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Gartlehner G, Thieda P, Morgan LC, et al. Drug Class Review: Targeted Immune Modulators: Final Report Update 2 [Internet]. Portland (OR): Oregon Health & Science University; 2009 Nov.

**This publication is provided for historical reference only and the information may be out of date.**

## Drug Class Review: Targeted Immune Modulators: Final Report Update 2 [Internet].

Show detailsThis glossary defines terms as they are used in reports produced by the Drug Effectiveness Review Project. Some definitions may vary slightly from other published definitions.

- Absolute risk
The probability or chance that a person will have a medical event. Absolute risk is expressed as a percentage. It is the ratio of the number of people who have a medical event divided by all of the people who could have the event because of their medical condition.

- Add-on therapy
An additional treatment used in conjunction with the primary or initial treatment.

- Adherence
Following the course of treatment proscribed by a study protocol.

- Adverse drug reaction
An adverse effect specifically associated with a drug.

- Adverse event
A harmful or undesirable outcome that occurs during or after the use of a drug or intervention but is not necessarily caused by it.

- Adverse effect
An

for which the causal relation between the intervention and the event is at least a reasonable possibility.*adverse event*- Active-control trial
A trial comparing a drug in a particular class or group with a drug outside of that class or group.

- Allocation concealment
The process by which the person determining randomization is blinded to a study participant’s group allocation.

- Applicability
see External Validity

- Before-after study
A type nonrandomized study where data are collected before and after patients receive an intervention. Before-after studies can have a single arm or can include a control group.

- Bias
A systematic error or deviation in results or inferences from the truth. Several types of bias can appear in published trials, including selection bias, performance bias, detection bias, and reporting bias.

- Bioequivalence
Drug products that contain the same compound in the same amount that meet current official standards, that, when administered to the same person in the same dosage regimen result in equivalent concentrations of drug in blood and tissue.

- Black box warning
A type of warning that appears on the package insert for prescription drugs that may cause serious adverse effects. It is so named for the black border that usually surrounds the text of the warning. A black box warning means that medical studies indicate that the drug carries a significant risk of serious or even life-threatening adverse effects. The US Food and Drug Administration (FDA) can require a pharmaceutical company to place a black box warning on the labeling of a prescription drug, or in literature describing it. It is the strongest warning that the FDA requires.

- Blinding
A way of making sure that the people involved in a research study — participants, clinicians, or researchers —do not know which participants are assigned to each study group. Blinding usually is used in research studies that compare two or more types of treatment for an illness. Blinding is used to make sure that knowing the type of treatment does not affect a participant’s response to the treatment, a health care provider’s behavior, or assessment of the treatment effects.

- Case series
A study reporting observations on a series of patients receiving the same intervention with no control group.

- Case study
A study reporting observations on a single patient.

- Case-control study
A study that compares people with a specific disease or outcome of interest (cases) to people from the same population without that disease or outcome (controls).

- Clinical diversity
Differences between studies in key characteristics of the participants, interventions or outcome measures.

- Clinically significant
A result that is large enough to affect a patient’s disease state in a manner that is noticeable to the patient and/or a caregiver.

- Cohort study
An observational study in which a defined group of people (the cohort) is followed over time and compared with a group of people who were exposed or not exposed to a particular intervention or other factor of interest. A prospective cohort study assembles participants and follows them into the future. A retrospective cohort study identifies subjects from past records and follows them from the time of those records to the present.

- Combination Therapy
The use of two or more therapies and especially drugs to treat a disease or condition.

- Confidence interval
The range of values calculated from the data such that there is a level of confidence, or certainty, that it contains the true value. The 95% confidence interval is generally used in Drug Effectiveness Review Project reports. If the report were hypothetically repeated on a collection of 100 random samples of studies, the resulting 95% confidence intervals would include the true population value 95% of the time.

- Confounder
A factor that is associated with both an intervention and an outcome of interest.

- Controlled clinical trial
A clinical trial that includes a control group but no or inadequate methods of randomization.

- Control group
In a research study, the group of people who do not receive the treatment being tested. The control group might receive a placebo, a different treatment for the disease, or no treatment at all.

- Convenience sample
A group of individuals being studied because they are conveniently accessible in some way. Convenience samples may or may not be representative of a population that would normally be receiving an intervention.

- Crossover trial
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.

- Direct analysis
The practice of using data from head-to-head trials to draw conclusions about the comparative effectiveness of drugs within a class or group. Results of direct analysis are the preferred source of data in Drug Effectiveness Review Project reports.

- Dosage form
The physical form of a dose of medication, such as a capsule, injection, or liquid. The route of administration is dependent on the dosage form of a given drug. Various dosage forms may exist for the same compound, since different medical conditions may warrant different routes of administration.

- Dose-response relationship
The relationship between the quantity of treatment given and its effect on outcome. In meta-analysis, dose-response relationships can be investigated using meta-regression.

- Double-blind
The process of preventing those involved in a trial from knowing to which comparison group a particular participant belongs. While double-blind is a frequently used term in trials, its meaning can vary to include blinding of patients, caregivers, investigators, or other study staff.

- Double-dummy
The use of two placebos in a trial that match the active interventions when they vary in appearance or method of administrations (for example, when an oral agent is compared with an injectable agent).

- Effectiveness
The extent to which a specific intervention

*used under ordinary circumstances*does what it is intended to do.- Effectiveness outcomes
Outcomes that are generally important to patients and caregivers, such as quality of life, responder rates, number and length of hospitalizations, and ability to work. Data on effectiveness outcomes usually comes from longer-term studies of a “real-world” population.

- Effect size/estimate of effect
The amount of change in a condition or symptom because of a treatment (compared to not receiving the treatment). It is commonly expressed as a risk ratio (relative risk), odds ratio, or difference in risk.

- Efficacy
The extent to which an intervention produces a beneficial result

*under ideal conditions*in a selected and controlled population.- Equivalence level
The amount which an outcome from two treatments can differ but still be considered equivalent, as in an equivalence trial, or the amount which an outcome from treatment A can be worse than that of treatment B but still be considered noninferior, as in a noninferiority trial.

- Equivalence trial
A trial designed to determine whether the response to two or more treatments differs by an amount that is clinically unimportant. This lack of clinical importance is usually demonstrated by showing that the true treatment difference is likely to lie between a lower and an upper equivalence level of clinically acceptable differences.

- Exclusion criteria
The criteria, or standards, set out before a study or review. Exclusion criteria are used to determine whether a person should participate in a research study or whether an individual study should be excluded in a systematic review. Exclusion criteria may include age, previous treatments, and other medical conditions. Criteria help identify suitable participants.

- External validity
The extent to which results provide a correct basis for generalizations to other circumstances. For instance, a meta-analysis of trials of elderly patients may not be generalizable to children. (Also called generalizability or applicability)

- Fixed-effect model
A model that calculates a pooled estimate using the assumption that all observed variation between studies is due to by chance. Studies are assumed to be measuring the same overall effect. An alternative model is the random-effects model.

- Fixed-dose combination product
A formulation of two or more active ingredients combined in a single dosage form available in certain fixed doses.

- Forest plot
A graphical representation of the individual results of each study included in a meta-analysis and the combined result of the meta-analysis. The plot allows viewers to see the heterogeneity among the results of the studies. The results of individual studies are shown as squares centered on each study’s point estimate. A horizontal line runs through each square to show each study’s confidence interval—usually, but not always, a 95% confidence interval. The overall estimate from the meta-analysis and its confidence interval are represented as a diamond. The center of the diamond is at the pooled point estimate, and its horizontal tips show the confidence interval.

- Funnel plot
A graphical display of some measure of study precision plotted against effect size that can be used to investigate whether there is a link between study size and treatment effect.

- Generalizability
See

*External Validity.*- Half- life
The time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%.

- Harms
See

*Adverse Event*- Hazard ratio
The increased risk with which one group is likely to experience an outcome of interest. It is similar to a risk ratio. For example, if the hazard ratio for death for a treatment is 0.5, then treated patients are likely to die at half the rate of untreated patients.

- Head-to-head trial
A trial that directly compares one drug in a particular class or group with another in the same class or group.

- Health outcome
The result of a particular health care practice or intervention, including the ability to function and feelings of well-being. For individuals with chronic conditions – where cure is not always possible – results include health-related quality of life as well as mortality.

- Heterogeneity
The variation in, or diversity of, participants, interventions, and measurement of outcomes across a set of studies.

- I
^{2} A measure of statistical heterogeneity of the estimates of effect from studies. Values range from 0% to 100%. Large values of I

^{2}suggest heterogeneity. I^{2}is the proportion of total variability across studies that is due to heterogeneity and not chance. It is calculated as (Q-(n-1))/Q, where n is the number of studies.- Incidence
The number of new occurrences of something in a population over a particular period of time, e.g. the number of cases of a disease in a country over one year.

- Indication
A term describing a valid reason to use a certain test, medication, procedure, or surgery. In the United States, indications for medications are strictly regulated by the Food and Drug Administration, which includes them in the package insert under the phrase “Indications and Usage”.

- Indirect analysis
The practice of using data from trials comparing one drug in a particular class or group with another drug outside of that class or group or with placebo and attempting to draw conclusions about the comparative effectiveness of drugs within a class or group based on that data. For example, direct comparisons between drugs A and B and between drugs B and C can be used to make an indirect comparison between drugs A and C.

- Intention to treat
The use of data from a randomized controlled trial in which data from all randomized patients are accounted for in the final results. Trials often incorrectly report results as being based on intention to treat despite the fact that some patients are excluded from the analysis.

- Internal validity
The extent to which the design and conduct of a study are likely to have prevented bias. Generally, the higher the interval validity, the better the quality of the study publication.

- Inter-rater reliability
The degree of stability exhibited when a measurement is repeated under identical conditions by different raters.

- Intermediate outcome
An outcome not of direct practical importance but 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 myocardial infarction (hear attack).

- Logistic regression
A form of regression analysis that models an individual’s odds of disease or some other outcome as a function of a risk factor or intervention.

- Masking
See

*Blinding*- Mean difference
A method used to combine measures on continuous scales (such as weight) where the mean, standard deviation, and sample size are known for each group.

- Meta-analysis
The use of statistical techniques in a systematic review to integrate the results of included studies. Although the terms are sometimes used interchangeably, meta-analysis is not synonymous with systematic review. However, systematic reviews often include meta-analyses.

- Meta-regression
A technique used to explore the relationship between study characteristics (for example, baseline risk, concealment of allocation, timing of the intervention) and study results (the magnitude of effect observed in each study) in a systematic review.

- Mixed treatment comparison meta analysis
A meta-analytic technique that simultaneously compares multiple treatments (typical 3 or more) using both direct and indirect evidence. The multiple treatments form a network of treatment comparisons. Also called multiple treatment comparisons, network analysis, or umbrella reviews.

- Monotherapy
the use of a single drug to treat a particular disorder or disease.

- Multivariate analysis
Measuring the impact of more than one variable at a time while analyzing a set of data.

- N-of-1 trial
A randomized trial in an individual to determine the optimum treatment for that individual.

- Noninferiority trial
A trial designed to determine whether the effect of a new treatment is not worse than a standard treatment by more than a prespecified amount. A one-sided version of an equivalence trial.

- Nonrandomized study
Any study estimating the effectiveness (harm or benefit) of an intervention that does not use randomization to allocate patients to comparison groups. There are many types of nonrandomized studies, including cohort studies, case-control studies, and before-after studies.

- Null hypothesis
The statistical hypothesis that one variable (for example, treatment to which a participant was allocated) has no association with another variable or set of variables.

- Number needed to harm
The number of people who would need to be treated over a specific period of time before one bad outcome of the treatment will occur. The number needed to harm (NNH) for a treatment can be known only if clinical trials of the treatment have been performed.

- Number needed to treat
An estimate of how many persons need to receive a treatment before one person would experience a beneficial outcome.

- Observational study
A type of nonrandomized study in which the investigators do not seek to intervene, instead simply observing the course of events.

- Odds ratio
The ratio of the odds of an event in one group to the odds of an event in another group. An odds ratio of 1.0 indicates no difference between comparison groups. For undesirable outcomes an odds ratio that is <1.0 indicates that the intervention was effective in reducing the risk of that outcome.

- Off-label use
When a drug or device is prescribed outside its specific FDA-approved indication, to treat a condition or disease for which it is not specifically licensed.

- Outcome
The result of care and treatment and/or rehabilitation. In other words, the change in health, functional ability, symptoms or situation of a person, which can be used to measure the effectiveness of care/treatment/rehabilitation. Researchers should decide what outcomes to measure before a study begins; outcomes are then assessed at the end of the study.

- Outcome measure
Is the way in which an outcome is evaluated---the device (scale) used for measuring. With this definition YMRS is an outcome measure, and a patient’s outcome after treatment might be a 12-point improvement on that scale.

- One-tailed test (one-sided test)
A hypothesis test in which the values that reject the null hypothesis are located entirely in one tail of the probability distribution. For example, testing whether one treatment is better than another (rather than testing whether one treatment is either better or worse than another).

- Open-label trial
A clinical trial in which the investigator and participant are aware which intervention is being used for which participant (that is, not blinded). Random allocation may or may not be used in open-label trials.

- Per protocol
The subset of participants from a randomized controlled trial who complied with the protocol sufficiently to ensure that their data would be likely to exhibit the effect of treatment. Per protocol analyses are sometimes misidentified in published trials as intention-to-treat analyses.

- Pharmacokinetics
the characteristic interactions of a drug and the body in terms of its absorption, distribution, metabolism, and excretion.

- Placebo
An inactive substance commonly called a “sugar pill.” In a clinical trial, a placebo is designed to look like the drug being tested and is used as a control. It does not contain anything that could harm a person. It is not necessarily true that a placebo has no effect on the person taking it.

- Placebo-controlled trial
A study in which the effect of a drug is compared with the effect of a placebo (an inactive substance designed to resemble the drug). In placebo-controlled clinical trials, participants receive either the drug being studied or a placebo. The results of the drug and placebo groups are then compared to see if the drug is more effective in treating the condition than the placebo is.

- Point estimate
The results (e.g. mean, weighted difference, odds ratio, relative risk or risk difference) obtained in a sample (a study or a meta-analysis) which are used as the best estimate of what is true for the relevant population from which the sample is taken. A confidence interval is a measure of the uncertainty (due to the play of chance) associated with that estimate.

- Pooling
The practice of combing data from several studies to draw conclusions about treatment effects.

- Power
The probability that a trial will detect statistically significant differences among intervention effects. Studies with small sample sizes can frequently be underpowered to detect difference.

- Precision
The likelihood of random errors in the results of a study, meta-analysis, or measurement. The greater the precision, the less the random error. Confidence intervals around the estimate of effect are one way of expressing precision, with a narrower confidence interval meaning more precision.

- Prospective study
A study in which participants are identified according to current risk status or exposure and followed forward through time to observe outcome.

- Prevalence
How often or how frequently a disease or condition occurs in a group of people. Prevalence is calculated by dividing the number of people who have the disease or condition by the total number of people in the group.

- Probability
The likelihood (or chance) that an event will occur. In a clinical research study, it is the number of times a condition or event occurs in a study group divided by the number of people being studied.

- Publication bias
A bias caused by only a subset of the relevant data being available. The publication of research can depend 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. In addition, a published report might present a biased set of results (for example, only outcomes or subgroups for which a statistically significant difference was found).

- P value
The probability (ranging from zero to one) that the results observed in a study could have occurred by chance if the null hypothesis was true. A

*P*value of ≤0.05 is often used as a threshold to indicate statistical significance.- Q-statistic
A measure of statistical heterogeneity of the estimates of effect from studies. Large values of Q suggest heterogeneity. It is calculated as the weighted sum of the squared difference of each estimate from the mean estimate.

- Random-effects model
A statistical model in which both within-study sampling error (variance) and between-studies variation are included in the assessment of the uncertainty (confidence interval) of the results of a meta-analysis. When there is heterogeneity among the results of the included studies beyond chance, random-effects models will give wider confidence intervals than fixed-effect models.

- Randomization
The process by which study participants are allocated to treatment groups in a trial. Adequate (that is, unbiased) methods of randomization include computer generated schedules and random-numbers tables.

- Randomized controlled trial
A trial in which two or more interventions are compared through random allocation of participants.

- Regression analysis
A statistical modeling technique used to estimate or predict the influence of one or more independent variables on a dependent variable, for example, the effect of age, sex, or confounding disease on the effectiveness of an intervention.

- Relative risk
The ratio of risks in two groups; same as a risk ratio.

- Retrospective study
A study in which the outcomes have occurred prior to study entry.

- Risk
A way of expressing the chance that something will happen. It is a measure of the association between exposure to something and what happens (the outcome). Risk is the same as probability, but it usually is used to describe the probability of an adverse event. It is the rate of events (such as breast cancer) in the total population of people who could have the event (such as women of a certain age).

- Risk difference
The difference in size of risk between two groups.

- Risk Factor
A characteristic of a person that affects that person’s chance of having a disease. A risk factor may be an inherent trait, such as gender or genetic make-up, or a factor under the person’s control, such as using tobacco. A risk factor does not usually cause the disease. It changes a person’s chance (or risk) of getting the disease.

- Risk ratio
The ratio of risks in two groups. In intervention studies, it is the ratio of the risk in the intervention group to the risk in the control group. A risk ratio of 1 indicates no difference between comparison groups. For undesirable outcomes, a risk ratio that is <1 indicates that the intervention was effective in reducing the risk of that outcome.

- Run-in period
Run in period: A period before randomization when participants are monitored but receive no treatment (or they sometimes all receive one of the study treatments, possibly in a blind fashion). 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.

- Safety
Substantive evidence of an absence of harm. This term (or the term “safe”) should not be used when evidence on harms is simply absent or is insufficient.

- Sample size
The number of people included in a study. In research reports, sample size is usually expressed as “n.” In general, studies with larger sample sizes have a broader range of participants. This increases the chance that the study’s findings apply to the general population. Larger sample sizes also increase the chance that rare events (such as adverse effects of drugs) will be detected.

- Sensitivity analysis
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.

- Side effect
Any unintended effect of an intervention. Side effects are most commonly associated with pharmaceutical products, in which case they are related to the pharmacological properties of the drug at doses normally used for therapeutic purposes in humans.

- Standard deviation (SD)
A measure of the spread or dispersion of a set of observations, calculated as the average difference from the mean value in the sample.

- Standard error (SE)
A measure of the variation in the sample statistic over all possible samples of the same size. The standard error decreases as the sample size increases.

- Standard treatment
The treatment or procedure that is most commonly used to treat a disease or condition. In clinical trials, new or experimental treatments sometimes are compared to standard treatments to measure whether the new treatment is better.

- Statistically significant
A result that is unlikely to have happened by chance.

- Study
A research process in which information is recorded for a group of people. The information is known as data. The data are used to answer questions about a health care problem.

- Study population
The group of people participating in a clinical research study. The study population often includes people with a particular problem or disease. It may also include people who have no known diseases.

- Subgroup analysis
An analysis in which an intervention is evaluated in a defined subset of the participants in a trial, such as all females or adults older than 65 years.

- Superiority trial
A trial designed to test whether one intervention is superior to another.

- Surrogate outcome
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.

- Survival analysis
Analysis of data that correspond to the time from a well-defined time origin until the occurrence of some particular event or end-point; same as time-to-event analysis.

- Systematic review
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 analyze data from the studies that are included in the review.

- Tolerability
For therapeutic drugs, it refers a drug’s lack of “nuisance side effects,” side effects that are thought to have no long-term effect but that are unpleasant enough to the patient that adherence to the medication regimen is affected.

The extent to which a drug’s adverse effects impact the patient’s ability or willingness to continue taking the drug as prescribed. These adverse effects are often referred to as nuisance side effects, because they are generally considered to not have long-term effects but can seriously impact compliance and adherence to a medication regimen.

- Treatment regimen
The magnitude of effect of a treatment versus no treatment or placebo; similar to “effect size”. Can be calculated in terms of relative risk (or risk ratio), odds ratio, or risk difference.

- Two-tailed test (two-sided test)
A hypothesis test in which the values that reject the null hypothesis are located in both tails of the probability distribution. For example, testing whether one treatment is different than another (rather than testing whether one treatment is either better than another).

- Type I error
A conclusion that there is evidence that a treatment works, when it actually does not work (false-positive).

- Type II error
A conclusion that there is no evidence that a treatment works, when it actually does work (false-negative).

- Validity
The degree to which a result (of a measurement or study) is likely to be true and free of bias (systematic errors).

- Variable
A measurable attribute that varies over time or between individuals. Variables can be

*Discrete*: taking values from a finite set of possible values (e.g. race or ethnicity)*Ordinal*: taking values from a finite set of possible values where the values indicate rank (e.g. 5-point Likert scale)*Continuous*: taking values on a continuum (e.g. hemoglobin A1c values).

- Washout period
[In a cross-over trial] The stage after the first treatment is withdrawn, but before the second treatment is started. The washout period aims to allow time for any active effects of the first treatment to wear off before the new one gets started.

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