See risk difference.

See concealment of allocation.

(synonyms: external validity, generalisability, relevance, transferability)
The degree to which the results of an observation, study or review hold true in other settings.

Systematic differences between comparison groups in withdrawals or exclusions of participants from the results of a study. For example, patients may drop out of a study because of side effects of the intervention. Excluding these patients from the analysis could result in an overestimate of the effectiveness of the intervention.

A systematic error or deviation in results or inferences. In studies of the effects of healthcare, bias can arise from systematic differences in the groups that are compared (selection bias), the care that is provided, or exposure to other factors apart from the intervention of interest (performance bias), withdrawals or exclusions of people entered into the study (attrition bias) or how outcomes are assessed (detection bias). Bias does not necessarily imply a prejudice, such as the investigators' desire for particular results. This differs from conventional use of the word in which bias refers to a partisan point of view. See also methodological quality, validity.

(synonym: masking) Keeping secret group assignment (e.g. to treatment or control) from the study participants or investigators. Blinding is used to protect against the possibility that knowledge of assignment may affect patient response to treatment, provider behaviours (performance bias) or outcome assessment (detection bias). Blinding is not always practical (e.g. when comparing surgery to drug treatment). The importance of blinding depends on how objective the outcome measure is; blinding is more important for less objective outcome measures such as pain or quality of life. See also single blind, double blind and triple blind.

An uncontrolled observational study involving an intervention and outcome for more than one person.

(synonyms: anecdote, case history, single case report) An uncontrolled observational study involving an intervention and outcome for a single person (or other unit).

See Cochrane Controlled Trials Register.

See Cochrane Database of Systematic Reviews.

The Cochrane Collaboration's register of studies which may be relevant for inclusion in Cochrane Reviews. Its development is guided by the CENTRAL/CCTR Advisory Group. See also Cochrane Controlled Trials Register.

Any statistical test based on comparison of a test statistic to a chi-square distribution.

See Confidence interval

(Cumulative Index of Nursing and Allied Health Literature) Electronic database covering the major journals in nursing and allied health. Years of coverage: 1983 - present.

A systematically developed statement for practitioners and patients about appropriate health care for specific clinical circumstances. (e.g. Scottish Intercollegiate or SIGN guidelines, Royal College of Physicians guidelines etc.)

(synonyms: therapeutic trial, intervention study) A trial that tests out a drug or other intervention to assess its effectiveness and safety. This general term encompasses randomised controlled trials and controlled clinical trials.

An international organisation that aims to help people make well informed decisions about health by preparing, maintaining and ensuring the accessibility of systematic reviews of the benefits and risks of healthcare interventions.

(CCTR) A database of references to controlled trials in health care. Cochrane groups and other organisations have been invited to contribute their specialised registers, and these registers, together with references to clinical trials identified on MEDLINE and other sources, form the CENTRAL register of studies. Records from CENTRAL, following quality control to try to ensure that only reports of definite randomised controlled trials or controlled clinical trials are included, make up The Cochrane Controlled Trials Register (CCTR). Trials included in the STEP process are derived from the Cochrane Stroke Group.

(CDSR) It brings together all the currently available Cochrane Reviews and is updated quarterly.

A Cochrane Review is a systematic, up-to-date summary of reliable evidence of the benefits and risks of healthcare. Cochrane Reviews are intended to help people make practical decisions.

In a randomised controlled trial, the application of additional diagnostic or therapeutic procedures to members of either or both the experimental and the control groups.

The process used to prevent foreknowledge of group assignment in a randomised controlled trial, which should be seen as distinct from blinding. The allocation process should be impervious to any influence by the individual making the allocation by having the randomisation process administered by someone who is not responsible for recruiting participants; for example, a hospital pharmacy, or a central office. Using methods of assignment such as date of birth and case record numbers (see quasi random allocation) are open to manipulation. Adequate methods of allocation concealment include: centralized randomisation schemes; randomisation schemes controlled by a pharmacy; numbered or coded containers in which capsules from identical-looking, numbered bottles are administered sequentially; on-site computer systems, where allocations are in a locked unreadable file; and sequentially numbered opaque, sealed envelopes.

(CI) The range within which the "true" value (e.g. size of effect of an intervention) is expected to lie with a given degree of certainty (e.g. 95% or 99%). Note: Confidence intervals represent the probability of random errors, but not systematic errors (bias).

[or Competing interests declaration] A statement by a contributor to a report or review of personal financial or other interests that could have influenced the findings or their interpretation.

A situation in which a measure of the effect of an intervention or exposure is distorted because of the association of exposure with other factor(s) that influence the outcome under investigation.

(healthcare consumer) Someone who uses, is affected by, or who is entitled or compelled to use a health related service.

In clinical trials, the unintentional application of the intervention being evaluated to people in the control group or inadvertent failure to apply the intervention to people assigned to the intervention group.

The conditions and circumstances that are relevant to the application of an intervention, for example the setting [in hospital, at home, in the air], the time [working day, holiday, night-time], type of practice [primary, secondary, tertiary care; private practice, insurance practice, charity], whether routine or emergency.

In clinical trials comparing two or more interventions, a control is a person in the comparison group that receives a placebo, no intervention, usual care or another form of care.

Refers to a study that compares one or more intervention groups to one or more comparison (control) groups. Whilst not all controlled studies are randomised, all randomised trials are controlled.

The process of assessing and interpreting evidence by systematically considering its validity, results and relevance.

A type of clinical trial comparing two or more interventions in which the participants, upon completion of the course of one treatment are switched to another. For example, for a comparison of treatments A and B, half the participants are randomly allocated to receive them in the order A, B and half to receive them in the order B, A. A problem with this design is that the effects of the first treatment may carry over into the period when the second is given.

See Database of Abstracts of Reviews of Effectiveness.

A collection of organised information, usually held on a computer. In some ways a database is similar to a filing system, but with important advantages: the information can be revised and kept up to date easily, and the computer can retrieve information from it very quickly. Electronic databases such as MEDLINE, EMBASE and the CDSR can be distributed on disk, CD-ROM or via the Internet.

(DARE) A collection of structured abstracts and bibliographic references of systematic reviews of the effects of healthcare.

(synonym: ascertainment bias) Systematic differences between comparison groups in how outcomes are ascertained, diagnosed or verified.

(synonym: binary data) Observations with two possible categories such as dead/alive, smoker/non-smoker, present/not present.

(synonym: double masked) Neither the participants in a trial nor the investigators (outcome assessors) are aware of which intervention the participants are given. The purpose of blinding the participants (recipients and providers of care) is to prevent performance bias. The purpose of blinding the investigators (outcome assessors, who might also be the care providers) is to protect against detection bias. See also blinding, single blind, triple blind, concealment of allocation.

1. A generic term for the estimate of effect for a study. 2. A dimensionless measure of effect that is typically used for continuous data when different scales (e.g. for measuring pain) are used to measure an outcome and is usually defined as the difference in means between the intervention and control groups divided by the standard deviation of the control or both groups. See standardised mean difference.

The extent to which a specific intervention, when used under ordinary circumstances, does what it is intended to do.

The extent to which an intervention produces a beneficial result under ideal conditions. Clinical trials that assess efficacy are sometimes called explanatory trials and are restricted to participants who fully co-operate.

(Excerpta Medica database) A European-based electronic database of pharmacological and biomedical literature covering 3,500 journals from 110 countries. Years of coverage - 1974 to present.

Empirical results are based on experience (or observation) rather than on reasoning alone.

The study of the distribution and determinants of health-related states or events in specified populations.

(synonym: treatment effect) In studies of the effects of healthcare, the observed relationship between an intervention and an outcome expressed as, for example, a number needed to treat, odds ratio, risk difference, relative risk, standardised mean difference, or weighted mean difference.

The proportion of participants in a group in whom an event is observed. Thus, if out of 100 patients the event (e.g. a stroke) is observed in 32, the event rate is 0.32.

A person with relevant content, methodological or user expertise who critically examines reviews in her/his area of expertise.

(synonyms: external validity, generalisability, relevance, transferability) The degree to which the results of an observation hold true in other settings. See also validity .

Most trials only consider a single factor, where an intervention is compared with one or more alternatives, or a placebo. In a trial using a 2x2 factorial design, participants are allocated to one of four possible combinations. For example in a 2x2 factorial, RCT of nicotine replacement and counselling, participants would be allocated to: nicotine replacement alone, counselling alone, both, or neither. In this way it is possible to test the independent effect of each intervention on smoking cessation and the combined effect of (interaction between) the two interventions.

The ascertainment of outcomes of an intervention at one or more stated times after the intervention has ended.

(synonyms: applicability, external validity, relevance, transferability) Generalisability is the degree to which the results of a study or systematic review can be extrapolated to other circumstances, in particular to routine health care situations.

The method, procedure or measurement that is widely accepted as being the best available against which new interventions should be compared.

Handsearching refers to the planned searching of a journal page by page (i.e. by hand), including editorials, letters, etc., to identify all reports of randomised controlled trials and controlled clinical trials.

In systematic reviews heterogeneity refers to variability or differences between studies in the estimates of effects. A distinction is sometimes made between "statistical heterogeneity" (differences in the reported effects), "methodological heterogeneity" (differences in study design) and "clinical heterogeneity" (differences between studies in key characteristics of the participants, interventions or outcome measures). Statistical tests of heterogeneity are used to assess whether the observed variability in study results (effect sizes) is greater than that expected to occur by chance. However, these tests have low statistical power. See also homogeneity.

Person or group for whom data were collected earlier than for the group being studied. Because of changes over time in risks, prognosis, healthcare, etc. there is a large risk of bias (in studies that use historical controls) due to systematic differences between the comparison groups.

In systematic reviews homogeneity refers to the degree to which the results of studies included in a review are similar. "Clinical homogeneity" means that, in trials included in a review, the participants, interventions and outcome measures are similar or comparable. Studies are considered "statistically homogeneous" if their results vary no more than might be expected by the play of chance. See heterogeneity.

The number of new cases of a disease or event in a population during a specific period of time.

(NLM), and a periodical index to the medical literature. Available in printed form, or electronically as MEDLINE.

An intention-to-treat analysis is one in which all the participants in a trial are analysed according to the intervention to which they were allocated, whether they received it or not. Intention-to-treat analyses are favoured in assessments of effectiveness as they mirror the noncompliance and treatment changes that are likely to occur when the intervention is used in practice, and because of the risk of attrition bias when participants are excluded from the analysis.

See validity.

Network of millions of computers worldwide. Computers on the Internet use compatible communication standards and share the ability to contact each other and share data. Users of the Internet communicate via electronic mail (e-mail), via Telnet (a process which allows a person to log in to a remote host), and via FTP. See also World Wide Web.

The degree of stability exhibited when a measurement is repeated under identical conditions by different raters. Reliability refers to the degree to which the results obtained by a measurement procedure can be replicated. Lack of inter-rater reliability may arise from divergences between observers or instability of the attribute being measured. See also Intra-rater reliability.

See Clinical trial.

The degree of stability exhibited when a measurement is repeated under identical conditions by the same rater. Reliability refers to the degree to which the results obtained by a measurement procedure can be replicated. Lack of intra-rater reliability may arise from divergences between instruments of measurement or instability of the attribute being measured. See also Inter-rater reliability.

See blinding.

(synonyms: arithmetic mean, average) The average value, calculated by adding all the observations and dividing by the number of observations.

(MEDlars onLINE) An electronic database produced by the United States National Library of Medicine. It indexes millions of articles in selected (about 3,700) journals. It is available through most medical libraries, and can be accessed on CD-ROM, the Internet and by other means. Years of coverage - 1966 to present.

(Medical Subject Headings) Terms used by the United States National Library of Medicine to index articles in Index Medicus and MEDLINE. Designed to reduce problems that arise from, for example, differences in British and American spelling. The MeSH system has a tree structure in which broad subject terms branch into a series of progressively narrower subject terms.

The use of statistical techniques in a systematic review to integrate the results of included studies. Sometimes used as a synonym for systematic reviews, where the review includes meta-analysis.

Multivariate meta-analytic techniques, such as logistic regression, used to explore the relationship between study characteristics (e.g. allocation concealment, baseline risk, timing of the intervention) and study results (the magnitude of effect observed in each study) in a systematic review.

(synonyms: validity, internal validity) The extent to which the design and conduct of a study are likely to have prevented systematic errors (bias). Variation in quality can explain variation in the results of studies included in a systematic review. More rigorously designed (better 'quality') trials are more likely to yield results that are closer to the 'truth'. See also external validity, validity.

A method of allocation used to provide comparison groups that are closely similar for several variables. It can be done with or without a component of randomisation.

A term often used to refer to a study that does not have "statistically significant" (positive) results indicating a beneficial effect of the intervention being studied. The term can generate confusion because it refers to both statistical significance and the direction of effect. Studies often have multiple outcomes, the criteria for classifying studies as "negative" are not always clear and, in the case of studies of risk or undesirable effects, "negative" studies are ones that do not show a harmful effect.

The statistical hypothesis that one variable (e.g. whether or not a study participant was allocated to receive an intervention) has no association with another variable or set of variables (e.g. whether or not a study participant died), or that two or more population distributions do not differ from one another. In simplest terms, the null hypothesis states that the results observed in a study are no different from what might have occurred as a result of the play of chance.

(NNT) The number of patients who need to be treated to prevent one bad outcome. It is the inverse of the risk difference.

(OR) The ratio of the odds of an event in the experimental (intervention) group to the odds of an event in the control group. Odds are the ratio of the number of people in a group with an event to the number without an event. Thus, if a group of 100 people had an event rate of 0.20, 20 people had the event and 80 did not, and the odds would be 20/80 or 0.25. An odds ratio of one indicates no difference between comparison groups. For undesirable outcomes an OR that is less than one indicates that the intervention was effective in reducing the risk of that outcome. When the event rate is small, odds ratios are very similar to relative risks.

A study design in which the investigator is aware which intervention is being given to which participant (i.e. not double blind). Some studies with an open label design are randomised trials, but some do not include a comparison group and, therefore, cannot be randomised. See also open clinical trial.

Data that are classified into more than two categories where there is a natural order to the categories; for example, non-smokers, ex-smokers, light smokers and heavy smokers. Ordinal data are often reduced to two categories to simplify analysis and presentation, which may result in a considerable loss of information.

Components of patients' clinical and functional status after an intervention has been applied.

A study in which participants or groups of participants are matched (e.g. based on prognostic factors) and one member of each pair is allocated to the experimental (intervention) group and the other to the control group.

(synonym: independent group design) A trial that compares two groups of people, one of which receives the intervention of interest and one of which is a control group. Some parallel trials have more than two comparison groups and some compare different interventions without including a non-intervention control group.

A refereeing process whose aim is to check the quality and importance of reports of research. An article submitted for publication in a peer reviewed journal is reviewed by other experts in the area. See also external peer reviewer (of a Cochrane Review).

Systematic differences in care provided apart from the intervention being evaluated. For example, if patients know they are in the control group they may be more likely to use other forms of care, patients who know they are in the experimental (intervention) group may experience placebo effects, and care providers may treat patients differently according to what group they are in. Blinding of study participants (both the recipients and providers of care) is used to protect against performance bias.

The first stage in testing a new drug in humans. Usually performed on healthy volunteers without a comparison group.

Second stage in testing a new drug in humans. These are sometimes randomised controlled trials.

Studies that are a full-scale evaluation of treatment. After a drug has been shown to be reasonably effective, it is essential to compare it to the current standard treatments for the same condition. Phase III studies are often randomised controlled trials.

Studies that are concerned with post-marketing surveillance. They are often promotional exercises aimed at bringing a new drug to the attention of a large number of clinicians, and may be of limited scientific value.

An inactive substance or procedure administered to a patient, usually to compare its effects with those of a real drug or other intervention, but sometimes for the psychological benefit to the patient through a belief that s/he is receiving treatment. Placebos are used in clinical trials to blind people to their treatment allocation. Placebos should be indistinguishable from the active intervention to ensure adequate blinding. Placebo effect A favourable response to an intervention, regardless of whether it is the real thing or a placebo, attributable to the expectation of an effect, i.e. the power of suggestion. The effects of many healthcare interventions are attributable to a combination of both placebo and "active" (non-placebo) effects.

A term used to refer to a study with results indicating a beneficial effect of the intervention being studied. The term can generate confusion because it can refer to both statistical significance and the direction of effect, studies often have multiple outcomes, the criteria for classifying studies as negative or positive are not always clear and, in the case of studies of risk or undesirable effects, "positive" studies are ones that show a harmful effect.

1. A measure of the likelihood of random errors in the results of a study, meta-analysis or measurement. Confidence intervals around the estimate of effect from each study are a measure of precision, and the weight given to the results of each study in a meta-analysis (typically the inverse of the variance of the estimate of effect) is a measure of precision (i.e. the degree to which a study influences the overall estimate of effect in a meta-analysis is determinedby the precision of its estimate of effect). 2. The proportion of relevant citations located using a specific search strategy, i.e. the number of relevant studies meeting the inclusion criteria for a trials register or a review) divided by the total number of citations retrieved.

The number of existing cases of a particular disease or condition in a given population at a designated time.

See cross-sectional study.

(synonyms: included study, original study) "Original research" in which data are first collected. The term primary research is sometimes used to distinguish it from "secondary research" (reanalysis of previously collected data), meta-analysis, and other ways of combining studies (such as economic analysis and decision analysis). However, because systematic reviews can provide answers not possible from individual studies they can also be considered to be primary research.

The function that gives the probabilities that a variable equals each of a sequence of possible values. Examples include the bionomial, chi square, normal and Poisson distributions.

(synomym: Cox model) A statistical model in survival analysis that asserts that the effect of the study factors (e.g. the intervention of interest) on the hazard rate (the risk of occurrence of an event, such as death, at a point in time) in the study population is multiplicative and does not change over time.

The plan or set of steps to be followed in a study. A protocol for a systematic review should describe the rationale for the review; the objectives; and the methods that will be used to locate, select and critically appraise studies, and to collect and analyse data from the included studies.

A bias in the published literature where the publication of research depends on the nature and direction of the study results. Studies in which an intervention is not found to be effective are sometimes not published. Because of this, systematic reviews that fail to include unpublished studies may overestimate the true effect of an intervention.

The probability (ranging from zero to one) that the results observed in a study (or results more extreme) could have occurred by chance. In a meta-analysis the P-value for the overall effect assesses the overall statistical significance of the difference between the intervention groups, whilst the P-value for the heterogeneity statistic assesses the statistical significance of differences between the effects observed in each study.

See methodological quality.

A method of allocating participants to different forms of care that is not truly random; for example, allocation by date of birth, day of the week, medical record number, month of the year, or the order in which participants are included in the study (e.g. alternation).

A trial using a quasi-random method of allocating participants to different forms of care. There is a greater risk of selection bias in quasi-random trials where allocation is not adequately concealed compared with randomised controlled trials with adequate allocation concealment.

Governed by chance. See randomisation.

A method that uses the play of chance to assign participants to comparison groups in a trial, e.g. by using a random numbers table or a computer-generated random sequence. Random allocation implies that each individual or unit being entered into a trial has the same chance of receiving each of the possible interventions. It also implies that the probability that an individual will receive a particular intervention is independent of the probability that any other individual will receive the same intervention. See also concealment of allocation, quasi-random allocation, randomisation.

(synonym: sampling error) Error due to the play of chance. Confidence intervals and P-values represent the probability of random errors, but not systematic errors (bias).

A method of randomisation that ensures that, at any point in a trial, roughly equal numbers of participants have been allocated to all the comparison groups. Permuted blocks are often used in combination with stratified randomisation.

(synonym: random sampling) A method of obtaining a representative, unbiased group of people from a larger population. Random selection that is not related to the allocation of participants to comparison groups is frequently used in cross-sectional and cohort studies. It is rarely used in randomised controlled trials. However, in older trial reports, the term is occasionally used instead of random allocation or randomisation.

(spelled randomization in US English) Method used to generate a random allocation sequence, such as using tables of random numbers or computer-generated random sequences. The method of randomisation should be distinguished from concealment of allocation because of the risk of selection bias despite the use of randomisation, if there is not adequate allocation concealment. For instance, a list of random numbers may be used to randomise participants, but if the list is open to the individuals responsible for recruiting and allocating participants, those individuals can influence the allocation process, either knowingly or unknowingly.

See concealment of allocation.

(RCT) (Synomym: randomised clinical trial) An experiment in which investigators randomly allocate eligible people into intervention groups to receive or not to receive one or more interventions that are being compared. The results are assessed by comparing outcomes in the treatment and control groups.

See randomised controlled trial.

See trials register.

(RR) (synonym: risk ratio) The ratio of risk in the intervention group to the risk in the control group. The risk (proportion, probability or rate) is the ratio of people with an event in a group to the total in the group. A relative risk of one indicates no difference between comparison groups. For undesirable outcomes an RR that is less than one indicates that the intervention was effective in reducing the risk of that outcome.

Refers to the degree to which results obtained by a measurement procedure can be replicated. Lack of reliability can arise from divergences between observers or measurement instruments, or instability in the attribute being measured.

A study in which the outcomes have occurred to the participants before the study commenced. Case control studies are always retrospective, cohort studies sometimes are, randomised controlled trials never are. See prospective study.

1. A systematic review. 2. A review article in the medical literature which summarises a number of different studies and may draw conclusions about a particular intervention. Review articles are often not systematic. Review articles are also sometimes called overviews. 3. To referee a paper. See referee, referee process, external peer reviewer.

Somebody responsible for preparing and, in the case of Cochrane Reviews, keeping up-to-date a systematic review. The term “reviewer” is also sometimes used to refer to an external peer reviewer, or referee.

(RD) (synonym: absolute risk reduction) The absolute difference in the event rate between two comparison groups. A risk difference of zero indicates no difference between comparison groups. A RD that is less than zero indicates that the intervention was effective in reducing the risk of that outcome.

An aspect of a person's condition, lifestyle or environment that increases the probability of occurrence of a disease. For example, cigarette smoking is a risk factor for lung cancer.

A period before a trial is commenced when no treatment is given. The data from this stage of a trial are only occasionally of value but can serve a valuable role in screening out ineligible or non-compliant participants, in ensuring that participants are in a stable condition, and in providing baseline observations. A run-in period is sometimes called a washout period if treatments that participants were using before entering the trial are discontinued.

See random error.

1. The methods used by a Collaborative Review Group (CRG) to identify trials within the Group's scope. This includes handsearching relevant journals, searching electronic databases, contacting drug companies, other forms of personal contact and checking reference lists. CRGs must describe their search strategy in detail in the Group's module. Reviewers can refer to the Group's search strategy when preparing a Cochrane Review, and if necessary supplement this with a description of their own additional searches. 2. The methods used by a reviewer to locate relevant studies, including the use of a CRG's trials register. 3. The combination of terms used to identify studies in an electronic database such as MEDLINE.

1. In assessments of the validity of studies of healthcare interventions, selection bias refers to systematic differences between comparison groups in prognosis or responsiveness to treatment. Random allocation with adequate concealment of allocation protects against selection bias. Other means of selecting who receives the intervention of interest, particularly leaving it up to the providers and recipients of care, are more prone to bias because decisions about care can be related to prognosis and responsiveness to treatment. 2. Selection bias is sometimes used to describe a systematic error in reviews due to how studies are selected for inclusion. Publication bias is an example of this type of selection bias. 3. Selection bias, confusingly, is also sometimes used to describe a systematic difference in characteristics between those who are selected for study and those who are not. This affects the generalisability (external validity) of a study but not its (internal) validity.

An analysis used to determine how sensitive the results of a study or systematic review are to changes in how it was done. Sensitivity analyses are used to assess how robust the results are to uncertain decisions or assumptions about the data and the methods that were used.

(synonym: single masked) The investigator is aware of the treatment/intervention the participant is getting, but the participant is unaware. See also blinding, double blind, triple blind.

See Register of trials.

The difference between two means divided by an estimate of the within-group standard deviation. When an outcome (such as pain) is measured in a variety of ways across studies (using different scales) it may not be possible directly to compare or combine study results in a systematic review. By expressing the effects as a standardised value the results can be combined since they have no units. Standardised mean differences are sometimes referred to as a d index.

The probability that the null hypothesis will be rejected if it is indeed false. In studies of the effectiveness of healthcare interventions, power is a measure of the certainty of avoiding a false negative conclusion that an intervention is not effective when in truth it is effective. The power of a study is determined by how large it is (the number of participants), the number of events (e.g. strokes) or the degree of variation in a continuous outcome (such as weight), how small an effect one believes is important (i.e. the smallest difference in outcomes between the intervention and the control groups that is considered to be important), and how certain one wants to be of avoiding a false positive conclusion (i.e. the cut-off that is used for statistical significance).

An estimate of the probability of an association (effect) as large or larger than what is observed in a study occurring by chance, usually expressed as a P-value. For example, a P-value of 0.049 for a risk difference of 10% means that there is less than a one in 20 (0.05) chance of an association that is as large or larger having occurred by chance and it could be said that the results are "statistically significant" at P = 0.05). The cut-off for statistical significance is usually taken at 0.05, but sometimes at 0.01 or 0.10. These cut-offs are arbitrary and have no specific importance. Although it is often done, it is inappropriate to interpret the results of a study differently according to whether the P-value is, say, 0.055 or 0.045 (which are quite similar values, not diametrically opposed ones).

In any randomised trial it is desirable that the comparison groups should be as similar as possible as regards participant characteristics that might influence the response to the intervention. Stratified randomisation is used to ensure that equal numbers of participants with a characteristic thought to affect prognosis or response to the intervention will be allocated to each comparison group. For example, in a trial of women with breast cancer, it may be important to have similar numbers of pre-menopausal and post-menopausal women in each comparison group. Stratified randomisation could be used to allocate equal numbers of pre- and post-menopausal women to each treatment group. Stratified randomisation is performed either by performing separate randomisation (often using random permuted blocks) for each strata, or by using minimisation.

See validity.

(synonym: intermediary outcomes; surrogate outcomes) Outcome measures that are not of direct practical importance but are believed to reflect outcomes that are important; for example, blood pressure is not directly important to patients but it is often used as an outcome in clinical trials because it is a risk factor for stroke and heart attacks. Surrogate endpoints are often physiological or biochemical markers that can be relatively quickly and easily measured, and that are taken as being predictive of important clinical outcomes. They are often used when observation of clinical outcomes requires long follow-up.

See bias.

(synonym: systematic overview) A review of a clearly formulated question that uses systematic and explicit methods to identify, select and critically appraise relevant research, and to collect and analyse data from the studies that are included in the review. Statistical methods (meta-analysis) may or may not be used to analyse and summarise the results of the included studies. See also Cochrane Review.

(synonym: Student t-test) The t-distribution is the distribution of a quotient of independent random variables, the numerator of which is a standardised normal random variable and the denominator of which is the positive square root of the quotient of a chi-square distributed random variable and its number of degrees of freedom. The t-test uses the t-distribution to test whether two means differ significantly or to test linear regression or correlation coefficients.

See statistical significance.

See clinical trial.

Used loosely to refer to an association or possible effect that is not statistically significant. A consistent movement across ordered categories, e.g. a change in the effect observed in studies grouped according to, for instance, intensity of treatment.

(synonym: triple masked) An expression that is sometimes used to indicate that knowledge of which study participants are in which comparison group is kept secret from the statistician doing the analysis as well as from the study participants and investigators (outcome assessors). See also blinding, single blind, double blind.

The unit that is assigned to the alternative interventions being investigated in a trial. Most commonly, the unit will be an individual person but, in some trials, people will be assigned in groups to one or other of the interventions. This is done to avoid contamination or for convenience and the units might be, for example, hospitals or communities. In other trials, different parts of a person (such as the left or right eye) might be assigned to receive different interventions. See unit of analysis error.

In some studies people are allocated in groups instead of individually (e.g. by practice, by hospital or by community). Often when this is done the unit of allocation is different from the unit of analysis, i.e. people are allocated by groups and analysed as though they had been allocated individually. This is sometimes called a unit of analysis error. Effectively, using individuals as the unit of analysis when groups of people are allocated increases the power of the studies by increasing the degrees of freedom. This can result in overly narrow confidence intervals and false positive conclusions that the intervention had an effect when in truth there is greater uncertainty than what is reflected by the P-value. In the context of a review, it can result in studies having narrower confidence intervals and receiving more weight than is appropriate.

Patients or healthcare professionals or policy makers using a review to make practical decisions about healthcare, and researchers conducting or considering further research.

(synonym: internal validity) Validity is the degree to which a result (of a measurement or study) is likely to be true and free of bias (systematic errors). Validity has several other meanings, usually accompanied by a qualifying word or phrase; for example, in the context of measurement, expressions such as "construct validity", "content validity" and "criterion validity" are used. The expression "internal validity" is sometimes used to distinguish validity (the extent to which the observed effects are true for the people in a study) from external validity or generalisability (the extent to which the effects observed in a study truly reflect what can be expected in a target population beyond the people included in the study). See also methodological quality, random error.

Any quantity that varies. A factor that can have different values.

A measure of the variation shown by a set of observations, defined by the sum of the squares of deviations from the mean, divided by the number of degrees of freedom in the set of observations.

The stage in a cross-over trial when treatment is withdrawn before the second treatment is given. Washout periods are usually necessary because of the possibility that the intervention administered first can affect the outcome variable for some time after treatment ceases. A run-in period before a trial starts is sometimes called a washout period if treatments that participants were using before entering the trial are discontinued.

(in meta-analysis) A method of meta-analysis used to combine measures on continuous scales (such as weight), where the mean, standard deviation and sample size in each group are known. The weight given to each study (e.g. how much influence each study has on the overall results of the meta-analysis) is determined by the precision of its estimate of effect and, in the statistical software in RevMan and CDSR, is equal to the inverse of the variance. This method assumes that all of the trials have measured the outcome on the same scale. See also standardised mean difference.

See weighted mean difference

(WWW) A part of the Internet with a graphical interface. "Web pages" or "home pages" are HyperText Markup Language (HTML) documents on the WWW. Hypertext allows users to jump from one place in a document to another, from one document to another, and from one computer on the WWW to another. A connection through a cable or over the telephone and a Web browser (software program), such as Netscape, are needed to access and view WWW documents.