BILL ANALYSIS Ó AB 159 Page 1 Date of Hearing: April 21, 2015 ASSEMBLY COMMITTEE ON BUSINESS AND PROFESSIONS Susan Bonilla, Chair AB 159 Calderon - As Amended April 13, 2015 NOTE: This bill is double referred, having been previously heard by the Assembly Committee on Health on April 14, 2015 and approved on a 17-0 vote. SUBJECT: Investigational drugs, biological products, and devices. SUMMARY: Permits a manufacturer of an investigational drug, biological product or 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 159 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 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). 2)Prohibits, in the Sherman Law, the sale, delivery or giving away of a new drug or device unless it is either: a) A new drug or new device for which DPH has approved a new drug or device application, and has not withdrawn, terminated or suspended that approval; or, AB 159 Page 3 b) A new drug, and a new drug application has been approved for it by the U.S. Food and Drug Administration (FDA), pursuant to federal law or it is a new device for which a premarket approval application has been approved, and that approval has not been withdrawn, terminated or suspended under the FDA. 3)Establishes the Protection of Human Subjects in Medical Experimentation Act which prescribes various protections for 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. 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. AB 159 Page 4 2)Prohibits any new drug from being introduced into interstate commerce unless an application has been approved by the FDA. 3)Under federal regulation: a) Requires clinical trial sponsors to submit an Investigational New Drug (IND) application to the FDA for clinical investigation of a new drug or new indication of an approved drug, with certain exceptions; b) Requires review and approval from an Institutional Review Board (IRB) before a clinical study can be initiated under an IND; c) Defines an IRB as an appropriately constituted group that has been designated to review and monitor biomedical research involving human subjects, to ensure that a clinical trial is ethical and that the rights of study participants are protected; and, d) Authorizes an IRB to approve, require modifications in, or disapprove research, or to suspend or terminate approval of research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects. AB 159 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). THIS BILL: 1)Allows the manufacturer of an experimental drug or device to provide an investigational drug or device to an eligible patient. 2)Specifies that the manufacturer may provide for free, or may charge the patient to pay for the costs of the drug or device. 3)Defines "eligible patient" as one who has met all the following criteria: a) Has a serious or immediately life-threatening disease or condition; b) Has considered all other treatment options currently approved by the FDA; c) Has been unable to participate in a clinical trial within 100 miles of their home, or has not been accepted; d) Has received recommendation from their physician for the AB 159 Page 6 drug or device; e) Has given written, informed consent; and, f) Has documentation form their physician attesting that the patient has met these requirements. 4)Defines "health benefit plan" as any plan or program that provides, arranges, pays for or reimburses the cost of health benefits and includes, but is 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. 5)Defines "immediately life threatening disease or condition" to mean a stage of disease in which there is a reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment. 6)Defines "serious disease or condition" to mean a disease or condition associated with morbidity that has a substantial impact on day-to-day functioning. 7)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 U.S. FDA, but has not been approved for general use by the FDA and remains under investigation in a clinical trial approved by AB 159 Page 7 the FDA. 8)Defines "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 MBC and the OMB. 10)Defines "written, informed consent" as a written document that has been approved by the physician's IRB or an accredited independent institutional review board, is signed by an eligible patient, or his or her legally authorized representative where the patient lacks the capacity to consent, and attested to by the patient's physician and a witness that, at a minimum, does all of the following: a) Explains the currently approved products and treatments for the serious or immediately life-threatening disease or condition from which the patient suffers; b) Attests to the fact that the patient, or where the patient lacks the capacity to consent, his or her legally authorized representative, concurs with the patient's physician in believing that all currently approved and conventionally recognized treatments are unlikely to prolong the patient's life; AB 159 Page 8 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; e) States that the patient's health benefit plan 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 them; f) 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; g) States that in-home health care may be denied if treatment begins; and, h) States that the patient understands and is liable for all expenses consequent to the use of the investigational drug, biological product or device. 11)Allows a health plan to provide coverage for the drug or AB 159 Page 9 device, or the costs of services related to the use of the drug or device. 12)Prohibits a state regulatory board form revoking, failing to renew, or taking any other disciplinary action against a physician's license based on the recommendation, prescription, or treatment of the drug or device, provided the recommendation or prescription is consistent with the medical standards of care. 13)Indicates that written, informed consent shall be consistent with the informed consent requirements of the Protection of Human Subjects in Medical Experimentation Act. 14)Specifics that health benefit plans are not required to provide coverage for the cost or use of any investigational drug, biological product or device or the costs of services. 15)States that if an eligible patient dies while being treated by an investigational drug, biological product of 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. 16)Prohibits a state agency from altering a recommendation made to the federal Centers for Medicare and Medicaid Services AB 159 Page 10 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 the drug or device. 17)Prohibits an official, employee, or agent of the state from blocking or attempting to block an eligible patient's access to an investigational drug or device pursuant to this article. Specifies that counseling, advice, or a recommendation consistent with medical standards of care from a licensed healthcare provider is not a violation of this section. 18)Specifies that this article does not create a private cause of action against a manufacturer of an investigational drug or device, or against any other person or entity involved in the care of an eligible patient using the drug or device, for any harm done to the patient resulting from the drug or device, so long as the manufacturer or other person or entity is complying in good faith with the terms of this article, unless there was a failure to exercise reasonable care. FISCAL EFFECT: Unknown. This bill is keyed fiscal by the Legislative Counsel. COMMENTS: 1)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. AB 159 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 AB 159 Page 11 protecting physicians, hospitals, and manufacturers from retribution." 2)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 AB 159 Page 12 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. AB 159 Page 13 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. The FDA draft guidance on the new application process is currently in the 60-day public comment period. 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 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) AB 159 Page 14 sought to address this issue by providing immunity to the manufacturer, distributor, administrator, sponsor or physician from suit or liability. If AB 159 is enacted, the MBC and 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. Similar legislation has been signed into law in the following states: 1) Colorado, 2) Louisiana, 3) Michigan and 4) Missouri. Arizona adopted a resolution to place the issue on the November 2014 ballot, where it was approved by voters. Presently, at least 20 other states are considering similar legislation. 3)Prior Related Legislation. SB 128 (Wolk) of the current legislative session, permits a competent, qualified individual who is a terminally ill adult to receive a prescription for aid in dying medication if certain conditions are met. STATUS: This bill is currently pending in the Senate Appropriations Committee. SB 149 (Stone) of the current legislative session, is largely similar to this bill, with differences primarily in definitions and liability exemptions. STATUS: SB 149 is pending in the Senate Business, Professions and Economic Development Committee. AB 159 Page 15 SB 715 (Anderson) of the current legislative session, is largely the same as this bill with some differences in definitions. STATUS: SB 715 is pending in the Senate Health Committee. ARGUMENTS IN SUPPORT: The Los Angeles County Board of Supervisors writes in its letter of support, "Five states, Colorado, Louisiana, Missouri, Michigan and Arizona, have recently enacted bi-partisan legislation or voter-approved ballot initiatives to establish "Right to Try" laws. 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." ARGUMENTS IN OPPOSITION: The California Medical Association opposes the bill and writes, "While we appreciate the good intentions behind the bill, we have significant patient safety concerns with allowing access to unproven drugs outside of the FDA's clinical trials and compassionate use programs. The FDA ensures efficacy and safety of using such drugs, and once they are removed from these processes there is no longer an ability to protect patients and provide proper oversight?In addition, since state law can't supersede federal law, companies may not want to provide their treatments outside of FDA processes. The key to current processes is that they be uniformly regulated and monitored to ensure both proper participation and consumer protection." AB 159 Page 16 The California Nurses Association/National Nurses United opposes the bill and writes in their letter, "While apparently well meaning, this legislation promises vulnerable patients and their families that there will be a state program for obtaining drugs that is similar to the FDA expanded access program only shorter. This short cut is purportedly a means of increasing access to drugs and devices for terminally ill patients. This 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 physician's recommendation to an eligible patient for prescription or treatment with the investigations drug or device. This bill also purports to provide protection by prohibiting a state agency from altering any recommendation made to the federal Medicare and Medicaid program for these activities." The Association of Northern California Oncologists (ANCO) also opposes the bill and states, "The ANCO Board cited several reasons to oppose AB 159, including the difficulty of identifying "terminally-ill" patient, the danger a "right to try" outside the context of a clinical trial would present to adult clinical trial enrollment, the lack of an informed consent process to protect patients seeking investigational drugs, and the lack of appropriate physician supervision of the use of these drugs. 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 slowing the development of cancer care in the future." AMENDMENTS: AB 159 Page 17 1)As was noted in the Assembly Committee on Health's analysis, the bill does not require any agency or company to track whether patients are able to acquire the experimental drugs or devices they are seeking. As such, the author should require the IRB to send a report of the status or results of requests made, the duration of treatments and costs paid by patients for the experimental drugs or devices to the DPH, the MBC and the OMB. On page 6, after line 36 add the following: (b) The physician's institutional review board or an accredited institutional review board is required to send a bi-annual report to the Department of Public Health, the Medical Board of California and the Osteopathic Medical Board with the following information: (i) The number of requests made (ii) The status of the requests made (iii) The duration of treatment (iv) The costs of the treatment paid by patients AB 159 Page 18 2)The bill specifies that a physician may prescribe a drug, "provided that the recommendation or prescription is consistent with the medical standards of care." However, when a physician prescribes a medication for off-label use, they are inherently deviating from the standards of care. Thus, the language of the bill should specify that the standards of care that the physician is adhering to are those that are approved by the institutional review board. To this end, the author should amend the bill as follows: On page 6, line 36, strike the following,medical standards of careand insert the following, protocol as approved by the institutional review board . 3)As has been done in other states that have proposed similar legislation, the author should address the premature ending of a clinical trial. On page 6, line 25, add the following: If the clinical trial is closed due to the lack of efficacy or toxicity, the drug must not be offered. If notice is given on a drug, product or device taken by a patient outside of a clinical trial, the pharmaceutical company and the patient's physician must notify the patient of the information from the AB 159 Page 19 safety committee of the clinical trial. 4)In order to confirm the patient's diagnosis of a terminal illness, the author should amend the bill to require the primary physician to retain verification from a consulting physician of the patient's diagnosis and prognosis. On page 3, line 22, add the following after "her": primary physician and a consulting physician On page 3, line 29, add the following after "her": primary physician and a consulting physician On page 4, line 17, add: AB 159 Page 20 "Primary"Pp hysician" On page 4, after line 19 add the following: "Consulting physician" means a physician and surgeon licensed under the Medical Practice Act or an osteopathic physician and surgeon licensed under the Osteopathic Act who shall perform all of the following (a) Examine the qualified individual and his or her relevant medical records. (b) Confirm in writing the attending physician's diagnosis and prognosis. (c) Verify, in the opinion of the consulting physician, that the eligible patient is competent, acting voluntarily, and has made an informed decision. AB 159 Page 21 REGISTERED SUPPORT: Los Angeles County Board of Supervisors REGISTERED OPPOSITION: California Medical Association California Nurse Association/National Nurses United Association of Northern California Oncologists Analysis Prepared by:Le Ondra Clark Harvey, Ph.D. / B. & P. / (916) 319-3301 AB 159 Page 22