Who Is an Intended-Use Operator in an IVD Study? Waived, Moderate Complexity and Lay Users

An intended-use operator is a study participant who matches the people who will run the test after it is on the market, given only the training those people will actually get. For a CLIA-waived test that means an untrained operator: in FDA’s words, “a test operator in waived settings and with limited or no training or hands-on experience in conducting laboratory testing.” For a moderate complexity test it is a trained operator who meets the CLIA testing-personnel qualifications. For an over-the-counter (OTC) test it is the lay user, often the patient testing themselves. Getting this wrong is one of the few study-design errors that cannot be fixed by adding samples afterward.

Primary sources used here: FDA’s CLIA waiver guidance (February 26, 2020), the dual 510(k) and CLIA waiver guidance (February 26, 2020), FDA’s Applying Human Factors and Usability Engineering to Medical Devices (originally issued 2016, current version August 3, 2026), and the CLIA regulations at 42 CFR Part 493. FDA guidance is nonbinding; where a study departs from it, the expected route is a Pre-Submission.

Who counts as an intended-use operator for each test category?

The answer depends on the test’s CLIA categorization and where it will be used. The three categories that matter for most diagnostics sponsors:

Category	Who the intended operator is	Defining source	Typical study setting
CLIA-waived (professional use)	Untrained operator / waived user: limited or no laboratory training or hands-on experience; no prior experience with the candidate test	CLIA waiver guidance, Section V and Appendix B	Sites holding a CLIA Certificate of Waiver: physician offices, urgent care, clinics
Moderate complexity	Trained operator: “meets the qualifications to perform moderate complexity testing”	42 CFR 493.1423	Clinical laboratories and non-waived point-of-care settings
OTC / home use	Lay user: the person who buys the test, testing themselves or someone in their care	Intended use statement; human factors guidance	Homes or a simulated home setting at a clinical site

Two points of regulatory context make the categories clearer. First, CLIA’s personnel qualification standards sit in Subpart M, titled “Personnel for Nonwaived Testing.” Waived testing has no CLIA personnel qualifications; a site with a Certificate of Waiver must instead “follow manufacturers’ instructions for performing the test” under 42 CFR 493.15(e). So the instructions are the only control on how the test is run. Second, under 42 CFR 493.15(b)(1), tests “cleared by FDA for home use” meet the criteria for waived tests, which is why OTC tests are also waived.

What does “untrained” mean for a CLIA-waived test?

For waived tests, the CLIA waiver guidance sets out who should be enrolled (Section V.C(2)(a)):

“Untrained operators should have limited or no training or hands-on experience in conducting laboratory testing and should not have previous training or experience with the candidate test, but may have limited experience with other waived or home use tests. Untrained operators should be personnel currently employed in the selected intended use sites…”

And it pushes toward the low end of experience: “We encourage you to enroll operators with the least amount of training that might be encountered at the types of sites for which this device is intended.”

Four tests follow from this text. Each one should be answered yes for every operator enrolled:

Employed at the site. Already working there, not hired or seconded for the study.
Not a laboratorian. No formal laboratory training sufficient to make them a moderate complexity tester in practice.
Naive to this device. Never trained on, used or watched the candidate test, including in feasibility work.
Representative of the least-trained plausible user at that type of site.

In practice this usually means medical assistants, nurses, and other clinical or support staff who run waived tests between patients. Published dual submissions describe operators the same way. In a point-of-care STI study, dozens of operators had no formal laboratory training and no training on the device. In a point-of-care molecular Strep A study, testing was by non-laboratory health professionals such as nurses, physician assistants and medical assistants.

For numbers, the guidance asks for “1-3 untrained operators at each site and at least nine (9) untrained operators across all sites,” at a minimum of three sites; see how many sites a CLIA waiver study needs for the arithmetic.

What training can untrained operators receive?

Only the materials that will ship with the product. The guidance (Section V.C(2)(c)):

“The untrained operators should receive no additional instructions (e.g., written or verbal training, coaching, or prompting). Likewise, untrained operators should have no opportunity to discuss the test with other participants or otherwise coach or observe each other. Untrained operators may call a toll-free help-line if such a service is to be provided for the device when it is marketed.”

The line between protocol training and device training is where most mistakes happen, so it is worth being explicit:

Allowed	Not allowed
Training on the protocol: consent, eligibility, specimen labeling, CRFs, shipping the comparator specimen	A demonstration of the candidate test
Training on universal precautions and site safety	A practice run, “dry run” or walkthrough of the test procedure
Handing over the final Quick Reference Guide and package insert as they will ship	Draft or annotated instructions, sponsor slide decks, or a tip sheet
A help line, if one will exist post-market, staffed to the same script	Answering device questions in person, by text or by monitor visit
A post-study questionnaire	Questions before or during the study that reveal what to look for
	Operators observing or coaching each other

The waiver guidance also expects the labeling itself to be simple: quick reference instructions “written at a level appropriate for untrained operators, which for a ‘simple’ device should be at a 7th grade reading level, or lower.” If an operator needs more than that to run the test, the finding is about the device or its labeling, not about the operator.

How is a moderate complexity operator different?

A trained operator is defined by regulation rather than by study design. The CLIA waiver guidance defines a trained operator as “a test operator who meets the qualifications to perform moderate complexity testing,” citing 42 CFR 493.1423. That section allows several routes, including a physician license, a laboratory science or nursing degree, an associate degree in those fields, or a high school diploma plus documented laboratory training covering specimen handling, each test method, instrument use, troubleshooting and calibration, quality control and result verification.

For a 510(k)-only submission of a moderate complexity test, the dual guidance notes that comparison and reproducibility studies “are often performed by trained operators.” Intended-use thinking still applies: if the device is meant for non-waived point-of-care settings, operators should look like the staff there, not only like central-laboratory technologists. The dual guidance makes this explicit for dual studies: where non-waived point-of-care patients are not represented by the waived sites, include “one or a few POC non-waived sites” in which “trained operators representative of those at intended POC non-waived sites should perform testing.” A 510(k) point-of-care PT/INR study is an example of a multi-operator design at intended-use professional sites, with a minimum of three operators per site.

Trained operators also run the comparator. In Option 4 and dual designs, they should hold the CLIA qualifications to perform the comparative method and have previous training or experience with it. Untrained operators are naive to the candidate test; trained operators should be experienced with whatever method they are running.

What changes for lay users and OTC tests?

For an OTC test the intended-use operator is not site staff at all. It is the consumer, and often a second user group: an adult testing a child or another adult. Three things change.

The participant is often the specimen source. Lay users usually self-collect and self-test, so collection technique becomes part of what is being evaluated. An OTC COVID-19 antigen 510(k) had subjects aged 14 and older self-sample and self-test “in a simulated home setting using only the labeling,” with children tested by an adult.

Usability evidence is usually expected alongside accuracy. FDA’s human factors guidance applies to the whole user interface, labeling included. Its participant-training rule matches the waiver guidance’s spirit: “If you anticipate that most or all users would receive minimal or no training, then the test participants in the human factors validation test should not be trained.” It also states that “a human factors validation test conducted after participants have been trained differently than they would be in actual use is not valid,” and that a manufacturer’s employees “should not serve as test participants” except in rare cases.

Distinct user populations each need their own sample. The human factors guidance says “the minimum number of participants should be 15,” and that a device with more than one distinct user population should include “at least 15 participants from each user population,” naming professional versus lay users and different age groups as examples. The OTC COVID-19 study above, for instance, ran usability with 25 self-testers and 25 adults testing another person.

Why 15? FDA’s Appendix A cites empirical work in which 15 users found at least 90% (mean 97%) of known problems, while cautioning that the simple probability models behind such figures rest on assumptions that do not reflect the real world. The simple model still shows why rare use errors slip through small samples. If each participant independently has probability p of encountering a given problem, the chance that at least one of n participants hits it is 1 − (1 − p)ⁿ:

Per-user probability of a use problem	n = 9	n = 15	n = 25	n = 30
5%	37.0%	53.7%	72.3%	78.5%
10%	61.3%	79.4%	92.8%	95.8%
20%	86.6%	96.5%	99.6%	99.9%

A use error affecting one user in twenty has roughly even odds of going unseen in a 15-person study. That is one reason clinical-performance data from lay users, which involves far more test runs, and the human factors study complement each other.

	Waived (professional)	Moderate complexity	OTC / lay user
Who runs the test	Untrained site staff	Qualified testing personnel (42 CFR 493.1423)	Consumer, or an adult testing someone else
Prior device training	None; labeling only	Per labeling and lab practice	None beyond labeling
Who collects the specimen	Usually site staff, sometimes patient on site	Site or lab staff	Usually the user
Key operator numbers	≥3 sites, 1–3 per site, ≥9 total (waiver guidance)	No fixed number in the guidances reviewed here	≥15 per distinct user population for HF validation
Setting	CLIA-waived sites in normal workflow	Laboratory or non-waived POC	Home or simulated home

How should operator selection be documented?

Document eligibility for each enrolled operator and the pool they were drawn from. The CLIA waiver guidance recommends that you “record and tabulate the education (including experience and training) and the occupation of each untrained operator,” and, for each site, “report the same information on other personnel that were available at the testing site but that were not chosen to participate.” A workable file per site:

Operator eligibility form: role, education, laboratory training, experience with waived or home tests, and an attestation of no prior exposure to the candidate device.
Site staffing roster: everyone who could have operated, enrolled or not, with the same fields, so FDA can see whether selection skewed toward the most experienced staff.
Labeling control log: the exact IFU and Quick Reference Guide version given to each operator.
Contact log: every help-line call and every monitor interaction touching device use.
Per-operator results: the guidance asks for, for each untrained and trained operator, total tests performed, initial invalids, retests and final invalids.
Operator questionnaire: given “after the completion of the clinical study, so the questions do not bias the untrained operators,” including reading example positive, negative and invalid results.

For OTC studies the equivalent is a participant demographics table (age, education, prior home-test experience, and any functional limitations relevant to the intended use), the human factors protocol’s description of any training given and the time elapsed before testing, and observed task success for each critical task.

Per-operator reporting matters because pooled numbers can hide an operator problem. The guidance asks for invalid rates “with a 95% two-sided confidence interval.” Using Wilson score intervals:

Data	Invalids / tests	Rate	95% Wilson interval
Study overall	6 / 300	2.0%	0.9% – 4.3%
One operator	4 / 30	13.3%	5.3% – 29.7%
Typical operator	1 / 30	3.3%	0.6% – 16.7%

(Illustrative figures; z = 1.95996.) A study-level 2% invalid rate looks acceptable, but if four of the six invalids came from one operator, that operator’s entire interval sits above the study-wide interval, and their experience with the device is a question FDA will ask about. The guidance also asks for “a rationale as to why the observed percentage of invalid results is clinically acceptable.”

What are the common failure modes?

Laboratorians enrolled as untrained operators. Usually because the site’s most capable person volunteered. The staffing roster exposes this.
Exposure before the study. Operators who attended a sponsor demo, joined feasibility testing, or watched a colleague.
Coaching by another name. A monitor who clarifies a step, a coordinator who checks the operator’s read, a “helpful” laminated tip card.
Study staff doing the testing. A dedicated research coordinator running every test is not “integrated into the daily workflow.”
Lay-user studies with clinical hand-holding. Staff who correct swab technique or read the result for the subject turn a lay-user study into a professional-use study.
Training used as a mitigation after the fact. The human factors guidance states that proposing “additional training” to mitigate observed use errors is not acceptable without data showing it works.
Missing second user group. An OTC test labeled for adults testing children that only enrolled self-testers.
No documentation of who was not chosen. Easy at start-up, hard later.

The CLIA waiver studies, dual submission studies and 510(k) studies pages describe where operator design fits in each pathway.

How Studybox approaches this

Studybox Research is an IVD-only CRO and site network; its team has supported 55+ FDA regulatory clearances across 510(k), dual 510(k)/CLIA waiver, OTC and EUA pathways. With 100+ pre-qualified U.S. urgent care, physician office and point-of-care sites, operator eligibility can be screened during site selection, before a site is committed to a protocol, rather than discovered at the initiation visit.

For lay-user and specimen-collection work, prospective collection can run under a pre-approved IRB protocol and launch in as little as one week. If you are deciding who your intended-use operators are, or how to document them, contact us or see what to ask an IVD CRO.

Studybox Research Guide October 5, 2026