Draft Research Plan
Draft Research Plan for Hepatitis B Virus Infection: Screening in Nonpregnant Adolescents and Adults
This opportunity for public comment expires on January 2, 2019 at 8:00 PM EST
Note: This is a Draft Research Plan. This draft is distributed solely for the purpose of receiving public input. It has not been disseminated otherwise by the USPSTF. The final Research Plan will be used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Review will form the basis of the USPSTF Recommendation Statement on this topic.
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
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In an effort to maintain a high level of transparency in our methods, we open our draft Research Plans to a public comment period before we publish the final version.
Draft: Proposed Key Questions to Be Systematically Reviewed
- What are the benefits of screening for hepatitis B virus (HBV) infection in asymptomatic, nonpregnant adolescents and adults on morbidity, mortality, and disease transmission?
- What are the harms of screening for HBV infection (e.g., labeling, anxiety, and harms of confirmatory tests, including biopsy)?
- What is the yield (number of new diagnoses per tests performed) and sensitivity of alternative HBV screening strategies (e.g., universal vs. targeted screening, or screening strategies based on alternative risk factors)?
- How effective is antiviral treatment at improving intermediate outcomes in nonpregnant adolescents and adults with chronic HBV infection, including virologic or histologic improvement, clearance of hepatitis B e-antigen (HBeAg) (as indicated by loss of HBeAg or acquisition of antibody to HBeAg [anti-HBe]), or clearance of hepatitis B surface antigen (HBsAg) (as indicated by loss of HBsAg or acquisition of hepatitis B surface antibody [anti-HBs])?*
- How effective is antiviral treatment at improving health outcomes in nonpregnant adolescents and adults with chronic HBV infection?*
- What are the harms associated with antiviral treatment of chronic HBV infection in nonpregnant adolescents and adults?*
- What is the association between improvements in intermediate outcomes as a result of antiviral treatment of chronic HBV infection and reduction in risk of HBV-related adverse health outcomes?
*Subpopulations of interest for Key Questions 4, 5, and 6 include those defined by age, race/ethnicity, sex, HBV genotype, HBeAg status, fibrosis stage, alanine transaminase level, and HBV deoxyribonucleic acid (DNA) level.
Draft: Proposed Contextual Questions
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
- What are the effects of different risk- or prevalence-based methods for screening for HBV infection in modeling studies?
- What is the accuracy of tools for identifying persons with chronic HBV infection?
- In persons with serologic evidence of HBV infection (positive for antibody to hepatitis B core antigen or positive for HBsAg), what is the likelihood of reactivation following exposure to immunosuppressant therapy, and what is the effectiveness of interventions to improve clinical outcomes associated with reactivation?
Draft: Proposed Research Approach
The Proposed Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions (KQs).
|Definition of Disease||Chronic HBV infection, defined as detectable HBsAg in blood serum for >6 months||Acute HBV infection|
|Populations||KQs 1–3: Nonpregnant adults (age ≥18 years) and adolescents (ages 13 to <18 years) with no signs or symptoms of HBV infection
KQs 4–7: Nonpregnant adults and adolescents with chronic HBV infection
|KQs 1–3: Symptomatic patients, children age <13 years, pregnant women, persons living with HIV or hepatitis C virus infection, persons who have been previously treated for HBV infection, and other special populations (e.g., persons undergoing hemodialysis or an organ transplant)|
|Interventions||KQs 1–3: Screening, including alternative screening strategies (KQ 3)
KQs 4–7: Antiviral treatments approved by the FDA for patients who have never been treated for HBV infection. Therapies will be classified as:
|KQs 4–7: Antiviral treatments not approved by the FDA; combination therapy|
|Comparators||KQs 1, 2: No screening
KQ 3: One screening strategy vs. an alternative screening strategy
KQs 4–6: No treatment; preferred vs. nonpreferred antiviral therapiesKQ 7: Effects on intermediate outcome (HBV DNA level, HBeAg status, alanine transaminase level, fibrosis) as a result of antiviral therapy vs. no effects on intermediate outcome
|Outcomes||KQs 1, 5, 7:
KQ 3: Yield (number of new diagnoses per number of persons screened) and sensitivity (number of diagnoses of HBV infection per number of total HBV diagnoses)
|KQ 4: Drug resistance; development of mutations or antibodies to drugs|
|Setting||All KQs: Primary care and primary care–referable settings (e.g., correctional settings, community care settings serving persons who inject drugs, men who have sex with men, or persons with sexually transmitted diseases)
KQs 1–3: United States and countries with similar HBV prevalence
KQs 4–7: All countries
|Study Designs||KQs 1–3: Randomized, controlled trials; cohort studies; and case-control studies; will also include cross-sectional studies for KQ 3
KQ 6: All of the above study designs, plus cohort studies of harmsKQ 7: Cohort studies examining the association between intermediate and clinical outcomes after antiviral treatment
|KQs 1–3: Uncontrolled studies (e.g., case studies, treatment series)|
Abbreviations: anti-HBe = antibody to hepatitis B e-antigen; anti-HBs = hepatitis B surface antibody; DNA = deoxyribonucleic acid; FDA = U.S. Food and Drug Administration; HBeAg = hepatitis B e-antigen; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus.
Internet Citation: Draft Research Plan: Hepatitis B Virus Infection: Screening in Nonpregnant Adolescents and Adults. U.S. Preventive Services Task Force. November 2018.