An investigational therapy is a drug, biologic or medical device that is in development and undergoing testing, but has not been approved by the FDA. There are several steps involved in the drug development and approval process, from early testing in a lab (non-human testing) to testing in clinical trials (human testing). To approve a new therapy, the FDA must determine that the potential benefits of the therapy outweigh the risks. This risk-benefit balance is determined based on the severity of the disease or condition, the level of unmet medical need, the perspectives of patients, and other considerations.
There are hundreds of investigational therapies undergoing testing at any given time. The most comprehensive resource to find investigational therapies under development is ClinicalTrials.gov, a registry of ongoing and completed clinical trials, studies and existing expanded access programs that is maintained by the National Library of Medicine at the National Institutes of Health. Information about clinical studies and expanded access is provided to ClinicalTrials.gov by the sponsor or investigator of the study. Your physician, cancer patient advocacy groups, rare disease organizations and other patient advocacy groups can also serve as resources for information or news on clinical trials.
Patients and their physicians can pursue access to investigational therapies and treatments through clinical trials, established expanded access programs (EAPs), and single-patient expanded access (EA). The most common way to access an investigational therapy is through a clinical trial, and, in fact, patients and their physicians must first confirm that clinical trials are not an option before pursuing expanded access programs or single-patient expanded access.
Clinical trials determine how well an investigational therapy works as compared to the existing standard of care or a placebo, and whether the potential therapy is safe and effective. Clinical trials also explore whether the benefits of the investigational therapy outweigh the risks.
All therapies have risks, and it is important to know that the investigational therapies in clinical trials are not yet approved by the FDA. In fact, many therapies tested in clinical trials never get approved. The testing process in a clinical trial follows a clear protocol, or study plan, which is overseen by regulatory bodies such as the FDA, and ethical bodies known as Institutional Review Boards (IRBs).
The biggest obstacle to completing a clinical trial is recruiting enough patients. Often, patients or their physicians are not aware of clinical trials that are open for enrollment. In other cases, many patients do not meet the study requirements and cannot be admitted to the trial. Eligibility requirements ensure that all trial participants share certain characteristics, such as age, gender, and medical condition, so that the results of the study are not affected by complicating factors. Clinical trial requirements may also help prevent patients from enrolling in studies that are not appropriate for them.
As a patient who is interested in participating in a clinical trial, you will first work with your physician to determine whether you are eligible and able to join a study. In addition to discussing the investigational therapy in question, you should also consider the clinical trial’s location, cost of transportation, childcare, meals, places to stay, and other costs that are often associated with trial participation.
Clinical trials are the first option to consider before exploring expanded access through a program or single-patient expanded access. Most pharmaceutical companies do not allow access to an investigational therapy via EA while a clinical trial is underway for the same therapy, as this could delay or jeopardize the trial’s completion for a variety of reasons. Delaying a clinical trial affects not only those in the trial, but the broader population, by slowing the therapy’s path to market. The successful completion of a clinical trial is an important step toward marketing approval, which assures the broadest availability of promising effective treatments to the patients who are most likely to benefit from them.
To determine the existence, location, and details of specific clinical trials, including eligibility criteria, you and your physician can search ClinicalTrials.gov. Contact information is provided for each trial recruiting patients and can be used to obtain more information. For a practical guide to navigating the ClinicalTrials.gov website, refer to our ClinicalTrials.gov User Guide. Other sites helpful in researching clinical trials for rare diseases include Trials Today at ResearchMatch.org and the National Organization for Rare Disorders. If you are researching cancer-related investigational therapies you can also search for clinical trials through the National Cancer Institute.
If your physician has told you that you are ineligible for or unable to participate in a clinical trial, keep reading for more information on established expanded access programs (EAPs) and single-patient EA.
If you are not able or eligible to participate in a clinical trial, an existing intermediate or large size expanded access program (EAP) may be an option. You and your physician will first need to determine if you can participate in an existing EAP before seeking single-patient expanded access.
Some reasons you may not be able to participate in a clinical trial, and therefore may be eligible for an EAP, include:
- The clinical trial’s strict inclusion and exclusion criteria
- Other health conditions
- The use of other medications that may interfere with efficacy or safety of the investigational treatment
- The inability to travel to the study location
An Expanded Access Program, or EAP, provides a defined group of people (for example, those with a serious rare disease lacking other treatment options) with access to an investigational treatment when there is enough clinical evidence that they may benefit from it. EAPs are coordinated by a pharmaceutical company, with authorization to proceed by the FDA. They follow a protocol with specific eligibility criteria.
In some ways, EAPs are similar to clinical trials, but data are collected differently and these programs are designed to accommodate patients who are not able to participate in a clinical trial. Sometimes, EAPs are opened to fill the gap in time between the end of clinical trials and potential FDA approval and availability on the market, but EAPs are not offered for all treatments.
Patients can use ClinicalTrials.gov to identify EAPs and review the eligibility requirements. (Refer to our ClinicalTrials.gov User Guide for tips on using ClinicalTrials.gov.) Physicians and patients should use the contact information provided in the EAP record on ClinicalTrials.gov to determine if the patient is eligible and able to participate.
If you are unable to participate in an established EAP, keep reading for more information on single-patient expanded access.
Single-patient expanded access is the use of an investigational treatment by a patient with serious or life-threatening disease or condition who lacks alternative treatment options and is ineligible or unable to participate in a clinical trial, an individual expanded access program or an intermediate-size patient population expanded access program.
Under these circumstances, the single-patient EA process allows a treating physician to request access to an investigational treatment from a pharmaceutical company on behalf of a single-patient. Applying for single-patient expanded access has several steps and requires physicians, patients, the FDA, IRBs, and pharmaceutical companies to work together.
If you and your physician decide to make a single-patient expanded access request, it is important to understand that there is no guarantee that access will be granted. Also, there is no standard timeframe for pharmaceutical companies to complete the process. This is because every request is unique to the individual, the specifics of their condition, the availability of information on the treatment and where the treatment is within its development and approval process. Once the FDA receives a completed Form FDA 3926 and required documentation it has up to 30 days to review the application but often reviews much more quickly – typically within two business days.
The FDA requires that a licensed physician apply for single-patient EA on your behalf. Your treating physician must complete each of the following steps to request single-patient expanded access for you:
- Request permission from the pharmaceutical company
- Request permission from the FDA
- Obtain approval from an IRB
- Obtain the patient’s informed consent
- Administer the treatment and report serious and unexpected adverse events and outcomes during the treatment
If your physician needs support in submitting an expanded access request specifically for a cancer therapy, he/she can contact Project Facilitate, a service offered through FDA's Oncology Center of Excellence.
Requesting EA from the Pharmaceutical Company
First, your physician will need to contact the pharmaceutical company to request use of the treatment. The pharmaceutical company will review the request, ask questions of the physician, and decide whether to grant access based on a number of considerations, including whether you are able to participate in a clinical trial, there is evidence to suggest you will benefit and that the potential risks do not outweigh the potential benefits. If the company does grant access to the treatment, they may work with your physician to develop a treatment plan. The company will also issue required documentation such as a Letter of Authorization (LOA) to your physician.
Requesting Permission from the FDA
After your physician’s request for EA has been approved by the pharmaceutical company, he or she must apply to the FDA for expanded access by submitting a completed form FDA 3926 and a copy of the required documentation. The FDA has up to 30 days to review the application but often reviews much more quickly – typically within two business days. During this time, the FDA will consider several factors, with an emphasis on weighing the potential risks against the potential benefits. The FDA may reach out to your physician with additional questions or to clarify the information provided. If the FDA allows the investigational treatment to proceed, they will provide the physician with an Investigational New Drug Application (IND) number.
Requesting Approval from an Institutional Review Board (IRB)
An IRB is a committee of medical and ethics experts (and community or legal representatives) who are charged with reviewing and approving biomedical research involving patients. Although EA is considered a treatment option and not formal research, because it involves investigational products, all patient safeguards must be adhered to, especially when it comes to conveying expectations and possible beneficial and harmful outcomes.
Your physician will present FDA forms, a treatment protocol, required documentation from the pharmaceutical company and the informed consent document to the IRB, which will review the application using a number of criteria.
Informed consent is critical to patient welfare and your physician is required by the IRB to obtain your informed consent for the proposed investigational therapy and protocol. Informed consent provides you with information about a protocol and clearly defines expectations and foreseeable outcomes and risks. Well-written informed consent includes an explanation of procedures, benefits and alternative treatment options (if they exist), as well as confidentiality of records and a clear explanation of your rights as a patient.
To ensure you understand all the information that your physician has provided:
- Ask your physician to clarify medical terms that you do not understand
- Ask for potential best- and worst-case scenarios and most likely outcomes
- Summarize what you have heard and ask your physician to confirm your summary
- Take notes and request written materials
Treatment and Next Steps
Once your physician has received informed consent from you and necessary permissions from the pharmaceutical company, the FDA and the IRB, the investigational treatment will be shipped from the pharmaceutical company for treatment. You will be expected to follow the treatment plan that your physician has outlined in his or her application process. During and after the treatment, your physician will report results and adverse events to the pharmaceutical company, the FDA and the IRB.
There are important considerations to bear in mind before pursuing any investigational therapy or treatment – whether through a clinical trial, an EAP, or single-patient expanded access. In addition to practical considerations like travel and treatment costs, there are medical considerations including potential risks and unknowns of the investigational treatment, the severity and stage of your condition, your other medical conditions, and the likelihood that the treatment will be effective.
Carefully consider how potential risks compare to the potential benefits of an investigational treatment, and be aware little may be known about the safety or efficacy of the treatment. The earlier a treatment is in the development and approval process, the less is known about the treatment and its possible effects. An investigational treatment could lead to adverse side effects, hospitalization, reduced quality of life, and even shortened life-expectancy.
It is also important to remember that there is no guarantee that access will ultimately be granted and, if it is granted, that insurance coverage will be available for physician's charges to administer treatment of investigational therapies or for the therapy itself. Because the policies and procedures of insurance providers and plans can differ substantially, it is important not only to discuss the best course of action with your physician but also to contact your insurer.