This single-center, qualitative usability evaluation consisted of a usability scenario simulation and an in-depth interview. HCPs specialized in hemophilia care from the Indiana Hemophilia & Thrombosis Center (Indianapolis, IN) were invited via email. Nurse practitioners, (pediatric) hematologists, physician assistants, pharmacists, and nurses were considered for inclusion. Exclusion criteria included lack of hematological experience, inability to communicate in English, or unwillingness to provide informed consent. The study aimed to include approximately 6 participants with diverse professional backgrounds.

The study adhered to the Declaration of Helsinki. The study protocol was approved by the Ascension St Vincent Hospital Institutional Review Board (study ID RIN20240003) and registered on ClinicalTrials.gov (NCT06369740). All participants were provided written information outlining the study procedures, including video recordings, and provided written informed consent. Video recordings were accessible only to authorized personnel, including members of the study team, auditors, and quality assurance and quality control reviewers. The recordings will be securely stored for 15 years. Participants provided explicit consent for their research data—including video recordings—to be accessed by the study sponsor, who is also the developer of the EnzySystem. Participants were provided with US $50 compensation for their participation in this study when participation occurred outside their regular working hours.

The results are reported in accordance with the COREQ (Consolidated Criteria for Reporting Qualitative Studies; Checklist 1) [22].

The EnzySystem is being developed by Enzyre B.V. as a novel platform for near-patient multiparameter testing. The EnzySystem HemA is designed to simultaneously measure FVIII activity levels and thrombin generation from 100 μL of whole blood within 1 hour. It consists of three integrated modules: (1) a disease-specific disposable EnzyCard (Figure 1A); (2) platform-specific software, the EnzyApp, that guides users through user tasks and displays results on a standard computer; and (3) the EnzyPad, a reusable processor into which the EnzyCard is inserted (Figure 1B).

The EnzyCard contains several elements: the external housing called the envelope (Figure 1A1) and an injection-molded microfluidic cartridge (Figure 1A2). Users only handle the envelope, which features a connector compatible with a standard 2.7 mL vacutainer for citrated blood. Upon insertion of a blood tube, blood is transferred into the EnzyCard by pressing a built-in syringe with an accompanying plastic plug. Inside the EnzyCard, plasma is separated from other blood components by a plasma separation membrane and enters the microfluidic cartridge. Capillary force drives plasma through the microfluidic channels, mixing it with buffer and dried-in reagents. Ultimately, the sample enters sixteen 110 nL detection chambers, where a chemiluminescent reaction occurs. Photons are generated proportionally to the analyte of interest and are quantified in real time by a sensor printed circuit board containing 16 single-photon avalanche diode optical sensors positioned above the detection chambers. The data are processed and sent via a USB cable to a computer for immediate display and interpretation.

In this study, a nonfunctional mockup of the EnzySystem HemA was used, consisting of the following components:

A nonfunctional mockup was used to enable efficient usability evaluation while avoiding known nonusability errors associated with the current prototype. Early usability evaluation with nonfunctional mockups is a well-established approach, supported by the Food and Drug Administration’s human factors guidance [24]. Blood collection was excluded from the scenario, as this is a standard clinical procedure and the focus of the study was on platform-specific tasks.

Two included participants were deliberately tasked to perform the usability scenario without using the QRI to evaluate the intuitiveness of the EnzySystem HemA. They were purposefully selected based on their prior exposure to the platform in a focus group session on its potential use.

In addition to the EnzySystem HemA components, a standard 2.7-mL citrated vacutainer filled with water mixed with red dye, disposable nitrile hand gloves, and a standard medical waste container were used.

All included participants attended an individual usability testing session on August 22 or 23, 2024, in a meeting room at the Indiana Hemophilia & Thrombosis Center. Each session lasted 1 hour and was moderated by 1 member of the research team (WT), assisted by the first author (ABA).

Participants were seated at a conference table with the testing materials placed before them. Baseline characteristics were gathered with a structured interview. The moderator outlined the study goals and the components available for use during the scenario, following a predetermined script (Multimedia Appendix 3). Participants were then instructed to perform an FVIII activity assay and to clean up afterward. Participants assigned to not use the QRI were instructed to open the EnzyApp as a first step. Participants were encouraged to talk out loud [25] and were informed that the waiting times during preheating (normally 3 min) and running the assay (normally up to 1 hour) were shortened. The actual waiting times were disclosed at the respective steps.

Following the scenario, a semistructured interview using a preconstructed interview guide (Multimedia Appendix 3) was conducted to assess the perceived acceptability, usability, effectiveness, and usefulness of the EnzySystem HemA.

The scenario and interview guides were constructed by the usability engineer in the research team (WT) based on medical input from the first author (AB). Both were refined based on 2 pilot sessions performed at the Radboudumc (Nijmegen, the Netherlands) with a nurse practitioner and a physician, both working in the field of hemophilia.

A total of 110 HCPs were invited to participate. Twelve (11%) responded, of whom 5 (42%) were excluded: 1 was unable to attend physically, and 4 had professions that did not meet the inclusion criteria. Seven (58%) HCP participants were included in the study. Baseline characteristics are depicted in Table 1. None of the participants had used the platform before. However, 3 (43%) participated in a prior EnzySystem study involving focus group discussions on current coagulation testing and potential use cases.

An overview of the success rate per task is depicted in Figure 2. Of the 7 participants, 5 (71%) performed the assay as intended, including HCP6 who did not use the QRI. The mean time to obtain a test result was 359 (SD 148) seconds, including two 20-second waiting periods for warming up and running the assay. Two (29%) HCPs were unable to perform the test as intended. One (14%) applied insufficient force when inserting the blood tube, expressing uncertainty on how much force could be applied before damaging the tube. The other, who performed the test without using the QRI, needed support to turn on the EnzyPad and insert the blood tube. This participant did not use the plastic plug to depress the syringe and transfer the blood sample into the microfluidic cartridge. Three (43%) other participants had difficulties completing this last task, hesitating over where to insert the plastic plug.

Only 2 of the 7 (29%) participants disposed of the EnzyCard as intended. Contrary to the instructions, 4 (57%) participants moved around with the used EnzyCard to discard it, and 4 (57%) removed the blood tube from the EnzyCard before disposal. The combined size of the EnzyCard and the blood tube constituted the main reason for difficulties with disposal, as together they did not fit into a standard US medical waste container.

Five interrelated themes were generated from the postscenario interviews: functional the way it is, utility through faster results and increased access, potential for patient engagement, financial investment and return, and ensuring accuracy (Table 2).

In this first usability study of the EnzySystem HemA with HCPs, the overall usability and perceived utility of the platform were high. While the platform was considered usable, 2 participants were unable to use the EnzySystem as intended due to critical issues with the user interface. In addition, there is a uniform need to improve the disposability of the EnzyCard, as most participants did not dispose of it as intended. The platform’s perceived benefits over existing systems mitigate the concerns about its shortcomings. However, evidence demonstrating the platform’s reliability and accuracy is needed before implementation.

Studies assessing human factor aspects of point-of-care in vitro diagnostics are scarce [27]. To our knowledge, no previous studies have evaluated the usability of products comparable to the EnzySystem HemA. However, research on attitudes toward POCT in general provides relevant insights. Notably, concerns about accuracy are not unique to the EnzySystem HemA. In a systematic review of primary care providers’ attitudes, uncertainty about accuracy was a key limitation of POCT [28]. Checking POCT results with conventional methods, as was suggested in this study, is also applicable to POCT in general [29]. Quinn et al [30] found that concerns about accuracy, data management, costs, and quality assurance were key barriers to POCT adoption in hospital settings, consistent with the findings of this study. However, regarding the EnzySystem HemA, 2 of the 7 (29%) participants suggested that implementation might reduce factor product use and related costs, aligning with broader discussions on the benefits of personalized medicine in hemophilia A [31-33].

The main envisioned benefits of the EnzySystem HemA also align with those described for POCT in general: shorter time to initiate treatment [29,34-37], improved communication with patients and patient engagement [29,34-37], and improved access to testing [35-37]. However, as no POCT is available for hemophilia A care at this time, the potential implications of these advantages, especially in this field, were described for the first time in this study.

Compared to most POCT platforms, a limitation of the current EnzySystem HemA is the need for a venipuncture, which limits the potential applicability for patient self-testing, as suggested in this study. An EnzySystem version compatible with a capillary blood collection system is planned for future development, but its usability for patients will require dedicated evaluation.

An experiential, inductive thematic analysis informed by a constructionist epistemology was used. Rather than seeking reproducible or externally generalizable results, the aim of qualitative research is to gain an in-depth, contextual understanding of participants’ experiences and the factors underlying the perceived acceptability and usability of the EnzySystem. This approach recognizes that both the participants’ perspectives and the researchers’ interpretations are influenced by subjective perspectives and that meaning is co-constructed throughout the research process.

To enhance the credibility of the analysis, quotes from participants were added to support the claims made. A codebook was maintained and is provided as supplementary material to communicate interpretative decisions and enhance methodological transparency (Multimedia Appendix 4). In addition, codes related to improvements of the EnzySystem Hem A were presented along with their frequency of mention (Table 3). While such counting techniques are uncommon in reflective thematic analysis—as frequency does not necessarily reflect the perceived importance of an issue [38]—they were included to highlight which improvements were most widely desired. Ultimately, however, the credibility of our findings rests on their ability to convincingly represent the participants’ experiences with the EnzySystem HemA and its perceived utility.

An inductive coding strategy was chosen, as this was the first usability evaluation of the platform, and no comparable platforms are available. However, the themes generated in this study relate to those commonly found in usability frameworks. For example, facets of Morville’s Usability Honeycomb [39], such as usability, usefulness, and credibility, relate strongly to themes 1, 2, and 5, respectively. As such, the generated themes do not exist in a theoretical vacuum but relate to the existing theoretical frameworks.

In reflective thematic analysis, it is acknowledged that researchers inevitably bring their own norms, values, and interpretive frameworks into the processes of data collection, analysis, and reporting [40]. Reflexivity in this study focused on the first author (AB)—who performed the coding and theme generation and assisted during the use scenarios—and the human factor engineer who moderated the scenarios (WT).

AB is a White Dutch male, a medical resident in internal medicine, and a PhD candidate at the Radboud University Medical Center (Radboudumc) in Nijmegen. He is employed by the developer of the EnzySystem during his PhD trajectory but holds no financial interests in the platform’s development. He received formal training in qualitative research, and his work focuses on personalized care in hemophilia A. He has no formal background in engineering or technological development.

WT is a White Dutch male senior product designer employed by Panton (Deventer, the Netherlands), a company specializing in medical innovation design. He has extensive experience in medical innovations, although this was his first project in the field of hemophilia A.

Both AB and WT had no prior relationship with any of the participants.

The current findings demonstrate high acceptance across HCPs for the EnzySystem HemA, despite some critical limitations of the user interface. To evaluate the effectiveness of potential modifications and ensure the platform’s suitability for broader implementation, future usability evaluations should be conducted in realistic use environments and include participants from diverse care facilities. The universal demand among participants for faster results and improved testing to monitor treatment in people with hemophilia A underscores the urgency of these next steps, along with the need to assess the platform’s usability for people with hemophilia A.