Key Takeaways
- Laboratory testing that produces patient-specific results generally triggers CLIA requirements, even if the testing occurs within a research protocol.
- IRB approval, CLIA certification, FDA oversight and research billing rules each address different aspects of laboratory testing — compliance under one framework does not satisfy the others.
- Research Use Only is an FDA product designation, not a CLIA safe harbor — an RUO-labeled product cannot be carried forward into clinical use simply because the surrounding activity is called research.
- Involving laboratory leadership during protocol development helps address regulatory, billing and specimen-use questions before enrollment begins.
Research protocols often include clinical laboratory testing, and seemingly routine decisions about that testing can implicate several regulatory frameworks. Where will the testing be performed? Will individual results be returned? Can specimens or data be used later? Who pays for the test? Will the result enter the clinical record? Institutional Review Board (IRB) oversight, Clinical Laboratory Improvement Amendments (CLIA) requirements, FDA regulation, research billing rules and patient-access requirements may affect those decisions.
Six areas deserve attention when research and clinical laboratory testing begin to overlap.
1. The distinction between research testing and clinical testing is regulatory, not scientific. A laboratory assay does not change its chemistry depending on whether the result is used for research or for clinical decision-making. The regulatory treatment of that result changes significantly. Laboratory testing performed solely for research purposes may not be subject to CLIA, though the boundary between research testing and clinical testing is not always clear. CMS guidance states that when patient-specific results are reported and will be or could be used clinically, CLIA is generally presumed to apply absent evidence otherwise.
2. Laboratory regulatory compliance applies independent of IRB approval. IRB review and laboratory regulation serve different purposes. An IRB may consider how laboratory testing affects research participants, including what specimens will be collected and whether individual results will be returned to study subjects. A separate analysis is needed to determine whether the testing is subject to CLIA and whether the laboratory performing it has the appropriate certification. Study teams should include the laboratory director in discussions when a protocol contemplates patient-specific testing, particularly if results may affect eligibility, treatment or other clinical decisions.
3. ‘Research Use Only (RUO)’ is an FDA designation, not a CLIA safe harbor. An RUO-labeled in vitro diagnostic product is intended for the laboratory research phase of product development and not for diagnostic procedures. The designation therefore does not answer whether laboratory testing falls within CLIA’s research exception. An RUO product cannot simply be carried forward into clinical use because the surrounding activity is called research. FDA distinguishes RUO testing from investigational testing involving human subjects and states that RUO products are not intended to assess a patient’s condition. This is different from permissible off-label use of an FDA-cleared or approved device: An RUO product has not been cleared or approved for clinical diagnostic use in the first place. A laboratory that moves from research testing to reporting patient-specific results therefore needs to assess the regulatory status of the test itself and satisfy the applicable CLIA requirements before reporting patient results.
4. Informed consent can determine what happens to specimens and data after the study. Research consent should address what testing will be performed, whether individual results will be returned, and what future uses of specimens and data are contemplated. Genetic and genomic research deserves particular attention because federal consent requirements address whole-genome sequencing and secondary use of identifiable specimens or information, while state laws may impose additional consent or privacy requirements. Consent that does not adequately authorize the proposed collection or future use can leave specimens scientifically valuable but unavailable for the next research project without additional consent, a waiver or another permissible basis for use.
5. Research billing requires its own compliance analysis. A laboratory test may be part of a research protocol and still represent routine clinical care that would have been provided absent the study. Conversely, a test may be performed only because the patient enrolled in the study. The protocol and research budget should distinguish those categories before enrollment and identify which services will be paid by the sponsor. For qualifying clinical trials, Medicare may cover routine costs, but not items or services provided solely to satisfy research data-collection needs or items or services customarily provided free by the sponsor. The laboratory order and billing workflow then need to implement the coverage analysis reflected in the protocol and budget.
6. One more issue: information blocking. The point at which a research result enters the clinical record can create a separate set of patient-access obligations under federal law and, in some states, specific rules governing the timing or release of laboratory results. The next issue of The Lab Protocol will address when research and laboratory results become electronic health information, when they must be released and when they may be held.
The Readout
Research and clinical laboratory testing can overlap without creating a regulatory problem. The important point is that IRB review, CLIA, FDA regulation, research billing and patient-access rules address different aspects of the same activity. Compliance under one framework does not necessarily answer the questions raised by others.
For study teams, that makes laboratory involvement during protocol development particularly useful. Decisions about how testing will be performed, whether individual results will be returned, how specimens and data may be used, and which services are sponsor-funded or billable can often be addressed more efficiently before enrollment begins.
The laboratory does not need to drive the research protocol. It should, however, have a seat at the table when the protocol depends on laboratory testing.
The Lab Protocol is for informational and educational purposes only and does not constitute legal, regulatory or compliance advice. Readers should consult qualified counsel regarding their specific circumstances.nly and does not constitute legal, regulatory or compliance advice. Readers should consult qualified counsel regarding their specific circumstances.