Engaging Patients in Precision Oncology: Development and Usability of a Web-Based Patient-Facing Genomic Sequencing Report

Abstract

PURPOSE

Evidence-based somatic and germline sequencing has transformed cancer care and improves patient outcomes. However, patients’ low genetic literacy and misunderstanding of their own genomic results poses a threat to the realization of precision oncology. To optimize patient genomic comprehension, we developed a Web-based, patient-directed, genomic sequencing education and return-of-results tool, HOPE-Genomics.

METHODS

The HOPE-Genomics prototype included somatic and germline sequencing results, embedded multimedia genomic education, and interactive features (eg, request for genetic counseling). Between January and April 2018, we elicited feedback on tool usability and comprehensiveness through participant surveys, 4 focus groups of patients with cancer and their family members, and 3 provider focus groups (comprising 8 patients, 5 family members, and 19 providers).

RESULTS

We identified themes in patient/family tool-related responses, including the desire to view a patient-friendly report, a desire to receive multiple types of genomic information (eg, prognostic and uncertain), high acceptability of report content, and interest in tool-enabled access to genetic counseling. Major themes from the clinician focus groups included believing the tool could help patients formulate questions and facilitate patients’ communication of results to family members. However, there were diverse responses from all participants in terms of tool implementation (ie, timing and nature of report release). Some participants preferred report release before meeting with the provider, and others preferred it during the appointment. Additionally, some clinicians were concerned about providing prognostic and treatment information through the tool.

CONCLUSION

There was high acceptability and interest from patients, family members, and providers in a patient-directed genomics report. Future work will determine whether direct-to-patient reporting of genomic results improves patient knowledge, care engagement, and compliance with genomically guided interventions.

INTRODUCTION

Somatic and germline panel sequencing has transformed cancer care. With testing, providers can identify patients who will likely respond to targeted therapy and those who have an inherited susceptibility to cancer. Multiple factors, including approval by the Centers for Medicare and Medicaid Services for somatic next-generation sequencing for advanced cancers, the growing number of US Food and Drug Administration–approved targeted therapies, and expanding indications for germline testing, will likely increase genomic test adoption.¹ Moreover, with commercial exome/genome sequencing now available, the number and types of genomic findings relevant to patient care will increase.

Despite this dramatic progress, patient misunderstanding of genomic information presents a major barrier to achieving precision medicine. Knowledge about genetics among the general public is limited.^2-4 Additionally, many patients undergoing cancer genomic testing fail to comprehend basic testing information.^5-9 Furthermore, our prior work suggests that tested patients with cancer often misunderstand the different implications of somatic and germline testing.¹⁰ Optimizing patient knowledge is essential, because there is a growing body of evidence demonstrating that increasing patients’ knowledge improves care. Greater patient knowledge is associated with cancer screening uptake, health-promoting behavior, medication adherence, completion of chemotherapy, and survival.^11-16

To eliminate gaps in patients’ knowledge of their own disease characteristics (ie, somatic or germline results) and the implications of cancer genomic testing, we created a dynamic Web-based patient-facing somatic and germline genomic report, “Helping Oncology Patients Explore Genomics” (HOPE-Genomics). To develop a highly patient-centered tool, we conducted patient/family and clinician focus groups to assess tool usability, an initial step in the tool development process.¹⁷ Qualitative methods offer an effective way to approach this task, allowing for the elicitation of open-ended responses and enabling the observation of user interaction with the tool.^18-21 Our ultimate goal for this line of research is to determine whether patients who use HOPE-Genomics have better knowledge of their disease, more effectively communicate with providers, and are more compliant with genomically guided therapy.

CONTEXT

• Key Objective

• Can a patient-facing, Web-based genomic education and return-of-results tool (HOPE-Genomics) be used to improve patients’ understanding of genomic test results, close genetic knowledge gaps, and improve the delivery of precision cancer care?

• Knowledge Generated

• We engaged patients, family members, and providers in a qualitative tool development study. Patients, family members, and providers were enthusiastic about the tool and felt that it could facilitate communication about, and improve patients’ understanding of, genomic information.

• Relevance

• The HOPE-Genomics tool is an e-health tool that holds promise to promote greater patient and family member engagement with genomic information and precision cancer care.

METHODS

Sample Selection

Adult patients with solid tumors at City of Hope (COH) were eligible to participate if they had somatic or germline genomic testing, spoke English, had an Eastern Cooperative Oncology Group status of ≤ 2, and could provide consent. Because genomic testing often affects family members, patients were offered the opportunity to invite 1 adult family member to participate. Clinicians who ordered somatic/germline genomic testing were recruited by convenience sampling. All study activities were approved by the COH Institutional Review Board.

The HOPE-Genomics Tool

The HOPE-Genomics tool was designed to be a “patient-friendly” version of a sequencing laboratory report with embedded genomic education. Focus groups interacted with a tool “mock-up” prototype on a hypothetical patient. This prototype consisted of 12 Web pages and included interactive features, visual cues to aid in comprehension (eg, result types consistently color coded), and hyperlinks to access external information (Table 1; mock-up images in Data Supplement; prototype animation at https://youtu.be/L2sDV7OuTp8). Unknown results (ie, variants of uncertain significance [VUS]) were reported separately from results with clinical utility. We used a figure to “bin” genomic results into 3 types: actionable cancer, additional, and unknown (ie, “actionability dial”). Prognostic information was “locked,” ensuring that disclosure of prognostic information only occurred after patient opt-in. To model the types of results that would be returned to patients, the focus group tool included clinical and sequencing data from a hypothetical patient with lung cancer.

TABLE 1.

Components of HOPE-Genomics

Focus Groups

We conducted four 90-minute focus groups with patients and family members (in person) and 3 with providers (Web conferencing; Table 2). Focus group participants viewed the prototype with data from the hypothetical lung cancer patient. Sessions were recorded and transcribed. Patient/family participants (1) were asked about their experiences with genomic testing, (2) were observed using the tool, (3) were asked to provide feedback on the prototype animation, (4) were guided through the tool, and (5) discussed tool use, clarity, and content. After the focus group, participants completed a survey about the usability of HOPE-Genomics (Fig 1). The provider focus group was similar, but providers were asked to review the tool before the focus group for efficiency.

TABLE 2.

Participant Characteristics

FIG 1.

Methods and workflow of focus groups.

Analysis

We used Atlas.ti version 8 to analyze qualitative content to examine participants’ perceptions of the tool content, format, and interactive elements.^22,23 Codes were both deductive or (defined a priori based on focus group questions and tool elements) and inductive (based on new topics found through the focus groups).²⁴ Inductive code development continued until we named all new topics (one form of data saturation).^25,26

RESULTS

Eight patients and 5 family members participated in 4 patient focus groups. Nineteen providers participated in 3 focus groups. In the following sections, we describe the views expressed by patient/family participants, followed by provider participants. The Discussion notes changes to the tool after feedback.

General Comprehension and Tool Usability

Patient/family participants were enthusiastic about the tool. Participants said the information was straightforward and the layout was easy to follow. They believed the tool would help them better understand their cancer and treatment. One participant remarked that the tool could serve as a “second opinion” from a more impartial source. Another participant noted, “If you have a little knowledge, then you know what to ask.” Participants requested some changes for clarity (eg, simplifying text, more white space). All the patients liked the hyperlinks (“I would follow them everywhere”).

Providers liked the layout of the tool and said the report simplified a lot of information (eg, the tool “was very clear and simple to use; easier to read than a 40-page report”). They also felt the tool would help patients “ask more insightful questions” and help patients understand differences between somatic and germline testing. Many commented that the tool, specifically the animation, would help with pretest counseling. Some expressed concerns about the copious text in the tool, whereas others worried that some content was oversimplified and might limit treatment implication comprehension.

Variant Reporting

Patient/family participants found the binning of results and the pages containing the somatic and germline reports to be clear and easy to read. Patient/family assessments of the “actionability” visual was mixed; some thought it needed more explanation.

The providers had mixed reactions to result binning. Some thought the bins were useful, whereas others worried they would confuse patients. They thought the terms “actionable” and “additional” were confusing and suggested that the tool distinguish what was actionable related to cancer. Furthermore, they suggested that the tool include functionality, allowing providers to add comments about treatment options. Providers acknowledged that explaining VUS was most difficult, but agreed that it should be included. They liked describing VUS results as “unknown” and thought they should be separate from actionable variants.

Visuals/Animation

Patient/family participants liked the animation content and length, stating that it “reminds me of Biology 101.” They found it easy to understand and liked the analogy used to explain genetic alterations (eg, genes are similar to a recipe). Several participants suggested that the narration be slowed. All participants wanted to receive various genetic data, including VUS. Patient participants thought that VUS results were “good to have just in case they figure it out in the future.”

Providers responded favorably to the animation, noting that it illustrated important concepts well. They requested more content distinguishing germline from somatic results. Some suggested using a pedigree or a family graphic for germline findings.

Prognostic Information

Patient/family participants had mixed reactions about the tool, including prognostic information. Some said they wanted “the facts,” whereas others did not. Some participants said that prognostic language should convey a sense of “hope.” Others thought the prognostic information should only be revealed during a doctor’s visit. Patients liked the locking mechanism for prognostic information because it required patients to take an extra step before revealing sensitive information.

Providers expressed concern about sharing prognostic information through the tool because it was “too nuanced.” They believed that providers should “sign off” to release prognostic information to patients. There was concern about who should be able to unlock this feature (patient v family member), and providers suggested that both they and the patient should sign in to unlock this feature together. One provider wanted to review prognostic information with patients before allowing them to unlock it to avoid “emergency calls” from patients.

Use of the Tool

Some patient/family participants noted that they would want to view the tool with their provider so that they could explain the report. Other patients believed that they would want to see the tool prior to meeting with their doctor so that they could formulate questions, reporting, “[the tool] gives you the big picture, and then you can discuss specifics with your doctor.” Others suggested that patients should be offered a choice to view the tool either before or after a provider visit. All participants said that they would like to access the tool at home to review it after a clinic visit and refer to it over time. When asked if they would like to have the tool designed as an application (app) for a smartphone, they felt that the content was too complex for a smartphone. All envisioned using the tool at home on their computers.

Many providers expressed concern about the timing of tool access. They believed it was important for providers to review the tool with the patients; however, many were concerned that time would limit the amount of information to cover during a visit. Some thought that they would have difficulty implementing the tool in a busy oncology setting without having a separate appointment to review results. Some had concerns about patients accessing the tool before reviewing the information with a provider and suggested that providers control when the results are released to patients.

Communication With Care Team

Patient/family participants reacted positively to the interactive features that allowed them to e-mail the care team; however, they wanted reassurance that the e-mail would be responded to, not “lost in cyberspace someplace.” They also wanted to know that the message would result in a response from their own provider. Regarding the functionality to request genetic counseling, some patients said they would use the link, whereas others expressed concerns that patients might not know what a genetic counselor does.

Although some providers said the electronic communication option could help patients ask questions and clarify information, they also raised concerns. They thought the link should be confined to simple questions and should not elicit questions too complex for e-mail exchange. There were concerns that patients might inappropriately ask genetic counselors treatment-related or other oncology-related questions and suggested a question triage function. They also wanted to prevent patients from hearing conflicting information from multiple providers. Furthermore, cancer-treating providers wanted to control the provision of genomically guided treatment information; as one oncologist said, “I’ll handle the cancer cell part.” However, they noted that they would be happy to “have someone get in touch with a genetic counselor” for germline findings.

Patient participants thought the tool might be helpful for sharing information with their family, friends, and other patients with cancer. One commented, “This is the greatest part of the report” because “[the tool] would make it easier for them if their kids [had] access just to look at it.” Some liked the fact that the tool could help them communicate the potential risks for family but suggested that the language be clarified to explain that germline findings do not confirm that family members had or would develop cancer. Although many would share the report with family, others said that they would first explain to family what they learned, particularly “if it’s a bad report and heredity is involved.”

Providers also liked the tool’s ability to facilitate sharing. They expressed the need for stronger language and emphasis about how germline findings could affect family.

Post–Focus Group Survey

The patient post–focus group survey results revealed that 100% had a high interest in “seeing a patient-focused Web-based report of their results,” and 88% had high levels of satisfaction with HOPE-Genomics. Although only 68% of patients said they would be interested in learning more about cancer genomics before the focus group, 100% reported they were interested in a tool after the focus group. Patient and family participants thought the tool was helpful (88%-100%) and easy to use (75%-100%). Ninety-four percent of providers reported interest in providing the tool to their patients.

DISCUSSION

As genomic testing becomes ubiquitous in cancer, mechanisms ensuring that patients understand their test results and their implications are urgently needed. In response, we developed a patient-facing genomic report to optimize patient knowledge and improve outcomes. We demonstrated that patients with cancer, family members, and providers are enthusiastic about patient-facing genomics reports and view the tool as beneficial.

Other experts have advocated for patient-friendly genetic reports and have developed e-health tools to engage patients and research participants with genomic information. Haga et al²⁷ argued that access to electronic health record (EHR) portals provides patients with information, including molecular testing reports, but that these data are elusive to patients. They proposed several avenues for improving patients’ comprehension of genetic test reports, including revising the report in a patient-friendly way. In addition, Tabor et al^28,29 have advocated that individuals engage in “self-guided management” of sequencing results and have developed a platform, My46, enabling research participants to self-manage test results for Mendelian diseases. Finally, Williams et al^30,31 at Geisinger developed a patient-facing genomic report, GenomeCOMPASS, and tested its use in a pediatric genetic conditions setting. Parents who viewed GenomeCOMPASS had improved communication with providers and nonhealth professionals (eg, educators), and reported that use was associated with high parent engagement and satisfaction.

Participants found the HOPE-Genomics tool highly appealing and useable. In line with prior work on patient-directed genomic decision aids, our participants thought the tool would facilitate patient engagement by helping patients formulate questions for providers.³² Interestingly, there was some diversity across patients/family members and providers in terms of tool delivery. Although there was not a clear consensus on whether the tool would be best used before, during, or after a provider appointment, patients generally responded that they would want to use the tool (preferably at home) and that it could help them better understand their cancer. Multiple delivery methods could be considered. In the Geisinger study, test results were first disclosed to parents during a clinic visit and, subsequently, results were sent to parents via the EHR patient portal. Consistent with the suggestions from some providers in our study, others have shown that releasing results to providers first, with a delay in the release of results to patients, may be an acceptable model. A genomic return-of-results study found that delaying the release of results to participants by 5-7 days gave providers more control of the results.³³ Alternately, some patients may prefer that results be sent to them and to providers concurrently. This model of delivery may help patients ask questions more effectively and prepare them for their provider visits. Additional work is needed to evaluate the different patient-directed return-of-results models.

Based on stakeholder feedback, we modified aspects of HOPE-Genomics and the animation (Fig 2: Table 3; beta prototype of application, https://sketch.cloud/s/bM11Z/a/p5Dn0G/play, final animation in English, https://youtu.be/_eJ6Y-R5Lqs; Data Supplement). However, we opted not to modify the tool in all cases. For example, we elected to include the opt-in mechanism for prognostic information but qualify the language around prognostic information. Specifically, we noted that genomic information has a limited impact on prognosis relative to other data (eg, stage). Given how quickly the clinical trial landscape changes and that multiple providers were concerned about including specific trial information in the tool, we decided to report only general information about clinical trials. Furthermore, we are developing HOPE-Genomics as an open-source Substitutable Medical Applications, Reusable Technologies (SMART) on the Fast Healthcare Interoperability Resources (FHIR) app (Health Level Seven International, Ann Arbor, MI), rather than a Web site. We think that using an interoperable platform that integrates with multiple EHRs will support greater tool integration into clinical care systems. Given the fact that HOPE-Genomics contains patient-level data, a question is whether it will fall to laboratories to create both clinician-directed and patient-facing reports. Patient-facing reports, whether Web-based or print, may improve genomic comprehension. We have designed HOPE-Genomics to be distributed to laboratories or health systems. Given the efforts to include structured genomic data into EHRs, automatic data population should be increasingly possible. Going forward, we will continue to work with laboratories and information technology groups to ensure scalability.

FIG 2.

HOPE-Genomics tool screenshots. (A) Report overview. (B) Summary of somatic findings. (C) Interactive function to e-mail report to family and friends.

TABLE 3.

HOPE-Genomic Adaptations

In addition to supplementing the patient-directed genomic reporting literature, our study aligns with prior work on patients’ preferences and attitudes. Consistent with several prior studies, patients in our study wanted to receive all types of genomic information.^34-36 Our work also provides data on direct-to-patient reporting of prognostic information. Some participants wanted all information, and others thought that prognostic information should only be provided by clinicians. This finding is supported by other work that describes a breadth of preferences for prognostic information among patients with cancer.^37,38 Providers also expressed concern about providing patients with prognostic information and wanted to have control over the release of such data. In response to these concerns, we plan to include future functionality that allows providers to release prognostic information to patients through the tool.

Although our study provides rich qualitative data on participants’ tool-related opinions, the sample size and qualitative approach limits generalizability. Patient and family member participants were recruited from an academic medical center and may not represent patients from other settings. Additionally, patients/family responded to hypothetical patient reports and may respond differently to personal health information. Although we note some differences in patient and provider reactions to the tool, we caution that these differences may not encompass all potential differences between patients and providers. The study was not designed to fully assess differences between patients and providers. The results offer next-step suggestions to improve usability and clarity. Finally, we cannot comment on the acceptability of the tool for non-English speakers; we plan to translate the tool into Spanish and Mandarin.

Our findings suggest high acceptability and usability of our HOPE-Genomics prototype. As the demand for genomic testing and patient engagement increases in oncology, a transition from relying on conventional in-person methods of returning genomic results to a hybrid approach, with greater patient-guided management of genomic information, is anticipated. HOPE-Genomics offers a scalable solution to facilitate patient engagement in cancer care. In future work, we will examine methods for optimizing tool implementation into clinical workflow and evaluate whether direct-to-patient return of genomic information improves patient outcomes.

AUTHOR CONTRIBUTIONS

Conception and design: Sarah McGraw, Adem Albayrak, Gil Alterovitz, Catherine Del Vecchio Fitz, Rachel A. Freedman, Stacy W. Gray, Ilana Solomon, Eliezer VanAllen, Melanie Davies, Lynette M. Sholl

Administrative support: Jenny Shen

Provision of study materials or patients: Sumanta Pal, Joanne Mortimer, Marwan Fakih, Karen L. Reckamp, Yuan Yuan

Collection and assembly of data: Ilana Solomon, Sarah McGraw, Jenny Shen, Lisa N. Lopez, Joanne Mortimer, Marwan Fakih, Sumanta Pal, Karen L. Reckamp, Yuan Yuan, Stacy W. Gray

Data analysis and interpretation: Ilana Solomon, Lisa Lopez, Sarah McGraw, Jenny Shen, Gil Alterovitz, Rachel A. Freedman, Lynette M. Sholl, Eliezer Van Allen, Stacy W. Gray

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Adem Albayrak

Employment: Health Catalyst

Stock and Other Ownership Interests: Health Catalyst

Honoraria: BC Platforms

Research Funding: Merck

Melanie Davies

Employment: InterSystems Corporation

Catherine Del Vecchio Fitz

Employment: Health Catalyst

Rachel A. Freedman

Research Funding: Puma Biotechnology (Inst), Eisai (Inst)

Lynette M. Sholl

Honoraria: AstraZeneca

Consulting or Advisory Role: Loxo Oncology, Foghorn Therapeutics

Research Funding: Genentech

Eliezer Van Allen

Stock and Other Ownership Interests: Syapse, Tango Therapeutics, Genome Medical, Microsoft, Ervaxx

Consulting or Advisory Role: Syapse, Roche, Third Rock Ventures, Takeda, Novartis, Genome Medical, InVitae, Illumina, Tango Therapeutics, Ervaxx

Speakers' Bureau: Illumina

Research Funding: Bristol-Myers Squibb, Novartis

Patents, Royalties, Other Intellectual Property: Patent on discovery of retained intron as source of cancer neoantigens (Inst), patent on discovery of chromatin regulators as biomarkers of response to cancer immunotherapy (Inst), patent on clinical interpretation algorithms using cancer molecular data (Inst)

Travel, Accommodations, Expenses: Genentech

Joanne Mortimer

Honoraria: Novartis

Consulting or Advisory Role: Novartis, Karyopharm, Puma

Marwan Fakih

Consulting or Advisory Role: Amgen, Array BioPharma, Genentech

Speakers' Bureau: Amgen, Taiho Pharmaceutical

Research Funding: Novartis (Inst), Amgen (Inst), AstraZeneca (Inst)

Sumanta Pal

Consulting or Advisory Role: Genentech, Aveo, Eisai, Roche, Pfizer, Novartis, Exelixis, Ipsen, BMS, Astellas

Consulting or Advisory Role: Pfizer, Novartis, Aveo, Myriad Pharmaceuticals, Genentech, Exelixis, Bristol-Myers Squibb, Astellas Pharma, Ipsen, Eisai

Research Funding: Medivation

Karen L. Reckamp

Consulting or Advisory Role: Amgen, AstraZeneca, Boehringer Ingelheim, Calithera Biosciences, Euclises, Genentech, Guardant Health, Precision Health Economics, Seattle Genetics, Takeda, Tesaro

Research Funding: AbbVie (Inst), ACEA Biosciences (Inst), Adaptimmune (Inst), Boehringer Ingelheim (Inst), Bristol Myers Squibb (Inst), Genentech (Inst), GlaxoSmithKline (Inst), Guardant Health (Inst), Janssen Oncology (Inst), Loxo Oncology (Inst), Molecular Partners (Inst), Seattle Genetics (Inst), Spectrum (Inst), Takeda (Inst), Xcovery (Inst), Zeno Pharmaceuticals (Inst)

Yuan Yuan

Consulting or Advisory Role: Novartis, Pfizer, Eisai, Genentech, Immunomedics

Speakers' Bureau: Eisai, Genentech, Eisai, Pfizer, Merck, Puma Biotechnology, Novartis, Genentech

Expert Testimony: Novartis

Stacy W. Gray

Stock and Other Ownership Interests: Magenta Therapeutics (I)

Consulting or Advisory Role: Grail Industries, Magenta Therapeutics (I)

Expert Testimony: Riley and Associates

No other potential conflicts of interest were reported.