BILL ANALYSIS Ó
SB 149
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Date of Hearing: June 30, 2015
ASSEMBLY COMMITTEE ON HEALTH
Rob Bonta, Chair
SB
149 (Stone) - As Amended May 5, 2015
SENATE VOTE: 39-0
SUBJECT: Investigational drugs, biological products, or
devices: right to try.
SUMMARY: Enacts the Right to Try Act, and permits a
manufacturer of an investigational drug, biological product, or
device to make available an investigational drug, biological
product, or device to an eligible patient. Specifically, this
bill:
1)Prohibits the provisions of this bill from being interpreted
as requiring a manufacturer make available an investigational
drug, biological product, or device 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 I of a clinical trial approved by the Food and
Drug Administration (FDA), but has not been approved for
general use and remains under investigation in an approved
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clinical trial.
3)Defines "eligible patient" as a person who:
a) Has a terminal disease as determined by that person's
physician and a consulting physician;
b) Has no comparable or satisfactory FDA-approved treatment
options, as determined by his or her physician, available
to diagnose, monitor, or treat the disease or condition
involved, and that the probable risk to the person from the
investigational drug, biological product, or device is not
greater than the probable risk from the disease or
condition;
c) Has received a prescription or recommendation from his
or her physician for an investigational drug, biological
product, or device;
d) Has given written informed consent for the use of the
investigational drug, biological product, or device. If he
or she is a minor or lacks the capacity to provide informed
consent, his or her parent, legal guardian, or legally
authorized representative must give written informed
consent on his or her behalf; and,
e) Has documentation from his or her physician that the
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patient has met the requirements of this bill.
4)Defines "terminal disease" means an incurable and irreversible
disease that has been medically confirmed and will, according
to reasonable medical judgment, result in death within six
months of diagnosis.
5)Permits manufacturers to:
a) Provide an investigational drug, biological product, or
device to an eligible patient without receiving
compensation;
b) Require an eligible patient to pay the costs of or
associated with the manufacture of the investigational
drug, biological product, or device; and,
c) Require an eligible patient to participate in data
collection relating to the use of the investigational drug,
biological product, or device.
6)Specifies that this bill does not require a health plan or any
state agency to provide coverage for the cost of any
investigational drug, biological product, or device, but
permits health plans to provide such coverage.
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7)Prohibits a state regulatory board from revoking, failing to
renew, or taking any other disciplinary action against a
physician's license based solely on the physician's
recommendation to an eligible patient regarding, or
prescription for, or treatment with, an investigational drug,
biological product, or device pursuant to this bill.
8)Prohibits a state agency from taking any action against a
health facility's license based solely on the facility's
participation in the treatment by or use of an investigational
drug, biological product, or device pursuant to this bill.
9)Specifies that this bill does not create a private cause of
action against a manufacturer of an investigational drug,
biological product, or device, or against any other person or
entity involved in the care of an eligible patient using the
investigational drug, biological product, or device, for any
harm to the eligible patient resulting from the
investigational drug, biological product, or device so long as
the manufacturer or other person or entity complies in good
faith with the terms of this bill and exercises reasonable
care.
10)Requires a manufacturer that provides an investigational
drug, biological product, or device to an eligible patient to
report all of the following information to the California
Department of Public Health (DPH):
a) The number of requests made for an investigational drug,
biological product, or device;
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b) The number of requests that were approved;
c) The duration of treatments;
d) The success or failure of the investigational drug,
biological product, or device in treating the terminal
disease with which the eligible patient was diagnosed;
e) Any adverse event for each investigational drug,
biological product, or device;
f) Costs paid by each eligible patient for each
investigational drug; and,
g) The consulting physician's diagnosis and prognosis, and
verification that the eligible patient is competent, acting
voluntarily, and has made an informed decision, or that the
consulting physician has determined that the person is not
an eligible patient.
11)Requires the information collected to be confidential and
collected in a manner that protects the privacy of the
patient, the patient's family, and any medical provider or
pharmacist involved with the patient.
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EXISTING STATE LAW:
1)Establishes the Sherman Food, Drug, and Cosmetic Law, which
regulates the packaging, labeling, and advertising of drugs
and devices, administered by DPH.
2)Prohibits, in the Sherman Law, the sale, delivery, or giving
away of a new drug or device unless it is either:
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
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duress. Imposes penalties for violations of these protections.
4)Requires health plans and insurers to provide an external,
independent review process to examine 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, Phase I-IV, if the
enrollee's treating physician, recommends participation in the
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)Under federal regulation:
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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 Institutional
Review Board (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
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
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advice on ethical and regulatory issues in biomedical and
social-behavioral research.
FISCAL EFFECT: According to the Senate Appropriations
Committee, one-time costs of $20,000 and ongoing costs of
$10,000 per year to review plan filings by the Department of
Insurance (Insurance Fund). Increased costs of $380,000 in
2015-16 to respond to requests for information about prior
independent medical review decisions and ongoing costs of
$210,000 per year to respond to consumer complaints and requests
for independent medical review for access to investigational
drugs by the Department of Managed Health Care (Managed Care
Fund). Uncertain impact on state-funded health CalPERS health
care coverage (General Fund and special funds).
COMMENTS:
1)PURPOSE OF THIS BILL. According to the author, terminal
patients who have exhausted their conventional treatment
options have difficulty obtaining access to potentially
life-saving investigational drugs. The patient can attempt to
enroll in a clinical trial, but many of the sickest
individuals do not qualify to join such a trial. This bill
would give a patient, who has exhausted all other treatment
options, a last-chance effort to save their life with an
option to try an experimental drug that has passed Phase 1 of
the FDA safety trials. The author states that this bill
ensures that terminal patients have the right to make their
own medical decisions, while providing important legal
protections for patients, doctors, insurance and
pharmaceutical companies.
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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. As of
March 2015 there are at least 36 states and Washington D.C.
that have examined or will examine legislation on the issue,
and 12 have already signed laws.
3)FDA AND STATE APPROVAL OF DRUGS. FDA has jurisdiction over
all drugs that are sold across state lines. State law gives
DPH the authority to approve for market a drug or device that
is sold 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
a few instances where California has approved a new drug or
device application.
4)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 what the drug's
most frequent side effects are in healthy volunteers, 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) 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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5)Expanded Access to investigational products through the FDA.
If a patient is unable to enroll in a clinical trial, the FDA
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 is able to apply for
expanded access under a single patient IND Application on
behalf of the patient. The supervising physician must be
willing to commit to oversee the treatment, work with the
manufacturing company and FDA, obtain the drugs, monitor the
patient during the course of treatment, and file necessary
paperwork. 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.
FDA directives allow 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.
6)FDA ACTION. 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
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days to a few months. On February 4, 2015, the FDA announced
that it would be streamlining the expanded use application
process, and stated that the proposed application will allow
physicians to apply for experimental drugs in just 45 minutes.
The FDA issued draft guidance and included a copy of the new
form, asking for comment until April 13, 2015. The FDA is now
in the process of reviewing the public comments and will not
likely finalize the guidance before late summer/early fall.
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. 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 full 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)INSTITUTIONAL REVIEW BOARDS ARE NECESSARY PATIENT SAFEGUARDS.
Federal law requires that any FDA expanded use requests for
any investigational drug be reviewed by an IRB, or ethics
committee; a group of medical experts that evaluates the risks
of an experimental treatment and ensures the patient
understands them as well. The IRB process protects the people
receiving the drug and ensures that the risks are reasonable
given the potential benefits. A physician submits the
proposed experimental protocol, including duration of
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treatment and the informed consent documents to an IRB, which
reviews them to make sure patients are fully aware of
potential risks and are willing to accept the level of
potential risk associated with the drug. IRBs are usually
associated with a hospital or research institution, but there
are independent IRBs available for physicians not associated
with such an institution. The OHRP requires and regulates the
use of IRBs for any research supported or conducted by HHS
(which includes National Institutes on Health funded
research). While OHRP oversees IRB processes in general, each
institution has their own review board, timelines, and
specific policies. Physicians are governed primarily by the
IRB committee policies set up by their specific institution.
9)CONTROVERSY OVER RESEARCH WITHOUT IRB APPROVAL. In 2012, two
neurosurgeons from the University of California, Davis (UC
Davis) were accused of performing an unapproved experimental
procedure on three dying brain cancer patients. In these
cases, the neurosurgeons obtained informed consent from the
patients but did not communicate to the patients that the
procedure had not been approved by the FDA as an
investigational new treatment for testing in human subjects.
The patients were also not informed that the research was not
approved by UC Davis' IRB. Two of the patients developed
sepsis and died within weeks of their surgeries. Both surgeons
involved were banned from performing surgery and later
resigned from the University. In response to these
incidences, UC Davis has since tightened its innovated use
policy to expressly prohibit any use of a non-FDA approved
drug, biologic, or device without formal IRB and, as required,
FDA approval, regardless of the purpose of the use.
10)Who will pay? If a patient is enrolled in an FDA-approved
clinical trial for cancer, California law requires that the
insurer pay for routine patient care costs. Health plans do
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not have to pay for experimental drug, but in most cases these
drugs are given to clinical trial participants at no cost by
the government agency, university medical center, or
pharmaceutical company that sponsors the trial.
This bill authorizes, but does not require any health plan,
insurer, or manufacturer to pay for the cost of the
medication. Typically, health plans limit coverage to only FDA
approved drugs and devices. In addition, when a plan reviews
potential drugs for their formulary, they review data on
clinical effectiveness, cost of the drug, potential side
effects or harm, and the costs associated with treating that.
Under current law, a patient denied coverage for an
experimental drug or device may appeal the decision and
request evaluation by Independent Medical Review, although
this can be a time-consuming process. Taken together, it is
unlikely that health plans would cover the cost of
experimental drugs obtained through this legislation.
In the expanded access use protocols the FDA allows, after
their review and approval, the manufacturer to charge a
nominal fee for the cost of providing the experimental drug or
device. This bill authorizes a manufacturer to charge for the
experimental drug or device, without any review or approval.
11)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 ALS Association
Golden West Chapter states that they support and advocate for
expanded access to experimental treatments for people living
with ALS.
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12)OPPOSITION. The Association of Northern California
Oncologists opposes this bill citing several reasons,
including the difficulty identifying "terminally-ill"
patients, the lack of an informed consent process to protect
patients seeking these drugs, and the lack of appropriate
physician supervision of the use of these drugs. The
California Medical Association states opposition due to
significant patient safety concerns with allowing access to
unproven drugs outside the FDA's clinical trials and
compassionate use programs. The FDA ensures efficacy and
safety of using such drugs, and once they are removed from
these processes there is no longer an ability to protect
patients and provide proper oversight. Additionally, this
bill may be both premature and unnecessary, and could also
potentially detract from the FDA rulemaking process that is
currently ongoing. 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".
13)CONCERNS. The Pharmaceutical Research and Manufacturers of
America (PhRMA) has concerns with this bill, writing that
while "the bill is well-intentioned, it could have serious
unintended consequences that must be taken into consideration"
and adds that this bill may be premature given recent
developments at the federal level. PhRMA states that
right-to-try legislation is unlikely to achieve the goal of
bringing innovative, safe and effective medicines to patients
as quickly as possible and cites the current robust nature of
the current clinical trial process, the FDA's current expanded
use protocols, and efforts underway to streamline the expanded
use procress as reasons for concerns.
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The Los Angeles County Board of Supervisors notes that that
this does not provide patients with comprehensive written,
informed consent. The Board "would support this bill if it
was amended to include such informed consent to help ensure
that patients are fully aware of the potential risks involved
with receiving experimental treatment".
14)RELATED LEGISLATION.
a) SB 715 (Anderson) is substantively similar to this bill.
The bill is currently pending in the Senate Committee on
Health.
b) SB 128 (Wolk) permits a competent, qualified individual
who is a terminally ill adult to receive a prescription for
aid in dying medication if certain conditions are met. SB
128 is currently pending in this Committee.
c) AB 159 (Calderon) is substantially similar to this bill,
and also creates a Right to Try Act, permitting a
manufacturer of an investigational drug, biological
product, or device to make available an investigational
drug, biological product, or device to an eligible patient.
AB 159 was approved by this Committee on April 7, 2015, by
a vote of 17-0 and is now pending in Senate Business,
Professions, and Economic Development Committee.
15)Double referral. This bill is double referred. Should it
pass out of this Committee, it will be referred to the
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Assembly Committee on Business and Professions.
16)POLICY CONCERNS.
a) Is this bill premature? In response to requests from
advocates, and the passage of several right-to-try bills in
states, the FDA is promulgating new regulations to
dramatically shorten the length of time it takes to apply
for expanded use access. Public comments on the proposed
regulations were accepted through April, 2015 and are
currently under review by the FDA. Given that the FDA may
arrive at the intended purpose of this goal in the very
near future, the committee may wish to consider whether
this bill is premature.
b) Will this bill achieve its intended goal? Shipping an
investigational drug across state lines is illegal without
an approved IND from the FDA. If a manufacturer outside of
California agreed to provide their investigational drug to
a patient under this bill, they would 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 regulation.
Similar bills in other states have been enacted too
recently to assess their impact. Anecdotal news reports
suggest that when approached by patients directly,
manufacturers are requesting that they go through the FDA
process instead.
c) FDA is not the limiting factor. The FDA approves 99% of
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expanded access requests. The ultimate decision to provide
the drug to the patient is currently made by the
pharmaceutical manufacturer; nothing in this bill would
address or change that.
d) Conflict with other bills this session. AB 159 already
approved by this Committee, is substantively the same as
this bill.
17)SUGGESTED AMENDMENTS.
a) As drafted, this bill requires that a patient has given
written, informed consent, but does not specify what
information must be included in that consent.
Additionally, informed consent requirements for
experimental treatments are already codified in the
"Protection of Human Subjects in Medical Experimentation
Act" (HSC 24170-24179). To ensure that patients are fully
aware of all risks and unique requirements of this state,
the author should amend the bill to explicitly state the
requirements of the informed consent, and also to
cross-reference the informed consent requirements already
codified in current law.
b) Even when treating a single, terminally ill patient, the
use of an unapproved drug is still considered human
experimentation and should be bound by the highest
scientific ethical standards. Lack of IRB oversight in
this bill weakens patient protections. Most institutions
have IRB policies in place that physicians must follow.
Because this bill does not specify IRB review of treatment
protocol and informed consent, physicians not bound and
their institutional policies might not undergo this ethical
review. This bill should be amended to require that the
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informed consent document and treatment protocol be
approved by the physician's institutional review board or
by an accredited independent institutional review board.
c) The definition of terminal disease used in this bill is
inconsistent with current law, as well as other measures
under consideration by this Committee this year. To be
consistent with AB 159, and remove conflict with SB 128,
the definition of eligible patient should be amended as
follows:
On page 3, line 3:
(a) "Eligible patient" means a person to whom all of the
following conditions apply:
(1) He or she has a terminal disease immediately
life-threatening disease or condition as determined by that
person's physician and a consulting physician.
On page 4, delete lines 12-15 and insert:
"Immediately life-threatening disease or condition" means a
stage of disease in which there is a reasonable likelihood
that death will occur within a matter of months.
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REGISTERED SUPPORT / OPPOSITION:
Support
ALS Association - Golden West Chapter
City of Murrieta
Union of American Physicians and Dentists/American Federation of
State, County and
Municipal Employees, AFL-CIO
Opposition
California Medical Association (unless amended)
California Nurses Association/National Nurses United
Association of Northern California Oncologists
Analysis Prepared by:Dharia McGrew / HEALTH / (916)
319-2097
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