Expanded Access to Experimental Therapies
“A major goal of drug regulation must be to speed the journey from laboratory to bedside of important new drugs for devastating illnesses.” (1) One example is that under certain circumstances, the FDA allows patients who are seriously ill or have life-threatening conditions to access investigational drugs not yet on the market.
Treatment use of experimental drugs is generally grouped into two categories according to the number of people treated: expanded access and single patient use. One type of expanded access program is called the Treatment IND (investigational new drug). It allows multiple patients for whom there are no other approved, satisfactory treatments available, to use investigational drugs that have shown promise in clinical trials, but have not yet reached the market.. Patients receive the treatments outside of the ongoing clinical trials.
Single patient use (sometimes called “compassionate use”) is an exception granted by the FDA for individual rather than group treatment use of experimental drugs when a patient might benefit from it, but is ineligible for the current clinical trial. In effect, the FDA allows an individual patient to become his or her own study.
The FDA may grant a compassionate use or Treatment IND if :
The patient gives informed consent, understanding that the drug is not approved and may cause side effects from mild to fatal.
No comparable or satisfactory alternative drug is available.
The drug does not expose patients to an unreasonable and significant additional risk of illness or injury.
The drug is under investigation in a controlled clinical trial (Phase II or III) or all clinical trials have been completed
The sponsor is pursuing marketing approval with “due diligence.”
However, in no case is the sponsor legally required to provide the experimental treatment to a terminally-ill patient. Even if the patient has obtained FDA permission, the government cannot compel the drug company to provide the treatment.
Should the sponsor agree to provide the drug, they would be responsible for reporting to the FDA. However, if the commercial sponsor is unwilling to assume responsibility for a special exception, an investigator or the patient’s doctor may take responsibility for treating the patient. They would then need to obtain the drug from a manufacturer, apply directly to the FDA for an IND and report information about the effects of the drug to the FDA. Additionally, an Institutional Review Board must evaluate the situation and grant approval.
“The FDA has worked diligently to balance two compelling, and sometimes competing, factors,” says FDA Commissioner Jane E. Henney, M.D. “On one hand, there is the need for the disciplined, systematic, scientifically controlled studies necessary to identify treatments that may improve patient health and that lead to the approval of new drugs. At the same time, there is the desire of seriously ill persons, with no effective options available, to have the earliest access to unapproved products that could be the best therapy for them.”
Are the risks greater than the benefits when trying an experimental medication? That depends on your viewpoint. Even if an unproven treatment does not increase the long-term survival prognosis, the patient and the family may feel better knowing that they have exhausted all available options. Staff from the Office of Special Health Issues and the Center for Drug Evaluation and Research’s drug information branch often explain the process for getting access to an experimental medication, but do not steer patients in one direction or the other. Information is provided so patients, in consultation with their physicians, can make their own informed decisions.
Differing viewpoints of Treatment INDs
In addition to benefiting individual patients, Treatment INDs may be of benefit to many in that they generate useful information about how specific drugs affect larger segments of the patient population than might otherwise receive it in a clinical study. The process:
Involves wider treatment use of unapproved agents.
Accelerates the FDA’s new drug application review process without compromising approval requirements for safety and effectiveness.
Shortens the time devoted to pre-approval drug testing, eliminating unnecessary, duplicative studies, and expediting the review of innovative agents for the most serious or life-threatening conditions.
Encourages FDA reviewers to help drug developers plan studies that generate information necessary to make decisions about approvability.
The Society for Clinical Trials, however, argues that Treatment INDs ultimately could destroy the clinical trial process, which remains “the surest way to determine whether a drug works and is safe.” The group argues that “Vastly broaden(ing) access to medications that have shown only limited evidence of safety and, often, none at all of efficacy …would devastate the clinical trial system that has fueled unparalleled medical progress over 45 years.”
Do Treatment INDS provide meaningful access?
Since the final treatment IND rule was published in 1987, through 2000, the FDA has made only about forty drug or biologic investigational products available to patients early and has approved thirty-six.
Critics of the FDA policy contend that “compassionate use” is not really a meaningful exception for the terminally and seriously-ill because there are few incentives in the current regulations that would encourage companies to agree to provide experimental therapies to individuals or groups outside of the clinical trial process. Most requests have been refused by drug sponsors, who fear that the legal and financial risks to their companies would outweigh the benefits.
Some solutions have been proposed. In December 2006, the FDA proposed new rules, clarifying the existing regulations for the treatment IND and expanding the situations where an experimental drug treatment is available to a terminally or seriously-ill patient. The FDA would be required to determine that providing the experimental drug “will not interfere with the ... clinical investigations that could support the marketing approval” of that drug.” It would also establish “clear eligibility criteria and submission requirements, the proposed rule would ease administrative burdens ... on sponsors willing to make promising unapproved therapies available for treatment use.” Other critics of the FDA policy say that the government should provide sponsors with more protections that would “eliminate the disincentives, including liability, cost recovery, and risks to achieving marketing approval, that prevent drug sponsors from providing INDs for treatment use.”
Legislative reforms have also been proposed, such as Access, Compassion, Care, and Ethics for Seriously Ill Patients Act (S3046). Backed by the Abigail Alliance for Better Access to Developmental Drugs, the bill would create a new conditional approval system for drugs, biological products, and devices that is responsive to the needs of seriously ill patients.
However, others agree with Dr. Henney that, “Continuing to shorten review times and work with industry to shorten development times for drugs, biologics and medical devices is the best way to provide all Americans with access to useful medical treatments,”
- FDA Consumer magazine, January-February 2000, “Experimental Treatments? Unapproved but Not Always Unavailable” by Larry Thompson. Accessed July 29, 2008 at: http://permanent.access.gpo.gov/lps1609/www.fda.gov/fdac/features/2000/100_exp.html
- Code of Federal Regulations 21CFR312.34, Treatment use of an investigational new drug
- Food and Drug Administration. Protecting human study subjects (?)
- Cerino, Joanna R. The Statutory Limits of Compassion: Can Treatment INDs, Provide Meaningful Access to Investigational Drugs for the Terminally Ill?, Temple Journal of Science, Technology & Environmental Law,
Food and Drug Administration. Protecting human study subjects (?), Spring, 2008
FDA Proposes Rules Overhaul to Expand Availability of Experimental Drugs FDA News.Dec. 11,2006. Accessed July 29, 2008 at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108798.htm