Trial Outcomes Flashcards
What is a Comparator?
A comparator is a group to which you compare your treatment group. It is often the current gold standard treatment
What are the 2 Situations that are possible for Comparing Groups?
Best Current Practice and Head to Head Trial
Comparing Groups: What is Best Current Practice?
When there is no established treatment, we compare the new treatment to the ‘best current practice’, which is often non-drug. We compare the best current practice + new drug to the best current practice + placebo
Comparing Groups: What is Head to Head Trial?
This occurs when there is already an established gold standard treatment, called the active comparator. The new treatment is compared to this gold standard
What is Required for Active Comparator Trials?
Why are they More Likely to Fail?
Active comparator trials require larger sample sizes due to the smaller potential effect sizes (since the current drug is already effective, how much more effective can the new one be? Need a large size to find these differences)
These trials are also more likely to fail since the current drug is the gold standard and is already quite good. If we don’t expect the new drug to be much more effective or efficacious, a non-inferiority trial may be better
What is a Primary Objective?
How many does a trial have?
What do they relate to?
The primary objective should be the main benefit of the treatment
Each trial will always have at least 1 primary objective, which is measured by a clinical outcome (e.g. objective of reducing mortality rates, measure by recording mortality).
These objectives relate to the main hypothesis of the trial and the trial must be adequately powered to answer this objective.
What are Secondary Objectives?
Secondary objectives are included into the study to show and evaluate the additional effects of the treatment, positive or negative. Side effects are an example. The trial does not need to be powered to these objectives
What is the Issue with determining the clinical outcome?
The issue with determining the clinical outcome and hence if the primary objective has been achieved is that for rare diseases, it may take a long time and a lot of money to get enough data to do so. As such, we can combine multiple clinical outcomes all related to the primary objective together into a composite outcome, or via surrogate outcomes
What are Composite Outcomes?
Composite outcomes consist of two or more outcomes, which are distinct events but are related to the primary objective. If a patient experiences any one of the outcomes, they are said to have experienced the composite outcome. A common composite outcome is combining MI, stroke and CVD
What are the Advantages of Composite Outcomes?
Increased statistical efficiency
Helps investigators avoid making a choice on which outcome to study
Can address more than one aspect of the patient’s health status.
What are the Disadvantages of Composite Outcomes?
Composites are often unreasonably combined (e.g. hospital admissions and deaths… not all hospital admissions end up as deaths)
This may create an exaggerated perception of how well the treatment works
What are Surrogate outcomes, or intermediate markers?
What is an Example?
Outcomes that are easily measured, but not a direct measure of harm or benefit. They can predict distant outcomes that are of clinical importance.
An example is blood pressure, which at the time is not a very important parameter, but can predict risk of CVD or mortality in the future. We are not measuring the clinical outcome, but something in between to act as a surrogate for that outcome
What are Surrogate outcomes, or intermediate markers used in Conjunction with?
What is an Example?
They are often used in conjunction with measuring the final, clinical outcome. We need to measure the clinical outcome to be sure the drug works, however in some cases we need at least some short-term evidence that the treatment may be effective, so measure surrogate outcomes in the meantime.
An example is measuring tumour size as a surrogate for death. If the drug is found to reduce tumour size in the short-term, this may be beneficial for cancer patients even if we are not sure it will reduce mortality. This is because we know that tumour size usually correlates with mortality.
