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Abigail Alliance Sues FDA to Allow Access to Investigational Drugs after Phase I Trials: ASCO, NCCS, AAMC File Amicus Brief

Fromer, Margot J.

doi: 10.1097/01.COT.0000267777.50071.4f
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In a precedent-setting case, the Abigail Alliance for Better Access to Developmental Drugs, an advocacy group in Fredericksburg, Virginia, headed by Frank Burroughs, whose daughter died of head and neck cancer at age 21, is suing the Food and Drug Alliance. The organization claims that terminally ill patients have a right to investigational drugs after Phase I trials—i.e., after only Phase I.

The crux of the issue is that Abigail Alliance contends that FDA, in denying access to Phase I drugs, has not struck the right balance between patients' rights and safety. The group argues that patients who are terminally ill and have no other treatment options face a unique risk-benefit ratio, and that delay can be fatal.

The Alliance says that patients “should have the ability to opt for a new treatment that has met a lower evidentiary hurdle with respect to safety and efficacy.” Also requested is that FDA allow early access based on “the risk of illness, injury, or death from the disease in the absence of the drug.”

The outcome of the case, especially if it is decided in favor of Abigail Alliance, could change forever the process of drug testing.

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Background

A three-judge panel heard arguments on October 21, 2005, and decided in favor of Abigail Alliance on May 2, 2006, thus reversing the decision of a lower court. The three were Chief Judge Douglas H. Ginsburg, Circuit Judge Judith Ann Wilson Rogers, and Circuit Judge Thomas B. Griffith.

The Alliance had sought to enjoin FDA from barring the sale of investigational drugs to terminally ill cancer patients after only Phase I trials. The contention was that FDA policy violates the Constitutional right to privacy and that the due process clause protects the right of terminally ill patients to decide, without FDA interference, whether to assume the risks of unapproved drugs.

The Alliance also maintained that only very few patients are enrolled in Phase II and Phase III clinical trials because, the group said, spaces are limited and enrollment criteria are exclusionary. All other patients are doomed to their fate, the Alliance says.

During the lower court hearing, the Alliance claimed recognition and enforcement of the right to life, translating this to the right to medical treatment—despite the fact that the law does not permit FDA to make drugs available after Phase I trials—except to patients enrolled in Phase II studies.

The Alliance acknowledged that the safety and efficacy of the drugs it sought are still in question, but it asked that the decision to assume such risks be left to the patient.

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Majority Opinion

Judge Rogers wrote the opinion for the majority, saying that the lower court had erred in dismissing the Alliance's complaint for three reasons:

  • ▪ First, because patients, upon the advice of a physician, have a right to potentially life-saving experimental drugs even when the drug carries risks.
  • ▪ Second, because throughout most of the nation's history, government has not blocked access to these drugs. It has done so only recently.
  • ▪ Third, because Supreme Court precedent holds that an individual has a due process right to refuse treatment. The Alliance's claim is similar but with the opposite effect. “In both instances, the key is the patient's right to make the decision about her life free from government interference.”

Judge Rogers acknowledged that there is no due process right of access to potentially life-saving treatment, but government's interest in regulating drugs has no bearing on the issue. “Rather, its interest is to be considered only after a court recognizes a fundamental right. Then the burden shifts to government to demonstrate a narrowly tailored ‘compelling interest’ in that right.”

In other words, the Alliance seeks the same access to experimental drugs as those “lucky enough to secure a spot in Phase II trials.” Therefore, the majority determined that if a drug is safe enough for Phase II trials, it is safe enough for a competent adult if he or she has no alternative treatment.

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Dissenting Opinion

Judge Griffith asserted that there is no evidence in American history of a right to experimental drugs, and that Abigail Alliance could have petitioned Congress, which regulates FDA and which “could strike a new balance between the need for understanding the toxicity and potential benefits of experimental drugs.”

In addition, he said, the Alliance could have worked with FDA to help expand access to promising new drugs beyond the programs now in existence.

Regarding the due process claim, Judge Griffith said, “The Alliance's proposed new constitutional right would exempt terminally ill patients from much of the legislative and regulatory approval process created by Congress and the FDA.”

Judge Griffith noted that FDA agreed that the Alliance raised important issues, but questioned whether the proposal would have the intended salutary effect on patients. He also said that the two other judges provided no evidence that the Alliance's asserted right has any place in American tradition, and it fails because it is not deeply rooted in liberty and other principles.

Moreover, “there is a tradition of courts rejecting arguments that the Constitution provides an affirmative right of access to particular medical treatments reasonably prohibited by the government.”

He dissented from the majority decision for two reasons, he wrote: First, the Alliance failed to present objective evidence establishing a deeply rooted right to experimental drugs; and second, FDA has a rational basis for ensuring that there is scientifically and medically acceptable evidence about the risks and benefits of such a drug.

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Amicus Briefs from (1) ASCO, NCCS, & AAMC; and (2) Drs. Emil Freireich & Stephen Strum

Prior to the March 1 hearing, two amicus curiae briefs were filed. The first, in support of FDA, was from three major organizations: ASCO, the National Coalition for Cancer Survivorship (NCCS), and the Association of American Medical Colleges (AAMC).

The other, in support of Abigail Alliance, was filed by two oncologists, Emil J. Freireich, MD, Professor, Executive Vice President, and Chief Academic Officer of the University of Texas M. D. Anderson Cancer Center; and Stephen Strum, MD, a private practitioner in Ashland, Oregon, who specializes in prostate cancer (and who had a poem published in OT's poetry column in 2005).

The first brief said that ASCO and its colleagues feel strongly that the right claimed by Abigail Alliance would pose substantial risk, not only to individual patients, but also to the entire clinical trial enterprise.

“Phase I data are not sufficient to establish the safety of new drugs, much less their efficacy. Moreover, we are concerned that access to unapproved drugs outside of clinical trials will deter trial participation. The Alliance position also would result in the commercialization of drugs with little or no evidence of their safety or clinical benefit, thus posing challenges to reimbursement for cancer therapy, as well as the risk of liability claims for treatments that prove excessively toxic or completely ineffective.”

In addition to the foregoing, the ASCO et al brief made the following points:

  • ▪ For the first time, drug companies would be permitted to profit from the sale of unproven therapies, thus making them less likely to move their drug through the clinical trial process.
  • ▪ FDA has long provided compassionate-use access to individual patients with no other treatment alternatives, and this past December it proposed a greatly widened and deepened program.
  • ▪ Abigail Alliance's lawsuit seeks to undermine FDA's drug-approval process. Moreover, there is no Constitutional right that guarantees “unfettered access to unproven drugs.”

In an interview ASCO EVP and CEO Allen S. Lichter, MD, noted that statistics show that only about 5% of drugs that pass through Phase I eventually reach the commercial market.

“We believe that Abigail Alliance and others have mistakenly assumed that a drug that has been through Phase I has been proven safe,” he said. That's just not so. A dose has been selected that can be further tested, but that doesn't mean the drug is safe. And it certainly doesn't mean the drug is effective.

“The clinical trials process is slow,” Dr. Lichter continued. We know that, but it has proved over time to be the best way to test drugs for safety and efficacy. Now there is a potential to degrade the process, which would affect tens of thousands of people. We also are afraid that purveyors of unproven drugs would peddle false hope to desperate people.

“Abigail Alliance means well, but they are espousing an obviously dangerous position that could create a scenario that is very, very frightening—not just for cancer patients but for those with other serious illnesses as well. That's why AAMC joined us and NCCS in the amicus brief.”

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Opposing the Brief

In the other brief, Drs. Freireich and Strum said that FDA “too often ‘protects’ the public from potentially beneficial treatments that could prolong or save their lives.”

In an interview, Dr. Freireich expressed that view even more strongly: “ASCO is an organization of 25,000 oncologists, and it should come down on the side of cancer patients, not FDA. This is sad—No, it's tragic.”

The brief went on to contend that the number of applicants for cancer trials significantly exceeds the number of available spaces, and that trials are designed with strict selection criteria. For these and other reasons, Drs. Freireich and Strum said, many terminally ill patients have no access to drugs that could be life saving.

The oncologists acknowledge that FDA has recently expanded access to trials—“Yet in practice these programs provide no hope for many terminally ill cancer patients.”

When OT asked Dr. Strum why he added his name to the brief, he replied, “The Abigail suit is the closest thing I want for patients, which is for FDA to provide some type of interim approval after Phase I.”

He did acknowledge that the law does not allow this: “A lot of people are dying because of the law. I'm just trying to jar the conservative stance of FDA.”

Dr. Freireich is angry at the agency. “Decisions about drug approval are in the hands of people who are not well trained; they're not experts, they have no achievements,” he said. They are far less expert than I am.

“FDA may know something about safety, but the only people who know anything at all about efficacy are those doing the research.” He added that FDA has become the oncologist of last resort, overriding the training and experience of practicing physicians.

The two physicians made several other points in their brief:

  • ▪ The clinical trial industry is big business with strong influence over FDA.
  • ▪ Access to Phase I drugs would be good public policy.
  • ▪ The biggest risk to the safety of terminally ill patients is getting no treatment at all. “The real issue is whether terminally ill patients not fortunate enough to participate in clinical trials will have the same chance for lifesaving drugs as those in trials.”
  • ▪ FDA seeks to sacrifice the lives of terminally ill patients in the interest of compelling participation in clinical trials by denying other options.
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Hearing En Banc

On March 1, the full DC Circuit heard the appeal. Arguing for the Alliance was James Scott Ballenger of the law firm Latham and Watkins in Washington, and for FDA. Jonathan F. Cohn of the US Department of Justice. Neither attorney was a match for the penetrating and insightful questions that flew off the bench from the outset of argument.

The case hinged on the question of whether access to post-Phase I investigational drugs is a fundamental right guaranteed by the Constitution.

“The case will be won or lost on that question,” said Sam Turner of the law firm Turner & Goss, LLP in Washington, DC, who represents both ASCO and NCCS. “FDA maintains that it is not, and I agree. It is not guaranteed in the Constitution, nor is there precedent in case law.”

Judge David S. Tatel said from the bench that this cannot be considered a fundamental right—i.e., one deeply rooted in American law and tradition—because too few people could claim it, and the drugs and situations in question are so new.

Mr. Cohn and Mr. Ballenger used a variety of analogies in their arguments (self-defense and the right to abortion, for instance), which the judges overruled as irrelevant. “Get beyond analogy and stick with the facts,” Judge Griffith snapped.

OT asked Mr. Turner if he thought the judges had a good grasp of the case. “Yes,” he replied immediately. “They were well versed in the issues—on top of the facts and very knowledgeable about the relevant case law. It's good to have the judges ask as many questions as they did because it shows they are interested and engaged.”

Mr. Burroughs agreed: “I thought the arguments were good, and the judges asked tough but penetrating questions.”

Mr. Turner noted that a majority of the DC Circuit judges were dissatisfied with the decision of the three-judge panel, which is why it was heard enbanc—i.e., by all judges. “Most seemed to be leaning toward the FDA position, which is significant.”

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‘Too Close to Call’

Mr. Burroughs said he felt sympathy from some of the judges but acknowledged that the decision is too close to call. “One thing about all this,” he said, “is that the case has elevated the issue. It has brought the problem of terminally ill patients being denied potentially lifesaving drugs into the public eye and has taught people a lot about clinical trials.”

The entire appeal lasted just over an hour. The decision could take several months, and a number of things could happen. If the DC Circuit finds in favor of Abigail Alliance, FDA will almost certainly appeal to the Supreme Court, Mr. Turner said, and the high court will probably hear it. If FDA wins, Mr. Burroughs said that the Alliance will definitely take it up a step.

In the event of a tie, the decision reverts to that of the District Court where it was first tried, which had found in favor of FDA.

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The Unique Status of the DC Circuit Court of Appeals

The US Court of Appeals for the District of Columbia Circuit, known informally as the DC Circuit, is a federal appellate court. It is the smallest of the 12 circuits in the country but probably the most important because it reviews decisions involving many federal agencies, including the Food and Drug Administration.

The Court has 12 judgeships, two of which are vacant. A judgeship on the DC Circuit is often thought of as a stepping stone to the Supreme Court (John Roberts, Antonin Scalia, Clarence Thomas, and Ruth Bader Ginsburg all first served on the DC Circuit), which adds to its judicial and political luster.

In general, three judges decide cases for the DC Circuit. Most cases go no further. However, the Court, solely at its discretion—and rarely—can decide to re-hear the decision of a three-judge panel en banc—that is, by all judges.

© 2007 Lippincott Williams & Wilkins, Inc.
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