Presentation
Follow-Up Analysis of How Design Differences in a CUHF Study Correspond With IFU Use
SessionPoster Session 1
DescriptionComparative analyses evaluate the user interfaces of a generic drug-device combination product against its reference listed drug (RLD) in order to identify design differences. Differences are categorized as "minor" if they do not affect how users perform a critical task that is necessary to use or administer the drug product. Differences between external design attributes that do impact critical tasks are considered “other design differences”. A comparative use human factors (CUHF) study assesses the potential impact of “other design differences” on safe and effective use by presenting existing RLD users with the proposed generic product and simulating drug administration. The hypothesis is that transfer of learning from the RLD to the generic will occur, and that minimizing “other design differences” will minimize negative transfer and maximize positive transfer.
Our previous research explored whether differences in the physical appearance of generic and RLD products were associated with differences in use of Instructions for Use (IFU), and whether IFU use was associated with a decreased risk in negative transfer between the RLD and generic product. Results showed that participants were more likely to refer to the generic IFU when more than five design differences (including “minor” and “other”) were identified between the RLD and generic product than when fewer than five differences were identified between the two. Participants who used the generic IFU experienced lower use event and use error rates when using the generic product compared to those who did not use the generic IFU (use error rates of 9% and 33%, and other use event rates of 11% and 22%, respectively).
The current research seeks to explore this previously-established relationship further. Additional data was collected in a sixth CUHF study when the U.S. Food and Drug Administration (FDA) commissioned a CUHF study to provide additional reference information to industry and to explore the application and challenges of the current Draft ANDA CUHF Study Guidance. Core Human Factors, Inc. conducted the research. The CUHF study compared a semi-automated pen injector, and a manual pen injector and focused on three “other” design differences of interest: dose selector extension, visibility of doses/markings, and injection mechanism.
IFU use data was also collected in a seventh CUHF study whose Sponsor and study product will remain blinded. Similarly to the FDA-commissioned study, three “other” differences were identified between the generic product and RLD pen injectors. In previous research, three differences were not enough to dramatically increase the rate of IFU use.
In the entire sample (composed of 91 RLD-experienced participants and 84 surrogate participants), 85% of participants did not refer to the RLD IFU, and 71% did not refer to the generic IFU. Subjects were asked why they chose to use or not use the IFU for both products. The most common reason cited (60% of recorded responses) for choosing not to read the IFU, whether for the RLD or the generic product, was perceived physical similarities between the pens. In short, because the pens looked the same, participants assumed they would function the same. Despite previous findings that showed use error rates decreasing when participants referred to the generic IFU, the data from these two additional CUHF studies showed very similar use error rates between those who did and did not use the generic IFU (use error rates of 9.8% and 9.7%, respectively).
This data replicates and extends previous research, suggesting that the more physically different a proposed generic device and an RLD look, the more participants will use the IFU. Therefore, when design differences between a generic and an RLD are unavoidable, manufacturers should consider making these differences more visually obvious to help cue users into reading the IFU.
Future research should extend and strengthen these findings by continuing to record and analyze participant reasoning for IFU use or non-use in CUHF studies. In addition, the data was collected from studies involving injection devices with minimal design differences from their corresponding RLD; thus, further analysis should be conducted to identify whether these outcomes are relevant for other types of combination products, such as inhalers, or generic combination products with many (i.e., 6 or more) design differences from their corresponding RLD.
This project was supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) through a contract 75F40123D00028/75F40123F19001. The presentation contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government.
Our previous research explored whether differences in the physical appearance of generic and RLD products were associated with differences in use of Instructions for Use (IFU), and whether IFU use was associated with a decreased risk in negative transfer between the RLD and generic product. Results showed that participants were more likely to refer to the generic IFU when more than five design differences (including “minor” and “other”) were identified between the RLD and generic product than when fewer than five differences were identified between the two. Participants who used the generic IFU experienced lower use event and use error rates when using the generic product compared to those who did not use the generic IFU (use error rates of 9% and 33%, and other use event rates of 11% and 22%, respectively).
The current research seeks to explore this previously-established relationship further. Additional data was collected in a sixth CUHF study when the U.S. Food and Drug Administration (FDA) commissioned a CUHF study to provide additional reference information to industry and to explore the application and challenges of the current Draft ANDA CUHF Study Guidance. Core Human Factors, Inc. conducted the research. The CUHF study compared a semi-automated pen injector, and a manual pen injector and focused on three “other” design differences of interest: dose selector extension, visibility of doses/markings, and injection mechanism.
IFU use data was also collected in a seventh CUHF study whose Sponsor and study product will remain blinded. Similarly to the FDA-commissioned study, three “other” differences were identified between the generic product and RLD pen injectors. In previous research, three differences were not enough to dramatically increase the rate of IFU use.
In the entire sample (composed of 91 RLD-experienced participants and 84 surrogate participants), 85% of participants did not refer to the RLD IFU, and 71% did not refer to the generic IFU. Subjects were asked why they chose to use or not use the IFU for both products. The most common reason cited (60% of recorded responses) for choosing not to read the IFU, whether for the RLD or the generic product, was perceived physical similarities between the pens. In short, because the pens looked the same, participants assumed they would function the same. Despite previous findings that showed use error rates decreasing when participants referred to the generic IFU, the data from these two additional CUHF studies showed very similar use error rates between those who did and did not use the generic IFU (use error rates of 9.8% and 9.7%, respectively).
This data replicates and extends previous research, suggesting that the more physically different a proposed generic device and an RLD look, the more participants will use the IFU. Therefore, when design differences between a generic and an RLD are unavoidable, manufacturers should consider making these differences more visually obvious to help cue users into reading the IFU.
Future research should extend and strengthen these findings by continuing to record and analyze participant reasoning for IFU use or non-use in CUHF studies. In addition, the data was collected from studies involving injection devices with minimal design differences from their corresponding RLD; thus, further analysis should be conducted to identify whether these outcomes are relevant for other types of combination products, such as inhalers, or generic combination products with many (i.e., 6 or more) design differences from their corresponding RLD.
This project was supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) through a contract 75F40123D00028/75F40123F19001. The presentation contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government.
Event Type
Poster Presentation
TimeMonday, March 234:45pm - 6:15pm EDT
LocationRhinelander Gallery
Medical and Drug Delivery Devices