Keywords
electronic health record - genetics - precision medicine
Background and Significance
Background and Significance
The process of incorporating genetic test results into the electronic health record
(EHR) is challenging and can be further complicated when conducted as part of a research
study where integration is required with unfamiliar clinical processes. While there
have been published reports about the purely technical challenges and solutions,[1]
[2]
[3]
[4] less has been published about unanticipated sociotechnological or practical communication
challenges involved in this process. Identifying and disseminating lessons learned
is a critical aspect of improving the design and implementation of health information
technology,[5] and may assist others embarking on genetic implementation projects to achieve a
smoother integration of genetic test results into the EHR.
In this case report, we describe our approach to return individual genetic research
results to patients and their physicians through the EHR as part of the third phase
of the National Human Genome Research Institute (NHGRI)-funded electronic Medical
Records and Genomics (eMERGE) consortium. We present unanticipated issues that arose
and suggest specific steps that other clinical sites take in future implementations
to avoid some of the issues encountered by our team. We also suggest potential future
design changes for subsequent versions of EHR systems to allow greater flexibility
in the return of genetic research results.
Methods
Within eMERGE 3, institutions were paired with one of two laboratories, Baylor College
of Medicine Human Genome Sequencing Center (HGSC) and Partners HealthCare Laboratory
for Molecular Medicine partnered with the Broad Institute (Partners). Blood samples
were tested using a set panel of 109 genes and 1,551 single-nucleotide variant (SNV)
sites and processed in a Clinical Laboratory Improvement Amendments (CLIA)-compliant
manner using a harmonized clinical sequencing pipeline at each laboratory.[6] The sequencing results from each laboratory were then returned to sites in the same
standard format as XML results with associated PDF interpretations.[7] Northwestern partnered with HGSC and established a secure download to receive results.
In a previous phase of eMERGE, we developed an Ancillary Genomics System (AGS),[2] which allowed us to take structured results from an external laboratory, perform
normalization and translation steps, and convert the results into a structured observation
sent to our Epic EHR (Epic Systems, Verona, Wisconsin, United States). We extended
the functionality of the AGS for eMERGE 3 to process the XML results provided by the
HGSC, store the specific variant(s) that were identified for a patient (if any were
found), and prepare a final result as a structured laboratory panel. One novel aspect
of our approach was that we were able to incorporate participant preferences around
the types of results they wanted to receive. For example, if a participant indicated
they did not wish to receive results related to cancer, and a pathogenic variant for
a cancer-related condition was identified, the AGS would suppress that finding altogether,
blinding the study team, patient, and clinical team from the result. A “break the
glass” option was built into the AGS to allow the study team to review the original
results, if necessary.
[Fig. 1] shows the high-level flow of data for the return of results. The results were reviewed
within the AGS by a genetic counselor on the study, and two formats were prepared:
a highly visual, formatted version used for printing and mailing, and a second plain
text representation used for placement in the EHR. When released to the EHR, the results
were transmitted as a Health Level Seven (HL7) v2 message. Because of the institutional
workflow used for provisioning and acquiring biological samples for the study, the
results are returned and displayed in the EHR but have no corresponding order record
associated with them. Multiple dates were associated with each result (i.e., date
of specimen collection and date processed by HGSC), but only one date would be displayed
in the EHR. We chose the date that the result was released to the EHR as the display
date, as a historical date may have caused the result to get lost with the acquisition
of more recent results. In addition, the HL7 message required an institutional physician
to be named as the requesting provider. We chose a coinvestigator who is a practicing
human geneticist and cardiologist, as she was established within the system, although
she did not routinely interact with patients receiving negative or noncardiac results.
These results were filed within the EHR alongside other laboratory results, which
allowed us to utilize existing EHR capabilities for their use and management. Our
results were configured to be automatically released to the patient portal (MyChart)
7 days after they were transmitted to Epic, and patients received a generic e-mail
indicating they had new results available in MyChart. The results accessed from MyChart,
because they were the plain text HL7 messages, had different formatting from the mailed
letter that the patient had received. The interpretation and recommendations, however,
were identical.
Fig. 1 Flow of genetic results from the sequencing center (Baylor) to Northwestern Medicine.
Multiple modalities were available for physicians and patients to access the results.
EHR, electronic health record.
Results
Enrollment for eMERGE 3 began at Northwestern on December 18, 2015, and was completed
on May 8, 2018. Genetic counselors returned “positive” results (i.e., pathogenic variants,
likely pathogenic variants, or risk alleles) in person or by phone between December
11, 2017 and June 26, 2019. Negative results were returned in the same timeframe via
letters mailed directly to participants (two individuals received results solely via
e-mail). The mean time between date of consent and return of results in-person, via
phone, or via mail was 526 days (SD = 85.7, range: 81–963 days). The electronic release
of results into the EHR took place July 9, 2019 through August 30, 2019.
Findings
Recognizing the lag between consent, initial return of results (in-person/phone/mail),
and electronic placement of results in the EHR, the study team attempted to communicate
with participants about the return of results process; an e-mail was sent to participants
1 week before EHR deposit to alert them they would be receiving a MyChart message
indicating genetic research results were available, and that these results were the
same as the results sent earlier by mail. Initially, investigators explored whether
it would be possible to customize the patient e-mail generated when test results are
placed in the EHR; however, because of local software and Health Insurance Portability
and Accountability Act (HIPAA) limitations, such customization was not possible. Therefore,
when research genetic results were deposited in the EHR, study participants were notified
with the standard generic e-mail indicating a new test result was available in MyChart.
Shortly after the release of genetic results into the EHR, multiple study participants
contacted our health system about “unexpected test results” appearing in MyChart;
many expressed concern that they may be being billed inappropriately for tests, or
were receiving someone else's medical information. No formal evaluation of the return
of results process was conducted, but in interactions with the study team, participants
reported initial confusion viewing an unfamiliar test name in MyChart (“eMERGE-Seq
Panel,” whereas they consented to “The Genetic Testing and Your Health Study”), as
well as an ordering physician who was unfamiliar to the most of patients. While not
explicitly stated, we also surmise confusion due to the fact that the plain text formatted
version of the report differed visually from their mailed copy. Had the participants
read the linked test results in detail, they would have received extensive information
about eMERGE 3, interpretation of the test results, and appropriate study contact
numbers to use in the event of any questions. At least three individuals reached out
to the ordering physician listed on the test result (either directly or via their
primary care doctor) and were appropriately directed to the eMERGE 3 study staff to
address their concerns. One individual contacted patient services, and then was directed
to risk management who began the process of removing the results (classified as a
misdirected laboratory report) from the EHR portal before contacting the ordering
physician. A second participant contacted patient services with a similar concern;
this concern was elevated to multiple offices within the health system over a 12-day
period before finally being brought to the attention of the ordering physician and
study staff. During this 12-day period, the health system decided to remove all similar
eMERGE 3 test results from the patient portal view, although they remained in the
EHR. The process to make the results available again in MyChart required internal
discussion with our health system's EHR team, approval from a clinical review committee,
and a process of approximately 8.5 weeks in which our local EHR team engaged the EHR
vendor to determine the appropriate way to rerelease the results.
Discussion
We believe these unexpected challenges in the return of research genetic results arose
because of four distinct issues as follows: (1) the length of time between enrollment,
result return to participants, and placement in the EHR; (2) inability to personalize
EHR e-mail messages announcing new test results in the EHR; (3) the limited space
for description of the test results in the EHR; and (4) the requirement to list a
specific ordering physician for all results including research results. As a result
of lessons learned from this experience, we have identified strategies to address
these issues that we recommend other institutions consider when implementing the placement
of genetic research results into the EHR.
Participant recall can vary (especially over time) about the details of participation
in research studies.[8]
[9] As we anticipate delays in future studies between enrollment of patients and the
return of results, we propose low-tech solutions that may be employed in the future
return of results. These solutions require no systemic changes in our EHR, as changes
to the EHR generally involve a great deal of time, resources, and multiple layers
of permissions, often not feasible to achieve in the time span and budget of a typical
research study. First, we propose that 48 hours before releasing results to a participant's
EHR, we will e-mail the participant a letter, explaining that they will receive a
generic e-mail from Northwestern Medicine about having a new test result available
for viewing and explain that this test result is from their participation in a specific
study. The letter should contain a screenshot of the generic results e-mail, and a
screenshot of how the study test results will appear in the participant's list of
test results in the portal, for further emphasis. Second, for future studies, we will
ask that any participants with a MyChart account provide the e-mail linked to their
MyChart account to study staff for purposes of study communication; we believe in
some cases our preparatory e-mail sent before return of eMERGE 3 results was not effective
because it went to a different e-mail account than the EHR notification e-mail. Third,
we propose using the word “RESEARCH” in the test name displayed for the study related
test results in the EHR portal, and have implemented this retrospectively for our
eMERGE 3 results. We believe this will better associate the result with this research
study in participants' minds, and we hope that this will avoid confusion for anyone
not receiving or not reading the preparatory e-mail.
In addition to the low-tech solutions described above, we recommend that EHR developers
consider adding flexibility to EHR software to permit customization in the return
of research results. One solution would be to create an e-mail template for test result
return that reads “You have a new RESEARCH test result. Please logon to the EHR portal
for more information.” A second solution would be to permit the listing of a research
study (or a doctor on behalf of a research study) under “ordering physician” in the
EHR.
Finally, this experience has allowed us to strengthen ties between research and clinical
operations at our organization. Recently, a clinical Research & Development (R&D)
team was developed that specifically liaises between research and clinical teams which
will be beneficial in future projects.
Conclusion
While returning research genetic test results to the EHR at our institution, we ran
into unanticipated challenges due to participants confusing research test results
with misdirected medical tests. As a result of this experience, we will preface future
research result return to the EHR with a preparatory e-mail, including screenshots.
We also suggest small changes that EHR developers can make in subsequent software
versions to allow slightly more customization in the return of research results.
Clinical Relevance Statement
Clinical Relevance Statement
The integration of genetic test results into the EHR, especially when originating
from a research study, requires careful planning to avoid unintentional confusion.
We identify lessons learned from a recent study and propose solutions for implementers
and EHR vendors.
