BILL ANALYSIS Ó SENATE COMMITTEE ON BUSINESS, PROFESSIONS AND ECONOMIC DEVELOPMENT Senator Jerry Hill, Chair 2015 - 2016 Regular Bill No: AB 1668 Hearing Date: June 27, 2016 ----------------------------------------------------------------- |Author: |Calderon | |----------+------------------------------------------------------| |Version: |March 7, 2016 | ----------------------------------------------------------------- ---------------------------------------------------------------- |Urgency: |No |Fiscal: |Yes | ---------------------------------------------------------------- ----------------------------------------------------------------- |Consultant|Sarah Mason | |: | | ----------------------------------------------------------------- Subject: Investigational drugs, biological products, and devices 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 AB 1668 (Calderon) Page 2 of ? 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: a) A new drug or new device for which DPH has approved a AB 1668 (Calderon) Page 3 of ? new drug or device application, and has not withdrawn, terminated, or suspended that approval; or, b) A new drug, and a new drug application has been approved for it by the FDA, pursuant to federal law, or it is a new device for which a premarket approval application has been approved, and that approval has not been withdrawn, terminated, or suspended under the FDA. (HSC § 111550) 1)Prohibits a person from manufacturing any drug or device in California unless he or she has a valid license from the DPH. (HSC § 111615) 2)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) 3)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.) 4)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 AB 1668 (Calderon) Page 4 of ? jail, a fine of not more than $10,000 per occurrence, or both the imprisonment and fine. (HSC §111825) 5)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) 6)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) 7)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.) 8)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: a) "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. AB 1668 (Calderon) Page 5 of ? b) "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. c) "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. d) "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. e) "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. f) "Primary physician" as a physician and surgeon licensed under the MPA or an osteopathic physician and surgeon licensed under the Osteopathic Act. g) "State regulatory board" as the MBC or the Osteopathic Medical Board of California (OMBC). AB 1668 (Calderon) Page 6 of ? h) "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: i) Explains that the currently approved products and treatments for the immediately life-threatening disease or condition from which the patient suffers. ii) 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. iii) Clearly identifies the specific proposed IDBPD that the patient is seeking to use. iv) 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. v) 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. vi) Clearly states that the patient's eligibility for hospice care may be withdrawn if the patient begins curative treatment and that care may be reinstated if the curative treatment ends and the patient meets hospice eligibility requirements. AB 1668 (Calderon) Page 7 of ? vii) Clearly states that in-home health care may be denied if treatment begins. viii) 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. 1) Clarifies that written consent must be consistent with the informed consent requirements of the PHSME Act. 2) 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. 3) 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. 4) Prohibits the Act from expanding or otherwise affecting coverage provided by health plans or insurers, the Medi-Cal program, or county organized health systems. 5) 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. 6) 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. 7) Clarifies that the heirs of an eligible patient, if he or she dies while being treated by an IDBPD made available pursuant AB 1668 (Calderon) Page 8 of ? to the Act, are not liable for any outstanding debt related to the treatment or lack of insurance for the treatment. 8) 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. 9) 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. 10)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. 11)Provides that a violation of the Act shall not be subject to penalties for other violations of provisions of the Sherman Act. 12)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, AB 1668 (Calderon) Page 9 of ? 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 AB 1668 (Calderon) Page 10 of ? 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 AB 1668 (Calderon) Page 11 of ? 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 AB 1668 (Calderon) Page 12 of ? 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. 3. 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. 4. 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 1668 (Calderon) Page 13 of ? 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.") 5. 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. 6.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 AB 1668 (Calderon) Page 14 of ? 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 -- END --