Dr. 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.
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.
The FDA even allows charging trial patients in some rare circumstances, but again that kind of practice especially combined with off-study experiments greatly raises the stakes for patients. If not handled carefully such a practice could become more akin to what is referred to as “pay-to-play”. Patient-funded research is not necessarily a bad thing and in fact especially in tight times of funding it could positively advance important clinical research, but it needs extremely careful planning and oversight. Patients should be given realistic expectations with no hype, the trial should have clear, thoughtful and transparent policies on its receiving of funds from patients and how that links up (or not) with specific patient access. Clinical trial participants should also be instructed to avoid promoting or even accidentally hyping the trial to other prospective participants. Overall, there may be ways to do this kind of thing carefully and with transparency. For example, some institutions have innovative care policies and sets of procedures to review and approve innovative approaches to patient care. Still requiring patients to pay to be trial subjects is risky.
For all these reasons, I’ve been asking myself how to learn more about the unusual, high-stakes situation with the Northwestern MS trial and their other trials using stem cells for additional autoimmune conditions. What I found over the past 12-18 months was a complex, mixed bag of exciting ongoing clinical science and some potentially very concerning clinical trial practices. I’ve summarized my concerns in the flow chart below of how patient experiences may unfold in these kinds of trials. Even though I have major concerns about aspects of this trial, I would note that as I’ve been learning about it I have not come across patients involved who said anything negative about Burt or the trial. They tend to be upbeat and enthusiastic. Unhappy patients could be out there, but so far at least I have not seen that.
Burt trial website with medical claims goes private
I started trying to learn more by asking myself, “what’s out there in the public domain?”
Northwestern’s Division of Immunotherapy has had a publicly-accessible stem cell trial page for years and I found that a good place to start to learn more. I was struck by the implied big medical claims as I was reading that trial home page. Note that it is now a password protected website that the public cannot access, which raises major concerns about transparency. But you can see for yourself what it is like in an archived version of the page here on Wayback Machine without a password requirement.
Click around on some of the pages there. Look especially at the videos and bold statements about patient outcomes. What’s your impression? My sense is that at the very least life changing, potential cures are implied there. The page includes an image of a magazine cover on a story on Dr. Burt’s work that unambiguously says “Curing Multiple Sclerosis” (see a version of the story image in the pic at the top of this post). Of course, the Burt team isn’t responsible for a magazine’s article title, but someone is responsible for including it on their patient website.
Keep in mind again that what is offered by Burt in the clinical trials he is doing for MS, scleroderma, and other autoimmune conditions is not yet conclusively proven to be safe or effective for patients overall. Randomized, properly controlled studies are needed and without those, nobody can really be sure how this will all turn out.
To try to learn more I also reached out to Dr. Burt. In the past few years I have emailed him a couple of times in a polite way asking a few questions, but got no reply either time. Their website on stem cells became password protected soon after I emailed him in 2016. I emailed him again last week and this time he replied, but just to say he would not be commenting and to not ask him again. I had hoped that he would be more open to dialogue and transparency given how unusual his trial is particularly in terms of how it has been publicly marketed to patients (see more on marketing and other issues in Part 2 of this series coming up soon) and how much financial and health-risk burden is placed on patients.
Pushing fundraising that publicly releases private patient health info
The Burt/Northwestern stem cell website also has a handbook for patients wanting access to investigational stem cells that contains some striking language. For instance, this section on patients having to pay up front makes it clear that there’s a major financial focus:
“A financial contract of the estimated cost of the procedure will be prepared. The financial contract costs vary depending on what type of stem cell transplant is needed. Your financial coordinator will tell you the cost of your specific transplant. All contracts must be paid in full before any medical treatment can be given. Many people fundraise to help pay for the treatment. Please see Appendix Fundraising Ideas for additional resources and assistance.”
Clinical trials are very expensive to run so the money side of things needs attention and without enough funding a trial often doesn’t even start so that may have been a consideration in the Burt trial requiring patient payment, but how much burden if any is reasonable to place on patients? How much can the average patient get from insurance and how many patients get no insurance coverage for these experimental stem cell therapies? Who knows? The phrasing in that quoted passage from the Burt team patient handbook is also notable in part because it focuses on “medical treatment” even though what’s being discussed there is not a proven, FDA-approved medical treatment, but rather access to a clinical trial with still investigational offerings. Are some patients getting the wrong impression?
The specific fundraising ideas mentioned in the handbook largely consist of encouraging patients to turn to family, friends, and also strangers online or elsewhere to ask for money for the patients to then pay to Northwestern. The below passages promoting fundraising as the way to go to prospective clinical trial participants raise particular concerns:
“Decide on Soliciting Methods/ Ways to Disperse Information
- Internet: fundraising websites, email, blogs, social media
- Face-to-Face: Schedule Appointments
- Written Requests/ Letters
- Media: News, TV stations, Newspapers, Radios”…
- Call your local media including the news stations, TV stations, newspapers and radio.
- Encourage them to do a special feature or human interest story for the cause.
- If planning a special event, ask for a news release a few days to one week prior to the event.”
Is Northwestern actively telling prospective clinical trial participants who are patients to do these things? One could get that impression. Keep in mind that the patient “information” mentioned as to be “dispersed” in the text of the Northwestern handbook is often going to be the patient’s private information including in certain cases some health data. Patients could try to fundraise online without releasing any of their private info, but that’s generally not going to work. You need to include your name, your condition, location, and some personal information to put together a compelling online fundraising story, right? It seems so.
Is it ethically permissible for a health care organization to encourage (in some sense, to require?) some patients to raise money online, on the radio, TV, newspapers, etc. and actively give up aspects of their medical privacy in doing so or otherwise these patients won’t be given access to a clinical trial? This is an extremely serious question. Could that practice, if it is in fact happening and even if it is indirect, be some kind of violation of the duty to protect patient confidentiality?
The big picture concern here is that for some patients there may be a kind of indirect trial coercion to tell the world about their health issues so as to get the funds needed for trial enrollment or else they could be denied access. In my view, it isn’t ethically permissible for there to be pressure even indirectly from an institution for their prospective clinical trial patients to do that or the consequence for the patient is to potentially be denied access. I wonder how often patients who cannot provide the money that Northwestern requires for these trials are turned away? Is it ethical to ever reject patients for a trial based on lack of money, insurance coverage issues, and such? Overall, since there are so many bioethical questions here I wondered at that point in my research whether Burt’s team had a bioethicist on board. There are several excellent bioethicists throughout the Chicago area.