Read the latest HealthWatch newsletter:  Newsletter 115, Spring 2021

By Caroline Struthers

“First Do No Harm”, the Independent Medicines and Medical Devices Safety Review focusing on three drug/devices aimed at women (aka the Cumberlege report) was published on 8 July 2020.(1) It should have welcome implications for much-needed change in the way patients are treated.

Two of the review’s proposals are that there be a new Patient Safety Commissioner and Redress Agency established. However, they would only look at harms from “medicines and medical devices”. The review did not consider potential harms to patients from psychosocial and behavioural interventions which are still widely recommended within the NHS for the ever-expanding range of patients who find themselves in the “medically unexplained symptoms” (MUS) swamp. Currently, patients with a range of unexplained conditions such as chronic fatigue syndrome (also known as myalgic encephalomyelitis) and irritable bowel syndrome would fall under the UK Government-funded IAPT (Improving Access to Psychological Therapies) remit.(2) The inclusion of MUS patients under IAPT signifies a massive expansion of its coverage, far beyond the patients with common mental health complaints where it originated. The benefit of this expansion to MUS patients is doubtful.(3)

There is currently no UK mechanism for recording or monitoring harms from these types of interventions, or for challenging the assumption that they are appropriate first-line treatment options for long-term conditions where either the cause or the perpetuating factors are unclear.

It is vital that the safety and effectiveness (or lack of effectiveness) of psychological and behavioural interventions is also covered by a future Patient Safety Commissioner and Redress Agency. This agency must also be prepared to look hard at the potential for conflicts of interest in those conducting any such research. When people have a financial or other vested interest in an intervention of any kind, they have already convinced themselves and their peers, and maybe also regulators, government policy makers, and insurance companies, that it has merit. There is no incentive to genuinely try and prove it doesn’t work. But that is what scientists are trained to do; to try and prove their hypotheses are wrong. If an investigator designs an experiment to try and prove that an intervention doesn’t work any better than placebo or an alternative treatment, and they can’t prove that ‘null hypothesis’, then it’s likely there is a genuine benefit. But this is not what happens in practice.

No one questions that developers of behavioural and psychological therapies can lead large publicly funded trials of therapies they have developed themselves. Why not?

There is, quite rightly, a huge fuss made about the fact that pharmaceutical companies are allowed to test their own products, and how this corrupts academia and harms patients.(4) Yet no one questions that developers of behavioural and psychological therapies can lead large publicly funded trials of therapies they have developed themselves, have been offering for years, and built their career and reputation upon. Why not? There is also no incentive for others “invested” in these treatments further down the line, including health service providers like the NHS, to carry out the same kind of post-marketing surveillance which could reveal the lack of long-term benefit, or evidence of harm which would not be picked up in a trial.

For example, myalgic encephalomyelitis (ME), sometimes known as chronic fatigue syndrome (CFS) is a debilitating illness which was been recognised as a disease of the central nervous system (ICD-10 G93.31) by the WHO since 1969.(5) Its hallmark symptom is post-exertional malaise (PEM) which is extreme debilitating fatigue even after a minor degree of physical or cognitive effort. Other symptoms include muscle pain, headaches, palpitations, sickness and orthostatic intolerance. There are no reliable biomarkers yet, and biomedical research to investigate the causes and potential treatments has been chronically underfunded.(6)

In 2011 the Lancet published results of the PACE Trial, a randomised trial designed to compare a number of different behavioural strategies to treat ME/CFS – including cognitive behaviour therapy (CBT) and graded exercise therapy (GET) – with standard medical care (SMC).(7) It concluded that CBT and GET can safely be added to SMC to moderately improve outcomes for patients.

The UK government would have hoped the treatments would save them money in disability payments

But was PACE effectively a “show trial”? Certainly it seemed to confirm the value of treatments that the triallists told the participants were evidence-based*. The UK government would have hoped the treatments would save them money in disability payments. It is the only trial ever to have been partly funded by the Department of Work and Pensions.(8)

However, PACE and the trials which came before it which claimed to provide evidence of benefit, relied on subjective outcome measures when the interventions could not be blinded. This is a well-known cause of significant bias.(9) Objective measures such as activity monitoring, school or employment records, or healthcare resource use were either not measured or null results were published separately and downplayed. The trial had numerous other methodological shortcomings, such as reducing one of the recovery criteria from what was specified in the protocol to a level low enough to be eligible to take part in the trial. In other words, a participant could get worse on that measure during the trial, and still be classed as recovered at the end. PACE has been widely criticized by the scientific research community, as well as by patients and clinicians.(10)

In the case of GET, a Cochrane review was published four years after PACE,(11) acknowledging “advice” from the lead PACE investigator. This 2015 review was the second update and the review is now in its 8th version.(12) Despite extensive comments on the review (13) and a formal complaint,(14) the latest amendment still attracts criticism.(15)

If post-marketing surveillance were ever done properly for psychosocial and behavioural interventions, it might reveal lack of long-term benefit - and even evidence of harm

If post-marketing surveillance were ever done properly for psychosocial and behavioural interventions, it might reveal lack of long-term benefit. In some cases, such as for people with ME, it might have revealed evidence of harm (16,17) a lot sooner. The lack of adequate follow up is discussed in McPhee et al.’s 2019 paper.(18)

The assumption that any intervention that isn’t a drug or device probably won’t do any harm, even if it doesn’t work, is preposterous. Behavioural and psychological treatments, like drugs and devices, cost money to deliver. They also require a huge amount of time and emotional investment from patients, and from the professionals trained to deliver them.

If these treatment approaches don’t work, or cause harm, and continue to be offered anyway, the money, time and emotional investment of both therapist and patient continues to be wasted. This is time and resources that could be spent on research to find treatments that do ‘work’, and on finding out what causes and perpetuates conditions like ME in the first place. It is cruel to patients to give reassurances and recommend treatment based on questionable untested and unproven theories about what is causing and perpetuating their symptoms.

In the case of people with ME in the UK and elsewhere, patients are still being prescribed GET and/or CBT by doctors who are following the current national treatment guidelines (19) in good faith. Patients have a well-founded fear that if they don’t do as advised by the professionals caring for them, they may risk forfeiting further medical help or benefits if the treatments don’t work or even make things worse.

There are many cases where the conflict of interest is less obvious

The irreparable damage done over decades in plain sight by the financially and professionally conflicted promoters of pelvic mesh, valproate, Primodos and other drug/device interventions is horrific. There are many cases, however, where the conflicts of interest are less obvious, such as in the case of behavioural and psychological treatments for applications in which their value is in question.

The interventions may be so well established and accepted by the medical establishment, that there is now no interest in conducting further trials, such as withdrawal trials or surveillance studies. There is not even a Yellow Card reporting system to raise the alarm.

Any commitment to listen to patients and protect them from harm must extend to behavioural and psychological treatments. The merit and safety of these interventions is often backed up by poor science which escapes the greater scrutiny given to research on drugs and medical devices. Patients who are treated with psychological or behavioural interventions are often blamed if they don’t get better and disbelieved if they report they have been harmed. They are also labelled anti-science if they point out obvious methodological flaws in the studies which rely on an embedded assumption that the interventions are both effective and safe when they are neither.

The Cumberledge review highlights the failings of regulators and drug and device makers, but huge failings in academic institutions and the medical establishment enabled and compounded these, and it is no different for behavioural and psychological interventions. It must stop.

Caroline Struthers, Senior EQUATOR Research Fellow, University of Oxford

This article develops a theme originally explored by the author in a rapid response and then a letter in the BMJ (BMJ 2020;370:m3593)

* From trial participant information sheets.

References

  1. First Do No Harm: The report of the IMMDSReview https://www.immdsreview.org.uk/downloads/IMMDSReview_Web.pdf
  2. NHS. The improving access to psychological therapies manual. England: NHS; 2018.
  3. Geraghty, K., Scott, M.J. Treating medically unexplained symptoms via improving access to psychological therapy (IAPT): major limitations identified. BMC Psychol 8, 13 (2020). https://doi.org/10.1186/s40359-020-0380-2
  4. The Illusion of Evidence-Based Medicine: Exposing the crisis of credibility in clinical research Jon Jureidini & Leemon B. McHenry Wakefield (2020)
  5. ICD-10 Version:2010: https://icd.who.int/browse10/2010/en#/G93.3
  6. Tack M. Why is ME/CFS getting so little research funding? https://mecfsskeptic.wordpress.com/2020/11/23/why-is-me-cfs-getting-so-little-research-funding/
  7. PD White, KA Goldsmith, AL Johnson, L Potts, R Walwyn, JC DeCesare, HL Baber, M Burgess, LV Clark, DL Cox, J Bavinton, BJ Angus, G Murphy, M Murphy, H O'Dowd, D Wilks, P McCrone, T Chalder, M Sharpe: Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial, The Lancet, Volume 377, Issue 9768, 2011, Pages 823-836, ISSN 0140-6736, https://doi.org/10.1016/S0140-6736(11)60096-2
  8. In the Expectation of recovery: misleading medical research and welfare reform: Faulkner (2016) https://www.centreforwelfarereform.org/uploads/attachment/492/in-the-expectation-of-recovery.pdf
  9. Michiel Tack, David M. Tuller & Caroline Struthers (2020) Bias caused by reliance on patient-reported outcome measures in non-blinded randomized trials: an in-depth look at exercise therapy for chronic fatigue syndrome, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2020.1848262
  10. Marks DF. Special issue on the PACE Trial. Journal of Health Psychology. 2017;22(9):1103-1105. doi:10.1177/1359105317722370
  11. Larun L, Brurberg KG, Odgaard‐Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database of Systematic Reviews 2015, Issue 2. Art. No.: CD003200. DOI: 10.1002/14651858.CD003200.pub3. Accessed 26 November 2020.
  12. Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database of Systematic Reviews 2019, Issue 10. Art. No.: CD003200. DOI: 10.1002/14651858.CD003200.pub8. Accessed 26 November 2020.
  13. Comments on: Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003200.pub8/read-comments
  14. Struthers C. My complaint to the Cochrane Governing Board about the Cochrane review of Exercise for chronic fatigue syndrome (November 2018) https://healthycontrolblog.wordpress.com/2018/11/29/my-complaint-to-the-cochrane-governing-board-about-the-cochrane-review-of-exercise-for-chronic-fatigue-syndrome/
  15. Tack M. My comments to the Cochrane review on exercise therapy for CFS https://mecfsskeptic.wordpress.com/2020/05/23/my-comments-to-the-cochrane-review-on-exercise-therapy-for-cfs/
  16. Geraghty K, Hann M, Kurtev S. Myalgic encephalomyelitis/chronic fatigue syndrome patients’ reports of symptom changes following cognitive behavioural therapy, graded exercise therapy and pacing treatments: Analysis of a primary survey compared with secondary surveys. Journal of Health Psychology. 2019;24(10):1318-1333. doi:10.1177/1359105317726152
  17. ME Association. Consolidated report: Evaluation of a survey exploring the experiences of adults and children with ME/CFS who have participated in CBT and GET interventional programmes, April 2019: https://meassociation.org.uk/wp-content/uploads/NICE-Patient-Survey-Outcomes-CBT-and-GET-Final-Consolidated-Report-03.04.19.pdf
  18. McPhee G, Baldwin A, Kindlon T, Hughes BM. Monitoring treatment harm in myalgic encephalomyelitis/chronic fatigue syndrome: A freedom-of-information study of National Health Service specialist centres in England. J Health Psychol 2019;1359105319854532. doi:10.1177/1359105319854532 pmid:31234662
  19. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management Clinical guideline (CG53) Published date: 22 August 2007: https://www.nice.org.uk/guidance/cg53
  20. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management In development (GID-NG10091) Expected publication date: 21 April 2021 https://www.nice.org.uk/guidance/indevelopment/gid-ng10091