The Food and Drug Administration's (FDA) Expanded Access Program (EAP) and the federal Right to Try (RTT) Act both increase patients' access to drugs and devices that have not yet been approved by the FDA. While the EAP has been in use for decades, the RTT law passed in 2018. It was applauded by many patients seeking experimental treatment. Each of these programs offers hope to patients who face serious or terminal illnesses — however, patients are not guaranteed acceptance.
These two programs entered the limelight in 2020, as the FDA issued Emergency Use Authorizations (EUAs) for experimental drugs and vaccines during the COVID-19 pandemic. An EUA is similar to EAP, but it is used for large-scale public health emergencies. Some patients and physicians called for access to already FDA-approved drugs for treatment or prophylaxis during the pandemic under the RTT law; however, this program also only applies to drugs that are not FDA approved.
If a patient asks about participating in a clinical trial or accessing an experimental treatment, OB/GYNs and other physicians should be well-informed and prepared to discuss both the benefits and drawbacks.
Understanding Drug Trial Phases
The American Cancer Society describes the different phases of drug studies as follows:
- Phase I trials determine whether a treatment is safe. Very few participants are enrolled and may be given different doses to see how participants react to the drug. Phase 1 trials do not determine whether a medication works.
- Phase II trials enroll more patients and determine whether the medication works in the way it was intended (efficacy) while assessing its safety for a second time.
- Phase III trials enroll even more participants. This phase often compares the study drug with an existing treatment or a placebo.
- Phase IV trials involve medications that have received FDA approval but are still being monitored for long-term safety. These drugs are approved for the market and can be prescribed.
Many drugs that pass Phases I and II may never reach Phase III trials because they are found to be unsafe or simply do not work as intended. Additionally, clinical trials have strict inclusion and exclusion criteria which may not allow for participants who have specific medical conditions. Trials often exclude potential participants who have comorbidities or a short life expectancy, because side effects and deaths are highly scrutinized in the FDA's consideration of whether to allow a study to continue. Right to Try advocates are often critical of the EAP for this very reason.
What Expanded Access and Right To Try Have in Common
Both programs require that a licensed physician participates in the process of seeking an experimental treatment for a patient facing a life-threatening condition for which no alternative treatments are available. Each program also requires that the patient be ineligible for an ongoing clinical trial. In both cases, patients must provide informed consent, the current drug trial must be ongoing and the sponsor/manufacturer must agree to provide the drug.
The RTT law allows patients access to therapies that have passed Phase I trials, but EAP is not specific about which phase experimental treatments must be in. Expanded access requires that both an Institutional Review Board and the FDA approve the individual's use of a treatment. The EAP also specifies that the individual's access "will not interfere with investigational trials that could support a medical product's development or marketing approval for the treatment indication." This is a broad disqualifier—it includes many factors, including the patient's condition, life expectancy or a limited amount of available medication.
While patients may be willing to enroll in drug studies, they may not meet eligibility criteria or may simply be unable to travel to the study site. According to Hospital Pharmacy, some patients are also hesitant to enroll in a clinical trial that involves randomization to treatment or placebo, fearing they will be placed in the placebo group.
Costs for the Patient
Under both EAP and RTT, the patient may be responsible for both the costs of the experimental drug and the associated care. The FDA states that Medicare or other third parties sometimes cover the costs of EAP treatments. However, patients should be warned that this is unlikely.
While there are ways that physicians can reduce patient costs, patients who need to be monitored more closely during an experimental treatment may find the cost itself to be a limiting factor. The FDA limits costs that can be charged by the manufacturer or sponsor under EAP to those which are justifiable and "limited to those necessary to recover costs of manufacture, research, development and handling."
The Physician's Role
The first step in this process, regardless of whether the patient wishes to access a drug under EAP or RTT, is to approach the drug manufacturer. Many pharmaceutical companies have boards that review these requests under EAP. The Right to Try advocacy website offers a form letter that can be modified for these requests.
A licensed physician must assist the patient in the FDA's expanded access process. The physician's responsibilities include:
- Ensuring that the patient is not eligible for another clinical trial by searching the FDA's website or ClinicalTrials.gov
- Determining that the patient qualifies for EA, and that either they have exhausted other treatments or available treatments have not worked
- Determining the type of request to submit
- Speaking with a representative from the product's sponsor to see if they will allow the patient to access their drug through the EAP program
- Completing necessary documentation and review, which includes obtaining informed consent, having the patient's participation reviewed through an Institutional Review Board (IRB) and reporting to the FDA
- Managing the patient's treatment and monitoring their health through lab work, ultrasound or MRI imaging, and reporting adverse effects to the FDA
Under RTT, the only role outlined for a licensed physician is certifying the patient's eligibility and obtaining written informed consent. The patient's participation does not have to be approved by the FDA or an IRB unless you work for a clinical institution that requires it. This also means that the physician will not have to report adverse effects to either of these bodies. The manufacturer is required to notify the FDA that an experimental use was granted under the law.
Health Affairs states that the FDA declines less than 1 percent of requests under EAP and usually approves applications within days. However, it argues that the RTT law does not remove patients' barriers to care, such as the costs associated with treatment and the willingness of pharmaceutical companies to provide medication.
Currently, neither EAP nor RTT offers an easy path to treatment, especially for a patient whose options are limited. The regulatory burden appears to be greater through the EAP, but patients who are granted access through the EAP are offered more protection from potential harms since there is outside oversight.
These patients also contribute to the overall drug development as a whole—being part of a clinical trial helps establish that appropriate treatments are safe and effective, helping more people in the future.
