BILL ANALYSIS Ó SENATE COMMITTEE ON HEALTH Senator Ed Hernandez, O.D., Chair BILL NO: SB 149 --------------------------------------------------------------- |AUTHOR: |Stone | |---------------+-----------------------------------------------| |VERSION: |April 14, 2015 | --------------------------------------------------------------- --------------------------------------------------------------- |HEARING DATE: |April 22, 2015 | | | --------------------------------------------------------------- --------------------------------------------------------------- |CONSULTANT: |Melanie Moreno | --------------------------------------------------------------- SUBJECT : Investigational drugs, biological products, or devices: right to try SUMMARY : Enacts the Right to Try Act, and 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. 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, 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it is either: a. A new drug or new device for which DPH has approved a new drug or device application, and has not withdrawn, terminated, or suspended that approval; or, b. A new drug, and a new drug application has been approved for it by the U.S. Food and Drug Administration (FDA),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law, or it is a new device for which a premarket approval application has been approved, and that approval has not been withdrawn, terminated, or suspended under the FDA. 3.Establishes the Protection of Human Subjects in Medical Experimentation Act which prescribes various protections for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, SB 149 (Stone) Page 2 of ? 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. SB 149 (Stone) Page 3 of ? 4. Establishes the Office for Human Research Protections (OHRP), which provides leadership in the protection of the rights, welfare, and well-being of subjects involved in research conducted or supported by the U.S. Department of Health and Human Services (HHS). OHRP helps ensure this by providing clarification and guidance, developing educational programs and materials, maintaining regulatory oversight, and providing advice on ethical and regulatory issues in biomedical and social-behavioral research. This bill: 1.Enacts the Right to Try Act, and 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 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 and remains under investigation in an approved clinical trial. 3.Defines "eligible patient" as a person who: a. Has a terminal illness as determined by that person's physician and a consulting physician; b. Has no comparable or satisfactory FDA-approved treatment options, as determined by his or her physician, available to diagnose, monitor, or treat the disease or condition involved, and that the probable risk to the person from the investigational drug, biological product, or device is not greater than the probable risk from the disease or condition; c. Has received a prescription or recommendation from his or her physician for an investigational drug, biological product, or device; d. Has given written informed consent for the use of the investigational drug, biological product, or device, or if he or she is a minor or lacks the capacity to provide informed consent, his or her parent, legal guardian, or legally authorized representative has given written informed consent on SB 149 (Stone) Page 4 of ? his or her behalf; and, e. Has documentation from his or her physician that the patient has met the requirements of this bill. 4.Defines "terminal illness" as a disease that, without life-sustaining procedures, will result in death in the near future or a state of permanent unconsciousness from which recovery is unlikely. 5.Permits manufacturers to: 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; and, c. Require an eligible patient to participate in data collection relating to the use of the investigational drug, biological product, or device. 6.Specifies that this bill does not require a health plan or any state agency to provide coverage for the cost of any investigational drug, biological product, or device, but permits health plans to provide such coverage. 7.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 pursuant to this bill. 8.Prohibits a state agency from taking any action against a health facility's license based solely on the facility's participation in the treatment by or use of an investigational drug, biological product, or device pursuant to this bill. 9.Makes a violation of this bill not subject to the Sherman Food, Drug, and Cosmetic Law. 10.Specifies that this bill does not create a private cause of action against a manufacturer of an investigational drug, SB 149 (Stone) Page 5 of ? biological product, or device, or against any other person or entity involved in the care of an eligible patient using the investigational drug, biological product, or device, for any harm to the eligible patient resulting from the investigational drug, biological product, or device so long as the manufacturer or other person or entity complies in good faith with the terms of this bill and exercises reasonable care. FISCAL EFFECT : This bill has not been analyzed by a fiscal committee. COMMENTS : 1.Author's statement. According to the author, for terminal patients who have exhausted their conventional treatment options, obtaining access to potentially life-saving investigational drugs is often extremely difficult. The patient can attempt to enroll in a clinical trial, but many of the sickest individuals do not qualify to join such a trial. For these patients, their only hope for obtaining these potentially life-saving drugs is to request that the FDA grant them expanded access. SB 149, otherwise known as "Right-to-Try", would allow a terminally ill patient a last-ditch effort to save their life. This bill would allow a patient to try an investigational drug only when certain conditions have been met, while providing important legal protections for all parties involved. 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 SB 149 (Stone) Page 6 of ? 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 2 of the 2,472 individual, non-emergency protocols, on 1 of 66 intermediate-size SB 149 (Stone) Page 7 of ? requests, and on none of the 41 widespread expanded-access protocols it received. The Health Affairs brief states that critics of the expanded access program have argued that the application process is unnecessarily burdensome and lengthy (it is estimated that the IND application requires about 100 hours to complete), which discourages doctors and manufacturers from applying. An IRB review adds an additional layer of paperwork and potential delay. These requirements were put in place in response to highly publicized incidents of harm caused by unsafe drugs. In the past decade, there have been several attempts made at the federal and judicial levels to further relax restrictions on the administration of experimental therapies to terminally ill patients. One, led by the Abigail Alliance for Better Access to Developmental Drugs, submitted a Citizen Petition to the FDA in 2003 requesting that it make experimental therapies available to terminally ill patients, provided that the drug had passed Phase I testing. Following several years of litigation, the DC Court of Appeals ruled against the Abigail Alliance, stating that terminally ill patients have no constitutional right to access experimental therapies. The US Supreme Court subsequently declined to review the case. Several bills have been introduced in the US Congress that aim to relax FDA restrictions on access to experimental therapies. The most recent of these (HR 4475, the Compassionate Freedom of Choice Act of 2014) failed to make it out of committee. 5.Other states. Over the past year, the issue of access to experimental therapies has been debated at the state level, in part due to efforts of the Goldwater Institute, a libertarian think tank that appears to be the source of this bill. In February 2014, the institute released a policy paper that outlines the major critiques of the FDA's expanded access program and proposes model legislation for states to adopt. According to the National Conference of State Legislatures (NCSL), legislation related to right-to-try have been introduced in 30 states. Arizona, Colorado, Louisiana, Michigan, and Missouri have laws on the subject. 6.FDA action. According to an article in the Wall Street Journal published on February 9, 2015, the FDA announced it would "simplify and accelerate" the application process for "unapproved investigational drugs" that have passed Phase I safety trials. It is estimated that the new application form SB 149 (Stone) Page 8 of ? will take 45 minutes to complete, asks attending physicians to fill in eight pieces of patient information, and requires only one attachment. The FDA issued draft guidance and included a copy of the new form, asking for comment until April 13, 2015. 7.NEJM article. The authors of the January 2015 NEJM article mentioned above call right-to-try laws misguided, and call for a more pragmatic approach. They suggest that states work collaboratively with the FDA to make expanded access more practical when it is appropriate. For example, since the FDA has acknowledged that gaining approval from an IRB can pose a barrier, states could partner with the FDA to fund multicenter IRBs that focus specifically on expanded-access requests. Such multicenter panels would conduct full reviews, but their subject-matter expertise and limited dockets would translate into faster review times. Practical obstacles to enhancing expanded access programs, including administrative burdens and industry costs, would also be best tackled by the states in partnership with the FDA. For example, a manufacturer's reluctance to provide product because of financial concerns could be addressed by permitting companies to charge amounts closer to the likely post approval cost of drugs. 8.Double referral. This bill is double referred. Should it pass out of this committee, it will be referred to the Senate Committee on Business and Professions and Economic Development. 9.Related legislation. SB 715 (Anderson), 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. SB 715 is pending in the Senate Health Committee SB 128 (Wolk and Monning), 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, such as two oral requests, a minimum of 15 days apart, and a written request signed by two witnesses, is provided to his or her attending physician, the attending physician refers the patient to a consulting physician to confirm diagnosis and competency of the patient, and the attending physician refers the patient for counseling, if SB 149 (Stone) Page 9 of ? appropriate. SB 128 passed by a vote of 6-2 when it was heard in the Senate Health Committee and by a vote of 5-2 when it was heard in the Senate Judiciary Committee AB 159 (Calderon), is substantially similar to this bill. AB 159 passed by a vote of 17-0 when it was heard in the Assembly Health Committee. 10.Support if amended. The Los Angeles County Board of Supervisors writes that that this bill does not provide patients with comprehensive written, informed consent, which their County Counsel's office deems necessary to help ensure that patients are fully aware of the potential risks involved with receiving experimental treatment and will support this bill if it is amended to provide such consent. 11.Opposition. The California Medical Association states that they have significant patient safety concerns with allowing access to unproven drugs outside of the FDA's clinical trials and compassionate use programs. They further argue that offering unapproved therapies without credible scientific rationale or controlled monitoring could lead to not only endangering terminally ill patients further but potentially exploiting their hopes and circumstances. The Association of Northern California Oncologists 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 entitled Practical, Legal, and Ethical Issues in Expanded Access to Investigational Drugs, 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. 12.Policy comment. This bill does not contain any mechanism to SB 149 (Stone) Page 10 of ? report data on the number of requests made for experimental drugs under this bill, whether those requests were approved or denied, the use of such drugs, the duration of treatments, the success or failure of the drugs, any adverse side effects, or costs paid by patients for the drugs. While the bill does permit a drug company to require a patient to participate in data collection, this is not mandatory, and even if it were, there is no requirement for a drug company to share this data with policy makers. Should the state move forward with allowing the use of experimental drugs outside of the clinical trial process, the Committee may wish to consider whether there should be some regulatory oversight, or at a minimum, some data collection and reporting, and perhaps a sunset date. SUPPORT AND OPPOSITION Support: None received. Oppose: Association of Northern California Oncologists California Medical Association California Nurses Association -- END --