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Who says ET is good for Medical Devices? The FDA! (James Bach’s Blog)

On August 18, 2011, in Syndicated, by Association for Software Testing
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In a new guidance document discussing the clinical testing of medical devices, the FDA includes a long section about the value of exploratory testing:

The Importance of Exploratory Studies in Pivotal Study

Medical devices often undergo design improvement during development, with evolution and refinement during lifecycles extending from early research through investigational use, initial marketing of the approved or cleared product, and on to later approved or cleared commercial device versions.

For new medical devices, as well as for significant changes to marketed devices, clinical development is marked by the following three stages: the exploratory (first-in-human, feasibility) stage, the pivotal stage (determines the safety and effectiveness of the device), and the postmarket stage (design improvement, better understanding of device safety and effectiveness and development of new intended uses). While these stages can be distinguished, it is important to point out that device development can be an ongoing, iterative process, requiring additional exploratory and pivotal studies as new information is gained and new intended uses are developed. Insights obtained late in development (e.g., from a pivotal study) can raise the need for additional studies, including clinical or non-clinical.

This section focuses on the importance of the exploratory work (in non-clinical and clinical studies) in developing a pivotal study design plan. Non-clinical testing (e.g., bench, cadaver, or animal) can often lead to an understanding of the mechanism of action and can provide basic safety information for those devices that may pose a risk to subjects. The exploratory stage of clinical device development (first-in-human and feasibility studies) is intended to allow for any iterative improvement of the design of the device, advance the understanding of how the device works and its safety, and to set the stage for the pivotal study.

Thorough and complete evaluation of the device during the exploratory stage results in a better understanding of the device and how it is expected to perform. This understanding can help to confirm that the intended use of the device will be aligned with sponsor expectations, and can help with the selection of an appropriate pivotal study design. A robust exploratory stage should also bring the device as close as possible to the form that will be used both in the pivotal trial and in the commercial market. This reduces the likelihood that the pivotal study will need to be altered due to unexpected results, which is an important consideration, since altering an ongoing pivotal study can increase cost, time, and patient resources, and might invalidate the study or lead to its abandonment.

For diagnostic devices, analytical validation of the device to establish performance characteristics such as analytical specificity, precision (repeatability/reproducibility), and limit of detection are often part of the exploratory stage. In addition, for such devices, the exploratory stage may be used to develop an algorithm, determine the threshold(s) for clinical decisions, or develop the version of the device to be used in the clinical study. For both in vivo and in vitro diagnostic devices, results from early clinical studies may prompt device modifications and thus necessitate additional small studies in humans or with specimens from humans.

Exploratory studies may continue even as the pivotal stage of clinical device development gets underway. For example, FDA may require continued animal testing of implanted devices at 6 months, 2 years and 3 years after implant. While the pivotal study might be allowed to begin after the six month data are available, additional data may also need to be collected. For example, additional animal testing might be required if pediatric use is intended. For in vitro diagnostic devices, it is not uncommon for stability testing of the device (e.g., for shelf life) to continue while (or even after) conducting the pivotal study.

While the pivotal stage is generally the definitive stage during which valid scientific evidence is gathered to support the primary safety and effectiveness evaluation of the medical device for its intended use, the exploratory stage should be used to finalize the device design, or the appropriate endpoints for the pivotal stage. This is to ensure that the investigational device is standardized as described in 21 CFR 860.7(f)(2), which states:

“To insure the reliability of the results of an investigation, a well-controlled investigation shall involve the use of a test device that is standardized in its composition or design and performance.”

This is what I’ve been arguing for a couple of years, now. If you want to test a medical device very well, then you have to test it in an exploratory way. This prepares the way for what the FDA here calls the “pivotal study”, which in software terms is basically a scripted demonstration of the product.

Yes, the FDA says, earlier in this guidance document, that it is intended to apply to clinical studies, not necessarily bench testing. But look at the reasoning: this exact reasoning does apply to software development. You might even say it is advocating an agile approach to product design.

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