Implementing Primary Care Mediated Population Genetic Screening Within an Integrated Health System

Sean P. David; Henry M. Dunnenberger; Raabiah Ali; Adam Matsil; Amy A. Lemke; Lavisha Singh; Anjali Zimmer; Peter J. Hulick

doi:10.3122/jabfm.2021.04.200381

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Figure 1.
Context for Supporting PCP Engagement in Population Genetic Screening. Figure Legend: The NorthShore Center for Personalized Medicine DNA10K program consisted of multiple components. (a) patient educational video and consent via the NorthShore Connect (NSC) patient portal, (b) PCP electronic clinical decision support and electronic health record (EHR) order, (c) access to a NorthShore lab for phlebotomy, (d) Color Genomics, Inc. genetic testing using a 74 gene next-generation sequencing panel, (e) discrete reporting of results available in the EHR, (f) coordination of results with PCP health maintenance visits, (g) automated patient messaging about next steps, (h) access to genetic counseling, (i) return of results on the patient portal, and (j) clinical follow-up with PCP and specialists. The NorthShore Institutional Review Board approved this study as an exempt quality improvement evaluation. Abbreviations: PCP, primary care physician; EHR, electronic health record.

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Table 1.

DNA10K Primary Care Physician-Mediated Genetic Screening Results^*

Variable	Overall No./Total (%) or Mean ± SD or Median (IQR)	FM No./Total (%) or Median (IQR)	IM No./Total (%) or Median (IQR)	OBGYN No./Total (%) or Median (IQR)	P value^{^†}
Clinical Demographics
PCPs	116	28	72	16	…
Patients contacted	49413	10640	32220	6553	…
Tests consented	14063/49419 (28.5%)	3143/10640 (29.5%)	8956/32220 (27.8%)	1964/6553 (30.0%)	.13
Orders placed	10933/14063 (77.7%)	2416/3143 (76.9%)	6920/8956 (77.3%)	1597/1964 (81.3%)	.60
Test completed	9797/10933 (89.6%)	2190/2416 (90.6%)	6255/6920 (90.4%)	1352/1597 (84.7%)	.24
Patient Demographics
Age	49.6 ± 6.4	46.5 ± 4.9	52.3 ± 4.9	40.5 ± 3.3	<.0001^{^‡,^§,^‖, ^¶}
Female	6464/9797 (66.0%)	1270/2190 (58.0%)	3844/6255 (61.5%)	1350/1352 (99.9%)	.80^**
African American	272/9797 (2.8%)	100/2190 (4.6%)	108/6255 (1.7%)	64/1352 (4.7%)	.02^{^‡}
American Indian/Alaskan Native	22/9797 (0.22%)	6/2190 (0.27%)	14/6255 (0.22%)	2/1352 (0.15%)	.86
Asian	679/9797 (6.9%)	234/2190 (10.7%)	368/6255 (5.8%)	77/1352 (5.7%)	.04^{^‖}
White	6528/9797 (66.6%)	1229/2190 (56.1%)	4424/6255 (70.7%)	875/1352 (64.7%)	.04^{^§}
Hispanic/Latino	461/9797 (4.7%)	145/2190 (6.6%)	218/6255 (3.5%)	98/1352 (7.2%)	.01^{^§,^¶}
Pacific Islander/Hawaiian Native	6/9797 (0.06%)	0/2190 (0%)	6/6255 (0.1%)	0/1352 (0%)	.20
Declined/Other	1829/9797 (18.7%)	476/2190 (21.7%)	1117/6255 (17.9%)	236/1352 (17.5%)	.69
Test Results
Cancer and cardiovascular disease variants^{^††}	813/9797 (8.3%)	177/2190 (8.1%)	537/6255 (8.6%)	99/1352 (7.3%)	…
Tier 1 pathogenic variants (HBOC, Lynch syndrome, and FH)^{^‡‡}	182/9797 (1.9%)	42/2190 (1.9%)	114/6255 (1.8%)	26/1352 (1.9%)	…
HBOC	116/9797 (1.2%)	27/2190 (1.2%)	73/6255 (1.2%)	16/1352 (1.2%)	…
Lynch Syndrome	38/9797 (0.39%)	3/2190 (0.14%)	28/6255 (0.45%)	7/1352 (0.52%)	…
FH	29/9797 (0.30%)	12/2190 (0.55%)	13/6255 (0.21%)	4/1352 (0.30%)	…
Non-Tier 1 pathogenic variants	631/9797 (6.4%)	135/2190 (6.2%)	423/6255 (6.8%)	73/1352 (5.4%)	…
Pharmacogenomic variants^{^§§}	9607/9797 (98.1%)	2154/2190 (98.4%)	6128/6255 (98.0%)	1325/1352 (98.0%)	…
Actionable pharmacogenomic variants	9599/9607 (99.9%)	2150/2154 (99.8%)	6124/6128 (99.9%)	1325/1325 (100%)	…
Test Results per PCP
Patients who completed test per PCP	68.5 (25.5 to 126)	62.5 (33 to 120)	66 (22.5 to 138)	75 (40 to 118.2)	…
Cancer and cardiovascular disease variants per PCP^{^‖‖}	7.5 (4.9 to 10.2)	6.8 (3.7 to 9.1)	7.8 (5.6 to 10.8)	7.4 (5.5 to 8.8)	.40
Tier 1 pathogenic variants per PCP (HBOC, Lynch syndrome, & FH)^{^¶}	1.4 (0 to 2.5)	1.5 (0 to 2.8)	1.4 (0 to 2.5)	1.3 (0 to 2.4)	.97
HBOC per PCP	0.8 (0 to 1.5)	0.7 (0 to 1.5)	0.7 (0 to 1.5)	1.0 (0 to 1.8)	.95
Lynch syndrome per PCP	0 (0 to 0.4)	0 (0)	0 (0)	0 (0 to 1)	.12
FH per PCP	0 (0)	0 (0)	0 (0)	0 (0-0.2)	.08
Non-Tier 1 pathogenic variants per PCP	5.8 (3.5 to 7.5)	5.0 (2.1 to 7.0)	6.1 (3.8 to 8.6)	5.8 (3.7-6.8)	.28
Actionable pharmacogenomic variants per PCP^{^††}	98.3(97.2 to 100)	98.6(97.5 to 100)	98.2(96.7 to 99.6)	97.9(97.3 to 100)	.39

Abbreviations: FH, familial hypercholesterolemia; FM, family medicine; HBOC, hereditary breast and ovarian cancer; IM, internal medicine; IQR, interquartile range; OBGYN, obstetrics/gynecology; PCP, primary care physician; SD, standard deviation.
↵* Results refer to patients who were contacted, agreed to consent to testing or did not agree to testing, and who had orders placed by PCPs before a scheduled annual physical and genetic tests performed and resulted between April 1, 2019, and January 22, 2020.
↵† P values are for the Kruskal-Wallis test unless otherwise indicated; P < .05.
↵‡ ANOVA with posthoc Tukey HSD Test.
↵§ FM versus IM, P < .05.
↵‖ IM versus OBGYN, P < .05.
↵¶ OBGYN versus FM, P < .05.
↵** Wilcoxon Rank Sum Test comparing females across FM and IM only.
↵† The Color Genomics, Inc. next generation sequencing panel includes the following genes:
Cancer risk (30 genes): APC, ATM, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A (p14ARF, p16INK4a), CHEK2, EPCAM, GREM1, MITF, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, POLD1, POLE, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53.
Cardiovascular disease risk (30 genes): ACTA2, ACTC1, APOB, COL3A1, DSC2, DSG2, DSP, FBN1, GLA, KCNH2, KCNQ1, LDLR, LMNA, MYBPC3, MYH7, MYH11, MYL2, MYL3, PCSK9, PKP2, PRKAG2, RYR2, SCN5A, SMAD3, TGFBR1, TGFBR2, TMEM43, TNNI3, TNNT2, TPM1.
↵‡‡ HBOC variants: BRCA1, BRCA2; Lynch syndrome variants: MLH1, MSH2, MSH6, PMS2; FH variants: LDLR, APOB, PCSK9.
↵§§ Pharmacogenomic (14 genes): CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, CYP4F2, DPYD, F5, IFNL3, NUDT15, SLCO1B1, TPMT, VKORC1.