BILL ANALYSIS Ó
SENATE COMMITTEE ON HEALTH
Senator Ed Hernandez, O.D., Chair
BILL NO: AB 1668
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|AUTHOR: |Calderon |
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|VERSION: |March 7, 2016 |
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|HEARING DATE: |June 22, 2016 | | |
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|CONSULTANT: |Melanie Moreno |
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SUBJECT : Investigational drugs, biological products, and
devices
SUMMARY :1) 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, as
defined. Prohibits this bill from requiring that a manufacturer
make available an investigational drug, biological product, or
device to an eligible patient.
Existing state law:
1)Establishes the Sherman Food, Drug, and Cosmetic Law (Sherman
Law), which regulates the packaging, labeling, and advertising
of drugs and devices, administered by the Department of Public
Health (DPH).
2)Prohibits, under 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withdrawn, terminated, or suspended that approval; or,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 U.S. Food and Drug
Administration (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not been withdrawn, terminated, or suspended under the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
AB 1668 (Calderon) Page 2 of ?
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 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 regulation: 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.
AB 1668 (Calderon) Page 3 of ?
4)Establishes the Office for Human Research Protections (OHRP),
which provides leadership in the protection of the rights,
welfare, and well-being 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.
This bill:
1)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, as
defined. Prohibits this bill from requiring that a
manufacturer make available an investigational drug,
biological product, or device to an eligible patient.
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 USDA and
remains under investigation in a clinical trial approved by
the FDA.
3)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 not been accepted to participate in the
nearest clinical trial to his or her home for the
immediately life-threatening disease or condition
within one week of completion of the clinical trial
application process, or, in the treating physician's
medical judgment, it is unreasonable for the patient
to participate in that clinical trial due to the
patient's current condition and stage of disease;
d) Has received a recommendation from his or her
primary physician and a consulting physician, as
defined, for an investigational drug, biological
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product, or device. Defines "consulting physician" as
a physician and surgeon or an osteopathic physician
and surgeon who:
i. Examines the qualified individual
and his or her relevant medical records;
ii. Confirms, in writing, the primary
physician's diagnosis and prognosis; and,
iii. Verifies, in the opinion of the
consulting physician, that the eligible patient
is competent, acting voluntarily, and has made an
informed decision.
e) Has given written informed consent for the use
of the investigational drug, biological product, or
device, or, if he or she lacks the capacity to
consent, his or her legally authorized representative
has given written informed consent on his or her
behalf. Defines "written informed consent" as a
written document that has been approved by the primary
physician's 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 that, at a minimum:
i. Explains the currently approved
products and treatments for the disease or
condition from which the patient suffers;
ii. Attests 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;
iii. Clearly identifies the specific
proposed investigational drug, biological
product, or device that the patient is seeking to
use;
iv. Describes the potentially best and
worst outcomes of using the investigational drug,
biological product, or device and describes the
most likely outcome, as specified;
v. Clearly states that the patient's
health plan or insurer, if any, and health care
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provider are not obligated to pay for the
investigational drug, biological product, or
device or any care or treatments consequent to
use of the investigational drug, biological
product, or device;
vi. Clearly states 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;
vii. Clearly states that in-home health
care may be denied if treatment begins; and,
viii. States that the patient understands
that he or she is liable for all expenses
consequent to the use of the investigational
drug, biological product, or device, 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,
biological product, or device.
4)Permits a manufacturer to provide an investigational drug,
biological product, or device to an eligible patient without
receiving compensation and to require an eligible patient to
pay the costs of or associated with the manufacture of the
investigational drug, biological product, or device.
5)Prohibits this bill from expanding or otherwise affecting
coverage provided by health plans or insurers, the Medi-Cal
program, or county organized health systems.
6)Specifies that this bill does not require a health plan or
insurer to provide coverage for the cost of any
investigational drug, biological product, or device, or the
costs of services related to the use of an investigational
drug, biological product, or device under this bill, but
permits one to provide such coverage.
7)Prohibits an investigational drug, biological product, or
device from being offered if a clinical trial for that
investigational drug, biological product, or device is closed
due to the lack of efficacy or for toxicity. Requires the
manufacturer and the patient's primary physician, if notice is
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given for an investigational drug, biological product, or
device taken by a patient outside of a clinical trial, to
notify the patient of the information from the safety
committee of the clinical trial.
8)Prohibits the heirs of an eligible patient, if he/she dies
while being treated by an investigational drug, biological
product, or device made available pursuant to this bill, from
being liable for any outstanding debt related to the treatment
or lack of insurance for the treatment.
9)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 if the recommendation or
prescription is consistent with protocol approved by the
physician's IRB or an accredited independent institutional
review board.
10)Requires the physician's IRB or an accredited institutional
review board to biannually report to DPH, the Medical Board of
California (MBC), and the Osteopathic Medical Board of
California (OMBC):
a) The number of requests made for an
investigational drug, biological product, or device;
b) The status of the requests made;
c) The duration of the treatment;
d) The costs of the treatment paid by eligible
patients;
e) The success or failure of the investigational
drug, biological product, or device in treating the
immediately life-threatening disease or condition from
which the patient suffers; and,
f) Any adverse event for each investigational
drug, biological product, or device.
11)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,
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biological product, or device.
12)Makes a violation of this bill not subject to the Sherman
Law.
13)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, including, but not limited to, product
liability, medical negligence, or wrongful death, 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 for harm done to the eligible
patient or his or her heirs resulting from the investigational
drug, biological product, or device, or the use or nonuse
thereof, if the manufacturer or other person or entity has
complied with the terms of this article in relation to the
eligible patient, unless there was a failure to exercise
reasonable care.
FISCAL
EFFECT : According to the Assembly Appropriations Committee:
1)Minor and absorbable costs to DPH, the Medical Board of
California, and Osteopathic Medical Board of California to
receive and review biannually reports from institutional
review boards on the requests for treatment with an
investigational product (various funds).
2)Costs of $380,000 in the first year of implementation, and
$200,000 ongoing to Department of Managed Health Care (DMHC)
(Managed Care Fund). First year costs are higher because of
probable additional legal analysis and processing Public
Records Act (PRA) requests for experimental procedures
previously authorized or rejected by health plans. Ongoing
costs are related to patient and provider inquiries to the
DMHC's Help Center. DMHC indicates any of the investigational
and/or experimental Independent Medical Review (IMR) requests
require thorough analysis to determine if literature and
studies on the treatments are available, and to review
clinical trials, if completed or available.
3)The California Department of Insurance may, similarly to DMHC,
experience unknown costs related to IMR requests, PRA
requests, or other requests for other assistance to the extent
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these requests increase. (Insurance Fund).
PRIOR
VOTES :
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|Assembly Floor: |77 - 2 |
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|Assembly Appropriations Committee: |20 - 0 |
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|Assembly Health Committee: |18 - 0 |
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COMMENTS :
1)Author's statement. According to the author, AB 1668 seeks to
allow terminally ill patients the right to pursue non-FDA
approved medications in hopes of saving their lives.
Terminally ill patients often do not have the luxury of
waiting for the FDA to grant compassionate use or
participating in the lengthy process of clinical trials. AB
1668 gives terminally ill patients a chance to try potentially
life-saving treatments after all other options have been
exhausted. AB 1668 removes barriers for patients and doctors
who believe an investigational drug or device could be their
last hope for survival, while also protecting physicians,
hospitals, and manufacturers from retribution.
2)Background. According to an April 9, 2015 Health Policy Brief
on the issue of right-to-try laws in Health Affairs, under
current federal regulations, patients with serious or
life-threatening illness have two primary options to access
experimental therapies that may treat their condition but that
have not yet been approved by the FDA: participate as a human
subject in a clinical trial or, for patients who cannot be
enrolled in that trial (because of their medical status or
geographic location, for example), apply to the FDA for access
to the experimental drug under the expanded access (also known
as compassionate use) program.
3)Clinical trials. According to the Health Affairs brief,
clinical testing of an experimental drug is typically a
three-phase process. Phase I trials are small (20 to 80
patients) and are used primarily to evaluate safety and dosing
ranges, usually in healthy volunteers. Phase II trials are
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larger (typically 100 to 300 patients) and are designed to
show early evidence of efficacy in the patients that the drug
is intended to treat. Phase III trials may include hundreds or
thousands of patients and are used to demonstrate that the
drug is effective compared to a control (such as a placebo or
a comparator drug). Typically, a manufacturer submits an
application to the FDA for marketing approval once a drug has
successfully completed Phase III trials. Any drug company
wishing to conduct a clinical trial must first submit an IND
application to the FDA, which allows the company to
manufacture the drug and ship it across state lines for use in
the trial. The drug may be only administered to patients who
are formally enrolled in that clinical trial. The study
population for that trial may be limited based on any number
of factors, including specific diagnosis, age, stage of
illness, or comorbidities.
4)Expanded access program. According to the Health Affairs
brief, the expanded access program is an attempt at
flexibility in the regulatory process and to allow patients
with no other treatment options a chance to try therapies they
may not otherwise have access to. The program allows patients
who meet certain eligibility requirements to receive an
experimental therapy outside of the formal clinical research
process. An application for expanded access can be submitted
by either the drug manufacturer or a licensed physician. There
are three categories of expanded access: treatment, single
patient, and intermediate, which are further split into two
subcategories. One is "expanded access INDs," through which
the manufacturer submits a separate IND for a patient or group
of patients, and the other is "expanded access protocols,"
whereby the manufacturer amends the protocol under an existing
IND to include the patient (or patients) seeking access. Under
treatment INDs, a relatively large group of patients (hundreds
or thousands) are permitted to access an experimental drug,
provided that the sponsor is actively pursuing FDA approval
and is in later stages of testing (or has already submitted
trial results to the FDA for review). According to an article
published in the January 15, 2015 New England Journal of
Medicine (NEJM), the FDA has permitted almost all expanded
access requests regardless of category. The FDA estimated that
by 2006, approximately 100,000 patients had obtained expanded
access to experimental drugs. Between 2010 and 2013, the FDA
imposed clinical holds on only two of the 2,472 individual,
non-emergency protocols, on one of 66 intermediate-size
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requests, and on none of the 41 widespread expanded-access
protocols it received.
The Health Affairs brief states that critics of the expanded
access program have argued that the application process is
unnecessarily burdensome and lengthy (it is estimated that the
IND application requires about 100 hours to complete), which
discourages doctors and manufacturers from applying. An IRB
review adds an additional layer of paperwork and potential
delay. These requirements were put in place in response to
highly publicized incidents of harm caused by unsafe drugs. In
the past decade, there have been several attempts made at the
federal and judicial levels to further relax restrictions on
the administration of experimental therapies to terminally ill
patients. One, led by the Abigail Alliance for Better Access
to Developmental Drugs, submitted a Citizen Petition to the
FDA in 2003 requesting that it make experimental therapies
available to terminally ill patients, provided that the drug
had passed Phase I testing. Following several years of
litigation, the DC Court of Appeals ruled against the Abigail
Alliance, stating that terminally ill patients have no
constitutional right to access experimental therapies. The US
Supreme Court subsequently declined to review the case.
Several bills have been introduced in the US Congress that aim
to relax FDA restrictions on access to experimental therapies.
The most recent of these (HR 4475, the Compassionate Freedom
of Choice Act of 2014) failed to make it out of committee.
5)Other states. Over the past year, the issue of access to
experimental therapies has been debated at the state level, in
part due to efforts of the Goldwater Institute, a libertarian
think tank that appears to be the source of this bill. In
February 2014, the Institute released a policy paper that
outlines the major critiques of the FDA's expanded access
program and proposes model legislation for states to adopt.
According to the National Conference of State Legislatures
(NCSL), legislation related to right-to-try have been
introduced in 30 states. Arizona, Colorado, Louisiana,
Michigan, and Missouri have laws on the subject.
6)FDA action. According to a June 2, 1016 statement from the
Commissioner, the FDA has finalized its efforts to streamline
the process used by physicians to request the expanded access
program, which was prompted due to reports that navigating
that process can be challenging and time consuming. According
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to the FDA statement, in order to make things simpler for
physicians and reduce the amount of time they spend filling
out a request for access to an investigational drug, the FDA
released the final Individual Patient Expanded Access
Investigational New Drug Application, which is much shorter
than the form previously used and should take about 45 minutes
for a physician to complete. The FDA also released
step-by-step instructions on how to complete it.
7)NEJM article. The authors of the January 2015 NEJM article
mentioned above call right-to-try laws misguided, and call for
a more pragmatic approach. They suggest that states work
collaboratively with the FDA to make expanded access more
practical when it is appropriate. For example, since the FDA
has acknowledged that gaining approval from an IRB can pose a
barrier, states could partner with the FDA to fund multicenter
IRBs that focus specifically on expanded-access requests. Such
multicenter panels would conduct full reviews, but their
subject-matter expertise and limited dockets would translate
into faster review times. Practical obstacles to enhancing
expanded access programs, including administrative burdens and
industry costs, would also be best tackled by the states in
partnership with the FDA. For example, a manufacturer's
reluctance to provide product because of financial concerns
could be addressed by permitting companies to charge amounts
closer to the likely post approval cost of drugs.
8)Double referral. This bill is double referred. Should it
pass out of this committee, it will be referred to the Senate
Committee on Business and Professions and Economic
Development.
9)Previous legislation. SB 149 (Stone of 2015) and AB 159
(Calderon of 2015) were substantially similar to this bill,
and enacts the 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, as defined. SB 149 was held on
the Assembly Appropriations Committee suspense file. AB 159
was vetoed by the Governor, who stated, "Patients 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
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expedited process a chance to work."
SB 715 (Anderson of 2015), would have permitted a
manufacturer of a drug, biological product, or device that has
not yet received federal or state approval to market to make
the product available to eligible patients with terminal
illnesses, as specified. SB 715 was set for hearing in this
Committee, but withdrawn at the request of the author.
SB 128 (Wolk and Monning of 2015), would have permitted a
qualified adult with capacity to make medical decisions, who
has been diagnosed with a terminal disease to receive a
prescription for an aid in dying drug if certain conditions
are met. SB 128 was set for hearing in the Assembly Health
Committee, but withdrawn at the request of the author.
AB X2 15 (Eggman, Chapter 1, Statutes of 2015-16 Second
Extraordinary Session)
is substantially similar to SB 128.
10)Support. The National Association of Social Workers writes
that approval for the FDA's expanded access program can take
several months and terminally ill patients who have exhausted
all other options are unable to wait months to gain access to
potentially life-saving investigation drugs and devices. The
Los Angeles County Board of Supervisors states that seriously
ill patients, who have exhausted their options to find a cure
and who have identified physicians and a pharmaceutical
company willing to assist them, deserve the right to
experimental treatments that could improve their health
conditions for prolonging their lives. The ALS Association
Golden West Chapter states that they support and advocate for
expanded access to experimental treatments for people living
with ALS.
11)Opposition. The Medical Oncology Association of Southern
California, Inc cite the difficulty of identifying a
terminally-ill patient, the danger a "right to try" policy
outside the context of a clinical trial would present to adult
clinical trial enrollment and the lack of an informed consent
process to protect patients seeking investigational drugs as
reasons for establishing their oppose position on the bill.
The California Nurses Association/National Nurses United (CNA)
maintain that this bill does nothing to address the real
barriers to "compassionate use" revealed in a recent article
AB 1668 (Calderon) Page 13 of ?
in the NEJM article specifically stating that nothing in this
legislation impacts the availability of drugs to terminally
ill patients unless the manufacturer of the drugs allow it to
be used in advance of FDA approval. The CNA goes on to state
instead of taking on the cost of drugs and challenging drug
manufacturers that charge excessive prices for all drugs sold
in California, this bill reinforces the status quo for
investigational drug costs.
SUPPORT AND OPPOSITION :
Support: (sponsor)
ALS (Amyotrophic Lateral Sclerosis) Association Golden
West Chapter
County of Los Angeles Board of Supervisors
National Association of Social Workers California
Chapter
Oppose:
California Nurses Association
Medical Oncology Association of Southern California,
Inc.
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