It seem like the old concept of “donating your body to science” for medical research has taken a whole new turn.
The New England Journal of Medicine just published a paper by a group of researchers at the University of Washington in Seattle studying whether condom use affected the probability of infection with Human Papillomavirus Infection (HPV), in which the researchers essentially asked female virgins to lose their virginity and report on their condom use at the big event, and for the subsequent 2-4 years. Furthermore, they failed to inform participants of all the risks of participating in the study — and in fact never even attempted to obtain consent of any kind, let alone informed consent, from more than half the subjects whose behavior was studied.
I’m sure you don’t believe me — no reasonable person would — so I’m going to quote directly from the article. (Italics in the original, boldface added.)
By the way, I don’t like the mainstream media’s practice of quoting anonymous “researchers” or claiming a study was done by a “university” rather than faculty, staff, or students acting on their own initiative, which is almost always what it is. The researchers have names, so I’m going to name them so they can take credit or blame. They are: Rachel L. Winer, Ph.D., James P. Hughes, Ph.D., Qinghua Feng, Ph.D., Sandra O’Reilly, B.S., Nancy B. Kiviat, M.D., King K. Holmes, M.D., Ph.D., and Laura A. Koutsky, Ph.D. All are from the Departments of Epidemiology, Biostatistics, or Pathology, or the Center for AIDS and STD, University of Washington, Seattle. And the authors state that the works was “Supported in part by grants (RO1-A138383 and T32-AI007140-24) from the National Institute of Allergy and Infectious Diseases.” Which means if you pay taxes in the United States, you paid for this study. The title of the article is “Condom Use and the Risk of Genital Human Papillomavirus Infection in Young Women” and it appears in the June 22, 2006 issue of the New England Journal of Medicine, Vol. 354, No. 25, pp. 2645-2654.
Now fasten your seatbelts, this is going to be um, an interesting ride:
Background To evaluate whether the use of male condoms reduces the risk of male-to-female transmission of human papillomavirus (HPV) infection, longitudinal studies explicitly designed to evaluate the temporal relationship between condom use and HPV infection are needed.
Methods We followed 82 female university students who reported their first intercourse with a male partner either during the study period or within two weeks before enrollment. Cervical and vulvovaginal samples for HPV DNA testing and Papanicolaou testing were collected at gynecologic examinations every four months. Every two weeks, women used electronic diaries to record information about their daily sexual behavior. Cox proportional-hazards models were used to evaluate risk factors for HPV infection.
We restricted eligibility to female University of Washington undergraduates who were 18 to 22 years old and who had never had vaginal intercourse or had first had intercourse with one male partner within the previous three months.
Now pay attention — they are later going to change that “within the previous three months” to within the previous two weeks.
In addition, the women had to have a cervix, could not be pregnant, had to be in good general health, and had to be able to provide written informed consent. Since the goal of the study was to enroll a population of healthy women (rather than women presenting to the student health clinic with gynecological problems), between December 2000 and June 2005, we mailed invitational letters to 24,201 women who met the age criterion and who released their names to the registrar.
Let’s restate that: These researchers mailed letters to more than 24,000 female college students asking if they’ve ever had sex, and if not would they like to for a medical study. (And if they’d just started very recently, it wasn’t too late.)
Questions for the peanut gallery: (1) If you were a female college student between the ages of 18 and 22, how would you feel about getting a letter like that. (2) If you had a daughter who was a female college student between the ages of 18 and 22, how would you feel about her university’s registrar releasing her name so she could get a letter like that from her university’s faculty?
Given the restrictive eligibility criteria, we assumed that the number of participants would be low in relation to the number of letters mailed.
Translation: We don’t think much of the morality of our university’s female students.
Well, that might be the translation if the researchers thought that morality and sex were related. I’d bet it never occurred to them to consider that possibility, so they did not actually intend that to be a smear on the female student (er,) body. I don’t know if that makes the claim more or less insensitive.
We also provided informational flyers to contraceptive counselors at the student health clinic. Of the 243 eligible women who responded, 210 agreed to participate (86.4 percent). The protocol was approved by the institutional review board at the University of Washington.
One might conclude from this sentence that what they “assumed” in the previous sentence was in fact correct — that there were only 243 female students out of 24,201 who met the “restrictive eligibility criteria” (never had sex, or at least not until two weeks ago). In other words, that 99% of University of Washington female undergraduates were sexually active more than two weeks ago.
However, we could also give them the benefit of the doubt and assume that some significant percentage of the students either didn’t want to start having sex, even for the sake of “science,” or just had better taste than the researchers. In fact, I think you’d be hard pressed to find any statement that’s true of 99% of any large group of undergraduates.
Later in the report we find this little gem — students were excluded from the study if they didn’t cooperate by losing their virginity:
Excluded from the study were 65 women who reported having had no vaginal intercourse, 3 women who did not record any information in their diaries regarding sexual behavior, and 60 women who reported having first had intercourse more than two weeks before enrollment.
They even have a neat little chart explaining all this.
Normally human research subjects are paid a small stipend for their trouble. I wonder if those enrollees who didn’t have sex still got paid. (If not, the researchers were arguably violating laws against prostitution — they were paying women to have sex.)
Of course, this all sounds very “scientific”:
Marginal Cox proportional-hazards models were used to determine risk factors for HPV infection. Data from diaries were summarized into risk-factor variables during the eight months before HPV testing, since most infections associated with a first partner (before the report of a second partner) occurred within eight months after a woman first had intercourse. Data recorded less than 20 days before a given visit were excluded, because 20 days was the shortest observed interval between the time a woman first had intercourse and the detection of an incident HPV infection in this study. The time to an event was measured from the time a woman first had intercourse to the report of infection with each type of HPV or the last clinic visit, with each woman contributing at-risk time for each of 37 HPV types. Analyses were stratified according to the type of HPV, assuming common relative hazards across HPV types while allowing the baseline hazards to vary. Robust variance estimates were used to account for correlation within subjects. Analyses were restricted to intervals in which intercourse was reported.
Yes, they use fancy terms like “time to an event” and “measured” and — my favorite — “Marginal Cox proportional-hazards models.” (Get your mind out of the gutter — “Cox” refers to the world-famous British statistician, Sir David Cox of Oxford University. And yes, it is a real type of statistical model.)
What sort of data did they collect?
Potential risk factors included the total number of instances of vaginal intercourse (continuous variable), the number of new partners (0, 1, or >1), the frequency of condom use by partners (<5 percent, 5 to 49 percent, 50 to 99 percent, or 100 percent), the partner’s circumcision status (circumcised, uncircumcised, or unknown), and the partner’s number of previous partners (0, .1, or unknown). The frequency of condom use was calculated by dividing the number of condoms used for vaginal intercourse by the number of instances of vaginal intercourse during the eight-month study period. If multiple new partners were reported during an eight-month period, the circumcision status and previous number of partners were summarized.
Now hold that thought for a minute and go back to a statement made earlier:
The protocol was approved by the institutional review board at the University of Washington.
Now this is kind of interesting. It happens to be a federal law (actually a regulation issued by the Department of Health and Human Services) that every institution that does any federally-supported research, and does any research on “human subjects” — that is, any research involving people in any capacity other than as researchers — have an institutional review board (IRB), and that all research projects involving human subjects be submitted to the IRB for approval. The IRB is supposed to make sure that, in the words of the Department of Health and Human Services, “Human Subjects Research Must be Guided by Ethical Principles.”
But whose ethics are they supposed to use?
By the ethics of most religions practiced in the United States, people aren’t supposed to have sex outside of marriage, most 18-22-year-olds aren’t married, and of course they are want data on the number of partners, which has to be greater than one for some significant fraction of of the women to produce statistically valid results. So the researchers are clearly aiming for behavior that a significant fraction of people regard as unethical.
Obviously, then, then don’t mean those ethics.
Perhaps then, they mean more “modern” ethics, by which it’s OK for anyone to have sex with anyone who agrees, as long as they use “protection.” But the whole point is to see if the “protection” works, by seeing the the effects are different for those who use it than for those who don’t. To do this, the researchers depend on some fraction of their subjects having unprotected sex. And it has to be a large enough fraction to generate statistically significant results.
Obviously, they can’t be encouraging condom use any more than they could be encouraging abstinence — either one would ruin their research!
What they mean is, “(a) The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, or (b) other appropriate ethical standards recognized by federal departments and agencies that have adopted the Federal Policy for the Protection of Human Subjects, known as the Common Rule.”
The Belmont Report was written in 1979 by government-appointed commission made up of three medical doctors, two lawyers, two non-physician scientists, a professor of bioethics, a professor of Christian ethics (is that constitutional?), and the then-president of the National Council of Negro Women. The report described three “Basic Ethical Principles”: Respect for Persons, Beneficence, and Justice. And it described three “Applications” of these principles: (1) Informed Consent, (2) Assessment of Risk and Benefits, and (3) Selection of Subjects.
In the section on Informed Consent, the commission stated:
Most codes of research establish specific items for disclosure intended to assure that subjects are given sufficient information. These items generally include: the research procedure, their purposes, risks and anticipated benefits, alternative procedures (where therapy is involved), and a statement offering the subject the opportunity to ask questions and to withdraw at any time from the research. …
Voluntariness. An agreement to participate in research constitutes a valid consent only if voluntarily given. This element of informed consent requires conditions free of coercion and undue influence. Coercion occurs when an overt threat of harm is intentionally presented by one person to another in order to obtain compliance. Undue influence, by contrast, occurs through an offer of an excessive, unwarranted, inappropriate or improper reward or other overture in order to obtain compliance. Also, inducements that would ordinarily be acceptable may become undue influences if the subject is especially vulnerable.
Now one interesting question is to what extent the consent given by the young women involved truly met the requirements above. I’m sure the staff was able to explain their purposes unambiguously. And they probably explained the “research procedure” quite well, if by that one means the procedure for filling out the electronic diaries — if not the procedure for, um, generating the information to put in the electronic diaries. This latter procedure was, by the nature of the requirements for the study, something with which the subjects were, um, necessarily unfamiliar. In fact, some of the “risks and anticipated benefits” were also something with which the subjects were necessarily unfamiliar. Obviously, the risk of HPV infection was there — that was the whole point of the study — and I’m sure the researchers could explain what that entailed, as well as the risks of other sexually transmitted diseases.
But what about the other “risks and anticipated benefits”? Prior to obtaining consent, did the researchers fully inform the subjects as to the emotional risks of engaging in sexual intercourse (a) for the purpose of a study, (b) if not for that purpose alone, then with the study in mind, ( c) with or without a committed relationship, (d) with the commitment level of the relationship formalized or not formalized in any particular way (e.g., marriage), (e) with more than one partner within the time frame of the study? What about the risks of increased emotional trauma when a relationship breaks up, if that relationship involved sexual intercourse? Did they fully inform the subjects of all this? I kind of doubt it.
And what about the “anticipated benefits”? Prior to obtaining consent, did the researchers fully inform their virgin subjects of the physical pleasures of sexual intercourse? What about the emotional pleasures that come from that form of intimacy? (Which, one might argue, turn negative without the appropriate level of commitment.) What about the benefits of parenthood, as opposed to the risks of pregnancy?
An even more interesting question is, did they get informed consent from the “male partners”? The study doesn’t mention that at all. They have copious detail about how the female subjects were recruited and screened, but the “male partners” are only mentioned when they (and their previous partners) are counted, and when it is asked whether they were circumcised. As far as we know, they were not informed of anything by the researchers — the researchers may not have even asked who they were. They female subjects were simply set loose in Seattle to involve unknowing males in a “research study.”
You might laugh, but this is precisely the sort of think the Belmont Commission was meant to address. One of the motivations for appointing the Belmont Commission was the Tuskegee Syphilis Study, in which 600 black men, 399 of whom had syphilis, were “studied” by being given medical care that, unbeknownst to them, did NOT include treatment for their disease. Neither they, nor their wives were informed the had syphilis, and they were “studied” until they died — in part to see how long it would take.
In this case, they aren’t even telling the male partners that they are part of a study. They are collecting personal information about them — such as whether the are circumcised, and the number of previous sexual partners they’ve had — and they are studying them in an environment in which the researchers know they are at risk at least for HPV, not to mention other things, and the are not informed of the risks, they are not informed they are being used for a study, and no consent of any kind, informed or not, has been obtained.
In short, this study is not only unethical from a “traditional values” point of view; it is also unethical from a “secular bioethics” point of view.
The fact that the University of Washington’s IRB was willing to approve this study calls into question whether the entire IRB system is just a bureaucratic rubber stamp for whatever some voyeuristic researchers want to do.