Perceived barriers related to testing, management and treatment of HCV infection among physicians prescribing opioid agonist therapy: The C‐SCOPE Study

Abstract The aim of this analysis was to evaluate perceived barriers related to HCV testing, management and treatment among physicians practicing in clinics offering opioid agonist treatment (OAT). C‐SCOPE was a study consisting of a self‐administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe and the United States between April and May 2017. A 5‐point Likert scale (1 = not a barrier, 3 = moderate barrier, 5 = extreme barrier) was used to measure responses to perceived barriers for HCV testing, evaluation and treatment across the domains of the health system, clinic and patient. Among the 203 physicians enrolled (40% USA, 45% Europe, 14% Australia/Canada), 21% were addiction medicine specialists, 29% psychiatrists and 69% were metro/urban. OAT physicians in this study reported poor access to on‐site venepuncture (35%), point‐of‐care HCV testing (16%), and noninvasive liver disease assessment (25%). Only 30% of OAT physicians reported personally treating HCV infection. Major perceived health system barriers to HCV management included the lack of funding for noninvasive liver disease testing, long wait times to see an HCV specialist, lack of funding for new HCV therapies, and reimbursement restrictions based on drug/alcohol use. Major perceived clinic barriers included the lack of peer support programmes and/or HCV case managers to facilitate linkage to care, the need to refer people off‐site for noninvasive liver disease staging, the lack of support for on‐site phlebotomy and the lack of on‐site delivery of HCV therapy. This study highlights several important modifiable barriers to enhance HCV testing, evaluation and treatment among PWID attending OAT clinics.


| INTRODUC TI ON
The global burden of hepatitis C virus (HCV) infection is significant, with over 71 million people living with HCV 1 and 6.1 million people with recent injecting drug use. 2 There is also a considerable burden of HCV among people with a history of injecting drug use and people receiving opioid agonist treatment (OAT) for opioid dependence.
High treatment completion and response to HCV therapy has been observed in people receiving OAT and people with recent injecting drug use. 3 The integration and co-location of care for HCV infection and OAT is associated with improved testing, linkage to treatment and retention in HCV care. [4][5][6][7] The high HCV prevalence among people who inject drugs (PWID) attending OAT clinics makes this an ideal setting for targeted strategies to enhance HCV care. However, there are still health system, structural, social, patient-level and provider-level barriers that are preventing broad uptake of HCV therapy among people receiving OAT or people with recent injecting drug use. [8][9][10] In some countries, people receiving OAT and people with recent drug use are still ineligible 11 or considered unsuitable by practitioners 12 to receive direct-acting antivirals (DAAs) , due to concerns of poor adherence, ongoing substance use, lower responses to therapy, medication price and the risk of reinfection. 9,12 In studies of general practitioners, a lack of confidence in initiating interferon-based HCV treatment appears to have driven the low HCV screening, evaluation and treatment rates among this provider group. 13 Low case numbers and inadequate HCV knowledge are important factors, with one study suggesting that primary care providers tend to underestimate efficacy and tolerability, and overestimate duration of DAAs, 14 although many report a desire for more HCV education. 15 Although qualitative interviews with providers have identified barriers to HCV care, 16,17 there are very few studies that have quantified potential modifiable barriers among physicians prescribing OAT.
The C-SCOPE study was an international cross-sectional study to evaluate clinic procedures and services, barriers, competency and attitudes towards HCV care among physicians practicing at clinics providing OAT. 18 The aim of this analysis was to evaluate perceived barriers related to HCV testing, management and treatment among physicians prescribing OAT in the C-SCOPE study.

| Study design, setting and participants
C-SCOPE was an international cross-sectional study that recruited physicians practicing at clinics providing OAT from Australia, Canada, Europe (Belgium, France, Germany, Italy, Portugal, Netherlands, Spain, Sweden and the United Kingdom) and the United States (US) from 14 April 2017 to 22 May 2017. 18 Inclusion/exclusion criteria have been described in detail previously. 18 Physicians must have spent at least 50% of time in clinics providing OAT treating patients or in management responsibilities, a minimum of 2 years treating patients in a clinic providing OAT, currently treating PWID with OAT, and working at a clinic, centre, department, or institution that is providing OAT and have been personally certified or allowed to prescribe OAT (Australia, Portugal and the United States only). Physicians working at the same clinic, centre, department or institution as two previous qualified respondents and those unwilling to comply with the study protocol were excluded.
Physicians were invited to participate via opt-in online web panels (M3 Global Research panel), research databases and/or public and proprietary lists of clinics providing OAT in each country. The M3 Global Research panel is an actively managed double opt-in online panel, for which physicians firstly opt-in via an initial recruitment form and are then sent an automated email to confirm that they want to join the panel. Upon agreement to join the panel, M3 Global Research has a stringent verification process in order to confirm a respondent's practicing status. In the United States, 100% of panellists are verified using the American Medical Association database.
Once identified, physicians were contacted via email or telephone and screened against the inclusion/exclusion criteria.
Eligible physicians were invited to participate in an online survey in their local language. Physicians were provided an email and link to an online internet-based survey. Approximately 2-4 days after the initial invitation, people who did not initially respond were sent an e-mail reminder. All participants gave written informed consent before study procedures started. Participating physicians Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government. JG is supported by a National Health and Medical Research Council Career Development Fellowship. see an HCV specialist, lack of funding for new HCV therapies, and reimbursement restrictions based on drug/alcohol use. Major perceived clinic barriers included the lack of peer support programmes and/or HCV case managers to facilitate linkage to care, the need to refer people off-site for noninvasive liver disease staging, the lack of support for on-site phlebotomy and the lack of on-site delivery of HCV therapy.

| Study assessments
As previously described, 18 physicians completed a survey to assess perceptions, self-reported competency, and barriers related to the testing, management and treatment of HCV infection among those being prescribed OAT. Where applicable, questions were adapted from previously published studies. 9,[19][20][21][22][23][24] The survey included information on physician characteristics including region (Australia, Canada, Europe and the United States), primary specialty, and number of years in practice, practice source of funding (public, private for profit, private not for profit), type of OAT institution (substance use clinic/centre, hospital department that treats people on OAT, OAT clinic/centre and other institution/ office that treats people on OAT), proportion of OAT therapy offered, OAT clinic setting (major metropolitan area, urban, suburb of large city, small city and rural/small town), number of patients managed on OAT who are PWID in past 12 months, number of patients personally managed on OAT who are PWID with HCV in the past 12 months, and training received. The survey also included information on OAT clinic characteristics including composition of teams that support OAT within the clinic, availability of HCV training for staff, existence of protocols and guidelines put in place, availability and location (on-site, affiliated off-site, not affiliated off-site) of HCV diagnostic services, availability and location of HCV assessments prior to or during treatment, support services offered to HCV patients, use of electronic health records. Lastly, the survey included information on perceptions of barriers to HCV screening, testing and treatment (health system-, clinic-and patients-related barriers) and attitudes and perceptions towards HCV management.

| Study outcomes and analysis
The availability of services for HCV testing and treatment at clinics among physicians who prescribe OAT were evaluated. Study endpoints also included physician-perceived barriers regarding HCV testing, management and treatment of HCV for PWID. Physicians were asked to evaluate potential barriers for OAT patients to entering pathways to HCV care (ie testing and diagnosis), and to evaluate potential barriers to continuing pathways to HCV care (ie HCV treatment management). A 5-point scale (1 = Not a barrier, 2 = Minor barrier, 3 = Moderate barrier, 4 = Major barrier and 5 = Extreme barrier) was used to measure barriers related to HCV testing, management and treatment. Barriers were categorized into those reporting greater than or equal to moderate barriers (eg moderate, major or extreme barriers). Analysis was performed using SAS 9.2 software (SAS Institute Inc., Cary, NC, USA).

| Participant characteristics
Among 660 physicians contacted for this study, 203 physicians were enrolled (Table 1). Among the 457 who did not enrol in the study, 266 did not meet the inclusion criteria; 91 started the survey and did not complete it; and 100 were 'over quota' (by the time they responded to the survey, the quota for the target sample size for their country had already been met). The characteristics of OAT prescribers included in this study are highlighted in Table 1.

| Existing team members to support agonist therapy within clinics providing OAT
The majority of physicians reported having nurses, nurse practitioners and medical assistants (71%), addiction medicine specialists (70%), psychiatrists (61%), primary care physicians (56%) and social workers (55%) as part of the team providing support for OAT at their clinic ( Figure S1). Only 27% of clinics had a HCV specialist (Infectious Diseases, Hepatology or Gastroenterology). Very few clinics had a link-to-care coordinator (20%), peer support worker (16%) or HCV educator (10%).

| Availability of HCV diagnostic services
Physicians reported a wide range of diagnostic services being available to OAT providers, either on-or off-site, with HCV testing (antibody and RNA) and noninvasive liver disease assessment being almost universally available ( Figure 1 and Table S1). Only a minority of physicians reported having access to on-site HCV antibody testing (40%), on-site venipuncture (35%), quantitative (28%) or qualitative (27%) HCV RNA testing, or liver disease assessment (25%). In cases where HCV testing is performed off-site, 97% of the clinics received the HCV test results from the same location where the tests are performed indicating that patients need to return to their OAT clinic to receive their results. On-site availability of point-of-care fingerstick-based (16%) and saliva-based (8%) testing was uncommon. A large proportion of physicians did not have access to point-of-care finger-stick-based (31%) or salivabased (38%) testing.

| Availability of testing protocols
A majority of physicians reported that their clinic has a protocol for HCV screening and diagnosis (n = 75, 37%) or that published guidelines are followed (n = 87, 43%; data not shown). From those 162 physicians, 86% reported testing all patients with history of injection drug use and 82% reported that HCV-positive people are referred for additional testing and assessment. However, only 56% of physicians reported testing all OAT patients for HCV at first visit, 58% of physicians reported that patients are re-tested on a regular basis, and 57% of physicians reported that patients receive test results and care referrals in one visit (Table S2).

| Availability of electronic health records
Access to an electronic health record system was reported by 74% of physicians (n = 150), with: 40% of these reporting having electronic alerts for patients who are eligible/need testing/re-testing; 30% reported that one of the elements of the system includes the generation of reports for those who were tested and the names of those who were HCV positive; 23% reporting that the system tracks, reports and facilitates reimbursement for HCV tests; and 14% report that the system provides an alert that patient is eligible for link-to-care services. Nearly half (42%) of the physicians did not report any of the above elements for the electronic health record system implemented in the clinic where they practice.

| Availability of support services offered for HCV testing and diagnosis
The most common support service offered to enhance testing/diagnosis was appointment scheduling for HCV specialist (75% of physicians offered this service at their clinic) and informational posters to educate patients on prevalence, risk factors and recommendations (71%). The least common support service was patient financial incentives to attend HCV specialist appointments for testing/diagnosis (12%) ( Table S3).

| Availability of assessments prior to HCV treatment
Physicians reported a wide range of pre-treatment assessments being available in OAT clinics ( Figure S2). Standard HCV evaluation TA B L E 1 Enrolment characteristics of physicians in the C-SCOPE study (n = 203)

| Availability of services for HCV treatment
Only 30% of the OAT physicians in this study reported that they personally treat HCV infection. Thirty-two per cent of physicians reported that they refer patients to HCV specialists in the same clinic and 62% reported that they refer HCV patients to other institutions for treatment. Overall, 26% of physicians reported that medication is dispensed at the OAT clinic, but most often, HCV medication is dispensed off-site.
The most common support services offered on-site to enhance HCV treatment included access to psychiatric treatment (66%) and one-on-one education with peers/staff (52%) ( Figure 2 and Table   S4). Other common support services offered on-site included psychoeducational support groups (44%), adherence support (42%), coordinator/counsellor for barriers such as financial, housing and food security (39%), directly observed therapy (35%) and HCV peer support (32%).

| Physician perceived barriers to HCV screening and testing
At the level of the health system, the most common perceived barriers to HCV screening/testing by OAT physicians included a lack of health system funding for noninvasive methods of liver disease screening (63% ≥moderate; Figure 3A,  Figure 3B, Table S5).
At the level of the patient, the most common perceived barriers to HCV screening and testing by OAT physicians included social circumstances/unstable housing/marginalized lifestyle (73% ≥moderate), patients not attending appointments (70% ≥moderate), lack of knowledge of HCV and its treatment (70% ≥moderate), general difficulty navigating through the system (69% ≥moderate), patient stigma (64% ≥moderate) and concerns with patient motivation to get tested (63% ≥moderate) ( Figure 3C, Table S5).
Other reported barriers included a lack of time for HCV testing due to competing responsibilities (47% ≥moderate) and that visits are too short and do not allow enough time for testing (41% ≥moderate) (Table S5).

| Physician perceived barriers for HCV treatment
At the level of the health system, the most common perceived barriers for HCV treatment by OAT physicians are that the patients cannot afford HCV treatment (65% ≥moderate, the United States only), the lack of health system funding for new HCV medications to treat HCV (60% ≥moderate) and the requirement for a period of abstinence from recent drug use for government reimbursement of HCV therapy (58% ≥moderate) ( Figure 4A, Table S6).
At the level of the clinic, the most common perceived barriers to HCV treatment by OAT physicians are the lack of delivery of therapy on-site (46% ≥moderate), case managers (44% ≥moderate) and of peer support programmes for treatment (42% ≥moderate) ( Figure 4B, Table S6). difficulty in navigating the healthcare system (65% ≥moderate), concerns around patient motivation to be treated for HCV (63% ≥moderate), stigma experienced by patients (56% ≥moderate) and mistrust of the healthcare system (50% ≥moderate) ( Figure 4C, Table S6).

| Physician attitudes towards HCV treatment in people receiving OST
Physicians were asked a variety of questions about HCV treatment in people receiving OAT. The most common barriers identified included the perceived need for stable alcohol use (58% ≥moderate), concerns of adherence (55% ≥moderate), requirement for stable OAT (52% ≥moderate) and the challenging and marginalized lives of patients (49% ≥moderate). Only 25% reported that treating patients for HCV infection in a clinic for substance use was a ≥moderate barrier ( Figure 5, Table S7). to explore strategies to address these barriers. Moving forward, the challenge will be tailoring successful interventions to the particular jurisdiction and/or setting, given that models of care will differ and one size will not fit all. 23

ACK N OWLED G EM ENTS
The authors would like to thank the survey participants for their contribution to the research. The authors acknowledge Errol J. Philip, PhD for assistance with literature review and writing, Debra Bronstein for assistance with the qualitative assessment of the survey and Joana Matos, PhD for assistance with revision of the manuscript.

CO N FLI C T O F I NTE R E S T
JG is a consultant/advisor and has received research grants from