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Center for Devices and Radiological Health
Office of Surveillance and Biometrics
Office of Device Evaluation
Office of In Vitro Diagnostics
Center for Biologic Evaluation and Research
In this glossary, terms are defined according to their specific interpretation as used in this particular guidance.
Active Control Investigation (Active Treatment Control Investigation)
A study that uses an intervention whose effectiveness has been previously established. In a device investigation, the active control could be a device (drug or biological product) approved or cleared for that indication or a surgical procedure.
Device intended to provide a desired change in visual appearance in the subject through physical modification of the structure of the body
A diagnostic clinical performance study that uses an independent assessment result other than a clinical reference standard to compare the investigational device output .
Bias is the introduction of systematic errors from the truth.
(see Clinical Study).
Clinical Outcome Study
A study in which subjects are assigned to an intervention and then studied at planned intervals using validated assessment tools to assess clinical outcome parameters or their validated surrogates to determine the safety and effectiveness of the intervention.
Clinical Reference Standard (CRS)
Best available method for establishing the true status of a subjects’ target condition; it can be a single method or combination of methods and techniques including clinical follow-up, but it should not consider the investigational device output.
Systematic study conducted to evaluate the safety and effectiveness of a therapeutic, aesthetic or diagnostic device using human subjects or specimens (see also Clinical Investigation).
A test that serves to assess the level of performance of the device that is currently under investigation. Often the comparator is another medical device.
Condition of Interest
See Target Condition.
A control based on data collected over the same time period as the investigational device.
Bias that arises due to prior knowledge or experience. Context bias can arise in reading images if the reader’s estimated prevalence of the target condition during the course of the study changes reading decisions (This type of context bias is sometimes called reading bias).
A device, drug, biological product or other medical procedure that is used to compare the device currently under investigation.
In a clinical study, the group of subjects or specimens who receive the control.
Controlled Clinical Study
A clinical study comparing the safety and effectiveness of the investigational device with a control.
A cross-over design ( cross-over study) is a study in which subjects receive a sequence of different interventions (or diagnostic tests). In the simplest case of a cross-over design study, each participant receives either the investigational device or the control in the first period, and the other in the succeeding period, with a suitable “washout” period between the two when necessary. The order in which investigational device or control is given to each subject is usually randomized.
Data monitoring committee (DMC)
A group of individuals with pertinent expertise that reviews on a regular basis accumulating data from one or more ongoing clinical studies A DMC may recommend that a study be stopped if there are safety concerns or if the study objectives have been achieved. Also sometimes called a Data Safety and Monitoring Board (DSMB).
Device Under Investigation
See Investigational Device.
Diagnostic Clinical Performance Study
Study in which a test is characterized by performance measures that quantify how well the diagnostic device output agrees with true subject status as determined by a clinical reference standard.
Device that provide results that are used alone or in the context of other information to help assess a subject’s target condition.
Medical device clinical development stage that includes initial development, evaluation, first-in-human and other feasibility studies.
A preliminary clinical study to see if a larger pivotal study is practical and to refine the study protocol for the pivotal study. A feasibility study is sometimes also called a pilot study.
Good Clinical Practice (GCP)
A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical studies that provides assurance that the data and reported results are credible and accurate, and that the rights, safety, well-being, integrity, and confidentiality of study subjects are protected.
Good Clinical Data Management Practices or GCDMP
Current industry standards for clinical data management that consist of best business practice and acceptable regulatory standards.
A control based on a group of subjects who were observed at sometime in the past.
Intervention refers to the application in the subject of an investigational device being studied in the clinical investigation or a control. The investigational device could be therapeutic or aesthetic or, for a diagnostic device, a strategy for subject management based on the outcome of the diagnostic device.
Method that assigns the study subjects to investigational or control groups.
1) An unapproved new device or a currently marketed device being studied for an unapproved use in a clinical investigation or research involving one or more subjects to determine the safety or effectiveness of the device. 2) A device, including a transitional device, that is the object of an investigation, where a Transitional device means a device subject to section 520(l) of the act, that is, a device that FDA considered to be a new drug or an antibiotic drug before May 28, 1976 (see Device Under Investigation and Test Device).
In Vitro Diagnostic (IVD) Device
A diagnostic device that is intended for use in the collection, preparation and examination of specimens taken from the human body .
Lead- time bias
Form of bias that can occur because earlier detection adds to the survival time relative to detection at a later time. Subject survival from the time of testing may be no better when a test result is known than when it is not, but can appear to be longer due to this bias.
Length-time Selection Bias
Form of selection bias that occurs when subjects who have the target conditions for a long period of time are more likely to be included in a clinical study than subjects who have the target condition for a short period of time As a result, estimates of survival can be longer than that expected in the target population.
Level of Evidence
The collective level of confidence about the validity of estimates of benefits and harms for any given intervention or diagnostic test.
A condition placed on an individual or group of individuals to keep them from knowing the intervention (or test) assignment of the subjects or subject specimens. For ophthalmic device studies, the term “blind” to describe this condition is inappropriate.
An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes.
A statistical synthesis of the data from separate but similar (i.e., comparable) studies, leading to a quantitative summary of the pooled results.
Study designed to demonstrate that the safety or effectiveness of an investigational device is not worse than the comparator by more than a specified margin.
A study in which there is no masking; also called an open-label study (see also Open-Label Study).
“No Intervention” Control
A control in which no intervention (including a placebo) is used on the subject. In a treatment study, this could also be referred to as a “no treatment” control.
Objective Performance Criterion (OPC)
A numerical target value derived from historical data from clinical studies and/or registries and may be used by FDA for the comparison of safety or effectiveness endpoints.
Study that draws inferences about the possible effect of an intervention on subjects, but the investigator has not assigned subjects into treatment groups.
A clinical study in which the participant, health care professional, and others know which intervention or diagnostic test under study is being given (see also Non-Masked Study).
The application of two or more interventions or diagnostic tests at the same point in time to the same subjects or subject specimens. This design may be not appropriate if the interventions or test interfere with each other.
Parallel Group Design
An (unpaired) design in which each study subject or subject specimen is assigned only one of several interventions or diagnostic tests being studied.
A numerical value (point estimate) that is considered sufficient by FDA for use as a comparison for a safety and/or effectiveness endpoint.
See Feasibility Study.
Clinical development stage for medical devices during which the evidence is gathered to support the evaluation of the safety and effectiveness of the medical device. The stage consists of one or more pivotal studies.
A definitive study during which evidence is gathered to support the safety and effectiveness evaluation of the medical device for its intended use.
A device that is thought to be ineffective. In clinical studies, experimental interventions are often compared with placebos to assess the intervention’s effectiveness (see placebo control study).
Placebo Control Study
A comparative investigation in which the results of the use of a particular investigational device are compared with those from an ineffective device used under similar conditions.
A physical or psychological change, occurring after an ineffective device is used, that is not the result of any special property of the device. The change may be beneficial, reflecting the expectations of the participant and, often, the expectations of the person using the device.
Protocol (Study Protocol)
A study plan on which the clinical study is based. A protocol describes, for example, what types of people may participate in the study, the schedule of tests, procedures, medications, and dosages; and the length of the study.
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.
A study in which participants are randomly (i.e., by chance) assigned to one of two or more interventions (or diagnostic tests) of a clinical study.
Reading Order Bias
Bias incurred due to the order in which the tests are sequentially interpreted (e.g., in radiology). When two tests are performed on the same subject and interpreted by the same reader, images that are read last tend to be more accurately interpreted than images read first.
The probable benefit to health from the use of a device weighed against any probable injury or illness from such use.
1) A type of bias caused by an error in the way subjects are assigned to groups in a clinical study. This can occur when the study and control groups are chosen so that they differ from each other in ways that may affect the outcome of the study. 2) The distortion of a statistical analysis, resulting from an inappropriate method of collecting samples.
Effect on estimates of diagnostic clinical performance introduced when the subjects included in the study do not represent the whole spectrum of disease or the target condition in the intended population. For example, if only subjects with clear and definite cases of the target condition are included in the study so that these subjects do not represent the subjects in clinical practice, estimates of performance can appear to be better than they truly are in clinical practice.
The discrete portion of a body fluid or tissue taken for examination, study, or analysis of one or more quantities or characteristics.
Medium or milieu in which the analyte of interest may be contained (e.g., cerebrospinal fluid, serum, blood, other tissue, or viral transport media). The discrete portion of a body fluid or tissue taken for examination, study, or analysis for one or more quantities or characteristics.
The division of a population into mutually exclusive and exhaustive sub-populations (called strata), which are thought to be more homogeneous, with respect to the characteristics investigated, than the total population.
Stratified (Subgroup) Design
Design in which the target population is divided into subject subsets (or strata) and subjects are selected separately from each subset (or stratum).
A primary or secondary outcome used to judge the effectiveness of an investigation.
Study designed to demonstrate that the safety or effectiveness of the investigational device is superior to that of the comparator.
The condition for which the device is to be used. In the context of diagnostic devices, a past, present, or future state of health, disease, disease stage, or any other identifiable condition within a subject; or a health condition that should prompt clinical action such as the initiation, modification or termination of treatment.
Bias resulting from comparing results separated by a significant time interval, e.g., using a historical control group that does not reflect current practice of medicine and may include a different subject population and/or outcomes than the contemporary study.
See Investigational Device.
Devices intended to treat a specific condition or disease.
2 See FDA’s Guidance for HDE Holders, Institutional Review Boards (IRBs), Clinical Investigators, and FDA Staff – Humanitarian Device Exemption (HDE) Regulation: Questions and Answers, for detailed information
3 A list of FDA’s good clinical practice (GCP) guidance documents is available at Clinical Trials Guidance Documents
4 See Medical Device Use-Safety: Incorporating Human Factors Engineering into Risk Management (July 18, 2000)
5 In some cases for in vitro diagnostic devices that are used as companion diagnostic devices for therapeutic products, a non-final version of the device is used in the clinical trial of the therapeutic product. When this occurs, careful advance planning and execution of “bridging” studies are needed to establish clinical validity of the commercial in vitro diagnostic device.
8 The best available method for establishing the target condition; this definition does not restrict the target condition to be dichotomous (present/absent); otherwise, this definition is identical to that for reference standard (FDA’s “Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests,” March 13, 2007, and Bossuyt et al) and diagnostic accuracy criteria (CLSI Harmonized Terminology Database; accessed February 2011),