TELL ME WHAT I NEED TO KNOW: A Patient Advocate’s guide to being a Patient Advocate

A few weeks ago I was at the CIRM Alpha Stem Cell Clinic Network Symposium at UCLA and was fortunate enough to hear Gianna McMillan speak about patient advocacy. It was a powerful, moving, funny, and truly engaging talk. I quickly realized I wanted to blog about her talk and so for the first few minutes I was busy taking notes as fast as I could.  And then I realized that a simple blog could never do justice to what Gianna was saying, that what we needed was to run the whole presentation. So here it is.

Gianna McMillan

Gianna McMillan at the CIRM Alpha Stem Cell Clinic Symposium: Photo courtesy UCLA

TELL ME WHAT I NEED TO KNOW

Gianna McMillan, MA – Patient/Subject Advocate, Bioethics Institute at Loyola Marymount University

Stem cell research and regenerative medicine are appealing topics because patients, families and society are weary of inelegant medical interventions that inflict, in some cases, as much harm as benefit. We are tired of putting poison in our loved ones to kill their cancer or feeling helpless as other diseases attack our own bodily functions. California, full of dreamers and go-getters, has enthusiastically embraced this new technology—but it is important to remember that all biomedical research— even in a new field as exciting and inspiring as stem cell therapeutics – must adhere to basic premises. It must be valid science and it must be based on an ethical partnership with patients and research subjects.

In the world of research ethics, I wear a lot of hats. I have been a subject, a care-giver, an Institutional Review Board (IRB) member (someone who actually reviews and approves research studies before they are allowed to proceed), and I have worked with the government on regulatory committees. These days I am finishing my doctoral studies in Bioethics, and while I love the interplay of philosophy and ethical principles, I most truly identify as an in-the-trenches Patient/Subject Advocate. I am compelled to champion patients who struggle with new and devastating diagnoses, hoping desperately for a cure, and who might be faced with decisions about participating in research for their own benefit and for the greater good of science.

In the old days, doctors made decisions on behalf of their patients— who, meekly grateful for the guidance, did whatever they were told. It is a little different now. Patients are better informed, often do their own homework, and demand to be an integral part of their treatment plan. The world of research has undergone similar changes. Instead of investigators “doing things to research subjects”, best practices involve patients in the design of clinical trials. Patients and experienced subjects help decide what specific questions should be the focus of the research; they identify endpoints in the research that are meaningful to the patient population being studied; and they assist in devising tools for patient-reported outcomes and delivery of study results.

The investigator and the research subject have come to be seen as partners.

While the evolution of this important relationship is healthy and wonderful, it should not be assumed that this is an equal partnership. Why? Because subjects are always at a disadvantage.  I realize that this might be an uncomfortable concept. Physician-investigators in charge of the study might want to qualify this statement it by insisting “but we do our best to accommodate their needs”. Subjects would also rather not admit this—because it is hard to make a decision with confidence while simultaneously acknowledging, “I am really at a disadvantage here.”

However, I have learned the hard way that an honest partnership requires addressing some uncomfortable realities.

A short personal story illustrates what I am talking about. When my oldest son was five years old, he was diagnosed with malignant brain cancer. Before meeting with our son’s treatment team for the first time, my husband and I decided that my husband, articulate and concise, would take the lead. He had a legal pad, with a list of questions… each question and answer would take us down the page until, at last, we would use all the information to make a decision—a life or death decision – on behalf of our young child.

In the meeting, the neurosurgeon pointed at brain scans and explained a few things. And then radiologist drew pictures of machines and treatment angles. The oncologist described risks and benefits and side effects. Then we all looked expectantly at my husband—because it was his turn. This lovely man opened his mouth. And closed his mouth. And then burst into tears, holding that legal pad over his chest like a shield. He could not speak. After a few seconds of horrified silence, I stammered out what few questions I could remember. The doctors answered, of course. Their mouths moved, and I leaned in and nodded while making eye contact – but I have no idea what they said.  All I heard was a loud white noise that filled my skull and my husband’s raspy breathing, and my own voice crying out in my head – “Oh my God! My child! My child!”

The point of this story is to illustrate that good people, educated and prepared, ready to bring their best selves to make the most important decision they would ever make, one that would affect the life of a beloved child— these people could not function. Despite this, in just a few days’ time, we were introduced to a research study, one that might cure our child while limiting the damage to his growing brain.  No matter how well-intentioned the research team was—no matter how desirous they were of a “partnership” with us, we were at such a distinct disadvantage, that the relationship we had with these investigators could not be categorized as one “among equals”.

Even now, more than twenty years later, it is painful for me to reflect on this. But I have learned, working with hundreds of families whose children went into clinical trials, that if we can be honest about the dysfunctional nature of this situation, we might take some action to improve it. Let me be specific about the ways research subjects are at a disadvantage.

  1. They often don’t speak the language of the disease.
  2. They are unfamiliar with the process of research.
  3. They are wrestling with emotions: despair, denial, anger and hope.
  4. Their life has been disrupted – and there are consequences.

Compare this with the research team, who knows the lingo, designed the research plan, is not personally affected by the scenario and well, this is business as usual: enroll a subject, let’s get going! How is the notion of “partnership” affected by such unequal circumstances?

Is a meaningful “partnership” even possible?

I say, yes! And this notion of “partnership” is especially important as new technologies come to invade intimate qualities of “self” and the building blocks of what makes each of us human. However, we need to be realistic about what this partnership looks like. It is not equal.  I am going to take a stand here and say that the partner who has the advantage (in this case, the researcher/scientist) is morally obligated to meaningfully address the disadvantage of the other party. This bears repeating. The partner who has the advantage is morally obligated to meaningfully address the disadvantage of the other party.

Over the years, families and subjects have told me what they want and need from the doctors and researchers they work with. They say:

  1. Tell me what I need to know.
  2. Tell me in a way I can hear it.
  3. Tell me again and again.

Let me expand on these a bit. First, if I am a patient new to a diagnosis, a treatment or research—I probably do not know what I do not know. Help me learn vocabulary, procedures, and systems. Tell me about the elements of informed consent so that I recognize them when I see them in the documents you want me to sign. Explain the difference between “standard of care” and “experimental treatment”. Help me understand the research question in the context of the disease (in general) and my own ailment (in particular). Give me the words to ask the questions that I should be asking.

Secondly, there are many different ways of sharing this information: print, video, websites, peer mentors, nurse-educators, and research team members. Hit the topic from all sides and in multiple formats. Thirdly, please realize that there is a learning curve for me— and it is closely tied to my emotional journey with my predicament. I may not be able to absorb certain facts at the very beginning, but a few weeks later I might be mentally and cognitively in a different place. And obviously, I might be an inexperienced research subject when I sign the consent form— but a few months later I will be vastly more sophisticated and at that time, I need the opportunity to ask my more considered and context-savvy questions.

I want to point out that researchers have access to a deep well of wisdom – a resource that can advise and support ethical actions that will help their disadvantaged partners: researchers can ask their experienced subjects for advice.

Remember those hundreds of families I worked with, whose children ultimately enrolled in clinical trials? These experienced parents say:

  • Let me tell you what I needed to know.
  • Let me tell you how I needed to hear it.

Getting input from these experienced subjects and caregivers does two things.

First, the research team is leveraging the investment they have already made in the participants of their studies; and secondly — very importantly — they are empowering the previously disadvantaged partner. Experienced subjects can to share what they have learned or give suggestions to the research team. Physicians and researchers might even build a stable of peer mentors who might be willing to help newbies learn about the process.

Everything I have said applies to all avenues of clinical research, but these are especially important considerations in the face of new and exciting science. It took a long time for more traditional research practices to evolve into an investigator/subject partnership model. Stem cell research and regenerative medicine has the opportunity to do this from the very start—and benefit from previous lessons learned.

When I was preparing my remarks for today, someone casually mentioned that I might talk about the “importance of balancing truth-telling in the informed consent process with respect for the hope of the family.” I would like to unequivocally state that the very nature of an “informed consent process” requires 100% truth, as does respect for the family—and that this does not undermine our capacity for hope. We place our hope in this exciting new science and the doctors and researchers who are pioneers. We understand that there are many unknowns in this new field. Please be honest with us so that we might sort out our thoughts and our hopes for ourselves, in our own contexts.

What message would I wish the scientists here, today, to take away with them?      Well, I am putting on my Patient/Subject Advocate hat, and in my Patient/Subject Advocate voice, I am saying: “Tell me what I need to know!”

 

 

A road trip to the Inland Empire highlights a hot bed of stem cell research

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Gillian Wilson, Interim Vice Chancellor, Research, UC Riverside welcomes people to the combined Research Roadshow and Patient Advocate event

It took us longer than it should have to pay a visit to California’s Inland Empire, but it was definitely worth the wait. Yesterday CIRM’s Roadshow went to the University of California at Riverside (UCR) to talk to the community there – both scientific and public – about the work we are funding and the progress being made, and to hear from them about their hopes and plans for the future.

As always when we go on the road, we learn so much and are so impressed by everyone’s passion and commitment to stem cell research and their belief that it’s changing the face of medicine as we know it.

Dr. Deborah Deas, the Dean of the UC Riverside School of Medicine and a CIRM Board member, kicked off the proceedings by saying:

“Since CIRM was created in 2004 the agency has been committed to providing the technology and research to meet the unmet needs of the people of California.

On the Board I have been impressed by the sheer range and number of diseases targeted by the research CIRM is funding. We in the Inland Empire are playing our part. With CIRM’s help we have developed a strong program that is doing some exciting work in discovery, education and translational research.”

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CIRM’s Dr. Maria Millan at the Roadshow Patient Advocate event

CIRM’s President and CEO, Dr. Maria T. Millan, and our Board Chair, Jonathan Thomas then gave a quick potted history of CIRM and the projects we are funding. They highlighted how we are creating a pipeline of products from the Discovery, or basic level of research, through to the 45 clinical trials we are funding.

They also talked about the Alpha Clinic Network, based at six highly specialized medical centers around California, that are delivering stem cell therapies and sharing the experiences and knowledge learned from these trials to improve their ability to help patients and advance the field.

Researchers from both UCR then gave a series of brief snapshots of the innovative work they are doing:

  • Looking at new, more efficient and effective ways of expanding the number of human embryonic stem cells in the laboratory to create the high volume of cells needed for therapies.
  • Using biodegradable materials to help repair and regenerate tissue for things as varied as bone and cartilage repair or nerve restoration.
  • Exploring the use of epigenetic factors, things that switch genes on and off, to try and find ways to make repairs inside the body, rather than taking the cells outside the body, re-engineering them and returning them to the body. In essence, using the body as its own lab to manufacture replacement.

Another CIRM Board member, Linda Malkas, talked about the research being done at City of Hope (COH), where she is the associate chair of the Department of Molecular and Cellular Biology, calling it an “engine for discovery that has created the infrastructure and attracted people with an  amazing set of skills to bring forward new therapeutics for patients.”

She talked about how COH is home to one of the first Alpha Clinics that CIRM funded, and that it now has 27 active clinical trials, with seven more pending and 11 more in the pipeline.

“In my opinion this is one of the crown jewels of the CIRM program. CIRM is leading the nation in showing how to put together a network of specialized clinics to deliver these therapies. The National Institutes of Health (NIH) came to CIRM to learn from them and to talk about how to better move the most promising ideas and trials through the system faster and more efficiently.”

Dr. Malkas also celebrated the partnership between COH and UCR, where they are collaborating on 19 different projects, pooling their experience and expertise to advance this research.

Finally, Christine Brown, PhD, talked about her work using chimeric antigen receptor (CAR) T cells to fight cancer stem cells. In this CIRM-funded clinical trial, Dr. Brown hopes to re-engineer a patient’s T cells – a key cell of the immune system – to recognize a target protein on the surface of brain cancer stem cells and kill the tumors.

It was a packed event, with an overflow group watching on monitors outside the auditorium. The questions asked afterwards didn’t just focus on the research being done, but on research that still needs to be done.

One patient advocate couple asked about clinics offering stem cell therapies for Parkinson’s disease, wondering if the therapies were worth spending more than $10,000 on.

Dr. Millan cautioned against getting any therapy that wasn’t either approved by the Food and Drug Administration (FDA) or wasn’t part of a clinical trial sanctioned by the FDA. She said that in the past, these clinics were mostly outside the US (hence the term “stem cell tourism”) but increasingly they are opening up centers here in the US offering unproven and unapproved therapies.

She said there are lots of questions people need to ask before signing up for a clinical trial. You can find those questions here.

The visit was a strong reminder that there is exciting stem cell research taking place all over California and that the Inland Empire is a key player in that research, working on projects that could one day have a huge impact in changing people’s lives, even saving people’s lives.

 

Stem Cell Agency Heads to Inland Empire for Free Patient Advocate Event

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I am embarrassed to admit that I have never been to the Inland Empire in California, the area that extends from San Bernardino to Riverside counties.  That’s about to change. On Monday, April 16th CIRM is taking a road trip to UC Riverside, and we’re inviting you to join us.

We are holding a special, free, public event at UC Riverside to talk about the work that CIRM does and to highlight the progress being made in stem cell research. We have funded 45 clinical trials in a wide range of conditions from stroke and cancer, leukemia, lymphoma, vision loss, diabetes and sickle cell disease to name just a few. And will talk about how we plan on funding many more clinical trials in the years to come.

We’ll be joined by colleagues from both UC Riverside, and City of Hope, talking about the research they are doing from developing new imaging techniques to see what is happening inside the brain with diseases like Alzheimer’s, to using a patient’s own cells and immune system to attack deadly brain cancers.

It promises to be a fascinating event and of course we want to hear from you, our supporters, friends and patient advocates. We are leaving plenty of time for questions, so we can hear what’s on your mind.

So, join us at UC Riverside on Monday, April 16th from 12.30pm to 2pm. The doors open at 11am so you can enjoy a poster session (highlighting some of the research at UCR) and a light lunch before the event. Parking will be available on site.

Visit the Eventbrite page we have created for all the information you’ll need about the event, including a chance to RSVP and book your place.

The event is free so feel free to share this with anyone and everyone you think might be interested in joining us.

 

 

Lessons Learned & Knowledge Shared: 3rd Annual Alpha Clinics Symposium Celebrates the Delivery of Stem Cell Treatments to Patients

The CIRM Alpha Stem Cell Clinics (ASCC) Network was launched in 2015 to address a compelling unmet medical need for rigorous, FDA regulated, stem cell-related clinical trials for patients with challenging, incurable diseases. Since its inception, the Network has treated more than 200 patients in over 40 clinical trials at six leading California medical centers: UC San Diego, City of Hope, UCLA and UC Irvine, UCSF and UC Davis. That has enabled the Network to accumulate a wealth of experience and insight into how best to deliver treatments to patients, and each year it celebrates and showcases this knowledge at the CIRM Alpha Clinics Annual Symposium.

The Network is celebrating the 3rd anniversary of the ASCC Symposium on April 19th on the campus of the University of California at Los Angeles. This year’s theme is the Delivery of Stem Cell Therapeutics to Patients. Clinical investigators, scientists, patients, patient advocates, and the public will engage in thoughtful discussions on how novel stem cell treatments are now a reality. The symposium will address advancements and accomplishments of the ASCC Network in addition to developments and applications in the field of stem cell-based therapeutics. Treatments for cancer, HIV/AIDS, spinal cord injury and stroke will be featured. In addition, this year’s featured keynote speaker is David Mitchell President and Founder of Patients for Affordable Drugs.

The symposium is open to the public and is free. You can find the full agenda for the symposium here and registration can be found on the UCLA ASCC Eventbrite page. The event is highly interactive allowing participants opportunities to ask questions, network and learn about the latest developments in stem cell treatments.

Researcher and patient advocate panel at a past CIRM Alpha Clinic symposium: L to R: David Higgins, CIRM Board; David Parry, GSK; Catriona Jamieson, UCSD: John Zaia, City of Hope; John Adams, UCLA

Patient advocates speak up at the City of Hope 2nd Annual ASCC Network Symposium. (Image courtesy of the City of Hope)


Related Links:

Video illustrates potential path to stem cell repair for multiple sclerosis

“Can you imagine slowly losing the ability to live life as you know it? To slowly lose the ability to see, to walk, to grab an object, all the while experiencing pain, fatigue and depression?”

These sobering questions are posed at the beginning of a recent video produced by Youreka Science and Americans for Cures about multiple sclerosis (MS), a debilitating neurodegenerative disorder in which a person’s own immune system attacks cells that are critical for sending nerve signals from the brain and spinal cord to our limbs and the rest of our body.

In recognition of Multiple Sclerosis Awareness Week, today’s blog features this video. Using an easy to understand narrative and engaging hand-drawn illustrations, this whiteboard “explainer” video does a terrific job of describing the biological basis of multiple sclerosis. It also highlights promising research out of UC Irvine showing that stem cell-based therapies may one day help repair the damage caused by multiple sclerosis.

But don’t take my word for it, check out the five-minute video below:

Related Links:

Using the courts to protect patients from unapproved stem cell therapies

A recent article in Nature looked at using lawsuits to help rein in the activities of clinics offering “unapproved” therapies. CIRM’s Geoff Lomax explains.

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When public health officials wanted to raise awareness about the dangers of smoking they filed lawsuits against the tobacco companies. They accused Big Tobacco of deceptive marketing and hiding the negative health effects of smoking. Ultimately, they won. Now a new study says a similar tactic could prove effective in combating clinics that offer unproven stem cell therapies.

CIRM works tirelessly to accelerate the delivery of stem cell treatments to patients with unmet medical needs. But, that doesn’t mean we support any treatment that claims to help people. CIRM only partners with projects that have been given the go-ahead by the US Food and Drug Administration (FDA) to be tested in people in a clinical trial.  That’s because FDA approval means the clinical trial will be monitored and evaluated under high scientific and ethical standards.

In contrast, there are numerous examples where “stem-cell treatments” not sanctioned by the FDA are being marketed directly to patients. For years the FDA, CIRM and others have been warning consumers about the risks involved with these untested treatments. For example, just last  November the FDA issued a warning and advice for people considering stem cell treatments.

Legal steps

Last year CIRM also helped author a new California law designed to protect consumers. The law requires health care providers to disclose to patients when using a treatment that is not FDA approved or part of an FDA-sanctioned clinical trial.

At CIRM, we frequently direct patients seeking treatments to our Alpha Stem Cell Clinics Network. The Alpha Clinics only perform clinical trials that have been given the green light by the FDA, and they provide expert consultation and informed consent to patients to help ensure they make the best choice for themselves. Further, the Alpha Clinics follow up with patients after their treatments to evaluate safety and the effectiveness of the treatments.

These are steps that clinics offering unproven and unapproved therapies typically don’t follow. So, the question is how do you let people know about the risks involved in going to one of these clinics and how do you stop clinics offering “therapies” that might endanger the health of patients?

Using the law to hit clinics where it hurts

In a recently published perspective in the journal Nature an international team of policy experts considered whether civil lawsuits may play a role in stemming the tide of unproven treatments. In the article the authors say:

“The threat of financial liability for wrongdoing is the primary means by which civil law governs behavior in the private sector. Despite calls for stepping up enforcement efforts, the US Food and Drug Administration (FDA) is currently restricted in its ability to identify and target clinics operating in apparent violation of regulations. The fear of tort liability {lawsuits} may provide sufficient incentive for compliance and minimize the occurrence of unethical practices.”

The authors identified nine individual and class action lawsuits involving clinics offering what they called “unproven stem cell interventions.” A few of those were dismissed or decided in favor of the clinics, with judges saying the claims lacked merit. Most, however, were settled by the clinics with no ruling on the merits of the issue raised. Even without definitive judgements against the clinics the authors of the article conclude:

“Stem cell lawsuits could intensify publicity and raise awareness of the harms of unproven treatments, set legal precedent, reshape the media narrative from one focused on the right to try or practice to one highlighting the need for adequate safety and efficacy standards, and encourage authorities to turn their attention to policy reform and enforcement.”

The authors suggest the courts may provide a forum where medical experts can inform patients, the legal community and the public about good versus harmful clinical practices. In short, the authors believe the legal process can be an effective forum for to provide education and outreach to those with disease and the public at large.

The better option of course would be for the clinics themselves to reform their practices and engage with the FDA to test their therapies in a clinical trial. Until that happens the courts may offer an alternative approach to curbing the marketing of these unproven and unapproved therapies.

It’s time to vote for the Stem Cell Person of the Year

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Paul Knoepfler

Oh well, it’s going to be another year of disappointment for me. Not only did I fail to get any Nobel Prize (I figured my blogs might give me a shot at Literature after they gave it to Bob Dylan last year), but I didn’t get a MacArthur Genius Award. Now I find out I haven’t even made the short list for the Stem Cell Person of the Year.

The Stem Cell Person of the Year award is given by UC Davis researcher, avid blogger and CIRM Grantee Paul Knoepfler. (You can vote for the Stem Cell Person of the Year here). In his blog, The Niche, Paul lists the qualities he looks for:

“The Stem Cell Person of the Year Award is an honor I give out to the person in any given year who in my view has had the most positive impact in outside-the-box ways in the stem cell and regenerative medicine field. I’m looking for creative risk-takers.”

“It’s not about who you know, but what you do to help science, medicine, and other people.”

Paul invites people to nominate worthy individuals – this year there are 20 nominees – people vote on which one of the nominees they think should win, and then Paul makes the final decision. Well, it is his blog and he is putting up the $2,000 prize money himself.

This year’s nominees are nothing if not diverse, including

  • Anthony Atala, a pioneering researcher at Wake Forest Institute for Regenerative Medicine in North Carolina
  • Bao-Ngoc Nguyen, who helped create California’s groundbreaking new law targeting clinics which offer unproven stem cell therapies
  • Judy Roberson, a tireless patient advocate, and supporter of stem cell research for Huntington’s disease

Whoever wins will be following in some big footsteps including patient advocates Ted Harada and Roman Reed, as well as scientists like Jeanne Loring, Masayo Takahashi,  and Elena Cattaneo.

So vote early, vote often.

LINK: Vote for the 2017 Stem Cell Person of the Year

Engaging the patient to create a culture of health citizenship

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Health Citizenship panel discussion at Partnering for Cures: L to R: Lucia Savage, Roni Zeiger,  Claudia Williams, Jennifer Mills, Kathy Hudson, Beth Meagher

One of the buzz phrases in healthcare today is “patient engagement”. It seems that you can’t go to a medical or scientific conference without coming across a panel discussion on the topic. A recent Partnering For Cures* event in San Francisco was no exception. But here the conversation took on a very different tone, one that challenged what the term meant and then said that if we are really serious about engaging patients, then doctors and drug companies need to change the way they think and operate.

That tone was set from the start of the discussion when moderator Claudia Williams said even the term “patient engagement” suggests that it is something “being imposed, or at least allowed, from the outside; by experts and doctors and those in charge.”

Williams quoted Erin Moore, the mother of a young boy with cystic fibrosis saying “No one is more engaged than the patient. I want the experts, the doctors, the pharmaceutical companies to be engaged.”

Need to train doctors

Dr. Roni Zeiger, the former Chief Health Strategist at Google, said doctors aren’t trained to truly listen to and engage with patients, and that has to change:

“I sometimes think of myself as a recovering paternal physician. When I listen to and learn from patients and families I am surprised, every time, at the breadth and depth of the conversations. All of the things that we, in the medical field, do from designing a waiting room to designing a clinical trial to deciding when and how to have a conversation, we bring a tremendous amount of assumptions to those. And those assumptions are often wrong. I think that on a daily basis we should be looking at the key work we do and ask are there assumptions here I should throw away and talk to those I serve and get their help in redesigning things in a way that makes more sense.”

Jennifer Mills, the Director of Patient Engagement (that phrase again) at biotech giant Genentech, said those mistakes are made by everyone in the field:

“The biggest assumption for me is thinking about patients with a capital P, as a homogeneous group, instead of realizing they are also individuals. We need to address them as a group and as individuals depending on the circumstances.”

Caregivers count too

For example as people get older and rely on a partner or spouse to take care of them it may be important to not just engage with the patient but also with the caregiver. And the needs for each of them may not be the same.

At that point the conversation turned to the use of data. Lucia Savage, the Chief Privacy and Regulatory Officer at Omada Health, said it is going to be increasingly important to give people control over their own medical data, and sometimes the medical data of others.

“Caregivers need access to healthcare records. For example, I can check my mom’s labs. If I message her doctors they can share that information with me. It’s great because it helps us help her lead an independent life as an 80 year old.”

Savage also pointed out that we need to be careful how we interpret data. She said she could go shopping and buy three extra-large bags of potato chips. On the face of it that doesn’t look good. But did she buy those chips for herself or her daughter’s soccer team. The data is the same. The implications are very different.

Partnership not patronizing

The discussion ended with an attempt to outline what being a good health citizen means. Just as citizenship involves both rights and responsibilities on the part of the individual and society, health citizenship too involves rights and responsibilities on the part of the individual and the biomedical research and health care world. Patients deserve to be treated as individuals who have a vested interest in their own health. They don’t need “experts” to talk down or patronize them or assume they know best.

Mills says she is seeing progress in this area:

“Companies are moving from assuming what patients need to asking what they need. We once assumed that if we were in the therapeutic area long enough we didn’t need to ask what patients need. I’m seeing that change.”

Deloitte Consulting’s Beth Meagher said we need to look beyond technology and focus on the people:

“Humility is going to be the killer app. The true innovators are really being humble and realizing that to have the kind of impact they are looking for, there is a need to work in a way they haven’t before. “

*Partnering for Cures is a project of Michael Milken’s FasterCures, whose goal is to save lives by speeding up and improving the medical research system.

 

Stories that caught our eye: How dying cells could help save lives; could modified blood stem cells reverse diabetes?; and FDA has good news for patients, bad news for rogue clinics

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Growing up I loved watching old cowboy movies. Invariably the hero, even though mortally wounded, would manage to save the day and rescue the heroine and/or the town.

Now it seems some stem cells perform the same function, dying in order to save the lives of others.

Researchers at Kings College in London were trying to better understand Graft vs Host Disease (GvHD), a potentially fatal complication that can occur when a patient receives a blood stem cell transplant. In cases of GvHD, the transplanted donor cells turn on the patient and attack their healthy cells and tissues.

Some previous research had found that using bone marrow cells called mesenchymal stem cells (MSCs) had some success in combating GvHD. But it was unpredictable who it helped and why.

Working with mice, the Kings College team found that the MSCs were only effective if they died after being transplanted. It appears that it is only as they are dying that the MSCs engage with the individual’s immune system, telling it to stop attacking healthy tissues. The team also found that if they kill the MSCs just before transplanting them into mice, they were just as effective.

In a news article on HealthCanal, lead researcher Professor Francesco Dazzi, said the next step is to see if this will apply to, and help, people:

“The side effects of a stem cell transplant can be fatal and this factor is a serious consideration in deciding whether some people are suitable to undergo one. If we can be more confident that we can control these lethal complications in all patients, more people will be able to receive this life saving procedure. The next step will be to introduce clinical trials for patients with GvHD, either using the procedure only in patients with immune systems capable of killing mesenchymal stem cells, or killing these cells before they are infused into the patient, to see if this does indeed improve the success of treatment.”

The study is published in Science Translational Medicine.

Genetically modified blood stem cells reverse diabetes in mice (Todd Dubnicoff)

When functioning properly, the T cells of our immune system keep us healthy by detecting and killing off infected, damaged or cancerous cells in our body. But in the case of type 1 diabetes, a person’s own T cells turn against the body by mistakenly targeting and destroying perfectly normal islet cells in the pancreas, which are responsible for producing insulin. As a result, the insulin-dependent delivery of blood sugar to the energy-hungry organs is disrupted leading to many serious complications. Blood stem cell transplants have been performed to treat the disease by attempting to restart the immune system. The results have failed to provide a cure.

Now a new study, published in Science Translational Medicine, appears to explain why those previous attempts failed and how some genetic rejiggering could lead to a successful treatment for type 1 diabetes.

An analysis of the gene activity inside the blood stem cells of diabetic mice and humans reveals that these cells lack a protein called PD-L1. This protein is known to play an important role in putting the brakes on T cell activity. Because T cells are potent cell killers, it’s important for proteins like PD-L1 to keep the activated T cells in check.

Cell based image for t 1 diabetes

Credit: Andrea Panigada/Nancy Fliesler

Researchers from Boston Children’s Hospital hypothesized that adding back PD-L1 may prevent T cells from the indiscriminate killing of the body’s own insulin-producing cells. To test this idea, the research team genetically engineered mouse blood stem cells to produce the PD-L1 protein. Experiments with the cells in a petri dish showed that the addition of PD-L1 did indeed block the attack-on-self activity. And when these blood stem cells were transplanted into a diabetic mouse strain, the disease was reversed in most of the animals over the short term while a third of the mice had long-lasting benefits.

The researchers hope this targeting of PD-L1 production – which the researchers could also stimulate with pharmacological drugs – will contribute to a cure for type 1 diabetes.

FDA’s new guidelines for stem cell treatments

Gottlieb

FDA Commissioner Scott Gottlieb

Yesterday Scott Gottlieb, the Commissioner at the US Food and Drug Administration (FDA), laid out some new guidelines for the way the agency regulates stem cells and regenerative medicine. The news was good for patients, not so good for clinics offering unproven treatments.

First the good. Gottlieb announced new guidelines encouraging innovation in the development of stem cell therapies, and faster pathways for therapies, that show they are both safe and effective, to reach the patient.

At the same time, he detailed new rules that provide greater clarity about what clinics can do with stem cells without incurring the wrath of the FDA. Those guidelines detail the limits on the kinds of procedures clinics can offer and what ways they can “manipulate” those cells. Clinics that go beyond those limits could be in trouble.

In making the announcement Gottlieb said:

“To be clear, we remain committed to ensuring that patients have access to safe and effective regenerative medicine products as efficiently as possible. We are also committed to making sure we take action against products being unlawfully marketed that pose a potential significant risk to their safety. The framework we’re announcing today gives us the solid platform we need to continue to take enforcement action against a small number of clearly unscrupulous actors.”

Many of the details in the announcement match what CIRM has been pushing for some years. Randy Mills, our previous President and CEO, called for many of these changes in an Op Ed he co-wrote with former US Senator Bill Frist.

Our hope now is that the FDA continues to follow this promising path and turns these draft proposals into hard policy.

 

Turning the corner with the FDA and NIH; CIRM creates new collaborations to advance stem cell research

FDAThis blog is part of the Month of CIRM series on the Stem Cellar

A lot can change in a couple of years. Just take our relationship with the US Food and Drug Administration (FDA).

When we were putting together our Strategic Plan in 2015 we did a survey of key players and stakeholders at CIRM – Board members, researchers, patient advocates etc. – and a whopping 70 percent of them listed the FDA as the biggest impediment for the development of stem cell treatments.

As one stakeholder told us at the time:

“Is perfect becoming the enemy of better? One recent treatment touted by the FDA as a regulatory success had such a high clinical development hurdle placed on it that by the time it was finally approved the standard of care had evolved. When it was finally approved, five years later, its market potential had significantly eroded and the product failed commercially.”

Changing the conversation

To overcome these hurdles we set a goal of changing the regulatory landscape, finding a way to make the system faster and more efficient, but without reducing the emphasis on the safety of patients. One of the ways we did this was by launching our “Stem Cell Champions” campaign to engage patients, patient advocates, the public and everyone else who supports stem cell research to press for change at the FDA. We also worked with other organizations to help get the 21st Century Cures Act passed.

21 century cures

Today the regulatory landscape looks quite different than it did just a few years ago. Thanks to the 21st Century Cures Act the FDA has created expedited pathways for stem cell therapies that show promise. One of those is called the Regenerative Medicine Advanced Therapy (RMAT) designation, which gives projects that show they are both safe and effective in early-stage clinical trials the possibility of an accelerated review by the FDA. Of the first projects given RMAT designation, three were CIRM-funded projects (Humacyte, jCyte and Asterias)

Partnering with the NIH

Our work has also paved the way for a closer relationship with the National Institutes of Health (NIH), which is looking at CIRM as a model for advancing the field of regenerative medicine.

In recent years we have created a number of innovations including introducing CIRM 2.0, which dramatically improved our ability to fund the most promising research, making it faster, easier and more predictable for researchers to apply. We also created the Stem Cell Center  to make it easier to move the most promising research out of the lab and into clinical trials, and to give researchers the support they need to help make those trials successful. To address the need for high-quality stem cell clinical trials we created the CIRM Alpha Stem Cell Clinic Network. This is a network of leading medical centers around the state that specialize in delivering stem cell therapies, sharing best practices and creating new ways of making it as easy as possible for patients to get the care they need.

The NIH looked at these innovations and liked them. So much so they invited CIRM to come to Washington DC and talk about them. It was a great opportunity so, of course, we said yes. We expected them to carve out a few hours for us to chat. Instead they blocked out a day and a half and brought in the heads of their different divisions to hear what we had to say.

A model for the future

We hope the meeting is, to paraphrase Humphrey Bogart at the end of Casablanca, “the start of a beautiful friendship.” We are already seeing signs that it’s not just a passing whim. In July the NIH held a workshop that focused on what will it take to make genome editing technologies, like CRISPR, a clinical reality. Francis Collins, NIH Director, invited CIRM to be part of the workshop that included thought leaders from academia, industry and patients advocates. The workshop ended with a recommendation that the NIH should consider building a center of excellence in gene editing and transplantation, based on the CIRM model (my emphasis).  This would bring together a multidisciplinary disease team including, process development, cGMP manufacturing, regulatory and clinical development for Investigational New Drug (IND) filing and conducting clinical trials, all under one roof.

dr_collins

Dr. Francis Collins, Director of the NIH

In preparation, the NIH visited the CIRM-funded Stem Cell Center at the City of Hope to explore ways to develop this collaboration. And the NIH has already begun implementing these suggestions starting with a treatment targeting sickle cell disease.

There are no guarantees in science. But we know that if you spend all your time banging your head against a door all you get is a headache. Today it feels like the FDA has opened the door and that, together with the NIH, they are more open to collaborating with organizations like CIRM. We have removed the headache, and created the possibility that by working together we truly can accelerate stem cell research and deliver the therapies that so many patients desperately need.