Opening the Black Box

by Sean Philpott, Director of the Center for Bioethics and Clinical Leadership

In a study published earlier this week, researchers found that pregnant women who take acetaminophen — a widely used drug found in such over-the-counter painkillers as Tylenol and Excedrin — are at increased risk of having children with hyperkinetic disorders like ADHD (attention deficit hyperactivity disorder).

Although the results of the study are not conclusive, children whose mothers used acetaminophen frequently while pregnant were nearly twice as likely to be diagnosed with ADHD by the time they were 7 years old.

This finding is surprising and troubling. Unlike other painkillers like aspirin and ibuprofen, acetaminophen has largely been considered safe for use during pregnancy. Nearly 50% of women in the United States take this drug at some point during pregnancy.

Pregnant women now face a difficult decision: whether or not to use a drug like acetaminophen when clinically indicated, despite the potential risks to the child. But this is not the first time that women have been faced with this choice. For example, antidepressant use during pregnancy raises a number of concerns, including the possibility of certain congenital defects. But stopping their use is also risky, particularly for the mental and physical wellbeing of the mother.

In an ideal world, pregnant women and their doctors would rely on objective information about the safety of drugs and the risks of forgoing treatment to make appropriate decisions. However, the truth is that we have almost no such data. Physicians and their patients are flying blind when it comes to the use of various medications during pregnancy. Moreover, the US Food and Drug Administration (FDA) — the federal agency tasked with ensuring the safety and effectiveness of drugs sold in the US — can do little to help.

Currently, the FDA classifies drugs according to possibility that they may birth defects if used during pregnancy. Drugs are sorted into one of five categories – A, B, C, D and X – based on the amount of animal and human safety data available.

Category A drugs are those that are safe for use during pregnancy, based on extensive animal and human testing. Category X drugs are those where there is conclusive animal and human data demonstrating fetal risk. Only a handful of drugs fall into category A. Far more drugs fall in category X.

The vast majority of drugs fall into categories B, C and D. For these compounds there may or may not be data from animal models or human studies to suggest that the drug is safe. Use of these drugs by pregnant women is essentially a crapshoot; women and their physicians have little guidance to help them weigh the risks and benefits of these treatments.

The problem is that there is a bit of a Catch-22 with respect to prescription drug use and pregnant women. We would like to collect data on the safety and effectiveness of new drugs during pregnancy, but these women are typically excluded from clinical trials.

For decades, regulatory agencies like the FDA have recommended that pregnant women be excluded from clinical trials out of fear that experimental drugs may pose a risk to the developing fetus. The images of severely deformed children following the thalidomide scandal of the late 1950s and early 1960s still resonate strongly among regulators and researchers alike.

Under existing guidelines, studies in pregnant women can be considered only when drug safety and efficacy has been demonstrated in the general population, when the drug has potentially significant therapeutic benefit to pregnant women, and when drug exposure not expected to pose undue risk to the woman or fetus. Those are very difficult requirements to meet, and there is little incentive for pharmaceutical companies to conduct additional studies in pregnant women once a drug has been approved for general use.

The vast majority of the data on the safety and effectiveness of drugs during pregnancy thus comes from two sources: pregnancy exposure registries in which women who use drugs are monitored for the effect of these compounds on fetal development, and retrospective studies like the acetaminophen trial.

Unfortunately, data from pregnancy exposure registries is biased. Physicians are more likely to report adverse birth outcomes than they are to report healthy deliveries, raising concerns about the safety of drugs during pregnancy where issues don’t really exist. These registries are also largely ineffectual in identifying problems that arise later in life, such as ADHD. Retrospective studies like the acetaminophen trial have similar problems, including the difficulty of proving a direct link between drug exposure and health issues in children.

It doesn’t make sense that we rely on such “natural experiments” rather than collect the necessary safety and effectiveness data by conducting controlled clinical trials using informed and willing participants. It’s time for us the reconsider existing guidelines on the inclusion of pregnant women in clinical trials: the mothers and their children deserve better.

[This blog entry was originally presented as an oral commentary on Northeast Public Radio on February 27, 2014. It is also available on the WAMC website. Its contents are solely the responsibility of the author alone and do not represent the views of the Bioethics Program or Union Graduate College.]


The Pelletier Family and Boston Children’s Hospital: The Battle Continues

by Theresa Spranger, Bioethics Program Alumna (MSBioethics 2012)

Last month I wrote an article about Justina Pelletier.  Justina is a 15 year old girl diagnosed with Mitochondrial Disease at Tuft’s hospital, if you are unfamiliar with her story to this point please read last month’s article, Hospital vs. Parent.

Over the past week this story has exploded.  Lou Pelletier, Justina’s father, broke the gag order placed by the court and has been speaking to the media.  Last week marked the one year point in the Pelletier Family’s battle with the Massachusetts Department of Children and Families, DCF, and Boston Children’s Hospital, BCH.

I have watched Mr. Pelletier in the two major interviews he did this past week: The Glenn Beck Program and  The Kelly Files,

In my opinion, Mr. Pelletier is amazingly calm and collected for a father in his position.  In each interview he tells his side of the story, a few of the points he makes are below:

–       He is breaking his silence (and defying the gag order) because he believes that Justina’s life is in danger because of the treatment she has received at Boston Children’s Hospital

–       In January of 2013 Justina was ice skating and living the life of a normal teen, now she is confined to a wheelchair and states that she is in constant pain.

–       The specialist the family went to BCH to see was physically removed from her room when he attempted to see the patient.

–       All medical procedures performed on Justina by Tufts Hospital were deemed necessary by physicians and were covered by insurance.  He also gives examples of the procedures and presents proof of why they were medically relevant.

–       The Pelletier Family feels that the treatment Justina received at BCH is mentally and physically abusive to their daughter.  Examples are:

  • Psychologists asking her why she allowed doctors to perform past medical procedures on her when they were unnecessary.
  • Justina has difficulty with bowel movements, some of her previous medical treatments were to resolve this problem.  According to Mr. Pelletier, Justina has been forced to sit on the toilet for hours at a time and has been told that her toileting issues are in her head and that she will sit on the toilet until she has a bowel movement.

–       Justina has been moved to another facility in Massachusetts that specializes in psychological issues and will not accept patients with medical conditions.  Mr. Pelletier states that the first time he saw Justina at the new facility she was brought outside in 18 degree weather with a wet head, each subsequent time she has had dirty, greasy, matted hair.  He does not believe his daughter is getting care she needs or the treatment she deserves at this facility.

As emotional a reaction as this information immediately stirs in us, we must keep in mind that all stories have two sides.  The frustrating thing about this tale is that the other side, BCH and DCF, are unable/unwilling to give any pertinent information.  The statement released by Boston Children’s Hospital is as follows:

“We are proud of their work and positive impact on the patient.  [O]ur clinicians are particularly distressed that the inaccuracies surrounding this case have caused undo concern for the many children and their families with mitochondrial disorders in our care. Misleading reports suggesting that the hospital holds patients in its inpatient psychiatric unit do not recognize the role of DCF as the legal guardian or the challenges inherent in finding appropriate lower acuity facilities for certain patients.” (source)

As expected and appropriately for the hospital, BCH is defending its physicians and shifting responsibility to Massachusetts DCF.

The interviews with Mr. Pelletier have been decent, but I feel the reporting has missed some major questions:

–       What is standard protocol for cases of alleged medical child abuse?  Are gag orders typically placed by the court in these cases?

–       What about the other families who have recently spoken up about similar experiences with BCH?  What are their stories?  Does BCH have a higher than normal number of cases reported to DCF than other pediatric hospitals?

–       It has been reported that BCH is the “go to” hospital for Massachusetts DCF when they have medical cases.  Is there a third party to review cases that involve BCH physicians?  What is the hospital that is called?  Did they review Justina’s case?  Has everyone involved been vetted for relevant conflicts of interest?

–       Why have the opinions of Justina’s physicians from Tufts not been treated with the same deference as the opinions of the BCH physicians?

Because the information is so limited in this case, I certainly don’t profess to have the right answer.  However, one glaring question cannot be ignored:

If BCH is correct in their new diagnosis, and their new treatment path is working, why, after a year on this new plan, have we seen Justina’s condition decline instead of improve?

Something feels wrong here, and for the safety of this little girl I think we need to figure out what that is and make it right.

[This blog entry was originally posted in a slightly edited form on Ms. Spranger’s blog on February 23, 2014. Its contents are solely the responsibility of the author alone and do not represent the views of the Bioethics Program or Union Graduate College.]

State Pregnancy Exclusions are Bad Law

This guest post is part of The Bioethics Program’s Online Symposium on the Munoz and McMath cases. To see all symposium contributions, in reverse chronological order, click here.

by Katherine Taylor, J.D., Ph.D.
College of Nursing and Health Professions, Drexel University

The Munoz case brought public attention to the Texas “pregnancy exclusion” law included in its Advance Directives Act, which says that life-sustaining treatment may not be withheld or withdrawn from a pregnant patient. Thankfully the state judge held that this law did not apply to Ms. Munoz because she was dead, and the hospital acceded to his order that Ms. Munoz’s body be released to her husband and put to rest.

These pregnancy exclusion laws exist not just in the “red” state of Texas, but in thirty-one states across the nation. I first wrote about these laws in a 1997 law journal article but the legal landscape remains essentially unchanged almost two decades later. Rather than using space summarizing these laws, I want to briefly sketch out some reasons why the exclusions are a very bad idea. The Munoz tragedy helps me illustrate my points.

What are the interests at stake in these cases? Ms. Munoz was dead, so some argue that she had minimal interests to be weighed against that of the state in the nonviable fetus (except there has been neglect of her, or society’s, interest in having her body respectfully treated rather than being used for experimental fetal gestation against her wishes and those of her family).  But other interests also have weight.

Ms. Munoz had an important interest in controlling in advance whether to refuse life-sustaining treatment. It is this interest that advance directive statutes convert into a legal right to execute a living will and appoint a health care proxy. Yet that right is given by these statutes with one hand and taken away by the other –the Texas pregnancy exclusion conferred on Marlise Munoz a lesser right than others to refuse life sustaining treatment in advance (as she orally did), because her right was made conditional on whether she was pregnant when the treatment would be removed.  The fact that she was only 14 weeks pregnant did not matter in Texas, and would not matter in most states that have enacted pregnancy exclusions. The question becomes whether women’s interest in prospectively making their end of life wishes known outweighs the state’s interests in a nonviable fetus. I believe it does.

Erick Munoz also had critical interests at stake. Surely Mr. Munoz had an interest in whether his wife’s body should be used to gestate the fetus, one that was not developing normally. Whether the child was healthy or not, Mr. Munoz would be the parent responsible for raising it. The Supreme Court made clear in Casey and other cases that persons have a liberty interest in controlling their procreation. Men’s procreative interest is rightly subordinated to a pregnant woman’s because of her bodily integrity. But when the woman is going to die, or is dead, the husband’s interest in avoiding reproduction should also come into play. The arguably experimental nature of the use of Ms. Munoz’s body also should require his permission. And again, family members should expect to be able to respectfully lay to rest the bodies of their loved ones. These interests, of Marlise and Erick Munoz, should outweigh the state’s interest in forcibly using a pregnant woman’s body to host a fetus that is not separate from its mother.

Yet that (more traditional) analysis is still incomplete because it is far too narrow. If we train a broader lens on the pregnancy exclusions, as we should, it becomes clear that the exclusions are part of a larger “pro-life” trend to treat fetuses as separate persons and patients. Nationwide, this trend translates into scary and grossly unjust scenarios where women lose their bodily integrity, autonomy, and inviolate legal personhood. Once the state sees the fetus as a separate person, it goes on to justify degrading pregnant women’s own legal status in numerous contexts of which we are all aware, from forcing pregnant women to undergo cesareans, criminally punishing them for causing the death of the fetus, to putting them in jail for having used drugs in their pregnancy. States have furthered that agenda by interfering with the ability of physicians to give good care to their patients according to accepted medical standards, and clearly the pregnancy exclusions do the same. When we do not explicitly recognize this larger context of women’s subordination, we ignore the injustice to all women that the pregnancy exclusions pose. Indeed, as I argue in my article, the pregnancy exclusions should constitute a violation of women’s equal protection rights.

Women’s extreme self-sacrifice, their role as the “moral proletariat” as Annette Baer described, is too often taken for granted. I end with summary thoughts from my article:

[The] pregnancy restrictions … accord women only conditional liberties, based on the social stereotype that women’s role as mothers appropriately requires of them extreme self-sacrifice for their offspring.  However, no matter how entrenched . . .  [that] stereotype may be . . . the state must protect against the legal imposition of that role, lest women become second-class citizens under law. Though women, like men, usually shoulder a complex set of relational identities, such as parent, child, sibling, and friend, it is of utmost importance that in the eyes of the state, women, like men, should be first and foremost independent persons with vital liberties deserving of vigilant protection.  Just as women’s moral agency should not be degraded because of their relational ties, so also their political agency should not be secondary to the uses to which they may be put for others.

Marlise Munoz’s body should not have been callously and forcibly used by the state as a means for fetal ends, and nor should any other pregnant woman’s body, whether she is dead or alive.

Doctor Knows Best?

by Theresa Spranger, Bioethics Program Alumna (MSBioethics 2012)

At one time or another we have all said something we regret. For Christina Schumacher that “something” happened last summer. Christina was in the midst of separating from her husband, claiming reasons of domestic abuse. At the time, she told her sister that if anything ever happened to her children she would kill herself. Christina and her husband had a 17 year old daughter and a 14 year old son.

On December 18th Christina’s estranged husband and their 14 year old son were found dead in an apartment. Dad had strangled his son and then hung himself.

The next day Christina went to her regularly scheduled appointment with her psychologist. Her doctor had decided, before she arrived, that she should check herself into the hospital psych ward and had the police ready and waiting in case Christina disagreed.

She didn’t agree, she wanted to be with her 17 year old daughter through their grief. This however, was not an option and she was taken to Fletcher Allen Health Care where she remained for the next 5½ weeks.

Christina was released, by order of a judge, about a week ago. The judge stated that he saw no legal reason she should have been committed or should remain in the hospital and ordered her immediate release.

Christina’s story raises some questions about the doctor/patient relationship in a mental health setting. What rights do psych patients have? How can we best assess their capability to make decisions? What is the line where involuntary commitment becomes necessary?

I understand the concern the psychologist must have felt, and how difficult it must be to determine if a patient needs to be committed. What if Christina had been unstable and harmed herself or her daughter? I am sure the doctor felt there was enough information from their past meetings to warrant the decision of commitment.

However, we never really know how we will react to tragedy. We often say things like: “I could NEVER do that.” Or “I would flip out if that were me.” I am no stranger to this kind of thinking, before my dad ended up in the hospital last fall my internal monologue was: “I wouldn’t be calm talking about taking someone off of a ventilator…especially someone I loved…I would be a puddle…there wouldn’t be enough tissue in the world…” Yet, there I was, in the exact situation I most feared, calm, collected, and making the tough decisions with tissue to spare. 

What we say we will do and what we do are often worlds apart. Christina’s psychologist would have been wise to keep this in mind during her appointment that December day.

[This blog entry was originally posted in a slightly edited form on Ms. Spranger’s blog on February 2, 2014. Its contents are solely the responsibility of the author alone and do not represent the views of the Bioethics Program or Union Graduate College.]