Appeals Court Finds Right to Post-Phase I Investigational New Drugs; Makes Controversial Comments about Off-Label Use and Promotion

May 5, 2006

On May 2, 2006, the United States Court of Appeals for the District of Columbia Circuit concluded in a two-to-one ruling that mentally competent, terminally ill adult patients have the right to obtain potentially life-saving investigational new drugs that FDA has determined, based on Phase I clinical trials, are sufficiently safe for expanded human trials. The D.C. Circuit determined that this right is protected by the Due Process Clause of the U.S. Constitution.

In 2003, the Abigail Alliance for Better Access to Developmental Drugs (the “Alliance”) and the Washington Legal Foundation sued FDA and HHS in the United States District Court for the District of Columbia to enjoin FDA from enforcing its policy that bars the sale of post-Phase I investigational new drugs to patients who are not enrolled in Phase II clinical trials. This lawsuit was the Alliance’s third attempt to assist mentally competent, terminally ill adult patients with no alternative government-approved treatment options to obtain access to such drugs. The Alliance had previously submitted a proposal to FDA for new regulations that would make post-Phase I investigational new drugs available to terminally ill patients who were not admitted to clinical trials. Upon FDA’s rejection of this proposal, the Alliance submitted a Citizen Petition challenging the agency’s policy. FDA failed to respond to the Citizen Petition.

According to the Alliance, keeping drugs that FDA has “determined” after Phase I clinical trials to be safe from mentally competent, terminally ill adult patients violates these patients’ rights to privacy, liberty, and life – substantive due process rights. The Alliance argued that spaces in Phase II clinical trials are limited, and that not all terminally ill patients who would like access to experimental drugs can enroll. Additionally, they asserted that FDA’s “compassionate use” programs – which permit drug companies to provide new drugs at cost during the pre-approval period – are available to only a fraction of the patients wanting such treatments. The Alliance emphasized that many patients with no government-approved treatment options are willing to assume the risks of drugs that have not yet been proven to be effective through Phase II clinical trials, and that the decision to assume known and unknown risks should be left to the terminally ill patient.

The district court dismissed the Alliance’s complaint, stating that the Alliance failed to state a valid claim. According to the district court, no court has “extended the Due Process Clause to cover a terminally ill patient’s right to receive medical treatment.”

On appeal, the D.C. Circuit held that the district court erred in dismissing the Alliance’s complaint, and held that the right of a mentally competent, terminally ill adult patient to use potentially life-saving medication that is available to patients who are enrolled in Phase II clinical trials is “an individual liberty deeply rooted in our Nation’s history and tradition of self-preservation.” According to the D.C. Circuit, for over half of our nation’s history, people could obtain new drugs without government interference. The court also stated that for many years after the enactment of the Federal Food, Drug, and Cosmetic Act, the government only regulated drugs based on safety; “[g]overnment regulation of drugs premised on concern over a new drug’s efficacy, as opposed to its safety, is of recent origin.”

The D.C. Circuit’s historical analysis of government regulation of drugs also included interesting and controversial statements about off-label use and promotion of drugs. In justifying access to drugs that have been deemed to be safe through a Phase I clinical trial, the D.C. Circuit stated that “even today, a patient may use a drug for unapproved purposes even where the drug may be unsafe or ineffective for the off-label purpose.” According to the D.C. Circuit, “it appears that FDA has never prohibited either off-label prescription or off-label use of drugs” and “[i]n recent years, the FDA has been moving to permit drug manufacturers to promote the use of their drugs for off-label purposes in limited circumstances.”

Based on this view of the history of drug regulation, the D.C. Circuit concluded that access by mentally competent, terminally ill adult patients to post-Phase I investigational new drugs is protected under the Due Process Clause. The D.C. Circuit remanded the case to the district court to determine whether FDA’s policy barring access to post-Phase I investigational new drugs by terminally ill patients is narrowly tailored to serve a valid government interest.

Alternatively, it is quite likely that FDA will seek to block future proceedings in the district court. FDA can, within forty-five days: (1) ask the three judges on the D.C. Circuit who heard the case to reconsider their decision and/or (2) ask those judges and the other members of the D.C. Circuit to overturn the three-judge decision. In addition, FDA may seek Supreme Court review of the decision, assuming that the D.C. Circuit does not change its mind.

Additional information available here.