Trial By Error: A Follow-Up to the Follow-Up Letter to Mahana

By David Tuller, DrPH

On the Mahana Therapeutics website, Robert Paull, the CEO and co-founder, explains in a statement that his personal interest in developing treatments for GI problems arose out of the longtime suffering of a family member. His account is heartfelt and compelling.

Unfortunately, Mr Paull and his company have placed their bets on the wrong horse. I am hard-pressed to understand this deal with King’s College London except as a failure of due diligence. Mahana now has the rights to a product that cannot honestly be marketed as a proven effective treatment for reducing symptom severity in patients suffering from irritable bowel syndrome.

Mr Paull likely has no idea why I have latched onto this issue and have no plans to let go. I thought it might be helpful to explain the context to him. So this morning I sent the following letter.

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Dear Mr Paull–

First, I wanted to let you know that I sympathize with your desire to bring some relief to patients suffering from gastrointestinal problems, as expressed in your heartfelt personal statement on the Mahana Therapeutics’ website. Your family’s story is moving, and I don’t doubt your sincerity.

To be clear, I have no beef against psychotherapeutic interventions for people with serious ailments as a way of helping them adapt to their circumstances and  address emotional challenges. But I object to claims that are not justified by the evidence–as is clearly the case with this web-based cognitive behavior therapy program for irritable bowel syndrome.

It occurs to me that providing some context for my concerns will help explain why I have focused on Mahana’s licensing deal with King’s College London.

In the UK, an influential group of investigators strongly believes that CBT is the optimal intervention for so-called “medically unexplained symptoms,” or MUS. Some of them serve as advisers to the National Health Service, which has sought to ramp up psychological treatment for MUS. For the NHS, that category includes both chronic fatigue syndrome and irritable bowel syndrome. Unfortunately, some research from this group is seriously sub-par.

For the last few years, I have been reporting on the PACE trial, which tested CBT and a graded exercise program as treatments for CFS. The first results were published in The Lancet in 2011. One of the three lead PACE investigators was also one of the two lead investigators of the IBS trial that examined the web-based CBT program. A member of the British Parliament has called PACE “one of the biggest medical scandals of the 21st century.” 

If you don’t know about PACE, I suggest you read my 15,000-word investigation of its egregious methodological and ethical flaws, which I published on Virology Blog in October, 2015. (Virology Blog is hosted by Columbia University microbiology professor Vincent Racaniello; I have cc’d him on this letter.) You might also read the open letter I organized about the trial and sent to The Lancet in August, 2018. The letter, which slammed the study’s lapses and demanded an independent investigation, was signed by more than 100 scientists, clinicians and other experts as well as more than 70 patient groups from around the world.

In addition, last summer the two lead investigators of the IBS study had to correct a major factual error in a BMJ Open paper involving another clinical trial under their direction. That correction occurred after I had pointed out that the paper’s first paragraph incorrectly cited the core finding of a seminal study in the MUS field–a domain in which the investigators claim expertise. The effect of their mistake was to triple the apparent cost of MUS to the NHS budget.

In fact, members of this group of researchers have made this same false claim about the cost of MUS repeatedly over many years. False claims in high-profile studies are unfortunately likely to negatively influence health policy going forward. It is certainly fair to regard other research from this group of investigators with a degree of skepticism.

Given this history, KCL’s promotion of the IBS study–and Mahana’s subsequently announced licensing deal–caught my attention. Despite what appear to have been good intentions on Mahana’s part, the data are the data–you now have rights to a program that cannot accurately be sold as having proven clinically significant benefits over treatment-as-usual in reducing symptom severity.
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Mahana could, I suppose, market the product by forthrightly acknowledging the lack of evidence related to symptom severity reduction while highlighting some reported improvements in more generic domains, such as work and social adjustment. But these improvements were meager at best. Moreover, the study was an unblinded trial relying solely on subjective outcomes–a research design known as likely to induce bias. So even these limited reported improvements cannot be taken at face value.

In any event, as I have said repeatedly, the study simply does not support what Mahana has been asserting–even after the removal of hyperbolic claims about “dramatic” and “potentially game-changing” results. I hope regulators in the UK and US recognize that reality.

Best–David
David Tuller, DrPH
Senior Fellow in Public Health and Journalism
Center for Global Public Health
School of Public Health
University of California, Berkeley

5 thoughts on “Trial By Error: A Follow-Up to the Follow-Up Letter to Mahana”

  1. Hope you get through to him. Offering unproven ‘treatments’ to people with serious diseases trivializes their pain, and diminishes their reasons to fight for their lives and quality of lives.

    This is a scandal in science.

  2. Richard Vallee

    It seems rather likely that Mahana were mislead by the same skilled persuasion that is at the core of the BPS model. Especially if someone has a sincere and personal stake in the matter, wanting to help a loved one and being persuaded by the usual misrepresentation. This thing definitely ain’t it.

    But the research itself is several levels below underwhelming. It’s hard to imagine anyone is actually convinced by the science, there simply isn’t any. But then again some medical authorities are actually all in on the LP so at this point I think it’s safe to assume that there is simply no level of expertise that immunizes someone from woo. Turns out you actually can fool enough people most of the time.

    Mahana will have very solid grounds for lawsuits against KCL and the researchers personally for making clearly misleading claims that they know are junk. If they can recognize and admit that they were duped. The alternative will likely be lawsuits with their name reversed on the X vs Y line. Escalation of commitment is best caught early, I hope this gets through to them.

  3. A relative of mine has also been through the mill with GI problems. What is clear to me is that the majority of GI consultants don’t really know enough and don’t ask the right questions. If only they admitted their shortcomings and were keen to search for answers we’d be in far better place, but most appear too arrogant to do this. Instead the false construct of MUS allows them to blame the patient rather than their own deficiencies or the lack of scientific progress in this field.

  4. Pingback: Trial By Error: A Follow-Up to the Follow-Up Letter to Mahana – Virology Hub

  5. ‘Medically unexplained symptoms (MUS) is a diagnosis which is made when you have persistent physical problems such as headaches, dizziness or pain which don’t seem to match any recognised medical condition.’

    We are missing the other diagnosis that travels hand in hand with MUS. It’s called ‘Lazy Doctor Syndrome.’

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