Johnson & Johnson announced today the establishment of an independent advisory board to review cases of terminally ill patients who petition Janssen Pharmaceuticals for expanded access to pre-approval experimental drugs, that is, those still undergoing clinical trials for safety and efficacy.
Known by the colloquial term, “compassionate use,” the process involves a patient’s qualified physician making a request of the sponsoring drug company, via the U.S. Food and Drug Administration, justifying medically why the patient should be given the experimental drug despite not qualifying for inclusion in any ongoing clinical trial.
From today’s press release:
In keeping with the company’s long-standing commitment to the highest standards of ethical decision-making that serves the needs of patients, Janssen Research & Development, LLC, has forged this new partnership with the Division of Medical Ethics at the NYU School of Medicine to obtain independent advice, further ensuring that the evaluation of requests for investigational medicines prior to their approval by the U.S. Food and Drug Administration (FDA) or other global health authorities are treated in the most fair and ethical manner.
The independent board, called the Compassionate Use Advisory Committee (CompAC), will be led by noted bioethicist Arthur Caplan, PhD of the Langone Medical Center of New York University School of Medicine. The 10-person group will be comprised of internationally-recognized medical experts, bioethicists and patient advocacy representatives. The CompAC will review the data submitted on behalf of patients with life-threatening diseases, and make recommendations to the company as to which cases are ethically justified and medically supported, assuming that enough of the limited amount of clinical trial drug is available.
This mechanism is an attempt to address how an organization that has already invested tens to hundreds of millions of dollars in a drug’s development should objectively administer a program that could delay or derail the drug’s approval while offering a medicine likely to help certain other patients not enrolled in clinical trials.
Is this right for “Right To Try” advocates?
Public support for compassionate use is high, as evidenced by the enactment of “Right To Try” laws by 17 states that absolve doctors of liability if they treat a terminally ill patients with an investigational drug that has passed preliminary human safety studies.
Spearheaded by the Goldwater Institute in Phoenix, these Right To Try laws, in my opinion, simply give patients false hope that an existing FDA mechanism will move faster. Unless the drug is somehow obtained or synthesized via channels other than the drug’s sponsor, the ultimate decision still lies with the drug company that is developing the drug. However, the Institute’s efforts may have driven a groundswell of attention that is leading the pharmaceutical and biotech industries to formalize their practices.
Since the FDA established this mechanism in 2009, known as “Expanded Access to Investigational Drugs For Treatment Use,” several high-profile cases have emerged where patients with public relations prowess appeal emotionally via social media tools to promote cases of loved ones with cancer, viral diseases, and others, in an attempt to pressure a drug sponsor to provide their investigational drug outside the qualifications and protections of ongoing clinical trials.
For example, we reported extensively on a case in 2014 where a small Durham, North Carolina, company with no existing products was vilified to the point of death threats against its CEO for being unable to provide its experimental antiviral drug to a boy dying of adenovirus infection.
The backstory: Chimerix, who are developing a broad-spectrum antiviral drugs called brincidofovir, was petitioned by a St. Jude Children’s Hospital doctor caring for then seven-year-old, Josh Hardy. The boy had developed the life-threatening viral infection after a stem cell transplant for a cancer he developed in infancy. Hardy had already received the only drug known to be useful against adenovirus, cidofovir (Vistide; Gilead) but had suffered a type of kidney damage known to occur with prolonged use.
Unfortunately, the boy did not qualify for any of the company’s ongoing clinical trials. Family and supporters mounted an online petition and social media campaign that grew so hostile that Chimerix required security detail and their then-CEO, Kenneth I. Moch, had to be taken with his family to an undisclosed location for their protection. The irony is that many of the boys’ supporters invoked Christian pleas to Chimerix while simultaneously wishing for its failure or unpleasant personal consequences if their prayers were not answered in the affirmative. (One example, “GIVE THE KID THE FREAKIN MEDICINE!! OTHERWISE, ROT IN ETERNAL HELL!!!!”)
Unbeknownst to the family, physicians, and the mob, Chimerix was working closely with the FDA to authorize a 20-patient, open-label trial for adenovirus-infected patients. The negotiations involved how to get the drug to the boy without compromising the ongoing trials that would support the drug’s ultimate approval. The FDA approved the trial within 24 hours and Josh Hardy received the first dose of brincidofovir within 48 hours. (A total of 120 hours passed between Hardy’s mother’s first Facebook post and the decision to enroll Josh as the first subject.)
The boy’s viral infection responded and he is apparently without disease today. But this a very unusual case for such a critically ill patient and I previously discussed why brincidofovir is an unusual, and accidental, advance in antiviral drug therapy.
“No simple, monolithic solution”
This is not the way that a civilized democratic society should make such decisions. An ethical public health conundrum becomes apparent when one looks from the viewpoint of other patients who might also be able to use the drug, before or after drug approval. As I wrote last summer:
No one wants to deny a family with photos of a sick boy battling an evil pharmaceutical company concerned only about profits. Tens of thousands sign petitions. Critics and supporters dash off 140 character bursts with #Save[PatientName]. Death threats can be immediately and anonymously dispatched. Traditional media smell and taste blood in the water and swarm for the kill.
But in hospitals around the country – or at home for those without intensive care access – thousands of faceless and nameless people suffer from similar infections sometimes without computers or internet access, most without the PR savvy to mount a similar campaign. We can’t say how long brincidofovir’s anticipated approval was delayed, but one can be certain that more than one person might have died while Chimerix saved Josh Hardy.
Moch, who left Chimerix a month after negotiating the boy’s access to brincidofovir but remains active in the global compassionate access discussion, reflected on the Josh Hardy case a year later in a March 16, 2014, Wall Street Journal piece:
This positive outcome should not lead anyone to assume that there is a simple, monolithic solution to expanded access. Each drug is different, the testing and data required for FDA approval are different, and patient populations are different. Expanded access is not a substitute for clinical trials.
Our current system is rife with ethical dilemmas and is not equitable. If we want critically ill patients to receive experimental medicines as a last resort, we need to find a balance between the immediate needs of individual patients and the equally important needs of future patients.
Indeed, while no simple, monolithic solution to the problem exists, the advisory committee approach adopted by J&J today derives from a model proposed by Caplan and Moch last year as at least one mechanism to level the playing field and adopt a more objective approach to fielding expanded access requests. In their Health Affairs essay, “Rescue Me: The Challenge of Compassionate Use in the Social Media Era,” they proposed the formation of an independent, national advisory board to review expanded use requests, similar to how an institutional review board (IRB) approves a clinical trial protocol and data safety monitoring plan.
When contacted this morning after the J&J announcement, Moch said via email that, “I believe this is a very positive step in helping to address a truly complex societal issue, and hopefully will provide a model for how both small and large companies can bring additional, thoughtful insights into the Expanded Access process.”
I welcome your feedback and comments below. This is not a simple issue, one in which I’m not disinterested: I’ve looked into requesting compassionate use for family members and have another family member who is a physician who has made compassionate use requests on behalf of her patients. Will the death threats just move from being directed at the company to this advisory committee? According to Katie Thomas at The New York Times, Caplan is not being paid for his service. But can NYU as an institution operate without any financial conflicts of interest, particularly if their physicians are running trials for other Janssen-sponsored drugs? Hence, I think that many of us will be watching closely to see how the J&J/NYU pilot project plays out.