About this Guideline - AIDS Institute Clinical Guidelines

July 2017

NYSDOH AIDS Institute HCV Guideline Committee

The New York State Department of Health (NYSDOH) AIDS Institute (AI) protects and promotes the health of New York State’s diverse population through disease surveillance and the provision of quality services for prevention, health care, and psychosocial support for those affected by HIV/AIDS, sexually transmitted diseases, viral hepatitis and related health concerns. In addition, the NYSDOH AI promotes the health of LGBT populations, substance users, and the sexual health of all New Yorkers. In response to the availability of effective new treatments for HCV, the AIDS Institute convened the HCV Guideline Committee in 2014 to develop a New York State guideline for the clinical care of HCV infection.

Makeup: The members of the HCV Guideline Committee (see Box 5: HCV Guideline Committee Leaders, Members, and External Reviewers) were appointed by the NYSDOH AI to ensure representation of clinical practice in all major regions of the state, relevant medical disciplines and sub-specialties, key NYS agencies, community stakeholders, and patient advocates. Individuals confirmed as Committee members are required to disclose any potential conflicts of interest; disclosures are reviewed and approved by the NYSDOH AIDS Institute Office of the Medical Director (see Funding and Financial Disclosure of Potential Conflicts of Interest).

Role: Committee members actively participate in guideline development, including evidence review, drafting of recommendations and text, manuscript review, consensus approval of all recommendations, and rating of recommendations.

Leadership: The HCV Planning Group of committee leaders refined the manuscript, facilitated consensus approval of all recommendations, addressed feedback from external peer and consumer reviewers, and elicited input from other key AI guideline committees, including the Medical Care Criteria Committee (Adult HIV guidelines) and the Perinatal Transmission Prevention Committee.

HCV Guideline Committee Planning Group:

Joshua S. Aron, MD, Co-Chair
Christine A. Kerr, MD, Co-Chair
David Bernstein, MD, FACG, AGAF, FACP, Contributing Committee Member
Colleen Flanigan, RN, MS, AIDS Institute Hepatitis Bureau Director
Charles J. Gonzalez, MD, AIDS Institute Deputy Medical Director
Christopher J. Hoffmann, MD, MPH, JHU Principal Investigator

Box 4: HCV Guideline Committee: Leadership, Contributing Members, Liaisons, and Guideline Reviewers

Committee Leadership

Co-Chair: Joshua S. Aron, MD, Elmhurst Hospital Center, Elmhurst, NY
Co-Chair: Christine A. Kerr, MD, Hudson River Healthcare, Beacon, NY
Medical Director: Bruce D. Agins, MD, MPH, New York State Department of Health AIDS Institute, New York, NY
Deputy Director: Lyn C. Stevens, MS, NP, ACRN, New York State Department of Health AIDS Institute, Albany, NY
Principal Investigator: Christopher J. Hoffmann, MD, Johns Hopkins University School of Medicine, Baltimore, MD

Contributing Members

Mary Angerame, MS, APN-BC, Jordan Health, Rochester, NY
Ayse Aytaman, MD, AGAF, FACG, Veterans Affairs New York Harbor Healthcare System, Brooklyn, NY
David Bernstein, MD, FAASLD, FACG, AGAF, FACP, Hofstra-Northwell School of Medicine Manhasset, NY
Lorna M. Dove, MD, MPH, New York-Presbyterian Hospital, New York, NY*
John J. Faragon, PharmD, BCPS, AAHIVP, Albany Medical Center, Albany, NY
Douglas G. Fish, MD, New York State Department of Health, Albany, NY
Alain H. Litwin, MD, MPH, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY
Kristen Marks, MD, Weill Cornell Medical College, New York, NY
Anthony D. Martinez, MD, University at Buffalo, Buffalo, NY
Brianna Norton, DO, MPH, Montefiore Medical Group, Bronx, NY
Russell Perry, MD, FAAFP, Bronx Lebanon Hospital, Bronx, NY
Ponni V. Perumalswami, MD, Icahn School of Medicine at Mount Sinai, New York, NY
Jeffrey J. Weiss, PhD, MS, Mount Sinai School of Medicine, New York, NY

Agency, Consumer, and Program Liaisons

Consumer Liaisons: Ivan Flores*, The Wellness Center at Port Morris, Bronx, NY; Cheryl Santoro, Hudson River Health Care, Peekskill, NY
Medical Society of the State of New York: William M. Valenti, MD, FIDSA, Trillium Health, Rochester, NY
New York City Department of Health and Mental Hygiene: Fabienne Laraque*, MD, MPH, Long Island City, NY
NYC Health + Hospitals: Vinh Pham, MD, PhD, Bellevue Hospital Center, New York, NY
New York State Department of Corrections and Community Supervision (NYS DOCCS): Paula R. Bozer, MD, Wende Correctional Facility, Alden, NY; and Carl J. Koenigsmann, MD, Albany, NY
New York State Office of Alcoholism and Substance Abuse Services Liaison: Michele Falkowski*, RN, BSN, CARN, Orangeburg, NY
Treatment Action Group (TAG): Annette Gaudino, New York, NY; Tracy Swan*, New York, NY

AIDS Institute Staff

Director, Bureau of Hepatitis Health Care: Colleen Flanigan, RN, MS, Albany, NY
Associate Medical Director for Science and Policy: Charles J. Gonzalez, MD, New York, NY
Medical Director, Clinical Education Initiative: Cheryl A. Smith, MD, New York, NY
Guidelines Program Manager: Laura Duggan Russell, MPH, Albany, NY
Guidelines Program Coordinator (former): Tracy Hatton, MPH, New York, NY

AIDS Institute HIV Clinical Guidelines Program Committee Reviewers

Medical Care Criteria Committee: Samuel T. Merrick, MD (Chair), New York-Presbyterian Hospital, New York, NY; Joseph P. McGowan, MD, FACP, FIDSA (Vice-Chair), Northwell Health, Manhasset, NY; Judith A. Aberg, MD, FIDSA, FACP (Chair Emeritus), Icahn School of Medicine at Mount Sinai, New York, NY
Committee for the Prevention of Mother to Child Transmission of HIV: Rodney L. Wright, MD, MS (Co-Chair), Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY

External Peer Reviewers

Douglas T. Dieterich, MD, Icahn School of Medicine at Mount Sinai, New York, NY
Ira M. Jacobson, MD, Mount Sinai Beth Israel, New York, NY
Oluwaseun Falade-Nwulia, MBBS, MPH, Johns Hopkins University School of Medicine, Baltimore, MD
Karla Thorton, MD, University of New Mexico School of Medicine, Albuquerque, NM
Susan Lee, PharmD, BCPS, CDE, Hofstra-Northwell School of Medicine Manhasset, NY

*These individuals participated in the early development of the HCV guideline but were no longer in their positions, or were not able to serve as liaisons, at the conclusion of the project.

Johns Hopkins University (JHU) Editorial Role

The JHU editorial team coordinated, guided, and documented all Committee activities, and edited the guideline material for clarity, flow, and style.

JHU editorial team:

Mary Beth Hansen, MA, JHU Project Director
Christina Norwood, MS, ELS, Senior Medical Editor
Jen Ham, MPH, JHU Medical Editor; Lead Editor
Johanna Gribble, MA, JHU Medical Editor
Celine Daly, MD, JHU, Contributing Editor
Jesse Ciekot, Program Coordinator

Funding and Disclosure of Potential Conflicts of Interest

July 2017

Funding: The Treatment of Chronic HCV with Direct-Acting Antivirals guideline was developed using New York State funds awarded as a grant to the Johns Hopkins University School of Medicine, Division of Infectious Diseases, from the New York State Department of Health AIDS Institute.

Conflicts of interest: All active committee members, invited consultants and coauthors, peer reviewers, and program staff are required to disclose financial relationships with commercial entities, including gifts that may be actual conflicts of interest or may be perceived as conflicts. These individuals must disclose financial relationships annually, for themselves, their partners/spouses, and their organization/institution. On their annual disclosures, committee members are asked to report for the previous 12 months and the upcoming 12 months.

No conflicts were reported by the Committee Chair and Co-Chair, the majority of Committee members, and all NYSDOH AI and JHU program staff. Box 6, below, lists the conflicts reported by eight Committee members.

Management of potential conflicts of interest: All reported financial relationships with commercial entities are reviewed by the NYSDOH AI guidelines program to assess the potential for undue influence on guideline recommendations made by the Committee. For the Committee members reporting conflicts, it was determined that: 1) in this guideline, no individual drug or device is recommended over another; and 2) individual committee members reported concurrent conflicts with competing pharmaceutical companies.

Any potential for undue influence is also mitigated by the consensus process. All guideline recommendations received consensus approval of the full HCV Committee. The Committee Chairs and the NYSDOH AI Medical Director, none of whom reported conflicts of interest, performed the final review and approve the guideline.

All external reviewers, including peer reviewers and representatives from other NYSDOH AI Clinical Guidelines committees, were also required to submit conflict of interest/financial disclosure information, which were similarly screened. Three reviewers reported conflicts, which are listed in Box 5.

Box 5: Reported Conflicts of Interest/Financial Disclosure Results
Committee/Guideline Role	Relationships disclosed for the previous and upcoming 12 months
Committee and Planning Group Member	Consultant to: AbbVie, Bristol-Myers Squibb, Gilead, Merck Research support from: Merck, AbbVie, Bristol-Myers Squibb, Gilead Speakers’ bureau for: BMS, Gilead, Merck, AbbVie
Committee Member	Consultant to: Bristol-Myers Squibb, Gilead, and ViiV Speaker: AbbVie, Janssen, Merck
Committee Member	Consultant to: Gilead Sciences, Merck Pharmaceuticals, AbbVie
Committee Member	Consultant to: Gilead, Bayer, Intercept Research support from: AbbVie, Salix, Gilead, AbbVie Speakers’ bureau for: Merck, Bayer, Intercept, Gilead, AbbVie, Salix
Committee Member	Advisory Board for: Gilead (Primary Care Advisory Board HCV) Speakers’ bureau for: AbbVie
Committee Member	Consultant to: Roche Diagnostics Research support from: Gilead
Committee Member	Consultant to: AbbVie Research support from: Gilead
Committee Member	Research support from: BMS, Gilead, and Merck
NYSDOH AI Medical Care Criteria Committee Reviewer	Consultant to: Merck Research support from: ViiV, Gilead
External Peer Reviewer	Consultant to: AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck
External Peer Reviewer	Consultant to: AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck: Achillion, Intercept, Trek Research support from: AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck Speakers bureau for: AbbVie, Bristol-Myers Squibb, Gilead, Janssen

Evidence Collection and Review

July 2017

The NYSDOH AI guideline development process is based on a systematic search and analysis of the published evidence. Box 6, below, illustrates the evidence review and selection process.

Box 6: Evidence Collection and Review Processes
Step 1	HCV Committee defines the goal of the guideline: To provide evidence-based clinical recommendations for primary care management of chronic hepatitis C infection, including screening, diagnosis, pretreatment assessment, treatment options, and post-treatment monitoring
Step 2	With individual authors, JHU editorial staff conducts a targeted literature search in PubMed using MESH terms. All searches limited to studies that 1) were published in the 5 years prior to the date of the literature search; 2) involved only human subjects; and 3) were published in English
Step 3	Authors review studies identified in searches; specific exclusion criteria include: 1) Studies involving interferon (IFN) treatment for chronic HCV infection; 2) Studies of HCV-associated comorbidities except those influencing HCV treatment decisions
Step 4	Authors and editorial staff conduct additional searches using PubMed and online databases to identify: Studies published prior to the 5-year search limit Studies published during the guideline development process Recent conference abstracts, such as the annual conferences of the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL). Committee authors also consulted the HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C Infectious Diseases Society of America, a website produced by the AASLD and IDSA, which features current guidelines for treating HCV. New York State epidemiologic data
Step 5	Development of guideline recommendations Authors review evidence and draft recommendations Planning Group members review, refine, and approve draft recommendations Full committee reviews and reaches consensus on recommendations Rating subcommittee reviews the cited evidence and assigns a two-part rating to each recommendation to indicate the strength of the recommendation and the quality of the supporting evidence; consensus is reached on ratings
Step 6	Ongoing Update Process JHU editorial staff continue to collect evidence related to original searches and monitor for new drug approval Planning Group reviews new evidence at least 3 times per year, more often if newly published studies, new drug approval, or drug-related warning indicates need for an immediate change to the published guideline. Committee reviews and approves changes to the guideline Committee initiates a full review of guideline 4 years after the original publication date NYSDOH AI publishes an update 5 years after the previous publication date

Recommendation Development and Rating Process

July 2017

The clinical recommendations presented in this guideline were developed by consensus based on a synthesis of the current evidence collected through the systematic search described above. If no data were available, the recommendations are based on expert opinion, and this status is indicated in the rating and in the text.

The Planning Group met via monthly teleconferences over 18 months to finalize the guideline and reach consensus on recommendations and rationale. Once consensus among the Planning Group members was reached, the guideline was reviewed by the full HCV Committee, including consumer liaisons, and consensus was reached on all recommendations. These deliberations were conducted by teleconference; committee members were invited to submit comments in writing as well. Full committee review discussions were recorded, and recordings were reviewed carefully to ensure that all decisions and changes were captured and integrated into the manuscript.

Members of the Planning Group then individually reviewed the evidence for each recommendation and assigned a two-part rating (see below). The individual ratings were compiled into a report distributed to all raters, and conference call discussions were held to deliberate ratings for which consensus was needed. Once all raters agreed on the interpretation of evidence and ratings for all recommendations, the guideline was sent to the NYSDOH AI for review and approval.

AIDS Institute HIV Clinical Guidelines Program Recommendations Rating Scheme
Strength of Recommendation	Quality of Supporting Evidence
A = Strong	1 = At least 1 randomized trial with clinical outcomes and/or validated laboratory endpoints
B = Moderate	2 = One or more well-designed, nonrandomized trial or observational cohort study with long-term clinical outcomes
C = Optional	3 = Expert opinion

External Review

July 2017

Five external peer reviewers recognized for their experience and expertise in the treatment of chronic HCV infection were identified by program leaders (see Box 5: HCV Committee: Leadership, Contributing Members, Liaisons, and Guideline Reviewers). These individuals submitted a financial disclosure statement for the purpose of identifying potential conflicts of interest before participating as peer reviewers. Disclosure information is included in Box 6: Reported Conflicts of Interest/Financial Disclosure Results.

Peer reviewers were asked to review the guideline for accuracy, balance, clarity, and practicality of the recommendations for primary care providers. The Planning Group addressed peer review feedback; any conflicting opinions were resolved by the Committee chairs.

Members of NYSDOH AI Medical Care Criteria Committee (Adult HIV Guidelines Committee) and the Perinatal Transmission Prevention Committee also provided reviews.

Guideline Updates

July 2017

Members of the HCV Committee will monitor developments in the field of HCV treatment in an ongoing structured manner to maintain guideline currency. Once the guidelines are published on the program website: www.hivguidelines.org, any updates will be made to the HTML document as needed as treatment of chronic HCV with DAAs is a rapidly evolving field.

Notification of newly published studies will be automated, and the Planning Group will review new data at least every 4 months. Newly published data that provide support for existing recommendations will be cited in the text, and the studies will be added to the reference list(s).

If newly published data prompt a revision to recommendations or rationale, the Planning Group will propose appropriate edits and determine whether the changes warrant full committee review and approval. If full committee review is required, a conference call will be convened for that purpose.

If a new medication or formulation is approved, the Planning Group will be convened via conference call to examine the data, consider inclusion in the guideline, and determine the need for full committee review and approval.

The full guideline will be reviewed and updated on the 4th anniversary of publication to prepare for publication of an updated guideline on or before the 5th anniversary of publication.