Description
For questions regarding this document, contact Kristen Meier at 301-796-6037, or send an e-mail tokristen.meier@fda.hhs.gov.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
7Devices compared to reference methods or gold standards
subjects are tested with two new tests (New Test A and New Test B)
subjects are tested with two new tests (New Test A and New Test B)
Product being evaluated for performance using sensitivity and specificity; studies evaluating diagnostic tests
Special Considerations for Diagnostic Devices
Designed to determine whether a target condition is present or absent in a subject from the intended use population.
For qualitative tests derived from an underlying quantitative result, FDA recommends you provide descriptive summaries.
Stakeholders
5Assists in clarifying issues and mediating meetings; Engaged prior to filing a formal request for review or for bias allegations
agreement can change depending on the condition prevalence in the study subject population
Recommended for consultation if study data include multiple samples from single patients
Those subjects/patients for whom the test is intended to be used.; those subjects/patients for whom the test is intended to be used
An expert panel (FDA advisory panel or other panel) may be able to develop a set of clinical criteria.
Regulatory Context
Regulatory Activities
3Premarket notification submission type
Premarket Approval Application
Evaluation of diagnostic test performance using subjects from the intended use population.
Document Types
5Cybersecurity information should be included in device labeling
As an alternate to the 4x2 Table 6A
Table of results comparing the new test with the non-reference standard; Format used for reporting results comparing a new test outcome to the reference standard; present these results as two separate 2x2 tables; The original 2x2 table of results used for agreement calculations; Misclassification in 2x2 tables
Labeling may include instructions for use to help ensure the product labeling is transparent.
FDA recommends the test label clearly describe the designated reference standard that was constructed.
Attributes
10Analysis by sex of clinical performance measures such as sensitivity
Correcting for verification bias in studies of diagnostic tests
the extent of agreement between the outcome of the new test and the reference standard
the proportion of test negative patients who do not have the target condition
the proportion of test positive patients who have the target condition
All agreement measures, including kappa
Scientific factor evaluated using epidemiological studies.; Factor #2: Prevalence of an IgE-mediated food allergy in the U.S. population; Key criterion for assessing public health importance of allergens.
measures of overall agreement can be misleading
Results that are intermediate, inconclusive, or otherwise not positive or negative
FDA recommends reporting results for subjects in the intended use population separately
Technical Details
Testing Methods
10Practice focused on in the guidance and its associated problems
Assessment of the clinical accuracy of laboratory tests
Evaluation of bias in diagnostic-test sensitivity and specificity estimates computed by discrepant analysis
The decision to use the resolver test depends on the outcome of the new test
how to calculate exact confidence intervals
Two-sided 95% score confidence intervals
Alternative statistical method for computing confidence intervals
A commonly used measure of agreement
The percentage of total subjects where the new test and the non-reference standard agree
Measure used when a new test is compared to a non-reference standard, analogous to specificity
Processes
2Study design where the reference standard is used on only a subset of subjects.
A two-stage testing process used when the new test and non-reference standard disagree; discrepant resolution is multi-stage testing involving a resolver test; a two-stage testing process that uses a resolver to attempt to classify patients for whom the new test and non-reference standard disagree
Clinical Concepts
5The condition for which the device is to be used, such as a state of health or disease.
Reproductive HCT/P donors who have been treated for or had Chlamydia trachomatis; Screening required only for reproductive donors
The specific disease or state the diagnostic test is intended to detect
Measures of diagnostic accuracy; cannot calculate unbiased estimates of sensitivity and specificity
Appropriate to describe how often a test is negative only in subjects from the intended use population; cannot calculate unbiased estimates of sensitivity and specificity
Identified Hazards
Hazards
1Analysis based only on subjects verified by reference standard; Ground truth being missing for some subjects
Standards & References
External Standards
9Assessment of the Clinical Accuracy of Laboratory Tests Using Receiver Operating Characteristic (ROC) Plots
Information about designing and performing precision studies; User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline
Reference for further details on terms.
STAndards for Reporting of Diagnostic Accuracy; Towards complete and accurate reporting of studies of diagnostic accuracy
Standards for Reporting of Diagnostic Accuracy used for definitions of target population and reference standard.
Reference for describing diagnostic accuracy and calculating predictive values.; User protocol for evaluation of qualitative test performance
Reference for measures that describe diagnostic accuracy.; Assessment of the clinical accuracy of laboratory tests using receiver operating characteristic (ROC) plots
Used for the diagnosis of myocardial infarction as an example of a reference standard.
Used for the diagnosis of lupus or rheumatoid arthritis as an example of a reference standard.
Specifications
3a set of clinical criteria that would serve as a designated reference standard.; The gold standard used to determine true condition status; The benchmark outcome to which the new test is compared to estimate sensitivity and specificity; three-way comparison between the new test result, the non-reference standard result, and the reference standard; the best available method for establishing the presence or absence of the target condition; Comparison of a screening test and a reference test
A comparative method other than a reference standard; A comparator that is not always correct, leading to biased estimates if sensitivity/specificity are used; comparing new test A to a non-reference standard; a test used for comparison that is not the gold standard reference
FDA recommends you define the conditions of use... specimen acceptance criteria.
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- Product Labeling for Laparoscopic Power Morcellators: Guidance for Industry and Food and Drug Administration Staff
- Postmarket Management of Cybersecurity in Medical Devices: Guidance for Industry and Food and Drug Administration Staff
- Non-Clinical and Clinical Investigation of Devices Used for the Treatment of Benign Prostatic Hyperplasia (BPH): Guidance for Industry and Food and Drug Administration Staff
- Factors to Consider Regarding Benefit-Risk in Medical Device Product Availability, Compliance, and Enforcement Decisions: Guidance for Industry and Food and Drug Administration Staff
- Arthroscopy Pump Tubing Sets Intended for Multiple Patient Use - Premarket Notification (510(k)) Submissions: Guidance for Industry and Food and Drug Administration Staff
- Minimizing Risk for Children's Toy Laser Products: Guidance for Industry and Food and Drug Administration Staff
- Investigational IVDs Used in Clinical Investigations of Therapeutic Products: Draft Guidance for Industry, Food and Drug Administration Staff, Sponsors, and Institutional Review Boards
- Premarket Notification [510(k)] Submissions for Chemical Indicators - Guidance for Industry and FDA Staff