What is it? Why is it important?

In a study, the risk-benefit ratio is the proportion of all possible risks over anticipated benefits. Its assessment serves to mitigate potential risks in order to protect participants.

Each study carries its own risks and benefits. There is never zero-risk, but it must be minimised as far as possible to guarantee risks remain acceptable to participants.

The risk-benefit ratio:

  • Of a study must be positive for the study to be initiated (study benefits are higher than risks). EC/RA only authorise studies where benefits are judged greater than risks
  • Is continuously assessed during study conduct. This is required to ensure the ratio remains unchanged. In the event of an unfavourable shift, additional protective safety measures must be implemented or the study is stopped

More

The EC is responsible to review and approve any expected study risks based on:

  • The ratio between the likely risks and burdens and the expected benefits to participants
  • Measures taken by the SP-INV / Site-INV to minimise risks and burdens

RA (e.g. Swissmedic) is responsible to:

  • Review safety and quality of IMP, IMD
  • Reflect the current state of scientific knowledge based on the information provided in the IB
  • Ensure that IMP/IMD risk-mitigating measures are taken into account by the SP-INV
  • Ensure risks, benefits, including risk mitigating measures are correctly reported in the study protocol

The expected level of risk depends on the:

  • IMP/IMD under investigation
  • The type of intervention or study design (e.g. placebo controlled, randomised, single arm)
  • Study phase (First-in-man, phase I, II and III for IMP / MP post-marketing stage or pilot / pivotal stage for IMD / MD for post-marketing stage)
  • Disease and current health status of participants (e.g. risk for severe AEs in multimorbid participants may be more acceptable than for healthy volunteers)
  • Study population (e.g. pregnant women, children, participants lacking capacity)

What do I need to do?

As a SP-INV:

  • Select a risk appropriate study design for the target group under investigation (e.g. health / disease status, vulnerable population such as children, pregnant women)
  • Identify and assess expected participant:
    • Risks and burdens with regard to the planned IMP/IMD intervention
    • Benefits (e.g. prevent progression of disease, improve quality of life)
  • Describe in the study protocol expected risks and benefits and set them in relation to the planned study population
  • Establish as applicable, SOPs, WIs and / or a safety management plan, a DSMB to monitor, evaluate and report risk occurrence during study conduct
  • Define and describe mitigating measures to reduce or control risks

For more information refer to Quality and Risk in this study guide.

More

  • Risks for study participants should never be disproportionate to or outweigh any expected benefits
  • In the event of an unfavourable shift in the risk-benefit ratio for participants:
    • Amend the patient information
    • Inform study participants
    • If applicable, ask the participant to re-consent to study participation

To be considered

  • For diseases with a high level of health impairment (e.g. multimorbid participants and cancer patients) a higher risk level is acceptable. However, for conditions with a low level of health impairment (e.g. headache), only low risks would be acceptable
  • During study conduct the risk-benefit ratio should be re-assessed on an ongoing basis or at least in the event of safety concerns

Where can I get help?

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

References

Declaration of Helsinki – see in particular principles

  • 4, 7-9, 14 General principles
  • 16-18 Risks, burdens and benefits
  • 20 Justification of research in vulnerable groups

Swiss Law

FEDLEX – laws are available online under numbers

  • 810.30 HRA
  • 810.305 ClinO
  • 810.306 ClinO-MD
  • 810.301 HRO

HRA – see in particular articles

  • Art. 12 Risks and burdens
  • Art. 15 Safety and protective measures

ClinO – see in particular articles

  • Art. 25 EC review areas
  • Art. 32 RA review areas

ClinO-MD – see in particular articles

  • Art.11 EC review areas
  • Art. 17 RA review areas

HRO – see in particular article

  • Art. 15 EC review areas
Abbreviations
  • AE – Adverse Event
  • ClinO – Clinical Trials Ordinance
  • ClinO-MD – Ordinance on Clinical Trials with Medical Devices
  • CTU – Clinical Trials Unit
  • DSMB – Data Safety Monitoring Board
  • EC/RA – Ethics Committee / Regulatory Authorities
  • FEDLEX – Publication Platform for Federal Laws
  • HRA – Human Research Act
  • HRO – Human Research Ordinance
  • IB – Investigator Brochure
  • IMD – Investigational Medical Device
  • IMP – Investigational Medicinal Product
  • MD – Medical Device
  • MP – Medicinal Product
  • RA – Regulatory Authorities
  • Site-INV – Site-Investigator
  • SOP – Standard Operating Procedures
  • SP-INV – Sponsor-Investigator
  • WI – Working Instructions
Concept ↦ Safety ↦ Safety in Studies ↦ Risk-Based Ratio
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): Concept ↦ Safety ↦ Safety in Studies ↦ Risk-Based Ratio

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