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HCV Screening USPSTF Draft Recommendations OPEN for PUBLIC COMMENT for 27 Days Explained
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from Jules: I just came from this meeting (The 2012 National Summit on HIV and Viral Hepatitis Diagnosis, Prevention, and Access to Care will take place November 26-28, 2012 in Washington, DC.), which was a gathering of about 200 stakeholders to discuss hepatitis & HIV concerns & included CDC, HHS, state & city health officials, researchers, industry, researchers & community. READ THE DRAFT Recommendations, link below. Public Comment is open from November 27 until Dec 24 2012, see link below. The USPSTF apparently at least in this case of HCV screening takes an undue amount of time, years, to review new evidence & new data, until it is too late to make reasonable impactful recommendations. In this case of HCV, we have new interferon-free orally administered HCV drugs, pills, that will be 2, 3 or 4 drug once or twice daily regimens that will have 95-100% SVR, cure, rates with 12 weeks duration of therapy. Recent data for these regimens was presented at the annual major liver meeting 2 weeks ago at AASLD in Boston. We know many individuals remain undiagnosed in the USA, its estimated that 75% are undiagnosed, millions of people are undiagnosed, and we also know that many people, many thousands, have advanced liver disease & will die not diagnosed (screening) and treated. The USPSTF recommendations apparently are relied on by insurance carriers on whether or not screening will be reimbursible & therefore utilized on a routine basis at doctor's offices, therefore directly affecting whether a doctor, nurse or patient use a HCV screening blood test to see if a person has HCV. Personally, I feel everyone should be screened for HCV, its a simple blood test that could be included in the routine blood work a person receives when they visit their doctor or nurse.
My understanding is that HHS Secretary Sebelius has the authority & power to overrule USPSTF, she could if she wants give HCV screening a grade A or B for baby boomers or for all as was recently recommended for HIV, routine screening for HIV for all for ages 15-64. So we all at this meeting decided to write & circulate a sign-on letter to her requesting her to do this. Unfortunately it took 6 years for the USPSTF to recommend HIV routine screening, we can't wait for an undue delay because many HCV+ people with advanced disease, aging baby boomers, those who could be detected with abnormal liver enzymes, those with cirrhosis could die having been undiagnosed waiting for adequate federal screening guidelines.
The USPSTF has in the recent past made very controversial recommendations that received quite a lot of criticism controversial 2009 recommendation of the United States Preventive Services Task Force (USPSTF) that routine screening mammography for breast cancer was unnecessary in women younger than 50.....USPSTF Recommends Against Prostate Cancer Screening ...Dec 29, 2011 - USPSTF Recommends Against Prostate Cancer Screening ... the U.S. Preventive Services Task Force (USPSTF) ignited controversy when it
Link to Draft Recommendations:
http://www.uspreventiveservicestaskforce.org/draftrec2.htm
Link to submit your public comment:
http://www.uspreventiveservicestaskforce.org/tfcomment.htm
Summary of Recommendations and Evidence
The U.S. Preventive Services Task Force (USPSTF) recommends screening for hepatitis C virus (HCV) infection in adults at high risk, including those with any history of intravenous drug use or blood transfusions prior to 1992 (see the Clinical Considerations for more information on risk factors).
This is a grade B recommendation.
The USPSTF recommends that clinicians consider offering screening for HCV infection in adults born between 1945 and 1965 (see the Clinical Considerations for more information on birth-cohort screening).
This is a grade C recommendation.
Rationale
Importance
HCV is the most common chronic bloodborne pathogen in the United States. It is a leading cause of complications from chronic liver disease. The prevalence of the antiHCV antibody in the United States is approximately 1.6%. From 1999 to 2008, about three fourths of patients in the United States with HCV infection were born between 1945 and 1965, with a peak prevalence of 4.3% in persons ages 40 to 49 years in 1999 to 2002 (1, 2). The strongest risk factor for HCV infection is a history of past or current intravenous drug use, with most studies reporting a prevalence of ≥50%. The yearly incidence of HCV infection averaged more than 200,000 cases per year in the 1980s, but had decreased to 25,000 cases per year by 2001. In 2009, the Centers for Disease Control and Prevention (CDC) estimated that 16,000 new cases of HCV infection occurred. There were an estimated 15,000 deaths from HCV infection in 2007. HCV-related end-stage liver disease is the most common indication for liver transplantation among U.S. adults (>30% of cases). Studies suggest that about half of the recently observed threefold increase in incidence of hepatocellular carcinoma is related to acquisition of HCV infection 2 to 4 decades earlier (1).
Detection
In 2004, the USPSTF concluded that the evidence is adequate that antiHCV antibody testing with confirmatory polymerase chain reaction testing accurately detects chronic HCV infection.
There is also adequate evidence that various noninvasive tests have good diagnostic accuracy in diagnosing fibrosis or cirrhosis.
Benefits of Detection and Early Intervention
The USPSTF found inadequate evidence of a direct benefit of screening for HCV infection in asymptomatic adults in reducing morbidity or mortality.
There is adequate evidence that HCV screening and tests to determine the presence of chronic HCV infection are accurate. Retrospective studies found that screening strategies that target individuals with risk factors for HCV infection (such as history of past or present intravenous drug use, sex with an intravenous drug user, or blood transfusion prior to 1992) are associated with high sensitivities (>90%) and small numbers needed to screen to identify one case of HCV infection (<20). Whether such high sensitivity can be achieved in clinical practice depends on how well clinicians elicit risk factors prior to screening, and how willing patients are to disclose them.
The USPSTF found adequate evidence that antiviral regimens result in sustained viral response (SVR). The USPSTF also found adequate evidence that SVR is associated with a reduction in the long-term clinical outcome of all-cause mortality. The USPSTF concluded that screening is of moderate benefit for populations at high risk. The USPSTF concluded that the benefit of screening all adults in the birth cohort born between 1945 and 1965 is at least small. The benefit is smaller given the lower prevalence in this population.
The USPSTF found inadequate evidence that counseling or immunization of patients with HCV infection improves health outcomes, reduces transmission, or changes high-risk behaviors. There was also inadequate evidence that knowledge of being positive for HCV infection reduces high-risk behaviors. There was inadequate evidence that labor management and breastfeeding strategies in HCV-positive women are effective at reducing risk of mother-to-child transmission.
Harms of Detection and Early Intervention
The USPSTF found inadequate evidence on the harms of screening for HCV. Potential harms of screening for HCV include anxiety, patient labeling, and feelings of stigmatization.
Adequate evidence was found regarding the harms associated with the diagnostic workup for guiding treatment decisions (i.e., liver biopsy). These include bleeding, infection, and severe pain in approximately 1% and death in <0.2% of individuals undergoing a liver biopsy. However, there is adequate evidence that the use of liver biopsy to guide treatment decisions is declining, and thus the absolute risk to individuals who are currently diagnosed and being treated is likely declining.
The USPSTF found adequate evidence that antiviral therapy regimens have small to moderate harms, such as fatigue, headache, flu-like symptoms, hematologic events, and rash. Serious adverse events are self-limited and typically resolve after treatment is discontinued. There is adequate evidence that the harms of treatment are no greater than small.
USPSTF Assessment
The USPSTF concludes with moderate certainty that screening for HCV infection in adults at increased risk (e.g., history of intravenous drug use) has a moderate net benefit.
The USPSTF concludes with moderate certainty that screening for HCV infection in the 1945-1965 birth cohort has at least a small net benefit.
Clinical Considerations
Patient Population Under Consideration
This recommendation applies to all asymptomatic adults without known liver disease or functional abnormalities.
Assessment of Risk
Established high-risk factors for HCV infection include blood transfusion prior to 1992 and past or current intravenous drug use. Because of screening programs for donated blood, blood transfusions are no longer an important source of HCV infection. In contrast, 60% of new HCV infections occur in individuals who report injecting drugs within the last 6 months (1).
Other risk factors include chronic hemodialysis, being born to an HCV-infected mother, incarceration, intranasal drug use, getting an unregulated tattoo, and other percutaneous exposures (e.g., in health care workers, having surgery prior to the implementation of universal precautions). Evidence on tattoos and other percutaneous exposures as risk factors for HCV infection is limited (1).
Large population-based studies report independent associations between high-risk sexual behaviors (multiple sex partners, unprotected sex, sex with a person infected with HCV, or sex with an intravenous drug user) and HCV infection. However, HCV appears to be inefficiently transmitted through sexual contact, and observed associations may be confounded by other high-risk factors.
In 1998, the highest prevalence rates of the antiHCV antibody were found in individuals with significant direct percutaneous exposures, such as intravenous drug users, persons with hemophilia, or recipients of blood transfusions (60% to 90%); moderate rates were found in individuals with less significant percutaneous exposures involving smaller amounts of blood, such as hemodialysis patients (10% to 30%). Individuals with mucosal exposures, such as those engaging in high-risk sexual behaviors (1% to 10%), and those with infrequent percutaneous exposures, such as health care workers (1% to 2%), had the lowest prevalence rates (3, 4).
Among patients with abnormal results on liver function tests (aspartate transaminase, alanine transaminase, or bilirubin) who were tested for reasons other than screening, evaluation of the cause of the abnormality often includes testing for HCV infection and is considered case-finding, not screening; therefore, it is outside the scope of this recommendation.
Birth-Cohort Screening
Persons born between 1945 and 1965 are more likely to be diagnosed with HCV infection, because they may have received blood transfusions prior to the introduction of screening in 1992, or have a history of other risk factors for exposure decades earlier (2). Many individuals with chronic HCV infection are unaware of their condition. A risk-based approach may miss detection of a substantial proportion of HCV-infected individuals in the birth cohort, due to either lack of patient disclosure or knowledge about prior risk status. As a result, clinicians may consider a birth cohort-based screening approach for patients born between 1945 and 1965 who have no other known HCV risk factors. Screening in the birth cohort for HCV infection may identify infected patients at earlier stages of disease, before they develop complications from liver damage.
Screening Tests
HCV antibody testing with subsequent polymerase chain reaction testing for viremia is accurate for identifying patients with chronic HCV infection. Various noninvasive tests with good diagnostic accuracy are possible alternatives to liver biopsy for diagnosing fibrosis or cirrhosis.
Screening Intervals
There is no evidence about how often screening should occur.
Treatment
The purpose of antiviral treatment regimens for chronic HCV infection is to prevent long-term health complications of HCV infection (such as cirrhosis, liver failure, and hepatocellular carcinoma).
The combination of pegylated interferon (alfa-2a or -2b) plus ribavirin has been the standard treatment for HCV infection. In 2011, the Food and Drug Administration (FDA) approved the protease inhibitors boceprevir and telaprevir for the treatment of HCV genotype 1 infection (the predominate genotype in the United States). Trials have found increased SVR rates in patients with HCV genotype 1 infection who received triple therapy with pegylated interferon, ribavirin, and boceprevir or telaprevir compared with dual therapy with pegylated interferon plus ribavirin. There is a lack of evidence on the comparative effects of antiviral treatments on long-term clinical outcomes. Regimens with protease inhibitors are usually shorter than dual therapy (24 or 28 weeks vs. 48 weeks). Triple therapy with protease inhibitors is associated with an increased risk of hematologic events such as anemia, neutropenia, and thrombocytopenia (boceprevir) and rash (telaprevir) compared with dual therapy. These adverse events are self-limited and typically resolve after the discontinuation of treatment (5).
Other Considerations
Research Needs and Gaps
Future areas of research include demonstrating individual or public health benefits from counseling, immunizations, and behavioral changes following a diagnosis of HCV in asymptomatic patients; studies examining the impact of antiviral treatments on quality of life; studies designed to understand the comparative effectiveness of antiviral treatments on patients with a variety of medical and psychological comorbidities; and studies assessing the long-term harms associated with antiviral regimens.
Discussion
Burden of Disease
HCV is the most common chronic bloodborne pathogen in the United States. The prevalence of the antiHCV antibody in the United States is approximately 1.6% (1).
An estimated 78% of individuals who test positive for the antiHCV antibody have HCV levels detectable in the blood (viremia), reflecting chronic infection. Individuals who have HCV and undetectable viremia are diagnosed as "cured," as demonstrated by absence of serum HCV ribonucleic acid (RNA) (1).
The prevalence of chronic HCV infection peaked in 2001 at 3.6 million persons. From 1999 to 2008, three fourths of patients in the United States with HCV infection were born between 1945 and 1965, with a peak prevalence of 4.3% in persons ages 40 to 49 years. During the 1980s, the yearly incidence of HCV infection averaged more than 200,000 cases per year, but had decreased to 25,000 cases per year by 2001. In 2009, the CDC estimated that 16,000 new cases of HCV infection had occurred (1, 2).
HCV infection is the leading cause of complications from chronic liver disease, with HCV-related end-stage liver disease being the most common indication for liver transplantation among U.S. adults. It is estimated that the total number of patients with cirrhosis will peak at 1 million in 2020; however, rates of hepatic decompensation and liver cancer are expected to rise for another 10 to 13 years due to the lengthy lag time between infection and development of cirrhosis and other complications. There were an estimated 15,000 deaths from HCV infection in 2007 (1).
Scope of Review
Two reviews from the Agency for Healthcare Research and Quality (1, 5) were commissioned to update the 2004 USPSTF recommendation on screening for and treatment of HCV infection in asymptomatic adults (6). These reviews focused on evidence gaps identified in the previous USPSTF recommendation and new studies published since 2004. The reviews also examined the evidence on HCV screening in pregnant women.
Accuracy of Screening Tests
In 2004, the USPSTF found that screening with later-generation enzyme immunoassay and confirmatory recombinant immunoblot assay accurately detects the antiHCV antibody. In this evidence update, the USPSTF considered the evidence on the diagnostic accuracy of various noninvasive confirmatory tests (6). The USPSTF found more than 100 studies (including eight of good quality) that compared various noninvasive laboratory-based diagnostic tests with liver biopsy as the reference standard. Sensitivity and specificity varied depending on the cutoff used to define a positive test result. Several of the blood indices were associated with an area under the receiver operating characteristic curve of 0.75 to 0.86 for fibrosis and 0.80 to 0.91 for cirrhosis (considered good to very good values for diagnostic accuracy) (1).
One study evaluated clinical outcomes associated with different strategies to evaluate patients with HCV infection for treatment. A retrospective cohort study of 156 HCV-positive patients who received interferon plus ribavirin therapy found no difference in SVR rates between patients who did not undergo biopsy prior to treatment compared with matched patients who did undergo biopsy (41% vs. 44%; p=0.87). About three quarters of the patients who did not undergo biopsy refused biopsy and about one quarter had contraindications. The study was not designed or powered to evaluate longer-term clinical outcomes, and did not report harms associated with biopsy (1, 7).
Clinical practice is moving toward less routine use of biopsy prior to antiviral treatment. There are no studies reporting current estimates of the proportion of patients who undergo biopsy prior to treatment.
Effectiveness of Early Detection and Treatment
There is no direct evidence of the benefit of screening for HCV infection in asymptomatic adults in reducing morbidity or mortality. No randomized trials or observational studies compared clinical outcomes between individuals screened and not screened for HCV infection.
Various screening strategies have been proposed; however, no randomized trials or observational studies compared clinical outcomes of different approaches to screening for HCV. Five studies compared screening approaches to determine the relative yield of the different strategies. These studies of targeted screening strategies in high-risk individuals were associated with high sensitivities (>90%) and small numbers needed to screen to identify one case of HCV infection (<20). The studies used various criteria for targeted screening, but all included current or past injection drug use, sex with an injection drug user, and blood transfusion prior to 1992. Very narrow screening strategies (e.g., targeting only intravenous drug use) had very low numbers needed to screen, but missed up to two thirds of infected patients. None of the studies used the birth-cohort screening approach. The studies were retrospective and had methodological issues that limit the overall ability to compare screening strategies (1).
The USPSTF examined the evidence regarding benefits from counseling, immunizations, and behavioral changes following a diagnosis of HCV infection. No studies were found that evaluated effects of counseling or immunizations on health outcomes or transmission risk. One randomized trial found that a self-management program was associated with small increases in 36-Item Short-Form Health Survey vitality scores compared with the use of educational materials after 6 weeks, but there were no effects on other quality of life measures (8).
Three retrospective studies showed reduced alcohol use after a diagnosis of HCV infection, but two prospective studies found no associations of sustainable behavior change (alcohol use or intravenous drug use) with knowledge of diagnosis. Two cross-sectional studies had conflicting results (1).
There is limited evidence regarding effective counseling methods in decreasing high-risk behaviors. Two randomized trials reported mixed results regarding effects of behavioral-based counseling interventions compared with simple educational interventions. A before-after study of HCV-infected patients who were heavy drinkers found that a counseling intervention was associated with a >50% reduction in alcohol use (1).
SVR is an intermediate outcome used to measure treatment efficacy in clinical trials and is a basis for FDA drug approval. SVR is defined as a decrease in HCV RNA to undetectable levels 24 weeks after antiviral treatment and is associated with a sustained loss of detectable viremia.
SVR rates are the principal outcome used to assess the benefit of antiviral regimens, due to a lack of direct evidence on long-term clinical outcomes. Two trials of boceprevir and three trials of telaprevir with pegylated interferon (alfa-2a or -2b) plus ribavirin were found to be more effective in increasing SVR rates compared with dual therapy with pegylated interferon (alfa-2a or -2b) plus ribavirin. SVR rates ranged from 60% to 92% (genotype 1) with triple therapy regimens compared with 42% to 52% (genotype 1) with dual therapy (5).
The link between SVR and clinical outcomes has been evaluated in a number of studies. The largest study was a cohort study with 16,864 patients from the Department of Veterans Affairs (VA) that adjusted for many confounders (demographic factors, comorbidities, laboratory characteristics, treatment characteristics). This fair-quality study demonstrated a decrease in the risk of all-cause mortality compared with no SVR across patient groups stratified by genotype. Hazard ratios were 0.71 (95% confidence interval [CI], 0.60-0.86), 0.62 (95% CI, 0.44-0.87) and 0.51 (95% CI, 0.35-0.75) for genotypes 1, 2, and 3, respectively (9). Eighteen smaller cohort studies (n=102 to 2,698) found that SVR was associated with decreased risk of all-cause mortality and hepatic complications associated with chronic HCV infection, including studies of populations with baseline cirrhosis. The smaller cohort studies had methodological limitations. For example, only five studies evaluated important confounders (age, sex, genotype, viral load, fibrosis); four studies reported patients excluded or lost to followup. In addition, 10 of the 18 studies were conducted in Asia, where the incidence of hepatocellular carcinoma in patients with chronic HCV infection is higher than in the United States, possibly limiting applicability. However, the hazard ratios in the 18 cohort studies had similar estimates compared with the VA cohort study (5).
Antiviral therapy is contraindicated in pregnancy due to potential teratogenic effects. Although evidence is limited, no labor management intervention has been clearly shown to decrease risk of mother-to-child transmission of HCV infection. Breastfeeding does not appear to be associated with increased risk of mother-to-child transmission (1).
The USPSTF also reviewed modeling studies that informed the CDC's 2012 recommendation on screening for HCV, which reported large estimated reductions in HCV-related mortality with a birth-cohort approach versus risk-based screening. These estimates assumed lifetime rates of progression to cirrhosis in untreated patients with HCV infection of over 75%, and mortality rates due to HCV infection of over 30%. Longitudinal studies with up to 20 years followup report cirrhosis in 10% to 20% of HCV-infected patients, and the longest-duration study reported HCV-related mortality in 5.9% patients after 45 years. In addition, estimates of clinical benefit assumed that risk of cirrhosis and other complications of HCV infection in patients who experienced an SVR after antiviral therapy reverted to the risk in persons never infected (4). These assumptions relate to important uncertainties regarding the natural history of HCV infection. If progression to cirrhosis or mortality are lower than assumed, the benefit from screening and treatment would also be lower.
Potential Harms of Screening and Treatment
Potential harms associated with screening for HCV infection include anxiety, labeling, and an impact on relationships. Five studies of patients diagnosed with HCV infection suggest potential negative psychological and social effects, but the sample sizes were small and the studies had methodological flaws, such as the lack of an unscreened comparison group (1).
In addition to the potential harms of screening, there are harms related to the diagnostic evaluation of patients who test positive for the antiHCV antibody. In a study of 2,740 patients with chronic HCV infection and an Ishak fibrosis score of ≥3 (no uncompensated cirrhosis) undergoing liver biopsy, serious adverse events occurred in 1.1% of patients, including 0.6% experiencing serious bleeding and 0.3% experiencing severe pain (1). No deaths were reported. In five large interventions series published since 2004, mortality was less than 0.2% and serious complications were found in 0.3% to 1.0% of more than 62,000 patients undergoing liver biopsy (1).
There are harms related to the medications used to treat HCV. The most common adverse events of the antiviral regimens were fatigue, headache, and other flu-like symptoms, which were seen in as many as half of patients in some trials. Triple therapy with protease inhibitors was associated with increased risk of hematologic events (anemia, neutropenia, and thrombocytopenia, particularly with boceprevir) and rash (telaprevir) compared with dual therapy. Few serious adverse events were reported in the trials, and they were generally self-limited and typically resolved after the discontinuation of treatment (5).
Estimate of Magnitude of Net Benefit
The USPSTF found moderate certainty of a linkage between SVR and the clinical outcome of all-cause mortality, and moderate net benefit. The evidence supporting this linkage includes 1) consistent large effect sizes on clinical outcomes and 2) a large U.S. study that controlled for many confounders and found a large and early mortality reduction in all viral genotypes among patients likely to be similar to those detected and eligible for treatment through U.S. screening programs. As a result of the decreasing use of liver biopsy prior to antiviral treatment and evidence that antiviral therapy regimens have harms that are no greater than small, the USPSTF concluded that screening for HCV infection is of moderate net benefit for high-risk populations with a high prevalence (e.g., blood transfusion recipients prior to 1992, intravenous drug users). The USPSTF concluded that the net benefit of screening adults in the birth cohort born between 1945 and 1965 is at least small, given the substantially lower prevalence in this population compared with high-risk populations.
How Does Evidence Fit With Biological Understanding?
The natural history of HCV is unclear. Chronic HCV infection is defined by the presence of HCV RNA in the blood for at least 6 months after acute infection. Chronic infection occurs in 78% of infected patients; however, there is an inability to determine which infected patients will develop cirrhosis and which patients will not. Many chronically infected patients do not develop histological evidence of liver disease or have mild liver disease, while others progress to cirrhosis, end-stage liver disease, or hepatocellular carcinoma. Cohort studies showed that approximately 7% to 24% of individuals will develop cirrhosis after 20 years of infection, with possible acceleration of cirrhosis after infection for 20 years, and up to 5% will die from liver-related complications (1).
SVR is associated with the absence of detectable serum HCV RNA, improved histologic changes, and normalization of liver transaminases. Its presence is considered to reflect resolution of HCV infection.
Update of the Previous USPSTF Recommendation
In 2004, the USPSTF recommended against screening for HCV infection in adults not at increased risk (D recommendation) and found insufficient evidence to recommend for or against screening in adults at high risk (I statement). The D recommendation in average-risk individuals was based on a low prevalence of HCV infection, the natural history of chronic HCV infection, a lack of direct evidence showing that screening or antiviral treatments improves important health outcomes, and the potential harms of screening. The USPSTF found insufficient evidence on the effects of screening or antiviral regimens on clinical outcomes and on the link between improved intermediate and clinical outcomes to determine the balance of benefits and harms of screening (6).
In this update, the USPSTF reviewed the indirect chain of evidence demonstrating the benefits of screening through improvement of the intermediate outcome SVR following triple-regimen antiviral treatments and resulting in the improvement of all-cause mortality. The USPSTF examined the evidence and accepted the association between SVR after antiviral treatments and improved clinical outcomes with moderate certainty. In reviewing the prevalence data on high-risk groups and the potential for reduced transmission, the USPSTF concluded that screening high-risk individuals (prevalence of ≥50%) would result in a moderate net benefit, while screening the birth cohort (prevalence of about 3% to 4%) would result in a net benefit that is at least small.
With regards to harms, the use of liver biopsy is decreasing, and the few serious adverse events reported in the trials were self-limited and typically ended after treatment discontinuation.
As a result of the evidence, the USPSTF changed its recommendations to a B recommendation for individuals at high risk and a C recommendation for the 1945-1965 birth cohort.
Recommendations of Others
The American Association for the Study of Liver Disease (10), the Infectious Diseases Society of America (11), and the American College of Gastroenterology (12) recommend screening in higher-risk patients. The CDC now recommends screening of high-risk patients and age cohort-based HCV screening in all persons born between 1945 and 1965 (4).
*The U.S. Preventive Services Task Force defines certainty as "likelihood that the USPSTF assessment of the net benefit of a preventive service is correct." The net benefit is defined as benefit minus harm of the preventive service as implemented in a general, primary care population. The USPSTF assigns a certainty level based on the nature of the overall evidence available to assess the net benefit of a preventive service.
References
1. Chou R, Cottrell EB, Wasson N, Rahman B, Guise JM. Screening for Hepatitis C Virus Infection in Adults. Comparative Effectiveness Review No. 69. AHRQ Publication No. 12-EHC090-EF. Rockville, MD: Agency for Healthcare Research and Quality; 2012. Accessed at http://www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productid=1283 on 20 November 2012.
2. Smith BD, Patel N, Beckett GA, Jewett A, Ward JW. Hepatitis C virus antibody prevalence, correlates and predictors among persons born from 1945 through 1965, United States, 1999-2008 [Abstract]. Hepatology. 2011;54:4(Suppl 1):554A-5.
3. Centers for Disease Control and Prevention. Recommendations for the prevention and control of hepatitis C (HCV) infection and HCV-related chronic disease. MMWR Recomm Rep. 1998;47(RR-19):1-39.
4. Smith BD, Morgan RL, Beckett GA, Falck-Ytter Y, Holtzman D, Teo CG, et al; Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep. 2012;61(RR-4):1-32.
5. Chou R, Hartung D, Rahman B, Wasson N, Cottrell E, Fu R. Treatment for Hepatitis C Virus Infection in Adults. Comparative Effectiveness Review No. 76. Rockville, MD: Agency for Healthcare Research and Quality; 2012. Accessed at http://www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productid=1298 on 20 November 2012.
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