Pricey pills for an even pricer problem: Editorial for "Direct Costs of Care for Hepatocellular Carcinoma in patients with Hepatitis C cirrhosis”

In October 2014, the Food and Drug Administration approved the first combined direct acting anti-viral drugs (DAA) for treatment of chronic hepatitis C (HCV) infection. Compared with older treatment regimens such as interferon and ribavirin, DAAs achieve much higher sustained virologic response rates with low incidence of side effects.^1–3 There is no debate about the efficacy of these drugs. The remaining question is: how much are we, as a society, willing to pay for them? A typical course of treatment costs $63,000–$95,000, and with over 3 million people in the United States infected with HCV⁴, simplistic arithmetic puts the potential price tag at over $200 billion.

Other parts of the cost equation must also be considered. The upfront cost of HCV treatment may seem high, but how does it balance out with downstream savings from prevention of complications related to HCV infection? In the United States, chronic HCV infection is the major cause of hepatocellular carcinoma (HCC). Estimates put HCC risk in a patient with HCV infection and cirrhosis at about 4% per year and treatment of HCC is a major cost driver in this population.⁵

In this issue of Cancer, Tapper et al. provide guidance on this important question by analyzing costs associated with treatment of HCC in a cohort of patients with HCV cirrhosis at a liver transplant center.⁶ They calculated the cost to payers of inpatient, outpatient, and pharmacy care for their cohort of 100 patients to be over $20 million, translating to a median monthly cost of $7,492 for transplanted and $4,830 for non-transplanted patients. While the authors also explore differences in survival and cost by treatment received, caution should be taken when interpreting these results. Substantial treatment selection bias is expected in these data collected as part of clinical care and unmeasured confounders likely persist, precluding causal inference about specific treatments received and outcomes.

The authors note that their total cost estimates are several times higher than those reported by other investigators.^7,8 The differences can be understood in the context of the specific study populations and methodology. Thein et al. studied all HCC patients from the Ontario Cancer Registry, not just those with HCV infection and cirrhosis, and derived incremental HCC costs by matching cases to controls with other terminal illnesses. Yabroff et al. similarly did not restrict their analysis to HCC in the setting of HCV infection and cirrhosis. Additionally, their study was restricted to the Medicare population and a lower proportion of these older patients would be expected to undergo aggressive (and costly) treatments.

McAdam-Marx et al. provide the most comparable population to the current study in their 2011 analysis of a large claims database, which included commercially insured patients of all ages.⁹ They estimated a median monthly HCC treatment cost of about $4,100 (in 2013 dollars) for patients with HCV infection and cirrhosis, excluding those who underwent liver transplantation. Two recent analyses on the cost-effectiveness of DAAs used cost estimates from the McAdam-Marx study. Chhatwal et al. calculated an incremental cost-effectiveness ratio (ICER) of $55,378 per quality-adjusted life years when considering lifetime cost and benefits for patients with all HCV genotypes and fibrosis stages.¹⁰ In the United States, treatments are generally considered cost-effective at ICERs of less than $50,000–100,000 per quality-adjusted life year. Even more favorable ratios were found for patients infected with HCV genotype-1 and non-cirrhotics with genotype-4. Notably, the probability of developing HCC was a variable that had a major impact on ICER. A more recent study performed by the non-profit Institute for Clinical and Economic Review also concluded that combined DAAs would cost less than $50,000 per quality-adjusted life year gained for all patients with HCV genotype-1 infection.¹¹

As with all models, the results are only as good as the inputs used. Tapper and colleagues’ estimate for non-transplanted patients is only about 15% higher than estimated by McAdam-Marx et al. As such, their study provides support that the HCC cost inputs used in these cost-effectiveness analyses were appropriate, if not somewhat conservative. If the downstream cost of HCC care is actually higher, then HCV infection treatment with DAAs is even more cost-effective. It should be also be mentioned that both analyses used wholesale acquisition drug costs. Actual prices borne by payers are often lower, further enhancing the cost-effectiveness of treatment.

None of the studies or analyses mentioned thus far has taken into account the larger societal cost of HCC, such as lost productivity and impact on families and caregivers of HCC patients. Cancer patients have over 2.5 times higher risk for bankruptcy¹² and caretakers of cancer patients report high rates of depression and psychological distress.¹³ The potential benefits from reduction of HCV transmission have also not been adequately appraised.

Despite the compelling economic and moral reasons to broadly provide treatment for HCV infection, there is a hefty immediate price required to treat the large prevalent population. This affordability problem is a tremendous one, and many payers should be applauded for their thoughtful efforts to maximize access to treatment within current budget constraints. Nonetheless, as some payers continue to restrict access for certain patients, they must be mindful that “kicking the can down the road” is not an acceptable solution when the proverbial can is a multibillion dollar one accompanied by unquantifiable human suffering and loss.