EXECUTIVE                                   SUMMARY                      Executive Summary • Terminal Patient AccessWE PRE...
therapies and devices for patients facing serious or immediately life-threatening illnesses.This promulgation led the Food...
to travel, and will know they will receive the therapy. Thus, patients will only face theprospect of unforeseen, detriment...
OUTLINEA. Approval and Use Standards for Terminal Patient Access   I. Ensure patients have the freedom and opportunity to ...
a) These physicians must provide a maximum two-page outline illustrating               what clinical trials are, how to us...
i. CHECKPOINT: All advertisements or marketing techniques must                     state these therapies have unproven ben...
There is a missing link here between people that have the courage to acceptunknown benefits and unforeseen consequences, b...
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Executive summary terminal patient access

  2. 2. EXECUTIVE SUMMARY Executive Summary • Terminal Patient AccessWE PRESENT THE NARRATIVE of this report and the recommendations which flowfrom it to the United States Congress, the President of the United States, applicableagencies, and the American public for their consideration. This report is the product ofnumerous discussions with statisticians, economists, clinical and preclinical researchers,physicians, patients, the general public, and ethicists. While it is fear that engulfs compassion, never in the history of our nation havewe let this fear triumph over the most fundamental of American values – freedom, hope,courage, and opportunity. It is the hope for one final bout with an illness, the courage toaccept unforeseen risks and unknown benefits, the opportunity to be aware this option toobtain experimental therapies outside of corresponding experimental studies exists, andthe freedom of patients to make this choice that has been silenced. And, it is thesefounding principles of hope, courage, freedom, and opportunity which we seek to plantfirmly in the roots of our nation through creating statutory guidance to modify incentiveprograms and regulatory checkpoints to be in the best interest of the American public,while stimulating terminal and seriously ill patients’ ability to access experimentaltherapies and maintaining the integrity of clinical trials.BACKGROUND When a person is diagnosed as terminally ill, a doctor is telling this person,“There are no effective therapies approved for your illness, and you are likely going todie.” If a person desires to keep fighting, he or she can continue previous treatments,pursue alternative therapies, or inquire about investigational therapies in clinical trial.However, a problem arises when patients battling serious illnesses do not meet theeligibility requirements for these trials--which are often very stringent and have longevityrequirements (i.e., a patient has to be projected to live for at least three months)--or areotherwise unable to enroll in an experimental trial, but have reason to suspect and thecourage to take an investigational therapy that may be beneficial for them.History For years, dying individuals have demanded access to experimental therapies,even though they have not met the clinical trial enrollment requirements, for the solereason they are fighting for their last hope at life and will die within months, sometimeseven weeks, if left without treatment. Many of these patients were (and are) willing toaccept unforeseen consequences and unproven benefits for the mere hope a therapy willgive them the additional two months to watch their grandchild graduate from college ordaughter walk down the aisle.Two Methods for Access This plea was answered by the Federal Food, Drug & Cosmetic Act, in Section561, through the creation of treatment investigational new drug applications andemergency use conditions to allow for the shipment and treatment use of investigational 2
  3. 3. therapies and devices for patients facing serious or immediately life-threatening illnesses.This promulgation led the Food and Drug Administration (“FDA”) to create two separateprotocols for treatment investigational use – expanded access programs andcompassionate use protocol (single patient investigational new drugs). Expanded accessprograms are programs initiated by therapy sponsors (manufacturers and distributors) toprovide access to their investigational therapy outside of experimental study, whereascompassionate use protocol is for individual patients seeking access to experimentaltherapies outside of such studies.Details and Associated Problems with Existing Protocols Upon review, the FDA established the requirement that only those therapieswhich have passed Phase I clinical trial should be approved for terminal patient accessunder expanded access and compassionate use protocols, based on the premise that thereshould be some minimal standards of efficacy, safety, and pharmacologic knowledgeprior to providing patients with access to these experimental therapies. (21 CFR 312.34) As well, sponsors of therapies are permitted to recover no more than the directcosts associated with this service. By creating a price ceiling at the average cost ofproducing such therapies, any financial incentive is thereby removed for a sponsor toprovide such a service. Not only does limiting sponsors to direct cost recovery eliminateany financial motivation, but many small capital pharmaceuticals consistently incurquarterly losses and cannot afford to pay the initial outlay of costs to start such programs.The result: A mere 8 of 8,000 clinical trials for the nation’s second leading cause ofdeath, cancer, offer a corresponding expanded access program to provide suchinvestigational therapies to patients with no other options. The second incentive offered to therapy sponsors to institute these programs—aside from direct cost recovery and pure compassion—is to obtain additional data outsideof a clinical trial on the safety and effectiveness of a therapy. This incentive has ledmany pharmaceuticals to outsource expanded access programs to clinical researchersrather than physicians, requiring controlled clinical settings, slightly loosened eligibilityrequirements, thereby leaving many seriously and terminally ill patients unable tocombine investigational therapies with other experimental or approved medications intheir final battle for survival. Lastly, many patients do not know this option exists, when they are diagnosed asterminally ill, and will die with this ignorance. Patients are not told because patients donot think to ask. Many patients may make a quick inquiry to their treating physicianregarding alternative treatments, and leave it at that. They are too weak to travel, viewclinical trials as random with the potential of getting a “sugar pill,” do not want to leavefamily and friends, and shutter at the potential cost of the trial itself and the chance thatan investigational therapy may not be effective or even harmful. Without a strong inquiry into clinical trials, it is unlikely a physician will mentionexpanded access or compassionate use protocol and the patient will ever find out aboutsuch an option. However, it is important not to neglect the notion that patients maydesire to continue fighting if they know they might be able to receive a therapy throughexpanded access / compassionate use protocols rather than through clinical trials, mostespecially if their ailment progresses beyond the hope of approved treatment options.(The negatives for entering compassionate use protocol are far less great than before –with compassionate use, a patient can be close to home, combine therapies, does not have 3
  4. 4. to travel, and will know they will receive the therapy. Thus, patients will only face theprospect of unforeseen, detrimental side effects, and the cost of the therapy itself.) Thispotential shift in perception of costs and benefits must be recognized as viable enough toensure patients know of this option exists when diagnosed as seriously or terminally ill.Summary of Problems 1. A lack of effective and economical incentives beneficial for patients and therapy sponsors (i.e., pharmaceuticals): a) Data collection leads to unethical and underutilized practices of Expanded Access. b) Only direct costs are able to be recovered. This constraint dissolves any adequate incentive for a therapy sponsor to provide serious or terminally ill patients with this access, most especially innovative small capital sponsors. 2. The FDA rarely approves this use for therapies in pre-phase II clinical study (21 CFR 312.34), effectively limiting patients’ options despite many patients’ willingness to accept the unforeseen risks associated with taking investigational therapies in numerous phases of study (some patients even willing to accept the risks associated with therapies in preclinical experimentation). 3. Many patients do not know this option exists.Advocacy organizations calling for change: • Care to Live • Accelerate Progress • Abigail Alliance • Team IPLEX • Give Patients a Fighting Chance • Life Raft Group • Colorectal Cancer Network • Huntington’s Disease Drug Works • MS Patients for Choice • Parkinson’s Pipeline Project • Pancreatica • Liddy Shriver Sarcoma Initiative • Sarcoma Foundation of AmericaRECOMMENDATIONSGENERAL Rewrite Section 561 of the Food, Drug, & Cosmetic Act, institute financial incentives for sponsors of therapies to initiate and offer Expanded Access (EA) / Compassionate Use (CU) programs, allow the marketing of EA/CU programs, and create a protocol where all patients are informed of EA/CU and clinical trials as options when diagnosed as seriously or terminally ill. 4
  5. 5. OUTLINEA. Approval and Use Standards for Terminal Patient Access I. Ensure patients have the freedom and opportunity to undertake this risk, if they have the courage to do so, at the earliest stage of drug development plausible, enacting one of the following two options: a) The minimum phase requirement for Expanded Access / Compassionate Use approval is post-animal experimentation. Each therapy is approved on a case-by- case basis, based on the mechanism of action of the therapy in question. Any drug that can show the potential to benefit a patient, based on that patient’s molecular, genetic, or disease characteristics and the therapy-in-question’s mechanism of action, is granted (assuming no known side effects) OR b) Leave the choice almost completely up to the patient by stipulating only the following to be necessary for the approval of EA/CU: • Sufficient proof of an informed decision by the patients applying and viable data (not necessarily clinical) on the potential benefits to the patient from the investigational therapy warrant approval. This level of viable data proving potential benefit necessary for approval is left up to the discretion of the Food and Drug Administration; but, let it be noted that this evidence does not need to be clinical proof of efficacy or safety, most especially if a patient is able prove he or she accepts the risks associated with any aspects still unknown about the devise or therapy and a lack of proven benefits. • CHECKPOINTS: i. The company producing the therapy is responsible for distributing the most purified therapy available and informing the physician of any purification processes yet to be performed. ii. If dosage is unknown, the physician is allowed to monitor and change dosage at his/her discretion and hire clinicians, or other individuals, if he or she is inclined. However, he or she must inform the patient of everything that is known and unknown, and potential consequences of anything unknown. For example, taking an unknown dosage may lead to a first-time overdose and potential death. II. Combining investigational therapies with approved or other investigational therapies needs to be permitted to give desperately (terminally) ill patients every opportunity to fight for their life. i. A physician is required to inform patients of unknown and potentially adverse side effects of combining therapies that have not been investigated for safety and efficacy in conjunction, prior to the administration of this potential therapy cocktail.B. Patient Information & Disclosures: Side Effects, Unknown Characteristics ofTherapies, and Opportunity for Access I. Physicians must inform patients of EA/CU (and clinical trials) upon diagnosing them terminally or seriously ill. The definition of these illnesses is left to the discretion of the Secretary of Health and Human Services (referred to as “the Secretary” for the remainder of this document). 5
  6. 6. a) These physicians must provide a maximum two-page outline illustrating what clinical trials are, how to use, listing existing alternative clinical trial search engines, as well as explaining what are and how to apply for Expanded Access and Compassionate Use protocol. i. This document is to be written by FDA officials or general contractors, but must be approved as honest, unbiased, and sufficient by the Secretary. ii. Distribution of this document is to be available through the FDA’s website and is permitted to be printed and viewed by any individual. iii. CHECKPOINT: Any physician who is found to have failed to inform terminal patients of this opportunity more than five times is subject to a per patient fine thereafter, payable to the FDA, as well as potential civil litigation penalties to the patient(s) involved. b) Full disclosure of all known and unknown information about an experimental therapy is given to a patient by the physician or drug sponsor prior to the administration of a therapy. This includes all known side effects, dosage, and pharmacological information. II. CHECKPOINT: Any patient found to lie about his or her status as terminal is subject to a substantial fine. Any physician found to lie about a patient’s status as terminal is subject to a substantial fine and potential criminal litigation.C. Incentive Structure & Regulations for Therapy Sponsors I. Sponsors are permitted to obtain profits for and subsidies are provided to aid in the formation of EA/CU programs. a) Therapy sponsors are permitted to charge a maximum 10% net profit markup on the direct costs, less subsidy or government aid, of the therapy in question. (Direct costs are as defined in current FDA Rules and Regulations.) b) The government is to provide subsidies or long-term, low interest loans to aid sponsors in the formation of EA/CU programs, recognizing this access as fundamental to our citizens’ opportunity to fight for their lives. i. These subsidies are to be provided by the Treasury Department and granted/distributed through applications to the FDA for this aid. Such applications and reviews must consider the capital levels of the applying sponsor in determining whether to grant or deny federal aid. ii. The amount of subsidies or long-term, low interest loans is to be included in the FDA’s annual budget submissions and determined by the Secretary. c) CHECKPOINT: Executives or employees found to abuse the privileges of profit charging by intentionally prolonging clinical trials or experimentation to obtain these profits must be subject to a substantial fine to each person(s) involved and an extremely substantial fine for the parent corporation or institution of such persons, collected by the FDA and fixed to the inflation rate, and potential criminal litigation. II. Marketing of EA/CU to the public and physicians is permitted. 6
  7. 7. i. CHECKPOINT: All advertisements or marketing techniques must state these therapies have unproven benefits and the potential for unknown consequences. III. No data collected from Expanded Access programs or Compassionate Use is to be grounds for approval or disapproval of a therapy with regards to the approval or disapproval of that therapy in experimental trials for the purpose of obtaining final FDA marketing approval.D. Food and Drug Administration Costs & Feature I. Necessary appropriations may be necessary for the FDA to implement these changes and improving II. A link for any expanded access programs available, and to apply for compassionate use, is to be placed on for each applicable study.E. Coverage I. A minimum 20% coverage of EA/CU therapies is mandated for all insurance providers.CONCERNS ADDRESSED IN RECOMMENDATIONS1. Maintaining clinical trial integrity.2. Patients or physicians may lie about being terminal to circumvent clinical trials and move directly to expanded access / compassionate use access.3. Information sharing between pharmaceuticals/sponsors and physicians with regards to side effects, pharmacologic information, and purification processes.4. Information sharing between physicians and patients with regards to EA/CU as an option, known and potential benefits, known and potential risks, and known pharmacologic information.5. Creating statutes to ensure patients have every opportunity in their final battle for survival, if they have the courage to and a comprehensive knowledge of potential consequences of undertaking such an opportunity.6. Minimum coverage standards for EA/CU access.CONCLUSION Terminal and seriously ill patients’ ability to access experimental therapies isrudimentary to the founding principles of our nation. This opportunity exemplifies hopeand courage in the face of doubt and fear. As elected representatives, federal employees,and people of this nation, we must ensure we the people have the knowledge of thisopportunity and this opportunity is viable and beneficial for patients. We must ensurethese patients have every opportunity to fight for survival in the final and most fiercebattle of their lives. Currently, terminal patients may have the courage to try an experimental therapy,but federal regulators may still deny these wishes. Even if a patient is allowed to accessan investigational therapy, often times therapy sponsors do not have adequate incentivesor resources to provide these programs. Moreover, thousands of terminal patients andresearchers do not know about expanded access programs or single patient investigationalnew drugs (compassionate use). 7
  8. 8. There is a missing link here between people that have the courage to acceptunknown benefits and unforeseen consequences, because a given therapy is their lastfighting chance, and those that can provide this chance to them. Patients can afford atherapy, desire a therapy despite unknown consequences, with a researcher that is willingto provide it; no known safety concerns or adverse effects to society, yet these terminalindividuals will not be able to realize their last hope at life. This year alone an average of1,500 Americans will take their last breath every day from cancer. This is one terminalillness. This is sixty-four Americans, who may not know all of their options or maydesire to continue fighting for their lives, hindered by the very regulatory agencies andlaws meant to protect them, that will die every hour. We must act swiftly. We look forward to a comprehensive discussion on the merits of what we haverecommended, and we will participate vigorously in this discussion. 8