Week Note 2017-7

Week of: 

August 14, 2017

August 14, 2017

Per our last weeknote, the CTSP team has developed a deceptively-simple one page document which describes our recommendations for the treatment development system, and we have been taking those ideas to meetings, conferences, and interviews to discuss them with any and every stakeholder in the system. What we’ve found concerning one specific recommendation, called “Get the Word Out”, has been both interesting and baffling.

“‘Get the Word Out” is about addressing the fact that many Americans do not understand how treatments come to market; we call this lack of understanding about the process called, somewhat crudely, ‘sausage making’. Just as many Americans are oblivious or don’t want to know what goes into their sausage, many are oblivious as to how treatments are developed and come to market. Young people don’t view treatment development as a career option, and even doctors, nurses, and pharmacists barely understand the process.

This lack of understanding has so many significant downstream impacts on our country and healthcare system that they are nearly too numerous to explain, so I’ll give you one very basic example that we’ve diagrammed in an oversimplified manner below.



Lack of knowledge about treatment development means that there is 1) little recognition that doing preclinical and clinical research requires special skill sets; 2) lack of guidance from professional societies to high schools, colleges, and graduate schools about how to teach students about treatment development; and 3) general lack of appeal ascribed to preclinical and clinical research jobs by many Americans who don’t see the excitement and reward when compared with other careers in healthcare.

This in turn leads to little desire among young people to learn about treatment development and less incentive for schools at all education levels to offer classes or programs about clinical and preclinical research. In the end, most people complete undergraduate and graduate school without ever having learned about how treatments come into existence; everyone assumes something happens, but all that matters is that they can get their prescription at the pharmacy.

As a result, there is an inordinately small population of people who are prepared and/or willing to work in treatment development, in basic science but especially human subjects research. This adds to the high upfront costs of treatment development, due to ad-hoc education for people who have never heard of clinical trials as an undergrad or didn’t develop the appropriate skills, high turnover among physician investigators who don’t understand what they are signing up for after lack of training in med school, and high burnout rates and turnover among those who do work through staffing shortages in clinical research.

At the very end of the line, high upfront costs of treatment development mean more costs passed onto patients. Lack of education means Americans don’t understand why their prescriptions cost so much and why everyone is arguing over re-importation and drug price negotiations. It means doctors, nurse practitioners, and physician’s assistants who aren’t well-informed and yet are expected to understand formularies and thoughtfully prescribe treatments in a way which helps patients balance treatment costs from the moment they begin to practice medicine. Treatment prices remain an unsolvable mystery as long as treatment development remains a mystery.

From our perspective, it’s critical for people to not only understand treatment development, but for the system to more broadly and meaningfully engage everyone. We have a greater role to play in the system beyond consumers-- whether it is sharing health data or participating in disease registries, biobanks, or clinical trials-- we will be prosumers in the treatment development system of the 21st century. Yet none of that is possible if people don’t understand how the system works or why their participation matters.

Everyone we’ve spoken with inside the system agrees that it is critical to engage Americans about treatment development, but how can we complement short-term “awareness” days, weeks, and months; educational walks and runs; and social media activism with long-term interventions? When we ask that at meetings, people’s face go blank and they sit quietly. Education always seems like a great idea but too few people rally their resources around it, citing reasons like curricula are already too full, no one has time, etc.

While those things are true, we would argue the only way to pull back the curtain on the mystery of treatment development is to educate. The only way to innovate and drag the system into the 21st Century is to have more minds, especially young minds, thinking about how to improve it.

As a lecturer at Johns Hopkins University, I believe that undergraduates preparing for careers in science and medicine should understand how the entire research system works, not just their lab’s tiny mouse-poop filled corner of it. People say it takes a village to raise a child, but I would tell my students that it takes nations to develop new treatments.

I want my students to know how mTOR inhibitors, such as rapamycin and its analogs, were discovered on Easter Island also known as Rapa Nui, a Chilean island  in the southeastern Pacific Ocean. This island is famous for its giant stone statues (see below), not for the 1972 discovery of a macrolide in the soil by a Canadian scientific team gathering plant and soil samples. I want them to know how that team shared (yes shared) their soil samples with a microbiology team at Ayerst-McKenna-Harrison in Montreal (later known as Wyeth).



Photo by: Horacio_Fernandez

A team at Ayerst led by Dr. Surendra Sehgal, PhD, who was born in Pakistan, trained in Canada, and later became a proud dual citizen of Canada and the US, isolated a new bio-chemical compound that not only had anti-fungal properties but also suppressed the immune system. Following his intuition that the compound had additional properties, Dr. Sehgal sent a sample of what later became known as rapamycin to the National Cancer Institute (NCI) Developmental Therapeutics Program and requested anti-tumor activity screening. Rapamycin had impressive activity against solid tumors. After their research program ended at Ayerst, Dr. Seghal and a small contingent of researchers continued to push the rapamycin’s development forward at Princeton University.

What follows in the rest of this story is decades of discoveries and millions of lives extended and saved. Rapamycin was developed into Rapamune, an immunosuppressant drug for patients as prophylaxis following organ transplantation to prevent organ rejection, which received priority approval by the FDA and regulatory agencies around the world. The compound’s properties drove research on the mTOR pathway, which transmits signals and controls a range of vital biological processes including cancer development. Various mTOR inhibitors are now approved for the treatment of advanced breast cancer, pancreatic neuroendocrine tumours, advanced renal cell carcinoma, and SEGA in patients with tuberous sclerosis; research for other forms of cancer continue to this day. Rapamycin itself is also used to prevent coronary artery re-stenosis and for the treatment of neurodegenerative diseases.

One compound impacts millions of lives, including the lives of the brave breast cancer patients I had the honor of treating while working in clinical research— mothers who only wanted to live long enough to see their children graduate college and get married.  

The development of this compound took thousands of people from academia, industry, and government from all over the world and thousands more patients volunteering for hundreds of clinical trials. And yet, so few people know this exciting story or the stories of many others that really provide a window into how the treatment development system works. It works through sharing and buying, failure and success, and most of all through the fierce tenacity of scientists like  Dr. Seghal and his team and patients like mine.

So while our recommendation to educate people about the clinical trials system makes some people yawn, it makes me yearn to tell these stories to anyone who will listen.



Week Notes Authors

Johns Hopkins University Co-Research Lead

Co-Research Lead

Jen Bernstein has 15 years experience working on WHO-, industry-, U.S. government-funded research studies and clinical trials.  She received her Master of Public Health at the Johns Hopkins Bloomberg School of Public Health and currently works as Part-Time Faculty in the Johns Hopkins Whiting School of Engineering. Jen is also a clinical research associate and independent research consultant providing research support for deliverables at all stages of project development including IRB submissions, journal articles, presentations, and grant submissions. Jen honed her skills at a variety of institutions including The Urban Institute, the Johns Hopkins Center for Communication Programs, and The Weinberg Center for Women's Health and Medicine at Mercy Medical Center. 

MIT Collaborative Initiatives

Ellie Carlough is currently Associate Director of MIT Collaborative Initiatives (MIT-CI) and has been with the organization since September 2007.  In this role, she is actively involved in project management, writing and strategic planning for MIT-CI, which applies a system-based approach to addressing widespread societal issues reaching a crisis point.

Ellie graduated from Mount Holyoke College and earned a Masters of Science in Non-profit Management from the New School for Social Research in New York, New York.  After working in Manhattan for 10 years in banking and most recently as Director of Corporate and Foundation Relations at St. Vincent’s Hospital and Medical Center of New York, Ms. Carlough spent a time in the challenging position of full-time mother mastering the art of multi-tasking and social networking before joining MIT-CI.

SITRA, MIT Collaborative Initiatives

Based in Boston, Justin is the Finnish Innovation Fund's (Sitra) academic liaison for North America and serves as Sitra's Senior Lead for Sustainable Development. He helped design and build the Low2No urban decarbonization initiative and manage its implementation, and served as Helsinki Design Lab's expert on energy, carbon and sustainability. 

Currently he is helping Sitra better align its endowment with its mission by developing ways to place capital in businesses, projects and funds that generate measurable social and environmental impact together with financial return. As part of Sitra’s Strategic Research team, he works to support and challenge Sitra's strategy and shared assumptions. His research includes developing a more comprehensive understanding of sustainable well-being and how Nordic countries can transition toward it with practical economic and public policy measures.

Justin is also an Adjunct Professor at the Rhode Island School of Design where he teaches graduate level design courses. He holds a Master of Architecture degree from the Harvard Graduate School of Design and a Bachelor of Arts from the University of Washington. Find him @justinwcook.

Johns Hopkins University

Viva Dadwal is a Visiting Scholar at Johns Hopkins University Bloomberg School of Public Health, where she is investigating the transfer of health innovations from low to high-income countries. She is a published academic, a Senior Fellow at the Centre on Governance at the University of Ottawa and a Deputy Editor of open-access global health journal, Globalization and Health. Previously, she worked as a Trade Policy Officer for Foreign Affairs, Trade and Development Canada. Viva has held prestigious internships at the World Health Organization and Permanent Mission of Canada to the United Nations and to the World Trade Organization in Geneva, Switzerland.

In her spare time, Viva promotes public astronomy in urban cities through a project called #popscope. She also guest blogs for World Bank’s youth blog, Youthink! Viva holds a B.Sc. (Hons) in Biology from the University of Windsor and an M.A. in Public and International Affairs from the University of Ottawa. Viva is a recipient of Fulbright Canada Award 2014-2015 and a member of the World Economic Forum Global Shapers community. Follow Viva's adventures on Twitter @vivadadwal.

Johns Hopkins University

Francisco Del Canto Viterale is Postdoctoral Researcher in the Systems Institute within the Whiting School of Engineering at Johns Hopkins University. Currently, he is working on two different research projects: “Complex International Innovation Partnerships”, and “Clinical Trials Systems”.

His core area of expertise is the intersection of Science Technology Innovation and Higher Education, and International Relations.

Francisco has been working in the academia for over seventeen years in several countries. He has an extensive experience working as a university lecturer in International Studies, International Migration and Latin American Studies; and also as a researcher in topics related to International Scientific Relations, Science and Innovation Policy and Interdisciplinary, Complex and Systems Approach.

He received his Ph.D. in International and Intercultural Studies from the University of Deusto (Spain) in January 2014. Prior to his doctorate, he earned a Bachelor of Science in International Relations (1998), a Diplomat in International Affairs and Diplomacy (1999) in Argentina, and a Masters in International Migrations and Social Cohesion (2011) in Spain.

Johns Hopkins University

Felipe Feijoo is a Postdoctoral researcher at the Systems Institute in the Whiting School of Engineering, The Johns Hopkins University.

He obtained his B.S. in Engineering Sciences at the Universidad de La Frontera, Chile. Thereafter, he pursued his Master degree (2011) and Ph.D. (2015) in Industrial Engineering at the University of South Florida, Tampa.  

His current research involves the application of stochastic complementarity models and economics to analyze the opening of clinical trials and the pharmaceutical market in the U.S. 

His research also focuses on the application of mathematical programming, game theory, and statistics for decision making in sustainable electricity markets. He worked on a mathematical-statistical framework to developed Pareto designs of cap-and-trade carbon policies with high penetration of green energy via micro-grids. Other research interests include health-economics and predicting-forecast modeling using machine learning techniques. Felipe has also worked and led several projects for the Tampa Electric Company (TECO), Florida.

Johns Hopkins University

Senior Advisor

Dr. Tak Igusa is a professor at the Johns Hopkins University who has been engaged in multi-disciplinary collaborations spanning a wide range of fields.  He currently holds appointments in the Departments of Civil Engineering, International Health, Earth and Planetary Sciences, and Applied Mathematics & Statistics.  To provide rigor to his collaborative activities, Dr. Igusa has been promoting systems science and methodologies, which has led to significant, new research programs within the university.  This includes projects funded by the NIH, Robert Wood Johnson Foundation, CDC and the National Science Foundation on systemic studies of childhood obesity, rheumatic disease, community resilience to natural disasters, and technology innovation in developing nations.  His work led to the establishment of the Johns Hopkins Systems Institute in 2011.

Dr. Igusa received an A.B. in Applied Mathematics from Harvard University and a PhD in Civil Engineering from University of California, Berkeley. At Johns Hopkins, he is currently the Director for Health of the Systems Institute and the Program Lead of the Education & Training Program at the Global Obesity Prevention Center.  He is also advising the development of systems research programs that bridge public health and engineering at the University of the Witwatersrand in Johannesburg, South Africa. 


Johns Hopkins University

Gary Lin is currently working on complex systems research with the Johns Hopkins Systems Institute and pursuing a Doctor of Philosophy in Civil Engineering at the Johns Hopkins University.  He has a variety of research interests which includes healthcare systems, infrastructure systems, supply chain and transportation networks, and human population dynamics.  Using his diverse background, Gary has been involved in numerous interdisciplinary projects that range from natural gas networks to environmental impacts of population growth.  He hopes to apply the systems approach towards large-scale, health and engineering issues that face present and future society.

Gary obtained his Bachelor of Science in Civil Engineering and Bachelor of Arts in Economics from the University of Colorado at Boulder.  He is also a registered Engineer-in-Training (EIT) in the state of Colorado and student member of the American Society of Civil Engineers.  In addition, Gary has experience working in food transportation logistics, financial administration, and construction marketing.  Gary enjoys disc golfing, cycling, and hiking in his spare time.

Johns Hopkins University

Paul Locke, an environmental health scientist and attorney, is an Associate Professor at the Johns Hopkins Bloomberg School of Public Health in the Department of Environmental Health Sciences.  He holds a joint appointment in the Department of Health Policy and Management.  Dr. Locke is also the Distinguished Visiting Professor of Animal Law and Science at the Northwestern School of Law of Lewis & Clark College.   Dr. Locke has an MPH from Yale University School of Medicine, a DrPH from the Johns Hopkins University Bloomberg School of Public Health and a JD degree from Vanderbilt University School of Law. 

At Hopkins, Dr. Locke leads an integrated public health research, practice and teaching program.  His program focuses on research-to-practice initiatives to better protect public health, especially in advancing evidence-based in vitro toxicology and radiation protection policy at federal and international organizations.  He has published widely in both law reviews and scientific and policy journals, and has developed three cross-disciplinary courses in environmental law and policy and animal law.  Dr. Locke also directs the School’s Doctor of Public Health program in Environmental Health Sciences and a certificate program in Humane Sciences and Toxicology Policy.

As a member of the clinical trials initiative team, Dr. Locke is helping to better understand the laws, regulations and policies that frame clinical trials and human subjects research, and seeking opportunities to utilize rapidly evolving in vitro toxicological methodologies and other new techniques in clinical trial decision-making.      

Dr. Locke is admitted to practice law in the state of New York and the District of Columbia, the Southern District Court of New York and is a member of the bar of the United States Supreme Court.

Muchieast, Rhode Island School of Design

Systems Innovation Design Lead

Enrique is the systems innovation and design lead for the project. He is the founder and director of Muchieast LLC, an international consultancy working at the intersection of social, cultural and urban contemporary practices by incorporating the principles of systems innovation and creative thinking. He is a Visiting Lecturer at Brown University and a Senior Critic at the Rhode Island School of Design. Enrique holds a Master in Architecture from the Universidad Politécnica de Madrid, Escuela Técnica Superior de Arquitectura de Madrid; and a Master in Industrial Design, with Honors, from the Rhode Island School of Design, where he was granted the Norman Bel Geddes award in 1998.

Johns Hopkins University, Bloomberg School of Public Health

Michele is currently a Senior Research Assistant at Johns Hopkins Bloomberg School of Public Health in the Department of Environmental Health Sciences. Her interests include risk management and communication, effective translation of science into policy, and more recently, using a systems approach to fix ineffective or outdated policy. Since obtaining a Master’s in Health Science and a Certificate in Risk Science and Public Policy in 2012, she has been working on communications with congressional offices on Capitol Hill, conducting legislative analysis, producing advocacy materials and organizing consultation meetings with congressional offices.

Johns Hopkins University Co-Research Lead

Co-Research Lead

Dr. Sauleh Siddiqui is an Assistant Professor of Civil Engineering with an appointment in AppliedMathematics & Statistics at Johns Hopkins University and is affiliated with the Johns Hopkins Systems Institute. He is also a Visiting Researcher and Lecturer at the Technical University of Berlin and the German Economic Research Institute (DIW Berlin). His research is on formulating and solving optimization and game theory models applicable to large-scale systems. Such systems arise when modeling problems in energy and environmental markets, public health, and transportation. He also models engineering design and develops novel algorithms along with supporting mathematical theory.

He has received research funding from the World Bank, Johns Hopkins Health System, the Environment Energy Sustainability Health Institute, and the Norwegian Research Council. In addition, he has collaborated on projects with the International Council on Clean Transportation, Institute of Medicine, National Academy of Engineering, and Bikemore. These projects have included modeling energy and climate markets, patient flow and staffing in hospitals, global vaccination strategies, and urban transport networks.       

He received an A.B. in Mathematics and Public Policy from Franklin & Marshall College and a Ph.D. in Applied Mathematics & Statistics, and Scientific Computation from the University of Maryland, College Park.