From Allan Flashcards
What is a confounder?
A factor, not the intervention being given, that may be responsible for creating a correlation between the intervention and the disorder of interest.
What is the problem when using historical controls?
Because a therapy being offered now is being compared to a therapy being offered in the past. The difference in time is likely to have an effect because it may reflect differences in patient characteristics, methods of diagnosis or standards of care.
Why might randomised trials not always be the appropriate trial design?
1) Sample size - if a large sample size is required to detect a difference between two treatments, it may be too large to be feasible to perform.
2) Bias -
What is a benefit of randomising a phase II trial?
It can provide information on the feasibility of a subsequent phase III trial, such as how willing subjects are to be randomised.
What are four key trial design features?
Inclusion and exclusion criteria
Randomisation
Blinding
Control group
What is the importance of exclusion and inclusion criteria?
Unambiguous definitions to make recruiting subjects easier. The criteria produces a population that should have little variability, making them more likely to respond to the intervention in a similar way, making it easier to detect subtle differences between each group.
What may be a problem associated with exclusion and inclusion criteria?
If many criteria were used, the population may not be generalisable, and not represent the actual population likely to receive the intervention.
What is a problem associated with using only few exclusion and inclusion criteria?
Whilst the results would have a more general application, the amount of variability between the patients would be high, making it more difficult to show if a treatment is effective. When there is much variability, sometimes only large effects can be easily detected.
When is it unethical to give a control group a placebo?
When an established treatment already exists.
What is randomisation?
A process of allocating subjects between different trial interventions. Each subject has the same chance of being allocated to any group, which ensures similarity in characteristics between the arms.
What effect does randomisation have on confounding factors?
It reduces the effect of both known and unknown confounding factors.
What effect does randomisation have on bias?
Minimises it. If either the researcher or trial subject is allowed to decide which intervention they are to receive, then subjects with certain characteristics could be over-presented in one of the trial arms.
What is selection bias?
Can occur if choosing a particular subject for the trial is influenced by knowing the next treatment allocation.
What is allocation bias?
Involves giving the treatment that the clinician or patient feels might be most beneficial. Sometimes, the researcher has access to the list of randomisations from which the next allocation can be determined, possibly creating allocation bias.
How can allocation bias be avoided?
By using a central office, or computer system in charge of randomisation, because the researcher has no control over the process (allocation concealment)
What is the main limitation of small trials?
The interpretation of their results. Due to their small size it is more likely that they will produce false-positive results or overestimate the magnitude of the treatment benefit.
Why are surrogate outcome measures used?
If a trial would be impractically large, or long because of a true endpoint with too few events to produce a reliable evaluation of an intervention. Surrogate endpoints are considered as precursors of the true endpoint and produce more events in a shorter space of time.
What surrogate marker is often used in clinical trials and is it a good marker?
Tumour response - not a good marker as tumour response often doesn’t correlate well with survival. It is appropriate for use in phase I/II trials, it wouldn’t be used in phase III.
What are the three types of outcome measure?
1) Counting people (how many have the health outcome of interest)
2) Take measurements on people
3) Time to event measurements.
Why should both arms of a trial receive their examinations at the same time (when the outcome measure is disease progression)
To prevent bias. For disease progression, the date of disease progression is required (time to event). Given that the time to event won’t actually be the day of the examination, the examinations must be at the same time to avoid progression appearing to be sooner/later in one intervention arm compared to the other.
Why are phase III trial patients seen more often? (with additional assessments)
To closely monitor the patient’s well being, also to try and get accurate dates of progression/relapse (usually an endpoint)
Why is there a need to balance the frequency of assessments in phase III trials?
Increased costs, inconvenience to patients, or increased radiation exposure (scans)
What are some main purposes of new cancer therapeutic interventions?
Cure the cancer
Extend life/ progression free survival (for late stage/advanced cancers)
Reduce symptoms of advanced disease (QOL)
What type of data is a time-to-event measure, and what is the name of its effect size?
Type = Time-to-event. Effect size = Hazard ratio
