Prescribing Experimental Drugs A great deal of time, money and research go into the development of a new drug and many of these drugs won’t even make it to the destined patient until it’s too late. Imagine having to tell someone with a life-threatening disease that there is a possible cure but it happens to be in the experimental phases of development, and they don’t qualify for the clinical trial. “It is estimated that, in 2006, nearly 1. million ’terminally ill’ patients in the United States lost their battle, many having been denied access to potentially lifesaving treatments” (Portell, 2008) Drug sponsors and manufacturers monitor the results of all stages of the development process to ensure that the drug is safe for general use. However, giving experimental drugs to patients before they are approved leaves room for erroneous trial outcomes and results in higher time and money costs for the manufacturers.
Drug sponsors have many steps to complete; applications to fill out, reviews to attend and clinical trials to perform, all while maintaining the ethical and legal standards set forth by the United States. “According to the Pharmaceutical Research and Manufacturers of America, the average drug on the market is the end result of 15 years of research and development from the earliest stages of drug discovery to FDA approval. ” (DeArment, 2009) In order to get a clear picture of how to obtain drugs while still in the experimental phase an in-depth look at the developmental and approval process is needed.
As well as an understanding of who is liable if the drug causes an adverse effect in these individuals. This report will also examine a group designed to help the terminally ill obtain these drugs. Patients who have a terminal illness are most often eager to try anything, including unapproved drugs or therapies because conventional medicine has offered little or no help. With all the many requirements and numerous years needed to get new drugs on the market, should patients have experimental drugs readily available for use before the FDA has given their approval? The Drug Development Process
The drug approval process is a long arduous journey, “In order to get governmental approval for new drugs, applicants must meet the safety and effectiveness standards established under the federal Food, Drug and Cosmetic Act of 1938 (FDCA), which requires “substantial evidence” of safety and efficacy prior to approval. ” (2003) According to the FDA, they estimate that “it takes approximately eight-and-a-half years to study and test a new drug before it can be approved. ” (1998) The purpose of Pre-Clinical research is to gather enough data to prove that it is reasonably safe to test the drug on humans.
During the pre-clinical development the FDA requires that a sponsor submit data demonstrating the drug to be reasonably safe for individuals to use in small-scale clinical studies. (1998, p. 5) The data submitted would include the “drug’s toxic and pharmacologic effects”, “Genotoxicity screening” (1998, p. 5) and other technical information. Synthesis and Purification All new drug research must start with a complete understanding of the human body and how it functions. Researchers have to be aware of the normal functionalities of a body as well as the abnormal ones, in order to understand how a drug will function within those confines.
In the synthesis and purification phase of the pre-clinical research scientists usually have to screen hundreds, sometimes thousands of compounds which are added one at a time to other substances in order to find which addition demonstrates some kind of effect. (1998) Another method is to test compounds that are made naturally by microscopic organisms like fungi, and molds. Sometimes, 100,000 or more are tested to see if any give a desirable effect. (1998) Animal Testing There are two types of animal testing, short-term testing which ranges from 2 weeks to 3 months and long-term testing which range from a few weeks to many years. 1998, p. 6) When drug companies have to use animals, they attempt to use as few as possible and to “ensure their humane and proper care. ” (1998) In some cases the animals are being tested well after the study has begun on humans, this concept is to gather the long term effects. Clinical Studies When enough data is collected that demonstrates a drug is safe, a clinical trial is put together in order to determine more information about the drug’s safety and effectiveness in humans. Institutional Review Boards The use of IRB’s in clinical research is to ensure the “rights and welfare” 1998) of everyone who participates in a clinical trial. An IRB is an independent committee that is monitored by the FDA consisting of at least 5 individuals (physicians, community advocates, statistician and more) with varying backgrounds and diverse training. This board will ensure that all risks (if any) are justified by the potential benefit of the research. Clinical Phases Clinical Trials generally include three phases. Phase I trials are conducted on a small group ranging from twenty to eighty healthy individuals and lasts an average of 6 months to 1 year.
This will be the first time the investigational new drug (IND) is tested on humans. This phase of trials are designed to “determine the metabolic and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness. (1998, p. 8) When enough sufficient information has been gathered about the drug, applicants can move on to Phase II. Phase II is designed to determine the effectiveness of the drug in treating patients with a specific illness.
This phase of testing will determine the “short term side effects and risks associated with the drug. (1998, p. 8) These studies are typically conducted on several hundred people and lasts an average of 2 years. Phase III gives a greater amount of information regarding the safety and effects of the drug. “Phase III studies usually include several hundred to several thousand people” (1998) and lasts an average of 3 years. “Approximately seventy percent of new experimental drugs proceed from Phase I to Phase II, and only about thirty-three percent reach Phase III. (Portell, 2008) When all three phases have been completed a new drug application (NDA) of about 100,000 pages is submitted to the FDA for approval which can take up to two years. Accessibility of Experimental Drugs to Patients Some patients, (especially the terminally ill), do not usually have the 9 years required for a new drug to be approved and they do not necessarily care if the drug meets the highest standards of safety. For this reason some policies allow for a limited number of these individuals to have access to investigational drugs before they are approved. Access Mechanisms
Drug companies are hesitant to give experimental drugs to patients because “it is extremely expensive for a drug company to make experimental drugs available to anyone who asks for them, especially considering that large numbers of promising drugs never make it out of the trials. ” (2008) Even with this being the case there are some access mechanisms that can be used to aid patients with terminal illnesses obtain drugs in the experimental stages of development. They are as follows: 1. Parallel Track: These drugs can be made available once the Phase I trials have completed.
The patient must have AIDS, be ineligible to enroll in a clinical trial, and have exhausted all other therapies. 2. Treatment IND: These drugs are not made available before Phase II. The patient must have a life-threatening disease, have exhausted all other therapies, and the patient is not eligible to enter a clinical trial. 3. Investigator IND’s (Compassionate IND): These are made available on a single-patient basis. Both FDA and Institutional Review Board (IRB) approval are needed, often easier to obtain than applying for a Treatment IND or Parallel Track.
This method must also be used when marketing the drug for a new suggestion. 4. Emergency Use IND: This expanded access protocol allows the FDA to authorize the drugs over the phone in an emergency situation that doesn’t allow for the time to submit an IND. These are also used for patients that don’t meet requirements for clinical trials or if trials do not exist. 5. Accelerated Development Review: “is a highly specialized mechanism for speeding the development of drugs that promise significant benefit over existing therapy for serious or life-threatening illness for which no therapy exists. (1998, p. 9) Legal and Ethical Issues “Ethicists and legal experts argue that access to unapproved drugs would undermine the scientific process that determines which drugs are effective as well as the ability of the FDA to determine drug safety. ” (Webb, 2008) Legal Issues In terms of liability there are a number of people who could be liable if a person is injured by an experimental drug. Firstly the manufacturing company must understand all the side effects, the dangers and the risks of using the drug as well as inform the public of these findings.
If they fail to do this they are liable. Many drug companies hesitate to give experimental drugs to patients that are not enrolled in a clinical trial because of the liability risks. The physicians are responsible for getting a patients informed consent and telling them everything about the drug and the risks involved and also detecting side effects when they first appear. The physician becomes liable when an injury is a direct result of a failure to do any of the above mentioned items. Abigail Alliance for Better Access to Developmental Drugs
The Abigail Alliance is an advocate group founded in 2001 by Frank Burroughs. His daughter was 21 years old when she died of head and neck cancer. While she was alive Frank “submitted a proposal to the FDA asking that post-Phase I INDs be made available to terminally ill patients who were not admitted to the FDA’s clinical trials” (Portell, 2008) The FDA denied the proposal and ignored the Citizen Petition they submitted. In 2003 they “filed suit against the FDA Commissioner, Andrew C. Von Eschenbach, M. D. , and the Secretary of the Department of Health and Human Services, Michael O.
Leavitt. ” (2008) However, the district court dismissed the charges. Abigail Alliance appealed to the U. S. Court of Appeals for the District of Columbia and in May 2006 they ruled in favor of the Abigail Alliance citing the constitution’s 5th amendment as “authority to recognize this right. ” (Portell, 2008) The FDA immediately appealed and in March 2007 the U. S. Court of Appeals for the District of Columbia reheard the trial en banc. In August 2007 the previous decision was reversed when they “rendered an eight to two decision” (Portell, 2008) against the Abigail Alliance.
The Abigail Alliance attempted to appeal with the Supreme Court, however, in January 2008 the Supreme Court declined to accept the case. “The Bush administration and the FDA urged the court not to hear the case, saying the appeal sought to “revive a brand of judicial intervention that this court foreswore long ago. ” (Stohr, 2008) Ethical Issues The ethical issues involved with experimental drugs and distributions before FDA approval are numerous. Starting with the IRB’s, if an IRB is for-profit there will be concerns about whether they are capable of an objective review.
Moving on to the testing facilities of these drugs, it is estimated that less than “1 percent” (Filber, 2008) of these sites are audited by the FDA; so who is monitoring the ethical treatment of participants and the integrity of the research findings? In clinical trials placebos are often used to gather data. During these trials if there is “effective, life-saving, or at least life-prolonging treatment” (2001) available the patients who are assigned to receive the placebos would more than likely suffer serious harm as a result.
Next are the issues of who receives the drugs, is it just the terminally ill or do patients who suffer unconscionable pain, or ones plagued with lifelong illness receive them as well? If so, will drug seekers take advantage of the system to obtain drugs to relieve the lifetime of “pain” they are living with? In conclusion FDA’s approval process needs to be modified. Nine years is too long to wait (especially for the terminally ill) for new drugs to be tested, approved and then marketed. The terminally ill should not have to wait until the phase III of testing has been completed.
If the palliative patient is facing imminent death and wants to “assume the risks associated with the use of an unapproved, but potentially lifesaving drug,” (Portell, 2008) they should have that right! Patients are allowed the right to refuse treatments and let themselves die, so the opposite should also be true and the patient should be able to pursue and obtain any treatment that could possibly save their life. ? REFERENCES Burroughs, J. J. (n. d. ). Abigail Alliance For Better Access To Developmental Drugs. Retrieved May 2009, from Abigail Alliance: http://abigail-alliance. rg DeArment, A. (2009, February 9). Drug makers aim to hasten drug approval process. Drug Store News , 31(2) , 33. Retrieved May 28, 2009 from Business Source Complete database. Department of Health and Human Services. (1998, March 16). The CDER Handbook. Retrieved May 13, 2009, from U. S. Food and Drug Administration: http://www. fda. gov/CDER/HANDBOOK Emanuel, M. P. , & Miller, P. F. (2001, September 20). The Ethics of Placebo Controlled Trials – A Middle Ground. The New England Journal of Medicine , 345 , 12. Bethesda, MD. Filber, S. (2008). Trials and Tribulations.
The Hastings Center Report , 38 (2) , 14-18. Retrieved May 2009, from Research Library Core database. (Document ID: 1462271511. Flannery, M. M. (2003, April 29). Research on the Terminally Ill: A Balancing Act Between Facilitating Access to Innovative Therapies and Protecting Vulnerable Subjects in Search of One Last Hope for Survival. Retrieved May 29, 2009, from LEDA at Harvard Law School : http://leda. law. harvard. edu/leda/data/547/Flannery. html Horwin, M. E. (2003, Summer). War on cancer’: why does the FDA deny access to alternative cancer treatments? Albany Law Journal of Science & Technology.
Retrieved May 29, 2009, from Health Reference Center Academic via Gale: http://find. galegroup. com. ezproxy. lib. fit. edu/itx/start. do? prodId=HRCA New Drug Approval Process. (n. d. ). Retrieved May 2009, from Drugs Information Online: http://www. drugs. com/fda-approval-process. html Portell, C. R. (2008). Live or Let Die: Will the Courts Recognize In Terminally Ill Patients a Fundamental Right to Choose Non-FDA Approved Drugs or Does the FDA’s Stringent Approval Process Carry Sufficient Merit? Retrieved May 29, 2009, from LexisNexis Academic: http://www. exisnexis. com. ezproxy. lib. fit. edu/us/lnacademic/results/docview/docview. do? docLinkInd=true=21_T6668031850=GNBFI=BOOLEAN=1=29_T6668031853=22_T6668031852=true=0=280859=3 Scientific American. (2007, October). Scientific American. Retrieved May 2009, from SciAm Digital: www. sciamdigital. com/index. cfm? fa=Products. ViewIssuePreview=E0EC9915-3048-8A5E-10FD3F1F5EC4 Stohr, G. (2008, January 14). U. S. Supreme Court Refuses to Expand Experimental-Drug Access.
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