Adapted from "The Revised CONSORT Statement for Reporting Randomized Trials: Explanation and Elaboration", Douglas G. Altman, DSc; Kenneth F. Schulz, PhD; David Moher, MSc; Matthias Egger, MD; Frank Davidoff, MD; Diana Elbourne, PhD; Peter C. Gøtzsche, MD; Thomas Lang, MA, for the CONSORT Group, Annals of Internal Medicine 2001;134:553-694.
Adjusted analysis: Usually refers to attempts to control (adjust) for baseline imbalances between groups in important patient characteristics. Sometimes used to refer to adjustments of P value to take account of multiple testing. See Multiple comparisons.
Adverse event: An unwanted effect detected in participants in a trial. The term is used regardless of whether the effect can be attributed to the intervention under evaluation. See also Side effect.
Allocation concealment: A technique used to prevent selection bias by concealing the allocation sequence from those assigning participants to intervention groups, until the moment of assignment. Allocation concealment prevents researchers from (unconsciously or otherwise) influencing which participants are assigned to a given intervention group.
Allocation ratio: The ratio of intended numbers of participants in each of the comparison groups. For two-group trials, the allocation ratio is usually 1:1, but unequal allocation (such as 1:2) is sometimes used.
Allocation sequence: A list of interventions, randomly ordered, used to assign sequentially enrolled participants to intervention groups. Also termed "assignment schedule," "randomization schedule," or "randomization list."
Ascertainment bias: Systematic distortion of the results of a randomized trial that occurs when the person assessing outcome, whether an investigator or the participant, knows the group assignment.
Assignment: See Random assignment.
Baseline characteristics: Demographic, clinical, and other data collected for each participant at the beginning of the trial, before the intervention is administered. See also Prognostic variable.
Bias: Systematic distortion of the estimated intervention effect away from the "truth," caused by inadequacies in the design, conduct, or analysis of a trial.
Blinding (masking): The practice of keeping the trial participants, care providers, data collectors, and sometimes those analyzing data unaware of which intervention is being administered to which participant. Blinding is intended to prevent bias on the part of study personnel. The most common application is double-blinding, in which participants, caregivers, and outcome assessors are blinded to intervention assignment. The term masking may be used instead of blinding.
Block randomization: See Permuted block design.
Blocking: See Permuted block design.
Comparison groups: The groups being compared in the randomized trial. Also referred to as "study groups"; "treatment groups"; "arms" of a trial; or by individual terms, such as "treatment group" and "control group."
Concealment: See Allocation concealment.
Confidence interval: A measure of the precision of an estimated value. The interval represents the range of values, consistent with the data, that is believed to encompass the "true" value with high probability (usually 95%). The confidence interval is expressed in the same units as the estimate. Wider intervals indicate lower precision; narrow intervals indicate greater precision.
Confounding: A situation in which the estimated intervention effect is biased because of some difference between the comparison groups apart from the planned interventions, such as baseline characteristics, prognostic factors, or concomitant interventions. For a factor to be a confounder, it must differ between the comparison groups and predict the outcome of interest. See also Adjusted analysis.
Deterministic method of allocation: A method of allocating participants to interventions that uses a predetermined rule without a random element (for example, alternate assignment or based on day of week, hospital number, or date of birth). Because group assignments can be predicted in advance of assignment in deterministic methods, participant allocation may be manipulated, causing selection bias. See also Selection bias; Allocation concealment.
Effect size: See Treatment effect.
Eligibility criteria: The clinical and demographic characteristics that define which persons are eligible to be enrolled in a trial.
End point: See Outcome measure.
Enrollment: The act of admitting a participant into a trial. Participants should be enrolled only after study personnel have confirmed that all the eligibility criteria have been met. Formal enrollment must occur before random assignment is performed.
External validity: The extent to which the results of a trial provide a correct basis for generalizations to other circumstances. Also called generalizability or applicability.
Follow-up: A process of periodic contact with participants enrolled in the randomized trial for the purpose of administering the assigned interventions, modifying the course of interventions, observing the effects of the interventions, or collecting data. See also Loss to follow-up.
Generation of allocation sequence: The procedure used to create the (random) sequence for making intervention assignments, such as a table of random numbers or a computerized random-number generator. Such options as simple randomization, blocked randomization, and stratified randomization are part of the generation of the allocation sequence.
Hypothesis: In a trial, a statement relating to the possible different effect of the interventions on an outcome. The null hypothesis of no such effect is amenable to explicit statistical evaluation by a hypothesis test, which generates a P value.
Imprecision: A quantification of the uncertainty in an estimate such as an effect size, usually expressed as the 95% confidence interval around the estimate. Also refers more generally to other sources of uncertainty, such as measurement error.
Intention-to-treat analysis: A strategy for analyzing data in which all participants are included in the group to which they were assigned, regardless of whether they completed the intervention given to the group. Intention-to-treat analysis prevents bias caused by loss of participants, which may disrupt the baseline equivalence established by random assignment and may reflect nonadherence to the protocol.
Interaction: A situation in which the effect of one explanatory variable on the outcome is affected by the value of a second explanatory variable. In a trial, a test of interaction examines whether the treatment effect varies across subgroups of participants. See also Subgroup analysis.
Interim analysis: Analysis comparing intervention groups at any time before formal completion of the trial, usually before recruitment is complete. Often used with stopping rules so that a trial can be stopped if participants are being put at risk unnecessarily. The timing and frequency of interim analyses should be specified in the original trial protocol.
Internal validity: The extent to which the design and conduct of the trial eliminate the possibility of bias.
Intervention: The treatment or other health care course of action under investigation. The effects of an intervention are quantified by the outcome measures.
Loss to follow-up: Loss of contact with some participants, so that researchers cannot complete data collection as planned. Loss to follow-up is a common cause of missing data, especially in long-term studies. See also Follow-up.
Minimization: An assignment strategy, similar in intention to stratification, that ensures excellent balance between intervention groups for specified prognostic factors. The next participant is assigned to whichever group would minimize the imbalance between groups on specified prognostic factors. Minimization is an acceptable alternative to random assignment (Table 3).
Multiple comparisons: Performance of multiple analyses on the same data. Multiple statistical comparisons increase the probability of a type I error: that is, attributing a difference to an intervention when chance is the more likely explanation.
Multiplicity: The proliferation of possible comparisons in a trial. Common sources of multiplicity are multiple outcome measures, outcomes assessed at several time points after the intervention, subgroup analyses, or multiple intervention groups.
Objectives: The general questions that the trial was designed to answer. The objective may be associated with one or more hypotheses that, when tested, will help answer the question. See also Hypothesis.
Open trial: A randomized trial in which no one is blinded to group assignment.
Outcome measure: An outcome variable of interest in the trial (also called an end point). Differences between groups in outcome variables are believed to be the result of the differing interventions. The primary outcome is the outcome of greatest importance. Data on secondary outcomes are used to evaluate additional effects of the intervention.
Participant: A person who takes part in a trial. Participants usually must meet certain eligibility criteria. See also Recruitment, Enrollment.
Performance bias: Systematic differences in the care provided to the participants in the comparison groups other than the intervention under investigation.
Permuted block design: An approach to generating an allocation sequence in which the number of assignments to intervention groups satisfies a specified allocation ratio (such as 1:1 or 2:1) after every "block" of specified size. For example, a block size of 12 may contain 6 of A and 6 of B (ratio of 1:1) or 8 of A and 4 of B (ratio of 2:1). Generating the allocation sequence involves random selection from all of the permutations of assignments that meet the specified ratio.
Planned analyses: The statistical analyses specified in the trial protocol (that is, planned in advance of data collection). Also called a priori analyses. In contrast to unplanned analyses (also called exploratory, data-derived, or post hoc analyses), which are analyses suggested by the data. See also Subgroup analyses.
Power: The probability (generally calculated before the start of the trial) that a trial will detect as statistically significant an intervention effect of a specified size. The prespecified trial size is often chosen to give the trial the desired power. See Sample size.
Precision: See Imprecision.
Prognostic variable: A baseline variable that is prognostic in the absence of intervention. Unrestricted, simple randomization can lead to chance baseline imbalance in prognostic variables, which can affect the results and weaken the trial's credibility. Stratification and minimization protect against such imbalances. See also Adjusted analysis, Restricted randomization.
Protocol deviation: A failure to adhere to the prespecified trial protocol, or a participant for whom this occurred. Examples are ineligible participants who were included in the trial by mistake and those for whom the intervention or other procedure differed from that outlined in the protocol.
Random allocation; random assignment; randomization: In a randomized trial, the process of assigning participants to groups such that each participant has a known and usually an equal chance of being assigned to a given group. It is intended to ensure that the group assignment cannot be predicted.
Recruitment: The process of getting participants into a randomized trial. See also Enrollment.
Restricted randomization: Any procedure used with random assignment to achieve balance between study groups in size or baseline characteristics. Blocking is used to ensure that comparison groups will be of approximately the same size. With stratification, randomization with restriction is carried out separately within each of two or more subsets of participants (for example, defining disease severity or study centers) to ensure that the patient characteristics are closely balanced within each intervention group (Table 3).
Sample size: The number of participants in the trial. The intended sample size is the number of participants planned to be included in the trial, usually determined by using a statistical power calculation. The sample size should be adequate to provide a high probability of detecting as significant an effect size of a given magnitude if such an effect actually exists. The achieved sample size is the number of participants enrolled, treated, or analyzed in the study.
Selection bias: Systematic error in creating intervention groups, causing them to differ with respect to prognosis. That is, the groups differ in measured or unmeasured baseline characteristics because of the way in which participants were selected for the study or assigned to their study groups. The term is also used to mean that the participants are not representative of the population of all possible participants. See also Allocation concealment, External validity.
Side effect: An unintended, unexpected, or undesirable result of an intervention. See also Adverse event.
Simple randomization: Randomization without restriction. In a two-group trial, it is analogous to the toss of a coin. See Restricted randomization.
Stopping rule: In some trials, a statistical criterion that, when met by the accumulating data, indicates that the trial can or should be stopped early to avoid putting participants at risk unnecessarily or because the intervention effect is so great that further data collection is unnecessary. Usually defined in the trial protocol and implemented during a planned interim analysis. See also Interim analysis.
Stratified randomization: Random assignment within groups defined by participant characteristics, such as age or disease severity, intended to ensure good balance of these factors across intervention groups. See also Restricted randomization.
Subgroup analysis: An analysis in which the intervention effect is evaluated in a defined subset of the participants in the trial, or in complementary subsets, such as by sex or in age categories. Sample sizes in subgroup analyses are often small, and subgroup analyses therefore usually lack statistical power. They are also subject to the multiple comparisons problem. See also Multiple comparisons.
Treatment effect: A measure of the difference in outcome between intervention groups. Commonly expressed as a risk ratio (relative risk), odds ratio, or risk difference for binary outcomes and as difference in means for continuous outcomes. Often referred to as the "effect size."