Your Easy Guide to Clinical Studies

Predefined rules regulate the premature discontinuation of a study. Termination criteria are:

• Defined in the study protocol and, if applicable, in the Statistical Analysis Plan (SAP)
• Assessed during planned interim analyses

 

Early termination criteria may include:

• Safety: unacceptable safety risks to participants (e.g. a higher number of adverse events in the intervention group compared to the control group, resulting in an unacceptable risk-benefit-ratio of the study)
• Futility: a high likelihood that the intervention is ineffective or has only minimal benefit
• Efficacy: An obvious beneficial treatment effect, allowing study success to be declared early. It would be unethical to keep the control/placebo group on an inferior treatment regimen if a positive treatment effect has been proven in the intervention group

As a SP-INV, assess risks associated with your study, and if necessary define:

• Criteria warranting early study termination/discontinuation
• The need of interim analyses to assess discontinuation criteria, including the time point and required frequency of interim analyses (i.e. when and how often to assess discontinuation criteria during study conduct)
• The requirement and composition of an Independent Data Monitoring Committee (IDMC) (i.e. also referred to as an independent Data Safety Monitoring Board (DSMB – with a focus on safety). An IDMC/DSMB evaluates the results of the interim analysis and makes impartial recommendations regarding the continuation/early termination of an ongoing study

 

Discuss potential termination criteria with a statistician and plan the:

• Required number and timing of interim analyses during study conduct
• Type of analysis performed during an interim analysis (e.g. analysis method)

References

ICH Topic E9 – see in particular

• 4.1 Trial monitoring and interim analysis
• 4.5 Interim analysis and early stopping
• 7.2.1 Efficacy data
• 7.2.2 Safety data