Part of the "Fourth Annual Health Law Year in P/Review" held at Harvard Law School on January 29, 2016. This symposium featured leading experts discussing major developments during 2015 and what to watch out for in 2016. The discussion covered hot topics in such areas as health insurance, health care systems, public health, innovation, and other issues facing clinicians and patients. This year's Health Law Year in P/Review was sponsored by the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School, the New England Journal of Medicine, Health Affairs, the Hastings Center, Harvard Health Publications at Harvard Medical School, and the Center for Bioethics at Harvard Medical School, with support from the Oswald DeN. Cammann Fund at Harvard University. Visit our website for more information: http://petrieflom.law.harvard.edu/events/details/fourth-annual-health-law-year-in-p-review.

1. 4th Annual Health Law Year in P/Review
Expanded Access and Right to Try Laws
PETRIE FLOM CENTER FOR HEALTH LAW POLICY,
BIOTECHNOLOGY AND BIOETHICS AT
HARVARD LAW SCHOOL
29 JANUARY 2016
Christine Mitchell, RN, MS, MTS
Executive Director

2. 2
Compassionate Use: use outside of a clinical trial of an
investigational medical product not yet approved by FDA
Expanded Access: typically refers to intermediate or large
size CU programs conducted by a sponsor prior to approval
of a drug
Pre-Approval Access: obtaining a medical drug, device or
biologic outside of a clinical research trial, prior to FDA
approval
Right to try: state laws that allow terminally ill patients to
request experimental drugs that have not been approved by
the FDA

3. 3
Paradigm Case: Josh Hardy
3

4. 4
Josh developed an adenovirus infection when
he was recovering from a BMT for
myelodysplastic disorder.
4

5. 5
His physicians asked Chimerix for
compassionate access to brincidofovir,
a drug in phase 3 trails
5

6. 6
NO
6
…we made the difficult
decision two years ago to cease
our Compassionate Use
program and focus on earning
FDA approval. This is the only
path to making brincidofovir
widely available to those who
need it in the fastest manner
allowed….

7. 7
Going viral
7
Our doctor told us…and he knows it will work.
However the drug company has refused
…basically they are not going to save a child’s
life for the money.

8. 8
My goal was to get Josh Hardy the drug.
If in fact the boy, Josh, died, I’d have
done everything in my power to destroy
the company and Mr. Moch.
8

9. 9
9

10. 10
Number of pre-approval access campaigns on
change.org
Source: change.org
2009
3
2010
4
2011
9
2012
12
2013
21
Average number of signatures
per campaign
0
500
15k
105k
270k
395k
2014
2013
2012
2011
2010
2009
Slide from Joanne Waldstreicher CMO J&J

11. 11
#Crowdsourcing medical decisions: Ethicists worry Josh
Hardy case may set bad precedent After a 7-year-old boy
receives an experimental treatment, ethicists wonder:
What about the rest? washingtonpost.com
11

12. 12
Josh Hardy epilogue…
Chimerix worked with FDA to create open-label
study and enrolled Josh as the only patient
Ken Moch was replaced as CEO of Chimerix
Josh improved and was discharged home
And ethicists and lawyers have been discussing this
case and cases like it since 2014
In 2015 several steps were taken to improve
change the process for pre-approval access to
experimental drugs and devices
12

13. 13
Two responses in 2015
Compassionate Use
Advisory Council
“Right to try” laws

14. 14
“Right to Try” laws
• First passed in Colorado
• Currently 24 states
• Leading Proponent—
Goldwater Institute
• Do not compel companies to
grant access
• As of today, no patient has
received compassionate
access via right to try laws
14

15. 15
Requirements of RTT
Although there is variability among the state RTT
laws, all permit patients to
 obtain investigational drugs that have completed
phase 1 safety testing
 when there is a physician willing to petition for and
oversee compassionate use, and
 a company willing to supply the drug (or device)
 State licensing boards are prohibited from taking
disciplinary action against physicians prescribing
investigational drugs
15

16. 16
Ethical Problems with RTT
• Inequitable access: dx terminal illness
• Potential exploitation: lack of oversight
• Promote therapeutic misconception
• False hope: Implies an entitlement but creates no duty
to provide
• Hollow promise: Really, just “a right to beg”
• Potentially harmful: May forfeit right to hospice, home
health care, and insurance
• Favors individual over common good
16

17. 17
Legal Problems with RTT
• No constitutional right of access
[US v Rutherford 1979; Abigail Alliance v vonEschenbach 2008]
• State laws cannot prevent the Drug Enforcement
Administration from rescinding registration of
physicians who prescribe experimental drugs
independent of the FDA
• Under the Supreme Court’s pre-emption doctrine,
state laws that conflict with federal law are without
effect
• RTT “unlikely to withstand constitutionality
challenge”
17

18. 18
Meanwhile…
18

19. 19
FDA
19
• For seriously or terminally ill patients with no alternative
treatments
• Requires evidence for believing the drug is safe and
sufficiently promising for patients to try it
• Requires IRB approval of expanded access
• Only permitted if no threat to clinical trial enrollment
• FDA has an access system to
apply for CU
• Feb 2015: announced
streamlined system (45 minutes)

20. 20
Translational bioethics
• Can we create a fair process for evaluating
CU petitions
• That balances the need of individual dying
patients with the needs of future patients
• Without undermining scientific clinical
research
20

21. 21
Compassionate Use Advisory Committee
21
 NYU Working Group
 To develop fair process for
evaluating requests for CU
 Art Caplan, Chair; Alison
Bateman-House, Deputy Chair
 Pilot: Darzalex (daratumumab) for
refractory multiple myeloma
 Requests come first to Janssen
 Then CompAC

22. 22
Conversation with Art Caplan
• Steep learning curve
• Fairness most important
• Scarcity of supply is real
• Rationing is real
• Provide evaluation and recommendation to J&J
• High level of interest
• JAMA publication in a few weeks
22

23. 23
In 2016+
We need to work on refining a
fairer,
faster,
safer system
for pre-approval use of experimental medical
products
that doesn’t undermine the clinical trial process
23

24. 24
Selected References
Bateman-House et al. Right to try laws: hope, hype and unintended
consequences Annals of Internal Medicine 2015
http://annals.org/article.aspx?articleid=2443961
Darrow et al. Practical, legal and ethical issues in expanded access to
investigational drugs NEJM 2015 http://www.nejm.org/doi/full/10.1056/NEJMhle1409465
Dresser. Right to try laws: the gap between experts and advocates
Hastings Center Report 2015 http://www.thehastingscenter.org/Publications/HCR/Detail.aspx?id=7406
US Food and Drug Administration. Expanded Access (Compassionate
Use) http://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/default.htm
http://blogs.fda.gov/fdavoice/index.php/2015/02/a-big-step-to-help-the-patients-most-in-need
NYU Langone Medical Center Working Group on Compassionate Use and
Pre-Approval Access http://www.med.nyu.edu/pophealth/divisions/medical-ethics/compassionate-use
24

25. 25
Join us at
Bioethics.hms.harvard.edu
Facebook.com/HMSbioethics
Twitter.com/HMSbioethics

26. 26
26