ICH E9 Glossary

Question 1

Bayesian Approaches

Answer 1

Approaches to data analysis that provide a posterior probability distribution for some parameter (e.g. treatment effect), derived from the observed data and a prior probability distribution for the parameter. The posterior distribution is then used as the basis for statistical inference.

Question 2

Bias (Statistical & Operational)

Answer 2

The systematic tendency of any factors associated with the design, conduct, analysis and evaluation of the results of a clinical trial to make the estimate of a treatment effect deviate from its true value. Bias introduced through deviations in conduct is referred to as ‘operational’ bias. The other sources of bias listed above are referred to as ‘statistical’.

Question 3

Blind Review

Answer 3

The checking and assessment of data during the period of time between trial completion (the last observation on the last subject) and the breaking of the blind, for the purpose of finalising the planned analysis

Question 4

Content Validity

Answer 4

The extent to which a variable (e.g. a rating scale) measures what it is supposed to
measure.

Question 5

Double-Dummy

Answer 5

A technique for retaining the blind when administering supplies in a clinical trial, when the two treatments cannot be made identical. Supplies are prepared for
Treatment A (active and indistinguishable placebo) and for Treatment B (active and indistinguishable placebo). Subjects then take two sets of treatment; either A (active) and B (placebo), or A (placebo) and B (active).

Question 6

Equivalence Trial

Answer 6

A trial with the primary objective of showing that the response to two or more
treatments differs by an amount which is clinically unimportant. This is usually
demonstrated by showing that the true treatment difference is likely to lie between a
lower and an upper equivalence margin of clinically acceptable differences.

Question 7

Frequentist Methods

Answer 7

Statistical methods, such as significance tests and confidence intervals, which can be interpreted in terms of the frequency of certain outcomes occurring in hypothetical repeated realisations of the same experimental situation.

Question 8

Full Analysis Set

Answer 8

The set of subjects that is as close as possible to the ideal implied by the intention-to treat principle. It is derived from the set of all randomised subjects by minimal and justified elimination of subjects

Question 9

Generalisability, Generalisation

Answer 9

The extent to which the findings of a clinical trial can be reliably extrapolated from
the subjects who participated in the trial to a broader patient population and a
broader range of clinical settings

Question 10

Global Assessment Variable

Answer 10

A single variable, usually a scale of ordered categorical ratings, which integrates objective variables and the investigator’s overall impression about the state or change in state of a subject.

Question 11

Independent Data Monitoring Committee (IDMC) (Data and Safety Monitoring Board, Monitoring Committee, Data Monitoring Committee)

Answer 11

An independent data-monitoring committee that may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial.

Question 12

Intention-To-Treat Principle

Answer 12

The principle that asserts that the effect of a treatment policy can be best assessed by evaluating on the basis of the intention to treat a subject (i.e. the planned treatment regimen) rather than the actual treatment given. It has the consequence that subjects
allocated to a treatment group should be followed up, assessed and analysed as members of that group irrespective of their compliance to the planned course of treatment.

Question 13

Interaction (Qualitative & Quantitative)

Answer 13

The situation in which a treatment contrast (e.g. difference between investigational product and control) is dependent on another factor (e.g. centre). A quantitative interaction refers to the case where the magnitude of the contrast differs at the different levels of the factor, whereas for a qualitative interaction the direction of the contrast differs for at least one level of the factor.

Question 14

Inter-Rater Reliability

Answer 14

The property of yielding equivalent results when used by different raters on different occasions.

Question 15

Intra-Rater Reliability

Answer 15

The property of yielding equivalent results when used by the same rater on different occasions

Question 16

Interim Analysis

Answer 16

Any analysis intended to compare treatment arms with respect to efficacy or safety at any time prior to the formal completion of a trial.

Question 17

Meta-Analysis

Answer 17

The formal evaluation of the quantitative evidence from two or more trials bearing on the same question. This most commonly involves the statistical combination of
summary statistics from the various trials, but the term is sometimes also used to refer to the combination of the raw data.

Question 18

Multicentre Trial

Answer 18

A clinical trial conducted according to a single protocol but at more than one site, and therefore, carried out by more than one investigator

Question 19

Non-Inferiority Trial

Answer 19

A trial with the primary objective of showing that the response to the investigational product is not clinically inferior to a comparative agent (active or placebo control).

Question 20

Preferred and Included Terms

Answer 20

In a hierarchical medical dictionary, for example MedDRA, the included term is the lowest level of dictionary term to which the investigator description is coded. The preferred term is the level of grouping of included terms typically used in reporting frequency of occurrence. For example, the investigator text “Pain in the left arm” might be coded to the included term “Joint pain”, which is reported at the preferred term level as “Arthralgia”.

Question 21

Per Protocol Set (Valid Cases, Efficacy Sample, Evaluable Subjects Sample)

Answer 21

The set of data generated by the subset of subjects who complied with the protocol sufficiently to ensure that these data would be likely to exhibit the effects of
treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of
major protocol violations.

Question 22

Safety & Tolerability

Answer 22

The safety of a medical product concerns the medical risk to the subject, usually assessed in a clinical trial by laboratory tests (including clinical chemistry and
haematology), vital signs, clinical adverse events (diseases, signs and symptoms), and other special safety tests (e.g. ECGs, ophthalmology). The tolerability of the medical product represents the degree to which overt adverse effects can be tolerated by the subject.

Question 23

Statistical Analysis Plan

Answer 23

A statistical analysis plan is a document that contains a more technical and detailed elaboration of the principal features of the analysis described in the protocol, and includes detailed procedures for executing the statistical analysis of the primary and secondary variables and other data

Question 24

Superiority Trial

Answer 24

A trial with the primary objective of showing that the response to the investigational
product is superior to a comparative agent (active or placebo control).

Question 25

Surrogate Variable

Answer 25

A variable that provides an indirect measurement of effect in situations where direct measurement of clinical effect is not feasible or practical.

Question 26

Treatment Effect

Answer 26

An effect attributed to a treatment in a clinical trial. In most clinical trials the treatment effect of interest is a comparison (or contrast) of two or more treatments.

Question 27

Treatment Emergent

Answer 27

An event that emerges during treatment having been absent pre-treatment, or worsens relative to the pre-treatment state.