Rein DB, Smith BD, Wittenborn JS, Lesesne SB, Wagner LD, Roblin DW, et al. The cost-effectiveness of birth-cohort screening for hepatitis C antibody in U.S. primary care settings. Ann Intern Med 2012;156: 263-270. (Reprinted with permission.)
BACKGROUND: In the United States, hepatitis C virus (HCV) infection is most prevalent among adults born from 1945 through 1965, and approximately 50% to 75% of infected adults are unaware of their infection. OBJECTIVE: To estimate the cost-effectiveness of birth-cohort screening. DESIGN: Cost-effectiveness simulation. DATA SOURCES: National Health and Nutrition Examination Survey, U.S. Census, Medicare reimbursement schedule, and published sources.TARGET POPULATION: Adults born from 1945 through 1965 with 1 or more visits to a primary care provider annually.TIME HORIZON: Lifetime.PERSPECTIVE: Societal, health care.INTERVENTION: One-time antibody test of 1945-1965 birth cohort.OUTCOME MEASURES: Numbers of cases that were identified and treated and that achieved a sustained viral response; liver disease and death from HCV; medical and productivity costs; quality-adjusted life-years (QALYs); incremental cost-effectiveness ratio (ICER). RESULTS OF BASE-CASE ANALYSIS: Compared with the status quo, birth-cohort screening identified 808,580 additional cases of chronic HCV infection at a screening cost of $2874 per case identified. Assuming that birth-cohort screening was followed by pegylated interferon and ribavirin (PEG-IFN+R) for treated patients, screening increased QALYs by 348,800 and costs by $5.5 billion, for an ICER of $15,700 per QALY gained. Assuming that birth-cohort screening was followed by direct-acting antiviral plus PEG-IFN+R treatment for treated patients, screening increased QALYs by 532,200 and costs by $19.0 billion, for an ICER of $35,700 per QALY saved. RESULTS OF SENSITIVITY ANALYSIS: The ICER of birth-cohort screening was most sensitive to sustained viral response of antiviral therapy, the cost of therapy, the discount rate, and the QALY losses assigned to disease states. LIMITATION: Empirical data on screening and direct-acting antiviral treatment in real-world clinical settings are scarce. CONCLUSION: Birth-cohort screening for HCV in primary care settings was cost-effective. PRIMARY FUNDING SOURCE: Division of Viral Hepatitis, Centers for Disease Control and Prevention.
“Americans can always be counted on to do the right thing…after they have exhausted all other possibilities.”
After all but ignoring screening for hepatitis C virus (HCV) for many years (not for lack of will, but from lack of funding), the Centers for Disease Control and Prevention (CDC) has recommended universal screening for Baby Boomers.1 In the United States, HCV prevalence is the highest in those born between 1946 and 1970; 1 in 30 Baby Boomers are infected with HCV. The majority acquired hepatitis C decades ago, before it was even identified (1989).2 Even more troubling is that by 2020, at least one third of them will already have progressed to cirrhosis with its apocalyptic effect on health and healthcare costs.3
Up to three quarters of individuals infected with HCV in the United States are unaware of their HCV status.1 The CDC HCV screening recommendations were, until recently, exclusively targeting individuals with high-risk behaviors.4 This is because screening of HCV has been shown to be cost-effective in populations with high prevalence.5 This method is undoubtedly high yield when both the right question is asked and the right answer is provided. However, some individuals have used intranasal or intravenous drugs only once and do not consider themselves at risk or are reluctant to report remote risky behaviors. Risk-based screening is also dependent on the screener's HCV awareness, willingness, and time to administer a high-risk behavior questionnaire during a medical visit. Risk-based screening might be a better tool to identify incident, rather than prevalent, cases of HCV. Because so many individuals are unaware of their infection, there is a need for improvement in the tools used to identify persons who are infected with HCV for years. Because 1 of 30 Baby Boomers is infected with HCV, birth-cohort screening may well be part of the solution.
Currently, we have almost 1 year's worth of experience with direct-acting antivirals (DAAs). The recent approval of a protease inhibitor (PI), in addition to pegylated interferon and ribavirin (Peg-IFN/RBV) has increased the rate of eradication of HCV genotype 1 from 40%-50%6 to 66%-75% in 2011, allowing shortened treatment duration (from 48 to 24-28 weeks) in more than half of the patients.7, 8 The availability of such effective therapy, known to decrease HCV-related morbidity and mortality, can justify the expansion of screening recommendations, even if the medication is enormously costly.
The article by Rein et al.9 demonstrates that birth-cohort screening for HCV in primary care settings is cost-effective in the United States based on mathematical models. By using cost-effectiveness simulation models that took into consideration the prevalence of HCV, its natural history, and the effect of antiviral treatment on morbidity and mortality, the investigators estimated that such an initiative would identify 808,580 new cases of chronic HCV among Baby Boomers at a screening cost of $2,874 per new infection identified. They simulated different scenarios, including a one-time birth-cohort screening of all people born from 1945 through 1965 unaware of their HCV antibody status. They either assumed (1) all identified patients would be offered Peg-IFN/RBV or (2) those with genotype 2 and 3 infection would be offered Peg-IFN/RBV, whereas those with genotype 1 infection would be offered triple therapy with Peg-IFN/RBV and a PI, which is the new standard of care and, consequently, the most plausible scenario. Compared with risk-based screening and assuming treatment with Peg-IFN/RBV for all, 82,300 deaths from HCV would be avoided at a cost of $15 700 per quality-adjusted life-years (QALYs) gained. Using new DAAs in combination with Peg-IFN/RBV, 121,000 deaths from HCV would be avoided at a cost of $35,700 per QALYs saved. In other words, the incremental cost-effectiveness ratio (ICER) of birth-cohort screening with DAAs plus standard treatment was $35,700 per QALYs saved, compared with risk-based screening. As pointed out by the investigators, there is no standard to determine what the acceptable cost-effectiveness level is, and each society may have different willingness-to-pay thresholds. With that said, this is comparable to other well-established screening initiatives that exist in the United States, such as cervical cancer or cholesterol screening.
The limitations of this study are mostly intrinsic to its design. Because it is a model simulation, assumptions have to be made. These assumptions may be close to, or veer far from, reality. For example, the probability of sustained virological response (SVR) with DAAs plus standard of care was estimated based on results of one clinical trial (ADVANCE).7 This trial used telaprevir, one of the two approved PIs, and led, among previously naïve patients, to the highest SVR rate of 75%. This percentage was multiplied by the ratio of the average SVR rate of Peg-IFN/RBV therapy (genotypes 1/4) in primary care setting divided by the SVR of Peg-IFN/RBV therapy observed in clinical trials (0.33:0.46). As we all know, the real-world response rates will undoubtedly be less than 75%, in part as the result of the higher proportion of patients with cirrhosis that will be treated, with cirrhosis being a clear negative predictive factor of response with triple therapy. There is no final data yet, but early data from the European Association for the Study of Liver Disease suggest, in patients with cirrhosis at least, lower response rates and more side effects, potentially leading to a higher discontinuation rate.10, 11 The assumed probability of SVR of 54% in the present study may or may not represent the real-life setting.
A study published by McGarry et al. in HEPATOLOGY this year showed similar results.12 Also, based on a Markov model of the natural history of HCV, the investigators assessed the potential costs and benefits of a birth-cohort screening program in the United States. In this model, screening 100% of U.S. residents born 1946-1970 over 5 years would avoid 78,000 HCV-related deaths, which is analogous to the data in the Rein et al. study. Similarly, the ICER of birth-cohort screening with DAAs plus standard treatment was $37,700 per QALYs saved, compared with risk-based screening, which is similar to the findings of Rein et al.
As the anniversary of the approval of DAAs approaches, the CDC has proposed “an expansion of its current risk-based guidelines to include a simple, one-time blood test for all baby boomers.”1 The cost-effectiveness analysis presented supports these recommendations. The investigators were wise to point out that these numbers are based on the published clinical trial data, which may overestimate the cure rates. On the other hand, at the pace at which HCV drug development is moving with the expected approval of two to four new DAAs in 2014 and many more after that, these lower real response rates may be a thing of the past. Indeed, with the growing evidence that an all-oral/IFN-free regimen with an excellent side-effect profile and shorter treatment duration will be available soon, the cost-effectiveness ratio of expanded screening may become even more acceptable. Kudos to the CDC for helping us take the first step toward the eradication of HCV. Other countries such as Canada should follow the CDC's lead on screening Baby Boomers.