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.
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 theirÂ circumstances andÂ 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 irritableÂ 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 stronglyÂ 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 irritableÂ bowel syndrome. Unfortunately, some research from this group is seriously sub-par.
For the last few years, I have been reporting onÂ the PACE trial, which tested CBT and a graded exercise program as treatments for CFS. The first results were published inÂ The LancetÂ in 2011. One of the three lead PACE investigators was also one of the two lead investigatorsÂ of the IBS trial that examined the web-based CBT program. A member of the British Parliament has called PACEÂ “one of the biggest medical scandals of the 21st century.”Â
If you don’t know about PACE, I suggest you readÂ my 15,000-word investigationÂ 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 readÂ the open letterÂ I organized about the trial and sent toÂ The LancetÂ 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 correctÂ a major factual error in a BMJ Open paperÂ 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 thisÂ 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 clinicallyÂ significant benefits over treatment-as-usual in reducing symptomÂ severity.
Mahana could, I suppose, marketÂ 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 notÂ 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.