Expanded Access Versus Right to Try: Two Doors to an Unapproved Drug

When your approved treatments have run out and no clinical trial fits, United States law still leaves two doors open to an investigational drug: FDA Expanded Access (long known as compassionate use) and the federal Right to Try pathway created in 2018. The doors lead to the same room. What differs is who checks the request on the way in, and when that check happens. Understanding that difference matters to you, because the label on the door says nothing about whether the drug on the other side actually helps.

Key points#

• Both routes require a serious or life-threatening condition, no satisfactory approved therapy, and no suitable trial to join.
• Expanded Access keeps two checks before treatment: an FDA risk and benefit review and an institutional review board (IRB) approval, plus documented informed consent.
• The Right to Try pathway removes those two front-end checks and replaces them with an annual report the manufacturer files after the fact.
• Under either route the drug company can say no. Regulatory permission does not create a supply.
• Neither route is evidence that the drug is safe or effective. An investigational drug is investigational for a reason.

The room both doors open into#

Start with what does not change. Both pathways address the same narrow situation: a person with a serious or immediately life-threatening illness, no satisfactory approved option, and no clinical trial they can enter. In both cases the product involved is investigational, meaning the FDA has not approved it for the use in question. And in both cases there is a gatekeeper who sits behind every regulatory step: the manufacturer.

This is the point most public debate skips. Coverage of access to unapproved drugs tends to frame the obstacle as government permission, as if clearing a regulator were the hard part. In practice the more common wall is the company itself. As a review indexed by the National Library of Medicine describes, a drugmaker is under no legal obligation to hand over an investigational product and may decline a request under either pathway, often because early supply is scarce or the company wants to protect an ongoing trial. The FDA authorizing a request does not compel anyone to fill it. Think of the two routes as different keys to the same locked room, where the manufacturer, not the regulator, owns the lock.

Door one: FDA Expanded Access#

Expanded Access works through an Investigational New Drug (IND) submission to the FDA. For a single patient, the treating physician usually files Form FDA 3926, a form the agency designed to make individual requests simpler. It sets out the diagnosis, a short clinical history, the physician's qualifications, and confirmation that the manufacturer has agreed to provide the drug.

Two independent checks then sit on top of that request. The first is the FDA itself, which weighs whether the possible benefit is worth the possible risk. For a non-emergency individual request, treatment may generally begin 30 days after the agency receives the application, or earlier if the FDA notifies the physician that it may proceed. The second check is an institutional review board. An IRB must review and approve the treatment use, though the rules allow a lighter-weight version for a single patient, in which the IRB chair or a designated member can concur without waiting for a full convened meeting.

Informed consent is not optional here. Because the FDA treats expanded-access use as a clinical investigation, its human-subjects protections apply, and the agency publishes a single-patient consent template that lays out the elements a physician must document. The FDA describes these forms and steps on its Expanded Access submission page. The net effect is that a second clinician-reviewer and an ethics body both see the plan before an unapproved drug is given, and safety information keeps flowing to the agency as treatment continues.

Door two: the federal Right to Try pathway#

The 2018 Right to Try Act built a parallel route that deliberately leaves out those two front-end checks. To qualify, a drug must have completed its first phase of human testing, must not be approved or licensed by the FDA for any use, and must still be in active development, meaning it is tied to an active application or an ongoing trial meant to support approval. When those conditions hold, the patient, physician, and manufacturer can arrange access without sending the request to the FDA beforehand and without IRB review.

Oversight is not gone; it moves from before treatment to after it. Under the framework the FDA sets out on its Right to Try pages, a manufacturer that supplies a drug this way files an annual summary with the agency listing the drug and IND number, how many doses were provided, how many patients were treated, the conditions treated, and any known serious adverse events. Those summaries are due each year on a fixed date and the FDA consolidates them. What is missing, compared with the first door, is the case-by-case federal weighing of risk against benefit and the independent ethics review at the front end.

What "investigational" still means#

Here is the caution both routes share, and it is the one that matters most. Completing the first phase of testing, the bar for Right to Try eligibility, mainly checks early safety and dosing in a small group of people. It says very little about whether the drug works. The published review makes the gap plain by noting how few compounds that enter early human testing ever reach approval. A drug reachable through either door is still investigational precisely because the evidence needed to call it safe and effective does not yet exist.

That framing clarifies the real trade-off. The first door exchanges some speed for two independent checks and continued FDA visibility. The second door exchanges those checks for a more direct arrangement among you, your physician, and the manufacturer. Under either one, you are accepting genuine uncertainty about both benefit and harm, which is exactly why an unhurried, plain-spoken conversation with the treating team carries so much weight.