This post is a part of our Bioethics in the News series. For more information, click here.

By Hannah Giunta

Earlier this month, major news outlets reported the story of 7-year-old Josh Hardy, a current end-stage cancer patient at St. Jude Children’s Research Hospital. Hardy has faced and overcome cancer four times after first being diagnosed with rhabdoid tumors of his kidneys when he was only nine months old. After treatment for his kidney cancer, he relapsed, and cancer was again found first in his thalamus and then in his lung. In November 2013, Josh was diagnosed with myelodysplastic syndrome and required a bone marrow transplant. The weakening of his immune system caused him to come down with a particularly vicious case of adenovirus, and current antivirals have failed to control that infection. After approved drugs failed, Hardy’s doctors suggested that the experimental agent brincidofovir might offer the only viable chance at a cure. St. Jude previously hosted a clinical trial where patients who received the drug demonstrated a decrease in adenovirus-specific viral load. Hardy’s parents petitioned manufacturer Chimerix to provide the drug through a compassionate use protocol, but the company refused, saying that giving the drug to Josh and other critically ill patients would likely slow down the drug’s approval process. Chimerix officials also explained that the drug had not been proven effective in advanced adenovirus cases like Josh’s and that they did not have a current clinical trial in which they could enroll Josh. Public outcry over Chimerix’s refusal of the request, which included death threats directed at company executives, eventually pushed Chimerix to reconsider its decision and work with the FDA to start a new clinical trial in which Josh could enroll.

Although Josh Hardy’s case has been uneasily resolved, at least for the time being, public reaction reveals that larger questions are still unanswered. First and foremost, we continue to struggle with distinguishing our research system from our clinical care system in the U.S., and the resulting therapeutic misconception causes dashed dreams and animosity between drug developers and well-meaning, though misinformed, patient advocates. The truth is that the medication Josh is receiving out of compassion may make his life worse in the end, and failure to recognize this reality means false hope for families and insufficient attention paid to Josh’s quality of life. Secondly, there is a conflict between the needs of current patients like Josh and the needs of future patients who will benefit most from a fully approved medication. That conflict can only be meaningfully resolved when we have an honest discussion about what compromises we are willing to make. We cannot have both a drug development system that releases cutting edge medications meeting our stringent safety standards efficiently and one that makes unproven medications available on demand. The clinical trial system is not designed to release experimental agents for public consumption, even when that consumption occurs according to compassionate use protocols. Failing to get to the bottom of these conflicts leads to unnecessary heartache and public outrage.

Philosophers, researchers, and clinicians have struggled for years with how to prevent and ameliorate the impact of the therapeutic misconception. Defined as the failure to appropriately distinguish between the goals of research and the goals of clinical care, the therapeutic misconception leads to patients and family members believing that clinical trials are actually cutting edge treatment options, rather than legitimate experiments designed primarily to yield generalizable knowledge. In an effort to maintain hope for current patients, clinicians recruit participants with end-stage disease in order to push a research agenda forward while anecdotally hoping that somehow the experimental agent might benefit the enrollees. Unfortunately, previous reviews of pediatric cancer protocols suggest that substantial survival time is relatively rare. In fact, significant survival time was actually less common than drug-related toxicity (Kim et al. 2008). In Josh Hardy’s case, brincidofovir has only been shown to be effective in patients who did not have advanced adenovirus infection. Even then, the drug only demonstrated the ability to decrease viral load, and with Josh’s weakened immune system, his body may still not be able to clear the infection. Tissue damage is likely already significant after two months of illness. Most importantly, Josh has other significant co-morbidities and has had multiple cancer relapses. After Josh received his first dose of the drug, his own father admitted that his son faces a long road and is in bad shape overall (Cohen 2014). Seeing Josh weak, frail, and seemingly miserable in his hospital bed should leave us wondering whether this little boy has suffered enough. Perhaps, he might be better off if we focused solely on palliation and allowed the time he has left to be more comfortable and meaningful for him and his family.

The unique goals of medical research stem largely from a need to standardize clinical trials as much as possible to meet FDA standards. In order to show efficacy and safety, researchers use the gold standard double-blind, placebo-controlled clinical trial design. While this design helps researchers show aggregate differences in outcomes, it makes it less likely that individual patients will benefit from trial enrollment. In the trial earliest stages, participants are often randomly assigned to dosage groups, meaning that some participants may not even be receiving a therapeutic dose. In subsequent phases, participants are still randomly assigned to treatment arms of the trial, and if clinician-researchers don’t know what treatment a participant is receiving, it’s unlikely that they can provide individualized medical care for their patients. Living up to the FDA approval system’s high scientific requirements is a reality for Chimerix and other pharmaceutical companies, so distributing a drug in a less controlled situation presents a conflict. Maybe it is time to consider whether or not more novel trial designs or blended designs where patients receive an experimental intervention in a less controlled setting might help address this problem. Pediatric oncologists have recently expressed this opinion in a major research journal (Kearns and Morland 2014). Until we decide how rigorous our drug review standards need to be, we are forcing companies to confront a constant conflict between the human need for compassion and the larger social goal of developing new treatments.

Josh Hardy may or may not survive his current illness, although I hope and pray that he prevails. But, no matter the outcome, the Josh Hardy case should not be the end of our discussion. Josh’s story should push us toward a national conversation that asks the big questions. Most importantly, it requires us to reconsider the popular notion that research can serve two masters (i.e. the public and current patients) as well as the idea that length of life ought always to be our barometer for ultimate success in the face of terminal illness.

References:

Cohen, Elizabeth. “Josh Hardy’s father says son faces ‘long road to recovery.’” 15 Mar 2014. Last accessed on 3/17/2014 at http://www.ksl.com/?sid=29075987&nid=157.

Kearns P, Morland B. New drug development in childhood cancer. Curr Opin Pediatr. 2014 Feb;26(1):37-42. doi: 10.1097/MOP.0000000000000054. PubMed PMID: 24362409.

Kim A, Fox E, Warren K, Blaney SM, Berg SL, Adamson PC, Libucha M, Byrley E, Balis FM, Widemann BC. Characteristics and outcome of pediatric patients enrolled in phase I oncology trials. Oncologist. 2008 Jun;13(6):679-89. doi: 10.1634/theoncologist.2008-0046. PubMed PMID: 18586923.

Lupkin, Sydney. “Dying Boy to Get Unapproved Drug After Family’s Plea.” 12 Mar 2014. Last accessed on 16 Mar 2014 at http://abcnews.go.com/Health/dying-boy-unapproved-drug-familys-plea/story?id=22873957.

Lupkin, Sydney.  “Family Petitions For Unapproved Drug To Save Son.” 11 Mar 2014. Last accessed on 16 Mar 2014 at http://abcnews.go.com/Health/family-petitions-unapproved-drug-save-son/story?id=22851791&singlePage=true. 

Hannah Giunta is a fifth year DO-PhD student pursuing a PhD in Philosophy and Bioethics.

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