BILL ANALYSIS                                                                                                                                                                                                    Ó



          SENATE COMMITTEE ON
          BUSINESS, PROFESSIONS AND ECONOMIC DEVELOPMENT
                              Senator Jerry Hill, Chair
                                2015 - 2016  Regular 

          Bill No:            SB 149          Hearing Date:    April 27,  
          2015
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          |Author:   |Stone                                                 |
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          |Version:  |April 14, 2015                                        |
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          |Urgency:  |No                     |Fiscal:    |Yes              |
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          |Consultant|Sarah Mason                                           |
          |:         |                                                      |
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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 an investigational drug, biological product, or  
          device available to an eligible patient as defined.  

           NOTE:  This bill was referred to the Senate Committee on Health  
          first, and was passed out of that Committee on April 22, 2015 by  
          a vote of 7-0.   

          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  
            of an approved drug, with certain exceptions; b) Requires  







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            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 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  
               new drug or device application, and has not withdrawn,  








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               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 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 ten thousand dollars ($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 jail, a fine of not more than ten  








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            thousand dollars ($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 (Act) 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)   "Eligible patient" as a person who has a terminal  
               illness as determined by that person's physician and a  
               consulting physician; his or her physician has determined  
               that the person has no comparable or satisfactory FDA  
               approved treatment options 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 (IDBPD) is not greater than  
               the probable risk from the disease or condition; he or she  
               has received a prescription or recommendation from his or  








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               her physician for an IDBPD; he or she has given written  
               informed consent for the use of the IDBPD, 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 his or her behalf; he or she has documentation  
               from his or her physician that the patient has met these  
               requirements.

             b)   "Health benefit plan" as any 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.

             c)   "Health facility" as a facility, place, or building that  
               is organized, maintained, and operated for the diagnosis,  
               care, prevention, and treatment of human illness, physical  
               or mental, including convalescence and rehabilitation and  
               including care during and after pregnancy, or for any one  
               or more of these purposes, for one or more persons, to  
               which the persons are admitted for a 24-hour stay or  
               longer, as specified. 

             d)   "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.

             e)   "Physician" means a physician and surgeon licensed under  
               the Act or an osteopathic physician and surgeon licensed  
               under the Osteopathic Act who is providing medical care or  
               treatment to the eligible patient for the terminal illness.  
                Specifies that physician does not include a primary care  
               physician.

             f)   "State regulatory board" means the MBC or the  
               Osteopathic Medical Board of California (OMBC).

             g)   "Terminal illness" means a disease that, without  
               life-sustaining procedures, will result in death in the  








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               near future or a state of permanent unconsciousness from  
               which recovery is unlikely.

          1) 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.

          2) Authorizes a manufacturer to provide an IDBPD to an eligible  
             patient without receiving compensation; requires an eligible  
             patient to pay the costs of or associated with the  
             manufacture of the IDBPD, and; requires an eligible patient  
             to participate in data collection relating to the use of the  
             IDBPD.

          3) Authorizes a health benefit plan to provide coverage for an  
             IDBPD, or device but, except as otherwise required by law,  
             does not require a health benefit plan or any state agency to  
             provide coverage for the cost of any IDBPD.

          4) 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.

          5) Prohibits a state agency, notwithstanding any other law, 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 IDBPD.

          6) Provides that a violation of the Act shall not be subject to  
             penalties for other violations of provisions of the Sherman  
             Act. 

          7) Clarifies that the Act does not create a private cause of  
             action against a manufacturer of an IDBPD, or against any  
             other person or entity involved in the care of an eligible  
             patient using the IDBPD, for any harm to the eligible patient  
             resulting from the IDBPD so long as the manufacturer or other  
             person or entity complies in good faith with the terms of  
             this article and exercises reasonable care.









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          FISCAL EFFECT:  Unknown.  This bill is keyed "fiscal" by  
          Legislative Counsel.  

          
          COMMENTS:
          
          1. Purpose.  The  Goldwater Institute is the  Sponsor  of this  
             bill.  According to the Author, this bill provides terminal  
             patients a path to access potentially life-saving drugs, free  
             of needless delays and a potential bureaucratic veto.  The  
             Author believes that the bill would give a patient, who has  
             exhausted all other treatment options, a last-chance effort  
             to save their life with an option to try an experimental drug  
             that has passed Phase 1 of the FDA safety trials.  According  
             to the Author, the current process is fraught with  
             deterrence, delays, and potential denials.  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.  
             
             The Author states that only a few hundred patients are lucky  
             enough to be granted individual expanded access each year  
             because of the complicated, time-consuming, and expensive  
             process currently required by the FDA.  According to the  
             Author, first, the patient must locate a doctor who is  
             willing to complete the required paperwork which the FDA  
             notes will take a minimum of 100 hours to complete. Few  
             doctors have the skill or time necessary to complete such an  
             undertaking, especially when their time is not reimbursed by  
             insurance.  Assuming the doctor is willing and able to  
             complete the paperwork and the patient can cover the cost of  
             doing so, the FDA then has a month to review the submission  
             and either grant of deny the request.

             The Author states that medical decisions, especially those of  
             terminal patients, should be made by doctors and patients,  
             not bureaucrats, and this bill ensures that terminal patients  
             have the right to make their own medical decisions, while  
             providing important legal protections for patients, doctors,  
             insurance and pharmaceutical companies.









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          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  
             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.  








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              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, 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  








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             Compassionate Freedom of Choice Act of 2014) failed to make  
             it out of committee.

             In response to criticisms, the FDA recently sought to provide  
             a streamlined alternative for submitting an Investigational  
             New 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.  
              It is estimated that the new application form 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.   
              https://www.federalregister.gov/articles/2015/02/10/2015-02561 
             /individual-patient-expanded-access-applications-form-fda-3926 
             -draft-guidance-for-industry  

          3. Efforts in Other States.  According to information provided  
             by the Author, 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 are considering the law this year.   
             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. Related Legislation This Year.   SB 715  (Anderson) is  
             substantively similar to this bill.  (  Status:   The measure is  
             currently pending in the Senate Committee on Health.)

              SB 128  (Wolk) permits a competent, qualified individual who  
             is a terminally ill adult to receive a prescription for aid  
             in dying medication if certain conditions are met.  (  Status  :   
             This bill has been referred to the Senate Appropriations  
             Committee.) 

              AB 159  (Calderon) permits a manufacturer of a drug,  
             biological product, or device that has not yet received  








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             federal or state approval to market to make the product  
             available to eligible patients with terminal illnesses, as  
             specified.  (  Status  :  This measure has been referred to the  
             Assembly Appropriations Committee.) 

          5. Arguments in Support.  The  Union of American Physicians and  
             Dentists/American Federation of State, County and Municipal  
             Employees (UAPD/AFSCME)  supports this bill, stating that to a  
             patient who is terminally ill, the current process to obtain  
             potential life-saving drugs is stressful with delays and  
             probable denials by insurance companies.

          6. Concerns and Arguments in Opposition.  The  Los Angeles County  
             Board of Supervisors (BOS)  writes that it supports this bill  
             if it is amended to provide comprehensive written, informed  
             patient consent.  According to the BOS, this bill does not  
             provide patients with comprehensive, 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.  

             The  Pharmaceutical Research and Manufacturers of America  
             (PhRMA)  have concerns with this bill, writing that while "the  
             bill is well-intentioned, it could have serious unintended  
             consequences that must be taken into consideration" and adds  
             that the bill may be premature given recent developments at  
             the federal level.  PhRMA states that right to try  
             legislation is unlikely to achieve the goal of bringing  
             innovative, safe and effective medicines to patients as  
             quickly as possible and cites the current robust nature of  
             the current clinical trial process, the FDA's current EAP,  
             and efforts underway to streamline the EAP as reasons for  
             concerns.

             The  Association of Northern California Oncologists (ANCO)  is  
             opposed to this bill, citing the difficulty of identifying  
             terminally ill patients, the danger of right to try outside  
             of the context of a clinical trial, the lack of an informed  
             consent process to protect patients and the lack of  
             appropriate physician supervision of the use of these drugs.   
             ANCO is concerned that any threat to adult clinical trial  
             enrollment would result in slowing the development of cancer  
             care in the future.









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             According to the  California Medical Association (CMA)  which  
             is also opposed to this bill, offering unapproved therapies  
             without credible scientific rationale or controlled  
             monitoring could lead to not only endangering terminally ill  
             patient lives further but potentially exploiting their hopes  
             and circumstances, as the impeded person and their families  
             may pay and try anything to save their lives.  CMA notes that  
             companies may not want to provide their treatments outside of  
             FDA processes and states that it shares the Author's goal of  
             streamlining access to investigational drugs but only when  
             the proper patient safety protections are in place. 

          7. Author's Amendments Following the Discussion in the Senate  
             Committee on Health.  The Author advises that he plans to  
             take the following amendments in response to concerns raised  
             by members of the Senate Committee on Health.  Specifically,  
             the amendments will :

             a)   Establish a mechanism for the manufacturer to report  
               data to the DPH on the following: the number of requests  
               made for experimental drugs under the Act established by  
               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. 

               On page 5, after line 11, insert:

                111546.4  (a) A manufacturer that provides an  
               investigational drug to an eligible patient under 111546.2  
               shall report all of the following to the department:
               (1) All requests for right-to-try medication.
               (2) All approved requests for right-to-try medication.
               (3)  The duration of treatments
               (4) The success or failure of the drug in treating the  
               terminal illness for which the eligible patient was  
               diagnosed.
               (5) Any adverse event for each investigational drug.
               (6) Costs paid by eligible patient for each investigational  
               drug. 
               (7) The consulting physician's diagnosis and prognosis, and  
               verification that the eligible patient is competent, acting  
               voluntarily, and has made an informed decision, or that the  
               consulting physician has determined that the individual is  








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               not an eligible patient.
               (b) The information collected shall be confidential and  
               shall be collected in a manner that protects the privacy of  
               the patient, the patient's family, and any medical provider  
               or pharmacist involved with the patient under the  
               provisions of this part.
                
             b)   Conform the definition of terminal illness contained in  
               SB 128 (Wolk) related to terminally ill patients receiving  
               a prescription for aid in dying medication.

               On page 4, line 3, after "Terminal", strike "illness means  
               a disease that, without"

               On page 4, strike lines 4 through 6.

               On page 4, after "Terminal", insert "disease" means an  
               incurable and irreversible disease that has been medically  
               confirmed and will, within reasonable medical judgment,  
               result in death within six months.

               (g) "Terminal  illness" means 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.  disease" means an incurable and irreversible  
               disease that has been medically confirmed and will, within  
               reasonable medical judgment, result in death within six  
               months.  

             The Author notes that he is still working to address concerns  
             regarding informed consent and will take amendments on that  
             subject at a future date.
          
          SUPPORT AND OPPOSITION:
          
           Support:  

          Union of American Physicians and Dentists/American Federation of  
          State, County and 
                Municipal Employees (UAPD/AFSCME)

           Concerns:








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          Los Angeles County Board of Supervisors
          Pharmaceutical Research and Manufacturers of America (PhRMA)

           Opposition:  

          Association of Northern California Oncologists
          California Medical Association (CMA)


                                      -- END --