Born in the USA (15 page)

Before we go any further, let's take a look at how this most recent case of vigilante obstetrics got started. In the late 1980s, a drug with the generic
name misoprostol (given the brand name Cytotec by its manufacturer, Searle Pharmaceutical, Inc., now a division of Pfizer) was approved by the FDA for use on adults with stomach ulcers. The manufacturer was well aware that one possible side effect of the drug was severe uterine contractions, so it stated on the label that it should
never be given to pregnant women
. There is even a silhouette of a pregnant women with a slanted line through it on the label. However, soon after the drug hit the market, obstetricians discovered that, because it causes uterine contractions, Cytotec can be used to induce or augment (speed up) labor. Completely disregarding the warning on the label, they began using it on pregnant women. In doing so, obstetricians are taking advantage of a significant loophole in our drug regulatory system. Once a drug is approved by the FDA for a specific medical indication and put on the market, there is no law preventing a doctor from using the drug for any purpose he chooses, in any dose he chooses, on any patient he chooses. Since the drug label includes those indications that are approved by the FDA, using the drug for purposes not shown on the label is called “off-label” use.
⁶

When obstetricians who use Cytotec for labor induction are confronted with the fact that they are unwilling to wait for the scientific evidence that will tell them whether or not the drug is safe, they invariably answer, “But we use drugs off-label all the time.” This answer has several serious problems. The most fundamental one is that obstetricians who say this are expressing a cavalier disregard for the safety of women and babies as well as a lack of faith in the drug regulatory system. But beyond this obvious flaw, it is important to recognize that using Cytotec to induce labor is not just “off-label,” it is “against label”—that is, the label states that this use is contraindicated (medically harmful). Given that drug companies have no incentive to limit the use of their products unnecessarily, we have to assume that if the Cytotec label explicitly states that the drug should not be given to pregnant women, there must be data that suggest possible serious risks involved in such use. So using a drug “against label” must be considered a higher level of risk than using a drug under conditions that are not mentioned on the label at all.

Another reason to be concerned with this standard response is that it lumps together all off-label drug use as though the risks involved were all equal. In Cytotec cases such as the three recounted in this book, in which the outcomes include death and severe disabilities, when the obstetrician offers the excuse, “But we use drugs off-label all the time,” we can compare the obstetrician to a driver who goes one hundred miles per hour in a
twenty-five-mile-per-hour zone. Imagine that the speeding driver causes a fatal car accident and then says, “Traffic laws are disobeyed all the time. Just last week there were dozens of parking tickets given out in this city.” You can't compare the risks of speeding with the risks of illegal parking. And you can't compare the risks of using Cytotec for labor induction with the risks of giving other drugs to pregnant women off-label.

A survey of pregnant women conducted in the 1990s revealed that ten drugs were given to them off-label.
⁷
Nine of the drugs mentioned in the survey carried very little risk. Only the tenth drug, prostaglandin E2, a close relative of Cytotec that was popular for labor induction before Cytotec came along, had serious risks.

When obstetricians found that they could use Cytotec to induce labor, they began using it more and more, playing around with the dosage and experimenting with how and when to administer it. For the most part, they did this without telling their patients that they were participating in an experiment, essentially treating their patients and their patient's babies as guinea pigs and lab rats rather than as human research subjects. The results of these informal experiments were then passed on to other doctors by word of mouth—informal chats in the doctors' lounge or the cafeteria. Incredibly, in my experience short conversations with other doctors are the most common way doctors learn about new drugs or techniques. Sadly, reading the results of scientific studies in medical journals or hearing reports of studies at professional meetings are not typically part of most obstetricians' practice.

With the advent of the Internet, doctors found another convenient way to exchange medical information, though for the most part it has not meant more safeguards as to the validity of that information. In the early 1990s, while surfing around in Internet chat rooms frequented by doctors, I began to read more and more about the use of Cytotec for induction of labor. One doctor wrote, “I must say I have heard some great things about Cytotec myself. Just be careful. The stuff turns the cervix to complete MUSHIE.”

That's when I went to the
Physicians' Desk Reference
and found that using Cytotec for induction of labor was “against-label-contraindicated.” I went on to check obstetric journals and textbooks, and found that the only published research into inducing labor with this drug involved far too few women to draw reliable conclusions about risks. I got a cold feeling in the pit of my stomach as I sensed that this drug would result in another widespread obstetric tragedy—and it has.

In the years that followed, when I gave lectures to obstetricians around
the country, more and more doctors told me that they were trying Cytotec, and I had the disturbing experience of seeing how rapidly “trying it out” solidified into accepted dogma. I remember one obstetrician in Sioux Falls, South Dakota, who proudly told me over lunch that he was the first doctor in his community to use Cytotec for labor induction and that he now urges other doctors to use it. He justified his actions by saying, “If we wait for the bureaucrats at the FDA to approve drugs, we'll wait forever. We must try them out ourselves if we want progress.” He admitted that he doesn't tell the women to whom he gives the drug that it is not approved for the purpose, nor does he ask for their consent. He scoffed at my observation that he is experimenting on women without their knowledge, much less their informed consent.

In 1995, when I was lecturing in Oregon, the Oregon State Health Department told me that Cytotec was the most common way of inducing labor in that state and was being used on thousands of laboring women. Around this time, a few more studies of Cytotec induction began to appear in obstetric journals, but all were still far too small to scientifically evaluate the level of risks.
⁸
The studies did report risk tendencies, however, such as the possibility that the drug could make the uterus contract too fast (uterine hyperstimulation); cause signs of fetal distress (such as the fetus passing meconium or a change in the baby's heart rate); and, for a few women, cause uterine rupture. In 1999, a review of the scientific evidence for using Cytotec for labor induction was published by the Cochrane Library. The review concluded that because of the lack of sufficient scientific evaluation and the reports of serious side effects, Cytotec “cannot be recommended for routine use at this stage.”
⁹

These worrisome studies had no apparent effect on the spread of the drug. It can be reliably estimated, using annual total U.S. births and induction rates, that during the five years 1995 through 1999, more than a half-million women in the United States had labor induced with this drug that was (and is)
not
approved

by the FDA,

by the drug regulatory agency of any other industrialized country,

by the pharmaceutical company that makes it,

by reliable and valid scientific evidence (the Cochrane database), or

by the British Royal College of Obstetricians and Gynaecologists.

According to the Centers for Disease Control and Prevention (CDC), the rate of drug-induced labor induction in U.S. births doubled from 10 percent to 20 percent of births in the 1990s, an increase almost certainly due to the rampant use of Cytotec.
¹⁰
A survey in 2002 showed that 44 percent of all births are induced with uterine stimulant drugs.
¹¹
Furthermore, data from the CDC tell us that much of this induction was done for convenience, as it parallels an increasing trend during the 1990s for vaginal births to take place Monday through Friday during daylight hours. So doctors' convenience has led to unnecessary labor induction, which has led to women's deaths.

The convenience factor is strong motivation for obstetricians to induce labor. Scheduling a labor induction, like scheduling a C-section, is a godsend to a busy, often sleep-deprived doctor. It offers the hope of practicing “daylight obstetrics.” Many doctors have told me with satisfaction that when they bring a woman to the hospital in the evening and induce her with Cytotec (weekday evenings only, never on weekends), she will typically give birth by late the next afternoon, so the obstetrician can be home in time for dinner.

Induction of labor is an important convenience not only for obstetricians but also for hospitals, as it allows hospitals to organize an induction assembly line, with slots into which doctors can fit their patients. This assembly-line approach is confirmed by the printed protocol in a large hospital in Florida, “Scheduling Induction for Labor.”
¹²

In about 10 percent of all births there is a medical reason to induce labor with drugs, and before 1990, 10 percent was the rate of induction in most industrialized countries. Pitocin, which is a synthetic version of the naturally occurring hormone oxytocin, has been used to induce labor for decades. It has been approved by the FDA for this purpose after adequate, careful scientific assessment of its efficacy and risks, and we know a great deal about how best to use it.

Given that there is already a well-tested drug that can be used for induction, why did obstetricians start using Cytotec? There are several reasons. One is that Pitocin is administered with an intravenous drip (IV), whereas Cytotec doesn't require an IV, so it's easier to administer. It is in pill form and is given orally or inserted into the vagina. However, the form of the drug presents special difficulties when used for labor induction. Because Cytotec is made for patients with stomach ulcers and was never intended for use on pregnant women, it comes only in 100 and 200 microgram tablets. After a decade of unauthorized experimenting, 25 micrograms has
emerged as the usual dose for labor induction. Have you ever tried to break a tablet that does not have a line down the middle or used a razor blade to cut it in half and then into quarters? Needless to say, the size of each quarter is never exact. Nevertheless, this is what some hospital pharmacies all over the country are doing. (Other hospitals find this unacceptable and do not allow induction with Cytotec because their pharmacies refuse to dispense inaccurate dosages.)

The convenience of using Cytotec is also a liability in that the drug is quickly absorbed and stays in the body for hours. Whereas a Pitocin IV can be pulled if any adverse effects arise, thus stopping the effect of the drug in seconds, when problems develop with Cytotec, there is very little that can be done to reverse its effects.

Another benefit of Cytotec that is frequently discussed among doctors is that it costs less than other drugs used for labor induction. It is surprising to hear doctors talk about saving money since, unless they have a financial interest in the hospital or clinic where they practice, it is not really their money. Cytotec is indeed far cheaper than other drugs used for induction of labor, but the question is, why is it so cheap? It is cheap because the pharmaceutical company has not spent the money on experimental clinical trials that would be required by the FDA to test the drugs' safety for labor induction. In other words, it is cheap because we don't know whether it's safe, and it is women on whom it is used who are paying the price. Of course, hospitals love to save money, but they must also realize that they are taking a huge financial risk when Cytotec is used to induce labor because they may well lose much more in litigation after a single bad outcome than they can save in years of using the cheaper drug.

In 1998, after Cytotec had been used for induction on millions of women in the United States, a paper was published about an experimental trial in which the drug was used for labor induction in women who had previously had C-sections who were having vaginal births after cesarean (VBACs). The study had to be stopped midway because too many women attempting VBACs with Cytotec induction ended up with ruptured uteruses, a catastrophic obstetric emergency that almost always means that the woman will not be able to have more children and that has a high risk of mortality for both the woman and the baby.
¹³
When the paper was published, I called ACOG and asked if the organization was aware of the sweeping use of Cytotec for induction. They replied that, yes, of course they were aware of it. I then asked why they were not doing anything about it. They replied that since it was off-label use and they had no position on off-label use, they were not prepared to take any position (thus turning their backs on this serious obstetric issue).