This study met institutional criteria for Quality Improvement and thus was not subject to review by the Institutional Review Board. The study was conducted from January 2018 to March 2021.

We used a hybrid type 1 implementation science framework and a collaborative user-centered design process to develop an interactive website intended to facilitate communication between familial hypercholesterolemia probands and their family members. The design was guided by US Department of Health and Human Services Guidelines [17] and International Organization for Standardization Quality Standards for Usability [18]—guidelines that address web design and evaluation as well as user experience optimization for knowledge dissemination. Probands can share their familial hypercholesterolemia diagnosis with relatives via the letter-to-family-member email template. Email allows for faster communication than that using traditional postal mail; the email contains information on the relative likelihood of family members also having familial hypercholesterolemia (given that it is passed on as an autosomal dominant trait) and a recommendation to get tested. The proband can include information about the specific pathogenic variant that was found in their genetic test report, to facilitate family member genetic testing. The website also enables probands to build a family tree utilizing a pedigree tool (AboutMe, Mayo Clinic) to include first-degree relatives and document family members who may be at increased risk for familial hypercholesterolemia. Once a pedigree has been built, it can be accessed each time the user logs on. The web-based tool also has a section, called Learn, with educational modules on familial hypercholesterolemia–related topics: (1) What is Familial Hypercholesterolemia, (2) Familial Hypercholesterolemia Considerations in Children, (3) Genetics, (4) Genetic Testing Frequently Asked Questions, (5) Treatment, and (6) Additional Resources. Through these modules, users (probands or family members) can expand their knowledge on familial hypercholesterolemia and access informative patient education materials and links to other educational tools and websites.

In its current form, FH Family Share will be available on the Mayo Clinic intranet and the internet; all aspects of the web-based tool will be available for public access, with the exception of the pedigree tool which requires the use of a Mayo Clinic patient username and password, to ensure security of protected health information.

The initial proof-of-concept prototype of the web-based tool was built by an external vendor using open-source PHP framework (Yii, version 2.0; Take The Wind). The graphical user interface was designed in HTML5 and CSS3 in conjunction with Jquery, connected to the MySQL database. It was developed as a responsive design for multiple screen sizes. The initial prototype underwent cognitive walkthrough—a technique applied to evaluate the usability of an app or system in the early stages of design. The cognitive walkthrough was conducted by 3 usability experts to assess exploratory learning—how well an end user can navigate the app for the first time without prior training [19-21]. The usability experts conducted the cognitive walkthrough at the Mayo Clinic Usability Laboratory and participated in 11 tasks that a first-time user was likely to undertake (Multimedia Appendix 1). The session lasted 2 hours and was observed by 5 study team members. Observers gave feedback on any difficulties they noted the experts encounter while navigating the website. The experts and observers discussed the feedback after each task, and points were documented on how to further improve the tool (Multimedia Appendix 2).

We evaluated user experience, satisfaction, and interface design of FH Family Share with usability testing that was informed by quality standards.[18]. A 1-year pilot testing program was launched in 2 phases (Rochester campus, Mayo Clinic), with genetic counselors as key stakeholders of the web-based tool. Purposive sampling was applied to recruit genetic counselors with varying clinical backgrounds, to obtain information-rich relevant insights on user experience and interface design. Genetic counselors were invited to participate in the usability testing sessions by email. A target sample size of 5 to 8 participants was established based on prior usability studies [22-25], in which approximately 80% to 85% of usability-related concerns were identified from the first 8 participants. We conducted 9 usability testing sessions in phase 1, and we conducted 7 usability testing sessions in phase 2.

Each usability session was 1-hour long; sessions were audiorecorded using a handheld recorder and transcribed using transcription software (version 2018; Otter.ai). Sessions were conducted by a user experience expert (AM) from an external company, to reduce any institutional or workflow driven biases. Study team members (HB and JHG) were also present during each session to observe and take notes. Participating genetic counselors were asked to assess educational content and interface design, as well as to provide insights on how FH Family Share would be integrated with their usual clinical workflows.

We used a digital platform (version 2011; InVisionApp Inc) to build an interactive clickable prototype of FH Family Share and to conduct user experience testing. The website prototype and 2 case scenarios (Multimedia Appendix 3) were presented to each genetic counselor; each participant was asked to verbalize their thoughts while navigating the prototype [26].

To facilitate feedback, genetic counselors were asked open-ended questions: “How do you feel each of the elements [on the website] might help you in your role?” “What do you think you will find when you click into this page?” “How might you share this website with a patient?” “What are some strengths and weaknesses [of the website]?” “Clicking that print button, what would you imagine would print out?”

Each round of user testing informed iterative refinements and modifications to the features of the prototype. User testing rounds were conducted until saturation was reached (ie, no new feedback was obtained) (Figure 1).

At the end of each usability testing session in phase 1, genetic counselors completed a 7-item satisfaction survey. Based on feedback from genetic counselors in phase 1, the survey was refined, and 4 additional questions were added (Multimedia Appendix 4); therefore, at the end of phase 2, genetic counselors completed an 11-item satisfaction survey.

To obtain insights from end users, we conducted usability testing sessions over a 3-month period with patients with familial hypercholesterolemia. Patients were recruited using convenience sampling with a target sample size of 8 to 10 participants [22-25]. Patients with a confirmed pathogenic/likely pathogenic genetic variant for familial hypercholesterolemia and who previously participated in familial hypercholesterolemia–related research studies at Mayo Clinic were eligible for inclusion. Patients with a confirmed genetic diagnosis of familial hypercholesterolemia were selected to participate in this study as they had either gone through the process of cascade testing or were currently doing so and could therefore share important feedback and insights on the usefulness and relevance of FH Family Share in facilitating cascade testing. Patients received a request to participate in the study via 1 of 3 methods: the institutional patient portal, a telephone call, or an email. If patients indicated that they were interested in participating, they were contacted by phone to schedule the usability testing session.

Due to the COVID-19 pandemic, usability testing sessions were conducted using videoconferencing software (Zoom Video Communications Inc). Each session lasted 1 hour. Both audio and video from sessions were recorded; audiorecordings were transcribed using Office Word (version 2021; Microsoft Inc). Each session was conducted by a user experience expert (AM); study team members (HB, AA, and JHG) were also present during each session. Patients were emailed a link to access the clickable prototype of the web-based tool and were asked to think aloud when navigating the prototype. Patients did not receive any compensation for participating in the study.

At the start of each session, patients were prompted to describe their individual diagnostic journeys for familial hypercholesterolemia and provide insights on their family structure: “When were you diagnosed with FH (provide your age at the time of diagnosis or the calendar year)?” “Tell me about your experience receiving your FH diagnosis (mode and duration of communication, formats it was received in, and any patient education material you may have been given at the time).” “How did the way in which you received your diagnosis make you feel?” “What resources, if any, did you use to look up more information about FH?” “How did you find these resources (did you reach out to providers, search the internet etc)?” “How many first-degree relatives (parents, siblings, children) do you have?” “Did you share any of the information pertaining to your diagnosis with family members (if so, in what context or format)?” “If you did not share your diagnosis with family members, were there any barriers that prevented you from doing so?” “How many of your family members, that you know of, have completed testing for FH?” At the end of each session, patients were asked to complete an 11-item survey using web-based software (QualtricsXM) (Multimedia Appendix 5).

Key themes that emerged from the cognitive walkthrough were design, format, navigation, terminology, instructions and learnability (Multimedia Appendix 6).

Given the ubiquitous use of electronic health records, the internet, and smartphones, digital tools can serve a central role in the delivery and implementation of genomic medicine [10,14,28]. Familial hypercholesterolemia is underdiagnosed, and there is limited uptake of cascade testing in the United States [3,29,30]. FH Family Share was designed to facilitate communication between familial hypercholesterolemia probands and their relatives, and to increase the uptake of cascade testing. It was iteratively refined through usability testing with genetic counselors and patients with familial hypercholesterolemia. The target sample size for participant recruitment was achieved in both phases of the pilot testing program, and based on study team consensus, additional participants were not recruited as feedback saturation was reached and majority of the usability issues had been identified.

Current guidelines [31,32] for familial hypercholesterolemia screening recommend the identification of a proband and cascade testing of family members, starting with first-degree relatives. Cascade testing for familial hypercholesterolemia has been identified as the most cost-effective strategy for identifying new familial hypercholesterolemia cases [33,34]. In traditional cascade testing, a proband sends a templated letter, using postal mail, to inform relatives of their diagnosis and to encourage them to get tested; however, there is no way to determine whether relatives receive the letter and seek testing for familial hypercholesterolemia. This approach to cascade testing has low uptake in the United States, in part due to the inability of health care providers to directly contact family members and the burden placed on probands to undertake this task, and in part due to the lack of an established national program with cascade testing that is centralized, coordinated, and aligned with local and regional needs and resources [35,36]. Although countries with nationalized health care systems have been able to implement centralized cascade testing programs, the United States is limited by several barriers. Well-designed usable digital tools can be used to bridge the gap in communication and increase uptake of cascade testing.

Usability testing is an integral part of the field of human–computer interaction and is used to evaluate interactive health apps to ensure effective design and development strategies, with a particular focus on the concept of user-centered design [37-41]. Genetic counselors and patients with familial hypercholesterolemia are the intended end users of the web-based tool, and feedback from these groups informed iterative refinements to FH Family Share after each phase of testing. Our extensive usability testing with genetic counselors revealed FH Family Share to be a resource worth returning to, with easy to find and easy to understand content that would likely improve patient follow-up care. Genetic counselors indicated that the tool was something they could share on their computer screens with patients during pre- and post-genetic testing counseling sessions. Genetic counselors also highlighted that the template email would assist patients in sharing their familial hypercholesterolemia diagnosis with relatives but that it needed to include sections in which either they (the genetic counselors) or the patients could insert gene and variant names, as this would be useful to family members when scheduling testing. Orlando et al [42,43] employed a similar process to develop a family health history and decision support tool, in which usability testing conducted with 10 genetic counselors resulted in a number of adaptations to the final tool, such as changes to interface design, navigation, and content, prior to its deployment.

Usability feedback from patients with familial hypercholesterolemia revealed that the majority of patients found content easy to understand, agreed that the tool could help them share their familial hypercholesterolemia diagnosis with family members, and was a resource worth returning to. A novel insight gained from patient usability testing was the importance of understanding the motivation for patients seeking genetic testing for familial hypercholesterolemia. Patients revealed that concern for their children, grandchildren, and family planning were the primary motivators. They highlighted that FH Family Share should contain an education module focused on considerations for children and family planning. This feedback led to the addition of a new topic module. Similar feedback was obtained in a study [44] conducted to identify motivators and barriers to cascade testing in families with familial hypercholesterolemia. Study participants indicated that they informed relatives of their risk of familial hypercholesterolemia to protect them from heart disease and allow them to make appropriate lifestyle changes [44].

FH Family Share will be implemented at all Mayo Clinic sites and the Mayo Clinic Health System and will also be available for public access on the internet. Once deployed, the tool’s content and resources will be updated as new knowledge emerges. The impact and metrics of FH Family Share will be assessed using a pilot implementation study. The findings described herein could be used to create similar digital apps for other genomic disorders.

Usability testing sessions were limited to genetic counselors and patients with familial hypercholesterolemia—input from family members of patients with familial hypercholesterolemia would be useful in ensuring effective implementation of the tool in nonclinical settings. Additionally, FH Family Share was not integrated with the electronic health record to enable ease of access in remote or underserved communities which may have different electronic health record systems in place. In some instances, feedback obtained from genetic counselors and patients with familial hypercholesterolemia varied on the same topic, for instance, most patients indicated the need for more illustrations on FH Family Share to increase engagement and interest, while genetic counselors suggested limiting the use of illustrations unless they served a specific purpose; feedback from both groups was harmonized by adding curated illustrations to increase patient engagement. Due to the COVID-19 pandemic, usability testing sessions conducted with patients were virtual and nonverbal cues could not be observed; however, screen sharing along with open-ended questions allowed us to obtain sufficient feedback which was often consistent across participants. The sample sizes for genetic counselors and patients with familial hypercholesterolemia were modest; however, the numbers were in line with those of previous usability studies [22-25] and allowed for thematic saturation to be reached.

FH Family Share can be used by probands to communicate their familial hypercholesterolemia diagnosis with family members, encouraging them to seek testing for familial hypercholesterolemia. Such a tool has the potential to increase uptake of cascade testing thereby allowing for earlier detection and treatment of familial hypercholesterolemia.