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Crowdfunding to pay to be a research subject in a clinical trial: The case of Lily Wythe [UPDATED 1/23/2020—see addendum]

Lily Wythe is a teenaged girl with a deadly brainstem cancer whose case has made international news because of her family’s crowdfunding to get her into a clinical trial. Should investigators be allowed to fund trials this way?

Given my long history of writing about the desperate parents of children with deadly brain cancers using online crowdfunding and persuading celebrities to help them raise funds to take their children to cancer quacks, a story spreading around the media, both old and new social media, the last week or two definitely raised my eyebrow. Once again, I encountered the tale of a child (in this case 13-year-old girl named Lily Wythe) stricken with a deadly brain cancer (in this case a cancer with which we’re well familiar, diffuse intrinsic pontine glioma, or DIPG), given how many times I’ve written about cancer quacks like Stanislaw Burzynski or those at Clínica 0-19 in Monterrey, Mexico or Hallwang Clinic in Germany, luring such families in with false hope and quackery. Once again, I got the sinking feeling that the crowdfunding campaign was being used to support a cancer quack.

This time, though, there was a twist, which has left me profoundly conflicted, and that twist is that it’s not quackery or a quack clinic for which funds are being raised. It’s a legitimate clinical trial at Seattle Children’s Hospital. However, unlike the usual case for clinical trials, in which patients do not pay for study-related expenses other than routine medical expenses that they would have paid anyway even if they weren’t on the study, that doesn’t sound like what is happening here, which is that Seattle Children’s Hospital appears to be requiring at least this patient to pay for the cost of being on the clinical trial. You might recall that “pay-to-play” clinical trials and fundraising for such trials are ethically very problematic, as I’ve recently discussed. This story resurrected those concerns and added the the even more troubling element of a family scrambling to pay for such a trial.

While I’m happy that, as you’ll see, Lily is doing so well currently and certainly would never discourage anyone from entering a clinical trial, least of all a patient with DIPG. However, the similarities between what I’m observing with the case of the Wythe family and what I’ve observed with, for example, Burzynski patients made me profoundly uncomfortable, and I’m not sure what the answer is to make such a situation less troubling.

Lily Wythe’s story

Lily’s story is heartbreakingly familiar to me (and certainly to regular readers). It’s told in articles with the same sorts of headlines that we’ve seen so many times before with Burzynski patients or Clínica 0-19 patients, such as this article in a UK paper, Teenager’s desperate bid to raise £300,000 for cancer treatment nears target:

A teenage girl has created a viral fundraiser in a bid to send her best friend to the US for revolutionary cancer treatment.

Lillie Cotgrove came up with the idea of ‘The One Pound Warriors’ Facebook group in which people donate at least a quid.

The grassroots fundraiser has now been backed by a host of celebrities, including Rachel Riley, Alfie Allen and Steven Gerrard, and is nearing its £300,000 target.

Lillie’s best friend Lily Wythe was diagnosed with an aggressive malignant brainstem tumour called Diffuse intrinsic pontine glioma H3 K27MK.

It is a tumour of the central nervous system that affects sight, hearing, speech, swallow, breathing and heart rate and has an average survival of eight to 12 months.

Lily, 13, has undergone radiotherapy but the family are pinning their hopes on a clinical trial in Seattle, USA.

The family created a GoFundMe page and Lillie, of Benfleet, Essex, also set up a crowdfunder to help.

The HJ3 K27MK mutation is a mutation in DIPG that is associated with particularly aggressive disease and early recurrence after radiation therapy, usually within 6-9 months.

I must say that, as I saw story after story like this, such as this story posted nearly a week ago, I was very much expecting the “punchline” of the family wanting to take Lily to Houston, or to Monterrey, or to Hallwang Clinic, or to some other dubious clinic of which I hadn’t yet heard. I decided that I had to look into the story in more depth because it brings up so many issues, some issues similar to those that come up with stories that I’ve written about before and some very different. All are difficult, and the overall situation leaves me very conflicted. Specifically, I was very curious what this clinical trial at Seattle Children’s Hospital involved such that it required £300,000 (~$391,590 US as of yesterday’s exchange rate) to enroll. After doing some searching, I’m pretty sure I know what trial it is. More on that in a moment.

First, let’s examine Lily’s clinical history in a little more detail. Because I’ve written so much about DIPG patients over the years, her clinical history sounds sadly familiar. From an article shortly after the Wythe family launched their crowdfunding campaign in late November, £300k plea to fund vital trial for Lily:

The bright and bubbly Eastwood Academy student, who also has a brother, Josh, 12, was diagnosed at Great Ormond Street Hospital in October.

After returning from a family holiday in August, Lily started suffering from morning headaches, vomiting and double vision.

Soon after came speech and co-ordination issues. After visiting healthcare professionals on five occasions, Lily finally had an MRI which revealed a tumour on her brain stem.

Lily was immediately admitted to GOSH for five days and put on steroids before the dreaded diagnosis followed a few weeks later.

She has undergone radiotherapy, which has reduced her symptoms, and she has had a life-saving operation to reduce pressure from her brain.

The community has rallied round to help, and so far, more than £14,000 has been raised, but this is a far cry from the cash needed to get Lily to Seattle for the trials, which start next spring 2020.

This story from two days ago provides more information. Overall, Lily is doing well now, radiotherapy having shrunk the tumor, although I’m not clear from the news reports about whether the tumor shrank away to undetectable or whether there is still observable tumor left on post-therapy scans. She also suffered some complications:

The last few months have taken its toll of Lily. She struggled to walk and dress herself going through the radiotherapy as well as having to learn to eat again.

Not long after starting radiotherapy in October to shrink the tumour, Lily got the flu and suffered aspiration, when you swallow food into your airways.

While recovering, Lily then suffered from hydrocephalus, which is when the brain swells and fluid gets stuck and puts pressure on the skull. She had to undergo intensive brain surgery.

“It is very intense and you do worry. But she had to have it because it can kill you,” Diane added.

She also had a shunt fitted from the brain to the stomach for any fluid to move to.

Stories like this one tear me up. They always have, ever since I started writing about these sorts of situations, albeit from the perspective of decrying quacks making huge sums of money selling false hope to patients like this. I’ve said it before many times. I can’t understand the parents’ desperation from personal experience, but I can empathize and understand as a fellow human being imaging what I would do in a similar situation, with a child whom I love more than anything in the world facing imminent death from brain cancer. I decry quacks like Stanislaw Burzynski and the doctors at Clínica 0-19 because they prey on the desperation such parents naturally feel, their willingness to do anything, to go to any length to save their child.

BrainChild-03: The clinical trial

Having covered so many stories like this on this blog, I can’t help but get a whiff, a hint, of the same sort of issue here, this time from Seattle Children’s Hospital. The Wythes and their friends have accomplished some truly prodigious fundraising. They’re nearing the needed £300,000, and Lily’s friend Lillie Cotgrove came up with the idea of The One Pound Warriors, in which she raises funds by having lots of people donate just one pound each, with amazing success. Thanks to the involvement of celebrities like Alfie Allen, who played Theon Greyjoy in Game of Thrones, the fundraising total has surpassed £250,000.

Alfie Allen raises funds for Lily Wythe

What is this treatment being tested in a clinical trial that costs £300,000 for a year when travel and lodging are factored in? A hint came from the very first post on the Facebook page set up by Lily’s family to fundraise and publicize Lily’s plight:

The passage:

After extensive research there are currently two suitable Clinical Trials in the US that show very promising results for Lilys type of Brain Cancer, a drug that starves the cancer and a new Immunotherapy treatment at Seattle Hospital.

Based on this, I knew it had to be either antiangiogenic therapy (“starving the tumor” by attacking the new blood vessels that supply a tumor with oxygen and nutrients) or, more likely given the high cost, CAR-T therapy. It didn’t take much Googling to figure out that the immunotherapy must be CART-T therapy. A quick trip to ClinicalTrials.gov led me to two trials:

The second trial was, according to ClinicalTrials.gov terminated by design, specifically it was topped “if fewer than 3 cohorts by molecular classification were with 10 participants or only 1 cohort enrolled at least 15 participants of 50” and thus appears to be no longer recruiting. Indeed, its results are published on ClinicalTrials.gov, with a reported 9 month survival rate of 64%. Moreover, this story published yesterday confirms that the family wants to take Lily to Seattle for CAR-T cell therapy. So it must be the first clinical trial.

The Seattle Children’s Hospital website describes the clinical trial, known as BrainChild-03, thusly:

In this trial, the patient’s own T cells are reprogrammed to recognize and target the protein B7-H3, a surface molecule that is on most CNS tumors.

The reprogrammed cells (now CAR T cells) will be put back into the patient’s body (infused) through a catheter, either into the place where the tumor has been removed or into the CNS ventricular system (intra-CNS). Placement will depend on the location of the tumor.

This study is open to all types of CNS tumors that have recurred or progressed and for children with DIPG.

This is the first CAR T-cell trial in the United States for children with DIPG and is open to patients with DIPG any time after radiation.

The principal investigator is Dr. Nicholas Vitanza.

For those not familiar with CAR-T-cell therapy, CAR T-cell stands for chimeric antigen receptor (CAR) T-cell. In brief, CAR-T cell therapy involves taking blood from the patient, isolating T-cells, and genetically modifying them, after which they are grown into large quantities of cells needed and reinfused into the body. This short video on the Seattle Children’s Hospital website provides a simple description of how these cells work suitable for a lay audience:

In this case, the cells will be injected either directly into the tumor resection cavity (for tumors that are resectable and therefore resected successfully, which is almost never the case for DIPG) or into the ventricular system through a catheter. This clinical trial is the third trial that’s part of an initiative by Seattle Children’s Hospital to cure pediatric brain cancer, called—you guessed it!—BrainChild, just as the studies are named BrainChild.

Lily Wythe: Crowdfunding for a phase I clinical trial

As I read the ClinicalTrials.gov entry for BrainChild-03 (ClinicalTrials.gov identifier: NCT04185038), it became apparent to me that requiring a patient’s family to pay for this particular trial is ethically problematic. Certainly, it’s not as problematic as for-profit stem cell clinics requiring patients to pay for phase I clinical trials of their almost certainly worthless therapies, which they then use more for marketing than anything else, co-opting ClinicalTrials.gov in the process, but it’s ethically problematic nonetheless. The reason is that this is a phase I trial. It looks like a scientifically sound phase I trial, but it’s still a phase I trial, and that means that it is not testing efficacy. It is testing safety

Here are its primary outcome measures:

  1. Establish the safety, defined by the adverse events, of B7H3-specific CAR T cell infusions delivered by a central nervous system (CNS) catheter into the tumor resection cavity or ventricular system. [ Time Frame: up to 7 months. ] The type, frequency, severity, and duration of adverse events as a result of B7H3-specific CAR T cell infusion will be summarized.
  2. Establish the feasibility, defined by the ability to produce and administer CAR T cell product, of B7H3-specific CAR T cell product infusions delivered by a central nervous system (CNS) catheter into the tumor resection cavity or ventricular system. [ Time Frame: 28 days. ] The proportion of products successfully manufactured and infused will be measured.

Here are the trial’s secondary outcome measures:

  1. Assess the distribution of CNS-delivered B7H3-specific CAR T cells distribution within the cerebrospinal fluid (CSF) and peripheral blood. [ Time Frame: up to 6 months.] The trafficking of B7H3-specific CAR T cell product through the CSF by measuring remaining CAR T cells from a prior infusion at the time of each infusion and the trafficking of B7H3-specific CAR T cells from the CSF into the peripheral blood will be evaluated.
  2. Assessment of disease response of B7H3-expressing DIPG and DMG tumors to B7H3 specific CAR T cell therapy delivered into the tumor cavity or into the CNS [ Time Frame: up to 6 months ] The response of DIPG and DMG tumors to B7H3-specific CAR T cell therapy delivered into the tumor cavity or into the CNS will be determined by evaluating CSF for tumor cells and by CNS imaging with MRIs.
  3. Assessment of disease response of B7H3-expressing refractory or recurrent central nervous system (CNS) tumors to B7H3 specific CAR T cell therapy delivered into the tumor cavity or into the CNS. [ Time Frame: up to 6 months. ] The response of refractory or recurrent CNS tumors to B7H3-specific CAR T cell therapy delivered into the tumor cavity or into the CNS will be determined by evaluating CSF for tumor cells and by CNS imaging with MRIs.

Yes, the investigators are doing measurements (MRIs, etc.) to see if there is any tumor response, but that is not the primary purpose of the study. Yes, there’s a possibility of tumor response. OF course there is! The investigators wouldn’t do a study like this, much less a study of a treatment that costs so much money, if they didn’t have high hopes that it would be better than currently existing therapies.

Here’s where I have to be very delicate. I always assume that the family will likely see what I write because if there’s one thing I’ve learned it’s that families crowdfunding to save their child very frequently have Google Alerts set up to alert them whenever anyone posts something to the web about them, the very last thing I want to do is to be perceived, either by the family or anyone else, as criticizing the family. I am not. In fact, I admire their devotion and industriousness in raising such prodigious sums of money in such a short period of time. I understand why they do it. I applaud them. My question lies in the ethics of requiring the family to do that to be on the clinical trial, of making it a choice between doing what the Wythe family is doing and not being on the clinical trial.

Whenever I see a story like this, I always have to ask: What have the investigators told the family about the trial and its likelihood of helping Lily? There is an inherent tension between downplaying expectations because this is a phase I trial and hyping expectations in order to recruit. There is even more of a tension when you’re placed in the horrible position of the Wythes of having to crowdfund huge sums of money. Just Google Lily Wythe’s name and look at the headlines that come up. Read some of the articles. You’ll see what I mean:

I can only imagine what the TV coverage in the UK has been like, with all those celebrities involved in helping to fundraise for Lily. I also hate—hate, hate, hate!—the spin in the headline of the last story mentioning the NHS. The NHS most definitely does cover brain cancer treatment and certainly would pay for effective palliative treatments for Lily. It just doesn’t cover experimental or unproven treatment, particularly experimental treatment outside of the UK, which is not an unreasonable policy for a single payer health care system—or any government health care system. I’ve noticed that the press in the UK loves to spin stories like Lily’s to portray the NHS as the callous and uncaring, as “sending the patient home to die,” leaving the patient and family with no choice but to look overseas, where sometimes they find quacks like Burzynski and sometimes they find legitimate clinical trials like this one. This sort of spin sends a horrible message to patients and the general public by not-so-subtly implying that palliative care for cancer is not “real” care and that curative treatments are “real” treatments.

I also noted another thing about this trial that is very problematic and of a piece with criticisms of pay-to-play trials that I’ve discussed before. There’s no mention in its ClinicalTrials.gov entry that this trial is pay-to-play, at least none that I could find. It is true that FDA regulations do allow such “pay-to-play” clinical trials in “extraordinary circumstances.” An example of such “extraordinary circumstances” is a situation when a drug being tested has a price tag so high that the trial can’t otherwise ever be run. I’m assuming that’s how Seattle Children’s Hospital is justifying charging Lily’s family so much money to be on this trial, given how expensive it is to make and administer CAR-T cells. However, to reiterate my previous concerns, I still have a hard time envisioning such a scenario that wouldn’t be predatory, whether intentionally (as in the case of quack stem cell clinics) or unintentionally (as in this case), and the case of Lily Wythe illustrates why.

I also cite again ethical and scientific concerns raised in STAT News:

But experts say these trials are ethically fraught for a number of reasons: At worst, they run the risk of being a guise for an enterprise looking to profit from desperate patients. But even when intentions are sound, the trials are likely to only enroll those patients who can afford to participate, thereby skewing the results. There could also be a weak study design, without blinding or a control group, because patients would likely be reluctant to pay for a placebo. And they may reinforce the common misconception among patients that clinical trials are a route to accessing treatments that are guaranteed to help them.

Precisely.

It’s also not clear to me from all my reading whether every patient enrolled on this trial has to pay or if Lily’s family only has to pay so much because they’re not from the US and don’t have US health insurance to cover the additional costs of treatment outside of the production and administration of the CAR T-cells. Some articles quote Lily’s mother as saying that the £300,000 is just for the treatment, a minimum amount of money needed, and that travel and lodging are extra. That doesn’t completely clarify the issue of how much is for the CAR T-cell treatment and how much for everything else or if every study participant is being asked to pay close to $400,000 to enroll in the study.

Incomplete narratives harm research and mislead patients

The press coverage for this story, as has been the case for pretty much every story I’ve ever covered of this type, has been an epic fail. More information is desperately required, and I don’t see it in any of the news stories about Lily. None of them that I’ve found thus far have bothered to look into this angle, in particular at why the Wythes are being required to pay so much money for a phase I clinical trial or at whether everyone is required to pay to be on this trial. No one has interviewed anyone at Seattle Children’s Hospital about the trial. Most stories, if they mention what the experimental therapy is at all—most don’t, other than to call it experimental, while some don’t even call it experimental, only “revolutionary” or “life-saving”—only refer to it as “immunotherapy.” (I’ve only found one story that even mentioned CAR-T cells.) None of them mention that the crowdfunding is for a phase I trial, explain what a phase I trial even is and that a phase I trial primarily tests safety and tolerability of the therapy, not efficacy, or asks Seattle Children’s Hospital why it is charging patients like Lily so much money to be on the trial. None of them explain what CAR-T cell therapy is, what’s known about it for brain cancer, or that CAR-T cells are not without risks, up to and including death, and it’s certainly not unreasonable to ask what additional risks there might be in administering them directly into the brain or cerebrospinal fluid. No one does.

In its hunger for feel-good stories showing a likable family do extraordinary things (and, make no mistake, the Wythes have done extraordinary things) to overcome incredible odds, the press hasn’t asked even the most basic questions to flesh out the rest of the story. They just present the story as a family heroically raising funds to save their brave daughter. That’s obviously the most appealing, emotional aspect of the story. However, it’s not the only aspect, and focusing solely on that aspect leaves unexamined the question of why: Why is this clinical trial set up so that it’s necessary for this family to go to such extreme lengths to raise so much money if they want to enroll their daughter on the trial, particularly given that it’s a phase I trial that is unlikely to help her? The family is likely aware of how long the odds are, even with this clinical trial, but the press sure doesn’t communicate that to the public. The press portrays this as Lily’s last chance and implies that there’s a good chance she’ll survive if only her family can come up with the money to pursue a treatment denied her by the “stingy” and “callous” NHS, the very same spin they put on stories of patients seeking treatment at the Burzynski Clinic, Hallwang Clinic, or Clínica 0-19. CAR-T cells are real treatment. Seattle Children’s Hospital is a top-notch academic hospital. We should expect better coverage.

I wish Lily Wythe and her family only the best. I hope they succeed in getting her on this clinical trial, and, as of when I wrote this last night, it looks as though they will. I hope she beats the odds. My purpose in writing this is not to dampen their optimism or criticize them in any way. My purpose in writing this is twofold. First, I want to take the press to task for not asking even just a little more about stories like this, to put them into proper context. I guarantee you that, even if the public knew what a phase I trial is and that this treatment had a small chance of curing Lily, they would still donate to fund a last ditch effort to save her life. More importantly, I ask whether a system of clinical trials that puts a family like the Wythes in the situation they’re in is ethical and what can be done to change its so there are no more families frantically raising money to save their daughter.

ADDENDUM: The PI of BrainChild-03 emailed me. I’m waiting to hear back from him, but he did wish to emphasize that the reason the Wythes are being charged is that they are international patients and do not have American health insurance to pay for the hospital stay. He states that the CAR-T cell therapy itself is provided at no cost. I’ll add more as I learn it.

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

40 replies on “Crowdfunding to pay to be a research subject in a clinical trial: The case of Lily Wythe [UPDATED 1/23/2020—see addendum]”

Question – is the funding for the trial itself or would it be for the family to travel / move to the US & cover the expenses for the timeframe involved.

I might have missed it in the article (I am severely caffeine-deprived at the moment), and just want to clarify what the money is for.

I explained what’s known about this in the post:

I’m also not clear if every patient enrolled on this trial has to pay or if Lily’s family has to pay because they’re not from the US and don’t have US health insurance to cover costs of treatment outside of the production and administration of the CAR T-cells. One article states that the £300,000 is just for the treatment, a minimum amount of money needed, and that travel and lodging are extra, but that doesn’t completely clarify the issue of how much is for the CAR T-cell treatment and how much for everything else or if every study participant is being asked to pay close to $400,000 to enroll in the study.

Basic travel costs–airfare, lodging, food, and local transportation–are likely to be in the $50k to $100k range for a year in Seattle, which is not a cheap place to live. Rent alone, assuming that Lily’s parents have the presence of mind to rent an apartment, is going to be somewhere north of $20k, and depending on the neighborhood could be easily double that. That’s before we get into inpatient room rates for Lily, whose family would likely be paying the list price because, being from the UK, they don’t have US health insurance. (Patients who do have US health insurance usually get a substantial discount on hospital costs because health insurance companies typically negotiate such discounts.) That’s going to be a big chunk of money as well–routine cancer or cardiac cases frequently accumulate bills in the six figures. I could see the whole thing costing Lily’s family close to $400k even if the people running the clinical trial aren’t charging for the drug.

As Orac says, there are probably things we don’t know about that are going on here. It may be the suits rather than the lab coats who are pushing this price tag (hospital management would want to be paid for the use of their facilities). I don’t know enough to commit either way on that point.

My only argument about housing is that there is a very large Ronald McDonald housing complex right next to Children’s and (weirdly given it’s generally a fancy neighborhood) there’s a lot of low-income housing around there too. So rent might not be quite that much. But you still need to eat, and maybe have a car, and what about any siblings, do they need to go to school?

As JustaTech says, I would think they would be able to get lodging for free. If they go to a church I would bet money that there is a church that can find them housing. Even if not the publicity must be generating at least one offer. The Ronald McDonald house near me is gifted with free food all the time. I doubt if they would have or need a car–the driving is on the wrong side of the road and it’s unlikely that anyone is going to work in Seattle. All they would need or want is a bus pass. The hospital will have some sort of restaurant. And I don’t know the area but typically hospitals are surrounded by convenience stores at least.
Likewise flights will be fairly cheap if they are flexible enough to take the crummy flight that leaves in the middle of the night. And I would not try to take the siblings except in the summer. They can facetime every day.
Also it’s not 100% clear how long she needs to be in Seattle. If they are going back and forth a lot that’s actually more expensive.
But like everyone else I’m not really getting how much they will be spending. £300,000 is an awfully round number for something priced in $.

“My only argument about housing is that there is a very large Ronald McDonald housing complex right next to Children’s and (weirdly given it’s generally a fancy neighborhood)”

Trust me, it was not a fancy neighborhood thirty years ago. I used to call it the low rent side of Sand Point Way. Not anymore.

as NHS won’t cover brain tumour treatment

I hate that spin. I positively hate that whole narrative of “soulless bureaucrats leading a death panel decide who will get treatment and who won’t”.
I’m not saying that government-lead healthcare is perfect and all.

But the basic assumption of this type of headlines – the story being sold – is that a proven effective treatment does exist, and moreso, is readily available.
When in fact, I have read too many stories where no such treatment exists – there are at best experimental drugs or protocols. And even in the cases a somewhat promising treatment may exist, there are ethical or material reasons withholding its availability to the patients put forward in the media.

I totally agree about your opinions on pay-to-play for legitimate trials, and it is something that I have noticed cropping up more and more in the last few years.

Whilst it is probably a good thing that less are actually fraudulent crooks, it does make one wonder about the whole process. Not least as we have now seen an enforcement for OHIP (Ontario Health Insurance Plan) to cover the costs for sending a child to a Phase I trial in Seattle. I see, with cases like that, a “good” opportunity for more trials to take advantage of pay-to-play, and possibly consider overseas “funding” if they can recover costs from justifying charges in that manner. As a consumer, of course, my concern is that phase I trials become an automatic secondary treatment option, and the publicly funded health care system will see its coffers drained at a rapid rate, once precedent is set.

As much as I want to joke about screaming Big Pharma or something, it is a good point about how this comes to be.

Are we seeing some expected use of trials, is this a grey area, or just something that needs reactive governance applied to the process.

The bigger question is whether we can expect much to happen, or will thousands of families be parted from millions of dollars to partake in the unknown, and likely, low odds of efficacious treatment in the future?

My guess would be that the chance of this being an effective and safe treatment for a currently incurable cancer was enough to convince the IRB to go along with it. The cynic in me also figures that it being revenue neutral or positive for the hospital, and the good press likely also helped.

Why would a scientifically sound phase I trial of CAR-T cells for a lethal pediatric cancer have trouble at IRB?

And if they are, in fact, unfairly charged (I don’t know, because as you point out, there isn’t information), raising awareness of what’s happening can help, if not them, other families that may be taken advantage of.

I think you’ve done the right thing. These kinds of exploitative situations need to be investigated, especially in this case where a legitimate hospital seems to be (Inadvertently or otherwise) copying tactics from outright quacks like Burzynski. The Merseyside Skeptics commented that this type of ‘feel good’ media coverage acts as free advertising for whatever treatment is on offer.

There is minimal published literature on B7-H3 specific CAR-T therapy for glioma. I could find only one cell-culture based study in medline (Tang 2019 Mol Ther Oncolytics 14, 279-287). That study doesn’t address the main challenges that have prevented success for other CAR-T glioma trials: access to the entire tumor, heterogenous antigen expression, emergence of non-antigen-expressing glioma cells, and poor persistence of CAR-T lymphocytes in the CNS environment, and response of surrounding brain to inflammation (a particular risk for brainstem disease). This is why the referenced trial is a phase 1 study, principally focused on evaluating safety.

My concern here is with informed consent. What could the parents have been told, to convince them to commit, to expend emotional energy, raise and spend money, travel, and subject their daughter to this trial? The history of CAR-T treatment of gliomas (in general, not just DIPG) has been fairly dim. Were they told that?

Disclosure: I’m a neurologist, and work for drug companies. I have worked on immunotherapy for gliomas, but not targeting this specific antigen and not using CAR-T cells. I have no involvement with the referenced trial.

There is minimal published literature on B7-H3 specific CAR-T therapy for glioma. I could find only one cell-culture based study in medline (Tang 2019 Mol Ther Oncolytics 14, 279-287).

How about this:
https://clincancerres.aacrjournals.org/content/early/2019/01/17/1078-0432.CCR-18-0432

That study doesn’t address the main challenges that have prevented success for other CAR-T glioma trials:

Are you sure? We have limited information about the trial (protocol is not in public domain) but we do have the CT.gov entry.

access to the entire tumor

How do you know that this was the problem, rather than the wrong CAR-T antigen, type, generation? Anyway, this could help: “CAR T cells are delivered via an indwelling catheter into the tumor resection cavity or ventricular system.”

heterogenous antigen expression, emergence of non-antigen-expressing glioma cells,

Wouldn’t this depend on the particular antigen? Is this an argument against CAR-T generally or against certain antigens specifically? How about B7-H3?

and poor persistence of CAR-T lymphocytes in the CNS environment, and response of surrounding brain to inflammation (a particular risk for brainstem disease).

What do you suggest? Selecting a new antigen, second-generation CAR-T design, and delivering locally seems like a good try.

My concern here is with informed consent. What could the parents have been told, to convince them to commit, to expend emotional energy, raise and spend money, travel, and subject their daughter to this trial?

Hope that a new treatment could work better than standard of care? Keep in mind this new treatment (unlike Burstinksi or Clinica 0-19 scams) is based on sound science. You believe they are operating clinical trials at Seattle Children without an independently reviewed and IRB-approved informed consent?

Pretty much all large academic children’s hospitals have a Ronald McDonald House. Our children’s hospital has one. The cost is basically negligible, and in the case of financial hardship it’s free. Our particular Ronald McDonald House states:

How much does it cost to stay at the House?

We request a donation of $10 per night. However, we will never turn a family away due to a lack of funds. If you need alternate financial arrangements, speak with your hospital-assigned social worker.

Who can stay at the House?

Adult parents, legal guardians, siblings, and other family members of sick children are eligible to stay with us.

How many people can stay in a room?

There is a four person limit on each room. Also note that each family is allowed one room.

Other Ronald McDonald Houses might work differently, but the idea is the same: A room that families of children undergoing cancer treatment can stay in for little or no money while the child is being treated.

ADDENDUM: I checked the Seattle Ronald McDonald House website. They request $30 a night, but waive the request for financial hardship. Even if you stay a month, that’s $900, which is way less than any imaginable other lodging in the area. They also provide food:

House A and House C each have a communal kitchen and pantry of non-perishable foods that are offered for free to all families. Each family has refrigerator and cupboard space where personal food can be stored. Outside volunteer groups regularly visit the House to make dinners for the families. Coke products are available in vending machines and free coffee is available in our pantry.

I have a lot of questions about this. Actually, I’ll be honest, I don’t believe it.
I know people who work at that group of labs at Seattle Children’s. They’re not scammers. I’ve also talked to them about how they are planning on moving out of clinical trials and into commercial production and I was told that they would “stay in clinical trials forever because that way the patients don’t have to pay”. That was about a year and a half ago. It seems an amazing leap to go from that to charging a UK patient ~$300k to be in a trial.

I could see needing money for the other parts of the hospitalization (since I guess that’s not covered by the NHS). I could see needing a lot (but not that much) for travel and housing (this city is stupid expensive, although there is an extensive Ronald McDonald housing complex by Children’s).

I don’t know anyone there well enough to just call up and ask (the one person I know somewhat closely isn’t in that program), but it just really doesn’t feel right. I think it’s much more likely that the news reports are imprecise and the message got garbled about what the money is for than that a respected research institution would suddenly and randomly start charging for Phase I trials, when they’ve never charged for trials before.
(Also, Children’s isn’t short of cash. They’re almost done their brand-new cell-therapy building and are well supported by the network of cancer research and treatment centers in the area.)

Oho, and I just remembered that two of the people from the CAR-T group at Seattle Children’s went to the ISCT (Internaitonal Society of Cell and Gene therapy) conference this year and that conference requires that you sign a ethics statement saying that you wouldn’t charge (mostly for stem cells) and you wouldn’t send your patients to sketchy pro-profit stem cell clinics.

It would be deeply weird to send staff to a conference about not charging for clinical trials and then charge for a clinical trial. I mean, suits are suits and out for cash any way they can, but it seems unlikely. Also, there’s no way this isn’t terrible press for Children’s (if true) and the last thing they need now is more bad press (they have a fungus problem). Honestly, I wouldn’t be surprised to see something in the newspaper about this tomorrow.

It is a deeply cynical thought that perhaps quacks like Burzynski are now telling families to fund raise but not list their quack clinic as the place of treatment (thanks to exposure by SBM advocates). Deeply cynical…but what would be the recourse if the money raised was used at another clinic? I suspect none whatsoever.

Nothing about this in the paper today.

@Christopher Hickie: That is the most nauseating idea. Lie to people who are generously offering you money and drag the name of a real research institution through the mud at the same time? Gross.

From what I know about the CAR-Ts at Children’s 1) it takes a while (couple of weeks?) to make the treatment after the patient gives the starting cells, and 2) the treatment cells are thawed at the patient’s bedside in the hospital, because of the risk of sudden and very severe cytokine release syndrome (cytokine storm). So even if the patient pays nothing for the treatment itself, I’m assuming the hospital needs to get paid for their bed in the oncology ward or ICU while they’re getting the treatment. If you had to pay cash on the barrelhead, could that potentially cost $300k? I have no idea. Maybe if the patient had a really bad reaction and needed a lot of intervention? Maybe this girl’s family was advised to get enough money to cover that eventuality?

This is really bugging me. I want more data!

Very glad I was wrong (as per the addendum). But that hospital cost … so wishing it wasn’t so prohibitively high for them.

Note the addendum. Dr. Nicholas Vitanza, the PI of BrainChild-03, emailed me. I’m waiting to hear back from him for more information, but he did wish to emphasize that the reason the Wythes are being charged is that they are international patients and do not have American health insurance to pay for the hospital stay. He states that the CAR-T cell therapy itself is provided at no cost on study. I’ll add more as I learn it.

Oh thank goodness.

Insert complex feelings about the cost of hospitalization in America. Still, it’s very weird because Children’s is all about treating every child, regardless of ability to pay.

Children’s may be all about “treating every child, regardless of ability to pay.” But probably not for the whole world.

Seattle Children’s provides necessary medical care to all children in our region, regardless of a family’s ability to pay. By filling in the gaps left by insurance shortfalls or the inability to pay, uncompensated care frees parents up to focus on getting their child well.This essential program fulfills Children’s founding promise to provide care to every infant, child and teen in Washington, Alaska, Montana and Idaho who needs us — regardless of insurance coverage or financial circumstances.

https://giveto.seattlechildrens.org/Uncompensated-Care

It is not unusual to charge international patients, since they are uninsured in the U.S. It is routine that insurance covers costs of standard-of-care treatments, scans, supportive care, and emergency care. This could add up quite a bit with someone with a life threatening illness, where ICU care may be needed. If Seattle Children’s hospital treated foreign patients gratis, they would be unable to care for the locals. Keep in mind, uninsured locals who walk in with an emergency get care even if they cannot pay.
I doubt they are charging for the trial, or any non-standard treatment. (Addendum noted, confirming this.)

The reason is that this is a phase I trial. It looks like a scientifically sound phase I trial, but it’s still a phase I trial, and that means that it is not testing efficacy. It is testing safety.

IMO, this is a silly argument. Sure a phase I trial has primary scientific goal of determining safety of an intervention. However, the possibility of effective treatment is the reason to seek it–why else would a patient or physician pursue it? We’d have to close up drug development entirely if there was no reason to enroll. (And yes, investors and pharma do look at efficacy before they decide to invest $millions in pursuing drug development).

IMO this is entirely above board. Also an exciting trial. As an investigator in oncology research, I’m all for it. If I was in the shoes the Wythe family, I would hope to do exactly the same!

I’m gonna donate to her GoFundMe now.

No, it’s not at all a silly argument in the context of raising massive amounts of money by touting the trial as a “last chance” and implying a far greater chance that it will benefit Lily than it actually has. Context matters.🙄

Yes, it’s a perfectly fine phase I trial, but selling it as something other than a phase I trial and not letting people know what a phase I trial is and isn’t is a failure of reporting that doesn’t give an accurate picture of the situation for people to base their decision to donate on. Moreover, I can say that the PI appears to have been unaware of Lily’s family’s campaign before encountering my post. I’m not sure whom the family was dealing with, but whoever it was clearly didn’t let the PI know.

Keep in mind, uninsured locals who walk in with an emergency get care even if they cannot pay.

Yes, thanks to EMTALA. That doesn’t mean they don’t get a bill even if they cannot pay.

I know several people in the labs that did the preclinical work for this trial and no one that I’ve talked to has heard about Lily Wythe or any fundraising to get her treatment. I’m really interested to hear what Dr. Vitanza has to say about this. Seattle Children’s really doesn’t need any additional negative publicity after the mold outbreak in the operating rooms.

Yeah, that’s exactly what I was thinking. Hopefully they can drum up a anonymous wealthy donor to cover her costs, because you know the Seattle Times would love to run them through the wringer some more. The Seattle Times is a good, independent paper that does a lot of rigorous investigative reporting. But they do seem to like to focus on the region’s hospitals more than, say, Amazon.

Or maybe it’s just that the hospitals have reporting requirements and Amazon doesn’t.

I’m really glad you covered this. I live in Southend, a couple of miles from where she does and this popped up on my Facebook page almost as soon as it was launched.

I asked exactly the same question on her page and was immediately given the same link as you..

Now I’m only a lowly ex scablifter (Royal Naval Slang for what the US Navy would call a Corpsman) but have spent enough time here and other Science Based Sites for this to ring alarm bells.

My reply was that it seemed rather unethical to charge for participation in a Clinical Trial (I confess I missed that it was a safety trial).

I haven’t seen anything in our local Dead Tree Press , it all seems to be celebrity online stuff. But I’ll keep my eye out and report back.

“Lily, 13, has undergone radiotherapy but the family are pinning their hopes on a clinical trial in Seattle, USA.”

I just noticed an interview with her mother that reveals Lily only did two and a half weeks of the six-week course.

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