Your Easy Guide to Clinical Studies

When describing study outcomes / endpoints one differentiates between:

• The primary outcome – used to determine whether an intervention has the intended effect
• Other or not-primary outcomes believed to be informative, but not directly used to answer the main research question.

 

Not-primary outcomes/endpoints are generally named

• Secondary: are additional variables monitored during study conduct with the aim to support the interpretation of the primary outcome/endpoint (e.g. in the diabetic study this could be the occurrence of adverse events, ease of drug administration by patients including compliance)
• Safety: are adverse events or negative effects experienced by participants during the course of a study. These outcomes are crucial to evaluate the safety and tolerability of a medical intervention. A safety outcome can be defined as a primary outcome if the primary objective of the study is to assess the safety of the intervention.
• Exploratory: include measurements researchers believe to be informative to generate hypotheses or explore potential effects; they are usually less definitive than secondary endpoints

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As a SP-INV:

• Define the primary and not-primary outcome(s)/endpoint(s) of your study during the concept phase of your study (e.g. at the time when selecting your study design)
• Ensure outcome(s)/endpoint(s) match with the research question. Keep in mind that the study is powered to detect a clinically meaningful effect on the primary endpoint, but may not have sufficient statistical power to detect differences in the other endpoints. Therefore:
  • Analyses of secondary outcomes should be interpreted with caution, as they are primarily supportive or exploratory rather than confirmatory
  • Effect estimates and their confidence intervals may be more informative and appropriate than formal statistical significance testing based on p-values

Useful External Links

COMET initiative - to standardize outcomes for clinical trials

References

ICH GCP E6(R3) – see in particular guidelines

• Principles of ICH GCP Nr. 8.2 The scientific objective of a study should be clear
• 3.9.8 Endpoint assessment
• 3.11.4 / 3.11.4.3 Monitoring of trial endpoints
• Appendix B. 4 Trial design - 4.1 Primary / secondary endpoints statement

ICH Topic E8(R1) General considerations for clinical studies - see in particular

• 5.5 Methods to reduce bias

ICH Topic E9(R1) Statistical Principles for Clinical Trials – see in particular

• 2.2.2 Primary and secondary variables
• 2.2.4 Global assessment variables
• 2.2.5 Multiple Primary Variables
• 2.2.7 Categorised variables