Direct-Acting Antivirals and Hepatitis C: The Ethics of Price and Rationing by Genotype

To the Editor—We read with interest the article by Hashem et al [1] on the IL28B genotype and postpartum spontaneous clearance of hepatitis C virus (HCV). The authors state that this genotype could be used “in the triage of HCV-infected pregnant women,” suggesting that highly effective and well-tolerated direct-acting antivirals (DAAs) be reserved for patients whose genotypes make them less likely to spontaneously clear chronic infection. We believe that the stratification of access to DAAs based on genotype raises several ethical concerns that merit analysis and discussion.

First is the cost of DAA medications. To facilitate access in low-resource settings, pharmaceutical companies that developed DAAs have offered tiered pricing schemes and licenses to generic manufacturers. However, drug prices remain high enough that the authors find it necessary to propose options for “triage.” They acknowledge that “in ideal circumstances, every patient with chronic infection would be treated with DAAs,” proposing triage in light of the realities of drug pricing and global inequality. This represents the acceptance of an unethical status quo. The current model of medical innovation positions high prices as necessary incentives, under the assumption that prices will fall eventually. However, while scholars have long debated whether the benefits of reducing drug prices would be countered by a related reduction in drug development, pharmaceutical profits vastly outweigh the costs of research and development [2].

Triage by genotype also raises questions regarding the ethical acceptability of rationing in general, and the means by which such decisions are undertaken. Here we have a set of patients who would clearly benefit from treatment, whose slightly elevated chances of recovery without medication would bar them from receiving DAAs—but what threshold is appropriate for applying such rationing decisions? If such rationing were implemented, patients who did not in fact have spontaneous virus clearance would need to receive DAAs in a timely fashion. Such spontaneous clearance occurred in only 36% of the patients carrying the favorable genotype, meaning that nearly two-thirds remain infected, with all the associated individual and public health consequences of untreated HCV infection.

Currently some US payers are rationing access to DAAs based on disease stage, but several active lawsuits are challenging the practice of covering DAAs only for patients with late-stage disease. Distributive justice argues for coverage for all, and there is a moral obligation to improve access by reforming approaches to drug pricing. If rationing of DAAs is necessary, doing so based on disease stage in turn raises tensions between the need to treat the sickest patients (those with late-stage disease) and the public health benefits of treating those with early-stage disease, who tend to be younger and may be more likely to transmit the virus to others but may also be more likely to be reinfected themselves [3, 4]. As with rationing based on genotype, rationing based on disease stage raises ethical issues related to acceptable cutoffs, the demographics of which patient groups are being excluded, ability within a health system to access “rescue” medication, and more. Although these issues are not unique to the use of genetic information, the ethical aspects of “genomic triage” warrant further discussion as part of the ethics of rationing and healthcare.

Notes

Potential conflicts of interest. A. W., A. B., G.G., C. L. T., and J. P. K. report grants from the National Human Genome Research Institute, during the conduct of the study. C. L. T. also reports grants from the National Institutes of Health and Gilead Sciences, outside the submitted work. All 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.