Investigational Drugs and the Constitution

In May 2006, a federal court of appeals issued a decision with radical implications for U.S. drug regulation. The ruling in Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach expands the terminally ill person's ability to gain access to drugs early in the testing process.¹ If the decision stands, it will restrict significantly the Food and Drug Administration's control over investigational drugs.

The decision was surprising in several respects. The decision itself was a surprise, for the case had previously attracted little national attention. Also, the decision adopted a much broader concept of constitutional rights than did the precedents it relied on, and it reflected a naive impression of drug development.

In these and other respects, the decision departs from the mainstream scientific and ethical understanding of clinical research policy. Indeed, the decision is interesting in that it embraces popular ideas about the miracles that can occur when terminally ill patients gain access to novel agents. It emphasizes the benefits available from early-phase investigational drugs and shows little awareness of the harms early access could produce.

The Abigail Alliance Case

Grass-roots patient advocacy lies at the heart of the case. The events leading to the lawsuit occurred in 2000, when drug companies were testing two new cancer drugs. Many patients not in the trials sought early access to the drugs. The drug companies voluntarily operated a small early access program, but they were unwilling to expand the program to satisfy patient demand.

Abigail Burroughs, a twenty-one-year-old college student, was one of the patients denied admission to the early access program.² After she died, her father founded the Abigail Alliance for Better Access to Developmental Drugs to promote speedier approval of new drugs. With the assistance of the Washington Legal Foundation, a libertarian law and policy center, the Alliance petitioned the FDA to liberalize its early access policies. The FDA denied the request. The Alliance then went to the federal district court, which dismissed the case on grounds that there were no constitutional claims that would justify overturning the FDA denial.

The appellate court was more sympathetic to the Alliance's point of view, however. Two judges on the three-judge panel agreed that terminally ill patients have a constitutional right "to decide, without FDA interference, whether to assume the risks of using potentially lifesaving investigational drugs that the FDA has yet to approve for commercial marketing, but that the FDA has determined, after phase I clinical human trials, are safe enough for further testing."

Existing FDA Policies

Current FDA regulations require three phases of human testing before a drug may be marketed for clinical use. Phase I tests are conducted on twenty to eighty subjects and are designed to measure adverse effects associated with increasing doses of a new agent. The regulations also establish a secondary objective for phase I trials: "if possible, to gain early evidence on effectiveness."

Drugs that appear to produce an acceptable safety profile may then enter phase II testing, which may involve up to several hundred subjects. Here, the goal is "to evaluate the effectiveness of the [new agent] and to determine the common short-term side effects and risks associated with the drug." If there is evidence that the agent produces an acceptable range of potential harms and benefits, the drug sponsor may conduct larger phase III trials. If these trials give acceptable evidence of effectiveness and safety, the sponsor may seek FDA approval for marketing to patients.

Current FDA regulations permit early access in certain situations. The FDA has a "compassionate use" program that allows companies to distribute drugs in voluntary programs, including one that governed access to the drugs Abigail Burroughs tried to obtain. The Accelerated Approval and Fast Track programs represent additional FDA efforts to hasten and expand seriously ill patients' access to new drugs.³ For the Abigail Alliance supporters, however, these programs are insufficient to meet patients' interests.

According to FDA critics, a major problem is the agency's prohibition on commercial marketing of drugs before they are approved for clinical use. The Abigail Alliance wants the FDA...