Endpoints and outcomes
Trials should have a clear primary outcome. Typically, this is the difference between the intervention and control groups in a specific variable – and will determine if your intervention is effective or not. The primary outcome should be an observation of significant clinical relevance – either to patients, doctors or to the health service (ideally, to all three groups). Examples of primary outcome include [difference in… or difference in change in…] blood pressure, recurrence of kidney stones, quality of life, pain score, death or albuminuria.
The ideal primary outcome is important to all stakeholders – especially to patients. Typical examples of patient-centred (i.e. important to patients) outcomes are adverse clinical events (such as infection, hospitalisation or death) or patient-reported outcome measures (PROMs) – typically captured by structured survey-type instruments like the Epworth Sleepiness Scale or the EuroQOL Five Dimensions. These tools provide a quantitative measure of the disease burden to patients.
Primary outcomes that are not directly important to the patient are called surrogate outcomes. These outcomes measure variables known to be associated with adverse events or other events important to patients. Good examples are blood pressure and albuminuria, which typically cause patients no distress but which are treated as we believe that lowering their values leads to better patient outcomes such as fewer cardiovascular events or to the preservation of renal function. Surrogate outcomes are common primary outcomes in nephrology as patient-centred outcomes such as end-stage kidney disease may take many years to develop. As such, it is more feasible to measure change in surrogate variables with the expectation that the surrogate outcome will be linked to the hard, longterm outcome. However, changes in surrogate outcomes due to new treatments do not always lead to the desired changes in clinical outcomes. This can only be proved by a long-term trial that actually measures the clinical outcome.