White House Precision Medicine Initiative: Are the Risks Worth the Gain?

“Doctors have always recognized that every patient is unique, and doctors have always tried to tailor their treatments as best they can to individuals.  You can match a blood transfusion to a blood type-that was an important discovery.  What if matching a cancer cure to our genetic code was just as easy, just as standard?  What if figuring out the right dose of medicine was as simple as taking our temperature?” -President Obama, January 30, 2015

In January 2015 during the State of the Union Address, President Obama announced his plans to launch The White House Precision Medicine Initiative (PMI), a revolutionary approach to the way we collect, conduct, and share disease research. 

The overarching goal of the White House PMI is to create a global warehouse of electronic medical and science data from diverse data sources including medical records, genomics, lifestyle and environment, and personal device/sensor data.  Currently these types of data are collected inconsistently, using different methods, and stored across organizations and agencies such as medical clinics, hospitals, healthcare and insurance systems, state and federal health departments and other state and federal agencies, clinical trial locations, and private pharmaceutical and biotechnology companies. 

Those in research are often frustrated by this reality because it takes a lot of time and money to request data from these various sources.  When data is provided it is aggregated and does not allow the researcher to link individuals across data sources, which would allow scientists to answer several important research questions.  For example, if set up correctly such a data warehouse would give scientists the ability to identify specific chemical or other environmental exposures, lifestyle habits, and genetics and molecular pathways associated with disease.  Knowing this will better enable public health to provide recommendations for maintaining good health and preventing disease.  It would allow regulatory agencies the ability to more accurately create safe exposure limits on chemicals in our environment.  And it would allow clinical researchers to develop tailored treatments for both common and rare diseases, and treatments that would be effective on an individual’s specific type of disease based on their genetics with minimal side effects. 

In March 2015, the White House convened an interagency working group charged with developing a set of privacy principles for PMI.  On July 8, the White House held a live-streaming conference to discuss the Precision Medicine Initiative and publicize the following:

·        White House PMI Website

·        Patients who have benefited from precision medicine

·        Individuals and Organizations who are supporting the PMI, known as White House Champions of Change (#whchamps)

·        The Interagency Working Group Proposed Privacy and Trust Principles for public comment (due by August 7, 2015).  

The President’s PMI plan is to focus on cancer first then build in other diseases including rare diseases such as ALS/MND.  The PMI will enlist 100,000 patients to volunteer in a pilot study that will help the Interagency Working Group to refine their procedures and policies required to implement the larger project.  In order for this to be a success, the White House needs patient buy-in that they are trying to garner through these Champions of Change supports, opportunity for public comment on proposals, and outreach through social media.    

PALS Campaign reviewed the Precision Medicine Initiative: Proposed Privacy and Trust Principles document.  We feel that the PMI is a very ambitious project with laudable goals, however we are gravely concerned about the inherent data privacy issues with attempting such a large-scale, and globally accessible project and have a number of questions.

Who will be the primary data holder(s) and what will this data system look like? How will the White House protect against cyber attacks and network hacking?  And how can we be assured that personal health information will be used strictly for the research purposes intended under the PMI? 

Having one entity responsible for warehousing the data, for example the National Institutes of Health (NIH) or Centers for Disease Control (CDC), would hopefully insure better data accuracy and consistency, however this would pose a greater data security risk.  Look at the recent U.S. federal data breach of 22.1 million federal employees and their family members where the Chinese government is said to have stolen American home addresses, social security numbers, mental and criminal background checks and fingerprints.  The size and nature of such a cyber attack does not really increase a sense of safety when it comes to signing over information on your full DNA profile and other personal health information.  And what about people who work for the agencies themselves?  What restricted access protocols will be in place to insure that data breaches don’t occur within the system? 

We believe the best architecture for a PMI data warehouse would be to operate it similarly to how other active health reporting/surveillance systems work.  Federal agencies will work with clinical researchers, epidemiologists, patients, advocacy organizations, etc… to develop a set core of measures and datasets that will be compiled.  These protocols will be provided to states with training.  State agencies work with the various data holders, e.g. medical clinics, hospitals, healthcare systems, etc… to link data sources to individuals.  The database is then cleaned so that errors are corrected and each individual is given a unique identifier known only to that agency.  States send their database updates to the responsible federal agency (e.g. CDC, NIH) who will compile state data into a national database.  In this architecture, individual data can be linked to the various data sources, but will be de-identified at the national level. No names, birthdates, or addresses will be associated with the dataset that researchers analyze, however it can be linked back at the state level using the states known unique identifier for reporting results back to the individual.  This architecture would not 100-percent guarantee that PMI at the state level would not be breached, but would reduce the chance of a major and severe data breach at the federal level. 

What will be the Institutional Review Board (IRB) process and who will sit on the committee?  How will the White House insure informed consent is upheld?

Fundamental Assumptions About the PMI Cohort (Number 3) of the PMI document states that the intended researchers will include academic, non-profit, and for-profit entities.  It also says the scope of research will be broad-based, not only for answering specific questions but also for hypothesis generation.  Patients and study participants are a lot more cautious about signing over their personal information for research given past research abuses.  Two research frameworks that we recommend the White House use include: Community-Based Participatory Research (Israel et al, 2005) and Reality-Based Research (Poupart et al, 2009).  These frameworks include study participants throughout the process, from project design to implementation and information dissemination.  What would this look like?  Patients, their caregivers, and advocates would be included on all planning and decision committees, including the IRB.  One issue previously raised was whether or not a personal record could be contained within the database once that person has passed away and could no longer provide consent for release of their records.  We feel that every effort should be made to get informed consent for records pertaining to genome information, however in the case of death or lost to follow-up an IRB consisting of people with the disease would be appropriate representation. All information provided to patients and their family members including informed consent forms and research results should be written in plain language, health literacy, and numeracy best practices.  In keeping with an authentic partnership under CBPR and RBR frameworks, information must be in a format that will be understandable.  Common medical and scientific jargon, including presentation of data in graphs and tables is confusing for most people.  The PMI should consult with health literacy experts to insure that forms and reports are understandable.           

How will this be paid for?

Lastly, how will this system be paid for?  The large nature of the project, multiple individuals that would need to be involved, database and security development will not come cheap.  If people must volunteer to become part of this database then will the data collected be truly representative at a population level? 

White House Precision Medicine Initiative: Are the Risks Worth the Gain?  That is up to you.  Public comment on the Precision Medicine Initiative: Proposed Privacy and Trust Principles is due August 7, 2015 using an online form available at the White House PMI Website.  PALSFirst Campaign encourages all PALS and CALS to read this document and provide feedback. 

 

References

Collins and Varmus.  A New Initiative on Precision Medicine.  The New England Journal of Medicine, 372 (9), February 2015.

Nakashmia, Ellen (2015, July 9).  Hacks of OPM databases compromised 22.1 million people, federal authorities say.  The Washington Post.

Poupart, Baker, and Red Horse (2009).  Research with American Indian communities: The value of authentic partnerships.  Children and Youth Services, 31(11): 1180-1186.

Israel, Eng, Schultz et al (2005).  Methods in Community-Based Participatory Research for Health, 1^st Edition.  Jossey-Bass.

The Precision Medicine Initiative.  The White House, 2015.

Precision Medicine Initiative: Proposed Privacy and Trust Principles.  The White House, July 8, 2015.

#WhiteHouse #PrecisionMedicine #whchamps #endals #nowhiteflags #ICantWait #ALSA  

Should companies be allowed to deny patients access to experimental treatments for life-threatening diseases?

Last year Arthur Caplan and Kenneth Moch published a very thought provoking article in the Health Affairs Blog, “Rescue Me: The Challenge of Compassionate Use in the Social Media Era.”  In the article they touch on the ethics and policies of denying access to potentially life-saving treatments. 

Caplan and Moch (2014) state, “The question of whether there is a duty to pay for the use of unproven and experimental therapies to attempt to rescue individuals in dire medical straits, even those with poor odds of success, is one that health policy makers have not acknowledged as part of ongoing national health care debates in the United States and other nations…The duty to seek to rescue those in very dire straits is a powerful norm in American society and in major religious traditions around the world.  Whether it is coal miners trapped in a mine, mountaineers stranded on a peak or a child fallen in a long abandoned well, it is very clear that, despite difficultly and cost, society wants strenuous rescue efforts to be made.  Health policy discussions often fail to reflect this deep moral concern as shown in the absence of attention to the issue of ‘rescue’ and in the lack of funding in public and private insurance for attempting to do so.”    

It would seem then that unless there is in-your-face coverage of the injuries and death caused by denying patients access to potentially life-threatening disease, there will be no movement towards Expanded Access or Accelerated Access Programs for ALS or other rare diseases. 

Caplan and Moch (2014) discuss the case of 7-year old Josh Hardy who in March 2013 was denied access to the experimental drug Brincidofovir (Chimerix, Inc.).  Chimerix, the North Carolina based pharmaceutical company had previously made brincidofovir available to over 430 critically ill patients under an Expanded Access Program initiated by several individual doctor-sponsored emergency INDs in 2009, and later funded for 215 more patients through funding from the Health and Human Services Biomedical Advanced Research and Development Authority (BARDA).  It was only after a social media cry for help (#SaveJosh) followed by a smear campaign against Chimerix (#SaveJosh), which lead to televised media coverage and letters and phone calls to politicians that Hardy received the necessary treatment.  The irony of the situation is that after Chimerix released the drug to Hardy, the company was applauded online and stocks rose by fifty-percent. 

So I ask myself, why are companies developing ALS and rare disease treatments denied expanded access left and right?  Why are there only a few companies that have clear, transparent policies on Expanded Access, procedures, and contacts listed on their webpage?  Why are people who do participate in these clinical trials taken off the treatment to observe for follow-up even when their clinical measures have improved?  Why do we not yet have FDA Guidelines specific for conducting clinical trials research and expanded access programs with ALS and other rare diseases that include input from those actually afflicted? 

Speaking to advocates in cancer, HIV/AIDS, and tuberculosis, diseases where you can actually find Expanded Access Programs available, you will hear that they have faced these same issues.  It is history repeating itself.  You would think that people suffering rare, fatal diseases today would not have to suffer through the same hurdles.  What we should be doing as PALS, CALS, and advocates is work with the U.S. FDA, HHS, NIH, politicians, public and private insurance companies and pharmaceutical/biotechnology companies to overhaul the current system. 

The FDA permits pharmaceutical/biotechnology companies to conduct clinical trials in the United States. Public dollars from NIH, DOD, etc…fund their research and FDA has provided them with additional funding and expedited status for those investigating rare diseases.  In the end the companies negotiate treatment costs and extend patents to the maximum to maintain their high rates.  How are people with the disease benefiting?  How are those who participate in clinical trials benefiting when the treatment is taken away after the trial has ended?

The solution is the political will to rescue people with potentially life-saving treatments like they do for those caught in an avalanche, or buried underground.  We could require companies who conduct trials in the United States to have clear policies on Expanded Access, procedures, and contacts posted on their websites.  We could also require companies to provide a minimum quota of expanded access patients for each clinical trial they conduct.  And also require that if a treatment that is shown to be safe and improve clinical measures to a patient enrolled in a clinical trial, that they be allowed to continue that treatment once follow-up measures have been made.  It would also behoove many to create clear FDA Guidelines for clinical trials research and expanded access programs for ALS and other rare diseases in collaboration with researchers, treating doctors, companies, patients and caregivers.  When all else fails, make some noise.  Social media and televised stories can be powerful tools.        

 

    

PALSFirst Campaign Leader Dies Friday from ALS

Cheryl Anne Beede-Sweeney, courageous wife, daughter, sister, and mother of three passed away Friday, July 3, 2015 in Duluth, Minnesota after a long battle with Amyotrophic Lateral Sclerosis (ALS)/Motor Neuron Disease (MND).  

ALS, also known as Lou Gehrig's Disease is a fatal disease that rips away your ability to move, eat, speak, and breathe. Every 90 minutes someone is diagnosed with ALS and another dies.  There is no cure for ALS.  Only one drug on the market exists that prolongs life on average only three months.  Like many people with ALS, Cheryl did not qualify to participate in clinical trials due to current lengthy diagnostic criteria and strict inclusion/exclusion criteria.  Years were spent trying to access BrainStorm Cell Inc.'s NurOwn stem cell treatment via the U.S. FDA Expanded Access Program, but BrainStorm Cell Inc. denied her access to this potentially life saving treatment, thus was the birth of the PALSFirst Campaign.   

Cheryl truly was the heart and soul of the PALSFirst Campaign.  She was a natural leader, advocate, and faith-based healer.  Her smile, continuous love for others, and hope that there would be a cure someday for ALS filled others with joy.   More than anything, Cheryl wished for others suffering from ALS to have the opportunity to try new treatments through clinical trial redesign, U.S. FDA Accelerated Access and Expanded Access Programs, and policy reform.  Cheryl's presence will be greatly missed, but her legacy will live on with the PALSFirst Campaign and all those who continue to fight for access to treatments.  

Cheryl Beede Sweeney's Obituary

Empathy in Science, Medicine, and All Policies

“The moral test of a nation is how it treats those who are at the dawn of life, the children; those who are in the twilight of life, the aged; and those who are in the shadow of life, the sick, the needy, and the handicapped.”  -Hubert H. Humphrey (1976) 

Today marks the end of ALS Awareness Month, but the fight lives on for those suffering with ALS, their caregivers, close family and friends, and advocates.  On this last day of May, PALS Campaign reflects on the future of ALS research, treatments, and the community stronghold and calls for Empathy in Science, Medicine, and All Policies.    

It is humbling to see the awareness and interest in private funding for ALS grow, peaked by the efforts of the ALS Ice Bucket Challenge, numerous films and personal accounts in the social media, the Steve Gleason Act, and rallying at the Capitol over GM604.  It is with great sadness that we also realize we are likely decades away from real change.

 

HIV/AIDS and Cancer-two diseases that rose in status from diseases no one wanted to acknowledge or were too overwhelmed or scared to deal with to widespread public awareness and finally major public and private financial investment and policy change that led to the advancement of and access to treatments.  What turned the needle in favor of critical change was the marriage of radical advocacy and science. 

After several years dancing the two-step with politicians, change advocates in HIV/AIDS and Cancer realized they needed to get more radical in order to gain the media attention needed to drive political pressure and shame companies into providing experimental treatments to those suffering and dying of their diseases.  These advocates became so well organized that they knew the date, time, and location of every investment meeting for experimental pharmaceuticals, every NIH, FDA and policymaker meetings and events and every location of the biotechnology and pharmaceutical company headquarters.  Why?  Because these are the ideal locations and times to hold rallies and protest companies that deny access to treatments.  These two movements held funeral processions at company headquarters, honoring those who had asked for treatments, were denied, and subsequently died.  The larger the rally or protest, the more media attention they received.       

           

This alone was not enough to fight the war.  They needed true scholars, people who empathized with those suffering, were well read, well educated and had the necessary skills to guide the movement in the right direction.  These individuals didn’t read a few journal articles or a few web pages on the Internet and assumed they knew everything.  They looked at the issue from all angles-science, medicine, policy, advocacy and sought out content experts, those in government and policy to understand the processes behind FDA rules and regulations, scientific limitations, etc…  They asked the right questions, identified hurdles and sought big picture solutions.  They didn’t focus on one drug or blamed all their woes on one government agency.  They changed how we fundamentally look at drug development, clinical trial design, and created the FDA Accelerated Access and Expanded Access programs.

Interviews with government agency heads and policymakers said the radical protests and rallies grabbed their attention, but it was the scholars that came to them with specific solutions and knew the language of science which allowed them to make real changes that made all the difference in the world.   

Competing interests, financial drain, and low political will prevents us from moving the needle from ALS awareness to fundamental changes: major public-private financial investment in research, developing new clinical guidelines and clinical trial designs for ALS, creation of a mandatory national ALS registry, creation of a health literate, consumer friendly clinical trial search engine, encouraging Accelerated Access of experimental drugs deemed reasonably safe and effective in Phase 2 trials and Expanded Access of experimental drugs and treatments that do not qualify for Accelerated Access.  These goals are within reach if the ALS Community marries radical rallies and protests with sound science.     

PALS Campaign also calls to action Empathy in Science, Medicine, and All Policies.  There are three ways in which we engage with a disease: sympathizing, empathizing, and understanding.  Sympathizing, is feeling compassionate towards someone’s suffering.  Empathizing is getting towards the core of your feelings, trying to picture yourself in that person’s shoes.  And understanding is when someone actually has the disease.  Those with the power of decision making, the doctors and scientists responsible for researching the disease and treating patients, the businesses that hold future treatments, and policymakers that make decisions on the processes and incentives in place may show sympathy towards those with ALS.  Unless they themselves have ALS, they can never truly understand what it is like.  But the call to action is this-Let Empathy drive your decisions in science, medicine and policy.  Imagine yourselves in the shoes of someone with ALS.  If you lost your ability to walk, eat, speak and move, how would you like to be treated in clinic?  What would your priorities be in scientific development?  Wouldn’t you want policymakers, industry, government, advocates to work together to provide more options for treatments?      

What ALS Can Learn from the Cancer Experience: To Move Forward We Must Look Back

To move forward, we need to reflect on the past.  The Spanish philosopher, essayist, poet and novelist George Santayana once famously said, “Those who cannot remember the past are condemned to repeat it.”  Not knowing your history can indeed have devastating consequences both in repeating mistakes but also not capitalizing on opportunities.

 

The Cancer Experience teaches us that developing successful treatments is not easy.  There are a lot of hurdles that must be overcome including technological, financial, political and socio-cultural.  Complicated diseases need a full-forced commitment of funding and political will.  It took decades, billions of dollars, and strong political commitment to fund cancer scientists and medical doctors whose research efforts helped lay the foundation for advancements in medical procedures, radiation therapy, chemotherapies, hormone and immune therapies that we benefit from today.     

This was made possible through huge financial investments not just from private donations, but also sizable public funding.  Mary Lasker and Dr. Sidney Farber spearheaded the private-public funding effort in the 1960s, which resulted in enactment of the 1971 Cancer Act, and billions of dollars in funding towards the National Cancer Institute.  The Ice Bucket Challenge was a major breakthrough in private funding for research, now we need equal commitment for public funding to support non-profit universities, teaching hospitals, institutes and government agencies.  Places such as the Robert Packard Center for ALS Research at Johns Hopkins, National Institutes of Neurological Disorders and Stroke, and ALS Treatment Development Institute. 

The Cancer Experience teaches us that it is important for grant dollars to be flexible and support a diverse workforce of researchers.  The most innovative, game changing cancer therapies came from the minds of new doctors and researchers in the field, people with fresh eyes, willing to take more risks and think out of the box.  People like Dr. Bernard Fisher who in 1958 went against an almost 70 year practice of the radical mastectomy and proved through randomized control trials that women who underwent breast conserving surgery also known as the lumpectomy had the same survival rates as women who underwent a radical mastectomy.  People like Dr. Sidney Farber who in 1947 went against the medical community by giving children suffering with leukemia the experimental chemotherapeutic, aminopterin.  The standard at the time was to make children comfortable until their inevitable death.  Aminopterin allowed some of the children to go into remission.  Had these medical renegades not been hired and given resources, evidence-based practices would not have been developed, advancements in treatment would have been lost.

Today, the lack of research dollars for the biomedical sciences has stymied advancements.  In order for new scientists and medical doctors to even be considered in the applicant pool of 300 or more people vying for the same job, they must already have funding.  To get funding, scientists and medical doctors must be affiliated with a university or a government facility.  A catch-22 occurs, resulting in small numbers of scientists and medical doctors, experienced but not necessarily game-changers; all competing for finite resources.  A substantial amount of grants require a significant amount of preliminary data generated by the Principal Investigator (lead scientist) and proof of success.  Therefore, high-risk projects that may challenge current paradigms or lead to new therapeutics are less likely to be funded compared to “inside the box” ideas.  The ALS Community must identify the Dr. Sidney Farbers and Mary Laskers and pave the way for real commitment through policy change and private-public funding.

What ALS Can Learn from the Cancer Experience: Introduction

It was 1969 and President Nixon declared a War on Cancer.  Despite being in the midst of a recession caused by the Vietnam War, billions of dollars were poured into cancer research and a new era in cancer’s history started.  Cancer was once a disease scientists knew little about, a disease no one wanted to discuss became a national priority.

This change didn’t come about suddenly.  As a field of science it has span time in memoriam, from early Egyptian papyrus that documented some of the earliest cases of breast cancer, to the invention of early treatments such as the radical mastectomy and radiation therapy of the 1890s, to the diverse chemotherapies, hormone therapy and immune therapy of today.  This success story has multiple heroes.  First there were the dedicated scientists with an insatiable appetite for discovery, conviction to eliminate human suffering, and defiance against the status quo.  Next on the scene were the entrepreneurs and visionaries that spearheaded private and public funding efforts, followed by American citizens who both suffered from the disease and watched their friends and family members die of the disease until a boiling point was reached and they said ‘We’re not going to take it anymore.”

The history, science, medicine, and politics of cancer were beautifully summarized in Siddhartha Mukherjee’s book, The Emperor of all Maladies: A Biography of Cancer, recently turned into a PBS documentary film by Director Ken Burns.  Most striking about this film is the parallels to other major diseases and public health funded projects in U.S. history; parallels that the ALS/MND Community can learn from and apply to advance ALS science, treatments, and access to experimental drugs and therapies outside of clinical trials.  

This post is one of a five part series on lessons learned from The Cancer Experience:

• Introduction
• To Move Forward We Must Look Back
• Identifyand Support Champions and Change Agents
• Bypassing Clinical Trials, A Cautionary Tale
• American Public Can be a Powerful Change Agent