Robert D. Truog, MD

Charlie Gard and Right-to-Try Laws

Frances Glessner Lee Professor of Medical Ethics, Anaesthesia, & Pediatrics, Harvard Medical SchoolDirector, Center for Bioethics, Harvard Medical SchoolSenior Associate in Critical Care Medicine, Boston Children's Hospital

Charlie Gard

• Born with the mitochondrial DNA depletion syndrome

• Most common: TK2 mutation – affects only muscles

• Charlie: RRM2B – very rare, more severe, causes brain damage

Truog RD. The United Kingdom Sets Limits on Experimental Treatments: The Case of Charlie Gard. JAMA 2017;318:1001

Charlie Gard

• Age 2 months, admitted to Great Ormond Street Hospital, London (GOSH)

• Over several months became ventilator dependent, developed uncontrollable seizures leading to severe brain damage

Dr. Michio Hirano, Columbia University

• Uses experimental nucleoside therapy for MDS

• Has treated 18 pts with the TK2 defect

• Most in Spain, Italy

• One American child

Arturito Estopinan

• 7 years old, has been treated for 6 years

• Has regained some movement of fingers and toes

• Still ventilator dependent, requires full care

Request for transfer to New York

• Requested transfer to Columbia University

• Columbia agreed to provide treatment as compassionate use

• Parents raised $1.6 million

• The GOSH physicians refused to permit transfer

The Court Battle

• The court noted that, under UK law, the case must be decided solely upon the objective best interests of Charlie Gard

• GOSH experts:– Only limited evidence of benefit for patients with the

TK2 mutation, the mildest form of this disease– No experience with Charlie’s mutation, which is much

more severe and with brain involvement– In addition, he had uncontrolled seizures which had

resulted in substantial additional brain injury– Argued that his best interests were to have palliative

care and withdrawal of life support

The Court Battle

• Dr. Hirano– Acknowledged his recommendation was theoretical

and based on very limited evidence– He said that the chances of meaningful brain recovery

would be small, even “vanishingly small”– He acknowledged that the brain damage was to a

large extent, if not entirely, irreversible.– “I would just like to offer what we can. It is unlikely to

work, but the alternative is that he will pass away.”

The Court Battle

• United Kingdom– High Court, Court of Appeal, and the Supreme Court

• European Court of Human Rights

• All courts affirmed the initial ruling that withdrawal of life support and palliative care were in Charlie’s best interest

International Attention

• Both Pope Francis and President Trump expressed support for the parents

• The Vatican offered to accept Charlie “for the time it will take for him to live.”

The end of the story…

• His parents finally agreed to withdrawal of life support

• He died on July 28, 2017

Right-to-Try Laws

Right-to-Try Laws

• Laws that purport to give patients access to experimental therapies that have completed Phase 1 testing but that have not been approved by the FDA

• Emotionally compelling– “These are real people facing their mortality with no

hope” Senator Ron Johnson, (R) WI

• Exceptionally popular– 38 states have enacted such laws (not MA)– FDA Reauthorization Act of 2017

Right-to-Try Laws: Political candy

• Do not require physicians to prescribe experimental therapies

• Do not require insurance companies to pay for them

• Do not require manufacturers to provide them

• FDA not an obstacle – 99% of requests approved

“Right-to-Try” is essentially “Right-to-Ask”

• Pharma have developed voluntary programs to give patients access to experimental drugs outside of clinical trials

– Expanded access programs: requests by groups of persons with the same disease

– Compassionate use programs: requests by individuals

Darrow JJ, Sarpatwari A, Avorn J, Kesselheim AS. Practical, legal, and ethical issues in expanded access to investigational drugs. N Engl J Med 2015;372:279

Requirements for Janssen Pharmaceuticals

• The patient must have a serious or life-threatening condition

• The patient must have exhausted all other options

• The patient is not eligible for a clinical trial

• Sufficient evidence that the benefits of the investigational medicine outweigh the risks

• Providing pre-approval access will not jeopardize the overall program to support FDA approval

Compassionate Use - Janssen

• Compassionate Use Advisory Committee (CompAC)– Advisory only– Includes physicians, bioethicists, patients, and patient

advocates

• Patients selected using principles of justice

– PRIMARY: not harming patients, needing to exhaust all existing approved treatments, the scientific likelihood of an efficacious response, patient functionality

– SECONDARY: prior participation in clinical trials, length of coping with the disease, support for dependents, and patient age.

Caplan AL, Ray A. JAMA 2016;315:979-80.

Are there lessons from Charlie Gard for right-to-try laws and compassionate

use programs?

Consumerism vs Professional Regulation

• Consumerism Model– Charlie’s parents were able and willing to pay for his

treatment at Columbia– Dr. Hirano and Columbia were willing to provide the

treatment

• Most compelling in the context of an isolated relationship between patient and investigator

• Less compelling is settings that involve use of communal resources

Professional Regulation:Setting standards of reasonableness

• Should the FDA take a more proactive role in setting standards for reasonableness?

– FDA not well suited for making highly contextualized judgments

– Right-to-try laws may disqualify FDA from this role

Professional Regulation:Setting standards of reasonableness

• Should CompACs be made mandatory?

– Better suited for contextualized case-by-case decisions

– But decisions are only partially patient-centered –compassionate use is denied if it jeopardizes the program supporting drug approval

Charlie Gard: tentative observations

• In my view, nucleoside therapy was not a “professionally reasonable” option for Charlie Gard

• The GOSH physicians were correct in recommending palliative care

Charlie Gard: tentative observations

• The case points to the need for professional oversight of access to experimental therapies

– The FDA is not well suited to the task, and may be disqualified by current federal regulations

– CompACs are an imperfect solution, given their COI between patient and corporate welfare, but are better than a market solution