FDA's Expanded Access: From Laetrile to Right to Try, Ethical Debates Over Early Drug Access

Christopher T. Robertson, JD, PhD, reviewed the history and ethical landscape of providing access to drugs before FDA approval, highlighting the crucial role of clinical trials and ethical safeguards at the 2025 Festival of Biologics USA. | Image Credit: wladimir1804 - stock.adobe.com

Despite a high approval rate for expanded access requests, the history of preapproval drug access underscores the critical importance of rigorous clinical trials and ethical considerations, advocating for a "proof-before-profit" approach to drug availability, according to Christopher T. Robertson, JD, PhD, professor at Boston University school of law.

Robertson spoke at the 2025 Festival of Biologics USA about the law and ethics of providing access to drugs before FDA approval, highlighting the FDA’s multistep process of proving drug safety and efficacy.

In the 1960s and 1970s, marketers presented laetrile to address the widespread cancer crisis, but the FDA rejected its approval, leading 27 states to attempt to legalize it. In 1979, United States v Rutherford, a case argued before the Supreme Court, saw patients with terminal cancer and their spouses argue against government interference in the sale of laetrile.

Ultimately, the active ingredient in laetrile, cyanide, cannot cure cancer. Robertson explained that critics have called the drug "the slickest, most sophisticated and certainly the most remunerative cancer quack promotion in medical history."

The FDA then decided to formalize and issue regulations, thus creating the expanded access program (EAP). This program enables patients with serious or life-threatening conditions to access investigational drugs or medical devices outside of clinical trials.

Robertson further highlighted that although many believe the FDA's purpose is to protect people from unsafe drugs, the Supreme Court decision and modern thinking about the FDA implicitly reveal its true purpose: to produce knowledge and largely solve the collective action problem of determining drug safety and effectiveness.

Additionally, the FDA responded to the AIDS crisis by making more drugs available through compassionate use. For example, in 2008, Abigail Alliance v Eisenstadt introduced constitutional questions about patients with terminal illnesses and their rights to override the FDA. In the end, the court ruled that states have regulated drugs since the 1700s and the federal government has done so since the 1840s, and it was unwilling to change this.

“One reason it's worth lingering on now, though, is the Supreme Court we have today is not a real big fan of unenumerated rights unless it speaks to a different political priority, so you may well see a case like this come back in another way,” Robertson stated.

In 2016, the 21st Century Cures Act declared that companies must have a policy on expanded access. However, challenges hinder access to drugs before approval, and companies often refuse to provide the medications. Robinson explored the potential benefits of providing preapproval access, such as gaining perspective from key opinion leaders and producing real-world data.

The Right to Try Act of 2017 allows patients with terminal illnesses to access drugs that have cleared phase 1 investigations but have not received FDA approval. This act prohibits the FDA from using data on these patients' outcomes and does not require their review, potentially immunizing physician and company negligence.

Physicians can request access from manufacturers during or after phases 1, 2, or 3 of clinical trials for patients to gain access through the EAP. The federal Right to Try Act grants patients access through physicians who can request access from manufacturers after phase 1 is completed and during or after phase 2 or 3 of clinical trials.

Robinson explained that if a company provides a product with a limited supply, the question arises: who receives it? Who should be prioritized? Who will gain the most benefit?

“Ultimately, the basic principles are proof before profit, prioritizing clinical trials to get the evidence so you can actually help more people in the end, and make sure there's reasonable risks, and informed consent,” Robinson concluded.

Reference

Robertson CT. Law and ethics of providing access to drugs before FDA approval. Presented at: Festival of Biologics USA; April 23-24, 2025; San Diego, CA.