Existing law, the federal Food, Drug, and Cosmetic Act, prohibits a person from introducing into interstate commerce any new drug unless the drug has been approved by the United States Food and Drug Administration (FDA). Existing law requires the sponsor of a new drug to submit to the FDA an investigational new drug application and to then conduct a series of clinical trials to establish the safety and efficacy of the drug in human populations and submit the results to the FDA in a new drug application.

Existing law, the Sherman Food, Drug, and Cosmetic Law, regulates the packaging, labeling, and advertising of drugs and devices and is administered by the State Department of Public Health. A violation of that law is a crime. The Sherman Food, Drug, and Cosmetic Law prohibits, among other things, the sale, delivery, or giving away of a new drug or new device unless either the department has approved a new drug or device application for that new drug or new device and that approval has not been withdrawn, terminated, or suspended or the drug or device has been approved pursuant to specified provisions of federal law, including the federal Food, Drug, and Cosmetic Act.

The Medical Practice Act provides for the licensure and regulation of physicians and surgeons by the Medical Board of California and requires the board to take action against a licensee who is charged with unprofessional conduct. The Osteopathic Act provides for the licensure and regulation of osteopathic physicians and surgeons by the Osteopathic Medical Board of California and requires the board to enforce the Medical Practice Act with respect to its licensees.

This bill would permit a manufacturer of an investigational drug, biological product, or device to make the product available to eligible patients with an immediately life-threatening disease or condition, as specified. The bill would authorize, but not require, a health benefit plan, as defined, to provide coverage for any investigational drug, biological product, or device made available pursuant to these provisions. The bill would prohibit the Medical Board of California and the Osteopathic Medical Board of California from taking any disciplinary action against the license of a physician based on the physicians 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 physicians institutional review board or an accredited institutional review board, and would require the institutional review board to biannually report specified information to the State Department of Public Health, among others. The bill would prohibit a state agency from altering any recommendation made to the federal Centers for Medicare and Medicaid Services regarding a health care providers 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, biological product, or device.

Existing law, the federal Food, Drug, and Cosmetic Act, prohibits a person from introducing into interstate commerce any new drug unless the drug has been approved by the United States Food and Drug Administration (FDA). Existing law requires the sponsor of a new drug to submit to the FDA an investigational new drug application and to then conduct a series of clinical trials to establish the safety and efficacy of the drug in human populations and submit the results to the FDA in a new drug application.

Existing law, the Sherman Food, Drug, and Cosmetic Law, regulates the packaging, labeling, and advertising of drugs and devices and is administered by the State Department of Public Health. A violation of that law is a crime. The Sherman Food, Drug, and Cosmetic Law prohibits, among other things, the sale, delivery, or giving away of a new drug or new device unless either the department has approved a new drug or device application for that new drug or new device and that approval has not been withdrawn, terminated, or suspended or the drug or device has been approved pursuant to specified provisions of federal law, including the federal Food, Drug, and Cosmetic Act.

The Medical Practice Act provides for the licensure and regulation of physicians and surgeons by the Medical Board of California and requires the board to take action against a licensee who is charged with unprofessional conduct. The Osteopathic Act provides for the licensure and regulation of osteopathic physicians and surgeons by the Osteopathic Medical Board of California and requires the board to enforce the Medical Practice Act with respect to its licensees.

This bill would permit a manufacturer of an investigational drug, biological product, or device to make the product available to eligible patients with an immediately life-threatening disease or condition, as specified. The bill would authorize, but not require, a health benefit plan, as defined, to provide coverage for any investigational drug, biological product, or device made available pursuant to these provisions. The bill would prohibit the Medical Board of California and the Osteopathic Medical Board of California from taking any disciplinary action against the license of a physician based on the physicians 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 physicians institutional review board or an accredited institutional review board, and would require the institutional review board to biannually report specified information to the State Department of Public Health, among others. The bill would prohibit a state agency from altering any recommendation made to the federal Centers for Medicare and Medicaid Services regarding a health care providers 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, biological product, or device.

Existing law, the federal Food, Drug, and Cosmetic Act, prohibits a person from introducing into interstate commerce any new drug unless the drug has been approved by the United States Food and Drug Administration (FDA). Existing law requires the sponsor of a new drug to submit to the FDA an investigational new drug application and to then conduct a series of clinical trials to establish the safety and efficacy of the drug in human populations and submit the results to the FDA in a new drug application.

Existing law, the Sherman Food, Drug, and Cosmetic Law, regulates the packaging, labeling, and advertising of drugs and devices and is administered by the State Department of Public Health. A violation of that law is a crime. The Sherman Food, Drug, and Cosmetic Law prohibits, among other things, the sale, delivery, or giving away of a new drug or new device unless either the department has approved a new drug or device application for that new drug or new device and that approval has not been withdrawn, terminated, or suspended or the drug or device has been approved pursuant to specified provisions of federal law, including the federal Food, Drug, and Cosmetic Act.

The Medical Practice Act provides for the licensure and regulation of physicians and surgeons by the Medical Board of California and requires the board to take action against a licensee who is charged with unprofessional conduct. The Osteopathic Act provides for the licensure and regulation of osteopathic physicians and surgeons by the Osteopathic Medical Board of California and requires the board to enforce the Medical Practice Act with respect to its licensees.

This bill would permit a manufacturer of an investigational drug, biological product, or device to make the product available to eligible patients with an immediately life-threatening disease or condition, as specified. The bill would authorize, but not require, a health benefit plan, as defined, to provide coverage for any investigational drug, biological product, or device made available pursuant to these provisions. The bill would prohibit the Medical Board of California and the Osteopathic Medical Board of California from taking any disciplinary action against the license of a physician based on the physicians 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 physicians institutional review board or an accredited institutional review board, and would require the institutional review board to biannually report specified information to the State Department of Public Health, among others. The bill would prohibit a state agency from altering any recommendation made to the federal Centers for Medicare and Medicaid Services regarding a health care providers 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, biological product, or device.

Existing law, the federal Food, Drug, and Cosmetic Act, prohibits a person from introducing into interstate commerce any new drug unless the drug has been approved by the United States Food and Drug Administration (FDA). Existing law requires the sponsor of a new drug to submit to the FDA an investigational new drug application and to then conduct a series of clinical trials to establish the safety and efficacy of the drug in human populations and submit the results to the FDA in a new drug application.

Existing law, the Sherman Food, Drug, and Cosmetic Law, regulates the packaging, labeling, and advertising of drugs and devices and is administered by the State Department of Public Health. A violation of that law is a crime. The Sherman Food, Drug, and Cosmetic Law prohibits, among other things, the sale, delivery, or giving away of a new drug or new device unless either the department has approved a new drug or device application for that new drug or new device and that approval has not been withdrawn, terminated, or suspended or the drug or device has been approved pursuant to specified provisions of federal law, including the federal Food, Drug, and Cosmetic Act.

The Medical Practice Act provides for the licensure and regulation of physicians and surgeons by the Medical Board of California and requires the board to take action against a licensee who is charged with unprofessional conduct. The Osteopathic Act provides for the licensure and regulation of osteopathic physicians and surgeons by the Osteopathic Medical Board of California and requires the board to enforce the Medical Practice Act with respect to its licensees.

This bill would permit a manufacturer of an investigational drug, biological product, or device to make the product available to eligible patients with an immediately life-threatening disease or condition, as specified. The bill would authorize, but not require, a health benefit plan, as defined, to provide coverage for any investigational drug, biological product, or device made available pursuant to these provisions. The bill would prohibit the Medical Board of California and the Osteopathic Medical Board of California from taking any disciplinary action against the license of a physician based solely on the physicians 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 physicians institutional review board or an accredited institutional review board, and would require the institutional review board to biannually report specified information to the State Department of Public Health, among others. The bill would prohibit a state agency from altering any recommendation made to the federal Centers for Medicare and Medicaid Services regarding a health care providers 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, biological product, or device.

Existing law, the federal Food, Drug, and Cosmetic Act, prohibits a person from introducing into interstate commerce any new drug unless the drug has been approved by the United States Food and Drug Administration (FDA). Existing law requires the sponsor of a new drug to submit to the FDA an investigational new drug application and to then conduct a series of clinical trials to establish the safety and efficacy of the drug in human populations and submit the results to the FDA in a new drug application.

Existing law, the Sherman Food, Drug, and Cosmetic Law, regulates the packaging, labeling, and advertising of drugs and devices and is administered by the State Department of Public Health. A violation of that law is a crime. The Sherman Food, Drug, and Cosmetic Law prohibits, among other things, the sale, delivery, or giving away of a new drug or new device unless either the department has approved a new drug or device application for that new drug or new device and that approval has not been withdrawn, terminated, or suspended or the drug or device has been approved pursuant to specified provisions of federal law, including the federal Food, Drug, and Cosmetic Act.

The Medical Practice Act provides for the licensure and regulation of physicians and surgeons by the Medical Board of California and requires the board to take action against a licensee who is charged with unprofessional conduct. The Osteopathic Act provides for the licensure and regulation of osteopathic physicians and surgeons by the Osteopathic Medical Board of California and requires the board to enforce the Medical Practice Act with respect to its licensees.

This bill would permit a manufacturer of an investigational drug, biological product, or device to make the product available to eligible patients with an immediately life-threatening disease or condition, as specified. The bill would authorize, but not require, a health benefit plan, as defined, to provide coverage for any investigational drug, biological product, or device made available pursuant to these provisions. The bill would prohibit the Medical Board of California and the Osteopathic Medical Board of California from taking any disciplinary action against the license of a physician based solely on the physicians 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 physicians institutional review board or an accredited institutional review board, and would require the institutional review board to biannually report specified information to the State Department of Public Health, among others. The bill would prohibit a state agency from altering any recommendation made to the federal Centers for Medicare and Medicaid Services regarding a health care providers 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, biological product, or device.

CONCURRENCE IN SENATE AMENDMENTS

CSA1 Bill Id:AB 1668

Author:(Calderon)

As Amended Ver:August 15, 2016

Majority vote

Original Committee Reference: HEALTH

SUMMARY: Authorizes the manufacturer of an investigational drug, biological product, or device (investigational drug) that is not yet approved by the United States Food and Drug Administration (FDA) to make the investigational drug available to a patient with a serious or immediately life-threatening disease, when that patient has considered all other treatment options currently approved by the FDA, has been unable to participate in a relevant clinical trial, and for whom the investigational drug has been recommended by the patient's primary physician and a consulting physician. Specifies other criteria and requirements for the use of investigational drugs.

The Senate amendments clarify that a health benefit plan, except to the extent the plan provided coverage, is not liable for any outstanding debt related to the treatment or lack of insurance for the treatment.

FISCAL EFFECT: According to the Senate Appropriations Committee:

1. 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).
2. One-time 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).
3. Uncertain impact on state-funded California Public Employees' Retirement System health care coverage (General Fund and special funds). (See previous fiscal analysis)

COMMENTS: 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 investigational new drugs but face a variety of hurdles. These patients may seek compassionate use 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.

Analysis Prepared by: Rosielyn Pulmano / HEALTH / (916) 319-2097 FN: 00047360003206

 THIRD READING  

Bill No: AB 1668

Author: Calderon (D), et al.

Amended: 8/15/2016 Senate

Vote: 21

SENATE HEALTH COMMITTEE: 9-0, 6/22/16

AYES: Hernandez, Nguyen, Hall, Mitchell, Monning, Nielsen, Pan, Roth, Wolk

SENATE BUS., PROF. & ECON. DEV. COMMITTEE: 9-0, 6/27/16

AYES: Hill, Bates, Block, Gaines, Galgiani, Hernandez, Jackson, Mendoza, Wieckowski

SENATE APPROPRIATIONS COMMITTEE: 7-0, 8/11/16

AYES: Lara, Bates, Beall, Hill, McGuire, Mendoza, Nielsen

ASSEMBLY FLOOR: 77-2, 5/31/16 - See last page for vote

SUBJECT: Investigational drugs, biological products, and devices

SOURCE: Author

DIGEST: This bill 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.

ANALYSIS:

Existing federal law:

1. Establishes the federal Food, Drug, and Cosmetic Act, which grants authority to the U.S. Food and Drug Administration (FDA) to oversee the safety of food, drugs, and cosmetics. Prohibits any new drug from being introduced into interstate commerce unless an application has been approved by the FDA.
2. Provides, under regulation, for the following:
   1. 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;
   2. Requires review and approval from an Institutional Review Board (IRB) before a clinical study can be initiated under an IND;
   3. 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
   4. 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.

Existing state law 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). Prohibits, under the Sherman Law, the sale, delivery, or giving away of a new drug or device unless it is either:

1. 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,
2. 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.

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 “eligible patient” as a person who:
   1. 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;
   2. Has considered all other treatment options currently approved by the FDA;
   3. 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;
   4. Has received a recommendation from his or her primary physician and a consulting physician, as defined, for an investigational drug, biological product, or device.
   5. 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, as specified.
3. 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.
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.
5. 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.
6. 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 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.
7. Prohibits the heirs and health benefit plan, as specified, 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.
8. 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.
9. Requires the physician’s IRB or an accredited IRB to biannually report to DPH, the Medical Board of California, and the Osteopathic Medical Board of California specified information about requests made under this bill.
10. 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, biological product, or device.
11. Makes a violation of this bill not subject to the Sherman Law.
12. 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.

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 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 the expanded access (also known as compassionate use) program.

1. 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 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.
2. 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, 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 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 U.S. Supreme Court subsequently declined to review the case.

1. 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 to the FDA, 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.

Comments

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.

FISCAL EFFECT: Appropriation: No Fiscal Com.: Yes Local: No

According to the Senate Appropriations Committee:

1. 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).
2. One-time 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).
3. Uncertain impact on state-funded California Public Employees’ Retirement System health care coverage (General Fund and special funds).

SUPPORT: (Verified 8/12/16)

ALS (Amyotrophic Lateral Sclerosis) Association Golden West Chapter

Los Angeles County Board of Supervisors

National Association of Social Workers, California Chapter

OPPOSITION: (Verified 8/12/16)

California Nurses Association

Medical Oncology Association of Southern California, Inc.

ASSEMBLY FLOOR: 77-2, 5/31/16

AYES: Achadjian, Alejo, Travis Allen, Arambula, Atkins, Baker, Bigelow, Bloom, Bonilla, Bonta, Brough, Brown, Burke, Calderon, Campos, Chang, Chau, Chávez, Chiu, Chu, Cooley, Cooper, Dababneh, Dahle, Daly, Dodd, Eggman, Frazier, Beth Gaines, Gallagher, Cristina Garcia, Eduardo Garcia, Gatto, Gipson, Gomez, Gonzalez, Gray, Grove, Hadley, Harper, Roger Hernández, Holden, Irwin, Jones, Jones-Sawyer, Kim, Lackey, Linder, Lopez, Low, Maienschein, Mathis, Mayes, McCarty, Medina, Melendez, Mullin, Nazarian, Obernolte, O'Donnell, Olsen, Patterson, Ridley-Thomas, Rodriguez, Salas, Santiago, Steinorth, Mark Stone, Thurmond, Ting, Wagner, Waldron, Weber, Wilk, Williams, Wood, Rendon

NOES: Levine, Quirk

NO VOTE RECORDED: Gordon

Prepared by: Melanie Moreno / HEALTH / (916) 651-4111

8/15/16 20:33:20

**** END ****

SENATE COMMITTEE ON

Senator Ricardo Lara, Chair

2015 - 2016 Regular Session

AB 1668 (Calderon) - Investigational drugs, biological products, and devices

*********** ANALYSIS ADDENDUM – SUSPENSE FILE ***********

The following information is revised to reflect amendments

adopted by the committee on August 11, 2016

Bill Summary:

AB 1668 would authorize the manufacturer of an investigational drug to make an investigational drug available to a patient, under certain circumstances.

Fiscal Impact:

• 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).
• One-time 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 CalPERS health care coverage (General Fund and special funds). (See below.)

Author Amendments:

Make a clarifying change.

-- END --

SENATE COMMITTEE ON APPROPRIATIONS

Senator Ricardo Lara, Chair

2015 - 2016 Regular Session

AB 1668 (Calderon) - Investigational drugs, biological products, and devices

This bill meets the criteria for referral to the Suspense File.

Bill Summary:

AB 1668 would authorize the manufacturer of an investigational drug to make an investigational drug available to a patient, under certain circumstances.

Fiscal Impact:

• 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).
• One-time 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 CalPERS health care coverage (General Fund and special funds). (See below.)

Background:

Under federal law and regulation, drug manufacturers must apply to the federal Food and Drug Administration for permission to market drugs. The application process includes a series of clinical trials to demonstrate the safety and effectiveness of new drugs. The clinical trial process includes a variety of requirements regarding informed consent for participants and reporting requirements on manufacturers. Current federal law also includes a process whereby seriously ill patients can access investigational drugs before they have been approved for general use and without the patient needing to be a participant in a clinical trial. In recent years, concerns have been raised that the process for approving such requests is slow and cumbersome for physicians, discouraging them from seeking such access for their seriously ill patients. However, in June 2016 the Food and Drug Administration revised the process for physicians to apply to provide an investigational drug to a seriously ill patient who is not participating in a clinical trial. According to the Food and Drug Administration, the revised application process should take much less time for a physician to complete than the prior application process.

Current state law generally prohibits the sale or giving away of new drugs unless the new drug has been approved by the state Department of Public Health or the drug has been approved for use by the federal Food and Drug Administration (including premarket approval). State law authorizes the experimental use of drugs and requires certain patient protections, such as oversight by a review committee and informed consent for the patient.

Current state law authorizes patients to seek an independent medical review when a health plan or health insurer denies coverage for an experimental or investigational drug when the patient has a life-threatening or seriously debilitating condition, the patient’s physician indicates that standard therapies have not been effective, and the patient’s physician has recommended an experimental or investigational drug. If the independent medical review finds that the required conditions are met, the health plan or health insurer is required to provide coverage for the experimental or investigational drug.

Statute governing the state’s Medi-Cal program generally limits the coverage for experimental drugs and prohibits coverage of experimental drugs if the experimental drug costs more than conventional therapies.

Proposed Law:

AB 1668 would authorize the manufacturer of an investigational drug to make an investigational drug available to a patient, under certain circumstances.

Specific provisions of the bill would:

• Authorize a manufacturer of an investigational drug, biological product, or device to make such product available to an eligible patient;
• Authorize a manufacturer to make an investigational product available to a patient without compensation or to require the patient to pay the costs of manufacturing the product;
• Specify that the bill does not require a health plan or state agency to provide coverage for the costs of an investigational product;
• Authorize a health plan to provide coverage for an investigational product;
• Prohibit a state regulatory board from taking disciplinary action against a physician based on the physician’s recommendation that a patient use an investigational product;
• Prohibit a state agency from taking regulatory action against a health facility based on a facility’s participation in treatment using an investigational product;
• Require a participating physician’s institutional review board or an accredited institutional review board to provide information to the Department of Public Health, the Medical Board, and the Osteopathic Medical Board on the use of investigational drugs under the bill.

Related Legislation:

• AB 159 (Calderon, 2015) was virtually identical to this bill. That bill was vetoed by Governor Brown.
• SB 149 (Stone, 2015) was substantially similar to this bill. That bill was held on the Assembly Appropriations Committee’s Suspense File.
• SB 715 (Anderson, 2015) was substantially similar to this bill. That bill was not heard in a policy committee.

Staff Comments:

The bill would authorize a manufacturer to make investigational drugs available to patients under limited circumstances. The bill itself does not require a patient’s health plan to provide coverage for the cost of the investigational drug. However, state law requires health plans to provide coverage for investigational drugs under certain circumstances. If a health plan denies coverage for an investigational drug, an enrollee can request an independent medical review of that decision. Based on the independent medical review, a health plan may be required to provide coverage for an investigational drug. It is possible that patients could use the independent medical review process to access coverage for investigational drugs provided by manufacturers under this bill. To the extent that patients enrolled in coverage provided by CalPERS do so, there could be additional costs to the state and/or local governments.

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SENATE COMMITTEE ON

BUSINESS, PROFESSIONS AND ECONOMIC DEVELOPMENT

Senator Jerry Hill, Chair

2015 - 2016 Regular

Bill No: Hearing Date: June 27, 2016

Subject:

SUMMARY: Permits 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 an immediate life threatening condition, as specified.

NOTE: This bill was referred to the Senate Committee on Health first, and was passed out of that Committee on June 22, 2016 by a vote of 9-0.

Existing federal law:

1. Establishes the United States Food and Drug Administration (FDA) to protect the public health by assuring the safety, effectiveness, quality, and security of human and veterinary drugs, vaccines and other biological products, and medical devices through the Food, Drug, and Cosmetic Act (FDCA). (21 United States Code (USC) § 301 et seq.)
2. Prohibits any new drug from being introduced into interstate commerce unless an application has been approved by the FDA. (21 USC § 505 (a))
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.
   (21 Code of Federal Regulations (CFR) Part 312)
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. (45 CFR Part 46)

Existing state law:

1. Establishes the Sherman Food, Drug, and Cosmetic Law (Sherman Law), administered by the State Department of Public Health (DPH), which regulates the packaging, labeling, and advertising of drugs and devices. (Health and Safety Code (HSC) § 109875 et seq.)
2. Establishes parameters for the experimental use of drugs, requiring review by a committee for the protection of human subjects, consent by the patient or patient’s parent or guardian, and prohibits a person having an ownership interest in a skilled nursing facility or intermediate care facility from prescribing an experimental drug for a patient in the facility. (HSC §§ 11115 – 111545)
3. Prohibits, in the Sherman Law, the sale, delivery, or giving away of a new drug or device unless it is either:
4. 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,

1. 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. (HSC § 111550)
2. Prohibits a person from manufacturing any drug or device in California unless he or she has a valid license from the DPH. (HSC § 111615)
3. Authorizes the DPH to require any manufacturer, wholesaler, or importer of any prescription ophthalmic device in California to obtain a license for each place of manufacture. (HSC §§ 111615 and 111620)
4. Establishes the Protection of Human Subjects in Medical Experimentation Act (PHSME 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. (HSC § 24170 et seq.)
5. States that any person who violates any provision of the Sherman Law, if convicted, is subject to imprisonment for not more than one year in the county jail or a fine of not more than $1,000, or both the imprisonment and fine. States that any person who violates the law by removing, selling, or disposing of an embargoed food, drug, device, or cosmetic without the permission of an authorized agent of the department or court shall, if convicted, be subject to imprisonment for not more than one year in a county jail or a fine of not more than $10,000, or both the fine and imprisonment. States that any person who purchases or sells a foreign dangerous drug or medical device, an illegitimate product, or suspect product, that is not approved or otherwise authorized by the FDA or that is obtained outside of the licensed supply chain regulated by the FDA, California State Board of Pharmacy, or DPH, is guilty of a misdemeanor and subject to imprisonment for not more than one year in a county jail, a fine of not more than $10,000 per occurrence, or both the imprisonment and fine. (HSC §111825)
6. 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. (HSC § 1370.4)
7. 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.
   (HSC § 1370.6)
8. Licenses and regulates physicians and surgeons under the Medical Practice Act (MPA) by the Medical Board of California (MBC) within the Department of Consumer Affairs (DCA). (BPC § 2000 et seq.)
9. Provides that the MBC shall take action against a physician who is charged with unprofessional conduct, as specified. (BPC § 2234)

This bill:

1. Enacts the Right to Try Act (Act).
2. Makes the following definitions:
3. “Consulting physician” as a physician and surgeon licensed under the MPA or an osteopathic physician and surgeon licensed under the Osteopathic Act who examines the qualified individual and his or her relevant medical records, confirms, in writing, the primary physician’s diagnosis and prognosis and verifies, in the opinion of the consulting physician, that the eligible patient is competent, acting voluntarily, and has made an informed decision.
4. “Eligible patient” as a person who has an immediately life-threatening disease or condition; has considered all other treatment options currently approved by the FDA, 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 and the treating physician’s medical judgment has not found it is unreasonable for the patient to participate in that clinical trial; has received a recommendation from his or her primary physician and a consulting physician for an investigational drug, biological product, or device (IDBPD); has given written informed consent for the use of the IDBPD or his or her legally authorized representative has given written informed consent on their behalf; has documentation from his or her primary physician and a consulting physician that the patient has met these requirements.
5. “Health benefit plan” as a plan or program that provides, arranges, pays for, or reimburses the cost of health benefits, including but not limited to, a health care service plan contract issued by a health care service plan, and a policy of health insurance issued by a health insurer.
6. “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.
7. “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.
8. “Primary physician” as a physician and surgeon licensed under the MPA or an osteopathic physician and surgeon licensed under the Osteopathic Act.
9. “State regulatory board” as the MBC or the Osteopathic Medical Board of California (OMBC).
10. “Written, informed consent” as a written document that has been approved by the primary physician’s institutional review board or an accredited independent institutional review board, is signed by an eligible patient or their 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, does all of the following:
11. Explains that the currently approved products and treatments for the immediately life-threatening disease or condition from which the patient suffers.
12. Attests to the fact that the patient, or when the patient lacks the capacity to consent his or her legally authorized representative, concurs with the patient’s primary physician in believing that all currently approved and conventionally recognized treatments are unlikely to prolong the patient’s life.
13. Clearly identifies the specific proposed IDBPD that the patient is seeking to use.
14. Describes the potentially best and worst outcomes of using the IDBPD and describes the most likely outcome, including the possibility that new, unanticipated, different, or worse symptoms might result and that death could be hastened by the proposed treatment. Requires the description to be based on the primary physician’s knowledge of the proposed treatment in conjunction with an awareness of the patient’s condition.
15. Clearly states that the patient’s health benefit plan, if any and health care provider are not obligated to pay for the IDBPD or any care or treatments consequent to use of the IDBPD.
16. 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.
17. Clearly states that in-home health care may be denied if treatment begins.
18. States that the patient understands that he or she is liable for all expenses consequent to the use of the IDBPD 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.
19. Clarifies that written consent must be consistent with the informed consent requirements of the PHSME Act.
20. Authorizes a manufacturer of an IDBPD to make the IDBPD available to an eligible patient pursuant to the Act, but clarifies that a manufacturers is not required to make the IDBPD available to an eligible patient.
21. Authorizes a manufacturer to provide an IDBPD 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 IDBPD.
22. Prohibits the Act from expanding or otherwise affecting coverage provided by health plans or insurers, the Medi-Cal program, or county organized health systems.
23. Specifies that the Act does not require a health plan or insurer to provide coverage for the cost of any IDBPD, or the costs of services related to the use of an IDBPD, under the Act, but authorizes a health plan or insurer to provide such coverage.
24. Prohibits an IDBPD from being offered if a clinical trial for that IDBPD is closed due to the lack of efficacy or for toxicity. Requires the manufacturer and the patient's primary physician, if notice is given of closure of a clinical trial for an IDBPD taken by a patient outside of a clinical trial, to notify the patient of the information from the safety committee of the clinical trial.
25. Clarifies that the heirs of an eligible patient, if he or she dies while being treated by an IDBPD made available pursuant to the Act, are not liable for any outstanding debt related to the treatment or lack of insurance for the treatment.
26. Prohibits a state regulatory board, notwithstanding any other law, 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 IDBPD if the recommendation or prescription is consistent with protocol approved by the physician’s institutional review board or an accredited independent institutional review board.
27. Requires the physician’s institutional review board or an accredited institutional review board to biannually report information to DPH, MBC and OMBC regarding the number of requests made for an IDBPD; the status of the requests made; the duration of the treatment; the costs of the treatment paid by eligible patients; the success or failure of the IDBPD in treating the immediately life-threatening disease or condition from which the patient suffers and; any adverse event for each IDBPD.
28. Prohibits a state agency from altering recommendations 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 on a recommendation that a patient have access to an IDBPD.
29. Provides that a violation of the Act shall not be subject to penalties for other violations of provisions of the Sherman Act.
30. Specifies that the Act does not create a private cause of action, and that actions taken pursuant to the Act 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 IDBPD, 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 IDBPD, 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: This bill is keyed “fiscal” by Legislative Counsel. According to the Assembly Committee on Appropriations analysis dated April 6, 2016, this bill will result in minor and absorbable costs to DPH, MBC, and OMBC to receive and review biannually reports from institutional review boards on the requests for treatment with an investigational product. The analysis notes that the bill will also result in $380,000 in the first year of implementation, and $200,000 in ongoing costs to the Department of Managed Health Care as well as possible unknown costs to the Department of related to independent medical review requests, Public Records Act requests or other requests for other assistance to the extent these requests increase.

COMMENTS:

1. Purpose. The Author is the Sponsor of this bill. According to the Author, while the FDA administers a compassionate use program which makes investigational drugs and devices available to terminally ill patients, it often takes months for patients to become approved for participation in the program. The Author notes that due to these long delays, the application process has been the subject of extensive review and a new streamlined application was created, however, the new streamlined application is still not yet in use, and patients still face a 30-day processing delay. The Author states that meanwhile, terminally ill patients are still waiting months to gain access to investigational drugs and treatments. The Author states that terminally ill patients do not have the luxury of waiting and this bill removes barriers for patients and doctors who believe an investigational drug or device could be their last hope for survival.
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: (1) participate as a human subject in a clinical trial or, (2) 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 Program (also known as compassionate use) (EAP).

According to the 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 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.

The EAP 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, 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 2 of the 2,472 individual, non-emergency protocols, on 1 of 66 intermediate-size requests, and on none of the 41 widespread expanded-access protocols it received.

The Health Affairs brief states that critics of the EAP 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 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.

In response to criticisms, the FDA has worked to provide a streamlined alternative for submitting an Investigational New Drug Application (IND) for use in cases of individual patient expanded access and announced it would simplify and accelerate the application process for unapproved investigational drugs that have passed Phase I safety trials. According to a June 2, 2016 statement from the Commissioner of the FDA, the FDA has finalized its efforts to streamline the process used by physicians to request the EAP and notes that 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 IND which is much shorter than the form previously used. The statement noted that the application should now take about 45 minutes for a physician to complete. The FDA also released step-by-step instructions on how to complete it.

1. Efforts in Other States. Right to try laws are already in place in Arizona, Arkansas, Colorado, Indiana, Louisiana, Michigan, Mississippi, Missouri, Montana, North Dakota, Oklahoma, South Dakota, Utah, Virginia, and Wyoming. Lawmakers in Tennessee have sent a similar bill to their governor for approval. Twenty additional states have considered the law in the past two years. Laws in many states generally allow terminally ill patients to have access to experimental drugs while others also allow health insurers to choose to provide coverage for the cost of these treatments and remove liability for physicians for recommending treatments.
2. Prior Related Legislation This Year. SB 149 (Stone) of 2015 was substantively similar to this bill and also 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. (Status: The bill was held in the Assembly Committee on Appropriations.)

SB 715 (Anderson) of 2015 was similar to this bill and SB 149 above and permits 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. (Status: The measure was not heard in a policy committee of the Senate.)

AB 159 (Calderon) of 2015 was virtually identical to this bill. (Status: The measure was vetoed by Governor Brown who stated in his veto message “[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.")

1. Arguments in Support. The Amyotrophic Lateral Sclerosis (ALS) Association Golden West Chapter writes in support of this bill, noting that there is no known prevention, cause or cure for ALS and that there is only one FDA-approved drug available to manage ALS symptoms which is known to extend life by a few months.

According to the Los Angeles County Board of Supervisors, 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 or prolong their lives.

The National Association of Social Workers notes that approval for participation in the compassionate use program can take several months and that terminally ill patients who have exhausted all other options are unable to wait months to gain access to potentially life-saving investigational drugs and devices.

1. Arguments in Opposition. The Medical Oncology Association of Southern California, Inc. (MOASC) is opposed to this bill citing the difficulty of identifying an “immediately life-threatening condition,” the lack of a sufficient informed consent process to protect patients seeking investigational drugs, and the lack of appropriate physician supervision of the use of these drugs. MOASC states “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.”

According to the California Nurses Association and National Nurses United, this bill promises vulnerable patients and their families that there will be a state program for obtaining drugs that is similar to the FDA EAP only shorter, the bill does not address the real barriers to compassionate use and nothing in this bill 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. The organizations state that the only right that is being promoted in this legislation is the right of wealthy individuals who can afford to fund the process and associated costs to access those drugs that pharmaceutical companies in their infinite greed and focused self-interest are willing to make available.

SUPPORT AND OPPOSITION:

Support:

Amyotrophic Lateral Sclerosis (ALS) Association Golden West Chapter

Los Angeles County Board of Supervisors

National Association of Social Workers

Opposition:

California Nurses Association

Medical Oncology Association of Southern California, Inc.

National Nurses United

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SENATE COMMITTEE ON HEALTH

Senator Ed Hernandez, O.D., Chair

BILL NO: AB 1668

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:
   1. 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,
   2. 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 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.
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:
   1. 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;
   2. Has considered all other treatment options currently approved by the FDA;
   3. 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;
   4. Has received a recommendation from his or her primary physician and a consulting physician, as defined, for an investigational drug, biological product, or device. Defines “consulting physician” as a physician and surgeon or an osteopathic physician and surgeon who:
      1. Examines the qualified individual and his or her relevant medical records;
      2. Confirms, in writing, the primary physician’s diagnosis and prognosis; and,
      3. Verifies, in the opinion of the consulting physician, that the eligible patient is competent, acting voluntarily, and has made an informed decision.
   5. 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:
      1. Explains the currently approved products and treatments for the disease or condition from which the patient suffers;
      2. 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;
      3. Clearly identifies the specific proposed investigational drug, biological product, or device that the patient is seeking to use;
      4. Describes the potentially best and worst outcomes of using the investigational drug, biological product, or device and describes the most likely outcome, as specified;
      5. Clearly states that the patient’s health plan or insurer, if any, and health care 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;
      6. 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;
      7. Clearly states that in-home health care may be denied if treatment begins; and,
      8. 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 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):
    1. The number of requests made for an investigational drug, biological product, or device;
    2. The status of the requests made;
    3. The duration of the treatment;
    4. The costs of the treatment paid by eligible patients;
    5. 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,
    6. 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, 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 these requests increase. (Insurance Fund).

PRIOR VOTES:

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 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 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.

1. 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.
2. 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 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.
3. 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.
4. 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.
5. 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 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.

1. 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.
2. 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 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.

-- END --

ASSEMBLY THIRD READING

ATR Bill Id:AB 1668

Author:(Calderon)

As Amended Ver:March 7, 2016

Majority vote

SUMMARY: Authorizes the manufacturer of an investigational drug, biological product, or device (investigational drug) that is not yet approved by the United States Food and Drug Administration (FDA) to make the investigational drug available to a patient with a serious or immediately life-threatening disease, when that patient has considered all other treatment options currently approved by the FDA, has been unable to participate in a relevant clinical trial, and for whom the investigational drug has been recommended by the patient’s primary physician and a consulting physician. Specifies other criteria and parameters for the use of such investigational drugs in this way.

FISCAL EFFECT: According to the Assembly Appropriations Committee:

1. Minor and absorbable costs to the California Department of Health Services (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 these requests increase. (Insurance Fund).

COMMENTS: 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 investigational new drugs but face a variety of hurdles. These patients may seek compassionate use 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.

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, at least 41 other states considered similar right-to-try legislation in 2015.

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.

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 manufacturer of a drug allows it to be used in advance of FDA approval.

Analysis Prepared by: John Gilman / HEALTH / (916) 319-2097 FN: 0003206

ASSEMBLY THIRD READING

ATR Bill Id:AB 1668

Author:(Calderon)

As Amended Ver:March 7, 2016

Majority vote

SUMMARY: Authorizes the manufacturer of an investigational drug, biological product, or device (investigational drug) that is not yet approved by the United States Food and Drug Administration (FDA) to make the investigational drug available to a patient with a serious or immediately life-threatening disease, when that patient has considered all other treatment options currently approved by the FDA, has been unable to participate in a relevant clinical trial, and for whom the investigational drug has been recommended by the patient’s primary physician and a consulting physician. Specifies other criteria and parameters for the use of such investigational drugs in this way.

FISCAL EFFECT: According to the Assembly Appropriations Committee:

1. Minor and absorbable costs to the California Department of Health Services (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 these requests increase. (Insurance Fund).

COMMENTS: 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 investigational new drugs but face a variety of hurdles. These patients may seek compassionate use 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.

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, at least 41 other states considered similar right-to-try legislation in 2015.

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.

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 manufacturer of a drug allows it to be used in advance of FDA approval.

Analysis Prepared by: John Gilman / HEALTH / (916) 319-2097 FN: 0003206

Date of Hearing: April 6, 2016

ASSEMBLY COMMITTEE ON APPROPRIATIONS

Lorena Gonzalez, Chair

ABPCA Bill Id:AB 1668

Author:(Calderon) – As Amended Ver:March 7, 2016

Urgency: No State Mandated Local Program: No Reimbursable: No

SUMMARY:

This bill sets up a legal structure whereby individuals with serious or immediately life-threatening conditions can gain access to investigational drugs, biological products, or medical devices (investigational products). Specifically, this bill:

1. 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 United States Food and Drug Administration (FDA), but has not been approved for general use and remains under investigation in an approved clinical trial.
2. Allows, but does not require, the manufacturer of an investigational product to make the product available to an eligible patient, as defined. Specifies that the manufacturer may provide the product for free or require a patient to pay for the costs of the product.
   
3. Defines an eligible patient as one who has met a number of specified criteria, including having a serious or life-threatening condition, as defined, and having considered all FDA-approved treatment options.
   
4. Allows, but does not require, a health plan or insurer to provide coverage for the investigational product, or the costs of services related to the use of the investigational product.
   
5. Prohibits a state regulatory board from taking disciplinary action against a physician's license based on the recommendation or prescription of, or treatment with, the investigational product, provided it is consistent with protocol approved by an institutional review board. Similarly prohibits a state agency from altering a 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 on such recommendation, prescription, or treatment.
   
6. Specifies it does not create a private cause of action against a manufacturer of an investigational product, or against any other person or entity involved in the care of an eligible patient using the investigational product, provided certain conditions are met.
7. Requires institutional review boards to report information about requests for investigational products to the California Department of Public Health (CDPH), the Medical Board of California (MBC), and the Osteopathic Medical Board of California (OBMC).

FISCAL EFFECT:

1. Minor and absorbable costs to CDPH, MBC, and OMBC to receive and review biannually reports from institutional review boards on the requests for treatment with an investigational product (various funds).
2. $380,000 in the first year of implementation, and $200,000 ongoing to Department of Managed Health Care (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 these requests increase. (Insurance Fund).

COMMENTS:

1. Purpose. 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 or device could be their last hope for survival. These patients may seek compassionate use exemptions from the FDA, but the process is cumbersome and approval comes too late for many. This bill removes barriers for patients who need to immediately obtain investigational treatments.
2. Background. Prior to being available for sale, drugs and devices must pass through clinical trials regulated by the FDA. Phase one of these trials establishes safety and assesses toxicity. Once a drug or device passes stage one, there are two more phases before being approved for sale. This bill would allow manufacturers to make available investigational products that have passed stage one trials to patients meeting specified criteria, and would protect from liability doctors who recommend or prescribe the investigational products, as well as manufacturers who make them available.

There are, however, other ways to gain access to drugs that are not yet approved. Experimental treatments are often available by participating in a clinical trial. 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 access on behalf of the patient. The 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 such applications per year, and has approved more than 99% of those applications. Critics of this process have raised concerns that the application is too cumbersome for physicians and patients to complete. In February 2015, the FDA proposed a new, much shorter form, which the agency has stated is a top priority to finalize. Based on regulatory timelines, it is possible this new form may be available later this year.

1. Support. The Los Angeles County Board of Supervisors and the Amyotrophic Lateral Sclerosis Association Golden West Chapter support this bill, they support expanded use of experimental treatments.
2. Opposition. The California Nurse Association and the Medical Oncology Association of Southern California oppose this bill. The oncologists believe this bill threatens the viability of adult clinical trial enrollment and would result in slowing the development of cancer care in the future.
3. Prior Legislation.
   1. AB 159 (Calderon) of 2015 was identical to this bill. It was vetoed by Governor Brown, 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 expedited process a chance to work." This bill is similar to AB 159 and does not appear to address the veto message.
   2. SB 149 (Stone) of 2015 was largely similar to this bill and to AB 159, and was held on the Suspense File of this committee.
   3. SB 715 (Anderson) of 2015 was also similar to this bill, and was referred to Senate Health Committee and not heard.

Analysis Prepared by: Lisa Murawski / APPR. / (916) 319-2081

Date of Hearing: March 29, 2016

ASSEMBLY COMMITTEE ON BUSINESS AND PROFESSIONS

Rudy Salas, Chair

ABPCA Bill Id:AB 1668

Author:(Calderon) – As Amended Ver:March 7, 2016

NOTE: This bill is double referred, having been previously heard by the Assembly Committee on Health on March 15, 2016 and approved on an 18-0 vote.

SUBJECT: Investigational drugs, biological products, and devices.

SUMMARY: Permits a manufacturer of an investigational drug, biological product or medical device to make the product available to eligible patients, with a serious or immediately life-threatening disease or condition, and authorizes a health benefit plan to provide coverage; prohibits the Medical Board of California and the Osteopathic Medical Board of California from taking any disciplinary action against a licensee based solely on the physician’s recommendation, prescription of a biological product or device or treatment of a patient with such products or devices; prohibits a state agency from altering any recommendation made to the federal Centers for Medicare and Medicaid Services regarding a provider’s certification to participate in the programs based solely on the recommendation that a patient have access to a drug, product or device; and prohibits an official, employee or agent of the state from blocking an eligible patient’s access to the drug, product or device.

EXISTING LAW:

The Business and Professions Code

1. Establishes the Medical Board of California (MBC), within the Department of Consumer Affairs (DCA), which provides for the licensure and regulation of physicians and surgeons, and requires the MBC to take action against a licensee who is charged with unprofessional conduct. (Business and Professions Code (BPC) § 2000 et seq.)
2. Provides for the licensure and regulation of osteopathic physicians and surgeons by the MBC within the DCA and requires the Osteopathic Medical Board (OMB) to enforce the Medical Practice Act. (BPC § 2000 et seq.)

The Health and Safety Code

1. Establishes the Sherman Food, Drug, and Cosmetic Law, which regulates the packaging, labeling, and advertising of drugs and devices, administered by the Department of Public Health (DPH). Health and Safety Code (HSC) § 109875 et seq.
   
2. Prohibits the sale, delivery or giving away of a new drug or device unless it is either: (HSC § 111550)
   1. 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,
   2. 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 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. (HSC § 24170 et seq.)
   
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. (HSC § 1370.4)
   
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. (HSC § 1370.6)

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. (Title 21 United States Code (USC) § 321 et seq.)
   
2. Prohibits any new drug from being introduced into interstate commerce unless an application has been approved by the FDA. (21 USC § 355)
   
3. Under federal regulation: (Title 45 Code of Federal Regulations (CFR) § 46.101 et seq.)
   1. 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;
      
   2. Requires review and approval from an Institutional Review Board (IRB) before a clinical study can be initiated under an IND;
      
   3. 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,
      
   4. 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). (45 CFR § §46.103)

THIS BILL:

1. Permits a manufacturer of an investigational drug, biological product, or device may make available the manufacturer’s investigational drug, biological product, or device to an eligible patient.
2. Specifies that a manufacturer may do both of the following:
   1. Provide an investigational drug, biological product, or device to an eligible patient without receiving compensation.
   2. Require an eligible patient to pay the costs of, or associated with, the manufacture of the investigational drug, biological product, or device.
3. Defines “consulting physician” as a physician and surgeon licensed under the Medical Practice Act or an osteopathic physician and surgeon licensed under the Osteopathic Act who performs the following:
   1. Examines the qualified individual and his or her relevant medical records.
   2. Confirms, in writing, the primary physician’s diagnosis and prognosis.
   3. Verifies, in the opinion of the consulting physician, that the eligible patient is competent, acting voluntarily, and has made an informed decision.
4. Defines “eligible patient” as a person who meets all of the following conditions:
   1. Has an immediately life-threatening disease or condition.
   2. Has considered all other treatment options currently approved by the United States Food and Drug Administration.
   3. Has not been accepted to participate in the nearest clinical trial to his or her home for the immediately life-threatening disease or condition identified in paragraph (1) 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.
   4. Has received a recommendation from his or her primary physician and a consulting physician for an investigational drug, biological product, or device.
   5. 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.
   6. Has documentation from his or her primary physician and a consulting physician attesting that the patient has met the requirements of this subdivision.
5. Defines “health benefit plan” as a plan or program that provides, arranges, pays for, or reimburses the cost of health benefits. “Health benefit plan” includes, but is not limited to, a health care service plan contract issued by a health care service plan, as defined in HSC § 1345, and a policy of health insurance, as defined in § 106 of the Insurance Code, issued by a health insurer.
6. 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.
7. Defines “investigational drug, biological product, or device” means 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.
8. Defines “primary physician” as a physician and surgeon licensed under the Medical Practice Act or an osteopathic physician and surgeon licensed under the Osteopathic Act.
9. Defines “state regulatory board” as the Medical Board of California or the Osteopathic Medical Board of California.
10. Defines “written, informed consent” means a written document that has been approved by the primary physician’s institutional review board or an accredited independent institutional review board, 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, does all of the following:
    1. Explains the currently approved products and treatments for the immediately life-threatening disease or condition from which the patient suffers.
    2. Attests to the fact that the patient, or when the patient lacks the capacity to consent his or her legally authorized representative, concurs with the patient’s primary physician in believing that all currently approved and conventionally recognized treatments are unlikely to prolong the patient’s life.
    3. Clearly identifies the specific proposed investigational drug, biological product, or device that the patient is seeking to use.
    4. Describes the potentially best and worst outcomes of using the investigational drug, biological product, or device and describes the most likely outcome. This description shall include the possibility that new, unanticipated, different, or worse symptoms might result and that death could be hastened by the proposed treatment. The description shall be based on the primary physician’s knowledge of the proposed treatment in conjunction with an awareness of the patient’s condition.
    5. Clearly states that the patient’s health benefit plan, if any, and health care 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.
    6. 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.
    7. Clearly states that in-home health care may be denied if treatment begins.
    8. 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.
11. Requires that written, informed consent shall be consistent with the informed consent requirements of the Protection of Human Subjects in Medical Experimentation Act (HSC § 24170 et seq.).
12. Specifies that a health benefit plan is not required 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.
13. Indicates if the clinical trial for an investigational drug, biological product, or device is closed due to the lack of efficacy or for toxicity, the investigational drug, biological product, or device shall not be offered. If notice of closure of a clinical trial is given for an investigational drug, biological product, or device taken by a patient outside of a clinical trial, the manufacturer and the patient’s primary physician shall notify the patient of the information from the safety committee of the clinical trial.
14. Indicates if an eligible patient dies while being treated by an investigational drug, biological product, or device made available pursuant to this article, the patient’s heirs are not liable for any outstanding debt related to the treatment or lack of insurance for the treatment.
15. Prevents 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 institutional review board or an accredited independent institutional review board.
16. Requires the physician’s institutional review board or an accredited institutional review board to biannually report the following information to the State Department of Public Health, the Medical Board of California, and the Osteopathic Medical Board of California:
    1. The number of requests made for an investigational drug, biological product, or device.
    2. The status of the requests made.
    3. The duration of the treatment.
    4. The costs of the treatment paid by eligible patients.
    5. 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.
    6. Any adverse event for each investigational drug, biological product, or device.
17. States that a state agency shall not alter 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, biological product, or device.
18. 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.

FISCAL EFFECT: Unknown. This bill is keyed fiscal by the Legislative Counsel.

COMMENTS:

Purpose. This bill is sponsored by the author. According to the author, “Terminally ill patients often do not have the luxury of waiting for the FDA to grant compassionate use of participating in the lengthy process of clinical trials. [This bill] gives terminally ill patients a chance to try potentially life-saving treatments after all other options have been exhausted. It removes barriers for patients who need to immediately obtain investigational treatments, while also protecting physicians, hospitals, and manufacturers from retribution.”

Background. The FDA has jurisdiction over all drugs that are sold across state lines. State law provides DPH with the authority to approve for market a drug or device that is sold in California. If a product has received the FDA approval, then the 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 the DPH, this has resulted in a few instances where California has approved a new drug or device application.

Independent from drug or device applications, manufacturers of drugs and devices must be licensed to manufacture in the state of California. The FDA does not approve manufacturers, but they do conduct inspections to ensure manufacturers are in compliance with good manufacturing practices. Under California Law, drug manufacturers must be licensed with the DPH even if not registered with FDA.

Clinical Trials. 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.

According to the author’s office, the FDA has been having great difficulty in getting patients to participate in clinical trials of investigational drugs, because patients do not want to take the chance that they will be in the control group and not receive the experimental drug.

Expanded Access. If a patient is unable to enroll in a clinical trial, the FDA expanded access exemption, also commonly referred to as “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 the 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.

The FDA 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.

Critics of the FDA process have raised concerns that the expanded access application is too cumbersome for physicians and patients to complete. 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. This process includes a 60-day public comment period. The FDA reviews the comments and makes revisions based on the comments. The FDA then seeks approval from the Office of Management and Budget, which includes an additional 30-day public comment period, which commenced on March 10, 2016.

Institutional Review Board (IRB). Any FDA expanded access requests for any investigational drug must be reviewed by an IRB in order to understand the risks of an experimental treatment and ensure that the patient understands them as well.

A physician submits the proposed experimental protocol, 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. Physicians are governed primarily by the IRB committee policies set up by their specific institution. The FDA maintains the right to overrule the physician and the IRB.

Physician Liability and Enforcement Action Against a Physician. Physicians may be concerned about facing a liability risk for investigational drugs, biological products or devices that they recommend to patients or help them gain access to. The Compassionate Access Act of 2010 (H.R. 4732) sought to address this issue by providing immunity to the manufacturer, distributor, administrator, sponsor or physician from suit or liability.

If AB 1668 is enacted, the MBC and the OMB would be prohibited from taking action against physician’s license for prescribing or treating a patient with an investigational drug, biological product or device.

Other States. Since 2014, several states have passed similar legislation including: 1) Alabama, 2) Arkansas, 3) Colorado, 4) Florida, 5) Indiana, 6) Louisiana, 7) Michigan, 8) Minnesota, 9) Mississippi, 10) Missouri, 11) Montana, 12) Nevada, 13) North Dakota, 14) Oklahoma, 15) South Dakota, 16) Tennessee, 17) Texas, 18) Utah, 19) Virginia, and 20) Wyoming. Additionally, Arizona passed a “Right to Try” ballot measure.

Current Related Legislation. SB 128 (Wolk) of the current Legislative Session, permitted a competent, qualified individual who is a terminally ill adult to receive a prescription for aid in dying medication if certain conditions were met. STATUS: This bill is pending in the Assembly Health Committee.

Prior Related Legislation. AB 159 (Calderon) of 2016 was identical to this bill. NOTE: This bill was vetoed by Governor Brown. In his veto message he 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 expedited process a chance to work.

SB 715 (Anderson) of 2015, is largely similar to this bill. NOTE: SB 715 died in the Senate Health Committee.

SB 149 (Stone) of 2015, was largely similar to this bill, with differences primarily in definitions and liability exemptions. NOTE: SB 149 was held on the Senate Appropriations suspense file.

ARGUMENTS IN SUPPORT:

The Amyotrophic Lateral Sclerosis (ALS) Association Golden West Chapter supports the bill and writes in their letter, “The ALS Association has a long history of supporting and advocating for expanded access to experimental treatments for people living with ALS. We are also champions of the research process, as robust enrollment and participation in clinical trials is essential to ultimately finding treatments and a cure for ALS.”

The County of Los Angeles Board of Supervisors also supports the bill and writes, “Patients with a life-threatening disease or condition, 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 or prolong their lives.”

The EveryLife Foundation for Rare Diseases strongly supports, “rational early access to safe and effective treatments for patients battling life-threatening illnesses. Patients with rare diseases and terminally ill patients have an urgent need and deserve an opportunity for treatment, especially when the risk of the disease far outweighs the risks of potential treatments.”

ARGUMENTS IN OPPOSITION:

The California Nurses Association/ National Nurses United opposes the bill and writes, “This bill does not address the real barriers to ‘compassionate use’ revealed in a recent article in the esteemed New England Journal of Medicine. Nothing in this legislation or any other 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. This legislation… is unlikely to withstand a constitutional challenge based on conflict with the FDA’s enabling legislation and existing expanded-access regulation under the Supreme Court’s long-standing preemption doctrine.”

The Medical Oncology Association of Southern California, Inc. writes in their opposition letter, “Concerns with AB 1668 include the difficulty of identifying an ‘immediately life-threatening condition,’ the lack of a sufficient informed consent process to protect patients seeking investigational drugs, and the lack of appropriate physician supervision of the use of these drugs…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 adults clinical trial enrollment, which hold the promise of the future of medicine. Despite very low adult clinical trial enrollments, this nation’s clinical trial system has resulted in the relatively rapid evolution of cancer care. Any threat to adult clinical trial enrollment would result in solving the development of cancer care in the future.”

REGISTERED SUPPORT:

Amyotrophic Lateral Sclerosis (ALS) Association Golden West Chapter

County of Los Angeles Board of Supervisors

EveryLife Foundation for Rare Diseases

REGISTERED OPPOSITION:

California Nurses Association/National Nurses United

Medical Oncology Association of Southern California, Inc.

Analysis Prepared by: Le Ondra Clark Harvey, Ph.D. / B. & P. / (916) 319-3301

Date of Hearing: March 15, 2016

ASSEMBLY COMMITTEE ON HEALTH

Jim Wood, Chair

ABPCA Bill Id:AB 1668 (

Author:Calderon) – As Amended Ver: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 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:
   1. 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;
   2. Has considered all other treatment options currently approved by the FDA;
   3. 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;
   4. Has received a recommendation from his or her primary physician and a consulting physician, as defined, for an investigational drug;
   5. 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 representative has given written informed consent on his or her behalf; and,
   6. 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:
   1. Explain the currently approved products and treatments for the disease or condition from which the patient suffers;
   2. 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;
   3. Identify the specific proposed investigational drug that the patient is seeking to use;
   4. Describe the potentially best and worst outcomes of using the investigational drug and describes the most likely outcome, as specified;
   5. 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;
   6. 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;
   7. State that in-home health care may be denied if treatment begins; and,
   8. State that the patient understands that he or she is liable for all expenses consequent to the use of the 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:
   1. Examine the qualified individual and his or her relevant medical records;
   2. Confirm, in writing, the primary physician’s diagnosis and prognosis; and,
   3. 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:
    1. The number of requests made for an investigational drug;
    2. The status of the requests made;
    3. The duration of the treatment,
    4. The costs of the treatment paid by eligible patients,
    5. The outcome of the treatment; and,
    6. 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:
   1. 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,
      
   2. 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 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:
   1. 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;
   2. Requires review and approval from an IRB before a clinical study can be initiated under an IND;
   3. 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,
   4. 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 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:
   1. It would allow access only to medications that have passed manufacturers’ Phase I clinical trials, or the first studies in humans;
   2. Access would be limited to use by terminally ill patients who have exhausted other available treatments;
   3. A medication would be made available only if the company manufacturing it chose to do so;
   4. 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,
   5. 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.
   
   1. 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.
      
   2. 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.
      
   3. 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.
      
   4. 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.
      
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 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.

1. 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.
   
2. 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.
   
3. 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."
4. 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."
5. 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.
6. POLICY COMMENTS.
   
   1. 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.
      
   2. 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.
      
   3. 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 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

Analysis Prepared by: Dharia McGrew / HEALTH / (916) 319-2097