Two federal bills, S.204: Trickett Wendler Right to Try Act of 2017 and a companion act in the House (H.R.878), claim to give terminally ill patients the "right to try" experimental drugs outside of a clinical trial. They don't.
If enacted, a federal right-to-try law will do nothing to make companies more likely to grant patients access to their experimental drugs and will only make patients more vulnerable to actors looking to profit from their desperation.
There are meaningful steps Congress can take to help desperate patients and their families, such as educating doctors and patients about the Food and Drug Administration's (FDA's) "expanded access" process and making participating in it more appealing to drug companies, but the right-to-try bills, if passed, will do more harm than good. Nonetheless, right-to-try proponents are making a strong push to have this legislation included in the user-fee legislation that funds the FDA, which is currently being negotiated.
Although promoted in many cases by individuals with benevolent intentions, the right-to-try approach is based on two myths. The first is that the FDA's expanded access program, which allows patients to use an experimental drug outside of a clinical trial if the drug's manufacturer agrees to provide it, is slow and ineffective. In fact, it is hard to envision how the agency could provide a faster turn-around time on expanded access requests while still conducting a thorough review of a patient's medical history and proposed treatment plan. The form that physicians must submit to the FDA for review after a company agrees to supply a patient with an experimental drug requires less than one hour to complete. The FDA approves more than 99 percent of these requests, and it does so, on average, within four days. For emergency requests, the agency responds in one day or less. And this is no "rubber stamp" review: A recent study found that FDA reviewers weighed in with valuable suggestions about how to improve the proposal, making it more likely to help than hurt the patient.
The second myth—one that is especially pernicious—is that right-to-try legislation will allow patients faster and more guaranteed access to experimental drugs by cutting out the bureaucratic "middleman" (the FDA). Indeed, the central objective of right-to-try legislation is to end FDA oversight over the use of experimental drugs. For terminally ill patients, ending FDA oversight over experimental drugs would expose the patients to exploitation without guaranteeing access to the drugs they seek. And weakening the FDA puts everyone else who takes drugs or uses medical devices or vaccines at grave risk.
Despite the perception of the FDA as an obstacle to access, it is actually drug companies that decide whether to provide their experimental drugs and other medical products to patients. Patients may ask for them, and drug companies are free to say yes, no, or, unfortunately, even not respond. So-called right-to-try legislation does not give patients a "right" to access experimental drugs. It simply gives them a right they have now—to beg.
The NYU School of Medicine Working Group on Compassionate Use and Pre-Approval Access (CUPA) has devoted three years to speaking with, listening to, and studying all the relevant stakeholders in this area—including patients and patient advocates, industry representatives, health care providers, health care institutions, government regulators, law firms, ethicists, and venture capitalists. Based on this work, we have identified several measures for facilitating access to experimental drugs for patients that would be more effective than a right-to-try law:
Explore, With The Pharmaceutical And Biotech Industries, Ways To Make Expanded Access A More Appealing Prospect To Companies, Large And Small
Industry has articulated its concern that the occurrence of severe adverse events in a patient using an experimental drug via expanded access may result in slowed development of the experimental drug or may pose problems for the drug when it is up for approval by the FDA. Drug companies also fear that adverse events related to the use of their investigational products may unsettle investors. The very fact that the patient is seeking expanded access—meaning they are too sick or otherwise unsuitable for enrolling in a company's clinical trial—makes it more likely that they will experience severe adverse events. For-profit companies seeking to bring a drug to market would be inclined to avoid such risks. There is no easy answer to this dilemma. Instead, legislators and industry must partner to mitigate these risks.
Legislators should require the FDA to expand its current guidance document on expanded access to include clear, specific information about the consequences of a severe adverse event occurring in the context of expanded access. The FDA has recently conducted audits on its response to serious adverse events in expanded access settings, and these reports show that companies rarely face obstacles in the drug approval process because of the occurrence of these events when the drug is provided through expanded access. These findings must be distributed and explained in writing to the pharmaceutical industry.
Even if a company is willing to take the risk of providing its experimental drugs to patients, there may be financial and personnel constraints that prevent them from doing so—particularly for small companies. Companies might not have the resources to produce enough of an experimental drug to simultaneously conduct clinical trials and participate in expanded access. Likewise, allowing the use of a company's drugs via expanded access requires dedicated, trained personnel to handle requests, assist requesting physicians, dispense the drug(s), field questions, and handle paperwork and reporting. Legislators and industry must work together to find ways to make these activities financially feasible for companies that have limited resources.
Companies asked to provide drugs through expanded access have expressed concerns about possible liability if a patient experiences a severe adverse effect. To address these concerns, the right-to-try bills give companies immunity from lawsuits. This isn't the answer. Immunity should be limited to instances that comply with the FDA's expanded access rules in which sellers and prescribers act with reasonable belief that the treatment is in a patient's best interests and in which the patient or an appropriate surrogate has given informed consent. Congress could also allow manufacturers to require a patient to sign a confidential waiver of liability, fully enforceable in state and federal courts, as long as the company has disclosed all safety and efficacy data in its possession to the patient and his or her physician.
Strengthen The FDA's 'Expanded Access' Program, Which Allows Patients To Use Experimental Medical Products Outside Of Clinical Trials. The Program Works, But It Can Be Improved
Despite its rhetoric, the main intent behind right-to-try legislation is not increasing patient access to experimental drugs but rather removing the FDA from any role in terminally ill patients' ability to gain access to experimental drugs outside of a clinical trial. However, the FDA's role in overseeing the use of unapproved medical products is vital. The agency's guidance protects patients from exploitation, as well as from well-intended but misguided therapeutic attempts that can cause even more harm or pain than patients are already experiencing from their underlying disease or condition.
FDA review of a physician's plan to use an experimental drug on a patient helps ensure that the physician uses the drug in the manner that is most likely to help—and not harm—the patient. A recent review found that in a sample of 150 randomly selected, expanded access proposals reviewed by the FDA, the agency recommended changes to dosing, safety monitoring, or informed consent 11 percent of the time. This shows that FDA review of expanded access proposals is useful to the patients who are seeking access to experimental drugs.
The FDA's Office of Health and Constituent Affairs and its Division of Drug Information—two entities that help physicians and patients with the expanded access process—need more resources, autonomy, and personnel to function optimally. Congress is currently negotiating the reauthorization of the Prescription Drug User Fee Act (PDUFA) of 1992 that funds the FDA, providing an ideal opportunity to make the necessary changes to these offices. Legislators should use PDUFA to require that the FDA develop and implement an outreach plan to address fears and misconceptions about patient access held by industry, advocacy organizations, patients, and the public.
Over the past few years, the FDA has streamlined the expanded access application process, most notably by revising the required paperwork a patient's physician must submit to the agency. The agency also assigned the Reagan-Udall Foundation for the FDA the task of creating a "navigator" to help physicians and patients find information about how to access to experimental drugs. To best help those in need, any navigator must be easy-to-use, up-to-date, accurate, and designed for both physician and patient users.
Allow The FDA To Require That Physicians Report Additional Data From Expanded Access Attempts To The Agency
The FDA requires doctors who use experimental drugs to report serious or unexpected outcomes. However, health care providers frequently do not submit this information, leaving the FDA in the dark about the occurrence of serious adverse events, which has consequences for being able to appropriately evaluate future plans to use that drug in other patients. The FDA needs to be able to get this information from physicians. This may entail hiring additional personnel or merely making it an agency priority to secure this information.
The FDA also ought to be able to require the reporting of other data, in addition to information about serious or unexpected adverse outcomes. Congress should give the FDA the authority to investigate the collection and use of outcome and patient-reported data from expanded access cases as a supplement to data gathered from clinical trials. This kind of real-world data may allow the agency and other entities involved in drug development to glean insights into how the experimental drug will work in patients who are sicker than the typical population of patients enrolled in clinical trials.
Encourage The FDA To Better Educate Health Care Professionals And Researchers On The Expanded Access Process
Legislators can mandate that the FDA help educate health care professionals and researchers on how to seek access to experimental drugs via expanded access. Too often, terminally patients are unable to access experimental drugs because doctors are not sure how to navigate the expanded access system.
Get Rid Of Institutional Review Board Oversight For Single-Patient Expanded Access Protocols
After reports of unethical treatment of humans in medical research, the United States adopted a policy that Institutional Review Boards (IRBs) must review all research activities involving human subjects. Because expanded access involves patients using experimental drugs, it falls under the auspices of IRB review. However, IRB members receive training to review and evaluate research that produces generalizable knowledge, not one-off therapeutic requests to try and benefit individual patients. As a result, IRB members often feel unqualified to review expanded access requests.
Furthermore, since not all medical centers conduct research, some lack IRBs. Even if a medical center has an IRB, not all IRBs meet frequently. Finally, IRBs across the country have inconsistent policies for handling expanded access, which makes it difficult for patient advocacy organizations to assist those dealing with IRBs. The result is that IRB approval can negatively impact how quickly an experimental medicine can reach a single patient. Despite seeking them, the Working Group found no instances of an IRB turning down an expanded access proposal. Thus, it appears that the requirement that such proposals undergo IRB review only slows down the process.
Use Legislative And Other Means To Promote Access To And Equity In Clinical Trial Enrollment
The safest and most valuable way for a patient to get access to an investigational drug is through enrollment in a clinical trial. However, clinical trial access is not available to all Americans. Some patients are unable to participate in clinical trials because of the cost of trial participation or an inability to travel to a trial site. Furthermore, criteria for inclusion in a trial is often stringent, thereby keeping some patients out of clinical trials. Legislators should promote and advance innovative trial designs that include a wider range of patients, including those who might be too ill to meet entry criteria of traditional clinical trials, and should devise ways to remove the barriers that keep clinical trial participation from being possible for all patients.
There is a troubled history in the United States of certain groups being excluded from clinical trial participation, including children, pregnant women, women of childbearing age, and minorities—a problem that persists today. Legislators must work to facilitate access to clinical trials for underrepresented groups by reevaluating the NIH Revitalization Act of 1993, which provides guidelines on the inclusion of women and minorities in human subjects research.
Despite good intentions, federal right-to-try legislation would fail to facilitate access to potentially life-saving drugs for terminally ill patients and may even make those patients more vulnerable to exploitation. Drug companies control access to their own drugs, so weakening the FDA will do nothing to remove obstacles to accessing investigational drugs. Those obstacles can only be removed through policies that incorporate the interests of patients, doctors, and industry to make it more practical and appealing for drug companies to provide terminally patients with investigational drugs.
Author's Note
Arthur L. Caplan serves as the unpaid chairperson of the Compassionate Use Advisory Committee (CompAC), an independent group of internationally recognized medical experts, bioethicists, and patient representatives, that advises Janssen/J&J about requests for compassionate use of some of its investigational medicines.
from Health Affairs BlogHealth Affairs Blog http://ift.tt/2qsbhP1
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