Today’s Food and Drug Administration (FDA) expanded access pathway has its roots in a 1970s decision to make investigational new drugs (INDs) available to some cancer patients who did not qualify for clinical trials. Although no official policy was enacted, FDA allowed the National Cancer Institute (NCI) to distribute “Group C” drugs to oncologists to treat cancer under protocols outside controlled clinical trials.

Central to the Group C drugs program were two principles—compassion and safety—that have guided FDA access to experimental medications ever since. FDA recognized the extreme circumstances of the cancer patients involved and responded. Equally important, FDA established the use of “treatment INDs” to provide access to experimental products without subjecting patients to undue risk.

That continued emphasis on safety is the key difference between the FDA expanded access pathway and the newer pathway created by recent national right-to-try legislation.

Responding to new and changing needs

In the 1980s, treatment INDs enabled dying AIDS patients, who were unable to participate in clinical trials, to access drugs that were still in development. By 1987, FDA established an official treatment IND regulatory pathway for this type of use and to make drugs available during the period between the completion of trials and marketing approval by FDA. While treatment INDs typically were used for large groups of patients, the FDA regulation also opened the way for individual patients in immediately life-threatening situations to seek access to experimental treatments when no other therapy was available.

Although FDA created the treatment IND and single patient pathways, for the most part, the decision to provide the investigational medicine lay primarily with the drug manufacturer. That remains the case today—for both the FDA and right-to-try pathways.

The most recent change to FDA regulations regarding experimental treatments came in 2009, when the agency created a new subpart in the Code of Federal Regulations (21 CFR 312 Subpart I). The change codified the two categories of access—for large populations (treatment INDs) and individual patients—and added another category, “intermediate patient population IND,” for smaller groups of patients. Subpart I consolidated all criteria and requirements related to treatment use of investigational products outside clinical trials and called this type of access “expanded access.”

A track record of approving requests

Over the years, use of these expanded access pathways has grown, and FDA has been very flexible in approving requests for access to drugs that are still in development. Because one of the first steps of the expanded access process is to ask the drug developer to make the investigational medication available, requests are essentially vetted by these companies before reaching FDA. In cases where the drug company approves the request, FDA allows more than 99 percent to proceed.

Safety remains a concern and a priority. How do you provide access to patients who have no other treatment alternatives without promoting unapproved products that have not been fully tested and proven to provide benefits that outweigh potential risks?

Expanded access decisions are based on likely benefits as demonstrated by clinical trials. Out of compassion for desperately ill patients, FDA tends to permit access to potential treatments at all stages of development. To help safeguard patients, FDA considers evidence of effectiveness, available safety data from animal studies and clinical trials, and the underlying risk posed by the disease or condition. FDA also requires informed consent so that patients understand that the product is not approved, that there are unknowns related to its use, and that they are agreeing to accept the added risks associated with an investigational product.

More flexible than right-to-try

The right-to-try movement began with claims that, despite FDA’s track record of approvals, the agency was a barrier to access. Proponents of right-to-try argued that desperately ill patients had to beg the government to try “lifesaving” investigational drugs. In fact, while some investigational products may be lifesaving, most are not. And some may do more harm than good.

Currently, 41 states have right-to-try laws that vary from state to state and cause confusion about patient benefits and protections. In May 2018, Congress passed national right-to-try legislation that creates an alternate pathway to the FDA process.

The legislation gives the impression that the right-to-try pathway provides more flexibility for patients. The truth is that right-to-try is more restrictive than the FDA pathway. Right-to-try allows access only to drugs actively under development for life-threatening illnesses—and only after a phase 1 study has been completed.

FDA’s pathway can provide access to promising drugs regardless of whether they are actively under development. If a drug manufacturer is willing to make its product available, access is possible at any point in the life cycle of the drug and even to certain drugs not in active development. FDA decisions are based on benefit/risk determinations and evidence that proper patient monitoring and protections are in place.

Proponents of right-to-try have done a disservice to patient communities on multiple fronts:

  • By promising a right that patients don’t have to unapproved drugs.
  • By suggesting that the process is solely in the hands of the treating physician and the patient.
  • By creating the belief that drugs in development are better or more effective than drugs already available.
  • And by compromising protections for patients by specifying no required elements for informed consent and removing oversight by the institutional review board (IRB) that plays an important role in ensuring that risks of treatment to the patient are minimized.

Patients deserve better—and for years they’ve been able to find it via FDA’s expanded access pathway.

An authority on expanded access, Richard Klein is the former director of the FDA’s Patient Liaison Program in the Office of Health and Constituent Affairs.