July 18, 2023
When it comes to integrating human factors engineering (HFE) activities with combination product development, a common question we receive is when human factors (usability) studies should occur in relation to clinical trials. Generally speaking, a human factors (HF) validation study should be separate from a major clinical study, and both types of studies are essential for maximizing the likelihood that a drug delivery product can be used safely and effectively. Therefore, manufacturers might wonder whether the U.S. Food and Drug Administration (FDA) requires an HF validation study to occur before a major clinical study or if they can wait to conduct their HF validation study until closer to their FDA submission.
FDA’s guidance on human factors studies for combination products
In Section V of the FDA’s 2016 draft guidance titled Human Factors Studies and Related Clinical Considerations in Combination Product Design and Development, FDA discusses their expectations for the relationship between human factors and major clinical studies for combination products. Related to timing, FDA says:
“Therefore, ideally, before conducting the major clinical study(ies), the HF Validation study should be conducted on the final finished combination product, including the user interface (e.g., instructions for use, training materials, and any other user labeling, if applicable). The HF Validated product would then be ready for further evaluation in the major clinical study(ies) that will be submitted in the marketing application. Noting that in some cases it may be appropriate to conduct your human factors studies in parallel to your major clinical studies or after your clinical studies to address modifications to your product…"
At first glance, the timing piece is straightforward: conduct the HF validation study before the major clinical study. However, the guidance is actually quite open-ended because it also indicates that there is flexibility in the timing and cases in which the HF validation study could occur in parallel to or after the clinical study. However, the FDA’s guidance does not specify or share examples to help manufacturers of combination products determine whether to conduct human factors studies before or after clinical trials.
Our experience optimizing the timing of HF validation studies and clinical trials
Our HF consulting team has supported many clients to navigate the timing of HF validation studies relative to clinical trials. FDA has explicitly required that some manufacturers conduct a complete HF validation study of their combination product before their major clinical study. Even in the absence of an explicit regulatory imperative, conducting an HF validation study before the clinical trial can increase the likelihood that the clinical trial will generate valid data. This is because a manufacturer can gain use-related insights regarding the combination product and associated labeling from representative users and even modify the product as needed ahead of the major clinical study to support correct use. This is particularly true for clinical trials involving lay users self-administering a drug; a thoroughly tested product user interface will help support proper use. For example, if users do not know to hold an injection device onto the skin or hold their breath after inhaling medication for a certain number of seconds, they might not receive the intended dose and the related clinical efficacy data could be invalid.
One barrier to conducting the HF validation study before the major clinical trial is that the HF validation study should evaluate the final, “production-equivalent” user interface, including the physical product and all associated labeling and training. Many manufacturers are unsure of their specific product commercialization plans before the major clinical study, and some manufacturers may plan to sell or license their product to a third-party to market. Therefore, it might be most practical to conduct an HF validation study that represents the product and training plans to be used in the clinical trial, rather than the (potentially unknown) to-be-commercialized versions. Specifically, test only the individuals who will administer the product in the clinical trial and include the product and associated packaging, labeling and training that will be used in the clinical trial, which might understandably differ from the launch version of those materials. Then, you can be more confident that clinical trial participants will understand how to use the product and that the IFU and training (if applicable) are effective for the generation of reliable clinical data.
Conducting a pre-clinical HF validation study before the major clinical trial means that additional HF validation testing will almost certainly be needed prior to market approval. Despite the need to conduct two rounds of HF validation testing, this staggered approach is most practical for many manufacturers. In many cases, the pre-clinical HF validation study can involve a smaller sample size (only the user group(s) administering the drug in the clinical trial) than the final validation study, but we recommend including a full 15 participants in each included user group. As for any HF validation study, we encourage communicating with FDA regarding your plans and seeking FDA’s guidance on your study protocol before proceeding.
Contact our global team to learn more about conducting HF validation activities to benefit your organization. Or, sign up for a complimentary account with OPUS, our team’s software platform that provides HFE training, tools and templates.
Andrea Dwyer is Associate Research Director and Allison Strochlic is Global Leader at Emergo by UL.
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