Informed deferral: A moral requirement for entry into the hepatitis C virus treatment warehouse

The US Food and Drug Administration's approval of the direct-acting antivirals (DAAs) telaprevir and boceprevir in May 2011 signified a new era of hepatitis C virus (HCV) treatment. The addition of the first-generation DAAs to pegylated interferon (PEG) and ribavirin (RBV) has offered truncated therapy for some patients and has increased sustained virologic response rates in genotype 1 patients from less than 50% to nearly 75%.1, 2 In the summer of 2011, patients who had previously deferred PEG/RBV therapy flooded many centers to be among the first to receive DAA-based treatments. The sudden influx of patients requesting therapy sparked debate over just distribution of DAA-based treatment.3 However, the queue of patients waiting for therapy has since dwindled, and the dilemma of resource allocation no longer exists for many centers. As we now pass the 1-year anniversary of the launch of telaprevir and boceprevir, it has become apparent that a smaller than expected percentage of patients interested in therapy have actually received DAA-based treatment. Although some of these patients have not been treated due to contraindications to current DAA-based therapy, many have found their way back into the HCV treatment “warehouse.” DAA, direct-acting antiviral; HCV, hepatitis C virus; PEG, pegylated interferon; RBV, ribavirin. The wait versus treat debate has begun once again with fervor. Proponents of deferring treatment for patients with early stage disease cite slow progression of HCV, toxicity of the current triple therapy, and the promise of more potent agents to come, as the backbone of justification to defer treatment. Those who advocate a “treat now” approach cite an inability to accurately stage and predict fibrosis progression, as well as uncertainty over the true release date of the next generation of DAAs, as reasons to recommend current therapy. In this editorial, we highlight the ethical ramifications of treatment deferral. The underlying principles of medical ethics tend to be stable over time; however, the interpretation of these principles must be tailored to fit the ever-changing scientific landscape. Deferring HCV therapy pushes the doctor-patient relationship—specifically, the concept of informed consent—past its current boundaries and has created a need for a new concept: informed deferral. Informed consent consists of five key elements: (1) competence, (2) disclosure, (3) understanding, (4) voluntariness, and (5) consent.4 Patient participation in health care decision-making prior to the twentieth century was characterized by “benevolent deception and nondisclosure” while “concealing most things from the patient while you are attending to him.”5, 6 In 1914, the landmark case of Schloendorff v Society of New York Hospital was pivotal in emphasizing the importance of patient autonomy.7 In this case, Mary Schloendorff agreed to an examination under anesthesia to determine whether a fibroid tumor was malignant, but specifically requested that no surgery take place. The surgeon removed the tumor nonetheless, and Mrs. Schloendorff sued the hospital for acting against her wishes. Ruling in favor of Mrs. Schloendorff, Judge Benjamin Cardozo stated: “Every human being of adult years and sound mind has the right to determine what shall be done with his own body,” hence creating the foundation of patient autonomy and shared medical decision-making. In discussing HCV therapy, the level of disclosure becomes germane. Standards of disclosure have evolved since the 1914 Schloendorff case from a “physician-centered” model to a “reasonable person” model, and finally to a “subjective standard” model. The “physician-centered” or professional practice model holds that a “professional community's customary practices determine adequate disclosure.”4 Although this was an improvement from the nondisclosure practices of the past, this standard of disclosure rests on shaky moral ground. First, a group of providers' collective expertise regarding a disease process and therapy does not necessarily include the pertinent information a patient may need to make an informed decision. Second, this “reasonable physician” model attempts to protocolize the foundation of the doctor-patient discussion and runs a high risk of limiting patient autonomy. The “reasonable person” model shifts the standard of disclosure from physician to patient by tailoring it to what a patient would want to know rather than what a physician thinks a patient should know.4 Although an improvement over the physician-centered model, this concept is problematic, because it creates a vague and hypothetical “one size fits all” patient that greatly differs from the heterogeneity of patients we see every day. Finally, the “subjective standard” model is the “preferable moral standard because it alone acknowledges the patient's specific individual needs.”4 This model emphasizes the importance of tailoring the consent process to the concerns and level of understanding of each individual patient, thereby creating a unique consent for each patient. For example, when obtaining consent from a patient with a long-standing history of depression who is contemplating initiating HCV therapy, the provider may appropriately go into more detail regarding psychiatric-related side effects of interferon that would be far beyond what is required by the reasonable physician or the reasonable patient standard. limitations in accurately staging liver disease with a biopsy (sampling error); limitations in our ability to predict progression of fibrosis; understanding that many promising agents in the HCV pipeline may not make it to market, and therefore the timing and availability of more potent and safer agents can be speculative; patient insurance status may change over time, and some may not have adequate coverage for future treatment; aside from progression of liver disease, new health comorbidities may arise over time, making deferred initiation of treatment more complicated; and for patients who engage in high-risk behaviors, deferring therapy may put others at risk of contracting the virus. Scientific advancement should be coupled with continued consideration of compliance with established moral values. The unique natural history of HCV infection, along with a deluge of promising new agents in the pipeline, has made the HCV treatment decision unlike any other disease process. Although waiting for new therapy is justifiable and appropriate for many patients, this decision should not be viewed as a mere default. With safe and effective therapy available, treatment deferral is no longer a passive decision, but rather an action in itself that requires its own unique consent process: an informed deferral.