BILL ANALYSIS Ó AB 1668 Page 1 Date of Hearing: March 15, 2016 ASSEMBLY COMMITTEE ON HEALTH Jim Wood, Chair AB 1668 (Calderon) - As Amended March 7, 2016 SUBJECT: Investigational drugs, biological products, and devices. SUMMARY: Authorizes the manufacturer of an investigational drug, biological product, or device (investigational drug) that is not yet approved by the U.S. Food and Drug Administration (FDA) to make the investigational drug available to a patient, under certain circumstances. Specifically, this bill: 1)Permits, and specifies that it does not require, a manufacturer to make available an investigational drug that has not yet been approved for market to an eligible patient, as defined. 2)Defines "investigational drug, biological product, or device" as a drug, biological product, or device that has successfully completed phase one of a clinical trial approved by the FDA, but has not been approved for general use by the FDA and remains under investigation in a clinical trial approved by the FDA. 3)Permits a manufacturer to either provide the investigational drug to the patient free of charge or to require the patient to pay the costs of or associated with the manufacture of the AB 1668 Page 2 investigational drug. 4)Prohibits this bill from expanding or otherwise affecting coverage provided by health plans or insurers, the Medi-Cal program, or county organized health systems, as defined. 5)Specifies that this bill does not require a health plan or insurer to provide coverage for the cost of any investigational drug, or the costs of services related to the use of an investigational drug under this bill, but permits one to provide such coverage. 6)Prohibits a manufacturer from continuing the make an investigational drug available to the patient if ongoing clinical trials of the investigational drug are closed due to lack of efficacy or for toxicity. Requires both the manufacturer and patient's primary physician to notify the patient if ongoing clinical trials for the investigational drug are closed. 7)Defines "eligible patient" as a person who: a) Has a serious or immediately life-threatening disease or condition. Defines "immediately life-threatening disease or condition" as a stage of disease in which there is a reasonable likelihood that death will occur within a matter of months; b) Has considered all other treatment options currently approved by the FDA; c) Has been unable to participate in the nearest clinical trial from their home for the serious or immediately life-threatening disease or condition, or has not been accepted to that clinical trial within one week of completion of the clinical trial application process; d) Has received a recommendation from his or her primary physician and a consulting physician, as defined, for an investigational drug; e) Has given written informed consent, as defined, for the use of the investigational drug, or, if he or she lacks the capacity to consent, his or her legally authorized AB 1668 Page 3 representative has given written informed consent on his or her behalf; and, f) Has documentation from their primary physician and a consulting physician attesting that the patient has met the requirements above. 8)Defines "written informed consent" as a written document that has been approved by the primary physician's Institutional Review Board (IRB) or an accredited independent IRB, is signed by an eligible patient, or his or her legally authorized representative when the patient lacks the capacity to consent, and attested to by the patient's primary physician and a witness. Requires the document to do the following: a) Explain the currently approved products and treatments for the disease or condition from which the patient suffers; b) Attest to the fact that the patient, or his or her legally authorized representative, concurs with the primary physician in believing that all currently approved and conventionally recognized treatments are unlikely to prolong the patient's life; c) Identify the specific proposed investigational drug that the patient is seeking to use; d) Describe the potentially best and worst outcomes of using the investigational drug and describes the most likely outcome, as specified; e) State that the patient's health plan or insurer, if any, and health care provider are not obligated to pay for the investigational drug, or any care or treatments consequent to use of the investigational drug; f) State that the patient's eligibility for hospice care may be withdrawn if the patient begins curative treatment and that care may be reinstated if the curative treatment ends and the patient meets hospice eligibility requirements; g) State that in-home health care may be denied if treatment begins; and, h) State that the patient understands that he or she is liable for all expenses consequent to the use of the AB 1668 Page 4 investigational drug, and that this liability extends to the patient's estate, except as otherwise provided in the patient's health benefit plan or a contract between the patient and the manufacturer of the drug. 9)Defines "primary physician" and "consulting physician" and requires the consulting physician to: a) Examine the qualified individual and his or her relevant medical records; b) Confirm, in writing, the primary physician's diagnosis and prognosis; and, c) Verify, in the opinion of the consulting physician, that the eligible patient is competent, acting voluntarily, and has made an informed decision. 10)Prohibits the heirs of an eligible patient, if he/she dies while being treated by an investigational drug made available pursuant to this bill, from being liable for any outstanding debt related to the treatment or lack of insurance for the treatment. 11)Prohibits a state regulatory board, as defined, from revoking, failing to renew, or taking any other disciplinary action against a physician's license based on the physician's recommendation to an eligible patient regarding, or prescription for or treatment with, an investigational drug if the recommendation or prescription is consistent with protocol approved by the physician's IRB or an accredited independent IRB. 12)Requires the physician's IRB or an accredited independent IRB to biannually report to the Department of Public Health (DPH), the Medical Board of California, and the Osteopathic Medical Board of California: a) The number of requests made for an investigational drug; b) The status of the requests made; AB 1668 Page 5 c) The duration of the treatment, d) The costs of the treatment paid by eligible patients, e) The outcome of the treatment; and, f) Any adverse events from the treatment with the investigational drug. 13)Prohibits a state agency from altering any recommendation made to the federal Centers for Medicare and Medicaid Services regarding a health care provider's certification to participate in the Medicare or Medicaid program based solely on the recommendation from an individual health care provider that a patient have access to an investigational drug. 14)Makes a violation of this bill not subject to the Sherman Food, Drug, and Cosmetic Law (Sherman Act). 15)Specifies that this bill does not create a private cause of action, and that actions taken pursuant to this bill do not serve as a basis for a civil, criminal, or disciplinary claim or cause of action, as specified. EXISTING STATE LAW: 1)Establishes the Sherman Act, which regulates the packaging, labeling, and advertising of drugs and devices, administered by DPH. Specifies penalties for violation of the Sherman Act. 2)Prohibits, under the Sherman Act, the sale, delivery, or giving away of a new drug or device unless it is either: AB 1668 Page 6 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 FDA, pursuant to federal law, or it is a new device for which a premarket approval application has been approved, and that approval has not been withdrawn, terminated, or suspended under the FDA. 3)Establishes the Protection of Human Subjects in Medical Experimentation Act which prescribes various protections for subjects of medical experimentation relating to a bill of rights; informed consent procedures and documentation; and, the provision of specified disclosures, including the right for a subject to give or withdraw consent freely and without duress. Imposes penalties for violations of these protections. 4)Requires health plans and insurers to provide an external, independent review process to examine a plan's coverage denials of experimental or investigational therapies for individual enrollees who have a life-threatening or seriously debilitating condition and who meet other specified criteria. 5)Requires health plans and insurers to provide coverage for all routine patient care costs relative to the treatment of an enrollee or insured diagnosed with cancer and accepted in an FDA-approved cancer clinical trial, Phases I-IV, if the enrollee's treating physician, recommends participation in the AB 1668 Page 7 clinical trial after determining such participation has a meaningful potential to benefit the enrollee or insured. EXISTING FEDERAL LAW: 1)Establishes the federal Food, Drug, and Cosmetic Act, which grants authority to the FDA to oversee the safety of food, drugs, and cosmetics. 2)Prohibits any new drug from being introduced into interstate commerce unless an application has been approved by the FDA. 3)Specifies under federal regulations the following: 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 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 AB 1668 Page 8 clinical trial is ethical and that the rights of study participants are protected; and, d) Authorizes an IRB to approve, require modifications in, or disapprove research, or to suspend or terminate approval of research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects. 4)Establishes the Office for Human Research Protections (OHRP), which provides leadership in the protection of the rights, welfare, and wellbeing of subjects involved in research conducted or supported by the U.S. Department of Health and Human Services (HHS). OHRP helps ensure this by providing clarification and guidance, developing educational programs and materials, maintaining regulatory oversight, and providing advice on ethical and regulatory issues in biomedical and social-behavioral research. FISCAL EFFECT: This bill has not yet been analyzed by a fiscal committee. COMMENTS: 1)PURPOSE OF THIS BILL. According to the author, this bill removes barriers to accessing potentially life-saving drugs for terminally-ill patients and doctors who believe an investigational drug could be their last hope for survival. The author further states that those patients that have exhausted all other treatment options, and are not eligible for clinical trials, often seek access to INDs, but face a variety of hurdles. These patients may seek compassionate use AB 1668 Page 9 exemptions from the FDA, but the process is cumbersome and approval comes too late for many. The author explains, this bill removes barriers for patients who need to immediately obtain investigational treatments, while also protecting physicians, hospitals, and manufacturers from retribution. 2)BACKGROUND. Patient requests for access to drugs and biologics prior to their approval have long created a dilemma for regulators, who must balance the needs of patients and their families who believe that an experimental product could save their life, with ensuring the safety of the greater population through tightly controlled clinical trials and drug approval. This issue has become increasingly visible and difficult in recent times, as views about the inherent right of patients in certain situations to unapproved products have been expressed by patients and their advocates, state legislators, members of Congress, and some court cases. In 2014 four states adopted legislation similar to this bill (Colorado, Louisiana, Michigan, and Missouri) and one state (Arizona) adopted a resolution to place the issue on the November 2014 ballot, where it was approved by voters. According to the National Conference on State Legislatures (NCSL), at least 41 other states considered similar right-to-try legislation in 2015. 3)MODEL LEGISLATION. According to the NCSL, the "Right to Try" proposed model legislation was designed and promoted by the Goldwater Institute, a free-market advocacy group in Arizona. Their "model legislation," now adopted in many states, typically addressed several concerns about patients' use of experimental drugs: a) It would allow access only to medications that have passed manufacturers' Phase I clinical trials, or the first AB 1668 Page 10 studies in humans; b) Access would be limited to use by terminally ill patients who have exhausted other available treatments; c) A medication would be made available only if the company manufacturing it chose to do so; d) A patient's request for access to an experimental drug would require a doctor to diagnose a terminal disease and declare that the drug represents the patient's best chance at survival; and, e) Patients would provide signed informed consent, thus limiting the legal exposure of the manufacturer of the drug. 4)FDA HAS JURISDICTION OVER DRUG APPROVAL. FDA has jurisdiction over all drugs that are sold across state lines. State law gives DPH the authority to approve a drug or device if it will be sold only in California. If a product has received FDA approval, then DPH automatically recognizes the product's approval. In rare instances when a drug or device will be sold only in the state of California, and will not be distributed through interstate commerce, then California would be the approving body. According to DPH, this has resulted in only a few instances where California has approved a new drug or device application. 5)THE CLINICAL TRIAL PROCESS. A clinical trial is a study that is carefully designed to test the benefits and risks of a specific medical treatment or intervention, such as a new drug. The FDA requires a multi-phase clinical trials process to be completed before deciding if an investigational medicine is safe and effective for a broader patient population. AB 1668 Page 11 a) Phase I is a clinical trial using a small group of healthy individuals (generally 20 to 80 volunteers). This stage is designed to assess the toxicity and dosing of a drug and whether or not there are harmful side effects associated with the drug. Phase I trial does not establish either the safety or efficacy of a drug. According to the FDA, the goal in this phase is to determine the drug's most frequent side effects, how the drug is metabolized and excreted, and whether there is an unacceptable level of toxicity associated with taking the drug. b) Phase II clinical trials involve control groups and experimental groups (up to 300 individuals total) to determine whether the drug is effective for the intended purpose on a particular disease or condition. This phase aims to obtain preliminary data on whether the drug works in people who have a certain disease or condition. c) Phase III begins if the drug proves to be effective in Phase II. These studies gather further information on the drug's safety and effectiveness on different populations (several hundred to about 3,000 participants) and tests varying levels of doses in combination or in comparison with different drugs. d) Phase IV studies are post-marketing studies the sponsor has agreed to do after the FDA approves a drug. These studies gather additional information on a product's safety, efficacy, and optimal use. AB 1668 Page 12 6)Expanded Access or "COMPASSIONATE USE" through the FDA. If a patient is unable to enroll in a clinical trial, the FDA's expanded access exemption, also called "compassionate use," provides a pathway for patients to gain access to investigational drugs or devices for serious diseases or conditions. A licensed physician applies, on behalf of a patient, for expanded access under a single patient IND Application. The supervising physician must be willing to commit to oversee the treatment, work with the manufacturer and the FDA, obtain the drugs, monitor the patient during the course of treatment, and file necessary paperwork. Critics of the FDA process have raised concerns that the Expanded Use application is too cumbersome for physicians and patients to complete. Critics claim that it currently requires an application that takes doctors 100 hours to fill out. The response time from the FDA ranges from a few days to a few months. The FDA also allows physicians to request expanded access for patients in an emergency situation over the phone or by "other rapid means of communication." The FDA states that authorization of the emergency use may be given by an FDA official over the telephone, provided the physician explains how the expanded access use will meet federal requirements for expanded access use and agrees to submit an expanded access submission within 15 working days of FDA's initial authorization of the expanded access use. The FDA states that they receive approximately 1,000 expanded use applications per year, and has approved more than 99% of those applications. In the last four years, the FDA has denied only 33 of nearly 6,000 expanded access requests. In February 2015, the FDA proposed a new form for individual patient expanded access requests that it estimated to take physicians only about 45 minutes to complete. The FDA has stated that finalizing the form is an Agency priority. However, finalizing a form requires FDA to complete a number of steps, many of which are required by law and/or regulation. After collecting public comment on the draft made public in AB 1668 Page 13 February 2015 for a period of 60 days, the FDA then carefully reviews these comments and considers revisions which would appear in the final form. The FDA then seeks approval for the information collections from the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995. OMB's review includes an additional 30-day public comment period which began on March 10, 2016. OMB has 30 days to review the comments submitted during this period. The FDA expects to issue the finalized form shortly after receiving OMB approval. 7)COURT HISTORY. In 2005, the Abigail Alliance for Better Access to Developmental Drugs, with the mission of facilitating access to experimental drugs for patients, sued the FDA, claiming a constitutional due process right for terminally ill patients to access unapproved drugs. In Abigail Alliance v. Von Eschenbach, a US District court disagreed and the case was heard by the US Court of Appeals for the District of Columbia Circuit. In 2006, a divided three-judge panel of the D.C. Circuit agreed with the Alliance, finding that where there are no other FDA-approved treatment options, a terminally ill patient has a constitutionally-protected "fundamental right" to access investigational drugs. In 2007, the D.C. Circuit reheard the case "en banc" and reversed the panel decision. The Alliance then filed a petition asking the U.S. Supreme Court to hear the case but the Supreme Court denied the petition, so for now the Court of Appeals decision stands. 8)SUPPORT. Supporters argue that patients with no other treatment options should be able to take on more risk than healthy patients would otherwise choose. The Los Angeles County Board of Supervisors supports this bill, stating that terminally ill patients, who have exhausted their options to find a cure and who have identified a physician and pharmaceutical company willing to assist them, deserve the right to experimental treatments that could prolong their lives. AB 1668 Page 14 9)OPPOSITION. The Medical Oncology Association of Southern California (MOASC) opposes, stating that "while we appreciate the interest in supporting patients, there are substantive dangers in a "right to try" outside the context of a clinical trial, including the damage to adult clinical trial enrollment, which hold the promise of the future of medicine." MOASC additionally raises concerns about the difficulty identifying an "immediately life-threatening condition", the lack of sufficient informed consent process to protect patients seeking these drugs, and the lack of appropriate physician supervision of the use of these drugs. The California Nurses Association (CNA) states that this bill erroneously suggests that consumers do not have access to these drugs because physicians fear their liability to practice medicine would be compromised and their liability increased if they were to recommend such treatment. CNA points out that "nothing in this legislation impacts the availability of drugs to terminally ill patients unless the manufacturers of the drugs allow it to be used in advance of FDA approval." 10)PREVIOUS LEGISLATION. AB 159 (Calderon) of 2015 was identical to this bill. It was vetoed by Governor Brown, stating "[p]atients with life threatening conditions should be able to try experimental drugs, and the FDA's compassionate use program allows this to happen. The proposed changes to this program will streamline access to these drugs. Before authorizing an alternative state pathway, we should give this federal expedited process a chance to work." 11)DOUBLE REFERRAL. This bill is double referred; upon passage in this committee, this bill will be referred to the Assembly Committee on Business and Professions. AB 1668 Page 15 12)POLICY COMMENTS. a) Governor's Veto of AB 159. In the veto of AB 159, which is identical to the provisions of this bill, the Governor stated his intent to let the new FDA process - discussed in 6) above - take effect before changing state law. The new streamlined FDA compassionate use application is expected to be finalized by the summer of 2016. The committee may wish to ask the author how he will address the Governor's veto message of AB 159. b) Will this bill achieve its intended goal? While the intended goal of this bill is meritorious, it should be noted that there are several barriers to implementation that cannot be addressed at the state level. If a manufacturer agreed to provide their investigational drug to a patient under this state law, they will still be in violation of federal law. Drug manufacturers are not exempted from FDA rules under this law, and therefore companies interested in gaining full regulatory approval for their products are unlikely to ignore federal law. Additionally, there is no evidence that investigational drugs have been made available to patients in any of the many states who have already passed similar legislation. The committee may wish to consider whether patients will be able to derive any benefit from this policy. c) Do payment provisions of this bill lack consumer protections? If a patient accessed the same experimental drug through a clinical trial, California law requires insurers pay for routine patient care costs, and the cost of the drug would be paid for by the government agency, university medical center or pharmaceutical company sponsoring the trial. Under this bill, plans and insurers AB 1668 Page 16 would not be required to cover the cost of the drug or the patient care costs. The FDA expanded use program allows the manufacturer, after review and approval by the FDA, to charge a nominal fee for the cost of providing the experimental drug. This bill permits a manufacturer to charge a patient for the costs associated with manufacturing the experimental drug, without any review or oversight. The committee may wish to consider whether these provisions could lead to overcharging a particularly vulnerable patient population. REGISTERED SUPPORT / OPPOSITION: Support ALS Association Golden West Chapter Los Angeles County Board of Supervisors Opposition California Nurses Association Medical Oncologists Association of Southern California AB 1668 Page 17 Analysis Prepared by:Dharia McGrew / HEALTH / (916) 319-2097