Bradley v. Weinberger, 73-1014.

• Decision Date: 31 July 1973
• Docket Number: No. 73-1014.,73-1014.
• Citation: 483 F.2d 410
• Parties: Robert F. BRADLEY et al., Plaintiffs-Appellees, v. Caspar W. WEINBERGER, Secretary of Health, Education and Welfare, et al., Defendants-Appellants.
• Court: U.S. Court of Appeals — First Circuit

483 F.2d 410 (1973)

Robert F. BRADLEY et al., Plaintiffs-Appellees, v. Caspar W. WEINBERGER, Secretary of Health, Education and Welfare, et al., Defendants-Appellants.

No. 73-1014.

United States Court of Appeals, First Circuit.

Heard and Argued June 5, 1973.

Decided July 31, 1973.

William A. Brown, Asst. U.S. Atty., with whom James N. Gabriel, U.S. Atty., Boston, Mass., Thomas E. Kauper, Asst. Atty. Gen., Anti-Trust Div., George Edelstein, Atty., Dept. of Justice, Peter Barton Hunt, Asst. Gen. Counsel, Joanne S. Sisik, Chief, App. and Sp. Proceedings Branch, and Arthur N. Levine, Atty., Food, Drugs, and Produce Safety Div., U.S. Dept. of Health, Ed. and Welfare, Washington, D.C., were on brief, for defendants-appellants.

Neil L. Chayet, Boston, Mass., with whom Harvey W. Freishtat, and Chayet & Sonnenreich, Boston, Mass., were on brief, for Robert F. Bradley and others, plaintiffs-appellees.

Before COFFIN, Chief Judge, and ALDRICH and McENTEE, Circuit Judges.

COFFIN, Chief Judge.

Plaintiffs, 178 physicians who treat diabetes and one diabetes patient who use oral hypoglycemic agents to control the disease by lowering the blood sugar level, brought suit to enjoin the defendants Secretary of Health, Education and Welfare and the Commissioner of the Food and Drug Administration (FDA) from enforcing and the defendant drug companies from complying with the FDA's proposal for altering the labeling of those drugs. The district court granted a preliminary injunction, being persuaded that there was a reasonable likelihood of success in showing that the FDA had failed to comply with the statutes and its own regulation requiring that under some circumstances labeling make reference to the existence of a serious medical controversy. We vacate the injunction for reasons important to the proper judicial role in reviewing administrative actions.

This controversy revolves around a long-term, federally funded study undertaken by the University Group Diabetes Program (hereafter the UGDP study) to determine the effects of oral hypoglycemic agents on vascular complications in patients with adult-onset diabetes. The study, involving twelve clinics and 1200 patients, consisted of four treatment groups: diet alone, diet plus regular insulin doses, diet plus varying insulin doses and diet plus fixed doses of either tolbutamide or phenformin (two hypoglycemic agents). After monitoring the patients for from five to eight years, the study concluded that the combination of diet and either tolbutamide or phenformin was no more effective than diet alone in prolonging life but that those oral agents might be more hazardous than diet or diet plus insulin insofar as cardiovascular mortality was concerned. The latter conclusion, which led the investigators to discontinue use of the agents in the study as an unethical risk, was based on findings that patients treated with the two agents used in the study suffered more than twice as many cardiovascular deaths than patients receiving the other treatments.

After the study received much publicity and criticism, the FDA convened an ad hoc committee of experts on May 21, 1970 to evaluate the study's findings and the following day issued a press release agreeing with the UGDP study's conclusions and indicating that the agency would require labeling changes to reflect those views. After more extensive evaluation, the FDA concluded that protection of the public required a strong warning to physicians recommending use of an oral agent only if other treatments were inadvisable and noting the UGDP's findings regarding the apparently increased danger of cardiovascular mortality. This evaluation and proposed labeling change was first formally published in the FDA Drug Bulletin of June, 1971.

On October 7, 1971, the Committee on the Care of the Diabetic, consisting of eminent doctors and experts in the field including some of the plaintiff doctors, submitted through its counsel a petition to the FDA. It asked the FDA to rescind its labeling recommendation, insure that all future FDA comments on the UGDP study include references to its alleged deficiencies and controversial nature, provide petitioners with the complete raw data of the study, and, "in accord with its policy of fair balance", disseminate with equal emphasis and frequency studies and individual expert opinions differing with the study. The petition was accompanied by a detailed scientific critique of the UGDP study and some 250 pages of scientific studies, papers and comments illustrating the nature and extent of the opposition viewpoint. The study was primarily criticized for inadequate patient selection controls and use of fixed, rather than variable, doses of the drugs, contrary to allegedly accepted medical practice. The FDA proposal was attached for extending the study's findings to all oral agents and patients despite the study's own warning that such extrapolation could not be made on a statistical basis. The petition also referred to two smaller studies which indicated no cardiovascular complications from oral agents. It was supplemented in January, 1972, by another 220 pages of scientific materials.

In the May, 1972, Drug Bulletin, the FDA published the "Final Labeling Approved For Oral Hypoglycemic Drugs", which proposed changes in the "indications" section of the label and the addition of a "special warning" section. The proposal speaks of "the increased cardiovascular hazard which appears to be associated with oral hypoglycemic agents", notes that the UGDP study was the basis for the change, recites its findings, states that these conclusions apply to all oral agents, not just those employed in the study, and ends with the comment that "Further studies are being undertaken to shed additional light on the role" of the oral agents. On June 5, 1972, the Commissioner formally replied to the Committee's position with an eleven-page, single-space letter addressing generally the legal and medical issues and with a 100 page appendix dealing specifically with the scientific criticisms of the study, criticizing the two contrary studies referred to by the petition, and appending the comments of major medical groups and various scientific papers supportive of the FDA's position. The Committee's counsel responded on July 13 with a four-page letter suggesting that the FDA's label might constitute misbranding in violation of two cited statutes, that this was one of the "rare cases" suggested by the Commissioner in which "substantial evidence" exists on both sides of an issue, making appropriate reflection of the controversy in the package insert. Counsel requested a formal evidentiary hearing, a stay of any further action pending final resolution, and the full patient records from the study. The Commissioner's response of August 3 stated that the petitioners were not entitled to a hearing and that only clinical studies were substantial evidence of drug effectiveness. He concluded by saying that, "we do not contend that you do not have standing either to prosecute your peition sic or to pursue an appeal to the courts" and that his two letters constituted final agency action reviewable by the courts pursuant to the Administrative Procedure Act.

This suit was filed on August 11, 1972 and a temporary restraining order issued that day. After a hearing and submission of affidavits of experts by both sides, the emergency district judge denied the preliminary injunction on August 30, finding that whatever irreparable injury might be suffered by the plaintiffs did not outweigh that suffered by the public represented by the defendants and that the plaintiffs had not demonstrated "a reasonable probability" of showing that the FDA's decision to require the warning was arbitrary or capricious. A second motion for a preliminary injunction was denied on September 21 by the judge to whom the case was permanently assigned because no new evidence or amendment of the complaint had been presented.

On October 17, 1972, the litigation entered an entirely new phase. On that date, plaintiffs filed a motion for leave to amend their complaint, supported by 13 affidavits by diabetes experts attesting to the controversy over the UGDP study, and new motions for a temporary restraining order and a preliminary injunction. The motions presented for the first time the argument that the FDA's proposed label was itself misleading and thus rendered the drug misbranded in violation of the statute, because it failed to reveal the existence of a "material weight of contrary opinion" among "experts qualified by scientific training and experience" as allegedly required by the agency's own regulation, 21 C.F.R. § 1.3. After oral argument, at which plaintiffs' counsel admitted this was an unprecedented case, being brought by the doctors and seeking to apply that regulation to the agency's own labeling recommendation, the district court in a Memorandum and Order granted on November 3, 1972, the motions to amend the complaint and for a preliminary injunction. It noted that "The application for preliminary injunction was heard on the affidavits filed by plaintiffs and defendants, and their arguments both oral and written" and stated that "the court is satisfied plaintiffs have made a showing that there is reasonable likelihood upon a full hearing on the merits they would be successful in establishing the defendants . . . have not in the order described in the May 1972 Bulletin complied with 21 C.F.R. § 1.3.; 21 U.S.C. § 321(n) and 21 U.S.C. § 352(a).", and that "there is absent an injunction a likelihood of irreparable injury to the plaintiffs" greater than would be visited upon the defendants by such relief.

The district court had jurisdiction to review the administrative action under the Administrative Procedure Act (APA), 5 U.S.C. § 704, because it was "final agency action for which there is no other adequate remedy in a court." See Abbott Laboratories v. Gardner, 387 U.S....