1. INNOVATION AND CHOICE
REPORT ON TERMINALLY AND SERIOUSLY ILL
PATIENTS’ ACCESS TO EXPERIMENTAL THERAPIES
OUTSIDE OF EXPERIMENTAL TRIAL
(‘TERMINAL PATIENT ACCESS’)
Executive Summary
Innovation and Choice
(202) 556-0614

2. EXECUTIVE
SUMMARY
Executive Summary • Terminal Patient Access
WE PRESENT THE NARRATIVE of this report and the recommendations which flow
from it to the United States Congress, the President of the United States, applicable
agencies, and the American public for their consideration. This report is the product of
numerous discussions with statisticians, economists, clinical and preclinical researchers,
physicians, patients, the general public, and ethicists.
While it is fear that engulfs compassion, never in the history of our nation have
we let this fear triumph over the most fundamental of American values – freedom, hope,
courage, and opportunity. It is the hope for one final bout with an illness, the courage to
accept unforeseen risks and unknown benefits, the opportunity to be aware this option to
obtain experimental therapies outside of corresponding experimental studies exists, and
the freedom of patients to make this choice that has been silenced. And, it is these
founding principles of hope, courage, freedom, and opportunity which we seek to plant
firmly in the roots of our nation through creating statutory guidance to modify incentive
programs and regulatory checkpoints to be in the best interest of the American public,
while stimulating terminal and seriously ill patients’ ability to access experimental
therapies and maintaining the integrity of clinical trials.
BACKGROUND
When a person is diagnosed as terminally ill, a doctor is telling this person,
“There are no effective therapies approved for your illness, and you are likely going to
die.” If a person desires to keep fighting, he or she can continue previous treatments,
pursue alternative therapies, or inquire about investigational therapies in clinical trial.
However, a problem arises when patients battling serious illnesses do not meet the
eligibility requirements for these trials--which are often very stringent and have longevity
requirements (i.e., a patient has to be projected to live for at least three months)--or are
otherwise unable to enroll in an experimental trial, but have reason to suspect and the
courage to take an investigational therapy that may be beneficial for them.
History
For years, dying individuals have demanded access to experimental therapies,
even though they have not met the clinical trial enrollment requirements, for the sole
reason they are fighting for their last hope at life and will die within months, sometimes
even weeks, if left without treatment. Many of these patients were (and are) willing to
accept unforeseen consequences and unproven benefits for the mere hope a therapy will
give them the additional two months to watch their grandchild graduate from college or
daughter walk down the aisle.
Two Methods for Access
This plea was answered by the Federal Food, Drug & Cosmetic Act, in Section
561, through the creation of treatment investigational new drug applications and
emergency use conditions to allow for the shipment and treatment use of investigational
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3. therapies and devices for patients facing serious or immediately life-threatening illnesses.
This promulgation led the Food and Drug Administration (“FDA”) to create two separate
protocols for treatment investigational use – expanded access programs and
compassionate use protocol (single patient investigational new drugs). Expanded access
programs are programs initiated by therapy sponsors (manufacturers and distributors) to
provide access to their investigational therapy outside of experimental study, whereas
compassionate use protocol is for individual patients seeking access to experimental
therapies outside of such studies.
Details and Associated Problems with Existing Protocols
Upon review, the FDA established the requirement that only those therapies
which have passed Phase I clinical trial should be approved for terminal patient access
under expanded access and compassionate use protocols, based on the premise that there
should be some minimal standards of efficacy, safety, and pharmacologic knowledge
prior to providing patients with access to these experimental therapies. (21 CFR 312.34)
As well, sponsors of therapies are permitted to recover no more than the direct
costs associated with this service. By creating a price ceiling at the average cost of
producing such therapies, any financial incentive is thereby removed for a sponsor to
provide such a service. Not only does limiting sponsors to direct cost recovery eliminate
any financial motivation, but many small capital pharmaceuticals consistently incur
quarterly losses and cannot afford to pay the initial outlay of costs to start such programs.
The result: A mere 8 of 8,000 clinical trials for the nation’s second leading cause of
death, cancer, offer a corresponding expanded access program to provide such
investigational therapies to patients with no other options.
The second incentive offered to therapy sponsors to institute these programs—
aside from direct cost recovery and pure compassion—is to obtain additional data outside
of a clinical trial on the safety and effectiveness of a therapy. This incentive has led
many pharmaceuticals to outsource expanded access programs to clinical researchers
rather than physicians, requiring controlled clinical settings, slightly loosened eligibility
requirements, thereby leaving many seriously and terminally ill patients unable to
combine investigational therapies with other experimental or approved medications in
their final battle for survival.
Lastly, many patients do not know this option exists, when they are diagnosed as
terminally ill, and will die with this ignorance. Patients are not told because patients do
not think to ask. Many patients may make a quick inquiry to their treating physician
regarding alternative treatments, and leave it at that. They are too weak to travel, view
clinical trials as random with the potential of getting a “sugar pill,” do not want to leave
family and friends, and shutter at the potential cost of the trial itself and the chance that
an investigational therapy may not be effective or even harmful.
Without a strong inquiry into clinical trials, it is unlikely a physician will mention
expanded access or compassionate use protocol and the patient will ever find out about
such an option. However, it is important not to neglect the notion that patients may
desire to continue fighting if they know they might be able to receive a therapy through
expanded access / compassionate use protocols rather than through clinical trials, most
especially if their ailment progresses beyond the hope of approved treatment options.
(The negatives for entering compassionate use protocol are far less great than before –
with compassionate use, a patient can be close to home, combine therapies, does not have
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4. to travel, and will know they will receive the therapy. Thus, patients will only face the
prospect of unforeseen, detrimental side effects, and the cost of the therapy itself.) This
potential shift in perception of costs and benefits must be recognized as viable enough to
ensure patients know of this option exists when diagnosed as seriously or terminally ill.
Summary of Problems
1. A lack of effective and economical incentives beneficial for patients and therapy
sponsors (i.e., pharmaceuticals):
a) Data collection leads to unethical and underutilized practices of
Expanded Access.
b) Only direct costs are able to be recovered. This constraint dissolves any
adequate incentive for a therapy sponsor to provide serious or terminally
ill patients with this access, most especially innovative small capital
sponsors.
2. The FDA rarely approves this use for therapies in pre-phase II clinical study (21
CFR 312.34), effectively limiting patients’ options despite many patients’
willingness to accept the unforeseen risks associated with taking investigational
therapies in numerous phases of study (some patients even willing to accept the
risks associated with therapies in preclinical experimentation).
3. Many patients do not know this option exists.
Advocacy organizations calling for change:
• Care to Live
• Accelerate Progress
• Abigail Alliance
• Team IPLEX
• Give Patients a Fighting Chance
• Life Raft Group
• Colorectal Cancer Network
• Huntington’s Disease Drug Works
• MS Patients for Choice
• Parkinson’s Pipeline Project
• Pancreatica
• Liddy Shriver Sarcoma Initiative
• Sarcoma Foundation of America
RECOMMENDATIONS
GENERAL
Rewrite Section 561 of the Food, Drug, & Cosmetic Act, institute financial
incentives for sponsors of therapies to initiate and offer Expanded Access (EA) /
Compassionate Use (CU) programs, allow the marketing of EA/CU programs,
and create a protocol where all patients are informed of EA/CU and clinical trials
as options when diagnosed as seriously or terminally ill.
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5. OUTLINE
A. Approval and Use Standards for Terminal Patient Access
I. Ensure patients have the freedom and opportunity to undertake this risk, if they
have the courage to do so, at the earliest stage of drug development plausible,
enacting one of the following two options:
a) The minimum phase requirement for Expanded Access / Compassionate Use
approval is post-animal experimentation. Each therapy is approved on a case-by-
case basis, based on the mechanism of action of the therapy in question. Any
drug that can show the potential to benefit a patient, based on that patient’s
molecular, genetic, or disease characteristics and the therapy-in-question’s
mechanism of action, is granted (assuming no known side effects)
OR
b) Leave the choice almost completely up to the patient by stipulating only the
following to be necessary for the approval of EA/CU:
• Sufficient proof of an informed decision by the patients applying and
viable data (not necessarily clinical) on the potential benefits to the patient
from the investigational therapy warrant approval. This level of viable
data proving potential benefit necessary for approval is left up to the
discretion of the Food and Drug Administration; but, let it be noted that
this evidence does not need to be clinical proof of efficacy or safety, most
especially if a patient is able prove he or she accepts the risks associated
with any aspects still unknown about the devise or therapy and a lack of
proven benefits.
• CHECKPOINTS:
i. The company producing the therapy is responsible for distributing
the most purified therapy available and informing the physician of
any purification processes yet to be performed.
ii. If dosage is unknown, the physician is allowed to monitor and
change dosage at his/her discretion and hire clinicians, or other
individuals, if he or she is inclined. However, he or she must
inform the patient of everything that is known and unknown, and
potential consequences of anything unknown. For example, taking
an unknown dosage may lead to a first-time overdose and potential
death.
II. Combining investigational therapies with approved or other investigational
therapies needs to be permitted to give desperately (terminally) ill patients
every opportunity to fight for their life.
i. A physician is required to inform patients of unknown and
potentially adverse side effects of combining therapies that have
not been investigated for safety and efficacy in conjunction, prior
to the administration of this potential therapy cocktail.
B. Patient Information & Disclosures: Side Effects, Unknown Characteristics of
Therapies, and Opportunity for Access
I. Physicians must inform patients of EA/CU (and clinical trials) upon
diagnosing them terminally or seriously ill. The definition of these illnesses is
left to the discretion of the Secretary of Health and Human Services (referred
to as “the Secretary” for the remainder of this document).
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6. a) These physicians must provide a maximum two-page outline illustrating
what clinical trials are, how to use clinicaltrials.gov, listing existing
alternative clinical trial search engines, as well as explaining what are and
how to apply for Expanded Access and Compassionate Use protocol.
i. This document is to be written by FDA officials or general
contractors, but must be approved as honest, unbiased, and
sufficient by the Secretary.
ii. Distribution of this document is to be available through the FDA’s
website and is permitted to be printed and viewed by any
individual.
iii. CHECKPOINT: Any physician who is found to have failed to
inform terminal patients of this opportunity more than five times is
subject to a per patient fine thereafter, payable to the FDA, as well
as potential civil litigation penalties to the patient(s) involved.
b) Full disclosure of all known and unknown information about an
experimental therapy is given to a patient by the physician or drug sponsor
prior to the administration of a therapy. This includes all known side
effects, dosage, and pharmacological information.
II. CHECKPOINT: Any patient found to lie about his or her status as terminal is
subject to a substantial fine. Any physician found to lie about a patient’s
status as terminal is subject to a substantial fine and potential criminal
litigation.
C. Incentive Structure & Regulations for Therapy Sponsors
I. Sponsors are permitted to obtain profits for and subsidies are provided to aid
in the formation of EA/CU programs.
a) Therapy sponsors are permitted to charge a maximum 10% net profit
markup on the direct costs, less subsidy or government aid, of the therapy
in question. (Direct costs are as defined in current FDA Rules and
Regulations.)
b) The government is to provide subsidies or long-term, low interest loans to
aid sponsors in the formation of EA/CU programs, recognizing this access
as fundamental to our citizens’ opportunity to fight for their lives.
i. These subsidies are to be provided by the Treasury Department and
granted/distributed through applications to the FDA for this aid.
Such applications and reviews must consider the capital levels of
the applying sponsor in determining whether to grant or deny
federal aid.
ii. The amount of subsidies or long-term, low interest loans is to be
included in the FDA’s annual budget submissions and determined
by the Secretary.
c) CHECKPOINT: Executives or employees found to abuse the privileges of
profit charging by intentionally prolonging clinical trials or
experimentation to obtain these profits must be subject to a substantial fine
to each person(s) involved and an extremely substantial fine for the parent
corporation or institution of such persons, collected by the FDA and fixed
to the inflation rate, and potential criminal litigation.
II. Marketing of EA/CU to the public and physicians is permitted.
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7. i. CHECKPOINT: All advertisements or marketing techniques must
state these therapies have unproven benefits and the potential for
unknown consequences.
III. No data collected from Expanded Access programs or Compassionate Use is
to be grounds for approval or disapproval of a therapy with regards to the
approval or disapproval of that therapy in experimental trials for the purpose
of obtaining final FDA marketing approval.
D. Food and Drug Administration Costs & ClinicalTrials.gov Feature
I. Necessary appropriations may be necessary for the FDA to implement these
changes and improving clinicaltrials.gov.
II. A link for any expanded access programs available, and to apply for
compassionate use, is to be placed on clinicaltrials.gov for each applicable
study.
E. Coverage
I. A minimum 20% coverage of EA/CU therapies is mandated for all insurance
providers.
CONCERNS ADDRESSED IN RECOMMENDATIONS
1. Maintaining clinical trial integrity.
2. Patients or physicians may lie about being terminal to circumvent clinical trials and
move directly to expanded access / compassionate use access.
3. Information sharing between pharmaceuticals/sponsors and physicians with regards to
side effects, pharmacologic information, and purification processes.
4. Information sharing between physicians and patients with regards to EA/CU as an
option, known and potential benefits, known and potential risks, and known
pharmacologic information.
5. Creating statutes to ensure patients have every opportunity in their final battle for
survival, if they have the courage to and a comprehensive knowledge of potential
consequences of undertaking such an opportunity.
6. Minimum coverage standards for EA/CU access.
CONCLUSION
Terminal and seriously ill patients’ ability to access experimental therapies is
rudimentary to the founding principles of our nation. This opportunity exemplifies hope
and courage in the face of doubt and fear. As elected representatives, federal employees,
and people of this nation, we must ensure we the people have the knowledge of this
opportunity and this opportunity is viable and beneficial for patients. We must ensure
these patients have every opportunity to fight for survival in the final and most fierce
battle of their lives.
Currently, terminal patients may have the courage to try an experimental therapy,
but federal regulators may still deny these wishes. Even if a patient is allowed to access
an investigational therapy, often times therapy sponsors do not have adequate incentives
or resources to provide these programs. Moreover, thousands of terminal patients and
researchers do not know about expanded access programs or single patient investigational
new drugs (compassionate use).
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8. There is a missing link here between people that have the courage to accept
unknown benefits and unforeseen consequences, because a given therapy is their last
fighting chance, and those that can provide this chance to them. Patients can afford a
therapy, desire a therapy despite unknown consequences, with a researcher that is willing
to provide it; no known safety concerns or adverse effects to society, yet these terminal
individuals will not be able to realize their last hope at life. This year alone an average of
1,500 Americans will take their last breath every day from cancer. This is one terminal
illness. This is sixty-four Americans, who may not know all of their options or may
desire to continue fighting for their lives, hindered by the very regulatory agencies and
laws meant to protect them, that will die every hour. We must act swiftly.
We look forward to a comprehensive discussion on the merits of what we have
recommended, and we will participate vigorously in this discussion.
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