. acceptable values below or above given parameters)
  • Describe causality relationship between AE and study intervention or procedures
  • Reflect the dynamic change resulting from the study intervention or procedures (e.g. evolution of AE)

Based on study risk category, requirement for AE documentation varies. For study risk category:

  • C: all AEs are documented in a standardised manner
  • B: only AEs mentioned in the protocol or requested by authorities are documented
  • A: no obligation of AE documentation exists

Still, irrespective of study risk category, the documentation and reporting of SAE is mandatory.

What do I need to do?

As a SP-INV describe in the study protocol:

  • Safety objectives and outcome measures (e.g. laboratory parameters, particular AEs)
  • The collection of adverse events and other safety related events
  • Timeframe for safety data collection. Documentation starts once the participant has signed the ICF until:
    • Study termination (e.g. last study participant at last study visit), or
    • The end of some predefined safety follow-up period
  • Procedures used for the assessment of safety events
  • Procedures used for the documentation and reporting of serious safety events (e.g. EC/RA, study SP-INV, marketing holder)
  • Study safety termination rules (e.g. based on safety analysis, DSMB support)
  • The risk-benefit assessment of your study, and how its ratio supports the safe conduct of your study safety

Access the swissethics website for applicable and mandatory protocol templates.

For more information on this topic refer to Protocol and Quality & Risk in this study guide.

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If a specific safety SOP describes how to handle safety during study conduct, the commitment to adhere to the SOP must be stated in the protocol.

Where can I get help?

Your local CTU can support you with experienced staff regarding this topic

External Links

Swissethics – see in particular

  • Templates / Checklists
    • Study protocols

References

ICH GCP E6(R2) – see in particular guidelines

  • 1.44 Protocol definition
  • 1.45 Protocol Amendment
  • 2.5, 2.6 Principles
  • 6 Clinical trial protocol and protocol amendment(s)

Declaration of Helsinki – see in particular principles

  • 21-22 Protocol requirements

ISO 14155:2020 Medical device (access liable to cost) - see in particular sections and annex

  • 6.4 Clinical Investigational Plan (CIP)
  • Annex A CIP

Swiss Law

FEDLEX – laws are available online under numbers

  • 810.305 ClinO
  • 810.301 HRO

ClinO – see in particular articles

  • Art. 19-20, 49, and 61 Categorisation

HRO – see in particular article

  • Art. 7 Categorisation
Abbreviations
  • AE – Adverse Event
  • ClinO – Clinical Trials Ordinance
  • ClinO-MD – Ordinance on Clinical Trials with Medical Devices
  • CIP – Clinical Investigation Plan
  • CTU – Clinical Trials Unit
  • DSMB – Data Safety Monitoring Board
  • EC/RA – Ethics Committee / Regulatory Authorities
  • FEDLEX – Publication Platform for Federal Laws
  • HRO – Human Research Ordinance
  • IB – Investigator’s Brochure
  • ICF – Informed Consent Form
  • ICH GCP – International Council for Harmonisation - Good Clinical Practice
  • IFU – Instruction for Use
  • IMD – Investigational Medical Device
  • IMP – Investigational Medicinal Product
  • ISO – International Organization for Standardization
  • MD – Medical Device
  • MP – Medicinal Product
  • SAE – Serious Adverse Event
  • SmPC / PI – Summary of Product Characteristics / Product Information
  • SOP – Standard Operating Procedures
  • SP-INV – Sponsor-Investigator
Development ↦ Safety ↦ Safety Documentation ↦ The Protocol
Study
Basic

Provides some background knowledge and basic definitions

Basic Protocol
Basic Statistics
Basic Monitoring
Basic Drug or Device
Basic Biobanking
Concept

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Protocol
Concept Statistics
Concept Drug or Device
Concept Biobanking
Development

Starts with confidence that the study is feasible

Ends after having received ethics and regulatory approval

Development Protocol
Development Statistics
Development Drug or Device
Development Biobanking
Set-Up

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Protocol
Set-Up Ethics and Laws
Set-Up Statistics
Set-Up Drug or Device
Set-Up Biobanking
Conduct

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Protocol
Conduct Statistics
Conduct Drug or Device
Conduct Biobanking
Completion

Starts with last study visit completed

Ends after study publication and archiving

Completion Protocol
Completion Statistics
Completion Drug or Device
Completion Biobanking
Current Path (click to copy): Development ↦ Safety ↦ Safety Documentation ↦ The Protocol

Please note: the Easy-GCS tool is currently under construction.