EMERGO BY UL SUMMARY OF KEY POINTS:

• US regulators reevaluating how to oversee nicotine replacement therapy (NRT) products;
• NRT manufacturers should utilize human factors in developing NRT product labels;
• Self-selection studies recommended for developing NRT product labeling.

Nicotine replacement therapy (NRT) drug products, such as patches, gum and lozenges, have been around for more than 30 years. More novel products such as e-cigarettes provide additional choices for people using NRT for smoking cessation. But, like any other drug delivery mechanism, there are risks as well as benefits when using NRT drug products. While the technology has been marching ahead, regulators have been taking an increased interest in how to manage the risks of harm associated with using such products.

FDA’s recently released draft guidance on NRT drug products continues to emphasize the importance of product labeling, and the critical role of human factors in developing labeling that is clear and understandable by users. The guidance highlights the nuances specific to drug development and trial design for NRT drug products. It also speaks to the need to apply human factors in the course of product development, pointing to FDA’s combination product and label comprehension guidance documents for more detail.

In summary, FDA recommends that studies related to the product label and Instructions for Use (IFU) be integrated with the sequential stages of NRT drug product clinical trials. An iterative approach to labeling design is recommended. Specifically, the guidance recommends the following process:

1. Conduct a formative label comprehension study on the product label and a formative human factors study if there is an IFU associated with the product.
2. During clinical trials, train the subjects to follow the label and IFU directions (thus providing evidence that the labelling is effective).
3. Update the product label and IFU based on learnings from the aforementioned clinical trial.
4. Conduct another label comprehension study and human factors study with the refined product label and IFU.
5. Conduct an actual-use clinical trial with no training from trial staff to represent a real-world scenario.

Manufacturers should also consider incorporating one or more self-selection studies during development to confirm that potential users can understand if they are a suitable user of the NRT drug product (and conversely, if they are not a suitable user). The guidance goes further to suggest that manufacturers might be able to incorporate a self-selection study into the actual-use clinical trial.

Although FDA provides no detail on how to design a self-selection study in this guidance, further detail may be found in an earlier guidance document.

In our experience a self-selection study would focus on a two-part research question:

• Can the intended users of a particular product determine that they are, indeed, a suitable user?
• Can people who are not suitable users of a particular product make this determination independently?

It’s an evolving landscape of product development and regulation, but it is clear that FDA is taking a keen interest in how human factors can reduce risk and guide users of NRT drug products to use them safely and effectively.

Stephanie Larsen is Managing Human Factors Specialist and Richard Featherstone is Research Director at Emergo by UL's Human Factors Research & Design (HFR&D) division.

Related human factors resources from Emergo by UL:

• Human factors research for healthcare products
• Medical device and healthcare products design evaluation
• Webinar: Human factors engineering for combination products