Respect for autonomy

Respect for autonomy is best described as an individual’s right to determine his or her own medical decision making. Although autonomy is often listed first among the ethical principles, it is important to recognize that autonomy does not supersede the other 3 principles. Physicians must ensure that patients make informed decisions without undermining the physician’s responsibility to promote beneficial and equitable choices. As such, when treating patients with CDI, the clinician should highlight the decreased recurrence risk with fidaxomicin over vancomycin, but also disclose that other potentially equally valuable patient outcomes, such as death, adverse events, and cure rates are equivalent between treatments. It is also important for the treating physician to disclose the potentially increased out-of-pocket cost of fidaxomicin and to understand whether the information regarding increased cost is perceived as an impediment or empowering knowledge. Armed with this information, 2 different patients, or even the same patient at different points in time, may choose different treatment options. For example, one patient battling recurrent CDI may prioritize the clinical benefit that fidaxomicin offers over vancomycin, and choose a treatment associated with higher out-of-pocket costs, whereas a different patient with a first episode of CDI may value the economic advantage of vancomycin instead. Neither is wrong; both are making informed, autonomous decisions based on an ethically informed discussion with their physician.

Antimicrobial stewardship program staff, healthcare system leadership, and pharmacy and therapeutics committees must self-reflect when considering the addition of fidaxomicin to their institutional guidelines and formularies. Discussing cost is unavoidable when balancing the patient’s right to select a medication against the institution’s ability to provide it. However, a candid consideration of these questions during the preimplementation stage will permit stewards and systems to respond to these requests. One potential solution is to partner with specialty pharmacies to create a referral network with other hospitals with access to fidaxomicin. If fidaxomicin in inaccessible or restricted at the health-system level, this decision should be reviewed in multidisciplinary meeting with all key stakeholders and defined in an institutional policy so the treating physician does not bear the responsibility for limiting a patient’s choice.

Beneficence and nonmaleficence

In the Hippocratic Oath, the phrase primum non nocere (first, do no harm) summarizes nonmaleficence, whereas beneficence goes one step further—acting to optimize benefit. When we discuss benefit and harm, are we beholden only to the patient’s clinical outcome, or should other outcomes, such as financial and social well-being be considered too? From a purely medical perspective, maximizing beneficence and minimizing harm supports fidaxomicin, given its superiority over vancomycin regarding recurrence rates, and similar adverse effect profile. The guideline authors explicitly acknowledge this by stating “this recommendation places a high value in the beneficial effects and safety of fidaxomicin.” ^{Reference Johnson, Lavergne and Skinner4}

However, patient harm may occur by undervaluing the challenges posed by fidaxomicin’s cost and availability. Currently, most guidelines do not account for the harms incurred by patients as a result of medication cost, or they give it less weight with respect to clinical outcomes. ^{Reference Sanabria, Kotzeva and Selva Olid19} Cost-effectiveness studies attempt to factor cost into medical decision making; however, the results of these studies are highly dependent on a priori assumptions for model inputs, and they are often performed from the perspective of the healthcare system and not the individual patient. This situation makes it challenging for physicians and patients to predict how financial harm could result in clinical harms. Patients could be forced to choose between paying for fidaxomicin versus other medications and necessities, which could exacerbate other comorbidities or cause transportation, housing, or food insecurity, which could influence routine medical care. Conversely, failing to prescribe fidaxomicin could result in costly hospitalization for CDI recurrence.

Finally, some pharmacies, stewardship programs, and healthcare systems may be unable to justify the cost of maintaining fidaxomicin on formulary, limiting its access to patients that meet specific criteria. Cost-effectiveness, healthcare outcomes, and implementation studies are needed to understand the impact of access limitations when caring for patients with CDI. Policies should be developed to protect patients who and healthcare systems that choose to assume this expense.

Justice

Justice in this context may be summarized by the statement, “All patients with similar cases of CDI should have equitable access to equivalent therapies.” However, due to variable copays and varying patient financial means, equitable financial access does not exist. Currently, fidaxomicin remains significantly more expensive when compared to oral vancomycin, which the focused update to the guidelines acknowledge by stating, “Implementing this recommendation [for fidaxomicin over vancomycin] probably reduces equity due to variation in medical insurance coverage.” ^{Reference Johnson, Lavergne and Skinner4} By prioritizing beneficence, justice was deprioritized, as remarked upon in the assessment that “Resource use (monetary costs and cost-effectiveness, for example) was rated as ‘of limited importance.’” ^{Reference Johnson, Lavergne and Skinner4}

Furthermore, pursuing justice also implies a desire to ensure equitable availability. Drugs are not often uniformly distributed at the local, national, and global level. Many pharmacies may not carry fidaxomicin, either secondary to its significant cost or the relative infrequency with which it is prescribed. How can prescribers or institutions adhere to guideline-based practice when many patients simply cannot access fidaxomicin? How can patients access fidaxomicin when their physicians may not have access?

Framing the challenge of therapeutic equity using these 2 questions, prescribers can invoke the guideline’s designation of oral vancomycin as an acceptable alternative to fidaxomicin. If oral vancomycin is a less acceptable alternative, given a patient’s needs and values, disclosing the limitations of access to fidaxomicin not only preserves the patient–physician relationship but also allows for exploration of ways in which a patient might obtain such access. Increased work by patient advocacy groups and greater public awareness are necessary to improve access to preferred medications.

Justice is not simply achieved by adding fidaxomicin to a formulary. We suggest that health systems, pharmacy and therapeutics committees, and antimicrobial stewardship programs make efforts to mitigate patient financial inaccessibility to fidaxomicin. If eliminating financial barriers is not possible, then entities wishing to maximum “fairness” should consider utilizing oral vancomycin in favor over fidaxomicin. Additionally, patients should receive support for accessing fidaxomicin, including strategies such as maintaining a list of local or regional pharmacies with supply, or partnership with mail-order pharmacies and patient assistance programs.