By David Tuller, DrPH
As I wrote yesterday, Mahana Therapeutics has recently licensed from Kingâ€™s College London an â€œinnovative digital therapeuticâ€â€”a web-based program delivering a course of cognitive behavioral therapy to patients with irritable bowel syndrome. A page on the Mahana site promoting this web-delivered IBS-CBT program furthers the impression that this deal is steeped mostly in hype.
A January 10thpress release announcing the deal declared the changes in symptoms produced by the web-based program to be â€œsubstantial,â€ which already seemed like an exaggeration. The companyâ€™s website has apparently upgraded this observation with its description of the symptom improvements as â€œdramatic and potentially game-changing for patients.â€ Wow!
(It should be noted that Professor Rona Moss-Morris of Kingâ€™s College London, one of the principal investigators of the study that road-tested the web-based program being licensed, has been paid as a consultant by Mahana and also owns stock options. Her ownership of Mahana stock options was not in the disclosure for the study of the web-based program but in her disclosure for a separate trial for people with persistent physical symptoms. Incidentally, that paper about the other trial had to be corrected last year after I pointed out that it included a false claim concerning the estimated costs of so-called “medically unexplained symptoms”–a claim based on a misreading by Professor Moss-Morris and her co-authors of a seminal study in their field of expertise.)
In the published papers, the web-based program was called Regul8. Mahana has re-branded it as Parallel. (Itâ€™s possible the academic investigators divided the material into eight chapters specifically so the name Regul8 would work and come across as clever. I donâ€™t know what â€œparallelâ€ refers to.) And hereâ€™s what weâ€™re told about CBT: â€œFor years, CBT has been used successfully to treat health issues like chronic pain, heart disease, and multiple sclerosis.â€
Really? I havenâ€™t heard of people recovering from MS through CBTâ€”which is what the sentence would likely mean to many or most readers. I assume Mahana intended to convey the notion that CBT is a helpful adjunct for alleviating some symptoms of MS and other complaints. Sure enough, the footnoted reference for the MS claim does not involve treatment of MS but of the fatigue that can accompany MS.
Did anyone proof-read or vet this website? Mahanaâ€™s apparent inability to understand or appreciate the distinction between treating a condition itself and addressing symptomatic relief is alarming for a company that presents itself as being on the cutting edge of science.
In its description of Parallel, Mahana prominently cites two pieces of evidence from the trial I wrote about last week.
- â€œ66% of patients reported significant and clinically meaningful reduction in the severity of their IBSâ€
This is a misleading claim. It is true that 66 % of those in the web-based CBT arm who responded at 12 months had a reduction in the scores on the IBS Symptom Severity Scale of 50 or more points. (A reduction of fifty or more points is considered clinically significant.) But it is not true that most of those changes can be attributed to the web-based program, which is what the statement appears to imply. Mahana does not mention that 44% of those in the treatment-as-usual arm who reported at 12 months also had a reduction in scores of 50 or more on the same scale. Given those numbers, it seems likely that many or most of the 66 % in the web-based arm could have reported those improvements anyway.
Moreover, the site does not make clear that only 70 % of the study sample provided data at 12 months. We canâ€™t know what the final results for the remaining 30 % would have been. That means we have no idea how those who dropped out from the web-based program arm felt about the intervention or whether it helped them. They were, in epidemiological terms, â€œlost to follow-up.â€
In any event, the studyâ€™s main analysis of the IBS-SSS scores used an â€œintention-to-treatâ€ strategy, which tries to account for this sort of missing data. At 12 months, the mean score for the web-based group was found to be 35.2 points lower than for the treatment-as-usual groupâ€”quite a bit less than the 50-point difference that would represent a clinically significant improvement for an individual.
- â€œOn average, reduction in IBSÂ severity was twice that of patients receiving medical care as usual.â€
Again true, and again misleading. When improvements are small, improvements that are twice the size are also pretty small. Just because something doubles does not automatically mean the change is of much clinical significance. The more telling statistic is often not the relative difference between groups–the kind cited in the above claim about average reductions of IBS severity–but the absolute difference. In this case, as I’ve already noted, the absolute difference in score between the means of the groups was 35.2 points–well under the 50 points that would represent a clinically significant change for an individual on that scale.
Besides the inaccurate marketing, a couple of other issues raise concerns.
First, is Mahana planning to present Parallel for use with therapeutic input? Thatâ€™s how it was road-tested. It cannot be assumed that findings from the study would be replicated in the absence of therapist guidance. Nothing in the press release about the licensing deal or on the Mahana website itself suggests that the web-based program will be delivered with some doses of human contact as well, but perhaps it will be.
Second, the Mahana website ignores the multiple reasons to be skeptical of even the unimpressive results reported in the study. These reasons include the possibility of bias in an open-label trial with solely subjective outcomes, the unfortunate decision to inform patients of CBTâ€™s purported effectiveness in treating IBS through information included in the trial manual, and the fact that patients getting the intervention were compared to a group of patients getting what was, for all practical purposes, little better than nothing.
In the end this big licensing deal seems like a lot of noise about very little. But I assume someone somewhere will be making money from it. Nice!
Judging by the website, Parallel is Mahana’s only product. But get ready for more good news down the line! Hereâ€™s what we also learn on the site:
Mahana is currently developing a personalized digital treatment for adolescents and adults with Inflammatory Bowel Disease. This product will be tested in a series of research studies and randomized, controlled trials. This treatment will tap into the power of Cognitive Behavioral Therapy (CBT) to help patients living with IBD.
It would be cheaper and cause less harm to pay these parasites to stay home and sit on their hands. Just like a classic mafia protection racket, patients will soon be required to submit to this useless non-treatment:
“Sure is a nice little disability pension ya got there. Be a shame if it got cancelled just because ya wouldn’t sign up for our little program…”
Wendy Boutilier says
Psychiatry has an obsessive fascination in group-abreactive phenomena that could rival snake-handling, healing revival meetings and voodoo. They have developed a belief that any treatment which produces a suitably powerful release of emotion in the patient is considered psychologically helpful. They are ignoring the obvious joy a patient feels when their current bout of irritable Bowel Syndrome has resolved as purely physical. Like all Witch doctors, psychiatrists rarely use modern intellectually oriented science. Itâ€™s mind boggling considering how many years they spend educating themselves only to evolve into brain washed egos.
Allison Haynes May says
Thank-you David, for keeping up with the motives, conflicts of interest, and deception of all the players involved. It is exhausting just to read it. So very much appreciated.
Lady Shambles says
My Independent Bull***t Sensor is flashing up ‘this stinks’.
David Tuller says
Lady Shambles, I’m not sure why you would say such a thing.
Peter Trewhitt says
It is a shame that researchers are devoting so much energy and resources in developing marketable CBT packages for poorly understood conditions such as ME/CFS and IBS, to the exclusion of developing any insight into the conditions themselves.
Yet another study replicating this flawed methodology of open labelled, effectively uncontrolled, trials relying on subjective outcomes suggests the motivation is not to establish a strong evidence rather it is a marketing exercise. Even as an undergraduate some forty years ago I was taught the problems of such research and that, despite the complexities of evaluating behavioural intervention in clinical settings, there are ways of addressing this:
– you use objective measures,
– you ensure you have a clear evaluated theoretical rationale,
– you seek convergent evidence rather than exclusively relying on a single experimental design
– and you take every step to eliminate possible sources of bias.
I suspect that this is part of a plan for the NHS to have a cost-cutting tech solution for almost everything (regardless of whether it works or not). As well as being a Mahana Therapeutics advisor, Harpreet Sood is involved with the NHS Digital Academy and the Global Digital Exemplar Programme at NHS England – https://www.england.nhs.uk/author/harpreet-sood/ . A risk with the Mahana CBT approach must surely be that misdiagnosed patients will be diverted to CBT for IBS when they have IBD instead, thus causing a delay to their correct diagnosis and treatment because they’re no longer visiting their doctors about their abdominal pain.
Iâ€™m so glad that an investigative journalist such as yourself, and some of the commentators here, are researching, writing about and trying to expose this nonsense and corruption for what it is.
Lady Shambles says
Not sure if you’re being ironic. My sarcastic acronym and observation were directed at the dodgy dealings of the BPS crew, not the messenger.
I scanned the reference list for the “ACTIB” trial referenced by Dr Tuller. I saw zero papers on IBS that discuss biology or physiology. Not even a paper that claims there are no abnormal physiology findings. How can that be? Do they need someone to teach them about PubMed and how to look for research papers?
Here is a tiny sample of what they might find if they learn to use these resources:
Burns et al:  “Fifty-one papers reporting discordant immune features”
Wouters et al:  “recent observations reveal low-grade mucosal inflammation and immune activation, in association with impaired epithelial barrier function and aberrant neuronal sensitivity” …
“It is well established that mast cell activation can generate epithelial and neuro-muscular dysfunction and promote visceral hypersensitivity and altered motility patterns”
Klooker et al:  “Ketotifen significantly decreased abdominal pain and other IBS symptoms and improved quality of life. The number of mast cells in rectal biopsies and spontaneous release of tryptase were lower in patients with IBS”
 Evidence for Local and Systemic Immune Activation in Functional Dyspepsia and the Irritable Bowel Syndrome: A Systematic Review; https://www.ncbi.nlm.nih.gov/pubmed/30839392
 The role of mast cells in functional GI disorders; https://www.ncbi.nlm.nih.gov/pubmed/26194403
 The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome; https://www.ncbi.nlm.nih.gov/pubmed/?term=klooker+tk+and+%22mast+cell+stabiliser%22
David Tuller says
Lady Shambles–understood. I was being ironic. I did not remotely feel anything was being directed at me.
Alicia Butcher Ehrhardt says
Who on Earth is approving this and allowing it to be sold? And will it next be used to say that people who don’t follow this ‘treatment’ are not allowed benefits because they are not cooperating with the treatment alternatives?
The amount of human suffering that follows this model – take our treatment or get no benefits – is appalling.
And in places with national health insurance, there are no alternative ways to get your particular insurance company to cover something, so the official endorsement is even worse because it applies to everyone not rich enough to pay for private treatment.
IBS is PHYSICAL. Ask anyone who has to deal with it on a daily basis.
Steve Hawkins says
*”Mahana is currently developing a personalized digital treatment for adolescents and adults with Inflammatory Bowel Disease. This product will be tested in a series of research studies and randomized, controlled trials. This treatment will tap into the power of Cognitive Behavioral Therapy (CBT) to help patients living with IBD.”*
This last quote says it all! Develop the package first: then tailor the ‘research’ to ‘prove’ it works, after you’re already committed.
Cart before horse overconfindence: or notice of intention to cheat?
Laura Whittington says
If CBT can magically “cure” it then the idea could be put forward that the patient is not “doing enough” to cure themselves, ergo the patient is to blame or not exhibiting desirable behaviour. The illness, the patient and the cost of treating the patient properly can all be tidily disposed of. I feel that it is at it’s core a fascist ideology.