Ethical Decision Making Framework in Previously Untreated Severe Hemophilia A Patients

Treatment recommendations and decision making for severe hemophilia A previously untreated patients (PUPs) have recently become a significant debate with an ethical valence. Primary prophylaxis, initiation of factor replacement prior to the second joint bleed and before the age of three, has been the recommended standard of care in resource rich countries for the last two decades. Since the widespread availability of recombinant factor VIII (rFVIII) products, the choice has been fairly straightforward for PUPs, whereby transmission of blood borne pathogens associated with plasma-derived FVIII (pdFVIII) products were avoided. The Survey of Inhibitors in Plasma-Products Exposed Toddlers (SIPPET) randomized controlled trial demonstrated a higher incidence of FVIII alloantibody inhibitors in PUPs started on rFVIII products compared to pdFVIII products (Peyvandi F, et al., 2016). This finding has had a tremendous controversial impact on the decision making of product choice for PUPs despite the supportive Medical and Scientific Advisory Council recommendations to consider starting a PUP on a pdFVIII product (MASAC, 2016).

For this patient population, we developed a modified utilitarian framework of decision making that employs clinical, public health, and research ethics. The framework recognizes that there are many stakeholders involved in the provision of FVIII products and health care of those with severe hemophilia A and provides guidance when there is concern for bias. Utilizing the premise of shared decision making, the framework takes a patient and family centered rather than a paternalistic approach. In discussions about care, it is recommended that the provider learn about relevant patient and family values. Doing so would better enable providers to inform the patient and family about the available treatments (including the risks, benefits and alternatives) and disclose any conflicts of interest and biases. Using shared decision making would serve to maximize understanding, minimize bias, respect informed consent or dissent, and provide care that aligns with patient values when medically and practically feasible.

The framework has three tiers. First, it evaluates whether resources are scarce or abundant, which is important in equitably allocating resources. Where life-saving FVIII products are scarce, there could be a direct impact on patient care and clinical research. Healthcare providers would be at risk of compromising not only standard of care but also their fiduciary responsibilities to patient care in bedside rationing. If FVIII products are scarce, we recommend developing a central supply for emergency use and then evaluating the needs of the severe hemophilia A patients. Prioritization of who receives the factor products would be decided by a designated team based on the availability of the factor products and clinical scenarios, with no preference given to those on research trials. However, if resources are abundant, treatment for acute bleeding and standard of care prophylaxis measures, including primary prophylaxis, could continue.

The second tier takes into account whether there is a new infectious epidemic or concern where the pathogen cannot be eliminated. If not, pdFVIII and rFVIII products are to be equally presented. If there is an epidemic, healthcare and public health workers may limit the use of pdFVIII products.

The third tier evaluates the clinical scenario and if there is an acute bleeding emergency or not. If there is an acute bleeding event, the immediately available resource should be recommended, along with bypassing and/or adjuvant resources as needed until the bleeding has resolved or improved. To align with patient and family preferences, attempts to have both pdFVIII and rFVIII products available at similar costs in institutions would be ideal.

The ethical framework we developed endeavors to balance autonomy, beneficence, nonmaleficence and justice. As treatment decisions are complex, the framework may help guide discussions among providers, PUPs with severe hemophilia A, and their families.

Disclaimer:

The findings and conclusions in this abstract are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention, Emory University, or Children's Healthcare of Atlanta.