December 12, 2017 The Sixth Annual Health Law Year in P/Review symposium featured leading experts discussing major developments during 2017 and what to watch out for in 2018. The discussion at this day-long event covered hot topics in such areas as health policy under the new administration, regulatory issues in clinical research, law at the end-of-life, patient rights and advocacy, pharmaceutical policy, reproductive health, and public health law. For more information, visit our website at: http://petrieflom.law.harvard.edu/events/details/sixth-annual-health-law-year-in-p-review

1. Robert D. Truog, MD
Charlie Gard and
Right-to-Try Laws
Frances Glessner Lee Professor of Medical Ethics,
Anaesthesia, & Pediatrics, Harvard Medical School
Director, Center for Bioethics, Harvard Medical School
Senior Associate in Critical Care Medicine,
Boston Children's Hospital

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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.”

9. 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

10. 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.”

11. The end of the story…
• His parents finally
agreed to withdrawal
of life support
• He died on July 28,
2017

12. Right-to-Try Laws

13. 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

14. 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

15. “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

17. 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

18. 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.

19. Are there lessons from
Charlie Gard for right-to-try
laws and compassionate
use programs?

20. 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

21. 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

22. 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

23. 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

24. 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