More Good News From CIRM-Funded Spinal Cord Injury Trial

It’s been less than a year since we last reported on the CIRM-funded Asterias Biotherapeutics trial for spinal cord injury (SCI), and we already have more – still preliminary – but good news to share. The company recently released encouraging long-term follow-up results from their original Phase 1 clinical trial that suggest their stem cell treatment is safe and possibly effective for treating SCI occurring in the back region.

astopc1Back in August 2015, the California-based company reported positive results for the second phase of the clinical trial, the ongoing Phase 1/2a trial, that is testing their AST-OPC1 brain progenitor cell treatment in patients with cervical or neck spinal cord injury. They treated three patients with a low dose of two million AST-OPC1 cells and observed no serious side effects after two months. You can read more about these initial results in our blog.

Asterias plans to expand their Phase 1/2a trial by enrolling more patients and administering higher numbers of cells in hopes that a higher dose might impact or improve motor function in SCI patients. But with any cell transplantation therapy, there is always concerns about whether it’s safe and whether it could cause any long-term consequences in patients.

Good news to those who wait

A news release by Asterias yesterday, puts some of these fears to rest. They report new long-term data on their original Phase 1 trial, which was carried out by Geron, that treated patients with thoracic or back SCI. In this trial, five patients were treated with two million AST-OPC1 cells between 7 and 14 days post injury. The patients were given immunosuppressive drugs for two months so they wouldn’t reject the cell transplant and then were monitored over the next 4-5 years.

During this time, none of the patients showed any signs of transplant rejection, and MRI scans revealed that four out of the five patients showed less cavitation in their spinal cords, a destructive process that occurs after severe spinal cord injury.

Thus it seems that AST-OPC1 does not pose any serious safety issues for SCI patients, at least at the five-year mark. Chief Medical Officer Dr. Edward Wirth explained:

Edward Wirth, CMO at Asterias

Edward Wirth, CMO at Asterias

“This new long term follow-up data continues to support the general safety of AST-OPC1 and indicate minimal risk of the transplanted cells having unintended effects. In detailed immune response monitoring of patients, the results are consistent with long-term cell engraftment, immune system tolerability, and an absence of adverse effects.  In short, AST-OPC1 does not appear to present any immunological or other long-term safety issues when administered to patients suffering from spinal cord injuries.”

These positive long-term results are perfectly timed for Asteria’s expansion of their Phase 1/2a trial where they aim to test doses of AST-OPC1 that they believe would improve motor function in SCI patients. Asterias CEO Steve Cartt commented:

Steve Cartt, CEO of Asterias Biotherapeutics

Steve Cartt, CEO of Asterias

“These new follow-up results are very encouraging and provide important further support for expansion of the ongoing Phase 1/2a clinical study in patients with complete cervical spinal cord injuries announced just last week. We are continuing to enroll patients in the second dose cohort of the current Phase 1/2a trial.  Patients in this cohort are receiving a significantly higher dose of 10 million cells, which we believe corresponds to the doses that showed efficacy in animal studies.”

But that’s not all folks!

Dr. Edward Wirth, Asterias Biotherapeutics

Dr. Edward Wirth from Asterias Biotherapeutics at the CIRM Alpha Clinics Meeting in May

CIRM got the inside scoop on the next steps of this Phase 1/2a trial last week at a CIRM Alpha Stem Cell Clinics Meeting held at UC Irvine. Dr. Edward Wirth was the guest speaker, and during lunch, he explained how their recent successes in both clinical trials has prompted the FDA to grant them clearance to expand their current Phase 1/2a trial from 13 to up to 35 patients.

Asterias can now enroll patients with both AIS A (complete injury) and AIS B injuries and has expanded the age range of trial participants to 18-69 years. Dr. Wirth added that the goal of this trial is to rescue some of the motor function in cervical SCI patients so that they can go from needing full time care to being able to carry out some functions on their own. He also indicated that these patients will be monitored for 15 years to evaluate the safety and success of their treatment.

We at CIRM are encouraged by these early positive results and hopeful that this clinical trial will result in a stem cell treatment that will improve the lives of SCI patients.


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How do you know what patients want if you never even ask them?

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Our mission at CIRM is to accelerate stem treatments to patients with unmet medical needs. But what if those needs are not just unmet, they’re also unknown? What happens when those developing treatments never even bother to ask those they are trying to help if this is what they really need, or want?

The question came up during a panel discussion at a meeting of the CIRM Alpha Stem Cell Clinics Network in San Diego earlier this month. David Higgins, a CIRM Board member and a Patient Advocate for Parkinson’s disease, highlighted the problem saying that if you ask most people what they think is the biggest problem for Parkinson’s sufferers, they would probably say the movement disorders such as tremors and muscle rigidity. But David said that if you ask people who have Parkinson’s what their biggest problems are, then movement disorder probably wouldn’t even come in the top five concerns that they really have.

David listed insomnia, severe fatigue, anxiety, and depression as far more pressing and important:

“Researchers study what they know and they look to solve the things they think they can solve, and it is sometimes very different than the things that patients would like them to solve to ease their concerns.”

That sparked a fascinating discussion about the gap between what researchers and scientists sometimes think they should be doing, the kinds of treatments they should be trying to develop, and what the people who have those conditions really want.

David Parry, who is with GlaxoSmithKline and worked in drug development and discovery for most of his career, said:

“If I told you how many times I sat in meetings with my medical discovery group and talked about what our targets should be then we’d be here all night. We focus on what we know, what we think we can fix and what will work, when maybe we need to be more mindful of what could really make a difference in the life of patients.”

Alpha clinic panelAlpha Stem Cell Clinics Network panel discussion: Left David Higgins, David Parry, Catriona Jamieson, John Zaia, John Adams

Clearly there is a gap between what we think we can fix and what we should try and fix, and the best way to close that gap is to have a conversation.

Patients and Patient Advocates need to speak up and tell researchers what their main concerns and problems are, to help the scientists understand that while they would dearly love something that saves their life, they would also appreciate something that helps improve the quality of their lives.

Researchers too need to take a step back and not just get caught up in the search for an answer to a scientific or medical puzzle, without first asking “is this a puzzle that people want solved?”

At CIRM we work hard to make sure the voices of the patients and Patient Advocates are heard at every level of the work we do; from deciding what to fund to how to design a clinical trial involving our funding. But clearly it’s important that those voices be heard at a much earlier stage, to help shape the direction the research takes long before it comes to us for funding.

Breaking down barriers

For too long there has been a communications barrier between researchers and patients. This is not something that was deliberately constructed, it is something that simply evolved over time. Now it’s time to break down that barrier, and make sure both groups are talking to each other.

When it comes to developing treatments for deadly diseases and disorders, patients and researchers should think of themselves as partners. Researchers put their minds to work developing these treatments. Patients put their bodies on the line testing them.

Without the research there is no hope. Without the patients there is no proof. So, let’s start talking to each other.

If you have any thoughts or suggestions on how we can get this conversation started we would love to hear from you.

A meeting of minds: breaking down communication barriers between patients and doctors

dp-relation

One of the things that has always surprised me about stem cell research, or any scientific research, is that so often the people with most at stake never meet. Researchers spend most of their time in the lab trying to develop new treatments so they don’t often get to meet the people who are depending on them to save or improve their lives, the patients.

To try and change that dynamic two Canadian medical groups recently brought together a mixture of researchers, health care professionals, patients and patient advocates to find ways to improve communications between these groups. The hope was that with better communication and better information they would collectively be able to make better decisions about how to manage patient health.

Communication barriers

Lisa Willemse, a writer who has worked with CIRM on some of our projects in the past, wrote a wonderful piece about the meeting for the online magazine Medium. In it she explores some of the areas that create communication barriers between these groups and how those barriers can be overcome.

The problems caused by these barriers are not trivial. They can result in patients not knowing about potentially life-saving clinical trials in the US, or turning to unproven, experimental therapies offered at overseas clinics. (Here’s a document that addresses some of those issues)

Lisa quotes one patient as saying:

“I didn’t know what I didn’t know! I had filled out an application online was accepted to a stem cell clinic in Panama. The cost per treatment was $21,000 and I didn’t know what questions to ask!”

Finding solutions

Happily the meeting came up with some thoughtful, really positive suggestions on ways to overcome these barriers. These include:

  • Ensuring specialists and other health care practitioners are kept up-to-date with clinical trial information, since these are where they turn first for advice.
  • Providing more support for patients from health care providers. They should not be expected to have all the answers but should at least be able to advise on informed consent and provide credible resources.
  • Developing improved ways to search for relevant clinical trials.
  • Creating basic explainers on clinical trials for patients to help them determine eligibility and understand protocol.

There were also suggestions on how researchers can do a better job of communicating with non-scientists, such as using jargon-free language to answer questions and providing a list of questions people should ask when considering any stem cell therapy. Here’s an infographic we put together on that topic.

Lessons learned

This meeting is a great example of the power and importance of bringing together these different groups, all of whom have shared interests and goals. It starts with a conversation that begins to break down barriers. Hopefully it gives doctors ideas on how they can better equip patients to make informed decisions about clinical trials; by meeting patients it helps researchers put a human face on the work they are doing; and hopefully it gives patients a sense that their voices are being heard, and their needs addressed.

This was one relatively small meeting in Canada but the lessons learned apply to every state, and every country and could point the way to creating a more responsive health care system that better meets the needs of all those involved.

 

Helping patient’s fight back against deadliest form of skin cancer

Caladrius Biosciences has been funded by CIRM to conduct a Phase 3 clinical trial to treat the most severe form of skin cancer: metastatic melanoma. Metastatic melanoma is a disease with no effective treatment, only around 15 percent of people with it survive five years, and every year it claims an estimated 10,000 lives in the U.S.

The CIRM/Caladrius Clinical Advisory Panel meets to chart future of clinical trial

The CIRM/Caladrius Clinical Advisory Panel meets to chart future of clinical trial

The Caladrius team has developed an innovative cancer treatment that is designed to target the cells responsible for tumor growth and spread. These are called cancer stem cells or tumor-initiating cells. Cancer stem cells can spread in the body because they have the ability to evade the body’s immune defense and survive standard anti-cancer treatments such as chemotherapy. The aim of the Caladrius treatment is to train the body’s immune system to recognize the cancer stem cells and attack them.

Attacking the cancer

The treatment process involves taking a sample of a patient’s own tumor and, in a laboratory, isolating specific cells responsible for tumor growth . Cells from the patient’s blood, called “peripheral blood monocytes,” are also collected. The mononucleocytes are responsible for helping the body’s immune system fight disease. The tumor and blood cells (after maturation into dendritic cells) are then combined and incubated so that the patient’s immune cells become trained to recognize the cancer cells.

After the incubation period, the patient’s immune cells are injected back into their body where they generate an immune response to the cancer cells. The treatment is like a vaccine because it trains the body’s immune system to recognize and rapidly attack the source of disease.

Recruiting the patients

Caladrius has already dosed the first patient in the trial (which is double blinded so no one knows if the patient got the therapy or a placebo) and hopes to recruit 250 patients altogether.

This is the first Phase 3 trial that CIRM has funded so we’re obviously excited about its potential to help people battling this deadly disease.  In a recent news release David J. Mazzo, the CEO of Caladrius echoed this excitement, with a sense of cautious optimism:

“The dosing of the first patient in this Phase 3 trial is an important milestone for our Company and the timing underscores our focus on this program and our commitment to impeccable trial execution. We are delighted by the enthusiasm and productivity of the team at Jefferson University (where the patient was dosed) and other trial sites around the country and look forward to translating that into optimized patient enrollment and a rapid completion of the Phase 3 trial.”

And that’s the key now. They have the science. They have the funding. Now they need the patients. That’s why we are all working together to help Caladrius recruit patients as quickly as possible. Because their work perfectly reflects our mission of accelerating the development of stem cell therapies for patients with unmet medical needs.

You can learn more about what the study involves and who is eligible by clicking here.

Pushing, pulling and dragging stem cell research forward

Government agencies are known for many things, but generally speaking a willingness to do some voluntary, deep self-examination is not one of them. However, for the last few weeks CIRM has been doing a lot of introspection as we develop a new Strategic Plan, a kind of road map for where we are heading.

Patient Advocate meeting in Los Angeles: Photo courtesy Cristy Lytal USC

Patient Advocate meeting in Los Angeles:
Photo courtesy Cristy Lytal USC

But we haven’t been alone. We’ve gone to San Diego, Los Angeles and San Francisco to talk to Patient Advocates in each city, to get their thoughts on what we need to focus on for the future. Why Patient Advocates? Because they are the ones with most skin in the game. They are why we do this work so it’s important they have a say in how we do it.

As Chris Stiehl, a Patient Advocate for type 1 diabetes, said in San Diego: “Let the patient be in the room, let them be part of the conversation about these therapies. They are the ones in need, so let them help make decisions about them right from the start, not at the end.”

A Strategic Plan is, on the surface, a pretty straightforward thing to put together. You look at where you are, identify where you want to go, and figure out the best way to get from here to there. But as with many things, what seems simple on the surface often turns out to be a lot more complicated when looked at in more depth.

The second bit, figuring out where you want to go, is easy. We want to live up to our mission of accelerating the development of stem cells therapies to patients with unmet medical needs. We don’t want to be good at this. We want to be great at this.

Dr. C. Randal Mills talking to Patient Advocates in LA: Photo courtesy Cristy Lytal, USC

Dr. C. Randal Mills talking to Patient Advocates in LA: Photo courtesy Cristy Lytal, USC

The first part, seeing where you are, is a little tougher: it involves what our President and CEO, Dr. Randy Mills, “confronting some brutal facts”, being really honest in assessing where you are because without that honesty you can’t achieve anything.

So where are we as an agency? Well, we have close to one billion dollars left in the bank, we have 12 projects in clinical trials and more on the way, we have helped advance stem cells from a fledgling field to a science on the brink of what we hope will be some remarkable treatments, and we have a remarkable team ready to help drive the field still further.

But how do we do that, how do we identify the third part of the puzzle, getting from where we are to where we want to be? CIRM 2.0 is part of the answer – developing a process to fund research that is easier, faster and more responsive to the needs of the scientists and companies developing new therapies. But that’s just part of the answer.

Some of the Patient Advocates asked if we considered focusing on just a few diseases, such as the ten largest killers of Americans, and devoting our remaining resources to fixing them. And the answer is yes, we looked at every single option. But we quickly decided against that because, as Randy Mills said:

“This is not a popularity contest, you can’t judge need by numbers, deciding the worth of something by how many people have it. We are disease agnostic. What we do is find the best science, and fund it.”

Another necessary element is developing better ways to attract greater investment from big pharmaceutical companies and venture capital to really help move the most promising projects through clinical trials and into patients. That is starting to happen, not as fast as we would like, but as our blog yesterday shows things are moving in this direction.

And the third piece of the pie is getting these treatments through the regulatory process, getting the Food and Drug Administration (FDA) to approve therapies for clinical trials. And this last piece clearly hit a nerve.

Many Patient Advocates expressed frustration at the slow pace of approval for any therapy by the FDA, some saying it felt like they just kept piling up obstacles in the way.

Dr. Mills said the FDA is caught between a rock and a hard place; criticized if it approves too slowly and chastised if it approves too fast, green lighting a therapy that later proves to have problems. But he agreed that changes are needed:

“The regulatory framework works well for things like drugs and small molecules that can be taken in pills but it doesn’t work well for cellular therapies like stem cells. It needs to do better at that.”

One Advocate suggested a Boot Camp for researchers, drilling them in the skills they’ll need to get FDA approval. Others suggested applying political pressure from Patient Advocacy groups to push for change.

As always there are no easy answers, but the meeting certainly raised many great questions. Those are all helping us focus our thinking on what needs to be in the Strategic Plan.

Randy ended the Patient Advocate events by saying the stem cell agency “is in the time business. What we do is time sensitive.” For too many people that time is already running out. We have to do everything we can to change that.

The best tools to be the best advocate

It’s hard to do a good job if you don’t have the right tools. And that doesn’t just apply to fixing things around the house, it applies to all aspects of life. So, in launching our new website this week we didn’t just want to provide visitors to the site with a more enjoyable and engaging experience – though we hope we have done that – we also wanted to provide a more informative and helpful experience. That’s why we have created a whole new section call the Patient Advocate Toolbox. shutterstock_150769385

The goal of the Toolbox is simple; to give patients and patient advocates help in learning the skills they need to be as effective as possible about raising awareness for their particular cause.

As an advocate for a disease or condition you may be asked to speak at public events, to be part of a panel discussion at a conference, or to do an interview with a reporter. Each of those requires a particular set of skills, in areas that many of us may have little, if any, experience in.

That’s where the Toolbox comes in. Each section deals with a different opportunity for you to share your story and raise awareness about your cause.

In the section on “Media Interviews”, for example, we walk you through the things you need to think about as you prepare to talk to a reporter; the questions to ask ahead of time, how to prepare a series of key messages, even how to dress if you are going to be on TV. The idea is to break down some of the mystique surrounding the interview, to let you know what to expect and to help you prepare as fully as possible.

If you are going to be asked questions about stem cell research there’s a section in the Toolbox called “Jargon-Free Glossary” that translates scientific terms into every-day English, so you can talk about this work in a way that anyone can understand.

There’s also a really wonderfully visual infographic on the things you need to know when thinking about taking part in a clinical trial. It lays out in simple, easy-to-follow steps the questions you should ask, the potential benefits and problems of being in a trial, including the risks of going overseas for unproven therapies.

The Toolbox is by no means an exhaustive list of all the things you will need to know to be an effective advocate, either for yourself or a friend or loved one, but it is a start.

We would love to hear from you on ways we can improve the content, on other elements that would be useful to include, on links to other sites that you think would be helpful to add. Our goal is to make this as comprehensive and useful as possible. Your support, your ideas and thoughts will help us do just that. If you have any comments please send them to info@cirm.ca.gov

Thomas Carlyle, the Scottish philosopher, once wrote: “Man is a tool-using animal. Without tools he is nothing, with tools he is all.” That’s why we want to give you the tools you need to be as effective as you can. Because the more powerful your voice, the more we all benefit.

When Hope Runs up against Reality: Balancing Patient Optimism with Medical Evidence

One of the big concerns among scientists – including many at the International Society for Stem Cell Research (ISSCR) conference in Vancouver, Canada – is that patient expectations about stem cells are often greater than researchers are able to deliver today. That can result in patients in search of a cure heading to overseas clinics that offer unproven therapies.

Megan Munsie – head of the Education, Ethics, Law and Community Awareness Unit at the University of Melbourne in Australia – wanted to find out what happens when patients’ hopes for new treatments come into conflict with scientific views on medical evidence. So she started with a small survey of 16 Australians, patients and patient-caretakers, who had travelled outside Australia for stem cell treatments for a variety of diseases including MS and cerebral palsy.

She says there were a number of interesting findings:

  • They all considered themselves pro-active and well-informed
  • They rejected advice from their own doctor but instead relied on the overseas doctor selling them the treatment for advice
  • They felt they had no choice but to travel overseas because they were running out of time and options in Australia
  • They didn’t consider the health risks, believing that the worst that would happen is that the “treatment” wouldn’t work and they would have spent a lot of money for nothing

Perhaps the most surprising finding was that all of them talked about the “benefits” they gained from going abroad for the treatment, that it gave them a sense of hope even if there was no evidence of medical benefit.

What happens when patients’ hopes for new treatments come into conflict with scientific views on medical evidence?

What happens when patients’ hopes for new treatments come into conflict with scientific views on medical evidence?

This led to a bigger study where Munsie surveyed patients and patient advocates but also stem cell scientists and physicians. Not surprisingly the researchers had a very different view of the subject than the patients.

Researchers/doctors said they felt that patients don’t understand science and don’t appreciate the subtleties of clinical trials

  • They said patients were basing their decisions not on science but desperation
  • They considered overseas providers as dubious, selling hope and taking advantage of a vulnerable patient population

What was interesting, however, is that many doctors said they didn’t try to persuade their patients not to go, instead they chose to respect their autonomy but did at least try to give them the facts so that they could make a decision based on knowledge not ignorance.

When asked why they didn’t tell patients not to go, they said they respected the patients’ need for hope and didn’t want to take that away from them because they had nothing they could offer to replace it.

Munsie says recently some doctors have started offering these kinds of unproven therapies in Australia. She talked to four of them asking how they could justify it. All four said there is a huge unmet medical need and it was better to offer these therapies in Australia than have patients travel to other countries for them. They also said that they felt competent to provide treatment because they had undergone some kind of training or had a license to use equipment needed for the therapy.

Ironically while they all considered themselves legitimate providers of a needed medical therapy – albeit an unproven one – and only interested in the science, they regarded others doing the same as “cowboys” and only interested in the money.

When asked if they would support more regulation of the kinds of therapies they were already offering they said yes, saying that the other doctors who claimed they were “self-regulating” is like “giving the keys to the asylum to the lunatics.”

Munsie says it’s clear that it’s not just patients who could benefit from some guidance on expectations about stem cell therapies.

She says we need to do a better job of managing patient expectations without robbing them of a sense of hope, perhaps by offering them information that is more tailored to their particular needs.

We also need to manage what she called “the unbridled enthusiasm of providers” who are offering speculative treatments as “medical practice”. That might take regulatory change by the government.

She says it’s difficult to strike a balance between hope and scientific evidence, in maintaining a patient’s sense of optimism while acknowledging the reality of the science and the risks posed by unproven treatments.

Kevin McCormack

When Hope Runs up against Reality: Balancing Patient Optimism with Medical Evidence

One of the big concerns among scientists – including many at the International Society for Stem Cell Research (ISSCR) conference in Vancouver, Canada – is that patient expectations about stem cells are often greater than researchers are able to deliver today. That can result in patients in search of a cure heading to overseas clinics that offer unproven therapies.

Megan Munsie – head of the Education, Ethics, Law and Community Awareness Unit at the University of Melbourne in Australia – wanted to find out what happens when patients’ hopes for new treatments come into conflict with scientific views on medical evidence. So she started with a small survey of 16 Australians, patients and patient-caretakers, who had travelled outside Australia for stem cell treatments for a variety of diseases including MS and cerebral palsy.

She says there were a number of interesting findings:

  • They all considered themselves pro-active and well-informed
  • They rejected advice from their own doctor but instead relied on the overseas doctor selling them the treatment for advice
  • They felt they had no choice but to travel overseas because they were running out of time and options in Australia
  • They didn’t consider the health risks, believing that the worst that would happen is that the “treatment” wouldn’t work and they would have spent a lot of money for nothing

Perhaps the most surprising finding was that all of them talked about the “benefits” they gained from going abroad for the treatment, that it gave them a sense of hope even if there was no evidence of medical benefit.

What happens when patients’ hopes for new treatments come into conflict with scientific views on medical evidence?

What happens when patients’ hopes for new treatments come into conflict with scientific views on medical evidence?

This led to a bigger study where Munsie surveyed patients and patient advocates but also stem cell scientists and physicians. Not surprisingly the researchers had a very different view of the subject than the patients.

Researchers/doctors said they felt that patients don’t understand science and don’t appreciate the subtleties of clinical trials

  • They said patients were basing their decisions not on science but desperation
  • They considered overseas providers as dubious, selling hope and taking advantage of a vulnerable patient population

What was interesting, however, is that many doctors said they didn’t try to persuade their patients not to go, instead they chose to respect their autonomy but did at least try to give them the facts so that they could make a decision based on knowledge not ignorance.

When asked why they didn’t tell patients not to go, they said they respected the patients’ need for hope and didn’t want to take that away from them because they had nothing they could offer to replace it.

Munsie says recently some doctors have started offering these kinds of unproven therapies in Australia. She talked to four of them asking how they could justify it. All four said there is a huge unmet medical need and it was better to offer these therapies in Australia than have patients travel to other countries for them. They also said that they felt competent to provide treatment because they had undergone some kind of training or had a license to use equipment needed for the therapy.

Ironically while they all considered themselves legitimate providers of a needed medical therapy – albeit an unproven one – and only interested in the science, they regarded others doing the same as “cowboys” and only interested in the money.

When asked if they would support more regulation of the kinds of therapies they were already offering they said yes, saying that the other doctors who claimed they were “self-regulating” is like “giving the keys to the asylum to the lunatics.”

Munsie says it’s clear that it’s not just patients who could benefit from some guidance on expectations about stem cell therapies.

She says we need to do a better job of managing patient expectations without robbing them of a sense of hope, perhaps by offering them information that is more tailored to their particular needs.

We also need to manage what she called “the unbridled enthusiasm of providers” who are offering speculative treatments as “medical practice”. That might take regulatory change by the government.

She says it’s difficult to strike a balance between hope and scientific evidence, in maintaining a patient’s sense of optimism while acknowledging the reality of the science and the risks posed by unproven treatments.

Kevin McCormack