Burt Northwestern Stem Cell MS Trial Part 3: Funding, Patient Perspectives, & the Future

Today’s post is the last of a three-part series on the Burt stem cell trials at Northwestern. This piece is focused on funding and the future of the trial, and also includes perspectives from patients.

You can read Part 1 here and Part 2 here, which focused on issues related to potential encouragement of patient fundraising that unintentionally releases private information and on concerns over marketing of the ongoing trial as already known to be something like curative for MS. I’ve summarized my overall concerns in a flow chart below.

Stem cells for MS trial concerns

Trial funding

Should patients ever be required to scrape together one or two hundred thousand dollars to pay to get enrolled in any clinical trial? We have to keep in mind that in such trials patients have no guarantee of any benefits and could be harmed because the patients are research subjects. And what happens to the potentially large number of patients who cannot obtain that kind of money? They are excluded simply on that basis?

There may be certain instances where patients paying for a trial can be a responsible, positive thing. However, this is new territory overall for stem cell clinical research and there are sizable risks to this different kind of approach as compared to the past and to some other more traditional clinical experiments when sometimes patients were the ones receiving some kind of payment. As I discussed earlier in this series, extremely careful planning is needed to address bioethical and practical issues that may arise and anticipated risks to patients in such trials where patients have to contribute monetarily.

Some patients have said on the Internet that they are required to pay as much as $150,000 for participation in the Northwestern MS stem cell trial or in parallel off-study experimental administration of experimental stem cells.  If we estimate that about 100 patients have been required to pay (one way or another, such as themselves or via insurance or via online fundraising) on average $100,000 then that is in total $10 million for Northwestern University. Not a small sum, but clinical trials are expensive. If there have been 200 patients paying that much on average the total number could swell to $20 million. The big money involved here is just one more reason that NW and its IRB need to be extra careful in how it oversees this trial.

Do trial participants get any kind of discounted price on medical tests and procedures? Does the university cover all the research-specific (versus treatment) costs itself? How much does insurance pay for the average participant? How much does philanthropy by NW help the average patient? These same questions could be asked of any other trials that require patient payments as well, but there seems to be little if any information that I could find in the public domain on other stem cell IND-based trials that require large patient payments. Continue reading

Burt Northwestern Stem Cell MS Trial Part 2: Marketing ‘Cure’-Like Outcomes?

Can science now cure MS in some patients with stem cells or is that near on the horizon? What about stem cells for other serious autoimmune disorders? What are the risks to patients in terms of health, money, and hope? What if patients must find $100,000 or $200,000 just to get into a clinical trial for this and insurance only sometimes helps in a big way? Will the trial conclude with an approved product that works and is safe enough? It’s always complicated with an ongoing clinical trial to make predictions.

Today’s post is Part 2 of a three-part series on the Dr. Richard Burt stem cell trials including for MS at Northwestern. You can read Part 1 here where I discussed the big picture of the trial, costs and ethical as well as practical issues, and Part 3 here. The point of this blog series is to start an open, diverse discussion and exchange of information about this unusual kind of clinical trial. In Part 2, I focus here on the apparent marketing of the trial.

This NW team has made headlines with exciting, novel approaches to autoimmune disease using stem cells for more than a decade including MS. As a stem cell scientist myself, I believe there is real potential here and hope that the trial is successful in the end. While there currently is no approved stem cell therapy for MS, patients understandably have high hopes including for the MS trial and you see these hopes articulated by the patients on the web.

‘I don’t use the word cure, but…’

Overall, what exactly do patients expect specifically from the Northwestern stem cell trials for MS and other conditions? In these Northwestern trials are many patients expecting cures or at least life-changing outcomes? My sense is that the answer is often “yes” based on all the comments and feedback I’ve gotten from patients and what I’ve read online, while other patients have more moderate expectations. After Part 1 of this series some patients already enrolled in the trial told me they believed they had their life changed by the clinical trial investigational therapy. It feels as though some patients perceive themselves as cured.

A different, but also very important question follows: are patients actively led to believe they will get cures or outcomes similar to cures by the language used by Northwestern? I’m not sure, but let’s take a look at answering that question.

A few quick Google searches and you can find an assortment of information about the NW trials including videos. For instance, you can see a video above with statements from Dr. Burt, those he works with, and patient testimonials about experimental stem cell treatments in clinical trials that he is testing for a variety of conditions. It’s a surprisingly glitzy marketing video and I believe not sufficiently cautious about avoiding giving patients too much hope from a clinical trial. Richard Burt Stem Cell VideoIn fact, the video, its music, the cool flashing lights, and the words spoken make for a very aspirational experience, but what about science and medicine? Data?

The flashy video also makes specific, perhaps still as yet unproven medical claims. Most dramatically, the video claims “a completely normal life not using medications” (see screenshot) is possible from the trial, a phrase that Dr. Burt also says in the video.

This big claim is probably going to be equal to a cure in the minds of many patients and such a statement may be hard to resist for those suffering. As I’ve communicated with patients with severe MS, I’ve tried to imagine myself in their shoes (some even asked me to do that) and in that hypothetical scenario a claim of “a completely normal life not using medications” would be like a magnet for me to that clinical trial, especially if I felt that standard chemical medications weren’t doing the job or had bad side effects. I’d interpret that phrase as meaning a cure or cure-like outcome being available if I were an MS patient.

But I’m not an MS patient and I don’t claim to have great insight there. I’m a skeptical scientist who has seen stem cells over-sold too many times over the years in general even as I wish for proven new stem cell therapies to come on the stage. If I had to predict, I would be optimistic that several stem cell therapies will be approved in the next decade, but where we are at today is more complicated. In part for that reason, in my view a “completely normal life” kind of statement is a questionable way of describing a still investigational stem cell therapy that may ultimately not be proven to be safe and effective for widespread use or that might work only temporarily or only work in a subset of patients.

Also included in that same video is an apparent trial patient specifically saying “I am cured” and in that context the patient is kind of like a spokesperson for the institution. Speaking of cures, on the now password-protected Northwestern stem cell immunotherapy website, which although external to the official Northwestern University web domain has its logo at the top, “Curing multiple sclerosis” jumps out at the visitor to the site right there in the middle of the page. It’s there without even a question mark in the form of an image from an article in The Economist about Burt’s work.  As I mentioned in Part 1 of this series, the magazine is responsible for its own title choice for an article, but why include that on a page for patients about your ongoing clinical trials? At the top left of the page a header says unequivocally, “stem cell therapies are changing lives”, which also suggests big success.

stem cells MS Northwestern University

Is all of this sufficiently cautious so as not to give patients who are considering enrolling the wrong ideas about where things stand? While I’m not a clinical trial expert, when I see an ongoing trial making bold claims it raises concerns. I don’t have direct experience with the team and as I said in Part 1, the NW folks seem unwilling to have a dialogue on this. Note that some patients have indicated to me that the Burt team does not mention a cure in person as they talk with patients and those patients view the NW team as appropriately cautious so that’s important to keep in mind for balance.

The state of the clinical science including research publications

An important caveat here is that maybe the Burt team has amazing preliminary trial data that has convinced them that they can back up big claims, but if so to my knowledge that data is not published. If that data exists it should be peer reviewed and published before big claims are made publicly that patients will see. For reference, see the 2016 ISSCR stem cell guidelines that provide a helpful framework on stem cell clinical studies.

What about already published papers that might support what Burt’s team is doing? Over the years Burt has published important, novel papers on his team’s experimental stem cell transplants for MS (and other autoimmune conditions including Type I diabetes) and some gave encouraging signs of short-term improvements. I think it is fair to say he’s a leader in his field. However, the publications do not contain conclusive results and as best as I could see the data in those papers on MS are not from RCTs. Hopefully new papers with additional data will be published soon that clarify where the MS trial stands more recently.

The past Type I diabetes stem cell clinical trial work from Burt’s team is worth a look for comparison to what is going on now with the MS trial and how it is characterized.

In 2007-2010 Burt’s research made a splash of a possible revolutionary, stem cell-based approach for Type 1 diabetes from work done with pediatric patients along with a team in Brazil collaborating with Dr. Julio Voltarelli. He said back then too that he doesn’t use the word cure, but there seemed to be pubic indications of at least dramatic changes for the better in patients. There seemed to be major science hype by the media itself about this. For instance watch the ABC News video above. Also, take a look at this quote from a Time Magazine piece:

“I wouldn’t use the word cure,” says Dr. Richard Burt, one of the co-authors from Northwestern University. “But it appears we changed the natural history of the disease. It’s the first therapy for patients that leaves them treatment-free — no insulin, no immune suppression for almost five years.”

Exciting, perhaps history-making work 10 years ago using a stem cell transplant with partial immune ablation for an autoimmune condition in the form Type 1 diabetes?

Whatever happened to this line of diabetes stem cell diabetes research? I don’t know. Their 2007 and 2009 JAMA papers were exciting, but after that I can’t find anything other than a withdrawn trial clinicaltrials.gov listing. If anybody is aware of what might have led to the possible end of or long-term pause on that line of research please let us know in the comments.

Again, I hope the ongoing MS trial is proven in the end to be a success because so many desperately ill people would be helped, but again clinical trials are tricky things to predict and often do not turn out as people hope. Science is more generally that way too and we have to see what the data teach us and what our peers think of the data and their views of our interpretations of the data.

Overall, there are many potential risks associated with elevated patient expectations for an ongoing clinical trial and associated marketing, and these issues are only magnified by requiring patients to pay large sums of money for access to a trial. In Part 3 of this series I discuss additional issues including funding, the future, and patient perspectives.

Burt Northwestern Stem Cell MS Trial Part 1: Big Promise & Tough Questions

Curing Multiple Sclerosis Stem CellsDr. Richard Burt of Northwestern University has been doing cutting edge research on the use of stem cells for autoimmune disorders for more than a decade. The core idea behind the work that Burt and other research teams are doing is that stem cells may have revolutionary potential to somehow counteract the autoimmunity that causes serious, life threatening diseases in many patients, including those suffering from particularly aggressive forms of Multiple Sclerosis (MS). Some have recently been characterizing Dr. Burt’s MS experiments as potential cures.

Are Burt’s ongoing stem cell clinical trials providing patients with severe MS and other autoimmune diseases a stem cell cure as some are claiming or is it too early to be making such claims? Are the results more intermediate or potentially only temporary? How risky are these trials for patients health-wise, hope-wise, and financially? The fact that interested patients have to pay (either themselves, through donors, or via insurance) $100,000 or more each to be research subjects definitely complicates things. Some patients have even mentioned on the web needing $200,000 for participating in the Burt MS trial.

What’s going on here?

Today’s post is Part 1 of a three-part series on the Burt stem cell trials at Northwestern that tackles the promise and concerns over these trials. The goal is to catalyze an open, diverse, and rigorous discussion. Because there is so much positive buzz about these trials that in some cases borders on hype, I’ve consciously tried to put on a skeptic’s hat (or lab coat). You can read Parts 2 and 3 here and here.

Burt’s trials are more on people’s radar screens lately because a few weeks back the FDA website indicated that it had sent him a lengthy warning letter a couple of months ago. The warning was related to a host of issues with his stem cell clinical trials including failure to promptly report 2 out of the 4 patient deaths. Such reporting delays took around a year or longer when patients dying should have been reported within 72 hours to the FDA and the IRB. For more on the warning letter see this analysis by a different site, but another FDA concern was that the Burt team may not be properly overseeing investigators in their trial in other countries. MS stem cell cure trial

There’s an urgent need for new options for patients with severe MS and Burt’s work has real promise to be game changing. The standard of care for patients with severe MS today is often so poor in terms of outcomes that we need innovation here and some patients are willing to take on sizable risks. However, in addition caution is required as there are so many vulnerable patients looking for hope and no FDA-approved stem cell treatments for MS. Even Burt’s experimental therapy is not yet fully FDA approved because the work is still ongoing. How a trial such as Burt’s is marketed, funded and run has major impact on and risks for patients.

The possible mechanisms of stem cell function in the studies by Burt and other teams in treating autoimmune diseases such as MS include tamping down autoimmunity through a kind of immunosuppressive function or, as is the focus of Burt’s work, promoting a “resetting” of the immune system via partial chemoablation of the immune system. Once specific portions of the existing dysfunctional immune system are killed, the patient is infused with their own isolated hematopoietic stem cells (HSC) and the hope is that these primitive HSCs will then make new mature immune cells that have little or no autoimmunity. It’s an exciting idea with definite promise, but it remains unproven.

Patients challenge me to learn more on the Burt trial

I’ve been following the stem cell work of Burt for years because it is so innovative and also in part because patients have regularly commented on this blog about his clinical trial practices. Some have asked me how the Burt work is different from what stem cell clinics are doing. For instance, see this comment written by a blog reader who has been upbeat about stem cell clinics, and check out other comments in that same thread.

Some patients have challenged me to learn more about the Burt stem cell clinical trials and some even said that he is “charging” patients to receive experimental treatments both inside and outside of clinical trials. That latter kind of “off study” practice is not necessarily against FDA rules if you get permission in advance for what the FDA calls “expanded access”, which is largely synonymous with the more commonly used term “compassionate use”, but it increases risks for patients. For example, investigational stem cell offerings in such contexts with less data backing them could make patients receiving them relatively more likely to suffer adverse outcomes that might otherwise have been anticipated and prevented based on the knowledge that would have been gained from pre-clinical or earlier clinical studies that were never done or are as yet still ongoing. Continue reading

FDA warns Northwestern’s Richard Burt on reporting patient deaths, other issues in stem cell trials

The FDA recently issued a lengthy warning letter to Northwestern University over the clinical trial practices of its Dr. Richard Burt and this letter just popped up on the FDA website. To my knowledge this is an unprecedented event as I’m not aware of another warning letter to a major university for a stem cell trial. Burt received the FDA warning letter late last year for a number of serious problems with his stem cell trial including failure to promptly report patient deaths to the FDA.

Richard Burt Warning Letter

Another issue noted by the FDA was lack of proper oversight of other participating investigators in the trial at locations around the globe. The list goes on and on of big problems detailed in this long letter. Notably the issues in this mid-November 2016 warning letter were reportedly “addressed” according to a follow up letter from the FDA (see close out letter link at bottom of the warning letter webpage) so hopefully that means at least some improvement.

However, this warning letter raises many longer term concerns. For instance, if Dr. Burt’s team did not report patient deaths properly to the FDA, did they also not tell future prospective trial participants about how often deaths occurred? As such, were trial participants properly consented in terms of being informed about potential risks to them?

The wording of the letter signals the seriousness of this situation and the FDA says at the start:

“We have determined that you violated regulations governing the proper conduct of clinical studies involving investigational new drugs, as published in Title 21, Code of Federal Regulations (CFR) Part 312…”

Has this big, complicated trial gone a bit out of control?

In addition and more broadly, other aspects of Dr. Burt’s stem cell clinical trial work have potentially problematic issues that still may not be resolved and that raise difficult bioethical questions. These other concerns will be the subject of a follow up post.

Guest blog from inside Vatican Stem Cell Meeting by John Carbona: Day 1

Vatican Stem Cell Meeting 2013The Vatican Stem Cell Meeting 2013 has started.

We are fortunate to have a guest blogger, John A. Carbona, CEO of BioLife Cell Bank, who is in attendance and kindly is giving us inside coverage of the meeting.

Below is a guest blog from John on Day 1 of the meeting. We even have pictures.

Thanks, John!

-Paul

Thursday, April 11, 2012

The Second International Vatican Adult Stem Cell Conference:

Regenerative Medicine – A Fundamental Shift in Science & Culture, taking place from within The Vatican

With a buffet fit for Caesar Augustus himself, the first day of the conference began. (Thanks Mesoblast for sponsoring breakfast!) The accommodations at the Westin Excelsior are grand. I think the amount of marble used in my gargantuan bathroom could, in fact, resurface the Colosseum. 

Vatican Stem Cell Meeting 2013Arriving at the Vatican and crossing the barriers (protected by the Swiss Guard) into the inner sanctum reserved for dignitaries was awe inspiring.  We were welcomed by: Meredith Vieira (NBC), Dr. Max Gomez (CBS), Bill Hemer (Fox), Peggy Noonan and Gianfranco Cardinal Ravasi. The sessions are taking place in an opulent auditorium with cushy, hi-tech seats that was the location of the cardinal’s general meeting prior to the conclave which elected Pope Francis.

A highlight of the morning session featured current multiple sclerosis (MS) patients of Dr. Richard Burt from Northwestern University. Each described miraculous recoveries after stem cell transplants. Jim Danhakl, a top gun fighter pilot, came to Dr. Burt as a bed-bound patient who had to use a wheelchair. Within two weeks after the transplant, he was taking his first steps! Today, he scrambled down to the podium to speak. As Dr. Burt’s patients thanked him, everyone was visibly moved by their emotion and gratitude. Another MS patient, Roxane Julia Beygi, brought the audience to tears reliving her journey. (She will be profiled soon—featured in a documentary.)Vatican Stem Cell Meeting 2013

Our first day of meetings has ended. Now, off to a private tour of the Vatican…

My best regards,

John A. Carbona

BioLife Cell Bank, CEO