Conduct↦Ethics and Laws↦Premature Study Termination↦Rationale
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)
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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
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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
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
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