Princeton Meningitis Vaccination: Experiment vs Public Health Emergency

by Robert Baker, Professor of Bioethics and Director Emeritus of the Center for Bioethics and Clinical Leadership

As this post is being written, Princeton University is plagued by an outbreak of type B bacterial meningitis, a disease that has a 10% mortality rate in a college-age population. The first and only vaccine against this form of meningitis, Bexsero®, was approved last year in the two jurisdictions where type B meningitis is most prevalent: Australia and the European Union. The US Food and Drug Administration (FDA), however, has not approved the vaccine for use in the US. Consequently, Princeton’s trustees are seeking emergency authorization from the US Centers for Disease Control and Prevention (CDC) to use the vaccine.

One of America’s best-known bioethicists, Arthur Caplan, has written two blog posts on the subject — here and here. He contends that since Bexsero, “has not been approved by the FDA or other federal advisory agency…[those vaccinated] should be treated more as research subjects than as patients.” Here, Caplan is referencing regulations enacted in the aftermath of a notorious incident: the thalidomide tragedy of 1960. Back then, a newly hired FDA bureaucrat, Francis Oldham Kelsey, refused to rubberstamp a pharmaceutical company’s application for the  morning sickness drug, even though the drug had been approved for use in over twenty countries. Intrepidly insisting on a comprehensive review, Kelsey uncovered data indicating that thalidomide was linked to severe birth defects. She single handedly squelched FDA approval, and is thus credited with preventing birth defects in thousands of American babies. (Next July she will celebrate her 100th birthday.) After the thalidomide incident, Congress required that the FDA independently review drugs approved in other jurisdictions before permitting their sale in the US. Bexsero is currently under review by the FDA but has not yet been approved for use in the US, so the Princeton trustees are appealing for an exemption from this requirement.

The circumstances surrounding the thalidomide case differ from those surrounding the Bexsero exemption. Thalidomide alleviated the symptoms of morning sickness, a non-lethal and non-infectious condition (albeit one that can be quite debilitating for some women). Delaying FDA approval to gather additional information on thalidomide’s safety did minimal harm to most pregnant women and protected the health of their unborn babies. Delaying an emergency exemption for Bexsero, by contrast, would allow the spread of an infectious disease that threatens the lives and health of the Princeton community, even though the known data offers no reason to suspect that the vaccine poses a safety risk.

Mindful of these facts Caplan concludes that Bexsero® should be offered to the Princeton students who, on his analysis, should be treated as if they were volunteering to serve as subjects in a study of an experimental drug. As potential subjects the students would be cautioned about unknown side effects and encouraged to reflect on their right to refuse to participate. I think this is the wrong model. Princeton students are not volunteering for a scientific study. They are members of a community at risk for contracting a sometimes disabling and often-fatal infectious disease. Emergency vaccination should thus be presented to them as the recommended choice. Students should of course be informed of the vaccine’s probationary status and of their right to refuse it; however, they should also be notified that if they refuse, unless they are isolated they may place not only their own health at risk but also the health of others. The Princeton trustees framed the issue properly when they notified students that, if the CDC grants an exemption, they recommendstudents…receive a vaccine that helps protect against meningococcal disease caused by serogroup B.”

[The contents of this blog entry are solely the responsibility of the author alone and do not represent the views of the Bioethics Program or Union Graduate College.]

Media Myths about Mammograms

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

Like most married couples, my husband and I have a morning routine. I tend to get up first, shower, get dressed, get a cup of coffee, and make lunch. Dan is a little slower to get started, and likes to listen to a program like Good Morning America or the Today Show while ironing our shirts.

Normally the television is just background noise to me, but last week I actually stopped and listened in disbelief as ABC News correspondent Amy Robach revealed publicly that she’d been diagnosed with breast cancer. She underwent a double mastectomy later that week.

Ms. Robach’s diagnosis came after an on-air mammogram conducted in early October as part of Good Morning America’s cancer screening promotion, timed to coincide with National Breast Cancer Awareness month. The 40-year-old journalist had not undergone a screening exam before, but was pushed to do so by her producers and by fellow correspondent and friend Robin Roberts, herself a cancer survivor. According to Ms. Robach, by pressuring her to get a mammogram (the first ever to be nationally televised no less), Robin Roberts “saved my life”.

This is all well and good, and I wish Ms. Robach a swift recovery. At the risk of sounding cold-hearted, however, let me explain exactly what is wrong with this story.

The benefits of hindsight aside, Amy Robach should have never received a mammogram in the first place. According to guidelines issued by the US Preventative Services Task Force, an independent and non-partisan group of healthcare experts, most women should not undergo regular mammography until they are at least 50 years old. That Ms. Robach was pressured to do for the sake of television ratings is problematic to begin with, despite the apparently positive outcome. Worse yet is the false narrative about the benefits of routine cancer screening that the story creates.

For women with no family history of breast cancer, the likelihood of developing it is 1 in 70 for those in their 40’s. That rises to 1 in 35 for those in their 50s, and to 1 in 25 for women in their 60’s. Those seem like pretty high odds, so why shouldn’t every woman be screened annually? They shouldn’t because routine mammograms for women like Ms. Robach actually yield little benefit. But they come with considerable expense and risk.

Despite the possibility of developing cancer at a young age, conducting annual mammograms for all women in their 40’s will not significantly reduce the number of cancer-related deaths. In fact, only a single death will be prevented for every 2000 women so screened. The cost of routing testing aside, many of these women may also be harmed. Consider, for example, the physical and psychological toll of false test results.

Although mammography is the best screening tool we currently have, it is also notoriously inaccurate. On average, it misses 20-30 percent of all cases of cancer (so called false negative results).

Mammography also has a high rate of false positives: findings that look like cancer but are later determined to be benign. The chance that a woman will have a false positive result increases with every mammogram. According to the Susan G. Komen Breast Cancer Foundation, after just 10 yearly mammograms more than half of women will receive a false positive test result. They will only be determined to be cancer free after additional testing, including invasive biopsies.

Moreover, the psychological effects of a false positive can be profound. One recent Danish study found that women who received such false results suffered from anxiety and depression. These symptoms continued for years, even after cancer had been definitively ruled out. Inconvenient facts like these do not make for good television. Heartwarming stories of survival do.

By coming forward with her own tale of diagnosis and treatment, Amy Robach hopes to “inspire every woman who hears it to get a mammogram, to take a self exam. No excuses. It is the difference between life and death.” It probably will inspire more than a few women to get mammograms. Just as Katie Couric’s live colonoscopy led to an uptick in the number of people being screened for colon cancer, so to will Ms. Robach’s on-air mammography lead to more women undergoing that procedure. A few lives may even be saved.

Despite this, Amy Robach’s story is likely to do more harm than good. It will perpetuate the myth that more screening, starting at an earlier age, is a winning strategy in the on-going war on cancer. It will continue to confuse patients and clinicians alike about the potential benefits and limitations of routine testing, and contribute to the problem of overdiagnosis and overtreatment.

Universal screening programs, as promoted by Ms. Robach and her producers at Good Morning America, are not the answer. Such programs save few lives and come at great cost, despite what media reports might suggest.

[This blog entry was originally presented as an oral commentary on Northeast Public Radio on November 21, 2013. 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 Dark Days

by Theresa Spranger, Bioethics Program Alumna (MSBioethics 2012)

 

When someone dies, the grief for those left behind comes in waves.  You have your good days, where the sun shines inexplicably and you know that there is joy in the world in spite of your loss.  But, you also have the dark days, the days when even seemingly insignificant events leave you weeping in the corner desperately wishing you could bring the person back healthy and whole.  Every member of my family has had and will continue to have our dark days after the loss of my dad.

Dad was a real presence in our life, he had a great sense of humor, cared deeply about what was going on in the lives of the people he loved, and had an opinion about everything.  Without him, there is a void.

My family is not unique, anyone who has experienced a significant loss knows this story, the ups, the downs, the days you are doing great and unexpectedly crash hard into, “I miss my Daddy.”  So, how does this melodrama and seemingly self-indulgent rant tie into the world of bioethics?  One word…guilt.

On the dark days we run events with the person we lost over and over: fights from months ago, days you went to visit and didn’t stay as long as you could have, times when you could have done something different to make him more comfortable, times when you were not as patient or kind as you should have been, or his last days and the events that led to it.  Even if you have little or nothing to feel guilty about, and are secure in the knowledge that you did the best you could with the tools and information at your disposal, feelings of false guilt, failure, and regret creep in on the dark days.

During my schooling I have read several end of life case studies, so not many of the turns we took in the ICU surprised me.  I knew on the day my father was taken to the emergency room that we may have to eventually make the decision to remove ventilator support and allow him to die.  I also know that this was the right decision.  However, I still have moments when the whole situation haunts me, when I wish there had been another way and when I feel responsible for my father’s death.

The current medical system made me take on that responsibility.  The doctors at the hospital chose to allow me and my family to start every conversation about removing Dad from life support.  The hospital’s policies forced us to make every difficult decision and bear the full weight of those decisions.  This is an unjust system!  What are we doing to families?  Families already wracked with grief, existing on fumes of adrenaline, and in a fog of sorrow and confusion.

To a person in this weakened state the medical community says, “make the most difficult and agonizing decision of your life, it’s all on you kiddo.”  I am not saying that the medical staff should take this decision solely upon themselves, there is a sense of closure that can come to the family from being part of the decision making process.  However, it should be a true team, with all members bearing responsibility, but the doctor perhaps taking the lion’s share.

The physician has chosen his/her profession, and in the profession of healing your patients will sometimes die.  Everybody will die eventually, and physicians play the role of gatekeeper, having to know when someone can be saved and when to let them go.  The day my father died, was just another work day for his nurses and physicians, as it should have been.  They didn’t know my dad, or love him like we do; they wouldn’t and shouldn’t be affected by his death like us either.  This makes them more able to bear the responsibility of the final decision, they won’t be haunted by guilt, regret, or questions for the rest of their days like the immediate family members will.

I think there is a happy medium between making the decision without family input and forcing the family bear all of the responsibility of the decision.  This is taking a team approach, ask the family to be part of the team, bring them into important conversations and explain what is happening in a way that they can understand.  The physician should lead this team and the conversations about removing life support, and should facilitate the final decision.  If Dad’s doctor had stepped up to lead the conversations my family would have felt like we weren’t alone in the decision making, and that the doctor was taking responsibility for his patient.  Without this, we felt like we were the only ones who cared about what was truly best for Dad.

Reflecting on our experience, I think poor hospital policy was what really shifted responsibility on to my family and off of the hospital and staff.  A few minor changes and I would have felt like a team member:

  1. The palliative care nurse had to ask us whether or not we would like to start my father on vasopressors because his blood pressure was increasingly unstable.  This in itself was not a problem; the problem was that she still had to ask us this during a conversation about taking my father off of all life support.
  2. The nurse practitioner had to tell us several times, that removing the life support would most likely lead to my father’s death and ask if we were sure this is what we wanted the medical staff to do.  Making sure the family understands the decision is important, but repeating it 3 and 4 times because of the hospital policy only forces the responsibility of the action on the grieving family and made me feel as if the hospital was washing their hands of what was about to happen.
  3. The hospital could enact policies and trainings that help physicians with communication skills for dealing with end of life issues.  Encourage the physicians to take on the responsibility with their patient’s family at this difficult time and take a team approach.

I will live the rest of my life carrying the memory of how my father died.  I know logically that we made the right choice for him, and that my family has nothing to feel guilty about, and when those natural feelings of guilt creep in, I can dismiss them.  However, I see no reason to put more families through what mine went through, and would really like to see hospitals and physicians work to change this broken system.

[This blog entry was originally posted in a slightly edited form on Ms. Spranger’s blog on November 16, 2013. Its contents are solely the responsibility of the author alone and do not represent the views of the Bioethics Program or Union Graduate College.]

Punishing the Promoters

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

Earlier this week, the US Justice Department announced that pharmaceutical giant Johnson & Johnson agreed to pay more than $2 billion in fines and penalties for illegally marketing the drug Risperdal to doctors and patients.

For nearly seven years, pharmaceutical reps pushed this drug as a way to manage some of the behavioral issues, such as agitation or hostility, that are often seen in patients with dementia or developmental disabilities. Those problems make caring for these patients difficult, particularly in a nursing or group home setting.

The company also pushed the drug to treat some of the symptoms associated with attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) in children.

However, the US Food and Drug Administration (FDA) only approved Risperdal for use in patients with schizophrenia and bipolar disorder. It was not approved for use in demented or developmentally disabled patients. Moreover, despite knowing that older patients were at increased risk of stroke when using the drug, Johnson & Johnson aggressively marketed the drug to gerontologists — doctors who treat the elderly. The cardiovascular risks to patients, and the very fact that the drug was only approved to treat schizophrenia, were downplayed.

The $2.2 billion dollar settlement is, surprisingly, not the largest of its kind. In 2009, for example, the pharmaceutical company Pfizer was fined $2.3 billion for improperly pushing the painkiller Bextra. That drug was removed from the market when it was found to increase a user’s risk of stroke nearly three-fold.

Similarly, just last year British drug maker GlaxoSmithKline (GSK) paid the US Justice Department $3 billion to settle allegations that it illegally promoted drugs like Paxil and Wellbutrin for unapproved uses. GSK also hid the fact that its anti-diabetes drug Avandia was linked to heart attacks.

In the last decade alone, over two-dozen such cases have been settled and nearly $15 billion in criminal fines and penalties paid. One might hope that substantial penalties like these would dissuade pharmaceutical companies from inappropriately marketing drugs for unapproved and potentially dangerous uses.

Nothing could be further from the truth. A $2 billion settlement is simply seen as the price of doing business, and it barely makes a dent in drug companies’ bottom line. In one year alone, Risperdal brought in over $3 billion in sales. Given that blockbuster drugs like Risperdal can dominate the market for a decade or more, the financial incentives to commit wrongdoing are immense.

Don’t get me wrong. I am a strong supporter of the pharmaceutical industry. I believe that companies like Johnson & Johnson have every right to earn a profit by developing and distributing new drugs. It is that very incentive that leads to improvements in medical care and treatment, improvements that benefit all of us. But drug manufacturers should be allowed to put profits before patients.

As I have argued in the past, pharmaceutical companies have a legal and moral responsibility to ensure that their drugs are safe. This requires that they not only seek FDA approval to sell these drugs, but also that they abide by that Agency’s rules for marketing these drugs to doctors and patients. Moreover, it also requires that they inform physicians and consumers about the potential risks associated with their use, rather than downplay or hide them as so often happens.

Although the US Supreme Court ruled in Citizens United v. Federal Election Commission that corporations are people too, companies like Johnson & Johnson are not people. They have no moral compass. In order to ensure that they meet their ethical obligations to patients, we as a society thus need to impose some form of conscience on these companies.

Despite what I implied earlier, financial penalties are the way to go. The problem is that the penalties imposed to date are not nearly enough. A $2 billion penalty is merely a slap on the wrist. We need to encourage the Justice Department to demand increasingly larger penalties — in the range of $20, $30 or even $40 billion. These fines must substantially affect, or even eliminate, the profit that these companies earn from promoting inappropriate or unsafe use of drugs like Risperdal. Until then, it will simply be business as usual.

[This blog entry was originally presented as an oral commentary on Northeast Public Radio on November 7, 2013. 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.]