BILL ANALYSIS Ó AB 1668 Page 1 Date of Hearing: March 29, 2016 ASSEMBLY COMMITTEE ON BUSINESS AND PROFESSIONS Rudy Salas, Chair AB 1668 (Calderon) - As Amended 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. AB 1668 Page 2 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(HSC § 111550) a) A new drug or new device for which DPH has approved a new drug or device application, and has not withdrawn, terminated or suspended that approval; or, b) A new drug, and a new drug application has been approved for it by the U.S. Food and Drug Administration (FDA), AB 1668 Page 3 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) § AB 1668 Page 4 321 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.) a) Requires clinical trial sponsors to submit an Investigational New Drug (IND) application to the FDA for clinical investigation of a new drug or new indication of an approved drug, with certain exceptions; b) Requires review and approval from an Institutional Review Board (IRB) before a clinical study can be initiated under an IND; c) Defines an IRB as an appropriately constituted group that has been designated to review and monitor biomedical research involving human subjects, to ensure that a clinical trial is ethical and that the rights of study participants are protected; and, d) Authorizes an IRB to approve, require modifications in, or disapprove research, or to suspend or terminate approval of research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects. AB 1668 Page 5 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: a) Provide an investigational drug, biological product, or device to an eligible patient without receiving compensation. b) Require an eligible patient to pay the costs of, or associated with, the manufacture of the investigational drug, biological product, or device. 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: AB 1668 Page 6 a) Examines the qualified individual and his or her relevant medical records. b) Confirms, in writing, the primary physician's diagnosis and prognosis. c) 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: a) Has an immediately life-threatening disease or condition. b) Has considered all other treatment options currently approved by the United States Food and Drug Administration. c) Has not been accepted to participate in the nearest clinical trial to his or her home for the immediately life-threatening disease or condition 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 AB 1668 Page 7 participate in that clinical trial due to the patient's current condition and stage of disease. d) Has received a recommendation from his or her primary physician and a consulting physician for an investigational drug, biological product, or device. e) Has given written informed consent for the use of the investigational drug, biological product, or device, or, if he or she lacks the capacity to consent, his or her legally authorized representative has given written informed consent on his or her behalf. f) 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. AB 1668 Page 8 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: a) Explains the currently approved products and treatments for the immediately life-threatening disease or condition from which the patient suffers. AB 1668 Page 9 b) 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. c) Clearly identifies the specific proposed investigational drug, biological product, or device that the patient is seeking to use. d) 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. e) 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. f) 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 AB 1668 Page 10 eligibility requirements. g) Clearly states that in-home health care may be denied if treatment begins. h) 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, AB 1668 Page 11 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: a) The number of requests made for an investigational drug, biological product, or device. AB 1668 Page 12 b) The status of the requests made. c) The duration of the treatment. d) The costs of the treatment paid by eligible patients. e) The success or failure of the investigational drug, biological product, or device in treating the immediately life-threatening disease or condition from which the patient suffers. f) 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. AB 1668 Page 13 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 AB 1668 Page 14 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 AB 1668 Page 15 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 AB 1668 Page 16 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 AB 1668 Page 17 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, AB 1668 Page 18 "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." AB 1668 Page 19 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 AB 1668 Page 20