Summary: Chapter IX.1
Scientific Research On Contraception: The “Abuse-of-Power” Ethos
This chapter aims to review some ethical aspects of clinical trials conducted by researchers who developed hormonal contraception. When reviewing the clinical studies on contraception in women, one detects in many of them the commission of irregularities of method and ethics of varied nature and intensity. In this chapter we analyze the studies that show the researchers’ “abuse-of-power” mentality over the subjects of their research.
The ethical standards of biomedical research of those years were scarce and, in various areas of biomedical research, abuses occurred Here the subjects of the research were the unfortunate victims. The first complaints by the patients and some doctors like Henry Beecher were not long in coming.
The ‘Ethos’ In The First Trials Of Hormonal Contraception
Upon rereading the works published by Pincus, Rock and their collaborators on their first field trials on the effectiveness and safety of the pill, the reader’s attention is powerfully drawn to the casual attitude of abusive control with which women were treated; in most studies, these subjects belonged to a lower socioeconomic and educational level, were anxious to limit the number of their children, and did not request information about the nature and risks of the trial.
I. A Paradigmatic Precedent Of The Abuse-of-Power Mentality
The chapter pays attention to the famous “embryo hunting” carried out by Hertig and Rock between 1938 and 1954, which resulted in the exceptional collection of human embryos from two to 17 days of age, preserved at the Carnegie Institution. The work has served for more than three quarters of a century of universally as accepted guidance regarding the temporal and morphological development of the initial human embryo. Hertig and Rock scheduled the day on which a hysterectomy should be performed on a group of women to obtain specimens from each of the days of post-conception development. While the subjects were on the waiting list, they were asked to give the researchers information on the chronology of their cycles, in order to calculate the date of ovulation using thermometric data; also included were the dates on which they had maintained marital relations without using any contraceptive method. The preserved documentation casts doubt on any assumption that the cooperation of the women who participated in the study was truly voluntary.
II. The Abuse-of-Power Mentality In The First Clinical Trials Of Oral Contraceptives
The supporters of the studies – Katherine McCormick and Margaret Sanger – urged the researchers to obtain immediate and positive results, with the aim of allowing the introduction of the pill for general use in society. This urgency led scientists to design trials devoid of methodological quality and ethical rigor.
These involved two minor clinical trials, carried out at the initiative of Pincus: the study of the effects of norethynodrel (a progestin medication) on the menstrual cycle, carried out on medical students in Puerto Rico; and the one conducted at Worcester State Hospital on the effect of the new progestins in psychiatric patients of both sexes. The ethical aspects of both essays have been severely criticized by many authors. The particulars include deception in obtaining the consent of the incapable participants; threats of academic reprisals against students to force them to be involved in the procedures; Poor design that did not allow a well-founded statistical analysis; and the unexplained absence of any corresponding control groups. In no way could these “pilot tests” be considered legitimate.
The clinical trials published also demonstrate ethical errors. The first study aimed to observe to what extent three new progestins were able to remedy unexplained sterility. Fifty women were involved in the study, searching for Rock’s” rebound effect” that would result in the opportunity to have offspring. As a by-product, the trial was also used to determine the anovulatory (contraceptive) efficacy of the three compounds tested, two of them at different doses. To enhance the appearance of statistical reliability, the computations do not refer to the participating women but to the menstrual cycles studied (50 control cycles, 112 cycles with medication). The article refers to an extra group of seven women (not included among the fifty cycles), whom the researchers caused to endure a significant laparotomy delay, which forced them to endure unnecessary pharmacological treatment. This was the first study that showed the anovulatory effect of the new 19-Nor steroids in women, and its findings were published in the journal Science.
III. The Abuse-of-PowerMentality And The Approval Of The Pill By The FDA
The chapter shows that the mentality was exercised by researchers not only before women who participated in subsequent trials, but also in their relations with the FDA to obtain authorization for the market launch of new hormonal contraceptives.
IV. The Control Mentality And Control Cases Of The Río Piedras Trial
Barbara Seaman published a serious accusation of fraud with respect to the controls used in the Rio Piedras experiment (New York Times 2000) based on the Pincus file. Seaman denounced that “… when the study was already in its advanced stages, the FDA informed Pincus of the necessity of a control group. Since the recruiter of the Family Planning Association of Rio Piedras (Puerto Rico) could not incorporate new volunteers, Pincus ordered her to remove the label from the files marked as ‘lost cases’ and mark them again as ‘control cases’.” Seaman made the additional accusation that in May 1959 the norethinodrel-only pill was changed to the definitive pill, added with estrogen. The so-called “control group” was a group of women excluded from the trial, and who had received successively pills of different composition.
The works published on the initial studies of Puerto Rico and Haiti make little reference to the control groups. In the Humacao trial it is indicated that the controls were recruited as matched controls (by age of the woman, number of children, number of pregnancies and years of marriage) with the experimental cases. But it was very difficult to have the control group so designed. This lack of data on the control groups, the variants in method followed in the different trials, and the low appreciation of the participants’ complaints about the side effects of the medication suggest that the researchers assigned little relevance to the experiments’ design.
V. The Persistence Of The Abuse-of-Power Mentality
Some of these episodes have acquired the dubious prestige of being designated as paradigms of research misconduct. This is the case of Joseph Goldzieher and his “contraceptive study of San Antonio,” carried out in 1971, in Texas. He is included, along with other scandalous events (Willowbrook, Tuskegee, Brooklyn Jewish Hospital), in biomedical research ethics courses, in order to sensitize investigators against the abuse of power.
Goldzieher’s experiment was a double-blind clinical trial, a control group with a placebo group, and a double cross-over with four experimental groups receiving different oral contraceptives. It was conducted to determine if the annoying side effects of the contraceptives had an objective physiological basis or were a consequence of psychogenic factors. The trial, in which 398 women participated, largely of Mexican descent, was seriously altered when the FDA banned the use of one of the contraceptives that were being investigated. With this, the statistical strength of the trial fell apart. Despite this setback, Goldzieher preferred to continue. What made the study famous was the contempt with which, in general, the women who participated in it were treated. Goldzieher was accused of committing serious failures in obtaining the consent of the participants and in regard to the information given. Many women were considered unable to understand the complex design of the study; many were not told that they would receive a placebo instead of the active pill. It was concluded that the study was based on deception and exploitation of a vulnerable and indigent population.
Nonetheless, the researchers were not censored, nor did they receive any sanctions; they continued to receive support from the sponsoring agencies (Planned Parenthood, USAID, and the South Central Texas and Southwest Foundation for Research and Education Foundation), all along enjoying prestige in the world of biomedical science.
FROM THE ORIGINS OF CONTRACEPTION TO HUMANAE VITAE: SUPPRESSED STORIES
Author: Gonzalo Herranz, University of Navarra. Email: [email protected]
The full chapter upon which this summary is based is available in Spanish only. Click here…