Development of inhaler devices is a complex process and any development needs to address a number of issues. Firstly, does the inhaler confuse the patients? Can patients recall the correct handling of each inhaler they use? How large is the risk that different inhaler devices pose to public health? In order to address these questions, human factors studies are conducted.
Human factors (HF) studies examine the interaction of people and technology ensuring the safety and effectiveness of that interaction in order to improve human/device compatibility. That includes the user interface, instructions, and training programs to avoid use error. Use errors can occur when the device is not being used as intended or the design features are less than optimal.
Therefore, HF testing, analysis, and validation helps to identify and eliminate use errors by informing appropriate mitigation strategies, which ensures the device design provides the optimum use of the drug through an inhaled device.
HF studies of drugs, intended for self-administration, assess the ability of the user to properly prepare and administer the drug at the prescribed dose. They also determine the user’s ability to mis-dose, under-dose or deliver a dose that assures safe disposal. What’s more, the user should be able to distinguish the product from other similar products.
Inhaled products can be considered complex when compared to an oral product, such as a tablet where the desired therapeutic outcome is achieved by the patient simply swallowing it. This contrasts with the inhalation product where it is necessary for the device to deliver the product to the patient in a consistent manner, which is a function of the formulation, the device design as well as the patient’s ability to use the device correctly. To achieve this, patients may be required to follow potentially complex handling instructions that may include a dose loading step, performing several device operations in a predefined order followed by the correct inhalation maneuver.
In practice, many patients do not achieve this. According to literature, error rates are significant, with rates of 74.6 percent for metered dose inhalers (MDIs) and 6.8–43.2 percent for three dry powder inhalers (DPIs) cited in one study and 24 percent for MDIs, and 17–24 percent for three DPIs in another study.
It is therefore important that the needs of the patient and, if appropriate, the caregiver are carefully considered during the initial development of an inhalation product so as to ensure the development of a robust and intuitive product. Similarly, this needs to be considered during the life cycle of the product when changes to the product are required.
HF studies that may require consideration for inhaler devices may include perception of the color and shape of an inhaler, the ability to perform handling steps, acceptability of forces needed to actuate the inhaler, perception of noise, mechanical robustness, confirmation of the successful inhalation of drugs, and the amount of drug left.
HF studies should evaluate interface in the absence of training. Pack inserts prepared should guide lay users (patients/caregivers) for self-administration and health care professionals for providing appropriate training.
Such studies should be designed appropriately to consider how frequently the training occurs as time required for learning inhaler use.
Additionally, knowledge assessments should be part of formal HF studies on inhaler devices. Some of the critical tasks that should be evaluated include, identifying the number of doses left, instructions pertaining to the expiry of the product, and understanding the labeling instructions for use.
HF studies are designed to capture the errors, challenges and associated risks for end users. Studies should be appropriately designed to include all possible end users. What’s more, they need to be population-based, requiring participation from larger groups to give conclusive inputs.
Timely completion of such studies can become challenging if the targeted end user population is not pre-identified. While unrealistic expectations and timeliness can further add delay to study completion, it is thought that standardizing the documentation requirements can help generate clean and timely data.
Furthermore, involving the same training staff at individual sites across the study can impact upon performance outcomes from participants. Changes in trainers can also lead to failure to record critical errors, higher dropouts, and participants making frequent errors, thereby increasing the time to learn.
Patient motivation can be challenging in the case of inhaler devices under investigation having a placebo. It becomes more challenging in studies involving healthy volunteers to participate and keep them motivated. Studies that are too long can lead to higher dropout rates and a shorter study will not be able to capture errors, especially in inhaler devices required for chronic use.
In developing countries, gender representation and equal contribution from expected end users is always a challenge, which can only be addressed with proper planning.
Information sheets that have complex and technical language without images/pictures can lead to improper learning of the inhalation device. However, including images on information sheets that illustrates how the device should be used is advantageous for the end user. Be sure to obtain feedback from end users as this is critically important to making inhalation devices user-friendly.
While participants tend to receive more detailed training on the use of the inhaler, this may not be representative of a real life situation where patients often receive their medication without specific explanation from caregivers, and are not regularly monitored. Simulating a real life situation in a controlled study is difficult.
Therefore, HF studies should be adequately monitored in order to identify training decays right at the beginning and apply mitigation strategies at the appropriate time.
HF studies are making headway in the clinical trial space with a steady increase in new drug applications involving the use of drugs and devices. Regulators require such studies to be appropriately designed to show that the patients and/or caregivers can use inhaler devices.
Across the industry there are various guidelines on what is required in human factors studies. While the regulatory guidance document released by US FDA in 2011 does provide insight, there are still many unanswered queries due to availability of limited studies.
Clinical Trial Leader – India Operations
PHOTO CREDIT: NIAID