Clear and accurate assessment of whether use of an assay in a clinical trial assay is considered exploratory or an “IVD” is necessary as implications extend to quality/regulatory pathways, assay development and validation strategy. All of which cascade through to impact program timelines and budgets. The delineation between an exploratory assay versus an “IVD” assay comes down to how the results are utilized. In the context of clinical trials in the EU, the terminology used is “medical purpose”.1 Simply stated, an assay has a medical purpose if the results are used to directly guide or impact medical care or follow-up of a patient. Medical care of a patient most often is considered inclusion into a trial or guiding therapy decision, which includes dosing level as well as initiation or termination of therapy. However, results used for exclusion from a trial as well as decisions on which arm of a trial the patient will be enrolled are also relevant in this context as they meet the definition of medical purpose.
Assays with a medical purpose do not always need to be those that are predictive for therapy (i.e. CDx biomarkers). For example, some markers are prognostic markers that inform the risk of disease outcome with no impact on therapy efficacy. If used with a medical purpose (e.g. inclusion/exclusion) in the clinical trial setting, they would have to meet appropriate regulatory requirements.
The regulatory impact of an assay with a medical purpose is significant. When a marker has a medical purpose, we understand it to mean that in the U.S. a risk assessment is required to determine whether the assay use in the study is considered “significant risk”, requiring FDA authorization prior to use via an IDE application. In the EU, under IVDR, clinical trial sponsors are required to include a performance study application to the relevant EU Competent Authorities for approval prior to study start. Additionally, there are other considerations such as requirements for a legal representative within the EU, as well as submissions to individual competent authorities ahead of EUDAMED being brought online.
Understanding medical purpose is one of the first questions our team seeks to clarify as this guides all following discussions regarding EU strategy. When gauging if an assay has a medical purpose, asking whether results will directly impact patient care is the litmus test. If the answer is “no”, then the assay is likely exploratory and requires a much lower regulatory bar. If “yes” or “maybe”, then further due diligence is warranted to ensure regulatory compliance.
- Medical Device Coordination Group Document Clinical Trials Expert Group Document. 2022. MDCG 2022-10.
- “IVDR at NeoGenomics”, James Yen, PhD, October 4, 2022