Compassionate Use: An Analysis of the Ethical Frameworks of Expanded Access Programs
By Kim Ngo
In March 2014, seven-year-old Josh Hardy caught a life-threatening adenovirus infection following a bone marrow transplant. With no treatment options available, Josh was left battling organ failure in the intensive care unit.
Fortunately, his physicians and family discovered an experimental drug, Brincidofovir, that had previously shown positive results in clinical safety and efficacy testing. They immediately requested expanded access from Brincidofovir's manufacturing company, Chimerix.
Expanded Access Programs (EAPs) allow severely ill patients with no alternative treatment options immediate access to FDA-unapproved investigational new drugs (INDs) outside of clinical trials. Also referred to as compassionate use, EAPs are meant to create fair medical access for those in extreme need of the treatment. Unfortunately, due to inconsistent application and variations in modern interpretation of medical responsibility, EAPs fail to embody fairness, resulting in ethical inefficiencies in its implementation.
In Hardy’s case, his initial requests for admission into Chimerix’s EAP for Brincidofovir were persistently rejected. Chimerix explained that it must devote full resources toward completing its ongoing Phase 3 clinical trial. However, undeterred, Hardy’s family launched a Facebook page and Twitter site for a national #SaveJosh campaign that rose to gain over one million views.
The campaign was a national success. People, including politicians and other prominent community members, rushed to contact Chimerix management through phone calls, emails, pleads, and death threats. Local and national TV networks began widespread coverage of #SaveJosh. Under escalating public pressure, Chimerix rearranged its stance and created a pilot trial available to Josh and 19 other patients.
Hardy’s story highlights a critical ethical issue: compassionate use is, in theory, centered on the prioritization of the terminally ill. How compassionate was Chimerix in its final decision regarding Hardy, considering its refusal of many other patients who had made the same request prior to Hardy, except without the success of a social media campaign? Was biased compassion responsible for Josh Hardy's treatment?
In practice, EAPs are not applied towards the direly ill. Instead, they are exploited by the most vocal, or in our age, the most skilled at manipulating social media. As stated by Dr. Craig Klugman, “The individual who has the education, access, and money to go through the application process, to put together and sustain a social media campaign, to get elected officials and celebrities advocating on the patient’s behalf, and to afford the drug and cost of treatment means that those of higher socioeconomic status are more likely to benefit. A person who lacks means, technology, or influence is far less likely to be able to benefit from compassionate use.”
Furthermore, can compassionate care further perpetuate health disparities through enforcement of negative stereotypes or prejudice? It remains largely undisputed that racism should not influence medical decisions, but medical decisions that are deeply questionable as having been made by such prejudices have been evident and present an ethical dilemma.
During the 2014-16 Ebola outbreak in West Africa, two infected, white American health care workers volunteering for the Ebola crisis were airlifted out of Liberia and given a highly experimental treatment, whereas hundreds of African citizens and doctors with Ebola who were also infected were not offered such options. The organization the aid workers were employed by had directly requested ZMapp, the company developing the experimental Ebola drug. Liberia and Nigeria had also inquired ZMapp for the IND yet were not granted approval.
The ethical quandary and practical considerations of ZMapp remain to this day: who, if anybody, should have received the treatment? And, when, if ever, does nationality deserve to play such a huge role in forming the ethical reasoning and ultimate decision of healthcare allocation?
A system of evaluations should have been in place to ensure the prevention of biased prioritization within health care so that it was not compassionate care for only some socially reputable individual, such as a select few Americans, but for all members of a society for a true practice of global and public health.
Henceforth why I can’t conceive of a valid reason why medical exceptions are not made more consistently. There should be a standard of evaluation for petitions to EAPs that require both the FDA and involved treatment provider to limit bias and favoritisms. Compassionate care requirements should have a degree of anonymization to prevent such influences. For example, all personal information aside the patient’s pertinent and relevant medical information would be removed electronically by software upon an electronic submission of the request form by the physician. Information that would be excluded on the forms would include name, nationality, hospital name, and all other factors inconsequential to the patient’s medical condition. Then, those with similarly severe medical conditions would have equal opportunity for EAPs, and not just those who were born into a certain country, armed a large enough fan base on Twitter, or with the most active television campaigns.
The extent to which social influence and other factors external to the severity of the patient’s illness play a role in defining medical compassion is extremely dangerous. With greater inclusion of social media and social influence in determining who is allowed EAP, healthcare becomes dictated by the exploitive hands of media and vulnerable to political and legal influences as well, leading to greater health care disparities.
Physicians, public officials, patient advocacy groups, institutional review boards, patients, and medical committees discuss EAPs with at times increasingly divergent opinions, yet all within the immense influence of health care must address the significance and application of the current mode of the meaning of compassionate health care. The consequences to leaving EAPs as they are would be a continuation of unethical and emotionally-driven irrationality with health care systems providing low-quality care and medicine to one community while allowing expanded medical access to a select few. Instead of allowing media-fueled demands of compassion to define the actions of medical professionals, the health care community must reason and consider that compassionate without equity and justice is not an act of compassion at all.