While well intentioned, State “Right to Try” bills are fraught with false hope and dangerous side effects.
There is nothing more heart breaking than the words “I am sorry, we have done all that we can do at this time.” It is not something any doctor wants to share or any patient or family member wants to hear.
As I write this, Arizona and other states are considering legislation based on policy that circumvents existing Food & Drug Administration (FDA) extended access and patient safety processes and would preempt federal law.
It is called “The Right to Try” and argues that “Patients should be free to exercise a basic freedom – attempting to preserve one’s own life” and that the existing FDA Extended Access Programs are too complicated and take too long.
While this policy sounds good on first read, it is in fact a severely flawed proposal that creates false hope for terminally ill patients and carries with it serious side effects in the form of ethical issues, financial issues for patients, implementation issues for pharmacies and hospitals, tort issues for healthcare providers and the companies trying to develop these new therapies, and constitutional issues for the States that try to implement it.
Basically, the “Right to Try” bills are unintentionally cruel to the sickest of patients. If they are passed, they cannot be properly implemented. Thus Patients and their families are given false hope when they are told that they have the right to try, when in reality they have little chance of succeeding outside of the current FDA system that these bills attempt to circumvent.
Since the early days of the AIDS epidemic, patients with life-threatening conditions have become increasingly vocal about demanding access to drugs still in development. The Food and Drug Administration in 1987 created new rules, amended in 2009, for expanded access or compassionate use to allow what it says is “broad and equitable access” to those treatments. But the program remains limited. Since 2009, the agency has approved an average of 1,030 applications each year; each request may be for multiple patients.[i]
Here is the summary provided for HCR 2005 on the Senate Fact Sheet at AZLeg.gov:[ii]
Subject to voter approval, statutorily allows manufacturers, health care institutions and physicians to make investigational drugs, biological products and devices that have completed phase one of a clinical trial but have not been approved by the U.S. Food and Drug Administration, available to eligible patients (patients).
Here are the issues this proposed policy creates:
- Safety – The “Right to Try” proposals would make available investigational drugs, biological products, and devices for “eligible patients” that have completed Phase 1 testing and are currently under investigation in a clinical trial. The clinical trial process has three phases. Here are the FDA descriptions: [iii]
- Phase 1 studies are usually conducted in healthy volunteers. The goal here is to determine what the drug’s most frequent side effects are and, often, how the drug is metabolized and excreted. The number of subjects typically ranges from 20 to 80
- Phase 2 studies begin if Phase 1 studies don’t reveal unacceptable toxicity. While the emphasis in Phase 1 is on safety, the emphasis in Phase 2 is on effectiveness. This phase aims to obtain preliminary data on whether the drug works in people who have a certain disease or condition. For controlled trials, patients receiving the drug are compared with similar patients receiving a different treatment–usually an inactive substance (placebo), or a different drug. Safety continues to be evaluated, and short-term side effects are studied. Typically, the number of subjects in Phase 2 studies ranges from a few dozen to about 300
- At the end of Phase 2, the FDA and sponsors try to come to an agreement on how large-scale studies in Phase 3 should be done. How often the FDA meets with a sponsor varies, but this is one of two most common meeting points prior to submission of a new drug application. The other most common time is pre-NDA–right before a new drug application is submitted.
- Phase 3 studies begin if evidence of effectiveness is shown in Phase 2. These studies gather more information about safety and effectiveness, studying different populations and different dosages and using the drug in combination with other drugs. The number of subjects usually ranges from several hundred to about 3,000 people.
As shown above, investigational products that have completed Phase 1 do not yet have either the safety or efficacy data properly established. There is not adequate data to support where the drug can help the patient or whether the benefits for the patient outweigh the risk of treatment.
- Striking a balance – Patient requests for access to drugs and biologics prior to their approval has long created a dilemma for biotechnology companies. Typically, these requests come from seriously ill patients or their families who believe an experimental product could save or prolong their lives. However, biotech companies must balance those interests with their responsibility to move products through the regulatory process to receive approval; a process that could be delayed or put at risk by providing access to the product outside of a clinical trial. [iv] The Biotech Industry Organization (BIO) Board Standing Committee on Bioethics published a detailed report on the challenges and background of the issue in 2010. The full report can be found at http://www.bio.org/sites/default/files/20100416.pdf.
- Movies, Media, and Crowd Sourcing Medical Decisions – From movies like the “Dallas Buyers Club” to news agencies telling heart wrenching stories and social medial campaigns designed to save dying patients, public pressure from the crowd is having a bigger impact on how medical decisions are made. On one side families fight to save THEIR loved one. On the other, people ask, why yours and not others. Crowd sourced medical decisions are made not on science and the medical facts, but based on who can create the biggest social media or public outcry.
“You couldn’t get a more troubling and impossible-to-resolve moral dilemma than this one,” said Arthur Caplan, director of the division of medical ethics at New York University’s Langone Medical Center. From the perspective of the public and future patients, it’s best for the company to focus on getting the drug approved as soon as possible so that the largest number of people can be helped, Caplan said. But from a patient’s point of view, getting immediate access to the drug is what’s important.” …. “It’s a trade-off between the public good versus self-interest,” Caplan said. “They conflict. There is no way of getting around it.”[v]
- Equal Access – The proposals state that neither the innovator company nor the insurers are required to cover the cost of these treatments. In addition, there is no coverage cost provided for medical treatment should side effects cause harm to the patient.
Additional Financial Issues for Patients:
Terminally Ill patients that are eligible and elect for hospice or palliative care are likely to lose their eligibility when electing to try an investigational drug. Patients risk losing access to the support of these caregiver services as well as the financial support of Medicare or Medicaid for their cost. [vi]
Additional Financial Issues for the States:
The Senate Fact Sheet provided for HCR 2005 on AZLeg.gov[vii] states that “There is no anticipated fiscal impact to the state General Fund associated with this legislation.” Unfortunately, this probably is not realistic. It is highly likely that should bills like HCR 2005 become law, there will be subsequent legal actions. As such, the State will bear the burden of these legal actions as the law is tested in the Federal courts system.
In addition, there is a risk of side effects with any therapy. Side effects often lead to healthcare costs. Determining what will and will not be paid for in a clinical setting through state funded healthcare programs will have some form of financial impact which is yet unknown.
Finally, as written, the “Right to Try” process occurs outside of the existing FDA process and there is no current administrative process at the State level. In addition, the “Right To Try” language precludes State employees from interfering. Thus, some new independent agency would need to be established to actually administer the process to ensure patient safety and legal compliance. Since the need is created by state law, it is not unrealistic to forecast that some of the financial burden of such an agency would fall to the State.
Implementation issues for pharmacies and hospitals
Patients treated with these drugs would most likely need to have treatment in a clinical setting. Hospitals and hospital pharmacies are required to follow the Federal guidelines and regulations established by CMS. As these guidelines do not allow for use of investigational products outside of an approved FDA process, the hospitals and hospital pharmacies would not be able to participate or provide the patient with the services needed to administer the therapy.[viii]
Implementation issues for the companies developing investigational therapies:
Even if a state law provides for patient access to investigational therapies outside of the approved FDA process, the companies that develop them are still bound by those FDA processes. So basically they can’t do so. While the state law might give them the option, the federal regulations do not. As such a state law might give the patient the right to try, but it does not give the company developing the product the ability to do so outside of the approved FDA parameters.
Tort issues for healthcare providers and the companies developing investigational therapies: According to testimony from David Blake, Colorado Deputy Attorney General for Legal Policy, state law does not override federal law. As such, the indemnifications provided in the Right to Try Bills are “hollow”. Although a State law may provide that the physician, care giver, hospital or company providing the therapy cannot be sued in state court; this law does not protect them in a case brought in federal court. According to Mr. Blake, “Should that happen, they would lose.” [ix]
Constitutional issues for the States that try to implement it:
Article VI, Section 2, of the U.S. Constitution provides that the “… Constitution, and the Laws of the United States … shall be the supreme Law of the Land.” This Supremacy Clause has come to mean that the national government, in exercising any of the powers enumerated in the Constitution, must prevail over any conflicting or inconsistent state exercise of power. The federal preemption doctrine is a judicial response to the conflict between federal and state legislation. When it is clearly established that a federal law preempts a state law, the state law must be declared invalid.
The proposed “Right to Try” bills would immediately create an issue under the Supremacy Clause as both federal law and the related federal regulations place the authority for both clinical trials and extended access to investigational products under the FDA.
While the “Right to Try” bills do not exempt claims of general malpractice, they do prevent state a regulatory board from taking negative action against an MD or DO physician’s license based solely on the physician’s recommendation to a patient to use an investigational drug, biological product or device and they prohibit a state agency from taking any action against a health care institution’s license based solely on the institution’s participation in the use of an investigational drug, biological product or device. They then go on step further, prescribing it a class 1 misdemeanor (6 months/$2500) in the case of an Arizona official, employee or agent who blocks or attempts to block access of a patient to an investigational drug, biological product or device.
Thus, the very safeguards we have in place to protect patients and ensure quality care would be eviscerated at the state level and action to protect patients would be very tricky should abuse occur under these programs.
So, if this is not the answer, what is?
As stated at the beginning, while well intentioned, State “Right to Try” bills are fraught with false hope and dangerous side effects. That does not mean that there is no hope that things will get better if we work within the federal systems instead of against them.
The life science industry (drug, biological product or device manufacturers) works closely with the FDA on making the process better and the FDA continues to offer updates and new guidance documents on the Extended Access Programs (EAP), the latest of which was released in May of 2013[x]. These updates and clarifications demonstrate the FDA’s focus on the importance of patient access, especially for patients and groups of patients facing serious and life-threatening diseases or conditions.
The Critical Path Institute (C-Path) , based in Tucson, Arizona, is a key partner with the FDA on its Critical Path initiative with a mission to improve health and save lives by accelerating the development of safe, effective medicines. C-Path’s work is focused on improving the drug development and clinical trials process across the board so that all products can navigate the processes more effectively. The more successful they are; the less exceptions will be needed.
Work with our Congressional representatives. FDA authority and the laws and related regulations start with Congress. The FDA is a critical partner in the industry’s efforts to bring safe and effective treatment options to patients. Without a strong and effective FDA, we cannot have a robust and competitive industry. Equally important, the FDA is the right place to center resources and information for the extended access process. Instead of attacking them, we need to work with them to get the FDA the resources needed to compassionately, safely, and efficiently manage this process better.
This is an important humanitarian and ethical challenge that faces the FDA, Industry, Patients and Physicians alike. Together we all need to work for better solutions. Unfortunately, State based Right to Try legislation is not the answer.
About the author:
Joan Koerber-Walker is the president and CEO of the Arizona Bioindustry Association. AZBio works with innovative life science companies, research institutions, healthcare providers, patient advocacy groups and our elected leaders to support the discovery, development and delivery of life science innovations.
[i] Crowdsourcing medical decisions: Ethicists worry Josh Hardy case may set bad precedent (Ariana Eunjung Cha, Published: March 23, Washington Post) http://www.washingtonpost.com/national/health-science/crowdsourcing-medical-decisions-ethicists-worry-josh-hardy-case-may-set-bad-precedent/2014/03/23/f8591446-ab81-11e3-adbc-888c8010c799_story.html
[v] Crowdsourcing medical decisions: Ethicists worry Josh Hardy case may set bad precedent (Ariana Eunjung Cha, Published: March 23, Washington Post) http://www.washingtonpost.com/national/health-science/crowdsourcing-medical-decisions-ethicists-worry-josh-hardy-case-may-set-bad-precedent/2014/03/23/f8591446-ab81-11e3-adbc-888c8010c799_story.html
[vi] http://azbio.tv/video/9775c0b16bbe4667a6dd34c4e1d00883 (Written Testimony of Beth Davis of True Care read into the record– begins at the 01:40:00 minute mark.)
[viii] http://azbio.tv/video/9775c0b16bbe4667a6dd34c4e1d00883 (Testimony of Janet Stevens of the Colorado Hospital Association– begins at the 01:26:37 minute mark.)
[ix] http://azbio.tv/video/9775c0b16bbe4667a6dd34c4e1d00883 (Testimony of Colorado Deputy Attorney General for Legal Policy David Blake– begins at the 01:30:15 minute mark.)