What is it? Why is it important?

A study can terminate prematurely, reasons include:

  • Study termination criteria defined in the study protocol are met during study conduct
  • An interim analysis, or study data analysis by the DSMB shows:
    • Early-evidence of futility and / or the inability of the study to achieve its objectives (e.g. unable to achieve statistical significance)
    • The risk-benefit evaluation is unacceptable with disproportionate risks to participants compared to benefits
    • Evidence of an early benefit. Thus, the study hypothesis is proven before the end of the study
  • Participant recruitment is low
  • New findings make the study obsolete
  • Inspection findings require for the study to be stopped (e.g. due to safety issues, serious quality assurance deviations)

More

A DSMB consists of a group of study independent experts (e.g. its composition depends on the type and complexity of the study). A DSMB charter defines membership responsibilities and details the requirements of its members, describes the data to be reviewed, how to hold meetings, including respective considerations and policies.

The set-up up a DSMB is recommended for studies which:

  • Have multi-centre settings (e.g. more than one centre)
  • Have a blinded design (e.g. treatment and placebo group allocation in study participants is unknown)
  • Involve high-risk intervention(s) to study participants
  • Involve vulnerable persons (e.g. participants without capacity, children, pregnant women)
  • Has death as a primary outcome
  • Has a high probability of early study termination due to safety or efficacy concerns

What do I need to do?

As a SP-INV:

  • Ensure to comply with the:
    • Statistical analysis plan of the study (e.g. defined in the study protocol)
    • Any pre-defined interim analyses (e.g. data analysis prior to study completion)
    • The data safety monitoring plan
  • If applicable, include a DSMB and define criteria for stopping the study
  • Report premature suspension / interruption of the study to the EC/RA, participating study sites, and study participants

As a Site-NV:

  • Promptly inform study participants
  • Implement applicable therapies and follow-up of participants, as required
  • If required, inform RA

It is unethical to:

  • Expose participants to new and added risks once these have been identified during study conduct (e.g. unacceptable toxicity)
  • Expose participants to less effective treatments after a treatment has proven to be effective (e.g. placebo and treatment control groups )
  • Postpone or suspend treatment in the medical community once it has been shown to be highly effective

More

During study conduct the DSMB will have access to un-blinded data (e.g. known treatment allocation), allowing for an evaluation of study futility and/or its risk-benefit ratio.

Where can I get help?

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

References

ICH GCP E6(R2) – see in particular guidelines

  • 1.25 Independent data-monitoring committee
  • 4.12 Premature Termination INV
  • 5.5.2 Trial management, data handling, and record keeping
  • 5.21 Premature Termination SP-INV

Declaration of Helsinki – see in particular principles

  • 16-18 Risks, burdens and benefits

ISO 14155:2020 Medical device (access liable to costs) – see in particular sections

  • 5.6.4 Continuing communication with the EC
  • 5.8.4 Information to be provided to the subject
  • 8.2 Suspension or premature termination of the clinical investigation

Swiss Law

FEDLEX – laws are available online under numbers

  • 810.305 ClinO
  • 810.301 HRO
  • 810.306 ClinO-MD

ClinO – see in particular articles

  • Art. 38 Notification and reporting upon completion, discontinuation or interruption of a clinical trial
  • Art. 57 Transplant studies -notifications and reporting
  • Art. 62 Other studies - applicable provisions

ClinO-MD – see in particular article

  • Art. 36 Reporting the conclusion, termination or interruption of a clinical trial

HRO – see in particular article

  • Art. 22 Notification upon completion or discontinuation
Abbreviations
  • ClinO – Clinical Trials Ordinance
  • ClinO-MD – Ordinance on Clinical Trials with Medical Devices
  • CTU – Clinical Trials Unit
  • DSMB – Data Safety Monitoring Board
  • EC – Ethics Committee
  • EC/RA – Ethics Committee / Regulatory Authorities
  • HRO – Human Research Ordinance
  • ICH GCP – International Council for Harmonisation - Good Clinical Practice
  • INV – Investigator
  • ISO – International Organization for Standardization
  • RA – Regulatory Authorities
  • Site-INV – Site Investigator
  • SP-INV – Sponsor Investigator
Conduct ↦ Ethics and Laws ↦ Premature Study Termination ↦ Rationale
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): Conduct ↦ Ethics and Laws ↦ Premature Study Termination ↦ Rationale

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