Between 45% and 85% of the approximately 4 million people

Transcription

1 CLINICAL Incresing Heptitis C Screening in Lrge Integrted Helth System: Science nd Policy in Concert Crl V. Rodriguez, PhD; Kevin B. Rubenstein, MS; Benjmin Lins, MD; Hihong Hu, MS; nd Michel Horberg, MD Between 45% nd 85% of the pproximtely 4 million people in the United Sttes with heptitis C virus (HCV) infection re unwre of their infection nd my infect others nd experience disese progression. 1-3 Furthermore, incomplete ptient follow-up impedes the provision of pproprite cre. In lrge cohort study of ptients with chronic heptitis B nd/or C, 38% of HCV ntibody positive ptients hd no follow-up HCV RNA testing documented in the electronic helth record (EHR). 4 Lrger cre gps exist for ptients coinfected with HIV nd HCV 5 nd for persons of color. 6 Enbling ptients to rech ech step of the HCV cscde of cre (including screening, confirmtion, medicl mngement, tretment, nd cure) ffords them the full benefit of pproprite tretment. 7,8 In response to growing evidence of silent epidemic, the CDC updted its guidelines in 2012 to recommend universl HCV screening of ll persons born from 1945 to 1965, the birth cohort with the highest burden of disese. 9 The 2012 recommendtions lso recommended confirmtory RNA testing for ll ptients with positive HCV ntibody results. However, the US Preventive Services Tsk Force (USPSTF) did not updte its rnking of birth cohort screening to B grde until June ,11 The USPSTF updte initited coverge requirements without dditionl expense to the insured under the Affordble Cre Act (ACA). 12 The ACA lso eliminted exclusions for pre-existing conditions, prohibited insurers from rescinding coverge, nd put n end to lifetime nd nnul coverge limits, further reducing brriers to dignosis nd linkge to cre. Lstly, the 2013 USPSTF recommendtions were relesed just months before the rollout of the first highly efficcious direct-cting ntivirls (DAAs) to hit the US mrket: simeprevir (November) nd sofosbuvir (December). 13 We previously nlyzed trends in HCV screening from 2004 to 2012 nd found stedy increse in HCV screening over time prior to the 2013 interventions. 14 Two other descriptive studies using commercil lbortory nd insurnce dtbses to exmine chnges in HCV screening over time found increses. 15,16 However, these studies were ecologicl nd did not formlly test differences in screening rtes before nd fter seminl events ABSTRACT OBJECTIVES: To evlute whether the updted 2013 US Preventive Services Tsk Force (USPSTF) heptitis C virus (HCV) screening recommendtions, relted Affordble Cre Act provisions, nd the impending vilbility of efficcious therpies were ssocited with incresed screening in n integrted helth system. STUDY DESIGN: We nlyzed 665,339 records of dult ptients visiting Kiser Permnente Mid-Atlntic Sttes clinics from 2003 to METHODS: We used Cox proportionl hzrds to estimte time to HCV screening nd confirmtion fter June 1, 2013, compred with prior. RESULTS: HCV screening stedily incresed over time, but it jumped 29% (P <.01) from 2013 to 2014 versus 4% (P <.01) from 2012 to The djusted hzrd rtio for HCV screening since June 2013 ws 2.40 (95% CI, ) times higher thn it ws pre-intervention mong the birth cohort (those born ) nd 2.00 (95% CI, ) times higher in those born in other yers, representing 1.20-fold (95% CI, ) greter increse in the screening rte mong the birth cohort. We lso identified vribility in those thought to be t higher risk of HCV infection. CONCLUSIONS: HCV screening hs been incresing in our helthcre system, more so since June 2013 nd mong the birth cohort. The vilbility of efficcious therpies nd coverge policies coincident with the USPSTF recommendtions my hve fcilitted ccess to screening nd tretment in wys tht were bsent t the time of the 2012 CDC recommendtions. Helth systems must lso be poised to mke resources vilble to clinicins nd ptients in order to incentivize screening. Future reserch should inform better understnding of incentives nd brriers to screening nd linkge to cre from ll stkeholder perspectives. Am J Mng Cre. 2018;24(5):e134-e140 e134 MAY

2 Incresing HCV Screening tht were intended to increse screening nd tretment of HCV. The objective of this study ws to describe whether HCV screening nd confirmtory testing, prticulrly mong the birth cohort, were elevted fter June 1, 2013, compred with prior. June 1, 2013, mrks the contemporneous introduction of the USPSTF recommendtions, ACA protections, nd DAAs in the United Sttes. We describe trends for 1) ntibody screening nd 2) confirmtory RNA nd genotype testing. This study will be the first to describe outcomes ssocited with these collective inititives to increse screening. METHODS Study Design, Setting, nd Prticipnts We conducted n observtionl study mong ptients 18 yers nd older with t lest 8 months of enrollment in the Kiser Permnente Mid-Atlntic Sttes (KPMAS) helth insurnce pln nd who ttended t lest 1 clinicl visit from Jnury 1, 2003, to Februry 28, For the screening nlysis, ptients were followed from the dte of this first clinic visit during the study period through December 31, Ptients testing positive for HCV ntibodies were followed through Februry 28, 2015, for confirmtory RNA or genotype testing. The investigtion followed the guidelines of the HHS regrding protection of humn subjects. The study protocol ws pproved nd renewed nnully by the KPMAS Institutionl Review Bord. KPMAS is well positioned to describe chnges long the HCV cre continuum over time. The verge retention of ptients in the helth system is more thn 4 yers. 14 Clinicl expertise, comprehensive service, nd competitive pricing re incentives to seek cre within the helth system. A robust EHR ensures ner-complete cpture of ll clinicl nd demogrphic dt, including dignosis, phrmcy, lbortory, behviorl, nd insurnce dt for ptients seeking cre in our integrted multispecilty prctices nd clinics. Study Vribles TAKEAWAY POINTS All study dt were collected from the KPMAS EHR. Primry outcomes were (1) ntibody screening nd (2) RNA or genotype (confirmtory) testing. A priori fctors of interest included birth cohort sttus, rce, gender, heptitis B virus (HBV) or HIV coinfection, re medin household income (defined by the residentil Census block), primry clinic loction (DC/suburbn Mrylnd, northern Virgini, or Bltimore/other), provider type t first encounter during the study period (dult medicine, emergency/urgent cre, obstetrics/ gynecology [OB/GYN], peditrics, or specilty/other), nd prior visit to gstroenterology or infectious disese (ID) specilist who This ws n observtionl study to mesure the increse in heptitis C screening since the implementtion of revised ntionl screening guidelines nd wide vilbility of novel directcting ntivirls (DAAs) strting in June 1, 2013, compred with prior. The vilbility of effective tretment my hve fcilitted greter increse in screening thn screening guidelines lone: In the yer following the revised US Preventive Services Tsk Force (USPSTF) recommendtions nd vilbility of novel DAAs (2013), heptitis C screening incresed by 29%. In comprison, heptitis C screening incresed just 4% in the yer fter the relese of updted screening guidelines by the CDC in Overll, we observed 2-fold increse in heptitis C screening since June 1, 2013, compred with prior nd djusting for fctors tht influence screening. The screening increse ws even greter mong those born between 1945 nd 1965 (defined s the birth cohort), who were the trget of the 2013 USPSTF recommendtions. provided HCV cre in our system. HBV nd HIV coinfections were identified through the KPMAS HBV nd HIV registries, respectively. During regulr clinicl cre, ptients re sked bout their history of ever using illicit drugs (including mrijun) nd men hving sex with men (MSM) sttus, nd results re recorded in the EHR. We included these vribles in descriptive tbles nd sensitivity nlysis, but we excluded them from our min nlysis becuse of high number with missing vlues (~30% for both vribles). We used the Byesin Improved Surnme Geocoding lgorithm to impute rcil probbilities in those missing reported rce/ethnicity. 17 Sttisticl Anlysis We estimted the nnul screening rte s the number of ntibodytested ptients per ptients enrolled in KPMAS from Jnury 1 to December 31 of ech yer. We removed those who hd been screened in previous yers from subsequent yer denomintors. Significnt differences in screening rtes between yers were compred using z test for difference in proportions. In seprte models, we used Kpln-Meier curves, log-rnk tests, nd multivrible Cox proportionl hzrds with robust stndrd errors 18 to ssess time to ntibody testing mong ll ptients nd time to confirmtory testing mong those who tested HCV ntibody positive. We followed ptients in clendr time from the first office visit (for screening nlysis) nd from positive ntibody test (for the confirmtory testing nlysis) until the time of event, disenrollment from the helth pln, deth, or the dministrtive end of study, whichever occurred first. Covrites were ssessed prior to the event nd up to 1 month fter first visit for the screening nlysis nd up to 14 dys fter the ntibody test for the confirmtory testing nlysis. We ctegorized time before nd fter June 1, 2013 (the erliest dte of the USPSTF recommendtions/aca protections nd DAA relese). We creted n interction term between birth cohort sttus nd pre- nd postintervention time to directly compre chnges in screening nd confirmtory testing before nd fter the intervention by birth cohort sttus. For time to screening, we lso strtified the nlysis by clinic loction THE AMERICAN JOURNAL OF MANAGED CARE VOL. 24, NO. 5 e135

3 CLINICAL FIGURE 1. Study Cohort HCV indictes heptitis C virus. to describe prctice differences cross loctions. As sensitivity nlysis, we include MSM nd illicit drug use, long with ll other vribles, in complete-cse nlysis. Dt compiltion, nnul time series, nd grphs were conducted in SAS 9.2 (SAS Institute; Cry, North Crolin). The stcox function in Stt 13 (SttCorp; College Sttion, Texs) ws used for proportionl hzrds modeling. Figures were creted in Stt 13 nd Microsoft Excel nd Word (Microsoft; Redmond, Wshington). RESULTS We observed 665,339 ptients over time for n verge of 33 months. Figure 1 describes the flow of ptients through the study. The cohort ws diverse; 37% of ptients were Blck nd 57% were femle. On verge, ptients resided in res where medin household income ws pproximtely $84,000/yer (Tble 1). HCV Antibody Screening Initil dult cohort (N = 665,339) HCV ntibody screened (n = 123,572; 19%) HCV ntibody positive (n = 4242; 3%) HCV RNA-/genotype-tested (n = 3643; 86%) Chronic HCV (n = 2818; 77%) Percentges refer to the proportion bsed on the prior cell. Screening rtes incresed from 23.6 per 1000 person-yers in 2004 to 70.8 in 2014 (Figure 2). The screening rte incresed by 29% (P <.01) from 2013 to 2014 (fter June 2013 interventions). In comprison, the screening rte incresed by 4% (P <.01) from 2012 to 2013 (fter the CDC recommendtions). In totl, 18.6% of ll dult ptients (17% of the birth cohort) were ever screened for HCV. The youngest ptients were screened t the highest rte, followed by the birth cohort; those born before 1945 hd the lowest rte of screening (Figure 3). However, the increse since the 2013 interventions ws 1.2 (95% CI, ) times greter in the birth cohort compred with those not in the birth cohort (Tble 2). The djusted hzrd rtio (HR) for HCV screening compring fter the intervention with prior ws 2.40 (95% CI, ) mong the birth cohort nd 2.00 (95% CI, ) mong those not in the birth cohort. These trends were consistent cross ll loctions (eappendix A [eappendices vilble t jmc.com]). Among ll ptients enrolled in the helth pln s of December 31, 2014, 23.8% (70,016/294,034) hd been ntibody-screened, including 22% (29,175/131,612) of the birth cohort. Other significnt predictors of screening included first encounter with primry cre provider (ie, internl medicine, OB/GYN, or fmily prctice), which is consistent with our clinicl prctice model, nd non-white rce. The djusted hzrds of screening (Tble 2) were notbly elevted mong those with HBV (HR, 4.42; 95% CI, ) nd HIV (HR, 6.84; 95% CI, ). Mles hd lower hzrds thn women (HR 0.96; 95% CI, ), s did those with higher compred with lower income (HR, 0.97; 95% CI, ). We observed some prctice vrition, with those whose first encounter ws in OB/GYN hving slightly incresed hzrds of screening compred with fmily prctice or internl medicine (HR, 1.24; 95% CI, ) nd those seen in Virgini clinics hving slightly lower screening hzrds compred with DC/ suburbn Mrylnd (HR, 0.96; 95% CI, ). Results from the complete-cse nlysis tht included MSM nd illicit drug use in the model were robust nd showed greter hzrd for screening in MSM compred with non-msm (HR, 1.99; 95% CI, ) nd in ptients who inject drugs (HR, 7.19; 95% CI, ) compred with those not using drugs (eappendix B). Confirmtory HCV RNA or Genotype Testing A totl of 4242 ptients tested positive for HCV ntibodies, of whom 3643 (86%) underwent subsequent confirmtory testing nd 2818 tested positive (2.3% of the 123,572 ptients screened). Medin time from ntibody test to RNA/genotype test ws less thn 1 month nd did not vry by birth cohort, sex, rce, income, provider type, or HIV or HBV sttus. The rte of confirmtory testing ws more thn 50% higher fter 2013 compred with before, nd the increse in confirmtory testing did not differ by birth cohort sttus. Ptients whose primry clinic loction ws in Bltimore (HR, 1.27; 95% CI, ) or Virgini (HR, 1.25; 95% CI, ) lso hd greter hzrds of confirmtory testing compred with those seen in DC/ suburbn Mrylnd, s did those with prior gstroenterology/id visit compred with no prior visit (HR, 1.39; 95% CI, ) (Tble 2). DISCUSSION In the yer following the relese of the 2013 USPSTF HCV screening recommendtions highlighting the need for birth cohort screening, e136 MAY

4 Incresing HCV Screening ssocited protections under the ACA, nd DAA vilbility, the djusted hzrd of HCV screening mong the birth cohort more thn doubled compred with prior yers. This increse ws 20% higher thn the increse observed in ptients outside of the birth cohort nd demonstrtes the influence of guidelines on chnges in prctice. In ddition, the overll screening rte incresed by 29% in the yer fter the interventions, compred with 4% in the yer fter the 2012 CDC recommendtion. The distinction between the CDC nd USPSTF recommendtions is tht, lthough both provided guidnce, the USPSTF recommendtions were supported by policy nd science tht fcilitted ccess to screening nd tretment in wys tht were bsent during the nnouncement of the CDC recommendtions. First, the USPSTF B grding for HCV screening triggered policy under the ACA to provide screening without dditionl cost to ll those covered under privte or public plns. 11 Cost hs been cited s brrier to screening for other chronic conditions, such s HIV nd brest cncer. 19,20 We observed n increse in the per popultion screening rte tht my be ssocited with removing brriers posed by the cost of screening. The vilbility of DAAs shortly fter USPSTF nnounced its recommendtion ws nother timely screening incentive. The gols of screening re to (1) stop trnsmission of HCV nd (2) identify disese in erly stges so tht it my be treted more effectively nd led to better outcomes thn would occur if it were treted t lter stge. Limited therpeutic options prior to 2013 mde these gols elusive nd my hve deterred screening. 21,22 Although the ge group with the gretest increse in HCV screening ws the birth cohort, trditionl risk fctors for HCV remin importnt predictors of screening. Ptients with HIV nd HBV infection, which re often ssocited with HCV, hd 4 to 7 times higher rtes of screening thn those without these infections. In our complete-cse nlysis, we show tht screening ws lmost 2-fold higher in MSM nd more thn 7-fold higher in ptients who inject drugs compred with those who denied using drugs. These dt suggest bis towrd screening in TABLE 1. Chrcteristics of Ptients 18 Yers nd Older, KPMAS, Age t enrollment, yers, men (SD) Medin re household income, b $, men (SD) Rce, c % Totl (N = 665,339) Birth Cohort (born ) (n = 260,822) Other Ages (n = 404,517) 42.2 (15.2) 49.5 (6.5) 37.5 (17.1) 83,980 (37,376) 86,366 (38,528) 82,559 (36,599) Non-Hispnic Blck Americn Indin/Alskn Ntive Asin/Pcific Islnder Hispnic Mixed rce Non-Hispnic White Sex, n (%) Femle 378,480 (56.9) 143,450 (55.0) 235,030 (58.1) Mle 286,859 (43.1) 117,372 (45.0) 169,487 (41.9) HBV+, n (%) 1710 (0.3) 664 (0.3) 1046 (0.3) HIV+, n (%) 3464 (0.5) 1755 (0.7) 1709 (0.4) MSM, n (%) 3983 (0.6) 1488 (0.6) 2495 (0.6) Non-MSM 464,377 (69.8) 180,636 (69.3) 283,741 (70.1) Unknown MSM sttus 196,979 (29.6) 78,698 (30.2) 118,281 (29.2) History of drug use, n (%) Never 436,906 (65.7) 171,462 (65.7) 265,444 (65.6) Yes, not intrvenous 2701 (0.4) 718 (0.3) 1983 (0.5) Yes, intrvenous 8 (<0.01) 4 (<0.01) 4 (<0.01) Unknown 225,724 (33.9) 88,638 (34.0) 137,086 (33.9) First visit provider, n (%) Other/specilty 84,371 (12.7) 38,976 (14.9) 45,395 (11.2) Adult medicine/fmily prctice 451,494 (67.9) 183,816 (70.5) 267,678 (66.2) OB/GYN 77,893 (11.7) 18,902 (7.3) 58,991 (14.6) ED/urgent cre 49,152 (7.4) 19,020 (7.3) 30,132 (7.5) Peditrics 2429 (0.4) 108 (0.04) 2321 (0.6) Gstroenterology/ID visit up to 30 dys fter first visit, n (%) No 625,777 (94.1) 242,020 (92.8) 383,757 (94.9) Yes 39,562 (6.0) 18,802 (7.2) 20,760 (5.1) Clinic loction, n (%) DC/suburbn Mrylnd 299,599 (45.0) 116,858 (44.8) 182,741 (45.2) Bltimore 105,517 (15.9) 42,101 (16.1) 63,416 (15.0) Virgini 260,223 (39.1) 101,863 (39.1) 158,360 (39.1) ED indictes emergency deprtment; HBV, heptitis B virus; KPMAS, Kiser Permnente Mid-Atlntic Sttes; ID, infectious disese; MSM, men who hve sex with men; OB/GYN, obstetrics/gynecology. All chrcteristics ssessed up to 30 dys fter first visit. b Source: US Census Bureu, Americn Community Survey. c Nonreported rce imputed using Byesin Improved Geocoding Surnme Algorithm. THE AMERICAN JOURNAL OF MANAGED CARE VOL. 24, NO. 5 e137

5 CLINICAL HCV Screening Rte/1000 p-y FIGURE 2. HCV Antibody Screening Rte Over Time, KPMAS, USPSTF recommendtion 10 Sofosbuvir introduced to US mrket Yer ACA CDC guidelines ACA indictes Affordble Cre Act; HCV, heptitis C virus; KPMAS, Kiser Permnente Mid-Atlntic Sttes; p-y, person-yers; USPSTF, US Preventive Services Tsk Force. Denomintor clculted s the number of enrollees in KPMAS helth insurnce pln in given yer mong those who hd t lest 1 visit from nd excluding those who were HCV ntibody tested in prior yers FIGURE 3. Time to HCV Antibody Test by Birth Yer HCV indictes heptitis C virus. Months Since First Clinic Visit Born before 1945 Born Born fter 1965 ptients thought to hve trnsmission risk fctors. Yet, 30% of the totl smple were missing informtion on MSM nd drug use sttus. Screening bsed on risk fctors will continue to be incomplete if ptient provider discussions regrding risk fctors re not routinely done We lso note lower screening rtes mong ptients from higher-income neighborhoods. Incresing HCV screening rtes in lower-income neighborhoods is responsive to known gp in delivering high-qulity cre for HCV. 1,26 However, if the opioid nd heroin epidemic continues to expnd beyond poor urbn nd rurl res into higher-income neighborhoods nd ffects the epidemiology of virl heptitis nd HIV, excluding ptients from HCV screening bsed on income will leve us vulnerble to underdignosing the infection. 27 Vribility in screening cross geogrphic res illustrtes the need for further eduction nd outrech. All ptients t risk of HCV infection should be screened in order to meet the ntionl nd interntionl gol of eliminting virl heptitis by ,29 Our results inform generl increse in HCV screening over time tht hs been described previously. 14,16 Our study is unique in tht we formlly estimted nd compred screening rtes before nd fter the occurrence of the collective ctivities of 2013 (ie, the USPSTF guidelines, ACA coverge, nd DAA vilbility) by ge group, djusting for individul-level fctors tht my confound the reltionship between popultion-level inititives nd screening. This nlysis llows us to mke inferences on the ssocition between policy mesures nd screening outcomes cross ge groups. Specificlly, we sw higher screening rtes fter these coordinted ctivities compred with before, prticulrly mong the birth cohort, who were primry trget of the updted USPSTF recommendtions. Our overll screening rtes were similr to those observed in other integrted helth systems, which were higher thn in the generl popultion nd lower thn rtes in the Veterns Affirs helth system. 4,6,30-33 Although no EHR chnges occurred during the course of this study, clinicl ledership ws engged to increse provider knowledge bout HCV, the need for screening, nd the coming vilbility of efficcious tretment in preprtion for new inititive to increse HCV screening nd linkge to cre. 34 Coopertive greements to ensure the vilbility of competitively priced mediction my hve further supported screening by providing ssurnce to clinicins tht they would be ble to offer therpy to ptients with infection. Clinicl ledership nd the bility to negotite coopertive greements re key components of our integrted system tht my hve contributed to our bility to quickly comply with screening guidelines. Limittions We cknowledge some limittions to this study. Although the screening recommendtions, ACA protections, nd vilbility of DAAs were universlly vilble to ll ptients in the study, we were unble to quntify how much ech of these plyed role in individul clinicin or ptient decisions to screen. Future reserch tht includes interviews with stff nd ptients might elucidte more specific understnding of the individul motivtions of ptients nd providers to promote nd ccept screening. Also, we did not study the effects of MSM nd substnce buse becuse they were missing in pproximtely 30% of the smple. This omission my hve bised the results wy from the null if MSM or substnce buse were ssocited with birth cohort sttus, time, nd screening, for exmple. However, results from complete-cse e138 MAY

6 Incresing HCV Screening nlysis tht included these vribles were robust for ll outcomes nd showed tht ptients with history of MSM nd illicit drug use were screened t higher rtes compred with those without such history. Future studies should describe strtegies tht llow for improved communiction between ptients nd providers on risk fctors for trnsmission nd disese progression, s well s educte providers on wys to improve documenttion of risk fctors. We did not include dt from outside the KPMAS helth system (ie, externl referrls) in this nlysis. As such, some dignostic nd visit dt were missing. KPMAS hs been working to internlize ID specilties. We will consider including dt from externl referrls in future nlyses. We recognize tht linkge to cre is n importnt follow-up to screening tht we did not ddress. Provider, ptient, nd helth system fctors ply importnt roles in linkge to cre, which re beyond the scope of the present nlysis. We focused this nlysis on screening becuse it is the most proximl effect of the interventions being investigted. We intend to investigte linkge to cre in future work. Finlly, limittion of ny helth system bsed cohort study is limited generlizbility to those without insurnce, the homeless, nd institutionlized popultions. Medicid expnsion from 2015 to 2018 under the ACA incresed our cpture of higher-need ptients nd enbles us to exmine the effect of interventions in this popultion. CONCLUSIONS HCV screening hs been incresing in our helthcre system, especilly mong the birth cohort, since June 2013 when the USPSTF updted its HCV screening recommendtion (invoking provisions under the ACA) nd DAAs becme widely vilble in the United Sttes. The vilbility of efficcious therpies nd ccess to cre nd tretment often justifies nd fcilittes disese screening. Additionlly, helth systems must be poised to hrness such resources nd inform clinicins of their vilbility. By the end of 2014, we screened just 22% of the KPMAS birth cohort. Bsed on known HCV prevlence (2.3%), there my hve been s mny s 13,000 undignosed HCV cses in the KPMAS popultion. Helth TABLE 2. Adjusted HRs of HCV Antibody nd Confirmtory Testing, KPMAS, Antibody Screening (n = 514,517 ) systems need to do much more to improve HCV screening in popultions with risk fctors for nd high burden of HCV. A better understnding of physicin nd ptient motivtions nd brriers to screening is nturl extension of this work tht will improve the implementtion of guidelines nd mximize vilble incentives to screen nd tret ptients with HCV. n Confirmtory Testing (n = 3231 ) Chrcteristic b HR 95% CI HR 95% CI Birth cohort Screening rte fter June 2013 vs prior (not in birth cohort) Screening rte fter June 2013 vs prior (in birth cohort) Difference in screening rte fter June 2013 vs before in birth cohort compred with sme difference mong those not in birth cohort Mle Rce c (ref, non-hispnic White) Non-Hispnic Blck Hispnic Asin/Pcific Islnder Americn Indin/Alskn Ntive Mixed rce Medicine specilty (ref, other/specilty) Fmily prctice/dult medicine OB/GYN ED/urgent cre Peditrics No events observed HBV HIV Prior visit with gstroenterology/id Medin re household income d (per $10,000 difference) Clinic loction (ref, DC/suburbn Mrylnd) Bltimore Virgini ED indictes emergency deprtment; HBV, heptitis B virus; HCV, heptitis C virus; HR, hzrd rtio; ID, infectious disese; KPMAS, Kiser Permnente Mid-Atlntic Sttes; OB/GYN, obstetrics/gynecology; ref, reference. Anlytic cohort number. Cohort reduced by 150,822 for ntibody screening nlysis nd 1011 for confirmtory testing nlysis from originl number due to missing covrites nd to events occurring before the strt of follow-up. b All chrcteristics ssessed up to 30 dys fter first visit (ntibody screening) or 14 dys fter HCV ntibody positive result (confirmtory testing). c Nonreported rce imputed using Byesin Improved Geocoding Surnme Algorithm. d Source: US Census Bureu, Americn Community Survey. HRs interpreted for every $10,000 difference. THE AMERICAN JOURNAL OF MANAGED CARE VOL. 24, NO. 5 e139

7 CLINICAL Acknowledgments The uthors thnk Drs Andres Mendez, Cbell Jons, Dn Slon, nd Berndette Loftus for their criticl review of the mnuscript nd Michelle Turner, MPH, for her help with mnuscript preprtion. Author Affilitions: Mid-Atlntic Permnente Reserch Institute, Kiser Permnente Mid-Atlntic Sttes (CVR, KBR, HH, MH), Rockville, MD; Deprtment of Epidemiology, School of Public Helth, Boston University (BL), Boston, MA; HIV Epidemiology nd Outcomes Reserch Unit, Section of Infectious Diseses, Boston Medicl Center (BL), Boston, MA. Source of Funding: This work ws supported by grnts from the Ntionl Institutes of Helth: R01 DA , P30 AI042853, nd P30 DA Author Disclosures: The uthors report no reltionship or finncil interest with ny entity tht would pose conflict of interest with the subject mtter of this rticle. Authorship Informtion: Concept nd design (CVR, BL, MH); cquisition of dt (HH); nlysis nd interprettion of dt (CVR, KBR, BL, MH); drfting of the mnuscript (CVR, BL); criticl revision of the mnuscript for importnt intellectul content (KBR, BL, HH, MH); sttisticl nlysis (CVR, KBR); provision of ptients or study mterils (HH); obtining funding (BL); dministrtive, technicl, or logistic support (CVR); nd supervision (CVR). Address Correspondence to: Crl V. Rodriguez, PhD, Mid-Atlntic Permnente Reserch Institute, Kiser Permnente Mid-Atlntic Sttes, 2101 E Jefferson St, 3W, Rockville, MD Emil: crl.v.rodriguez@kp.org. REFERENCES 1. Denniston MM, Jiles RB, Drobeniuc J, et l. Chronic heptitis C virus infection in the United Sttes, Ntionl Helth nd Nutrition Exmintion Survey 2003 to Ann Intern Med. 2014;160(5): doi: /M Edlin BR, Eckhrdt BJ, Shu MA, Holmberg SD, Swn T. Towrd more ccurte estimte of the prevlence of heptitis C in the United Sttes. Heptology. 2015;62(5): doi: /hep Armstrong GL, Wsley A, Simrd EP, McQuilln GM, Kuhnert WL, Alter MJ. The prevlence of heptitis C virus infection in the United Sttes, 1999 through Ann Intern Med. 2006;144(10): doi: / Moormn AC, Gordon SC, Rupp LB, et l; Chronic Heptitis Cohort Study Investigtors. Bseline chrcteristics nd mortlity mong people in cre for chronic virl heptitis: the chronic heptitis cohort study. Clin Infect Dis. 2013;56(1): doi: /cid/cis Grhm CS. Heptitis C nd HIV co-infection: closing the gps. JAMA. 2015;313(12): doi: /jm Bckus LI, Belperio PS, Loomis TP, Mole LA. Impct of rce/ethnicity nd gender on HCV screening nd prevlence mong U.S. veterns in Deprtment of Veterns Affirs Cre. Am J Public Helth. 2014;104(suppl 4):S555-S561. doi: /AJPH Colvin HM, Mitchell AE, eds. Heptitis nd Liver Cncer: A Ntionl Strtegy for Prevention nd Control of Heptitis B nd C. Wshington, DC: Ntionl Acdemies Press; Lins BP, Brter DM, Leff JA, et l. The heptitis C cscde of cre: identifying priorities to improve clinicl outcomes. PloS One. 2014;9(5):e doi: /journl.pone Smith BD, Morgn RL, Beckett GA, et l; CDC. Recommendtions for the identifiction of chronic heptitis C virus infection mong persons born during MMWR Recomm Rep. 2012;61(RR-4): Moyer VA; US Preventive Services Tsk Force. Screening for heptitis C virus infection in dults: U.S. Preventive Services Tsk Force recommendtion sttement. Ann Intern Med. 2013;159(5): doi: / Edlin BR. Heptitis C screening: getting it right. Heptology. 2013;57(4): doi: /hep Ktes J. Implictions of the Affordble Cre Act for people with HIV infection nd the Ryn White HIV/AIDS Progrm: wht does the future hold? Top Antivir Med. 2013;21(4): Afdhl NH, Zeuzem S, Schooley RT, et l; New Prdigm of HCV Therpy Meeting Prticipnts. The new prdigm of heptitis C therpy: integrtion of orl therpies into best prctices. J Virl Hept. 2013;20(11): doi: /jvh Lins BP, Hu H, Brter DM, Horberg M. Heptitis C screening trends in lrge integrted helth system. Am J Med. 2014;127(5): doi: /j.mjmed Whl PM, Luo D, J, McLeroth P, Anstssopoulos KP. Recent heptitis C screening trends in the United Sttes: n nlysis of dt from lrge lbortory service provider. Pper presented t: Interntionl Society of Phrmcoeconomics nd Outcomes Reserch 21st Annul Meeting; My 21-25, 2016; Wshington, DC. ispor.org/reserch_pdfs/52/pdffiles/pmd84.pdf. Accessed October 15, Isenhour CJ, Hriri SH, Hles CM, Vellozzi CJ. Heptitis C ntibody testing in commercilly insured popultion, Am J Prev Med. 2017;52(5): doi: /j.mepre Elliott MN, Fremont A, Morrison PA, Pntoj P, Lurie N. A new method for estimting rce/ethnicity nd ssocited disprities where dministrtive records lck self-reported rce/ethnicity. Helth Serv Res. 2008;43(5 pt 1): doi: /j x. 18. Lin DY, Wei LJ. The robust inference for the Cox proportionl hzrds model. J Am Stt Assoc. 1989;84(408): Wgner Z, Wu Y, Sood N. The Affordble Cre Act my increse the number of people getting tested for HIV by nerly 500,000 by Helth Aff (Millwood). 2014;33(3): doi: /hlthff Msi CM, Blckmn DJ, Peek ME. Interventions to enhnce brest cncer screening, dignosis, nd tretment mong rcil nd ethnic minority women. Med Cre Res Rev. 2007;64(suppl 5):195S-242S. doi: / Fried MW, Shiffmn ML, Reddy KR, et l. Peginterferon lf-2 plus ribvirin for chronic heptitis C virus infection. N Engl J Med. 2002;347(13): doi: /NEJMo Hdziynnis SJ, Sette H Jr, Morgn TR, et l; PEGASYS Interntionl Study Group. Peginterferon-lph2 nd ribvirin combintion therpy in chronic heptitis C: rndomized study of tretment durtion nd ribvirin dose. Ann Intern Med. 2004;140(5): doi: / Korthuis PT, Josephs JS, Fleishmn JA, et l; HIV Reserch Network. Substnce buse tretment in humn immunodeficiency virus: the role of ptient-provider discussions. J Subst Abuse Tret. 2008;35(3): doi: /j.jst Tir DA, Sfrn DG, Seto TB, Rogers WH, Trlov AR. The reltionship between ptient income nd physicin discussion of helth risk behviors. JAMA. 1997;278(17): doi: /jm Brdley KA, Lphm GT, Hwkins EJ, et l. Qulity concerns with routine lcohol screening in VA clinicl settings. J Gen Intern Med. 2011;26(3): doi: /s Omlnd LH, Osler M, Jepsen P, et l. Socioeconomic sttus in HCV infected ptients risk nd prognosis. Clinicl Epidemiol. 2013;5: Jones CM, Logn J, Gldden RM, Bohm MK. Vitl signs: demogrphic nd substnce use trends mong heroin users United Sttes, MMWR Morb Mortl Wkly Rep. 2015;64(26): Ntionl Acdemies of Sciences, Engineering, nd Medicine. A Ntionl Strtegy for the Elimintion of Heptitis B nd C. Wshington, DC: The Ntionl Acdemies Press; World Helth Orgniztion. Globl Helth Sector Strtegy on Virl Heptitis : Towrds Ending Virl Heptitis. Genev, Switzerlnd: World Helth Orgniztion; Denniston MM, Klevens RM, McQuilln GM, Jiles RB. Awreness of infection, knowledge of heptitis C, nd medicl follow-up mong individuls testing positive for heptitis C: Ntionl Helth nd Nutrition Exmintion Survey Heptology. 2012;55(6): doi: /hep Bourgi K, Brr I, Bker-Genw K. Helth disprities in heptitis C screening nd linkge to cre t n integrted helth system in southest Michign. PloS One. 2016;11(8):e doi: /journl.pone Buntin MB, Burke MF, Hoglin MC, Blumenthl D. The benefits of helth informtion technology: review of the recent literture shows predominntly positive results. Helth Aff (Millwood). 2011;30(3): doi: /hlthff Btes DW, Lepe LL, Cullen DJ, et l. Effect of computerized physicin order entry nd tem intervention on prevention of serious mediction errors. JAMA. 1998;280(15): doi: /jm Jons MC, Rodriguez CV, Redd J, Slone DA, Winston BJ, Loftus BC. Stremlining screening to tretment: the heptitis C cscde of cre t Kiser Permnente Mid-Atlntic Sttes. Clin Infect Dis. 2016;62(10): doi: /cid/ciw086. Full text nd PDF t e140 MAY

8 eappendix A. Adjusted HRs of HCV Antibody Testing by Loction DC/Suburbn Mrylnd Bltimore Virgini Chrcteristic HR 95% CI HR 95% CI HR 95% CI Birth cohort Effect of time fter June 2013 (not in birth cohort) Effect of time fter June 2013 (birth cohort) Difference in effect of time fter June 2013 in birth cohort vs not in birth cohort Mle Rce b (ref, non-hispnic white) Non-Hispnic blck Hispnic Asin/Pcific Islnder Americn Indin/Alskn Ntive Mixed rce Medicl specilty (ref, other/specilty) Fmily prctice/dult medicine OB/GYN ED/urgent cre Peditrics HBV HIV Prior visit with GI/ID Medin re household income c (per $10,000 difference) ED indictes emergency deprtment; GI/ID, gstroenterology/infectious disese; HBV, heptitis B virus; HCV, heptitis C virus; HR, hzrd rtio; OB/GYN, obstetrics/gynecology; ref, reference. All chrcteristics ssessed up to 30 dys fter first visit. b Nonreported rce imputed using Byesin Improved Geocoding Algorithm. e Source: US Census Bureu, Americn Community Survey. HRs interpreted for every $10,000 difference.

9 eappendix B. Complete Cse Anlysis of Adjusted HRs of HCV Antibody Testing, including Men Who Hve Sex With Men nd Illicit Drug Use Antibody Screening Chrcteristic HR 95% CI Birth cohort Effect of time fter June 2013 (not in birth cohort) Difference in effect of time fter June 2013 in birth cohort vs not in birth cohort Mle Rce b (ref, non-hispnic white) Non-Hispnic blck Hispnic Asin/Pcific Islnder Americn Indin/Alskn Ntive Mixed rce Medicl specilty (ref, other/specilty) Fmily prctice/dult medicine OB/GYN ED/urgent cre Peditrics HBV HIV Prior visit with GI/ID Medin re household income c (per $10,000 difference) Clinic loction (ref, DC/suburbn Mrylnd) Bltimore Virgini Men who hve sex with men History of illicit drug use (ref, never used) Yes, nonintrvenous Yes, intrvenous Unknown ED indictes emergency deprtment; GI/ID, gstroenterology/infectious disese; HBV, heptitis B virus; HCV, heptitis C virus; HR, hzrd rtio; OB/GYN, obstetrics/gynecology; ref, reference. All chrcteristics ssessed up to 30 dys fter first visit. b Nonreported rce imputed using Byesin Improved Geocoding Algorithm. c Source: US Census Bureu, Americn Community Survey. HRs interpreted for every $10,000 difference.