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.
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.
Another issue here with the NW work is that as best as I can tell the Burt team has no current NIH funding for this clinical trial work. As many of us know first-hand, getting NIH funding is really tough these days, but has his team tried for funding recently? Sometimes it takes a lot of work to get the funding and multiple grant submissions, but it is worth going for it. If the team’s unpublished data is truly groundbreaking then perhaps they have a good chance of getting the funding.
Obtaining NIH funding in this case would shift some of the great financial burden off of the patients and provide another level of peer review. There has been recent NIH-funded stem cell clinical trial research for MS and additional autoimmune diseases by others (e.g. see here and screenshot above), which to my knowledge did not require large patient payments, but if I’m wrong about that last point on charging please let me know. The point is that in theory at least it is possible to get NIH funding for this kind of clinical trial work and that should take some burden off of patients.
How to view this clinical trial study in the big picture?
Quite a few patients apparently believe Burt saved their lives, but with the trial still ongoing, how sure overall can we be about broader efficacy and safety? How will this experiment end up comparing to standard of care overall when the data are objectively analyzed and peer reviewed in the end? What about longer-term potential positive and negative outcomes? In that regard, will benefits last long term for the average patient and could they face some longer-term risks?
With all the complicated aspects to this trial including its charging patients big fees, its promotion of what is offered to prospective participants as potentially already known to be curative, its nebulous status in between an experiment and a treatment, unusual large number of off-study patients, crossover of maybe nearly all control subjects who know and expect in advance to be crossed over later, open label status, and more issues, will the data in the end yield concrete conclusions? Could some of these things be confounding variables? How convinced will reviewers be? Will journal reviewers even be aware of these issues? Maybe not. The bigger question is how the medical and scientific community will view this trial long term.
Patient perspectives
I’ve asked readers of this blog including patients for comments and here is one from a past recipient of stem cells from Burt’s trial:
“Imagine you are a patient with an incurable degenerative autoimmune disease. You’ve taken most of the drugs (Avonex, Betaseron, Aubagio, Tecfidera, and Gilenya) and you’re still showing disease progression every time you get an MRI. A new radical interventional treatment (not a new drug that does jack shit) becomes available and is already in phase III. In varying forms it is being administered in multiple locations all over the world, with extremely promising results. According to peer reviewed literature, it has a higher chance 5 years out of preventing relapses than any other treatment. These statistics are reasonably consistent across the multiple centers. It might not work, but if it buys you time, then maybe something else will be on the market or an updated treatment will be available. In the meantime, you may have slowed or even halted progression, for at least a little while.What would you do?”
As I replied to this patient, honestly I would consider all options if I was in that situation as a patient myself. But as a biomedical scientist I also have to ask myself what I would do hypothetically on the flip side as an investigator considering doing this trial.
I also received a comment from another Burt trial patient:
“Dr Burt completely turned my life around. I used to find it impossible to even perform mundane tasks such as buttoning up my shirt or walking without support. Normal medication did not work. The treatment almost completely reversed this. Dr Burt did not promise a cure. On the contrary, he said at best this will arrest the condition. He also clearly stated the risks. I believe the treatment has helped hundreds.”
These patient perspectives are helpful and important.
Burt MS stem cell trials as compared to stem cell clinics
Getting back to the past challenge given me by some other patients/readers of this blog in the past (see the beginning of Part 1 for more on that challenge), overall what Burt is doing is quite different from the stem cell clinic approach. His team seems focused on data and rigorous science. They also work with the FDA and have regularly published their findings in strong peer-reviewed journals in the past. Still, my sense is that there are some concerning issues here even if the trial technically has FDA permission for much of this and even if this is almost 100% different than what most stem cell clinics do.
What would be helpful moving forward?
As a start, Northwestern and Dr. Burt should revisit how this trial has been handled. I think they should also be more transparent about answering questions with so much at stake in a high-risk, high reward kind of trial. They should shift more financial burden off of patients, they should consult a bioethicist if they haven’t already, and they should greatly tone down or entirely stop what I see as their trial marketing of something akin to a cure. As to that last point, taking down all the Internet videos that have possible marketing aspects in them might be worth serious consideration. The fact that the NW Immunotherapy stem cell trial website that had some marketing-like material is no longer publicly accessible (you need a password now) might be a first step in this kind of direction (contrary to how I originally saw its removal from the public domain as a hit to transparency), but we don’t know if the team is still allowing prospective trial participants to visit the site via a password.
I’m not sure what NW or its IRB should (or at this point even could) do about the enormous number of their trial patients doing public fundraising for the trial on Gofundme and in the process in many cases releasing their private information to the world or making medical claims about the trial that they’ve heard. But that situation is very concerning and the fact that many if not most of them were potentially encouraged to do this fundraising by NW itself raises thorny bioethical questions.
To be clear this type of research is very promising. My hope looking to the future at a medical level is that this trial and others like it run by additional teams ultimately prove the new investigational stem cell-based therapies have a sufficient safety profile and have clear efficacy from additional work including RCTs so that they can help the patients with severe MS and other autoimmune conditions who are in desperate need. The current medications available are just not working and/or have incredibly bad side effects for a substantial number of patients.
Bigger picture: the new model of trials in which patients pay?
At a broader level we should be asking ourselves, “how many other groups are conducting similarly structured trials?” Is it possible that the Burt trial is not that unusual and we mostly just don’t know about the many other trials that also engage in these kinds of practices? One that drew attention last year is the so-called “young blood” anti-aging trial for which patients must pay $8,000 to enroll, but what about others?
Is this kind of trial model going to become much more common in coming years? If so, it requires far more discussion in advance about the risks as well as bioethical and practical considerations needed for protecting patients on many levels. The Burt trial is a case study that depending on one’s perspective either encourages more teams to follow this model or discourages others from following suit. We’ll see in coming years how it plays out overall.
Final note: It’s tough for me to do a blog post series like this. The somewhat concerning information that I found after patients challenged me to learn more, in combination with the recent FDA warning letter to Burt, are together what prompted me to finally post this series. Some people strongly disagree with my perspectives here. In fact, some have been letting me have it on the web since I started posting this series. That’s no picnic for me. However, I understand that in many cases they have gone through a lot, they have strong perspectives to share, and possess more direct knowledge of what patients go through so I don’t take it personally. In this time of big change in clinical trial practices, more discussion of how clinical trials and stem cell-based clinical trials specifically are designed and managed is needed, and more open, diverse dialogue cannot help but be beneficial to patients and the field in the long run. For these reasons, I decided to go ahead with this series.
Every month I write a check for $1897 to cover my portion of the fee to big pharma to pay for my MS medication. This is the 6th different medication I have tried over 10 years to halt this disease. Most came with a similar price tag. In looking at the financial side I have spent over $225,000 to still develop new lesions, symptoms, issues. This does not include the $3000-5000 each month my insurance has paid. Making big pharma approximately $700000 richer over the past 10 years. I am but 1 patient. There is a reason why when any pharmaceutical company rolls out a new MS treatment their stock value raises 1000% overnight. This is the sad reality. Imagine for a moment the # of patients in the US on a preventative. Let’s say 30,000. 30000 x (average low) $5000 per month. That is an impressive $150,000,000!! PER MONTH.
Now to me that million or so dollars that NW has collected seems pretty insignificant. Particularly when most of NW patients have seen little to no progression and those of us on meds have.
This is not a new concept, (charging for experimental treatment). People have been traveling to foreign countries for years to have experimental cancer and other ailments treated. Even here in the US people have shelled over millions on trials for treatment of other diseases.
I think the more important issue you should be raising is why big pharma has been allowed to “take advantage” of such sick patients.
I think the word “Cure” is more of a reflective term used by patients who, after years of continued negative progression, finally have been able to stop and breathe in our MS pool rather than keep drowning. We will always have MS but if MS doesn’t have us for even a few years it can feel like a temporary “CURE”.
My wife was treated by Dr Burt in 2014. 5 years later she is 100% still in remission. 5 years of remission = cure. You use so many words, yet there is such little insight. You do not grasp the science of why a stem cell transplant is indeed curative for many autoimmune diseases. In fact, transplants are proving to be amazing for a wide range of diseases and infections, most recently HIV. Your “analysis” lacks depth of scientific merit and instead you focus on your distaste for the marketing and costs (although truth be told there is zero real marketing behind this). Welcome to America, where you get the best treatment in the world but only if you can fight for it and can pay for it. If you want to write about the moral issues of the american medical system then have at it. But dont be a hack and attack this treatment when you clearly lack any depth of understanding.
@Matthew,
I’m glad that your wife is doing well.
As to the other stuff you wrote in your comment, you are wrong. I do understand the science. I have appropriately high expectations for clinical trial conduct and following FDA rules. I also believe that patients should not have to pay for still experimental offerings.
I have CIDP and am considering Dr Burt’s treatment. I have seen very few comments here about CIDP. Are there CIDP patients of Dr Burt that can give their experiences? Thanks.
Thank you everyone for participating in the discussion here.
I’m eager to try HSCT. I have (anti-MOG+) NMOSD, a very rare illness that’s like MS and is treated at MS clinics. I find it hard to understand why my doctors are staunchly opposed to me pursuing HSCT.
AND I THANK YOU for publishing this series, Dr Knoepfler! I think it’s clear you’ve tried to be evenhanded. The FDA letter really scared me, as it should have. I’m still excited! Even though the still-shrill marketing scares me too. I’m not gung-ho (that is, thoughtless); the risk-reward ratios are just so compelling*!
As noted at https://ipscell.com/2017/04/burt-northwestern-stem-cell-ms-trial-part-1-big-promise-tough-questions/#comment-36589 , HSCT is a bargain. Compared to taking Rituxan for the rest of my life, and the hospital costs of the occasional relapse, the cost of HSCT is … negative – it saves money!
No one here is shouting conspiracy theories. “Big pharma isn’t going to back a research project like this” isn’t conspiracy. It’s fact. It’s also a fact that that HSCT “is a possible cure or the closest thing to a cure to date.” Claiming the latter is the reason for the former, without evidence, would be a conspiracy. But that claim wasn’t made. But it’s likely that it is a factor. But “Dr Burt’s HSCT treatment isn’t patent-able” is almost certainly a major factor too.
Big Pharma does a lot of great work. And it’s got MAJOR problems. (What major industry doesn’t?) They get lots of media scrutiny. And that’s a good thing. So is this article. To whomever threatened Dr Knoepfler: Shame on you!
-Mr E
*For my illness, there’s more uncertainty than for MS, but the prognosis is also worse than for MS. If I get HSCT, the odds that it will give me an amazing life I won’t otherwise have are around 10x higher than the odds it’ll kill me. I did a fairly detailed numerical analysis, but that’s what it boils down to. The stakes are high, but it seems to me I’d have to be ignorant, innumerate, or a fool to not want to place a bet when the odds are so strongly in my favor and the reward so enormous.
@Mr E,
Thanks for your comment and support of open dialogue about this important, but complicated HSCT research situation.
Paul
I read that recently a couple of people, one I read about in detail 11/17 passed, RIP ;(
I’ve been considering HSCT but difficult to get facts on negative results. Have you heard anything?
@JR,
Do you have a link to what you mentioned reading on the possible recent deaths?
From facebook HSCT group obviously a sensitive subject no one wants to talk about but as someone considering it I want to know why it happened. I cannot find any reports yet FDC, etc.
I’m one of Dr. Burt’s patients who, after a year and a half, is still in remission. The term “cure” is misleading, though, on both science’s part and patients’ parts. People who have been successfully treated for cancer are considered in remission. Perhaps it’s the word “cure” that is messing up peoples’ impressions of Dr. Burt’s team’s work; perhaps we ALL, patients and researchers alike (although Dr. Burt has never said the word, in my presence) need to start using the word remission rather than cure; like people would for cancer treatment. Like cancer, MS is a chronic disease, and even remission (while not a permanent cure) is a treatment goal for many, many people. Let’s face it, folks: nobody on earth is guaranteed a long, healthy life forever with no possibility of any illness or injury. We can all go outside and be hit by a bus, so let’s all just view this with perspective and look at long-term remission as someone might who was successfully treated for breast cancer: “I’m in remission, which to me feels like a cure.”
Hi Jackie,
I’m glad you are doing well in remission at this point and hope it continues for a very long time. I also hope this ends up being the experience of a significant # of patients in these trials.
Thanks for sharing your story. I appreciate your really clear, common sense-based perspective on this. One of my concerns that led to doing the series of posts was that the word “cure” kept coming up as I tried to learn more and sometimes phrases that in my view were equivalent to “cure” were used and not just by hopeful patients.
Your comment resonated with me also because I’m in long-term remission from a serious form of cancer. I don’t see it as a cure necessarily. I hope it is effectively a cure, but you never know. My hope is to die some day far down the road of something else besides this cancer or even better, of old age.
Paul
Hi, I enjoyed your exploratory nature in these posts. Neither denying or affirming something that you can’t be sure about, but instead bringing up questions that should be asked (and answered) as this moves forward. As a patient who has determined the risks of stem cell treatments to be too risky for myself at this time, I often find people who are considering themselves “cured” criticizing my decision in harsh language and offensive ways. I support their choice and pray that they have truly been cured, but I hate to see their rage filled posts of “fake news” and angry assumptions that Dr. Burt is the victim of some horrible big pharma conspiracy to shut down stem cell research. I have stopped looking online for real information about stem cells and refuse to discuss it in various groups I attend. I think we should do a lot more to encourage questions and I appreciate you doing that.
@Jennifer,
I really appreciate your feedback and support. I have received a lot of hate and even threats because of these posts, including from some of his patients, but overall most people have been positive about it and found this series to provide useful insights and questions. Paul
You seem to flip flop back and forth between supporting these trials and bad mouthing and scaring patients away from trying these studies. I’m 1 year post transplant and I’m probably a little worse than I was prior to transplant, but I still believe HSCT is/was the best chance I had at stopping the progression of my MS. I’ve read your series yet still don’t really understand your view on HSCT. You say things like it’s “very promising” yet say it needs more peer review or how can they require patients to pay that kind of money. The truth is, if this were another drug, a pharmaceutical company would actually pay me to take their drug. Big pharma isn’t going to back a research project like this that is a possible cure or the closest thing to a cure to date. I wish I didn’t have to pay the kind of money I had to pay, but when I look at the overall situation with our healthcare system, paying for it or fighting with insurance was the only choice for me because giving up wasn’t an option. I appreciate your views, but often times when I read your blog, I can’t tell if you’re for stem cell therapy or treatment or against it. You’re really neutral as if to not step on “anyone’s toes” which is fine, but if you’d talk to more patients about Dr. Burt, I think you find that he has a huge amount of respect from his patients. Everyone that I know that went through transplant including myself and even the ones who were accepted for transplant, but didn’t get insurance approval will tell you that Dr. Burt told them in a very serious demeanor (almost as if he was trying to talk you out of going through transplant) that you could die from the procedure and at best may not be able to have kids after the transplant and should consider banking. He’s by far the best doctor I’ve ever had and really cares about his patients and doing what’s best for them even if it means not offering the transplant as an option.
@Daniel,
Thanks for the comment.
I have mixed feelings about these trials and that probably comes through in these blog posts. Something can be promising, but still unproven and in the end not work out. And it can be that a trial is promising scientifically/medically but aspects of how it is managed, marketed, etc. are really problematic and bioethically questionable.
Paul