Key definitions

Question 1

Clinically-meaningful

Answer 1

Represents a meaningful advance in healthcare/ patient outcomes

Question 2

Reliable

Answer 2

Results can be trusted, reproducible if trial is repeated

Question 3

Internal validity

Answer 3

Observed differences can be correctly attributed to the intervention

Question 4

External validity

Answer 4

Trial results can be generalized to the real-world population

Question 5

Superiority trials

Answer 5

Test whether new drug is better than comparator e.g. placebo or current best treatment

Question 6

Equivalence trials

Answer 6

Test whether a new drug is the same as an existing treatment

Question 7

Clinical equivalence trials

Answer 7

Test whether clinical outcomes for a new drug are the same as for an existing treatment

Question 8

Bioequivalence trials

Answer 8

Test whether pharmacokinetic parameters e.g. blood concentration or receptor occupancy for a new drug are the same as for an existing treatment

Question 9

Non-inferiority trials

Answer 9

Test whether a new treatment is no worse than an existing treatment

Question 10

Bias

Answer 10

Systematic distortion of the results of a clinical study away from the truth

Question 11

Selection bias

Answer 11

Systematic differences in way subjects are enrolled or treatments allocated

Question 12

Bias in study management

Answer 12

Treatment groups not handled equally (e.g. participants, samples, investigational medicinal product)

Question 13

Observer ascertainment bias

Answer 13

Participants and/or investigators are influenced by knowledge of treatment assignment

Question 14

Introduced by exclusions after randomisation

Answer 14

Missing data due to participant dropouts or lack of individual measurement

Question 15

Publication bias

Answer 15

Positive trial outcomes more likely to be published than negative outcomes

Question 16

Intention-to-treat analysis

Answer 16

Analysis includes all randomised participants, irrespective of what happened to them during the study

Question 17

Per-protocol analysis

Answer 17

Analysis includes only participants who completed the protocol fully

Question 18

Confounder

Answer 18

A parameter that is related to both the study treatment and the outcome, but is not caused by the treatment. Confounders can interfere with the ability of a trial to produce a true result and should be controlled for in study design by randomisation

Question 19

Randomisation

Answer 19

A process of allocating participants to study groups that gives everyone an equal chance of being allocated to any group

Question 20

Stratification

Answer 20

Randomisation within subgroups of key confounders

Question 21

Minimisation

Answer 21

Dynamic method of randomisation that assigns participants to treatment groups in an order that minimises overall imbalance between groups for a number of selected confounding factors

Question 22

Type 1 error

Answer 22

Rejecting the null hypothesis when it is true, false positive result
Designated as alpha, usually set at 0.05 (5%)

Question 23

Type 2 error

Answer 23

Failing to reject the null hypothesis when it is false, false negative result
Designated as beta, usually set at 20%

Question 24

Sample size

Answer 24

The number of people to be enrolled in a trial or study

Question 25

Power

Answer 25

The ability of a study to find a significant result if one exists Calculated as 100-beta (if beta is 20%, power is 80%)

Question 26

Sample

Answer 26

A set of observations from the population

Question 27

Population

Answer 27

The complete set of possible observations

Question 28

Multiplicity

Answer 28

Performing many statistical tests on one clinical trial - increases the risk of a type 1 error/false positive result

Question 29

Risk of type 1 error

Answer 29

[1-(1-alpha)n], where n is the number of tests performed and alpha is the type 1 error rate

Question 30

Repeated measurements

Answer 30

Measurements at multiple timepoints

Question 31

Interim analysis

Answer 31

Analysis conducted during the trial for ethical or economic reasons - trial may be terminated early if significant differences in efficacy or safety are identified

Question 32

Bonferroni correction

Answer 32

Reducing the alpha of statistical tests to reduce the risk of a false positive result - divide 0.05 by the number of tests to set the significance level for the subtests

Question 33

Covariate

Answer 33

Baseline characteristic (e.g. age, sex) that accounts for some of the variance in an outcome measured in a clinical trial (e.g. age is associated with increased risk of mortality). May modify the effect of a new treatment (e.g. drug may work in younger but not older patients)