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?      

The Case for a Mandatory ALS Registry

There are a lot of scientific questions that we do not have the answers to yet; answers that would allow scientists and healthcare professionals to make prevention recommendations and tailor treatments.  Why do some people get symptom onset in their 30s and others in their 50s and 60s?  Why are some people with ALS such as Stephen Hawking able to live with the disease for over 20 years when most will live only 2 to 5 years after diagnosis?  Why do some people get bulbar onset ALS, which holds a poorer prognosis, and others get limb onset ALS?  Is ALS purely genetic or could there possibly be environmental triggers such as insufficient Vitamin D intake or inability to properly metabolize Vitamin D, psychological stress, viruses and bacteria, or chemicals such as hormone disruptors?  Experts believe there are likely multiple pathways to developing ALS.

Incomplete Information in Existing ALS Registry

The only way to really answer these questions is through lab-based research, observational clinical studies and epidemiological investigations.  Money from the Ice Bucket Challenge is being poured into lab-based research, but will take several months to years to see the results.  Ongoing genetic studies based on blood, spinal fluid, and tissues are identifying and investigating the role of familial linked and other genes.  However, there is no mandatory ALS registry like there is for cancer and infectious diseases in the United States, with the exception of the State of Massachusetts.   

In 2008, Congress enacted the ALS Registry Act (PL 110-373) which charged the Centers for Disease Control and Prevention (CDC) with developing and managing the registry.  It consists of existing administrative data maintained by Medicare, Medicaid, the Veterans Health Administration and the Veterans Benefits Administration, coupled with self-reported data collected via a secure, web portal that was launched on October 19, 2010, to identify additional people who would not be captured by the administrative data.  People registering on the web portal are asked screening questions to verify their ALS diagnosis.  They are also asked information on possible risk factors such as age, race, education, income, work and military history, physical activity, alcohol and tobacco use, and family history of neurodegenerative diseases.  In addition, the Agency for Toxic Substances and Disease Registry, a branch of CDC, funds state and metropolitan registries to obtain more reliable and timely data, including demographic information such as age, sex and race and compares this data with the national registry to determine if certain groups are likely underrepresented in the U.S. statistics.  Areas that have received funding include Florida, New Jersey, and Texas State, and the metropolitan areas of Atlanta, Chicago, Baltimore, Detroit, Las Vegas, Los Angeles, Philadelphia and San Francisco. 

The current ALS Registry is a fairly rigorous registry, but certainly does not capture everyone with possible, probable, or diagnosed ALS because it is not a Census.  That is, with the exception of the State of Massachusetts (Section 26 of Chapter 140 of the Massachusetts Acts of 2003), ALS is not a mandatory notifiable disease.  Secondly, the registry cannot estimate ALS incidence (all new cases of ALS) due to the fact that 68% of the cases in the large administrative data do not have a date of diagnosis.  Third, the online ALS Registry is self-report data, which means anyone could register him or herself as having ALS.  A list of screener questions are used to try to weed out those with suspected or perceived ALS from those who actually have ALS.  However there is no good method for accurately verifying someone in this dataset has actually received a doctor’s diagnosis.    

Diseases that are designated as law binding notifiable diseases such as many infectious diseases require doctors and other healthcare providers and labs to report to the authoritative state agency any case that meets the definition for that disease ensuring almost complete capture of everyone diagnosed with ALS.  This would benefit the ALS Community because it would allow public health agencies to more accurately assess incidence (all new cases of ALS) and prevalence (overall the number of people with ALS at any given point in time).  The current registry likely underestimates the number of people with ALS, which means under times of financial strain they may not receive full priority for research dollars and resources.  It also means that agencies will not be able to detect ALS clusters and possible causal links or priority areas to focus limited resources.        
 
If you want ALS to be a national priority, tell your legislators that you want ALS to be a nationally notifiable disease. 

Reference

Mehta et al (2014).  Prevalence of Amyotrophic Lateral Sclerosis-United States, 2010-2011.  CDC MMWR Surveillance Summary, 63(SS07): 1-14.  http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6307a1.htm

What ALS Can Learn from the Cancer Experience: Bypassing Clinical Trials, A Cautionary Tale

Dr. Siddhartha Mukherjee’s, author of the book, The Emperor of all Maladies: A Biography of Cancer in the PBS Documentary said, “Medicine being the most humane science…sometimes scientists are caught doing inhumane things which is denying experimental drugs.  However, putting a drug on the market too early has had historically devastating events.” 

What Mukherjee is referring to is the consequences of releasing an experimental drug or treatment via Accerlated Access before Phase 3 clinical trials have been undertaken.  An example of this is the STAMP treatment for breast cancer in the 1980s and 1990s.

In 1983, Dr. Peters and Dr. Frei started breast cancer clinical trials on a new therapy previously shown to have some success at treating childhood leukemia, known as the Solid Tumor Autologous Marrow Program (STAMP).  STAMP involved extracting bone marrow from the participant and freezing it, then wiping out their cancer with extremely high doses of chemotherapy, and injecting the bone marrow back into the person so that the high-dose chemotherapy wouldn’t kill them.  Promising success in Phase 1 and 2 clinical trials with breast cancer patients encouraged women who could not participate in the trials to seek accelerated approval of the treatment.  Soon 30,000 some women received access to the experimental therapy between 1985 and 1998 at the cost of millions of dollars.  The study could not recruit people for the Phase 3 clinical trials because no one wanted to be in the control group.  About 1 in 5 women died from the treatment and it was later shown that the higher dose of chemotherapy was not any more successful than the lower doses in improving women’s survival.  And in fact there was a higher chance of death due to the bone marrow implants.  Those who did survive the procedure suffered long term cognitive problems such as short term memory loss.     

    

Some of you might still be asking yourselves, so what’s the big deal?  The women at least got a chance to try something?  The big deal is that an experimental treatment that has not gone through the full round of required clinical trials carries a higher risk of actually shortening the person’s life if not killing them.  Perhaps someone who is near the tail end of their disease is willing to take this risk, but what if you are someone who is early on in their disease?  By foregoing clinical trials you risk shortened lifespan, death, and the right to try other treatments that might become available.  That’s right, clinical trials have strict inclusion and exclusion criteria.  Meaning, in order for the researchers to know without a doubt that their treatment is having an effect, they cannot allow anyone into the trial that has taken other experimental drugs.  Moreover, what if a drug is approved for Accelerated Access and a large number of people start taking the drug and suddenly have major toxic reactions or die.  Even if this is unrelated to the treatment itself, such an event might trigger the FDA to remove the treatment from the market altogether…that’s it.  A possible beneficial treatment to some people with ALS will never reach them.        

  

I’m not saying we should not seek treatments through Accelerated Access period. I’m simply saying there is a time and place.  The U.S. FDA Evaluation team is in place to insure consumer safety.  If companies can satisfy their requirements that show scientifically that their treatment warrants Accelerated Access based on evidence that is safe and efficacious than this is a good thing.  If not, we should consider other options for treatments outside clinical trials such as Widespread and Group Expanded Access, which is politically more kosher with the U.S. FDA and doesn’t hinder the clinical trial process. 

On May 10, let’s ask our policy-makers to work with ALS advocates, pharmaceutical and biotechnology companies, the Centers for Medicare and Medicaid Services and the U.S. FDA to remove barriers for companies to offer Expanded Access to People with ALS.

What ALS Can Learn from the Cancer Experience: Identify and Support Champions and Change Agents

The Cancer Experience is full of champions and change agents, people who were passionate about discovering novel treatments and funding those endeavors to help humankind.  We’ve already discussed the science and medical pioneers Dr. Sidney Farber and Dr. Brian Fisher in our previous post who at the time were villonized for going up against the status quo, but prevailed by their unrelenting persistence to practice evidence-based medicine and help others.        

Dr. Dennis Slaman from the UCLA Medical Center was also a champion and change agent in The Cancer Experience.  During the 1990s oncogenes responsible for the development of cancer were discovered.  One such gene known as Her2 was implicated in some forms of breast cancer.  Genentech, a biotechnology company, recruited Slaman to help gather Her2 positive breast cancer tissue samples for testing with Dr. Ulrich and Dr. Shepard’s Her2 antibody therapy called Herceptin (chemical name Trastuzumab).  Dr. Slaman felt that herceptin was so promising that he wanted Genentech to apply for an FDA application to go to clinical trial, but the company refused because at the time it was a small company and the expenses for clinical trial would be too enormous.  Slaman kept lobbying the company until they finally agreed to trials among people with late-stage metastatic breast cancer.  Herceptin received FDA approval in September 1998.  Today herceptin is used to treat Her2 positive metastatic breast cancer, stomach and esophageal cancers.  Had Slaman not been on the scene advocating for clinical trials, this life-saving drug may not be available on the market today.     

Lastly, Mary Lasker, wealthy socialite, who in the 1940s through 1970s built political support and private-public funding that made cancer a national priority and advanced cancer treatments that saved millions of lives.  Mary Lasker grew up in a small town in Wisconsin where she grew an appreciation for illness and suffering having experienced life-threatening illness herself and seeing her beloved caretaker die in a breast cancer ward.  She grew her wealth and influence building her own dress pattern business and marrying her second husband Albert Lasker, business advertiser for Lucky Strike cigarettes.  Mary Lasker had an unwavering desire to help people suffering from cancer.  She started her journey hosting fundraisers in their home.  In 1944, she established the American Society for the Control of Cancer (renamed the American Cancer Society) to raise cancer awareness, reduce stigma, and raise money for research. 

After her husband died from colon cancer in 1952, Lasker partnered with Dr. Sidney Farber (Dana Farber Cancer Research Institute), founder of the Children’s Cancer Research Foundation and a change agent in science and medicine for his breakthroughs in chemotherapy.  Lasker and Farber focused their efforts to build a cancer research infrastructure known as the National Cancer Institute.  They recruited a diverse group of scientists, including Dr. Gordon Zubrod, an infectious disease doctor who previously worked with malaria in the army to head the recently well funded National Cancer Institute (NCI).  The researchers started a worldwide search for plant compounds in search of new cancer drugs.  Large clinical trials for childhood cancers and their families flocked to the institute.  Changes in the delivery of chemotherapy emerged, including the 1952 VAMP trials, which looked at delivering four chemotherapeutics instead of one to fight cancers that were outmaneuvering a single chemotherapy.  She soon realized that private funding alone was insufficient and began lobbied presidents for policy change and public funding.  Her efforts led to President Nixon’s 1969 Declaration of a War on Cancer. 

In 1971, a cancer bill with bipartisan sponsorship from Senator Edward Kennedy (Democrat) and Jacob Javits (Republican) went into legislative action.  Lasker’s journalist friend at the New York Post, Ann Landers wrote an article to influence the public to write into their politicians titled “If you want to be part of an effort that might save millions of lives-maybe your own-please stay with me.”  Thousands of letters poured into the capital mailrooms.  The result was a $1.6 billion dollars in the first three years towards cancer research known as the 1971 American Cancer Act.   

                   

What qualities did Lasker, Farber, Slayman and other change agents in The Cancer Experience have in common?  And how can knowing this help the ALS Community? 

Malcom Gladwell in his book The Tipping Point: How Little Things Can Make a Big Difference (2000) says ideas, products, messages, and behaviors spread like viruses until they become a type of viral epidemic or what he refers to as a ‘social epidemic.’  In any social epidemic leading to major societal changes 80-percent of the work will be done by 20-percent of the participants.

Three types of people are required for the “tipping point” to occur, the point at which a threshold or boiling point is reached where an idea, message, or behavior turns to real societal change.

(1)   Connectors

(2)   Mavens

(3)   Salespeople          

Connectors are the people in a community who know large numbers of people and who are in the habit of making introductions.  They usually know people across an array of social, cultural, professional and economic circles and make it a habit of introducing people who work or live in different circles.  They have an extraordinary knack for bringing the world together. 

Mavens are information specialists or people we rely upon to connect us with new information.  They accumulate knowledge, especially about the marketplace and know how to share it with others.  A maven is someone who wants to solve other people’s problems generally by solving his own.  Mavens start word-of-mouth epidemics due to their knowledge, social skills and ability to communicate.  They are information brokers, sharing and trading what they know. 

Salespeople are persuaders, charismatic people with powerful negotiation skills.  They tend to have an indefinable trait that goes beyond what they say, which makes others want to agree with them. 

Some people have two of these skills.  Most only have one.  Farber and Slayman were both Mavens and Salespeople, experts in science and medicine who could communicate their specialized knowledge to the layperson and sell their ideas to sponsors to fund the research and pursue clinical trials.  Mary Lasker was indeed a unique individual because she was a Connector, Maven, and Salesperson.  She was well read and learned more about research and needs through scientists like Farber.  She was an extrovert, had a large and diverse social network, and knew how to use her skills to connect the right people at the right time and persuade policy makers and entrepreneurs to fund the War on Cancer.  Certainly there were other game changers in the field that made significant contributions, but without major funding and political will to make real advancements in cancer we would not have the multiple treatment options we have today.  

  

The hope to have effective treatment options for ALS/MND is not out of reach.  We must identify our Connectors, Mavens, and Salespeople to educate, communicate the research and policy reform needs of the ALS community, and rally policy makers and entrepreneurs to get on board.  

May is ALS awareness month.  On May 10 the ALS Community will stand strong at the Capitol.  We need to think BIG.  Think Mary Lasker and Sidney Farber.  Think War on Orphan Diseases, War on ALS.  We need sufficient private AND public funding for research.  And we need policy reform that provides real incentives for pharmaceutical and biotechnology companies to provide treatments for people with ALS NOW through Accelerated Access and Expanded Access Programs.  Policy reform with Accelerated Access and Expanded Access Programs will not only affect those living with ALS but those suffering other diseases.  Think BIG.  If we can garner this much support with the ALS Community, imagine how much support there would be if we connected with people suffering other illness. 

As the saying goes, “Don’t put your eggs in one basket.”  Don’t focus on one treatment.  Think BIG.  We want MANY TREATMENT OPTIONS.  Most FDA requests for Expanded Access (90-99%) are approved.  But only when the companies say ‘yes.’  Companies are hesitant to provide treatments to people outside clinical trials for several reasons. (1) They do not want to be sued if someone has major side effects or becomes worse even if it is not due to the treatment, (2) They do not want to pay for the treatment and costs associated with the delivery of that treatment, (3) They do not want to risk possible bad results that would jeopardize their chance of continuing to bring the treatment to market.  ALS Community, Please focus your efforts here.  Work with patient advocates, policy makers, industry, FDA, and insurance companies to come to an agreement.  Find a policy solution to make it easier for companies to say ‘YES’ to Accelerated Approval and Expanded Access Programs.