Regarding randomised clinical trials, explain the following terms:
a) External validity. (20% marks)
b) Allocation concealment. (20% marks)
c) Stratification. (20% marks)
d) Sensitivity analysis. (20% marks)
e) Fragility Index. (20% marks)
These SAQs are the output of a Random Statistics Definition Generator. All of these definitions have appeared in past paper questions, just not all of them in the same question. Links on the bolded answer headings below lead to past papers where the examiners left us with their formal official answers. The fragility index was the only new one.
a) External validity: the extent to which the study results can be generalised to the greater population, which is influenced by a vast array of factors:
- The setting and the population from which the sample was selected
- The inclusion and exclusion criteria
- The "randomness" of the sample, and the baseline chacteristics of the patients
- The difference between the trial control group and the routine practice
- The changes in practice since the publication of the trial
- The use of patient centered outcomes
- The degree to which the surrogate outcome measures are related to patient-centered outcomes
b) Allocation concealment: Procedure for protecting the randomization process and ensuring that the clinical investigators and those involved in the conduct of the trial are not aware of the group to which the subject has been allocated
- This is a technique of preventing selection bias.
- The selection of patients is randomised, and nobody knows what treatment the next enrolled patient will receive.
- A truly random sequence of allocations prevents the investigators from being able to predict the allocated treatment on the basis of previously allocated treatments.
- Allocation concealment prevents the investigators from predicting who is getting what treatment before the patient is enrolled, whereas blinding prevents the investigators from knowing who is getting what treatment after the patient is enrolled.
c) Stratification is a process that protects against imbalance in prognostic factors that are present at the time of randomisation.
- Stratification is the partitioning of subjects and results by a factor other than the treatment given.
- Stratification ensures that pre-identified confounding factors are equally distributed, to achieve balance. The objective is to remove "nuisance variables", eg. the presence of neutropenia in a trial performed on septic patients. One would want to ensure that the treatment group and the placebo group had equal numbers of these haematology disasters.
d) Sensitivity analysis is the analysis of data from the trial with a change or alteration to one or more underlying assumptions used in the original analysis.
- Analysis of the data from a clinical trial where some of the assumptions are intentionally changed
- One example of this is to assume that all the patients lost to follow-up or who dropped out of the study have failed treatment.
e) The fragility index is a number indicating how many patients would be required to convert a trial from being statistically significant to not significant (p ≥ 0.05)