BILL ANALYSIS Ó
AB 1668
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Date of Hearing: March 15, 2016
ASSEMBLY COMMITTEE ON HEALTH
Jim Wood, Chair
AB 1668
(Calderon) - As Amended March 7, 2016
SUBJECT: Investigational drugs, biological products, and
devices.
SUMMARY: Authorizes the manufacturer of an investigational
drug, biological product, or device (investigational drug) that
is not yet approved by the U.S. Food and Drug Administration
(FDA) to make the investigational drug available to a patient,
under certain circumstances. Specifically, this bill:
1)Permits, and specifies that it does not require, a
manufacturer to make available an investigational drug that
has not yet been approved for market to an eligible patient,
as defined.
2)Defines "investigational drug, biological product, or device"
as a drug, biological product, or device that has successfully
completed phase one of a clinical trial approved by the FDA,
but has not been approved for general use by the FDA and
remains under investigation in a clinical trial approved by
the FDA.
3)Permits a manufacturer to either provide the investigational
drug to the patient free of charge or to require the patient
to pay the costs of or associated with the manufacture of the
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investigational drug.
4)Prohibits this bill from expanding or otherwise affecting
coverage provided by health plans or insurers, the Medi-Cal
program, or county organized health systems, as defined.
5)Specifies that this bill does not require a health plan or
insurer to provide coverage for the cost of any
investigational drug, or the costs of services related to the
use of an investigational drug under this bill, but permits
one to provide such coverage.
6)Prohibits a manufacturer from continuing the make an
investigational drug available to the patient if ongoing
clinical trials of the investigational drug are closed due to
lack of efficacy or for toxicity. Requires both the
manufacturer and patient's primary physician to notify the
patient if ongoing clinical trials for the investigational
drug are closed.
7)Defines "eligible patient" as a person who:
a) Has a serious or immediately life-threatening disease or
condition. Defines "immediately life-threatening disease
or condition" as a stage of disease in which there is a
reasonable likelihood that death will occur within a matter
of months;
b) Has considered all other treatment options currently
approved by the FDA;
c) Has been unable to participate in the nearest clinical
trial from their home for the serious or immediately
life-threatening disease or condition, or has not been
accepted to that clinical trial within one week of
completion of the clinical trial application process;
d) Has received a recommendation from his or her primary
physician and a consulting physician, as defined, for an
investigational drug;
e) Has given written informed consent, as defined, for the
use of the investigational drug, or, if he or she lacks the
capacity to consent, his or her legally authorized
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representative has given written informed consent on his or
her behalf; and,
f) Has documentation from their primary physician and a
consulting physician attesting that the patient has met the
requirements above.
8)Defines "written informed consent" as a written document that
has been approved by the primary physician's Institutional
Review Board (IRB) or an accredited independent IRB, is signed
by an eligible patient, or his or her legally authorized
representative when the patient lacks the capacity to consent,
and attested to by the patient's primary physician and a
witness. Requires the document to do the following:
a) Explain the currently approved products and treatments
for the disease or condition from which the patient
suffers;
b) Attest to the fact that the patient, or his or her
legally authorized representative, concurs with the primary
physician in believing that all currently approved and
conventionally recognized treatments are unlikely to
prolong the patient's life;
c) Identify the specific proposed investigational drug that
the patient is seeking to use;
d) Describe the potentially best and worst outcomes of
using the investigational drug and describes the most
likely outcome, as specified;
e) State that the patient's health plan or insurer, if any,
and health care provider are not obligated to pay for the
investigational drug, or any care or treatments consequent
to use of the investigational drug;
f) State that the patient's eligibility for hospice care
may be withdrawn if the patient begins curative treatment
and that care may be reinstated if the curative treatment
ends and the patient meets hospice eligibility
requirements;
g) State that in-home health care may be denied if
treatment begins; and,
h) State that the patient understands that he or she is
liable for all expenses consequent to the use of the
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investigational drug, and that this liability extends to
the patient's estate, except as otherwise provided in the
patient's health benefit plan or a contract between the
patient and the manufacturer of the drug.
9)Defines "primary physician" and "consulting physician" and
requires the consulting physician to:
a) Examine the qualified individual and his or her relevant
medical records;
b) Confirm, in writing, the primary physician's diagnosis
and prognosis; and,
c) Verify, in the opinion of the consulting physician, that
the eligible patient is competent, acting voluntarily, and
has made an informed decision.
10)Prohibits the heirs of an eligible patient, if he/she dies
while being treated by an investigational drug made available
pursuant to this bill, from being liable for any outstanding
debt related to the treatment or lack of insurance for the
treatment.
11)Prohibits a state regulatory board, as defined, from
revoking, failing to renew, or taking any other disciplinary
action against a physician's license based on the physician's
recommendation to an eligible patient regarding, or
prescription for or treatment with, an investigational drug if
the recommendation or prescription is consistent with protocol
approved by the physician's IRB or an accredited independent
IRB.
12)Requires the physician's IRB or an accredited independent IRB
to biannually report to the Department of Public Health (DPH),
the Medical Board of California, and the Osteopathic Medical
Board of California:
a) The number of requests made for an investigational drug;
b) The status of the requests made;
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c) The duration of the treatment,
d) The costs of the treatment paid by eligible patients,
e) The outcome of the treatment; and,
f) Any adverse events from the treatment with the
investigational drug.
13)Prohibits a state agency from altering any recommendation
made to the federal Centers for Medicare and Medicaid Services
regarding a health care provider's certification to
participate in the Medicare or Medicaid program based solely
on the recommendation from an individual health care provider
that a patient have access to an investigational drug.
14)Makes a violation of this bill not subject to the Sherman
Food, Drug, and Cosmetic Law (Sherman Act).
15)Specifies that this bill does not create a private cause of
action, and that actions taken pursuant to this bill do not
serve as a basis for a civil, criminal, or disciplinary claim
or cause of action, as specified.
EXISTING STATE LAW:
1)Establishes the Sherman Act, which regulates the packaging,
labeling, and advertising of drugs and devices, administered
by DPH. Specifies penalties for violation of the Sherman Act.
2)Prohibits, under the Sherman Act, the sale, delivery, or
giving away of a new drug or device unless it is either:
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a) A new drug or new device for which DPH has approved a
new drug or device application, and has not withdrawn,
terminated, or suspended that approval; or,
b) A new drug, and a new drug application has been approved
for it by the FDA, pursuant to federal law, or it is a new
device for which a premarket approval application has been
approved, and that approval has not been withdrawn,
terminated, or suspended under the FDA.
3)Establishes the Protection of Human Subjects in Medical
Experimentation Act which prescribes various protections for
subjects of medical experimentation relating to a bill of
rights; informed consent procedures and documentation; and,
the provision of specified disclosures, including the right
for a subject to give or withdraw consent freely and without
duress. Imposes penalties for violations of these
protections.
4)Requires health plans and insurers to provide an external,
independent review process to examine a plan's coverage
denials of experimental or investigational therapies for
individual enrollees who have a life-threatening or seriously
debilitating condition and who meet other specified criteria.
5)Requires health plans and insurers to provide coverage for all
routine patient care costs relative to the treatment of an
enrollee or insured diagnosed with cancer and accepted in an
FDA-approved cancer clinical trial, Phases I-IV, if the
enrollee's treating physician, recommends participation in the
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clinical trial after determining such participation has a
meaningful potential to benefit the enrollee or insured.
EXISTING FEDERAL LAW:
1)Establishes the federal Food, Drug, and Cosmetic Act, which
grants authority to the FDA to oversee the safety of food,
drugs, and cosmetics.
2)Prohibits any new drug from being introduced into interstate
commerce unless an application has been approved by the FDA.
3)Specifies under federal regulations the following:
a) Requires clinical trial sponsors to submit an
Investigational New Drug (IND) application to the FDA for
clinical investigation of a new drug or new indication of
an approved drug, with certain exceptions;
b) Requires review and approval from an IRB before a
clinical study can be initiated under an IND;
c) Defines an IRB as an appropriately constituted group
that has been designated to review and monitor biomedical
research involving human subjects, to ensure that a
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clinical trial is ethical and that the rights of study
participants are protected; and,
d) Authorizes an IRB to approve, require modifications in,
or disapprove research, or to suspend or terminate approval
of research that is not being conducted in accordance with
the IRB's requirements or that has been associated with
unexpected serious harm to subjects.
4)Establishes the Office for Human Research Protections (OHRP),
which provides leadership in the protection of the rights,
welfare, and wellbeing of subjects involved in research
conducted or supported by the U.S. Department of Health and
Human Services (HHS). OHRP helps ensure this by providing
clarification and guidance, developing educational programs
and materials, maintaining regulatory oversight, and providing
advice on ethical and regulatory issues in biomedical and
social-behavioral research.
FISCAL EFFECT: This bill has not yet been analyzed by a fiscal
committee.
COMMENTS:
1)PURPOSE OF THIS BILL. According to the author, this bill
removes barriers to accessing potentially life-saving drugs
for terminally-ill patients and doctors who believe an
investigational drug could be their last hope for survival.
The author further states that those patients that have
exhausted all other treatment options, and are not eligible
for clinical trials, often seek access to INDs, but face a
variety of hurdles. These patients may seek compassionate use
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exemptions from the FDA, but the process is cumbersome and
approval comes too late for many. The author explains, this
bill removes barriers for patients who need to immediately
obtain investigational treatments, while also protecting
physicians, hospitals, and manufacturers from retribution.
2)BACKGROUND. Patient requests for access to drugs and
biologics prior to their approval have long created a dilemma
for regulators, who must balance the needs of patients and
their families who believe that an experimental product could
save their life, with ensuring the safety of the greater
population through tightly controlled clinical trials and drug
approval. This issue has become increasingly visible and
difficult in recent times, as views about the inherent right
of patients in certain situations to unapproved products have
been expressed by patients and their advocates, state
legislators, members of Congress, and some court cases. In
2014 four states adopted legislation similar to this bill
(Colorado, Louisiana, Michigan, and Missouri) and one state
(Arizona) adopted a resolution to place the issue on the
November 2014 ballot, where it was approved by voters.
According to the National Conference on State Legislatures
(NCSL), at least 41 other states considered similar
right-to-try legislation in 2015.
3)MODEL LEGISLATION. According to the NCSL, the "Right to Try"
proposed model legislation was designed and promoted by the
Goldwater Institute, a free-market advocacy group in Arizona.
Their "model legislation," now adopted in many states,
typically addressed several concerns about patients' use of
experimental drugs:
a) It would allow access only to medications that have
passed manufacturers' Phase I clinical trials, or the first
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studies in humans;
b) Access would be limited to use by terminally ill
patients who have exhausted other available treatments;
c) A medication would be made available only if the company
manufacturing it chose to do so;
d) A patient's request for access to an experimental drug
would require a doctor to diagnose a terminal disease and
declare that the drug represents the patient's best chance
at survival; and,
e) Patients would provide signed informed consent, thus
limiting the legal exposure of the manufacturer of the
drug.
4)FDA HAS JURISDICTION OVER DRUG APPROVAL. FDA has jurisdiction
over all drugs that are sold across state lines. State law
gives DPH the authority to approve a drug or device if it will
be sold only in California. If a product has received FDA
approval, then DPH automatically recognizes the product's
approval. In rare instances when a drug or device will be
sold only in the state of California, and will not be
distributed through interstate commerce, then California would
be the approving body. According to DPH, this has resulted in
only a few instances where California has approved a new drug
or device application.
5)THE CLINICAL TRIAL PROCESS. A clinical trial is a study that
is carefully designed to test the benefits and risks of a
specific medical treatment or intervention, such as a new
drug. The FDA requires a multi-phase clinical trials process
to be completed before deciding if an investigational medicine
is safe and effective for a broader patient population.
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a) Phase I is a clinical trial using a small group of
healthy individuals (generally 20 to 80 volunteers). This
stage is designed to assess the toxicity and dosing of a
drug and whether or not there are harmful side effects
associated with the drug. Phase I trial does not establish
either the safety or efficacy of a drug. According to the
FDA, the goal in this phase is to determine the drug's most
frequent side effects, how the drug is metabolized and
excreted, and whether there is an unacceptable level of
toxicity associated with taking the drug.
b) Phase II clinical trials involve control groups and
experimental groups (up to 300 individuals total) to
determine whether the drug is effective for the intended
purpose on a particular disease or condition. This phase
aims to obtain preliminary data on whether the drug works
in people who have a certain disease or condition.
c) Phase III begins if the drug proves to be effective in
Phase II. These studies gather further information on the
drug's safety and effectiveness on different populations
(several hundred to about 3,000 participants) and tests
varying levels of doses in combination or in comparison
with different drugs.
d) Phase IV studies are post-marketing studies the sponsor
has agreed to do after the FDA approves a drug. These
studies gather additional information on a product's
safety, efficacy, and optimal use.
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6)Expanded Access or "COMPASSIONATE USE" through the FDA. If a
patient is unable to enroll in a clinical trial, the FDA's
expanded access exemption, also called "compassionate use,"
provides a pathway for patients to gain access to
investigational drugs or devices for serious diseases or
conditions. A licensed physician applies, on behalf of a
patient, for expanded access under a single patient IND
Application. The supervising physician must be willing to
commit to oversee the treatment, work with the manufacturer
and the FDA, obtain the drugs, monitor the patient during the
course of treatment, and file necessary paperwork.
Critics of the FDA process have raised concerns that the
Expanded Use application is too cumbersome for physicians and
patients to complete. Critics claim that it currently
requires an application that takes doctors 100 hours to fill
out. The response time from the FDA ranges from a few days to
a few months. The FDA also allows physicians to request
expanded access for patients in an emergency situation over
the phone or by "other rapid means of communication." The FDA
states that authorization of the emergency use may be given by
an FDA official over the telephone, provided the physician
explains how the expanded access use will meet federal
requirements for expanded access use and agrees to submit an
expanded access submission within 15 working days of FDA's
initial authorization of the expanded access use. The FDA
states that they receive approximately 1,000 expanded use
applications per year, and has approved more than 99% of those
applications. In the last four years, the FDA has denied only
33 of nearly 6,000 expanded access requests.
In February 2015, the FDA proposed a new form for individual
patient expanded access requests that it estimated to take
physicians only about 45 minutes to complete. The FDA has
stated that finalizing the form is an Agency priority.
However, finalizing a form requires FDA to complete a number
of steps, many of which are required by law and/or regulation.
After collecting public comment on the draft made public in
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February 2015 for a period of 60 days, the FDA then carefully
reviews these comments and considers revisions which would
appear in the final form. The FDA then seeks approval for the
information collections from the Office of Management and
Budget (OMB) under the Paperwork Reduction Act of 1995. OMB's
review includes an additional 30-day public comment period
which began on March 10, 2016. OMB has 30 days to review the
comments submitted during this period. The FDA expects to
issue the finalized form shortly after receiving OMB approval.
7)COURT HISTORY. In 2005, the Abigail Alliance for Better
Access to Developmental Drugs, with the mission of
facilitating access to experimental drugs for patients, sued
the FDA, claiming a constitutional due process right for
terminally ill patients to access unapproved drugs. In
Abigail Alliance v. Von Eschenbach, a US District court
disagreed and the case was heard by the US Court of Appeals
for the District of Columbia Circuit. In 2006, a divided
three-judge panel of the D.C. Circuit agreed with the
Alliance, finding that where there are no other FDA-approved
treatment options, a terminally ill patient has a
constitutionally-protected "fundamental right" to access
investigational drugs. In 2007, the D.C. Circuit reheard the
case "en banc" and reversed the panel decision. The Alliance
then filed a petition asking the U.S. Supreme Court to hear
the case but the Supreme Court denied the petition, so for now
the Court of Appeals decision stands.
8)SUPPORT. Supporters argue that patients with no other
treatment options should be able to take on more risk than
healthy patients would otherwise choose. The Los Angeles
County Board of Supervisors supports this bill, stating that
terminally ill patients, who have exhausted their options to
find a cure and who have identified a physician and
pharmaceutical company willing to assist them, deserve the
right to experimental treatments that could prolong their
lives.
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9)OPPOSITION. The Medical Oncology Association of Southern
California (MOASC) opposes, stating that "while we appreciate
the interest in supporting patients, there are substantive
dangers in a "right to try" outside the context of a clinical
trial, including the damage to adult clinical trial
enrollment, which hold the promise of the future of medicine."
MOASC additionally raises concerns about the difficulty
identifying an "immediately life-threatening condition", the
lack of sufficient informed consent process to protect
patients seeking these drugs, and the lack of appropriate
physician supervision of the use of these drugs. The
California Nurses Association (CNA) states that this bill
erroneously suggests that consumers do not have access to
these drugs because physicians fear their liability to
practice medicine would be compromised and their liability
increased if they were to recommend such treatment. CNA
points out that "nothing in this legislation impacts the
availability of drugs to terminally ill patients unless the
manufacturers of the drugs allow it to be used in advance of
FDA approval."
10)PREVIOUS LEGISLATION. AB 159 (Calderon) of 2015 was
identical to this bill. It was vetoed by Governor Brown,
stating "[p]atients with life threatening conditions should be
able to try experimental drugs, and the FDA's compassionate
use program allows this to happen. The proposed changes to
this program will streamline access to these drugs. Before
authorizing an alternative state pathway, we should give this
federal expedited process a chance to work."
11)DOUBLE REFERRAL. This bill is double referred; upon passage
in this committee, this bill will be referred to the Assembly
Committee on Business and Professions.
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12)POLICY COMMENTS.
a) Governor's Veto of AB 159. In the veto of AB 159, which
is identical to the provisions of this bill, the Governor
stated his intent to let the new FDA process - discussed in
6) above - take effect before changing state law. The new
streamlined FDA compassionate use application is expected
to be finalized by the summer of 2016. The committee may
wish to ask the author how he will address the Governor's
veto message of AB 159.
b) Will this bill achieve its intended goal? While the
intended goal of this bill is meritorious, it should be
noted that there are several barriers to implementation
that cannot be addressed at the state level. If a
manufacturer agreed to provide their investigational drug
to a patient under this state law, they will still be in
violation of federal law. Drug manufacturers are not
exempted from FDA rules under this law, and therefore
companies interested in gaining full regulatory approval
for their products are unlikely to ignore federal law.
Additionally, there is no evidence that investigational
drugs have been made available to patients in any of the
many states who have already passed similar legislation.
The committee may wish to consider whether patients will be
able to derive any benefit from this policy.
c) Do payment provisions of this bill lack consumer
protections? If a patient accessed the same experimental
drug through a clinical trial, California law requires
insurers pay for routine patient care costs, and the cost
of the drug would be paid for by the government agency,
university medical center or pharmaceutical company
sponsoring the trial. Under this bill, plans and insurers
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would not be required to cover the cost of the drug or the
patient care costs. The FDA expanded use program allows
the manufacturer, after review and approval by the FDA, to
charge a nominal fee for the cost of providing the
experimental drug. This bill permits a manufacturer to
charge a patient for the costs associated with
manufacturing the experimental drug, without any review or
oversight. The committee may wish to consider whether
these provisions could lead to overcharging a particularly
vulnerable patient population.
REGISTERED SUPPORT / OPPOSITION:
Support
ALS Association Golden West Chapter
Los Angeles County Board of Supervisors
Opposition
California Nurses Association
Medical Oncologists Association of Southern California
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Analysis Prepared by:Dharia McGrew / HEALTH / (916) 319-2097