Introduction
The in vitro diagnostic (IVD) device industry operates at the intersection of technology and biostatistics. The complexity of this relationship was on display at the 15th Annual FDA/AdvaMed Medical Device Statistical Issues Conference, where DCN Dx’s clinical research team attended to gain insights into trends and best practices in statistical methodologies. One of the standout discussions centered on statistically appropriate practices for the validation of diagnostic device output. Emphasis was placed on critical considerations for IVD migration studies, particularly for Next-Generation Sequencing (NGS) and Companion Diagnostic (CDx) assays.
Here, we delve into the essential takeaways from the conference and how they relate to critical considerations for IVD migration studies.
Migration of IVD Devices to New Systems Explained
The migration of IVD devices to new systems refers to the process of transferring or adapting a particular assay or diagnostic test from an existing platform or system to a different one. This is often necessary when introducing a new instrument or technology that offers better efficiency, scalability, or compatibility. Migration must be carried out with extreme precision, ensuring that the new system performs equivalently to the old one in all key aspects. Failure to maintain the performance characteristics during migration can lead to inconsistencies and inaccuracies in diagnostic results, with potential implications for patient care.
In particular, the alignment of statistical parameters is essential to guarantee that the new system performs equivalently to the old one, a challenge that demands precise statistical methods and a deep understanding of assay characteristics.
Critical Considerations for IVD Migration Studies
Migration studies are central to IVD device adaptation and heavily grounded in statistical reasoning. Key considerations from a biostatistical standpoint include:
- Intended Use and Indications: The intended use and indications for the device should remain consistent, with the exception of the inclusion of the new system.
- Reagent and Assay Parameters: These should be unchanged except for minor differences such as slight alterations in incubation times that optimize the assay on the new system.
- Assay and System Technologies: It’s vital that these remain unchanged to maintain the fidelity of the results.
- No Expected Change to Assay Performance: The new system should not affect the assay’s performance.
- Invalid Rate Estimation: Several presenters at the conference highlighted the importance of estimating an invalid rate for validation studies such as Limit of Blank (LoB), Limit of Detection (LoD), Precision, Comparison, etc. The invalid rate should be meticulously reported for each level and subsequently evaluated and compared between the old system and the new system in migration studies. This comparison is vital in ensuring that the new system maintains the reliability and integrity of the established diagnostic measurements.
- For NGS CDx Assay Migration:
a. Sufficient Challenging Samples: A careful selection of samples should be evaluated in the assay migration studies to support the performance comparison of the new system relative to the old system.
b. Unchanged Assay Performance: Parameters such as assay sensitivity, precision, and accuracy are expected to remain consistent between the new and old system.
c. Complex Study Design for NGS-Based CDx: The study design will require intricate planning to assess the impact on both CDx variants and variants from other claims, such as tumor profiling.
Conclusion
The migration of IVD devices to new systems is a complex process requiring meticulous attention to detail. The recent FDA/AdvaMed Medical Device Statistical Issues conference provided valuable insights into best practices and considerations.
At DCN Dx, our clinical research services team is committed to staying at the forefront of industry standards and advancements. We recognize the importance of these migration studies in maintaining the robustness and reliability of diagnostic devices.
We draw on our expertise in assay development, device design and engineering, clinical research, and manufacturing to provide comprehensive support for IVD developers. By adhering to the critical considerations for migration studies as outlined above, we strive to ensure that each diagnostic device retains its efficacy, accuracy, and dependability.
For further information on how DCN Dx can support your IVD migration studies, we welcome you to contact us.
About the Author
Veronika has more than 15 very successful and rewarding years in the therapeutic and diagnostic industries as well as in the academic environment. Before joining DCN, she worked for Carl Zeiss Meditec Inc. (Medical Device – Scanning Laser Polarimeter for detection of glaucoma), Prometheus Therapeutics (therapeutic and diagnostic products), and Invivoscribe (IVD). She has also worked as a statistical consultant for numerous health related studies over the years. At Invivoscribe, she helped to develop CE-IVD and RUO MiSeq assays for hematology-oncology. Assay development included V&V studies, Clinical bridging studies as well as setting specifications for analyte-specific reagents and DNA and RNA controls.
Veronika has extensive experience in clinical trials and evaluation of medical device performance. She is well versed in regulatory 510(k), PMA, and IVDR submissions.
She holds a M.Sc. in applied statistics from Purdue University.
