Topic: Drugs and Drug Industry

Fighting Back Against A Critical Shortage of Vital Pediatric Drugs

Berman Institute of Bioethics faculty member Yoram Unguru, an assistant professor at the Johns Hopkins School of Medicine and a pediatric hematologist/oncologist at The Children’s Hospital at Sinai, has spent years sounding the alarm about the skyrocketing number of drug shortages in the United States.

But even he wasn’t prepared for the notice he received one Sunday evening last month. Unguru, along with pediatric oncologists across the country, were notified of an imminent national shortage of vincristine, the single most widely used chemotherapy agent in childhood cancer.

“This was truly a nightmare situation.  Vincristine is utilized by children with nearly every type of cancer, including leukemias, lymphomas, brain tumors, bone tumors, musculoskeletal tumors, neuroblastoma, and more,” said Unguru.

“In 2016, colleagues and I published a paper in the Journal of the National Cancer Institute about the ethical allocation of childhood cancer drugs during a shortage. We came up with two hypothetical worst-case scenarios to set the stage – the primary case was a vincristine shortage and now was coming true.”

Unguru swung into action that evening, contacting a New York Times reporter who had interviewed him previously about drug shortages. A story in the next morning’s paper, “Faced With a Drug Shortfall, Doctors Scramble to Treat Children With Cancer,” followed by an appearance on NPR, helped launch a news cycle that created national awareness of the impending shortage and its potential impacts.

“This will inevitably result in many difficult decisions in the coming weeks as nearly every child with cancer in the United States will be affected by this shortage,” said Unguru, who traced the origins of the shortage to earlier in 2019 when Teva, one of only two pharmaceutical companies manufacturing vincristine sulfate injection, made a business decision to discontinue production. Afterward, the other and sole producer of vincristine, Pfizer, faced manufacturing delays.

Teva immediately faced a major backlash. A petition calling upon the company to resume manufacturing gathered more than 215,000 signatures. Another petition sent to the White House asking the government to intervene in the shortage gathered more than 100,000 signatures. In the face of public pressure, Teva announced last week that it will resume production of vincristine.

“I was pleasantly surprised to see the announcement, and it’s the right decision. Patients are going to benefit but it won’t help immediately,” Unguru told Forbes in an interview. “The cynic in me says that this will be one more story that people forget about. But I’m hoping that through advocacy work, the recent federal Mitigating Emergency Drug Shortages Act that Senators Collins and Smith have introduced might make a difference. I don’t believe drug shortages will be resolved until the government steps in.”

Dr. Unguru is a pediatric hematologist/oncologist with joint faculty appointments at The Herman and Walter Samuelson Children’s Hospital at Sinai and The Johns Hopkins Berman Institute of Bioethics, where he is a Core Faculty member. He is also an Assistant Professor in the Johns Hopkins School of Medicine. Dr. Unguru is a member of the Children’s Oncology Group, and leads a multidisciplinary, transnational working group examining the ethical and policy implications of chemotherapy shortages in childhood cancer.

Travis Rieder Publishes New Book, “In Pain”

For Travis Rieder, Research Scholar and Director of the MBE Program at the Berman Institute, experience with opioids began after a 2015 motorcycle accident. The medication helped him through six operations but, as he recovered from the injuries, he discovered that withdrawal from the drugs caused excruciating pain of its own. Rather than risk addiction by following his doctors’ advice to return to the opioids, Rieder endured the struggle of withdrawal. Combining this harrowing experience with his professional training, Rieder has written In Pain, a new book published this week by HarperCollins.

Media coverage associated with the book’s publication includes:

Rieder’s experience exposes a dark secret of American pain management: a healthcare system so conflicted about opioids, and so inept at managing them, that the crisis currently facing us is both unsurprising and inevitable. As he recounts his story, Rieder provides a fascinating look at the history of these drugs first invented in the 1800s, changing attitudes about pain management over the following decades, and the implementation of the pain scale at the beginning of the twenty-first century. He explores both the science of addiction and the systemic and cultural barriers we must overcome if we are to address the problem effectively in the contemporary American healthcare system.

Kirkus Reviews calls In Pain “A bioethicist’s eloquent and riveting memoir of opioid dependence and withdrawal—a harrowing personal reckoning and clarion call for change not only for government but medicine itself, revealing the lack of crucial resources and structures to handle this insidious nationwide epidemic.”

The book arose from a 2017 essay Rieder published in Health Affairs,entitled “In Opioid Withdrawal, With No Help in Sight.” An essay adapted from In Pain appeared in the June 17 Wall Street Journal.

Viewing Drug Shortages as a Public Health Crisis

In resource-rich countries, 5-year survival rates for children with cancer approach 85%. However, shortages in the drugs which make up the backbone of many proven and life-saving pediatric oncology regimens have become commonplace in the United States, with far-reaching consequences. In a paper published in the March 4 JAMA Pediatrics, Berman Institute professor Yoram Unguru and colleagues explore the causes and impacts of drug shortages, and call for government intervention to address this growing public health crisis.

“Typically we only get one chance to cure disease. If that opportunity is missed, it is rare we are able to cure childhood cancer,” says. Dr. Unguru. “Direct consequences of drug shortages include increased medication errors, delayed administration of life-saving therapy, inferior outcomes, and patient deaths.”

“At the height of the shortages, a survey of medical oncologists found that a staggering 83% of oncologists weren’t able to prescribe their preferred chemotherapy agent. More than 75% had to make a major change in treatment such as choosing a different treatment regimen or substitute different drugs during the treatment. And over 40% had to delay the start of treatment. Two surveys of childhood cancer specialists, in 2015 and in 2017 , found that two out of three pediatric oncologists reported that their patients’ clinical care was compromised by the shortages.”

Dr. Unguru and his co-authors argue that the U.S., like many other countries already have, should establish an essential medicines list. As defined by the WHO, essential medicines satisfy the priority health care needs of the population. Medicines included in the essential medicines listare both clinically effective and cost effective and are to be available within the context of functioning health systems at all times in adequate amounts and dosage forms, with assured quality and at an affordable price.The current WHO Essential Medicines List for Children includes 18 chemotherapy agents and 4 supportive care medicines.

“It may shock you to hear, but over the past 2.5 years, nearly two-thirds of these essential medicines for children with cancer have been or are currently in short supply in the U.S.  In fact, at this time, 5 of the 18 essential medicines, nearly 30%, are in short supply in the U.S.,” said Dr. Unguru.

Dr. Unguru is a pediatric hematologist/oncologist with joint faculty appointments at The Herman and Walter Samuelson Children’s Hospital at Sinai and The Johns Hopkins Berman Institute of Bioethics, where he is a Core Faculty member. He is also an Assistant Professor in the Johns Hopkins School of Medicine. Dr. Unguru is a member of the Children’s Oncology Group, and leads a multidisciplinary, transnational working group examining the ethical and policy implications of chemotherapy shortages in childhood cancer.

Vaccine Guidance Gains Global Attention

Health and Bioethics Experts: “The treatment of pregnant women in vaccine research
and deployment is unacceptable. Business as usual simply cannot continue.”

New Report Lays out Recommendations for Policymakers, Researchers, and Global Health Organizations on Including Pregnant Women in Epidemic Vaccine Development and Deployment

Even as health care responders valiantly battle the ongoing Ebola outbreak in the Democratic Republic of Congo, one highly vulnerable group is being denied a potentially life-saving vaccine: pregnant and lactating women. This and other recent epidemics of Zika, Lassa Fever, and Hepatitis E have shown how infectious disease outbreaks can severely – and at times uniquely – affect the health of pregnant women and their offspring. Despite a significantly higher risk of serious disease and death, vaccines against these devastating diseases are rarely developed and approved for pregnant women.

Changing institutional and government practices so that we have vaccines to offer pregnant women in an epidemic is one of 22 long overdue recommendations contained in the new report Pregnant Woman & Vaccines Against Emerging Epidemic Threats: Ethics Guidance for Preparedness, Research and Response, issued in December 2018 by the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group – a multidisciplinary, international team of 17 experts specializing in bioethics, maternal immunization, maternal-fetal medicine, obstetrics, pediatrics, philosophy, public health, and vaccine research and policy. The report, aiming to ensure that pregnant women are no longer excluded from receiving vaccines against emerging infectious diseases, has received widespread media attention, including:

“The self-perpetuating cycle of excluding pregnant women from research and from the benefits of vaccination must end,” said Carleigh Krubiner, a lead author of the report jointly appointed at the Johns Hopkins Berman Institute of Bioethics and the Center for Global Development. “With global efforts now underway to develop a range of vaccines against devastating epidemic threats, we have to make sure pregnant women are on the agenda, so they will never again be left unprotected in the face of future outbreaks.”

The report lays out concrete steps for equitably addressing the needs of pregnant women in public health preparedness, vaccine research and development, and the deployment of vaccines during epidemics. Its recommendations include:

  • During an epidemic, the default should be to offer vaccines to pregnant women—not the reverse.
  • Vaccines that can be safely given to pregnant women need to be developed. For these vaccines, evaluation in pregnancy needs to occur as early in the clinical development process as possible.
  • During an epidemic, decisions about whether pregnant women will be offered vaccines should consider not only any potential risks of the vaccine but also, and importantly, the risks pregnant women and their babies face if vaccine is denied.
  • All decisions about inclusion or exclusion of pregnant women should be informed by those with the relevant expertise in maternal and neonatal health as well as in vaccinology and virology.
  • The perspectives of pregnant women themselves should inform vaccine research and deployment decisions that may mean life or death for them and/or their babies.

The full recommendations are available at http://vax.pregnancyethics.org/prevent-guidance.

“The way we have treated pregnant women in vaccine research and deployment is utterly unacceptable. Business as usual cannot be permitted to continue,” said Ruth R. Faden, a lead author of the report and founding director of the Johns Hopkins Berman Institute of Bioethics. “Ensuring that pregnant women affected by outbreaks have safe and effective vaccines is not only a matter of justice and health equity, it’s also critical to the public health response.”

That pregnant women affected by the ongoing Ebola crisis in the Democratic Republic of the Congo are not being offered vaccine demonstrates how urgent and serious the consequences are of the status quo exclusions of pregnant women from vaccine research and delivery. In recent UNICEF interviews, pregnant women “clearly articulated that they wanted to choose whether to be vaccinated or not.”  As one woman said, ‘now there is no option, you just send us to death.’”

“As we continue to develop new vaccines against pathogens with serious and often lethal consequences in pregnancy, pregnant women must be on the agenda every step of the way,” said Ruth A. Karron, a lead author of the report and director of the Center for Immunization Research and the Johns Hopkins Vaccine Initiative at Johns Hopkins Bloomberg School of Public Health. “We simply can’t continue to fail pregnant women as we develop new vaccines against emerging threats.  We need to generate an evidence base for safe and effective use of these vaccines during pregnancy.”

To read the full report visit vax.pregnancyethics.org/prevent-guidance. In conjunction with the report release, PREVENT has also released a video that discusses the risks of the status quo, and describes why urgent action is needed. You can watch the video at vax.pregnancyethics.org.

PREVENT is a grant-funded project led by faculty at Johns Hopkins University alongside co-investigators at Georgetown University and the University of North Carolina at Chapel Hill, with external contributions from Working Group Members. The PREVENT Project is funded by the Wellcome Trust (203160/Z/16/Z).

 

Jeremy Greene, MD, PhD

Greene’s most recent book, Generic: The Unbranding of Modern Medicine, narrates the history of generic drugs as a means of exploring problems of similarity and difference in modern medicine.   Generic drugs are never fully identical to the brand name products they imitate.  Rather, their claims to being ‘the same’ lies in proof that they are similar enough in ways that matter to be functionally interchangeable. As the market for generic substitutes has grown–from only 10% of the American pharmaceutical market in 1960 to nearly 80% by 2010–so too have epistemological and epidemiological conflicts over how one can prove that generics are truly equivalent to their brand-name counterparts.   These debates over generic drugs reveal fundamental conflicts over what it means to practice rational medicine, and what role consumers, physicians, insurers, and others should have in defining that rationality.

He has begun work on a new project, Medicine At a Distance, which examines how changing expectations of instantaneous communications through electric, electronic, and digital media transformed the nature of medical knowledge.  Most histories of medical technology focus on heroic diagnostic and therapeutic innovations–like X-rays and artificial hearts–which stand as visible symbols of medical modernity.   His research is focused on recapturing how more  mundane technologies of communication enabled and altered the production, circulation, and consumption of medical knowledge, from telegraph to text pager, telephone to telemedicine, fax machine to Facebook.  This work is supported by a  Faculty Scholars Fellowship from the Greenwall Foundation.

Yoram Unguru, MD, MS, MA

Full Bio

Dr. Unguru is a pediatric hematologist/oncologist with joint faculty appointments at The Herman and Walter Samuelson Children’s Hospital at Sinai and The John Hopkins Berman Institute of Bioethics, where he is a Core Faculty member.  He is also Associate Professor in the School of Medicine, Johns Hopkins University.  His B.A. in historical studies and M.A. with a concentration in the history of medicine and medical ethics were granted at the University of Maryland, Baltimore County. Dr. Unguru also received a Master of Science (valedictorian) in interdisciplinary studies in biological and physical science at Touro College / Barry Z. Levine School of Health Sciences. He earned his M.D. (valedictorian) at the Technion – Israel Institute of Technology / Bruce Rappaport Faculty of Medicine. He completed his pediatric residency at the Children’s Hospital at Sinai and his pediatric hematology/oncology fellowship at Children’s National Medical Center in Washington DC.  Dr. Unguru was a postdoctoral Greenwall Fellow in Bioethics and Public Policy at Johns Hopkins University.  Dr. Unguru is board certified both in pediatrics and in pediatric hematology/oncology.

Dr. Unguru’s research interests include clinical and research ethics.  His scholarship and publications have focused on the role of children and providers in facilitating shared decision-making, end-of-life decision-making, allocation of scarce lifesaving medications, and ethics education.   Dr. Unguru has served as a consultant to the American Academy of Pediatrics Committee on Pediatric Research, the American Medical Association Council on Ethical and Judicial Affairs, the Food Drug and Administration, and the US Senate Committee on Homeland Security and Governmental Affairs.  He is on the Editorial Board of Pediatric Ethicscope and serves as a peer reviewer for leading academic medical journals.  Dr. Unguru is Chair of the Children’s Oncology Group, Bioethics Steering Committee and past member of the American Society of Clinical Oncology, Ethics Committee.

Dr. Unguru is the Chairman of the Ethics Committee at Sinai Hospital of Baltimore where he implemented and directs a clinical ethics curriculum for the pediatric house staff at The Herman and Walter Samuelson Children’s Hospital at Sinai.  He is past recipient of “Teacher of the Year” as chosen by the pediatric house staff at The Herman and Walter Samuelson Children’s Hospital.

Dr. Unguru leads a multidisciplinary, transnational working group examining the ethical and policy implications of chemotherapy shortages in childhood cancer and is a member of the Maryland health system consortium tasked with operationalizing scarce resource allocation processes for public health catastrophes, including the COVID-19 pandemic.

Select Media Appearances

Rieder continues Seminar Series with talk on America’s Opioid Crisis

Bioethics, Pain Medicine and America’s Opioid Crisis

More than 72,000 Americans died from drug overdose in 2017, which is more than were killed at the height of the HIV/AIDS epidemic. This epidemic continues to be driven by opioids, which were involved in more than 49,000 of those deaths. Despite the scale of this problem, the opioid crisis has received fairly little sustained attention in the bioethics literature. In his Berman Institute Seminar Series talk, Travis Rieder argued that we must fill in this gap, and begin to show just how much specifically bioethics work needs to be done in this area.

Travis Rieder, PhD, is the Assistant Director for Education Initiatives, Director of the Master of Bioethics degree programand Research Scholar at the Berman Institute of Bioethics. He is also a Faculty Affiliate at the Center for Public Health Advocacy within the Johns Hopkins School of Public Health.

Jeremy Sugarman, MD, MPH, MA

He was the founding director of the Trent Center for Bioethics, Humanities and History of Medicine at Duke University where he was also a professor of medicine and philosophy. He was appointed as an Academic Icon at the University of Malaya and is a faculty affiliate of the Kennedy Institute of Ethics at Georgetown University.

Dr. Sugarman was the longstanding chair of the Ethics Working Group of the HIV Prevention Trials Network. He is currently a member of the Scientific and Research Advisory Board for the Canadian Blood Service and the Ethics and Public Policy Committees of the International Society for Stem Cell Research. He co-leads the Ethics and Regulatory Core of the NIH Health Care Systems Research Collaboratory and is co-chair of the Johns Hopkins’ Institutional Stem Cell Research Oversight Committee.

Dr. Sugarman has been elected as a member of the American Society of Clinical Investigation, Association of American Physicians, and the National Academy of Medicine (formerly the Institute of Medicine). He is a fellow of the American Association for the Advancement of Science, the American College of Physicians and the Hastings Center. He also received a Doctor of Science, honoris causa, from New York Medical College.