Your Drug Or Mine? Managing Drug Delivery Device Differentiation Hazards

Developing medical products that are safe, effective, and fit user needs is critical to ensuring success once they are on  the market. This not only applies to complex devices such as infusion pumps or pacemakers, but also to drug delivery devices like syringes and autoinjectors.  These seemingly simple drug delivery devices are frequently used in hospital or clinical environments, but they are also increasingly moving to use in the home. A poorly designed product can lead to poor outcomes in any environment, but due to factors such as lack of medical training and the novelty of using a drug delivery device, putting these products in the hands of lay users increases risk of misuse and confusion that can lead to serious medication errors.¹

Many pharmaceutical developers are aware of these issues, and they research, develop, and iterate the design of physical products to support safe and effective use.  This is expected, as the design of the injection device itself is a key factor in the ability of the end user to correctly administer medication. However, before a user even delivers the drug, they encounter other parts of the user interface, such as the instructions and packaging, which also need to be designed well to ensure correct product identification and selection. These “differentiation” tasks are critical because where and how devices are stored before use (e.g., in pharmacies, closets, or refrigerators; in or out of the carton; alongside other similar devices or different doses of the same drug) is not always predictable, and product mix-ups can occur if users mistakenly choose the wrong product due to poor product differentiation characteristics.²

To ensure that patients receive the correct product and medication dosage and to minimize the potential for medication error, drug delivery devices must be designed both to be differentiable from similar products and also to facilitate distinguishability between varying doses of the same medication. Subsequently, proper usability evaluation is needed to ensure that the risk of  injecting the wrong  medication or dose is reduced as much as possible for all end user populations. There is no universal design or evaluation method for every product, but there are important design and evaluation best practices that should be considered.  The following provides some design techniques and usability evaluation methods that can be used to enhance patient safety.

Design Considerations

The first point of user interaction is typically with the outer product carton or packaging. Designing with product differentiation in mind is critical for packaging because both clinical and home users may be in situations in which they need to select a product that is near other products. Just as pharmacies may keep many drugs and drug delivery devices stocked in close quarters, households may also keep a variety of self-administered drug products on-hand at any one time, or they may have several patients whose conditions require administration of multiple drugs or dosages at different times. If, for example, more than one drug delivery device is stored in a shared bathroom cabinet or on the same refrigerator shelf,  the probability of choosing the wrong device increases.

Though the carton and packaging design is a key consideration for differentiation, packages are sometimes discarded, leaving only the device (and on-device labeling) as the means of differentiation. For example, a nurse working in a clinical setting may remove autoinjectors from their packaging and store them upright in jars to reduce the amount of space needed in the refrigerator. If different drugs or doses are stored in the same jar, a hurried nurse could inadvertently select the wrong item, particularly in urgent situations with high levels of stress and distraction. For instances like these, distinguishing factors on the device are also important since many devices use the same “off-the-shelf” components commonly used across the drug delivery device industry.

When approaching design, developers must be thoughtful about what products could be stored together and how they might be stored in the effort to select the correct design elements for differentiation. Though it is not possible to predict all combinations of competitors’ drug delivery devices that may be stored similarly, some combinations are more likely than others. One of the most obvious pairings is newly formulated products with multiple doses. This is particularly important for products that at one time required a user to administer several injections for a single dose but the number of required injections has changed. This user may be more likely to select an unintended dose if the cartons or devices are very similar. Competitor products that treat the same condition should also be given special attention since home users may be switching brands and have excess stock. Additionally, pharmacies may have special considerations for differentiation based on where and how products are stored.

A variety of design elements can be used to maximize the users’ ability to differentiate between products, and these can often be applied to both packaging and on-device labeling. Some of the key design elements include:

• Color. Using different color schemes for both devices and cartons is one of the most obvious ways to make products differentiable. For this to be effective, use of color should be prominent and not simply applied to small parts of the interface, like the drug name. With salient use of color, a user is more likely to either immediately notice the difference or to recover from an incorrect selection. It is, however, advisable to use color as a redundant signal only, as this differentiating factor is less useful for people who are color blind or have other visual impairments.
• Shape and size. Though it may not be possible to change the fundamental design of a syringe or autoinjector to be distinctly different from competitor products, the size and the dimensions of the carton may be manipulated to promote differentiation. If a user detects an unexpected size, it could influence a double check that the correct product has been selected.
• Symbols. Cartons and labels use required regulatory symbols to indicate dosing. Designers often add branding and symbols to denote package contents and dosing frequency that may appear similar in size, shape, and placement. To a novice user, the combination of these symbols can be confusing and difficult to distinguish from one another. Designers can consider possibilities like increasing the size of symbols, incorporating contrast between shapes and background colors and using redundancy by displaying information that is critical to differentiation (e.g., medication dosage) in multiple places.
• Graphics and text. Depending on the size of the carton or label, graphics and text can also be used to further differentiate products. For example, syringes of varying volumes can use graphics on the carton that reflect differences in physical appearance of the device, and text can be added to emphasize the product differences. Inner packaging (e.g., trays, Tyvek lids) should also be clearly marked with data such as the drug product, manufacturer’s name, drug indication, new formulation, and type and number of devices. An important note with text, however, is that text changes are often overlooked by users when all other design elements are the same. Designers should be cautious of relying only on text as a reliable risk mitigation for incorrect product choice.

By using multiple differentiable elements in design, developers can give users every opportunity to make correct choices and deliver drugs as intended. However, this is not always easy with the competing priorities of various stakeholders. Some developers may have a marketing team that is more focused on aesthetic appeal rather than mitigating use errors. Larger companies that produce many drugs or devices may also have internal branding standards that are difficult to change. Thus, it becomes a balance of meeting these conflicting goals. The most important consideration from a usability (and regulatory) perspective is to mitigate use-related risk to the extent reasonable or possible, so if a product introduces the potential for safety-critical mix-ups, this should be one of the top considerations for any developer.

Evaluation Methods      

Developing products with adherence to good design principles to improve differentiability is a good starting point, but a formal evaluation process is critical to ensure the effectiveness of design decisions intended to facilitate safe and correct product choice. This can be done in several different ways, including stand-alone studies that focus on differentiation or larger-scale studies that simulate the full range of product use.

Both types of evaluations have advantages and disadvantages. While stand-alone studies allow human factors engineers to focus on gathering very specific data points without confounding variables, incorporating differentiation tasks into a more comprehensive usability assessment provides a better snapshot of the full context of use. If, for example, participants perform only differentiation tasks but are not asked to continue the typical task flow of using the product after they choose it, they will not have an opportunity to realize any potential product choice mistakes. Thus, recoverability will not be captured.

Whatever the study method, the key to capturing the most useful data is appropriate study design. Both types of studies should consider specific factors such as:

• Simulated use environment. Incorporating a robust and realistic simulated use environment is key. Environments for both pharmacies and homes are inherently variable and there is no single simulation that will accurately represent all potential environmental factors. However, elements such as space available for storage, inclusion of other items that might be nearby, and other factors such as lighting and noise that could affect the user’s ability to make a correct choice should be considered. It can be valuable to stress test product design by evaluating against the worst-case foreseeable environmental situation.
• Presentation order. When multiple differentiation tasks are tested in the same study, the order of presentation can influence study results. Typically, it makes sense to test the different components of the product in logical task order [i.e., first the carton, then the secondary packaging (if applicable), then the unpackaged device]. However, other realistic use cases should be considered as well. In the example of multiple autoinjectors stored in a jar in a clinical environment, this could be the first point of contact with the device for new nurses who may have never seen the packaging. Evaluating these unique storage scenarios may encourage developers to consider not only intended use, but unintended use as well.
• User instructions. Study design should also consider how to incorporate written prescriptions and pharmacy labels. The goal here is to ensure that the instructions given to the user regarding which product they should choose is sufficiently representative. If an unrealistic method is used, such as the study moderator verbally describing the correct product or handing the participant a sheet of paper with a detailed written description, study results may yield false positives. Users should only receive the minimum information that would be provided to them in a realistic situation. If incorporated correctly, this data can also provide insight into how information presentation can influence product selection.

Case Study

A recent case study of autoinjectors illustrates some of the considerations and best practice methods described above.

A home-use drug product, when initially launched, required two 50-mg autoinjectors for one full 100-mg dose. A new autoinjector with a 100-mg dose was developed, allowing patients to administer 100 mg with only one injector. Although the 50-mg and 100-mg autoinjectors were designed using different colors, the carton colors and drug concentration symbols were identical, other than the 50-mg or 100-mg designation within the symbol. Several studies were conducted to evaluate whether making these changes would impact user performance or perception of the product.

The first study involved a panel in which participants were asked to remove their prescribed dose of 100 mg from a refrigerator containing only 50-mg cartons. The behavior was established and reinforced during several visits over a three-week period. On week four, users were told a new form of the drug had been created, and they were asked to retrieve their 100-mg dose from a refrigerator containing both 50-mg and 100-mg cartons.  

Results demonstrated that many participants chose two 100-mg cartons, which could lead to a medication overdose if it occurred in a real-world situation. Follow-up interviews revealed that the identical carton colors and perceived similarity of the boxes (although they were slightly different sizes), as well as misunderstanding or overlooking of the drug concentration symbol, often influenced behavior. As a result of the study, distinct symbols with different shapes were developed for each carton, as well as two subtly different carton colors.

A second study was conducted to evaluate the new carton designs. Results of the study indicated improved results based on incorporation of distinct symbols, but color differentiation was a major factor in distinguishing the products. The case study demonstrates the importance of incorporating distinguishable design elements into similar products, particularly when they may be used by the same user population. Transitioning from one product or dosage form to another can pose unexpected issues, and usability evaluations are useful tools in the identification of these issues.

Conclusion

To ensure that patients receive the right product and medication dosage, developers of drug delivery devices must be thoughtful about differentiation in product design. Following good design principles is a start, but human factors considerations, such as the discrete characteristics of the users and use environments, are critical components. Follow-up evaluations are required to ensure that designs conform to user needs and expectations. As with other aspects of the human factors process, differentiation should be considered early and often in product development to ensure ample time to evaluate, iterate, and validate. 

References:

1. Meredith, S., Feldman, P. H., Frey, D., Hall, K., Arnold, K., Brown, N. J., & Ray, W. A. (2001, June). Possible medication errors in home healthcare patients. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11454109
2. Wollitz, A., III, C. H. B., Lyndon, A., Adelman, J. S., Abramson, E., & Weber, R. J. (n.d.). Medication Mix-Up: From Bad to Worse. Retrieved from https://psnet.ahrq.gov/web-mm/medication-mix-bad-worse

About The Authors:

Natalie Abts is the head of human factors engineering at Genentech, where she manages a team of engineers conducting human factors assessments for drug delivery devices. Before joining Genentech, she worked as a consultant providing advisement on human factors considerations for medical products. She has specialized experience in planning and executing both formative stage usability evaluations and validation studies for medical devices and combination products on the FDA approval pathway. Abts holds a master’s degree in industrial engineering, with a focus on human factors and ergonomics, from the University of Wisconsin, where she was mentored by Dr. Ben-Tzion Karsh.

Valerie Fenster is the director of insights and human factors at Kaleidoscope Innovations in Cincinnati, where she and her team ensure users remain the top consideration in device design solutions. Prior to Kaleidoscope, Fenster founded Amgen’s human factors engineering group and successfully guided many combination products and wearable devices through the human factors engineering process. At Abbott, formerly St. Jude Medical, she helped design and develop its remote care connectivity system for patients with pacemakers or defibrillators.

Leah Taylor is a biomedical engineer and human factors engineering consultant at Agilis Consulting, where she works with sponsors to design, conduct, and manage medical device and combination product human factors projects in support of global regulatory submissions. She has extensive experience helping sponsors clear drug products for clinical and non-clinical use. Prior to joining Agilis, her graduate studies included assessment of performance in the operating room and collaboration with cross-functional teams of surgeons, medical residents, nurses, and different types of medical technicians, followed by a research engineering position at Mayo Clinic.