By David Tuller, DrPH
Last year, The Lancet published a paper from Christopher Burton and colleagues called “Effectiveness of a symptom-clinic intervention delivered by general practitioners with an extended role for people with multiple and persistent physical symptoms in England: the Multiple Symptoms Study 3 pragmatic, multicentre, parallel-group, individually randomised controlled trial.” Per the norm for research on psycho-behavioral interventions for conditions that get dumped into the wastebasket category of “persistent physical symptoms,” the trial was unblinded and relied solely on subjective outcomes for its claims of “effectiveness.”
This study design is known for generating an unknown amount of bias. As repeatedly happens in such trials, the reported benefits on the primary outcome–in this case the mean of a health-related quality of life measure called the PHQ-15–were statistically significant but fell below the threshold designated as the minimal clinically important difference (MCID). The MCID is obviously a statistical construct, it is meant to approximate the level at which an improvement has practical or real-world impact on a patient’s experience of whatever it is.
Claiming effectiveness or success based on clinically insignificant findings is one of the strategies often deployed by investigators in Professor Burton’s field. It is disturbing that peer reviewers for major journals allow these claims to go unchallenged. The same can be said for the editorial team.
My friend and colleague Joan Crawford, a counseling psychologist, and I wrote a letter to The Lancet about this issue. It has just been published, along with a response from the investigators. (Thanks to Joan for spearheading this and shepherding it through the always irritating back-and-forth with the publisher.) The rebuttal is non-responsive to the concerns raised. It is always impossible to know to what extent the results in an unblinded trial relying solely on subjective measures are a measure of bias rather than genuine response to the intervention. That’s the point. It is unknowable. So any “positive” results cannot be taken at face value.
Beyond that, the mean results for the primary outcome in this trial fell below the MCID threshold. By definition, the reported change–whatever the source–is meaningless from a clinical perspective at a population level. (That doesn’t mean none of the participants experience clinically significant improvements. Of course some proportion of them do.) In their vacuous response, the authors don’t mention or own the MCID problem. Instead, they suggest we are overlooking the “explanatory power of recent symptom science”–even though that purported “power” produced these embarrassing findings.
I have posted the published exchange below.
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Response to treatment in the Multiple Symptoms Study 3 trial
Joan Crawford, David Tuller
Christopher Burton and colleagues1 conducted an unblinded trial of a consultative intervention for 354 people with persistent physical symptoms but no identifiable “organic” cause. Patient Health Questionnaire-15 (PHQ-15) score, which is a brief, subjective, self-administered screen of severity of somatic complaints, was the primary outcome. This kind of trial design can be expected to produce modest positive outcomes, via expectation bias alone.2 No real-life, objective assessment of functioning was conducted.
The intervention involved up to four sessions with a general practitioner, offering patients “rational explanations” for their symptoms in the absence of known, falsifiable causes and helping patients to develop strategies for managing symptoms. Although the “rational explanations” are not described, they presumably did not include “organic” diseases or conditions.
Scores on the PHQ-15 range from 0 to 30. Recruited patients had scores from 10 to 20, indicating moderate severity. At the end of the study, the adjusted between-group difference of –1·82 did not reach the minimal clinically important difference of 2·3.3 The change is well within what would be expected from bias alone. The results therefore confirmed that the intervention was of limited, if any, practical benefit. However, the paper presents the findings as though they had shown the opposite.
Instead of the “rational explanations” promoted by the investigators, more straightforward and honest explanations—for example, we do not know what is causing symptoms—could easily have produced similar results. Patients desire resolution of symptoms and recovery of functions. The trial did not achieve this result. Post-intervention, participants continue to have an impaired quality of life and poor experiences of health care.
DT holds an academic position at the Center for Global Public Health at UC Berkeley, which is largely supported by crowdfunded donations directly to the university, many of them from patients with myalgic encephalomyelitis or chronic fatigue syndrome and related conditions that fall under the heading of persistent physical symptoms. JSC declares no competing interests.
References
1. Burton, C ∙ Mooney, C ∙ Sutton, L ∙ et al. Effectiveness of a symptom-clinic intervention delivered by general practitioners with an extended role for people with multiple and persistent physical symptoms in England: the Multiple Symptoms Study 3 pragmatic, multicentre, parallel-group, individually randomised controlled trial. Lancet. 2024; 403:2619-2629
2. Edwards, J. PACE team response shows a disregard for the principles of science. J Health Psychol. 2017; 22:1155-1158
3. Toussaint, A ∙ Kroenke, K ∙ Baye, F ∙ et al. Comparing the Patient Health Questionnaire-15 and the Somatic Symptom Scale-8 as measures of somatic symptom burden. J Psychosom Res. 2017; 101:44-50
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Response to treatment in the Multiple Symptoms Study 3 trial – Authors’ reply
Christopher Burton, Vincent Deary, Cara Mooney, Laura Sutton, Cindy Cooper
We thank Joan S Crawford and David Tuller for their interest in our Article.1 Persistent physical symptoms are heterogeneous and, by definition, do not tend to go away easily. In the absence of perfect knowledge about their pathophysiology, we believe that interventions to help people with multiple persistent physical symptoms should apply the knowledge that we currently have.2
Pragmatic interventions should have pragmatic evaluations (finding out whether something can be useful) rather than explanatory ones (using an effect to prove a mechanistic hypothesis).3 Multiple Symptoms Study 3 was a pragmatic trial of a complex, pragmatic intervention.1
The study evaluated outcomes shortly after treatment, at 6 months and 12 months. Although outcomes at the end of treatment might reflect a feeling of being heard, it is unlikely that this is the mechanism explaining the statistically significant difference between conditions at the 12-month follow-up point. Rather, we should look to the qualitative process evaluation (an expected part of a complex intervention trial4) to understand and interpret the findings.
Although feeling heard was important to patients, making sense of symptoms using current science and being offered a choice of actions based on this understanding were also valued by patients.5
Encouraging health professionals to proclaim “we do not know what is causing symptoms” in response to persistent physical symptoms, as Crawford and Tuller recommend, underestimates the explanatory power of recent symptom science and is likely to perpetuate the frustration and hopelessness of both clinicians and patients, which is all too common in this field.
CB has received publisher royalties and speaker honoraria in relation to persistent physical symptoms. All other authors declare no competing interests.
References
1. Burton, C ∙ Mooney, C ∙ Sutton, L ∙ et al. Effectiveness of a symptom-clinic intervention delivered by general practitioners with an extended role for people with multiple and persistent physical symptoms in England: the Multiple Symptoms Study 3 pragmatic, multicentre, parallel-group, individually randomised controlled trial. Lancet. 2024; 403:2619-2629
2. Löwe, B ∙ Toussaint, A ∙ Rosmalen, JGM ∙ et al. Persistent physical symptoms: definition, genesis, and management. Lancet. 2024; 403:2649-2662
3. Loudon, K ∙ Treweek, S ∙ Sullivan, F ∙ et al. The PRECIS-2 tool: designing trials that are fit for purpose. BMJ. 2015; 350, h2147
4. Skivington, K ∙ Matthews, L ∙ Simpson, SA ∙ et al. A new framework for developing and evaluating complex interventions: update of Medical Research Council guidance. BMJ. 2021; 374, n2061
5. Sanders, T ∙ Fryer, K ∙ Greco, M ∙ et al. Explanation for symptoms and biographical repair in a clinic for persistent physical symptoms. SSM Qual Res Health. 2024; 5, 100438
“Explanatory power”. Wow, that sounds out of this world! How could anyone possibly underestimate that? Who wouldn’t want to give that a go?
Thank you to both David and Joan. You must be exasperated! But your application is very welcome.
Following on from my comment above, I need to put joking aside and get serious, because people are suffering and dying because of doctors’ false illness beliefs around persistent physical symptoms (PPS)/medically unexplained symptoms (MUS)/functional somatic syndromes etc. etc. Accurate diagnosis requires doctors to be objective about unexplained symptoms, but the second response above strongly suggests that they are not – the respondents appear to consider doctors’ feelings to be important in the diagnostic process when they shouldn’t be. What both doctors and patients feel should be immaterial if objectivity in diagnosis is going to be preserved. When symptoms are unexplained, leaving the diagnosis open isn’t a choice, it’s a must to avoid misdiagnosis.
A major problem with the whole PPS/MUS shebang is that there’s been so little effort to determine how many patients are suffering and dying as a result of their diagnoses not being kept open to further consideration and investigation by the approach that doctors have been persuaded to take as the right one. Instead, doctors and practitioners have apparently been instructed to brand/code patients with labels such as ‘somatic symptom disorder’ with a view to dissuading other doctors from investigating them further. So patients going back to their doctors with their symptoms, often repeatedly pleading for help, are not only likely to be ignored and neglected, but worse than that. Their repeated attendance may well entrench an erroneous PPS/MUS label/diagnosis that should never have been seen as a diagnosis. They, like GP Lisa Steen -https://blogs.bmj.com/bmj/2016/08/25/lisa-steen-the-wilderness-of-the-medically-unexplained/, could end up wandering in a medical wilderness where nobody is listening to them.
One might have thought that that posthumous account by Lisa Steen in 2016 would have been a wake up call to doctors about the dangers of the MUS/PPS construct, but it seems not. Instead of there being an urgent call for patients so labelled to be closely followed to assess the rate of misdiagnosis arising from the MUS/PPS approach, it seems there’s been silence from the medical community on the subject, at least until recently. The two Sloan et al papers that David covered in his last blog have now flagged up a considerable problem of patients with autoimmune diseases (majority female) being misdiagnosed with medically unexplained symptoms or with mental health disorders, and have together exposed some of the harms that those misdiagnoses have caused, including years of delay to correct diagnosis and mistrust of the healthcare system. With autoimmune patients suffering AVERAGE delays of 6+ years to correct diagnosis, it’s clear that patients who’ve been labelled with PPS/MUS will need to be followed up for many more years than that to see what harms PPS/MUS/similar mental health labels are causing.
Thankfully, that research is being noticed -https://www.amjmed.com/article/S0002-9343(22)00396-5/pdf . I’d say that “conceit” is quite an appropriate word for doctors who overrate their skills and performance and who fail to put their own feelings and prejudices aside to listen to what their patient is trying to tell them. ‘Hubris’ could be another.
I think that those respondents to the Crawford and Tuller response (see the author’s reply above) might benefit from reading this -https://www.degruyterbrill.com/document/doi/10.1515/dx-2018-0033/html and from paying particular attention to figure 2 in it.
“Encouraging health professionals to proclaim “we do not know what is causing symptoms” in response to persistent physical symptoms, as Crawford and Tuller recommend, underestimates the explanatory power of recent symptom science and is likely to perpetuate the frustration and hopelessness of both clinicians and patients, which is all too common in this field.”
The preference for “explanatory power” over actual truth is RFK’s modus operandi.
I don’t think people should underestimate the power of a special relationship.
I commented above: “What both doctors and patients feel should be immaterial if objectivity in diagnosis is going to be preserved.”
To be clear, I didn’t mean that patients’ feelings about their diagnosis or lack of diagnosis don’t matter, but that in the diagnostic process itself they should be irrelevant. For example, if a doctor finds cancer then should they reject that diagnosis because of the effect it might have on their patient or on them personally having to deal with it and break the news to their patient? Of course not. The same applies to not finding a cause for a patient’s symptoms. I’d say that the responsible thing to do in that case is to leave the diagnosis open. How that is conveyed to the patient is another matter – the patient’s feelings are important and should be taken into consideration, but any explanation they’re given should be truthful and should get across a) that the diagnosis is to be left completely open and b) that the patient is most welcome to return for further objective evaluation if the symptoms don’t resolve or deteriorate. I don’t think an explanation should include theoretical causes or hypotheses, no matter how ‘rational’ doctors consider them to be.
If a physical diagnosis requires a positive/abnormal result (or results) from a robust test (or tests), as seems to be the case these days, then shouldn’t the same also be required before a PPS/MUS label is dished out? As far as I know, there are no robust tests for PPS/MUS, it is a label attached when doctors don’t know what is causing the symptoms. To my mind, Crawford and Tuller are being the honest ones here, saying it as it is. The responding authors appear to be assuming that PPS patients will feel frustrated and hopeless at there being no clear answers, as they perhaps do themselves but, in my experience, patients value honesty in their healthcare above gooeyness from their doctors. Didn’t we move past patients being sheltered from their cancer diagnoses a long time ago? I imagine that most patients, if asked, would say that they’d rather have no diagnosis than the wrong diagnosis and no treatment than a harmful incorrect one. [Of course, having a diagnosis can sometimes bring substantial benefits in terms of state support (welfare and healthcare), workplace adjustments and help and acknowledgement of suffering from family and friends, but a PPS/MUS label seems to convey very few of those and could even be detrimental, and I’d say is probably not really worth any paper it’s written on.] From what I’ve seen, patients also value their symptoms being taken seriously and don’t take too kindly to being fobbed off with inadequate explanations for them.
To me, good doctors are those who do take what their patients report seriously, who are completely honest and who don’t let their own feelings, prejudices and personal beliefs get in the way of objective care. It looks like the GMC broadly agrees with that for doctors in the UK, but it’s possible that other patients think differently to me. Perhaps there are those who’d like to be protected from the truth because they would feel frustrated and hopeless if doctors told them that they don’t know what’s causing their symptoms? I’d be interested to hear their viewpoint, if that’s the case.
(I’d just like to add that I’ve just been reading the paper that is reference 5 above and that shares several co-authors with the author’s reply posted above in this blog. From what I’ve read, it seems that their approach to persistent symptoms is similar to an approach for management of pain that appears to have gained traction with doctors in recent years. I’m not saying that that pain management approach won’t help any patients with their pain but I think it has the potential to cause immense biopsychosocial harm to some or many patients and also damage the wider economy if people can’t work because their pain hasn’t been adequately medically or surgically addressed. I’m not surprised that economic inactivity in the UK due to ill health is rising. It seems that patients with severe pain who would previously have been medically or surgically treated to get them back to work aren’t being so treated anymore. Psychotherapy and physio-/exercise therapy seem to be the order of the day instead. Something’s clearly going badly wrong. Could these approaches offer any explanations, I wonder?)
Promotion of psychotherapy for Long Covid/ME/CFS patients has vampire like resilience. No matter how often studies like PACE are discredited, they will be revived because of 2 powerful factors – economic incentives and the beguiling easy road which is the product of narcissism, sloth, and arrogance by medical practitioners. The disability industry, both for profit and governments, offer financial and prestige benefits to those who choose not to see disability and save insurers and governments money by touting less expensive treatments. A second major factor is the human capacity for self delusion and self gratification. Doctors are smart people who are successful in the game of life. If they do not understand what is happening to a patient, the most rewarding and least effort solution is to blame the patient. Doctors have drunk the insurance company koolaid that their purpose in life is to be goalkeepers out to protect the public from people out to “get something” from the system. There is a more personal motivation by doctors to blame the patient which can be explained by arrogance or complacency. In the case of arrogance, Doctors who overestimate their knowledge think “I am a smart doctor so if I can’t come up with an explanation, it must be that the patient is somaticizing or fabricating symptoms. Arrogant doctors may or may not be dedicated, but complacent doctors win by applying an algorithm that works most of the time. There are many dedicated doctors who want to help these patients, but a large number prefer to make their lives easier. Learning about a condition or disease not taught in medical school, like Long Covid, ME/CFS, or MCAS is hard work. Choosing door number 1, the patient’s mindset, saves complacent doctors both work and guilt.