By David Tuller, DrPH
One of Mahana Therapeutics’ business advisers is Dr Harpreet Sood, identified as the National Health Service’s associate chief clinical information officer. (Actually, Mahana seems to have it wrong; it looks like Dr Sood is still be at the NHS but moved on a while ago to another position. I guess accuracy isn’t Mahana’s strong suit. But hey–that’s ok. I make mistakes too!).
Since I haven’t heard back yet from Mahana’s CEO or the scientific advisers I contacted, I thought I’d reach out to Dr Sood as well. I sent the following letter this morning to what I hope is the correct e-mail address.
So far, it hasn’t bounced back!
Dear Dr Sood–
I am a senior fellow in public health and journalismÂ at the Center for Global Public Health at the University of California, Berkeley. I write frequently about research on illnesses in the category of so-called “medically unexplained symptoms.” Much of my workÂ appears onÂ Virology Blog, a science site hosted by Vincent Racaniello, a professor of microbiology at Columbia.
I am writing to you in your capacity as a business adviser to Mahana Therapeutics, as listed on its website. (Although Mahana identifies you as associate chief clinical information officer at NHS, it appears that you moved to another position last year.)Â In January and February, I reported in several posts on Virology Blog that Mahana was making unjustified claims about its new web-based cognitive behavior therapy program for irritable bowel syndrome.
I assume the company would like to convince regulators in the UK and US that this program is an effective, evidenced-based treatment providing clinically significant relief from IBS symptoms. This is clearly untrue–per the data from the study that road-tested the program. At best, Mahana could claim that the program demonstrated very modest benefits in more generic domains like work and social adjustment.
Before the pandemic took hold, I reached out to Rob Paull, the chief executive officer, as well as some of Mahana’s science advisers. No one responded to my concerns.Â (I have cc’d Mr Paull on this letter, as well as Professor Racaniello. For transparency, I plan to post the letterÂ on VirologyÂ Blog.)
Now I am trying to get back to work–especially since the Mahana website continues to include misleading information.
To recap: Mahana announced in January that it had licensed the web-based CBT program from Kingâ€™s College London. My concerns involved statements in a press release and on Mahanaâ€™s website that clearly exceeded the data from the relevant study. The press release described the web-based programâ€™s impacts on symptom severity as â€œsubstantialâ€ and â€œdurable.â€ The website called them â€œdramaticâ€ and â€œpotentially game-changing.â€
As I have pointed out, these descriptions cannotÂ be justified.Â At 12 months, the mean score for the web-based group in the intention-to-treat analysis was 35.2 points lower than for the treatment-as-usual groupâ€”much less than the 50-point difference that is considered a clinically significant improvement.Â At 24 months, the reported benefits were neither statistically nor clinically significant. Given the weak results for this core indicator, it is hard to understand why Mahana decided to license the program in the first place.Â
When I rechecked recently, it appeared that Mahana had changed the website’s description of the program’s purported benefits and no longer characterizes them as “dramatic” and “potentially game-changing.” I was pleased to see this change. However, the site currently states that “patients enrolled in a minimal-contact digital CBTÂ program experienced significant and clinically meaningful reduction in the severity of their IBS.”
This is an empty statement, since it would be true if only two patients in the web-based arm had achieved this “significant and clinically meaningful reduction” in symptom severity. It could also easily be said about the treatment-as-usual arm, since at least two patients in that arm also achieved “significant and clinically meaningful reduction” in symptom severity.Â The relevant question is whether the program provides clinically meaningful benefits over and above what is achieved through treatment-as-usual. And this is not the case, according to the study’s own symptom severity results–as I pointed out above.
The two data points Mahana includes on the website to highlight the program’s purported benefits are not the central findings for IBS symptom severity. To cite them out of context in this manner is unacceptable.
First, according to the website, â€œ66% of patients reported significant and clinically meaningful reduction in the severity of their IBS.â€
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 at least 50 points–the threshold for clinical significance. But it is not true that most of those changes can be attributed to the web-based program, which is what the statement implies. Mahana does not mention that 44% of those in the treatment-as-usual arm who reported at 12 months also had a reduction in score of 50 or more points. That means 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 would have been for the remaining 30%–those considered “lost to follow-up” in epidemiological terms. That means we have no idea how participants who dropped out from the web-based program arm felt about the intervention, or whether it helped or harmed them. At 12 months, as I have already noted, the mean score for the web-based group in the intention-to-treat analysis was 35.2 points lower than for the treatment-as-usual groupâ€”much less than the 50-point difference that is considered a clinically significant improvement.
Mahana’s website also states:Â 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 marginal, improvements that are twice the size are also pretty small. Just because something doubles does not mean the change is of much or any clinical significance. The more telling and relevant statistic is often not the relative difference between groups but the absolute difference. In this case, as Iâ€™ve already noted, the absolute difference in score between the means of the groups was 35.2 pointsâ€“well under the 50 points that is considered a clinically significant change.
Unfortunately for Mahana, this web-based CBT program cannot be accurately marketed as having clinically meaningful impacts on reducing symptom severity beyond treatment-as-usual. The coronavirus epidemic certainly heightens the potential appeal of effective web-based therapies, but the data from this study cannot be twisted to mean what they don’t. Patients–and customers–deserve honesty, not hype.
Thanks for your attention to this matter.
David Tuller, DrPH