By Tim Reeves, PhD CHFP
This month, I had the pleasure of giving an invited presentation at the 25th Annual Meeting of the Society of Clinical Research Associates (SOCRA) in Montreal, Canada. Over 1,000 people attended the three-day event.
My presentation focused on the role of human factors testing in the development of combination products, and how human factors studies “complement” traditional clinical trials in establishing combination product safety and effectiveness.
Combination products (a drug packaged with its own delivery device) are increasing ubiquitous in healthcare as the costs of providing therapy have pushed the responsibility for administration of many drugs to patients themselves. But while drug delivery devices designed with patients in mind (such as auto-injectors, inhalers, and transdermal patches) may seem simple to use, usability testing and post-market reports show otherwise. Even devices that seem simple enough (e.g., a transdermal patch) can be difficult for patients and lay caregivers to use correctly. Injection devices, inhalers, and transdermal patches have well known and documented usability issues. When used incorrectly, these combination products have the potential to harm patients or compromise their medical therapy.
In an effort to reduce the risks associated with use-related issues for combination products, the FDA and other regulatory bodies have turned to the discipline of human factors, including human factors testing.
Human factors validations studies differ from clinical trials in many respects. For example, a typical clinical trial may have a 1,000 participants or more, while a typical human factors study may have 60 or as few as 15. Clinical trials have statistical endpoints, while human factors studies are qualitative only. Arguably, the most meaningful difference between a phase 3 clinical and a human factors study is how each deals with potential problems participants may have with the drug delivery device – so called use errors or use-related hazards. To borrow from the ISO definition, a use error arises whenever anyone uses your device in a way that, as the manufacturer, you hadn’t intended. Some use errors have the potential to harm the patient or compromise their medical therapy. Phase 3 trials are tightly controlled, to try and minimize the influence of use errors. After-all, the focus of a phase 3 trial is on the safety and efficacy of the drug. Is the drug safe at these doses? To get the cleanest data possible, clinical studies are designed to minimize use errors. Patients and investigators are highly trained. Drug administration is monitored and controlled. Researchers want to minimize the potential for error in how the drug is given so as to minimize dosing errors.
Human factors validation studies are quite different. For a human factors study, the focus is on use errors. They are, in experimental design parlance, the dependent variable in a human factors study. These studies are designed as post-market simulations. Participants are trained only to the extent that they would be trained when the product is released commercially. Often this means patients and caregivers are left to learn how to use combination product devices on their own. Human factors studies put participants in realistic situations, including those where situational factors, such as poor lighting or fatigue might contribute to use errors. And participants are given use scenarios that reflect what might be expected to happen, in real life. The goal is to demonstrate that the device is designed such that the risk of use errors, including their potential for harm, have been minimized as much as possible. A successful human factors study is one in which few if any use errors are observed, and the risk associated with those errors, should they arise in actual use, post market, is as low as possible.
But while human factors studies and clinical studies differ in important ways, they are complementary, as both are required to establish the safety and efficacy of a combination product. Human factors testing is required to demonstrate that the devicecomponent can be used to deliver the drug safely and reliably, and clinical testing is required to establish that the drug component is safe and effective at recommended doses.