Presenting Genomic Sequencing Information in Primary Care

Meron Mezgebe, Mercer University College of Pharmacy

Clinical exome and genome sequencing has been shown to provide advantages in molecular diagnosing to patients with rare genetic events and new mutations. Results presented in whole genome sequencing (WGS) provide more complex results than simpler gene- or gene panel-based testing. [1] With the limited access to genetic professionals, non-geneticist physicians and primary care physicians (PCPs) can present genomic information to patients. A study found that physicians appear underprepared, and perceived that they lack sufficient knowledge and confidence to incorporate genomic testing and pharmacogenetics testing into practice. [2] Furthermore, a qualitative analysis found PCPs to be concerned about their general genomic knowledge. [3]

Evaluation of highly heritable conditions [1], prenatal screening [4], and cancer treatment [5] through genome sequencing has been shown to be beneficial. However, the risk of anxiety and unnecessary medical costs might outweigh the benefits of sequencing for healthy individuals. [6]

The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients [7]
Design Pilot, randomized trial; N= 100
Objective To describe the effect on clinical care and outcomes of adding whole-genome sequencing (WGS) to standardized family history (FH) assessment in primary care
Study Groups FH alone (FH group; n= 50); FH in combination with an interpreted WGS report (FH + WGS group; n= 50)
Methods Individual email outreach and presentations were used to recruit a convenience sample of nine primary care physicians (PCPs) from one academic network of outpatient practices. Approximately 10 patients were recruited per PCP. Before enrolling patients, the PCP participants had a brief educational course on the genome report.

Patients 40-65 years old, with no history of cardiovascular disease or diabetes mellitus and deemed generally health by their PCP were eligible for inclusion.

At the baseline visit, all patients reported FH using a modified version of the U.S. Surgeon Generals My Family Health Portrait Web Tool and had a sham blood draw (FH group) or a blood draw for WGS (FH + WGS group). The PCP received the pedigree resulting from the FH web tool for all patients, and the interpreted WGS report for the FH + WGS group.

Duration Six months
Primary Outcome Measure Effect in health care use, anxiety, depression, perceived health and health behaviors when WGS is added to FH
Baseline Characteristics
Variable FH group

(n = 50)

FH + WGS group

(n = 50)

Mean age, years (range) 55 (41-68) 55 (41-66)
Female, n (%) 30 (60) 28 (56)
Median Charlson comorbidity score (range) 0 (0-1) 0 (0-0)
White, n (%) 44 (88) 45 (90)
Annual household income, n (%)
< $99, 999 16 (35) 8 (16)
$100,000 – $149,000 8 (17) 7 (14)
³$150,000 22 (48) 34 (69)
Highest educational attainment, n (%)
High school or lower 5 (10) 1 (2)
Some college or associate’s degree 6 (12) 2 (4)
College graduate 21 (42) 14 (28)
Master’s or doctoral degree 18 (36) 33 (66)
Results
Health Care Use and Costs 6 Months After PCP-Patient Discussion of FH with or without WGS Results
Variable FH group

(n = 50)

FH+WGS group

(n=50)

Total Per Patient Total Per Patient
Laboratory tests, n 186 3.72 271 5.42
Imaging tests, n 44 0.88 58 1.16
Cardiac tests, n 7 0.14 20 0.40
PCP visits, n 37 0.74 35 0.70
Non-PCP visits, n 108 2.16 124 2.48
Mean costs per patient, $ 1,142 1,490
Median costs per patient, $ (range) 548 (0-10,704) 694 (0-15,026)
Patient-Reported Outcomes at Baseline and 6 Months After PCP-Patient Discussions of FH With or Without WGS Results
Variable FH group

(n = 50)

FH+WGS group

(n=50)

Baseline 6 months Baseline 6 months
Perceived Health, n (%)
Poor 0 (0) 0 (0) 0 (0) 1 (2)
Fair 2 (4) 1 (2) 2 (4) 0 (0)
Good 8 (16) 10 (23) 4 (8) 7 (14)
Very Good 24 (48) 23 (52) 21 (42) 24 (49)
Excellent 16 (32) 10 (23) 23 (46) 17 (35)
Health behavior, n (%)
Exercise 7 (16) 13 (27)
Diet 9 (20) 16 (33)
Supplements 4 (9) 2 (4)
Medications 4 (9) 6 (12)
Other 3 (7) 1 (2)
Any change 13 (30) 20 (41)
Adverse Events n/a
Study Author Conclusions WGS may prompt additional clinical actions without evidence of short-term distress or clinical utility. Furthermore, some PCPs can manage the results appropriately.

This study used a standardized design, validated instruments, and electronic health record data to assess medical care. The limitations include a small sample size with limited ancestral, geographic and socioeconomic diversity. This research supports the inclusion of WGS in primary care visits for healthy individuals by PCPs.

References

[1] Yang Y, Muzny DM, Xia F, et al. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA. 2014 Nov 12;312(18):1870-9.

[2] Selkirk CG, Weissman SM, Anderson A, Hulick PJ. Physicians’ preparedness for integration of genomic and pharmacogenetic testing into practice within a major healthcare system. Genet Test Mol Biomarkers. 2013 Mar;17(3):219-25.

[3] Christensen KD, Vassy JL, Jamal L et al. Are physicians prepared for whole genome sequencing? A qualitative analysis. Clin Genet. 2016 Feb;89(2):228-34.

[4] Beaudet AL. Using fetal cells for prenatal diagnosis: History and recent progress. Am J Med Genet C Semin Med Genet. 2016 Jun;172(2):123-7.

[5] Gagan J, Van Allen EM. Next-generation sequencing to guide cancer therapy. Genome Med. 2015 Jul 29;7(1):80. doi: 10.1186/s13073-015-0203-x. eCollection 2015.

[6] Kohane IS, Hsing M, Kong SW. Taxonomizing, sizing, and overcoming the incidentalome. Genet Med. 2012 Apr;14(4):399-404.

[7] Vassy JL, Christensen KD, Schonman EF, et al. The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients: A Pilot Randomized Trial. Ann Intern Med. 2017 Jun 27.

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