How Intended User and Use Setting Impact Study Design and Regulatory Requirements.


The performance of IVD products depends not only on the accuracy of a test, but also on the user performing the test and the testing environment. Because of this, defining the intended user and intended use setting of an IVD is one of the most important considerations for development, figuring into risk-based classification, test complexity, appropriate regulatory submission(s), and study design requirements.

In general, more stringent regulatory requirements are associated with tests that have a higher likelihood of error by the intended user.

In general, more stringent regulatory requirements are associated with tests that have a higher likelihood of error by the intended user. In cases where user error is more likely, a waived IVD may receive a higher risk classification (Class II vs. Class I), and require more regulatory oversight (e.g., a Clinical Laboratory Improvements Amendments of 1988 (CLIA) waiver application that includes additional studies) to ensure that users can reliably conduct the test and interpret it correctly.

The likelihood of error by the user is influenced by:

Effect of user and use environment on regulatory pathways:

A test that is intended to be used near patients (a point-of-care [POC] test) may be considered higher risk and require a more stringent regulatory pathway than one that is conducted in a laboratory setting. Consider the case of a cholesterol test, used in the diagnosis and treatment of disorders involving excess cholesterol in the blood. In the U.S., when conducted in a central laboratory, the test is classified as lowest risk, Class I, and is exempt from premarket notification procedures such as 510(k). However, the exemption from premarket notification no longer applies if the same test is intended for near patient (POC) testing.

Effect on regulatory requirements:

The user and use environment may also impact the “complexity” of the test, which, in turn, affects regulatory requirements. Specifically, in the U.S., an IVD’s test complexity will inform whether laboratory certification by CLIA is needed, or whether manufacturers will need to submit a CLIA waiver application. All U.S. facilities that perform laboratory testing on human samples for medical reasons are regulated under CLIA, which established quality standards for laboratory testing to ensure the accuracy and reliability of results in the intended use setting.

The FDA categorizes clinical laboratory tests by their complexity — from the least to the most complex: waived tests, moderate complexity tests, and high complexity tests. The FDA determines test complexity by reviewing the package insert test instructions in the premarket submission using the criteria listed in 42 CFR 493.17. The tests that are not waived by regulation under 42 CFR 493.15 and are not cleared or approved for home use or for over-the-counter use may be categorized either as moderate or high complexity.

In addition to submitting premarket notification, manufacturers whose tests are intended to be used for near-patient testing (POC), must also submit a CLIA Waiver by Application, which can be submitted separately from the 510(k) submission or through a dual 510(k) and CLIA Waiver by Application (Dual Submission) 510(k).

In general, a CLIA waiver requires the following additional studies:

Effect on clinical research study design:

In studies, IVD testing must be conducted by the intended users of the product. Study site and personnel considerations need to be planned for IVDs that require more technical skill sets and specific equipment to ensure that these resources are available and that the location is appropriately qualified to conduct laboratory testing. Likewise, a testing-naïve population would be required in the design of studies in which patients collect the samples or conduct the tests themselves, as in the case of IVDs designed for home use.

Additional IVD study considerations — such as the need for informed consent or a Waiver of Informed Consent in the U.S. or General Data Protection Regulation (GDPR) disclosure in the EU – will depend on the type and nature of the patient information to be collected during the clinical study and the type of study procedures to be performed, including study-specific sample collection, and any risks to the patient.


The IVD intended use encompasses the intended user, intended use setting, the indication for which the test will be used (e.g., oncology, sickle cell disease, infectious disease), and what the test results will be used for, such as prognosis, diagnosis, screening, monitoring, or management or prediction of treatment. Some IVDs are also intended to provide information, which guides the use of a corresponding therapy.

A properly defined intended use is critical to identifying the appropriate risk classification of an IVD, the regulatory pathway and associated study design considerations.

A properly defined intended use is critical to identifying the appropriate risk classification of an IVD, the regulatory pathway and associated study design considerations. As part of a quality management system, a sponsor should assess the risk associated with the design, manufacture, and intended use of the IVD. Based on this assessment, relevant standards, references, and regulatory requirements can be identified and studies can be designed as a means to mitigate those risks.

Of note, companion diagnostics (CDx), which are used, for example, to identify patients who are most likely to benefit from a particular therapeutic product, may have rigorous regulatory requirements and considerations that are distinct from other types of IVDs. Because companion diagnostics provide information that is essential for the safe and effective use of a corresponding drug or biological product, companion diagnostics are often classified as Class III devices in the U.S., requiring premarket approval.


Sponsors face many decisions when planning to place their IVD on one or more markets. There are a wide range of interconnected considerations that can impact both timelines and budget. Ensuring that the product development and study designs are aligned with the regulatory strategy and requirements is critical.

Companies planning to commercialize an IVD should consider all applicable regulatory requirements as early as possible in the development process. In our experience, sponsors benefit from working with a full-service CRO partner with IVD services experience to ensure (1) a thorough understanding of all the regulatory requirements; (2) the proper design for the appropriate number and type of studies; and (3) the effective implementation of study protocols.

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