BILL ANALYSIS                                                                                                                                                                                                    Ó



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          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  








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            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  








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               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  








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               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;








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             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: 










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             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  








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            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  








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               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  








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            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  








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               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.    








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             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.











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          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  








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            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.  









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          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.









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          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  








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               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 












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          Analysis Prepared by:Dharia McGrew / HEALTH / (916) 319-2097