Editorial Commentary: Decision Science at Work: The Case of Hepatitis C Virus Postexposure Prophylaxis

Clinical Infectious Diseases, Dec 2016

Joshua A. Barocas, Benjamin P. Linas

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Editorial Commentary: Decision Science at Work: The Case of Hepatitis C Virus Postexposure Prophylaxis

CID Decision Science at Work: The Case of Hepatitis C Virus Postexposure Prophylaxis Joshua A. Barocas 2 Benjamin P. Linas () 0 1 0 Boston Medical Center , Massachusetts 1 Boston University Schools of Medicine and Public Health 2 Division of Infectious Diseases, Massachusetts General Hospital HCV prevention; prophylaxis; HCV treatment; decision analysis. - In this issue of Clinical Infectious Diseases, Naggie et al discuss clinical decision making and present the results of a decision analysis examining the cost of hepatitis C virus (HCV) postexposure prophylaxis (PEP) among healthcare workers who experience a needlestick exposure to HCV-positive body fluids. The authors discuss that, in an era when we can cure essentially all HCV infections, there are only 3 motivations for PEP. First, it may make sense to use PEP to prevent infections if doing so would decrease HCV transmission during the period of active HCV viremia. The paper succinctly reviews the evidence and quickly makes clear that among healthcare workers in the United States with a known HCV exposure, basic universal precautions reduce the risk of forward transmission to essentially zero. A second motivation might be cost. Given that HCV medications are expensive, a shorter course PEP may be cost saving compared with full treatment for HCV infection. To address the possible economic rationale for PEP, the authors developed a decision tree to estimate the costs of PEP for HCV in a hypothetical cohort of 100 healthcare workers who had suffered a needlestick injury. They used the model to compare the outcomes with PEP to those with a strategy of “no PEP and treat only patients who develop chronic HCV infection.” A few notable assumptions were made—namely, that PEP was 100% effective at preventing infection, while treatment for chronic HCV was only 98% effective with the first line of therapy. In addition, individuals who failed first-line treatment for chronic HCV infection were retreated with 100% efficacy. Ultimately, clinical outcomes were the same for the 2 strategies—no patient lived with chronic HCV for more than a few months and no patients progressed to late-stage infection. The difference between strategies was entirely one of treatment duration and cost. With these assumptions, the authors found that the cost of PEP for 100 exposed patients was nearly 14 times that of the cost of HCV treatment of acute HCV infections ($1 857 272 vs $132 870). In sensitivity analyses, the PEP strategy generally remained more costly. Only with a 71% reduction in the cost of medications would PEP be cost saving compared to a strategy of waiting to see who establishes chronic HCV infection and treating those patients for cure. This decision analysis demonstrates quite clearly why PEP is not cost saving: It requires treating 100% of patients to prevent infection among <2%. The third motivation for PEP, however, might be to mitigate the anxiety caused by needlestick exposure and watchful waiting. The authors acknowledge that their analysis does not account for such quality-oflife losses, but suggest that it is difficult to imagine the anxiety could amount to such a large difference in cost. Decision analysis provides a framework for considering anxiety and a means of integrating anxiety into quantitative results via net monetary benefit analysis (NMB). The NMB of a treatment, intervention, or policy is simply the total monetized value minus its total cost. When competing 2 strategies, the one with the highest NMB provides the greatest value, because its net benefit is greatest [1]. The conceptual challenge of NMB is that it requires that benefits be translated to currency, such that we can subtract costs and arrive at the NMB. The goal of such an exercise is not to make moral judgments about how much a life is worth, but rather, to provide a framework by which one can quantify the impact of different health states and incorporate them in the analysis. Translating clinical benefit to dollars requires 2 constructs: First, it is necessary to quantitatively express an individual’s quality of life. Typically, decision analysts use quality-adjusted life-years (QALYs) to express quality of life. QALYs are a measure of quality of life. They assume that health can be measured based on willingness to spend time in various health states and to trade time between health states. Second, we need a measure of the value of one QALY. This explicit valuation of a QALY is perhaps the most controversial aspect of cost-effectiveness analysis, as it requires us to acknowledge that life has finite value. Society values life every day, however, when making resource allocation decisions. Absent an explicit measure of the societal willingness to pay (WTP) to save one QALY, such decisions likely reflect the hidden biases and agendas of decision makers, rather than thoughtful reflection on social norms. Explicitly naming a WTP to prevent the loss of one QALY does not introduce the concept that life has finite value, but it does require us to confront that reality. Equipped with a measure of the QALYs lost to anxiety about HCV exposure, and the societal WTP to prevent those QALY losses, it is possible to integrate anxiety concerns into this decision analysis. The cost of the “no PEP” strategy is: Cost of treatment þ ðQALYs lost to anxiety WTP to save one QALYÞ: Cost-effectiveness analyses in the United States typically cite a WTP of $50 000– $100 000, but that threshold is not certain [2, 3]. Indeed, accepted interventions for human immunodeficiency virus (HIV) prevention, such as preexposure prophylaxis (PrEP) among men who have sex with men, cost as much as $300 000 for every QALY saved [4]. The WTP employed in NMB analysis is critical, and it is important to explore the impact of WTP on conclusions. We expanded the authors’ decision analysis to quantitatively incorporate anxiety and lost quality of life in the “no PEP” strategy. We assigned a range of QALY losses attributable to anxiety about HCV exposure without PEP, and we experimented with 3 WTP thresholds. We assumed that there is a 6-month period during which HCV status is unknown and anxiety-provoking. We varied the health state utility during that time period from 1.0 ( perfect health) to 0.5, which is approximately the health state utility of decompensated cirrhosis [5, 6]. Under nearly all circumstances, the “no PEP” strategy had a higher NMB than “PEP,” suggesting that PEP is not an efficient use of resources even when one does explicitly incorporate anxiety into the analysis (Figure 1). If WTP is $300 000 per QALY, which is similar to the cost of HIV PrEP on a cost per QALY basis, then the PEP strategy is somewhat more economically attractive. Even with a $300 000 WTP, however, PEP only provides adequate value if the quality of life while waiting is <0.9, similar to that of living with partially controlled asthma [7]. At the more commonly cited WTP of $100 000 per QALY, PEP was preferred only when anxiety resulted in a health state utility <0.65, which is approximately the health state utility of someone with compensated cirrhosis [6]. Thus, while a complete accounting of quality of life lost to anxiety after HCV exposure without PEP could impact decision making, it only does so if the societal WTP is very high and anxiety is extremely debilitating. This article by Naggie et al represents an ideal application of clinical decision science. Using a simple, transparent model, the authors explore the costs and benefits of PEP and demonstrate quite convincingly that there is no real clinical argument for PEP, nor is there an economic rationale. While addressing anxiety and lost quality of life after needlestick is one of the important goals of PEP, in an era in which we can cure 100% of chronic HCV infections, that anxiety does not rise to a level that offsets the high cost of PEP. Close follow-up, postexposure testing, continued reassurance, and early treatment with directacting antiviral combination therapy in the event that HCV transmission occurs continue to be the paradigm for HCV postexposure care. Note Potential conflict of interest. Both authors: No potential conflicts of interest. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. 1. Hunink MGM , Weinstein MC , Wittenberg E , et al. Decision making in health and medicine: integrating evidence and values . 2nd ed. Cambridge, UK : Cambridge University Press , 2014 . 2. Grosse SD . Assessing cost-effectiveness in healthcare: history of the $50,000 per QALY threshold . Expert Rev Pharmacoecon Outcomes Res 2008 ; 8 : 165 - 78 . 3. Neumann PJ , Cohen JT , Weinstein MC . Updating cost-effectiveness-the curious resilience of the $50,000-per-QALY threshold . N Engl J Med 2014 ; 371 : 796 - 7 . 4. Paltiel AD , Freedberg KA , Scott CA , et al. HIV preexposure prophylaxis in the United States: impact on lifetime infection risk, clinical outcomes, and cost-effectiveness . Clin Infect Dis 2009 ; 48 : 806 - 15 . 5. Grieve R , Roberts J , Wright M , et al. Cost effectiveness of interferon alpha or peginterferon alpha with ribavirin for histologically mild chronic hepatitis C. Gut 2006 ; 55 : 1332 - 8 . 6. Chong CA , Gulamhussein A , Heathcote EJ , et al. Health-state utilities and quality of life in hepatitis C patients . Am J Gastroenterol 2003 ; 98 : 630 - 8 . 7. Zafari Z , Lynd LD , FitzGerald JM , Sadatsafavi M. Economic and health effect of full adherence to controller therapy in adults with uncontrolled asthma: a simulation study . J Allergy Clin Immunol 2014 ; 134 : 908 - 915 .e903.

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Joshua A. Barocas, Benjamin P. Linas. Editorial Commentary: Decision Science at Work: The Case of Hepatitis C Virus Postexposure Prophylaxis, Clinical Infectious Diseases, 2017, 100-101, DOI: 10.1093/cid/ciw680