Glossary for Study Design Taxonomy

 

‘Analytic’ study

Unhelpful descriptor, since many studies involve analysis and could be described as analytic.

 

Basic Research

The primary outcomes are not measured in living human subjects. Includes animal studies; cell, biochemical, and genetic investigations; and studies on the properties of drugs and materials.

 

Before-After study

The same outcomes were measured before and after the intervention/exposure in one group (uncontrolled). Before-After studies are quasi-experimental. It is misleading and incorrect to use the word “trial” to describe a “quasi-experimental” study (such as ‘uncontrolled trial’ or ‘single-arm-trial’). Even if the order of assignment of interventions was random, this was not a randomized trial. Even if the subject(s) receive blinded placebo or intervention, this was not a randomized trial. Sometimes, Before-After study is called a Pre-Post study.

Interrupted Time Series: A Before-After study where 3 or more measures were taken before and 3 or more measures were taken after (interrupted by) the intervention/exposure. Risk of bias includes regression to the mean.

N-of-1 study: A Before-After study in only 1 subject.

 

Case Control study

Subjects were selected based upon the presence (case) or absence (control) of known outcome(s) of interest (disease). Exposure status is then collected based on the subjects’ past. Subject group characteristics should be similar and controls must be representative of those individuals who would have been selected as cases, had they developed the disease. Case Control studies are always retrospective.

            Nested Case Control study: Subjects were selected from the population of a prospective cohort study.

 

Case Report

Presents the outcome(s) of one to few individual case(s). May or may not describe an intervention/exposure.

 

Case Series

Descriptive report of an aggregation of individual cases. The cases were defined by similar diagnoses/disease state or having undergone the same intervention/procedure.  Case series are non-comparative (uncontrolled) and therefore cannot test, report, or conclude about treatment safety or effectiveness. Calculation of an absolute risk or a rate for the outcome is not possible in a case series.

Ideally, case series report on consecutive cases from a well-described study population with a well-defined intervention using validated outcome measures. Case series are a commonly reported study design, but the label "case series" is rarely used, and sometimes incorrectly.

Prospective Case Series are unusual, and require that the investigator designed the study, obtained ethics board approval, and patient consent to participate in a clinical research study, prior to commencing any of the interventions. Prospective case series often have a small sample size and are described as exploratory or pilot. Prospective case series resemble before-and-after studies or time series (uncontrolled). If the investigator compared the same primary outcomes before-and-after the intervention, then the study would qualify as a Before-After study.

Retrospective Case Series are the most common type. The investigator may have used clinical records, registries, or databases.  

Case series are valuable for studying symptoms and signs, creating case definitions, hypothesis generation, or detection of rare adverse events.

 

Clinical Research

The primary outcomes were measured in living human subjects. Clinical research includes epidemiologic research.

 

Cluster Randomized Controlled Trial (see Randomized Controlled Trial)

 

Cohort

A group of individuals (or other organizational units) who have one or more common features/traits at the time that they assembled (examples: birth year, place of employment, medical condition, place or time period of medical treatment, military unit). This term should not be used in the report of a study that was not a Cohort Study.

 

Cohort Study

Prospective Cohort Study

A research study that pre-specified 2 or more groups of individuals (who were alike in many ways but differed by a certain characteristic), after designing the study, and then followed them for a period of time, and compared an outcome of interest among the groups. The target group(s) and the control group(s) were created at the same time (concurrent).

The groups may be well-matched, poorly matched, or moderately well-matched. Corrections may be made, using regression analysis statistical techniques, to “control for” or adjust for differences in the groups that could tend to bias the differences (or lack of difference) in outcomes.

Retrospective Cohort Study

A research study that created 2 or more groups of individuals (who were alike in many ways but differ by a certain characteristic), using information that was available before designing the study (determined in the past), and then compared an outcome of interest among the groups. The data/information may be from clinical records, registries, or databases. The target group(s) and the control group(s) may have been created using contemporaneous data/information (concurrent). The controls may be historic or non-concurrent.

The groups may be well-matched, poorly matched, or moderately well-matched. Corrections may be made, using regression analysis statistical techniques, to “control for” or adjust for differences in the groups that could tend to bias the differences (or lack of difference) in outcomes.

A retrospective cohort study might utilize data/information that had all been documented prospectively (by entry into a medical record or database). It would be misleading and incorrect to use the descriptive term ‘prospective’ in the Methods if the study was designed after ‘the event’.

 

Consent

There are three different consents relevant to study design. Patient consent to treatment is not sufficient for reporting human research. Patient specific consent for the use of patient images is essential for a case report or other study that includes such images in the report. Consent to be a participant in a clinical research study is essential for any experimental study. Consent to be a participant in a clinical research study is usually necessary for a prospective cohort study.

Clinical research studies require an ethics approval or waiver, with exceptions for a case report or a small case series, where specific consent has been obtained from the patient(s).

 

Controlled study

There were 2 or more groups, with different intervention/exposure, and outcomes were measured in all groups and compared between groups.

 

Controlled Before-After Study

The same outcomes were measured before and after the intervention/exposure in 2 or more groups. A type of non-randomized trial.

Controlled Interrupted Time Series: A Controlled Before-After study where 3 or more measures were taken before and 3 or more measures were taken after (interrupted by) the intervention/exposure.

 

Cross-sectional study

Both the exposure and the outcome status in the subjects were assessed concurrently. Causation cannot be determined.  Commonly examine the relationship between disease and other variables of interest at one particular point in time. A common tool is the survey.

 

‘Database’ study

Unhelpful term that should not be used in Methods or to describe the study design. Likely to be retrospective. Could be comparative or non-comparative. The database is simply the repository of the data/information (rather than a paper clinical record, or an electronic medical record, or a registry).

 

Descriptive studies

Descriptive studies are: cross-sectional studies, case series, case reports, trend studies, and focus group studies. They are non-comparative and may not be used to determine association, causation, or treatment effectiveness. They are important for hypothesis generation for future research, and are often the first emerging evidence.   

 

Diagnosis/screening study designs

Diagnostic studies may be comparative or non-comparative; comparative may refer to between tests or between groups.

The most relevant patient-centered outcome is optimal for assessing the impact of diagnostic tests on patient outcomes; often a previously validated surrogate was used. Alternatively, sometimes disease modeling studies may be used to examine patient outcomes.

Diagnostic accuracy case-control study

An observational design for diagnostic/screening studies; the subjects were selected by known diagnosis, (or clinical suspicion, or clinical outcome, or disease state), followed by inclusion/exclusion criteria to select the study group suspected to have the target condition. The control group was selected using similar inclusion/exclusion criteria, with a critical difference to identify a group presumed not to have the target condition. Both an index test and a reference standard test were performed (either in series or simultaneously).

There is a level of uncertainty regarding the diagnosis (outcome) in the target group at entry; this may be very low (likely true/established diagnosis, most approximates case control study), or this may be moderate (an estimate based on symptoms and clinical suspicion, most resembles a cross-sectional study).

Diagnostic accuracy cohort study

Two or more groups were selected from a representative population, based upon inclusion/exclusion criteria that included test results (either dichotomous or above and below a cut-point of a continuous test result). Each subject then underwent the experimental test and the reference standard. Testing may have been done in series or in parallel. There may or may not have been blinding of the reference result. Results are restricted to diagnostic accuracy (sensitivity, specificity, likelihood ratios, diagnostic odds ratios). Efforts to minimize confounding should be documented. Diagnostic accuracy cohort studies are not directly tied to patient outcomes. Only when diagnostic accuracy is coupled with effective therapy (or noxious therapy) can outcomes be influenced.

Diagnostic accuracy cross-sectional study

One group was selected from a representative population, based upon inclusion/exclusion criteria of a defined clinical presentation. The subjects may have been consecutive, or non-consecutive. Each subject then underwent the experimental test and the reference standard. Testing may have been done in series or in parallel. There may or may not have been blinding of the reference result. Results are restricted to diagnostic accuracy (sensitivity, specificity, likelihood ratios). 

Diagnostic randomized controlled trial (RCT)

Randomized comparisons of two diagnostic interventions (one experimental and one reference standard control) were made with identical therapeutic interventions, based on the results of the competing diagnostic interventions (for example, disease: yes or no), and with the study outcomes being clinically important outcomes consequent to diagnostic accuracy.  

The study may have been blinded or un-blinded; in a blinded study, both tests are done for both groups but only the allocated test result is known for decision making until the study ends.

Diagnostic reliability study

A comparison is made between different machines, laboratories, observers, raters for variability in results. A type of cross-sectional study, without a reference standard. Human observers and raters may or may not have been blinded to each other’s determinations. Results are reported as kappa values.

            Diagnostic yield study

Non-comparative observational report of one test performed in one group of pre-selected patients. Reports of the number of cases identified among the study population. A type of case series study. Usually considered to be an exploratory or pilot study. If there is only one test performed in one subject, the study is a case report.

Non-randomized diagnostic trial

Non-randomized comparisons of two diagnostic interventions (one experimental and one reference standard control) were made with identical therapeutic interventions, based on the results of the competing diagnostic interventions (for example, disease: yes or no), and with the study outcomes being clinically important outcomes consequent to diagnostic accuracy.  

The study may have been blinded or un-blinded; in a blinded study, both tests are done for both groups but only the allocated test result is known for decision making until the study ends.

 

Experimental study design

Investigators had direct control over the assignment of the intervention (or exposure), and the timing and selection of outcome measures. All experimental studies are prospective. Examples include randomized controlled trial, nonrandomized trial, quasi-experimental study.  

 

Interrupted time series (without a comparison group) - see Before-After study

 

Nested Case Control study – see Case Control study

 

Non-comparative observational studies

All subject(s) received the same intervention(s)/exposure, and did not have the same primary outcome(s) measured before as after. These are always retrospective because the design and conduct of the study commenced after the intervention or exposure occurred. Includes: retrospective case series, case report(s), time series, and focus group.

 

Non-concurrent cohort study

A retrospective study in which 2 or more groups of individuals were identified on the basis of common features, but at different time points. Individuals in each group were classified according to exposure status (exposed or unexposed) at the time the groups existed or were created. They were followed to determine if the development of the outcome of interest was different in the exposed or unexposed groups.  

 

Non-randomized controlled trial

An experimental study in which individuals or groups of individuals were assigned to the intervention or control by a method that was not random (date of birth, date of admission, judgment of the investigator, personal preference, etc.). Individuals or groups were followed prospectively to assess differences in the outcome(s) of interest.

The objective of the study could be to determine superiority, equivalence, non-inferiority, or to disprove the null hypothesis.

Selection bias is frequently an issue in nonrandomized studies. Because the assignment was not randomized, assessment of matching between groups is important. The groups may be well-matched, poorly matched, or moderately well-matched. Corrections may be made, using regression analysis statistical techniques, to “control for” or adjust for differences in the groups that could tend to bias the differences (or lack of difference) in outcomes.

 

Observational study design

A study in which the investigator did not control/assign the exposure/ intervention status of the study participants. Some are analytic (prospective cohort) and some are descriptive (case series). Examples are: Case Control, Cohort, Cross-sectional, Case Series, and Case Report.

 

Prospective study

The subjects were enrolled in the study after the study had been designed and approved, and the subjects were followed for some period of time.

 

Prospective Case Series – see Case Series study

 

Prospective Cohort study - see Cohort study

 

Pseudo-primary research

The same investigator used data from one or more previous studies for the current study.

 

Quasi-experimental study - see Before-After study

 

Randomized Controlled Trial (RCT)

An experimental comparative study in which participants are randomly assigned to intervention or control and followed over time to measure differences in outcomes. Concealment of the allocation of the randomized assignment is important. Known and unknown prognostic factors (confounders) should be evenly distributed between the groups.

There are many sub-classifications of RCTs:

-The unit of allocation and analysis may be the individual, or the group (cluster = hospitals, schools, neighborhoods, or entire communities).

-Variations in methodology include factorial, cross-over, parallel, stepped wedge, and Solomon four-group.

-RCTs may be un-blinded (open label) or single/double/triple/quadruple-blinded. Except for outcomes that do not involve any subjective judgment, blinding of outcome assessors, patients, healthcare providers, and investigators is important to minimize bias.

-The objective of the study could be to determine superiority, equivalence, non-inferiority, or to disprove the null hypothesis.

-The design could be explanatory (traditional) or pragmatic (naturalistic).

A disadvantage of explanatory RCTs is that study populations are often highly selected, the setting well-defined and controlled, and results therefore sometimes represent the maximum effect and lack generalizability (external validity). The pragmatic RCT is designed to test interventions in the full spectrum of everyday clinical settings in order to maximize applicability and generalizability, and usually has a large sample size, simple design, and diverse settings.

-The RCT could be registered or not registered. The International Committee of Medical Journal Editors (ICMJE) acknowledged the vested interests, academic biases, and market forces (including insurance coverage policies and reimbursement issues) that influence the selective reporting of RCTs. The ICMJE member journals agreed to require the registration of any RCT submitted for review   

 

Retrospective Case Series – see Case Series

 

Retrospective study

The study started after the data/information had been collected.

 

Retrospective Cohort study – see Cohort study

 

Trend study

A study in which data are collected at a series of points in time on the same population to observe trends in the outcome(s) of interest. There is no intervention/exposure, and no comparative group.

 

Trial

A term restricted to research studies with control group(s): randomized or nonrandomized controlled trials.