Basic↦Statistic Methodology↦Research Question↦Study Primary Outcome / Endpoint
Was betrifft es? Warum ist das wichtig?
Study outcomes/endpoints are variables measured during the conduct of a study to answer (a) research question(s).
The Primary Outcome(s) /Endpoint(s): is the most important variable(s) to researchers, as it answers the main study question / determines whether the intervention had the intended effect (e.g. positive effect of a new diabetic medication on blood glucose concentration after 2 weeks of treatment.
Defining the primary outcome is challenging. Suppose you want to evaluate the effect of discontinuing antihypertensive drugs on patient health. To mention a few, there are many endpoints to choose from: death, number of hospitalizations, functionality, quality of life. All these measures are relevant, but for different reasons. A primary endpoint may be chosen because it is:
- Clinically important: it captures the clinical consequences of an intervention (e.g. mortality, disease progression)
- Patient-centered: it reflects patient experiences or well-being (e.g. quality of life)
- Health-economic relevant: it captures impact on healthcare costs or resource (e.g. hospitalizations, treatment costs, cost-effectiveness)
Mehr
Co-primary outcome: Generally, there is only one primary outcome. However, when the research question addresses multiple aspects simultaneously, it may be necessary to define more than one primary outcome (e.g. does the intervention improve diabetic control AND reduce the risk of hospitalization?).
A precise definition of the outcomes type. For example, if you are interested in re-hospitalization: do you want to draw conclusions about the occurrence (yes or no), the number as a count or as categories (e.g., 0, 1 to 3, more than 3), or the time relapsed until the first re-hospitalization?
As any variable, study outcome/endpoint variables, can be of different types, such as:
- Continuous variables (e.g. weight, lab values such as cholesterol-, blood pressure values)
- Categorical variables (e.g. such as the categorisation into bad/normal/good)
- Binary variables (e.g. expressed as binary categories such as, dead/alive, yes/no, normal/abnormal, accepted/rejected)
- Count variables (e.g. number of hospital visits)
- Time-to-event variables (e.g. time to initial cardiovascular event)
Was muss ich befolgen?
As a SP-INV:
- Define the 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 it matches the research question
For example, you are interested in re-hospitalisation. Aspects to include are:
- The definition of outcome type. Do you want to draw conclusions about the:
- Occurrence (yes or no)?
- Number or categories (e.g. 0, 1 to 3, more than 3)?
- Time relapsed until the first re-hospitalization?
- The time point(s) of interest: are you interested in any re-hospitalization occurring in the first 3 months after surgery, or the “number of re-hospitalizations” during a two-year follow-up?
The choice of the primary endpoint is a critical component of the study design, as the sample size calculation (i.e., the estimation of the number of participants required to adequately answer the study question) will be based on this endpoint.
Mehr
The choice of the primary endpoint should be discussed with a statistician to determine whether the resulting sample size is realistically achievable within the available resources, recruitment capacity, and study timeframe.
WARNING: Co-primary outcomes require careful statistical consideration as assessing several endpoints simultaneously affect the overall power.
Wo kann ich Hilfe anfordern?
Your local Research Support Centre↧ can assist you with experienced staff regarding this topic
Basel, Departement Klinische Forschung (DKF), dkf.unibas.ch
Lugano, Clinical Trials Unit (CTU-EOC), ctueoc.ch
Bern, Department of Clinical Research (DCR), dcr.unibe.ch
Geneva, Clinical Research Center (CRC), crc.hug.ch
Lausanne, Clinical Research Center (CRC), chuv.ch
St. Gallen, Clinical Trials Unit (CTU), h-och.ch
Zürich, Clinical Trials Center (CTC), usz.ch
SCTO Research Tools & Resources
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
- 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 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
Swiss Law
ClinO – see in particular article
- Art. 2b Definition of intervention