BILL ANALYSIS                                                                                                                                                                                                    



          SENATE COMMITTEE ON HEALTH
                          Senator Ed Hernandez, O.D., Chair

          BILL NO:                    SB 149    
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          |AUTHOR:        |Stone                                          |
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          |VERSION:       |April 14, 2015                                 |
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          |HEARING DATE:  |April 22, 2015 |               |               |
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          |CONSULTANT:    |Melanie Moreno                                 |
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           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                    withdrawn, terminated, or suspended that approval; or,  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                    not been withdrawn, terminated, or suspended under the  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,  







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            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. 









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             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  








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                    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,  








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            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  








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            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  








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            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  








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            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  








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            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  








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            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

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