The Twenty-Five-Year FDA Approval Controversy

Judith Weisz's story of the politics of drug risk management shifts its focus to Depo-Provera's lengthy FDA marketing approval process. Here her story explores the scientific and political controversy over the FDA's assessment of the drug's risk and its policy judgments about the risk acceptability of its marketing approval. The controversy was dominated by the fear that the drug could cause breast, endometrial, and cervical cancer, and by Depo-Provera's uniqueness as a long-acting contraceptive and its use in international population control programs. The controversy began when the FDA relied on its Obstetrics and Gynecology Advisory Committee to grant the drug limited marketing approval in 1974, which it withdrew after congressional criticism, and then, following an intra-agency review, disapproved the drug for general contraceptive marketing which, once again, brought congressional scrutiny because of its impact on international family planning programs. An FDA Public Board of Inquiry, convened at Upjohn's request and chaired by Judith Weisz, conducted an intensive scientific assessment of the drug's animal and human studies at its 1983 hearings and then made a recommendation, accepted by the FDA in 1986, to disapprove the drug for general contraceptive marketing.

Marketing Approval and Litigation

Judith Weisz's story returns us to the national politics of drug risk management and finds an altered risk assessment environment for Depo-Provera, because the FDA decided to eliminate animal studies and rely solely on improved World Health Organization human clinical trial data, which paved the way for the agency to approve the drug for contraception in 1992. Marketing approval came with the condition that Upjohn conduct a post-approval study of a new risk: osteoporosis. When clinical trials confirmed this risk, the FDA revised the drug’s package insert in 2004 to include a black box warning of the risk of osteoporosis and a recommendation that the drug's use be limited to two years. In Depo-Provera's post-approval world, Anne MacMurdo's story is told by women who claimed that the drug caused their osteoporosis. Their stories, like hers, raise medical malpractice and products liability issues, and they, too, faced formidable obstacles. None of their cases, unlike hers, went to trial. Pfizer, Upjohn's corporate heir, had their cases dismissed on motions for summary judgment. Her story explains how Pfizer was able to use Depo-Provera’s package labelling, state products liability law, the learned intermediary doctrine, and expert evidence to avoid liability.

The Grady Hospital Study

Judith Weisz's story of the politics of drug risk management begins with the FDA’s limited control of Depo-Provera's contraceptive research. After the agency authorized Upjohn to conduct human clinical trials, drug testing was the responsibility of the company and its researchers. Her story begins at the Grady Memorial Hospital Family Planning Clinic, which conducted Depo-Provera's major domestic clinical trial by administering the drug to 11,400 women, principally poor African American women, from 1967 to 1978. When the FDA audited the Grady Clinic's study, it found serious deficiencies in the design and conduct of the clinic's testing protocol, including inaccurate screening, defective informed consent procedures, and no follow-up of the women. The FDA audit team concluded that the clinic had sacrificed scientific assessment of the drug’s health risks to its acceptability in promoting family planning goals. The agency terminated the clinic's program, but its risk management flaws were not publically exposed and its research was not discredited until the FDA's Public Board of Inquiry, chaired by Judith Weisz, held hearings in 1983. Yet the women whose health had been harmed by their participation in the Grady Clinic's study went without a legal remedy.

Conclusion

The odyssey of Depo-Provera has been told as three stories of the politics of contraceptive drug risk management. The stories have joined the national struggle over Upjohn’s FDA application to have the drug licensed as a female contraceptive to the state medical malpractice and products liability issues raised by its contraceptive use and the criminal justice issues raised by its use as a probation and parole condition for sex offenders....

Chemical Castration

Judith Weisz's story of the politics of drug risk management comes full circle by returning to the FDA's limited control over Depo-Provera's experimental use first explored in Chapter 1. Now her story focuses on the drug's use by Dr. Fred Berlin at the Johns Hopkins Clinic and his failure to acquire FDA approval to test the drug on convicted sex offenders, to receive informed consent from his subjects, and to provide credible scientific evidence of the drug's safety and effectiveness as a means for chemical castration. In this setting, Roger Gauntlett's story joins Judith Weisz's when he is convicted of criminal sexual conduct and sentenced by a Michigan trial court judge to five years’ probation on the condition that he use Depo-Provera at the Johns Hopkins Clinic program, a sentence overturned by the state supreme court. His story analyzes the risk management roles of state trial judges who impose Depo-Provera as probation condition and state legislatures that grant trial judges the authority to mandate the drug's use as a parole condition. To protect themselves from Depo-Provera's serious side effects, his story tells these convicted sex offenders to use their federal constitutional rights to challenge Depo-Provera sentencing conditions.

Contraceptive Chaos

Judith Weisz's story of the politics of drug risk management now turns from the national controversy over Depo-Provera to join Anne MacMurdo's story of the drug’s unapproved contraceptive use and the personal risks faced by women. The FDA’s limited authority over Upjohn's marketing practices and over physicians, mental health facilities, and family planning clinics nationwide, permitted the drug to be prescribed for contraception without the informed consent of women. Unlike Judith Weisz's story of Depo-Provera's long-term risk of cancer, Anne MacMurdo's concerns the drug's short-term side effects, such as excessive menstrual bleeding, depression, and weight gain. Her story began when an injection of the drug in 1974 was followed by a hysterectomy to stop her continuous bleeding. Shebrought a products liability suit against Upjohn, but her case was not tried until 1986, when a Florida jury awarded her $186,000, a verdict reversed on appeal by the state supreme court. Her story exposes the failure of Upjohn and physicians to manage the drug's risk, the limited access of women, often poor white women and women of color, to a legal remedy, the risk management role of courts, and the limited ability of state civil law to address the drug's short-term side effects.

Introduction

The Pill, the IUD, and Norplant have dominated public awareness and debate over contraceptive technologies. Depo-Provera, a three-month injectable drug, held out the promise that it could also play a leading role in the contraceptive revolution, but it has not received much more than episodic public attention....