Embargo broken: Bristol University Professor to discuss trial of quack chronic fatigue syndrome treatment.

An alternative press briefing to compare and contrast with what is being provided by the Science Media Centre for a press conference on Wednesday September 20, 2017.

mind the brain logo

This blog post provides an alternative press briefing to compare and contrast with what was provided by the Science Media Centre for a press conference on Wednesday September 20, 2017.

The press release attached at the bottom of the post announces the publication of results of highly controversial trial that many would argue should never have occurred. The trial exposed children to an untested treatment with a quack explanation delivered by unqualified persons. Lots of money was earned from the trial by the promoters of the quack treatment beyond the boost in credibility for their quack treatment.

Note to journalists and the media: for further information email jcoynester@Gmail.com

This trial involved quackery delivered by unqualified practitioners who are otherwise untrained and insensitive to any harm to patients.

The UK Advertising Standards Authority had previously ruled that Lightning Process could not be advertised as a treatment. [ 1 ]

The Lightning is billed as mixing elements from osteopathy, life coaching and neuro-linguistic programming. That is far from having a mechanism of action based in science or evidence. [2] Neuro-linguistic programming (NLP) has been thoroughly debunked for its pseudoscientific references to brain science and ceased to be discussed in the scientific literature. [3]

Many experts would consider the trial unethical. It involved exposing children and adolescents to an unproven treatment with no prior evidence of effectiveness or safety nor any scientific basis for the mechanism by which it is claimed to work.

 As an American who has decades served on of experience with Committees for the Protection of Human Subjects and Data Safety and Monitoring Boards, I don’t understand how this trial was approved to recruit human subjects, and particularly children and adolescents.

I don’t understand why a physician who cared about her patients would seek approval to conduct such a trial.

Participation in the trial violated patients’ trust that medical settings and personnel will protect them from such risks.

Participation in the trial is time-consuming and involves loss of opportunity to obtain less risky treatment or simply not endure the inconvenience and burden of a treatment for which there is no scientific basis to expect would work.

Esther Crawley has said “If the Lightning Process is dangerous, as they say, we need to find out. They should want to find it out, not prevent research.”  I would like to see her try out that rationale in some of the patient safety and human subjects committee meetings I have attended. The response would not likely be very polite.

Patients and their parents should have been informed of an undisclosed conflict of interest.

phil parker NHSThis trial served as basis for advertising Lightning Process on the Web as being offered in NHS clinics and as being evaluated in a randomized controlled trial. [4]

Promoters of the Lightning Process received substantial payments from this trial. Although a promoter of the treatment was listed on the application for the project, she was not among the paper’s authors, so there will probably be no conflict of interest declared.

The providers were not qualified medical personnel, but were working for an organization that would financially benefit from positive findings.

It is expected that children who received the treatment as part of the trial would continue to receive it from providers who were trained and certified by promoters of the Lightning Process,

By analogy, think of a pharmaceutical trial in which the influence of drug company and that it would profit from positive results was not indicated in patient consent forms. There would be a public outcry and likely legal action.

astonishingWhy might the SMILE create the illusion that Lightning Process is effective for chronic fatigue syndrome?

There were multiple weaknesses in the trial design that would likely generate a false impression that the Lightning Process works. Under similar conditions, homeopathy and sham acupuncture appear effective [5]. Experts know to reject such results because (1) more rigorous designs are required to evaluate efficacy of treatment in order to rule out placebo effects; and (b) there must be a scientific basis for the mechanism of change claimed for how the treatment works. 

Indoctrination of parents and patients with pseudoscientific information. Advertisements for the Lightning Process on the Internet, including YouTube videos, and created a demand for this treatment among patients but it’s cost (£620) is prohibitive for many.

Selection Bias. Participation in the trial involved a 50% probability the treatment would be received for free. (Promoters of the Lightning Process received £567 for each patient who received the treatment in the trial). Parents who believed in the power of the the Lightning Process would be motived to enroll in the trial in order to obtain the treatment free for their children.

The trial was unblinded. Patients and treatment providers knew to which group patients were assigned. Not only with patients getting the Lightning Process be exposed to the providers’ positive expectations and encouragement, those assigned to the control group could register the disappointment when completing outcome measures.

The self-report subjective outcomes of this trial are susceptible to nonspecific factors (placebo effects). These include positive expectations, increased contact and support, and a rationale for what was being done, even if scientifically unsound. These nonspecific factors were concentrated in the group receiving the Lightning Process intervention. This serves to stack the deck in any evaluation of the Lightning Process and inflate differences with the patients who didn’t get into this group.

There were no objective measures of outcome. The one measure with a semblance of objectivity, school attendance, was eliminated in a pilot study. Objective measures would have provided a check on the likely exaggerated effects obtained with subjective seif-report measures.

The providers were not qualified medical, but were working for an organization that would financially benefit from positive findings. The providers were highly motivated to obtain positive results.

During treatment, the  Lightning Process further indoctrinates child and adolescent patients with pseudoscience [ 6 ] and involves coercion to fake that they are getting well [7 ]. Such coercion can interfere with the patients getting appropriate help when they need it, their establishing appropriate expectations with parental and school authorities, and even their responding honestly to outcome assessments.

 It’s not just patients and patient family members activists who object to the trial. As professionals have gotten more informed, there’s been increasing international concern about the ethics and safety of this trial.

The Science Media Centre has consistently portrayed critics of Esther Crawley’s work as being a disturbed minority of patients and patients’ family members. Smearing and vilification of patients and parents who object to the trial is unprecedented.

Particularly with the international controversy over the PACE trial of cognitive behavior therapy  and graded exercise therapy for chronic fatigue syndrome, the patients have been joined by non-patient scientists and clinicians in their concerns.

Really, if you were a fully informed parent of a child who was being pressured to participate in the trial with false claims of the potential benefits, wouldn’t you object?

embargoed news briefing

Notes

[1] “To date, neither the ASA nor CAP [Committee of Advertising Practice] has seen robust evidence for the health benefits of LP. Advertisers should take care not to make implied claims about the health benefits of the three-day course and must not refer to conditions for which medical supervision should be sought.”

[2] The respected Skeptics Dictionary offers a scathing critique of Phil Parker’s Lightning Process. The critique specifically cites concerns that Crawley’s SMILE trial switched outcomes to increase the likelihood of obtaining evidence of effectiveness.

[3] The entry for Neuro-linguistic programming (NLP) inWikipedia states:

There is no scientific evidence supporting the claims made by NLP advocates and it has been discredited as a pseudoscience by experts.[1][12] Scientific reviews state that NLP is based on outdated metaphors of how the brain works that are inconsistent with current neurological theory and contain numerous factual errors.[13][14

[4] NHS and LP    Phil Parker’s webpage announces the collaboration with Bristol University and provides a link to the officialSMILE  trial website.

{5] A provocative New England Journal of Medicine article, Active Albuterol or Placebo, Sham Acupuncture, or No Intervention in Asthma study showed that sham acupuncture as effective as an established medical treatment – an albuterol inhaler – for asthma when judged with subjective measures, but there was a large superiority for the established medical treatment obtained with objective measures.

[6] Instructional materials that patient are required to read during treatment include:

LP trains individuals to recognize when they are stimulating or triggering unhelpful physiological responses and to avoid these, using a set of standardized questions, new language patterns and physical movements with the aim of improving a more appropriate response to situations.

* Learn about the detailed science and research behind the Lightning Process and how it can help you resolve your issues.

* Start your training in recognising when you’re using your body, nervous system and specific language patterns in a damaging way

What if you could learn to reset your body’s health systems back to normal by using the well researched connection that exists between the brain and body?

The Lightning Process does this by teaching you how to spot when the PER is happening and how you can calm this response down, allowing your body to re-balance itself.

The Lightning Process will teach you how to use Neuroplasticity to break out of any destructive unconscious patterns that are keeping you stuck, and learn to use new, life and health enhancing ones instead.

The Lightning Process is a training programme which has had huge success with people who want to improve their health and wellbeing.

[7] Responsibility of patients:

Believe that Lightning Process will heal you. Tell everyone that you have been healed. Perform magic rituals like standing in circles drawn on paper with positive Keywords stated on them. Learn to render short rhyme when you feel symptoms, no matter where you are, as many times as required for the symptoms to disappear. Speak only in positive terms and think only positive thoughts. If symptoms or negative thoughts come, you must stretch forth your arms with palms facing outward and shout “Stop!” You are solely responsible for ME. You can choose to have ME. But you are free to choose a life without ME if you wish. If the method does not work, it is you who are doing something wrong.

skeptical-cat-is-fraught-with-skepticism-300x225Special thanks to the Skeptical Cat who provided me with an advance copy of the press release from Science Media Centre.

 

 

 

 

 

 

 

Before you enroll your child in the MAGENTA chronic fatigue syndrome study: Issues to be considered

[October 3 8:23 AM Update: I have now inserted Article 21 of the Declaration of Helsinki below, which is particularly relevant to discussions of the ethical problems of Dr. Esther Crawley’s previous SMILE trial.]

Petitions are calling for shutting down the MAGENTA trial. Those who organized the effort and signed the petition are commendably brave, given past vilification of any effort by patients and their allies to have a say about such trials.

Below I identify a number of issues that parents should consider in deciding whether to enroll their children in the MAGENTA trial or to withdraw them if they have already been enrolled. I take a strong stand, but I believe I have adequately justified and documented my points. I welcome discussion to the contrary.

This is a long read but to summarize the key points:

  • The MAGENTA trial does not promise any health benefits for the children participating in the trial. The information sheet for the trial was recently modified to suggest they might benefit. However, earlier versions clearly stated that no benefit was anticipated.
  • There is inadequate disclosure of likely harms to children participating in the trial.
  • An estimate of a health benefit can be evaluated from the existing literature concerning the effectiveness of the graded exercise therapy intervention with adults. Obtaining funding for the MAGENTA trial depended on a misrepresentation of the strength of evidence that it works in adult populations.  I am talking about the PACE trial.
  • Beyond any direct benefit to their children, parents might be motivated by the hope of contributing to science and the availability of effective treatments. However, these possible benefits depend on publication of results of a trial after undergoing peer review. The Principal Investigator for the MAGENTA trial, Dr. Esther Crawley, has a history of obtaining parents’ consent for participation of their children in the SMILE trial, but then not publishing the results in a timely fashion. Years later, we are still waiting.
  • Dr. Esther Crawley exposed children to unnecessary risk without likely benefit in her conduct of the SMILE trial. This clinical trial involved inflicting a quack treatment on children. Parents were not adequately informed of the nature of the treatment and the absence of evidence for any mechanism by which the intervention could conceivably be effective. This reflects on the due diligence that Dr. Crawley can be expected to exercise in the MAGENTA trial.
  • The consent form for the MAGENTA trial involves parents granting permission for the investigator to use children and parents’ comments concerning effects of the treatment for its promotion. Insufficient restrictions are placed on how the comments can be used. There is the clear precedent of comments made in the context of the SMILE trial being used to promote the quack Lightning Process treatment in the absence of evidence that treatment was actually effective in the trial. There is no guarantee that any comments collected from children and parents in the MAGENTA trial would not similarly be misused.
  • Dr. Esther Crawley participated in a smear campaign against parents having legitimate concerns about the SMILE trial. Parents making legitimate use of tools provided by the government such as Freedom of Information Act requests, appeals of decisions of ethical review boards and complaints to the General Medical Council were vilified and shamed.
  • Dr. Esther Crawley has provided direct, self-incriminating quotes in the newsletter of the Science Media Centre about how she was coached and directed by their staff to slam the patient community.  She played a key role in a concerted and orchestrated attack on the credibility of not only parents of participants in the MAGENTA trial, but of all patients having chronic fatigue syndrome/ myalgic encephalomyelitis , as well as their advocates and allies.

I am not a parent of a child eligible for recruitment to the MAGENTA trial. I am not even a citizen or resident of the UK. Nonetheless, I have considered the issues and lay out some of my considerations below. On this basis, I signed the global support version  of the UK petition to suspend all trials of graded exercise therapy in children and adults with ME/CFS. I encourage readers who are similarly in my situation outside the UK to join me in signing the global support petition.

If I were a parent of an eligible child or a resident of the UK, I would not enroll my child in MAGENTA. I would immediately withdraw my child if he or she were currently participating in the trial. I would request all the child’s data be given back or evidence that it had been destroyed.

I recommend my PLOS Mind the Brain post, What patients should require before consenting to participate in research…  as either a prelude or epilogue to the following blog post.

What you will find here is a discussion of matters that parents should consider before enrolling their children in the MAGENTA trial of graded exercise for chronic fatigue syndrome. The previous blog post [http://blogs.plos.org/mindthebrain/2015/12/09/what-patients-should-require-before-consenting-to-participate-in-research/ ]  is rich in links to an ongoing initiative from The BMJ to promote broader involvement of patients (and implicitly, parents of patients) in the design, implementation, and interpretation of clinical trials. The views put forth by The BMJ are quite progressive, even if there is a gap between their expression of views and their actual implementation. Overall, that blog post presents a good set of standards for patients (and parents) making informed decisions concerning enrollment in clinical trials.

Simon McGrathLate-breaking update: See also

Simon McGrath: PACE trial shows why medicine needs patients to scrutinise studies about their health

Basic considerations.

Patients are under no obligation to participate in clinical trials. It should be recognized that any participation typically involves burden and possibly risk over what is involved in receiving medical care outside of a clinical trial.

It is a deprivation of their human rights and a violation of the Declaration of Helsinki to coerce patients to participate in medical research without freely given, fully informed consent.

Patients cannot be denied any medical treatment or attention to which they would otherwise be entitled if they fail to enroll in a clinical trial.

Issues are compounded when consent from parents is sought for participation of vulnerable children and adolescents for whom they have legal responsibility. Although assent to participate in clinical trials is sought from children and adolescents, it remains for their parents to consent to their participation.

Parents can at any time withdraw their consent for their children and adolescents participating in trials and have their data removed, without requiring the approval of any authorities of their reason for doing so.

Declaration of Helsinki

The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical principles for medical research involving human subjects, including research on identifiable human material and data.

It includes:

In medical research involving human subjects capable of giving informed consent, each potential subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study and the discomfort it may entail, post-study provisions and any other relevant aspects of the study. The potential subject must be informed of the right to refuse to participate in the study or to withdraw consent to participate at any time without reprisal. Special attention should be given to the specific information needs of individual potential subjects as well as to the methods used to deliver the information.

[October 3 8:23 AM Update]: I have now inserted Article 21 of the Declaration of Helsinki which really nails the ethical problems of the SMILE trial:

21. Medical research involving human subjects must conform to generally accepted scientific principles, be based on a thorough knowledge of the scientific literature, other relevant sources of information, and adequate laboratory and, as appropriate, animal experimentation. The welfare of animals used for research must be respected.

There is clearly in adequate scientific justification for testing the quack Lightning Process Treatment.

What Is the Magenta Trial?

The published MAGENTA study protocol states

This study aims to investigate the acceptability and feasibility of carrying out a multicentre randomised controlled trial investigating the effectiveness of graded exercise therapy compared with activity management for children/teenagers who are mildly or moderately affected with CFS/ME.

Methods and analysis 100 paediatric patients (8–17 years) with CFS/ME will be recruited from 3 specialist UK National Health Service (NHS) CFS/ME services (Bath, Cambridge and Newcastle). Patients will be randomised (1:1) to receive either graded exercise therapy or activity management. Feasibility analysis will include the number of young people eligible, approached and consented to the trial; attrition rate and treatment adherence; questionnaire and accelerometer completion rates. Integrated qualitative methods will ascertain perceptions of feasibility and acceptability of recruitment, randomisation and the interventions. All adverse events will be monitored to assess the safety of the trial.

The first of two treatments being compared is:

Arm 1: activity management

This arm will be delivered by CFS/ME specialists. As activity management is currently being delivered in all three services, clinicians will not require further training; however, they will receive guidance on the mandatory, prohibited and flexible components (see online supplementary appendix 1). Clinicians therefore have flexibility in delivering the intervention within their National Health Service (NHS) setting. Activity management aims to convert a ‘boom–bust’ pattern of activity (lots 1 day and little the next) to a baseline with the same daily amount before increasing the daily amount by 10–20% each week. For children and adolescents with CFS/ME, these are mostly cognitive activities: school, schoolwork, reading, socialising and screen time (phone, laptop, TV, games). Those allocated to this arm will receive advice about the total amount of daily activity, including physical activity, but will not receive specific advice about their use of exercise, increasing exercise or timed physical exercise.

So, the first arm of the trial is a comparison condition consisting of standard care delivered without further training of providers. The treatment is flexibly delivered, expected to vary between settings, and thus largely uncontrolled. The treatment represents a methodologically weak condition that does not adequately control for attention and positive expectations. Control conditions should be equivalent to the intervention being evaluated in these dimensions.

The second arm of the study:

Arm 2: graded exercise therapy (GET)

This arm will be delivered by referral to a GET-trained CFS/ME specialist who will receive guidance on the mandatory, prohibited and flexible components (see online supplementary appendix 1). They will be encouraged to deliver GET as they would in their NHS setting.20 Those allocated to this arm will be offered advice that is focused on exercise with detailed assessment of current physical activity, advice about exercise and a programme including timed daily exercise. The intervention will encourage children and adolescents to find a baseline level of exercise which will be increased slowly (by 10–20% a week, as per NICE guidance5 and the Pacing, graded Activity and Cognitive behaviour therapy – a randomised Evaluation (PACE)12 ,21). This will be the median amount of daily exercise done during the week. Children and adolescents will also be taught to use a heart rate monitor to avoid overexertion. Participants will be advised to stay within the target heart rate zones of 50–70% of their maximum heart rate.5 ,7

The outcome of the trial will be evaluated in terms of

Quantitative analysis

The percentage recruited of those eligible will be calculated …Retention will be estimated as the percentage of recruited children and adolescents reaching the primary 6-month follow-up point, who provide key outcome measures (the Chalder Fatigue Scale and the 36-Item Short-Form Physical Functioning Scale (SF-36 PFS)) at that assessment point.

actigraphObjective data will be collected in the form of physical activity measured by Accelerometers. These are

Small, matchbox-sized devices that measure physical activity. They have been shown to provide reliable indicators of physical activity among children and adults.

However, actual evaluation of the outcome of the trial will focus on recruitment and retention and subjective, self-report measures of fatigue and physical functioning. These subjective measures have been shown to be less valid than objective measures. Scores are  vulnerable  to participants knowing what condition they are assigned to (called ‘being unblinded’) and their perception of which intervention the investigators prefer.

It is notable that in the PACE trial of CBT and GET for chronic fatigue syndrome in adults, the investigators manipulated participants’ self-reports with praise in newsletters sent out during the trial . The investigators also switched their scoring of the self-report measures and produced results that they later conceded to have been exaggerated by their changing in scoring of the self-report measures [http://www.wolfson.qmul.ac.uk/current-projects/pace-trial#news ].

Irish ME/CFS Association Officer & Tom Kindlon
Tom Kindlon, Irish ME/CFS Association Officer

See an excellent commentary by Tom Kindlon at PubMed Commons [What’s that? ]

The validity of using subjective outcome measures as primary outcomes is questionable in such a trial

The bottom line is that the investigators have a poorly designed study with inadequate control condition. They have chosen subjective self-reports that are prone to invalidity and manipulation over objective measures like actual changes in activity or practical real-world measures like school attendance. Not very good science here. But they are asking parents to sign their children up.

What is promised to parents consenting to have the children enrolled in the trial?

The published protocol to which the investigators supposedly committed themselves stated

What are the possible benefits and risks of participating?
Participants will not benefit directly from taking part in the study although it may prove enjoyable contributing to the research. There are no risks of participating in the study.

Version 7 of the information sheet provided to parents, states

Your child may benefit from the treatment they receive, but we cannot guarantee this. Some children with CFS/ME like to know that they are helping other children in the future. Your child may also learn about research.

Survey assessments conducted by the patient community strongly contradict the suggestion that there is no risk of harm with GET.

alemAlem Matthees, the patient activist who obtained release of the PACE data and participated in reanalysis has commented:

“Given that post-exertional symptomatology is a hallmark of ME/CFS, it is premature to do trials of graded exercise on children when safety has not first been properly established in adults. The assertion that graded exercise is safe in adults is generally based on trials where harms are poorly reported or where the evidence of objectively measured increases in total activity levels is lacking. Adult patients commonly report that their health was substantially worsened after trying to increase their activity levels, sometimes severely and permanently, therefore this serious issue cannot be ignored when recruiting children for research.”

See also

Kindlon T. Reporting of harms associated with graded exercise therapy and cognitive behavioural therapy in myalgic encephalomyelitis/chronic fatigue syndrome. Bulletin of the IACFS/ME. 2011;19(2):59-111.

This thorough systematic review reports inadequacy in harm reporting in clinical trials, but:

Exercise-related physiological abnormalities have been documented in recent studies and high rates of adverse  reactions  to exercise have been  recorded in  a number of  patient surveys. Fifty-one percent of  survey respondents (range 28-82%, n=4338, 8 surveys) reported that GET worsened their health while 20% of respondents (range 7-38%, n=1808, 5 surveys) reported similar results for CBT.

The unpublished results of Dr. Esther Crawley’s SMILE trial

 A Bristol University website indicates that recruitment of the SMILE trial was completed in 2013. The published protocol for the SMILE trial

[Note the ® in the title below, indicating a test of trademarked commercial product. The significance of that is worthy of a whole other blog post. ]

Crawley E, Mills N, Hollingworth W, Deans Z, Sterne JA, Donovan JL, Beasant L, Montgomery A. Comparing specialist medical care with specialist medical care plus the Lightning Process® for chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME): study protocol for a randomised controlled trial (SMILE Trial). Trials. 2013 Dec 26;14(1):1.

States

The data monitoring group will receive notice of serious adverse events (SAEs) for the sample as whole. If the incidence of SAEs of a similar type is greater than would be expected in this population, it will be possible for the data monitoring group to receive data according to trial arm to determine any evidence of excess in either arm.

Primary outcome data at six months will be examined once data are available from 50 patients, to ensure that neither arm is having a detrimental effect on the majority of patients. An independent statistician with no other involvement in the study will investigate whether more than 20 participants in the study sample as a whole have experienced a reduction of ≥ 30 points on the SF-36 at six months. In this case, the data will then be summarised separately by trial arm, and sent to the data monitoring group for review. This process will ensure that the trial team will not have access to the outcome data separated by treatment arm.

A Bristol University website indicates that recruitment of the SMILE trial was completed in 2013. The trial was thus completed a number of years ago, but these valuable data have never been published.

The only publication from the trial so far uses selective quotes from child participants that cannot be independently evaluated. Readers are not told how representative these quotes, the outcomes for the children being quoted or the overall outcomes of the trial.

Parslow R, Patel A, Beasant L, Haywood K, Johnson D, Crawley E. What matters to children with CFS/ME? A conceptual model as the first stage in developing a PROM. Archives of Disease in Childhood. 2015 Dec 1;100(12):1141-7.

The “evaluation” of the quack Lightning Treatment in the SMILE trial and quotes from patients have also been used to promote Parker’s products as being used in NHS clinics.

How can I say the Lightning Process is quackery?

 Dr. Crawley describes the Lightning Process in the Research Ethics Application Form for the SMILE study as   ombining the principles of neurolinguistic programming, osteopathy, and clinical hypnotherapy.

That is an amazing array of three different frameworks from different disciplines. You would be hard pressed to find an example other than the Lightning Process that claimed to integrate them. Yet, any mechanisms for explaining therapeutic interventions cannot be a creative stir fry of whatever is on hand being thrown together. For a treatment to be considered science-based, there has to be a solid basis of evidence that these presumably complex processes fit together as assumed and work as assumed. I challenge Dr. Crawley or anyone else to produce a shred of credible, peer-reviewed evidence for the basic mechanism of the Lightning Process.

The entry for Neuro-linguistic programming (NLP) in Wikipedia states

There is no scientific evidence supporting the claims made by NLP advocates and it has been discredited as a pseudoscience by experts.[1][12] Scientific reviews state that NLP is based on outdated metaphors of how the brain works that are inconsistent with current neurological theory and contain numerous factual errors.[13][14

The respected Skeptics Dictionary offers a scathing critique of Phil Parker’s Lightning Process. The critique specifically cites concerns that Crawley’s SMILE trial switched outcomes to increase the likelihood of obtaining evidence of effectiveness.

 The Hampshire (UK) County Council Trading Standards Office filed a formal complaint against Phil Parker for claims made on the Lightning Process website concerning effects on CFS/ME:

The “CFS/ME” page of the website included the statements “Our survey found that 81.3 %* of clients report that they no longer have the issues they came with by day three of the LP course” and “The Lightning Process is working with the NHS on a feasibility study, please click here for further details, and for other research information click here”.

parker nhs advert
Seeming endorsements on Parker’s website. Two of them –Northern Ireland and NHS Suffolk subsequently complained that use of their insignias was unauthorized and they were quickly removed.

The “working with the NHS” refers to the collaboration with Dr. Easter Crawley.

The UK Advertising Standards Authority upheld this complaint, as well as about Parker’s claims about effectiveness with other conditions, including  multiple sclerosis, irritable bowel syndrome and fibromyalgia

 Another complaint in 2013 about claims on Phil Parker’s website was similarly upheld:

 The claims must not appear again in their current form. We welcomed the decision to remove the claims. We told Phil Parker Group not to make claims on websites within their control that were directly connected with the supply of their goods and services if those claims could not be supported with robust evidence. We also told them not to refer to conditions for which advice should be sought from suitably qualified health professionals.

 As we will see, these upheld charges of quackery occurred when parents of children participating in the SMILE trial were being vilified in the BMJ and elsewhere. Dr. Crawley was prominently featured in this vilification and was quoted in a celebration of its success by the Science Media Centre, which had orchestrated the vilification.

Captured cfs praker ad

The Research Ethics Committee approval of the SMILE trial and the aftermath

 I was not very aware of the CFS/ME literature, and certainly not all its controversies when the South West Research Ethics Committee (REC) reviewed the application for the SMILE trial and ultimately approved it on September 8, 2010.

I would have had strong opinions about it. I only first started blogging a little afterwards.  But I was very concerned about any patients being exposed to alternative and unproven medical treatments in other contexts that were not evidence-based – even more so to treatments for which promoters claimed implausible mechanisms by which they worked. I would not have felt it appropriate to inflict the Lightning Process on unsuspecting children. It is insufficient justification to put them a clinical trial simply because a particular treatment has not been evaluated.

 Prince Charles once advocated organic coffee enemas to treat advanced cancer. His endorsement generated a lot of curiosity from cancer patients. But that would not justify a randomized trial of coffee enemas. By analogy, I don’t think Dr. Esther Crawley had sufficient justification to conduct her trial, especially without warnings that that there was no scientific basis to expect the Lightning Process to work or that it would not hurt the children.

 I am concerned about clinical trials that have little likelihood of producing evidence that a treatment is effective, but that seemed designed to get these treatments into routine clinical care. it is now appreciated that some clinical trials have little scientific value but serve as experimercials or means of placing products in clinical settings. Pharmaceutical companies notoriously do this.

As it turned out, the SMILE trial succeeded admirably as a promotion for the Lightning Process, earning Phil Parker unknown but substantial fees through its use in the SMILE trial, but also in successful marketing throughout the NHS afterwards.

In short, I would been concerned about the judgment of Dr. Esther Crawley in organizing the SMILE trial. I would been quite curious about conflicts of interest and whether patients were adequately informed of how Phil Parker was benefiting.

The ethics review of the SMILE trial gave short shrift to these important concerns.

When the patient community and its advocate, Dr. Charles Shepherd, became aware of the SMILE trial’s approval, there were protests leading to re-evaluations all the way up to the National Patient Safety Agency. Examining an Extract of Minutes from South West 2 REC meeting held on 2 December 2010, I see many objections to the approval being raised and I am unsatisfied by the way in which they were discounted.

Patient, parent, and advocate protests escalated. If some acted inappropriate, this did not undermine the righteousness of others legitimate protest. By analogy, I feel strongly about police violence aimed against African-Americans and racist policies that disproportionately target African-Americans for police scrutiny and stoppng. I’m upset when agitators and provocateurs become violent at protests, but that does not delegitimize my concerns about the way black people are treated in America.

Dr. Esther Crawley undoubtedly experienced considerable stress and unfair treatment, but I don’t understand why she was not responsive to patient concerns nor  why she failed to honor her responsibility to protect child patients from exposure to unproven and likely harmful treatments.

Dr. Crawley is extensively quoted in a British Medical Journal opinion piece authored by a freelance journalist,  Nigel Hawkes:

Hawkes N. Dangers of research into chronic fatigue syndrome. BMJ. 2011 Jun 22;342:d3780.

If I had been on the scene, Dr. Crawley might well have been describing me in terms of how I would react, including my exercising of appropriate, legally-provided means of protest and complaint:

Critics of the method opposed the trial, first, Dr Crawley says, by claiming it was a terrible treatment and then by calling for two ethical reviews. Dr Shepherd backed the ethical challenge, which included the claim that it was unethical to carry out the trial in children, made by the ME Association and the Young ME Sufferers Trust. After re-opening its ethical review and reconsidering the evidence in the light of the challenge, the regional ethical committee of the NHS reiterated its support for the trial.

There was arguably some smearing of Dr. Shepherd, even in some distancing of him from the action of others:

This point of view, if not the actions it inspires, is defended by Charles Shepherd, medical adviser to and trustee of the ME Association. “The anger and frustration patients have that funding has been almost totally focused on the psychiatric side is very justifiable,” he says. “But the way a very tiny element goes about protesting about it is not acceptable.

This article escalated with unfair comparisons to animal rights activists, with condemnation of appropriate use of channels of complaint – reporting physicians to the General Medical Council.

The personalised nature of the campaign has much in common with that of animal rights activists, who subjected many scientists to abuse and intimidation in the 1990s. The attitude at the time was that the less said about the threats the better. Giving them publicity would only encourage more. Scientists for the most part kept silent and journalists desisted from writing about the subject, partly because they feared anything they wrote would make the situation worse. Some journalists have also been discouraged from writing about CFS/ME, such is the unpleasant atmosphere it engenders.

While the campaigners have stopped short of the violent activities of the animal rights groups, they have another weapon in their armoury—reporting doctors to the GMC. Willie Hamilton, an academic general practitioner and professor of primary care diagnostics at Peninsula Medical School in Exeter, served on the panel assembled by the National Institute for Health and Clinical Excellence (NICE) to formulate treatment advice for CFS/ME.

Simon Wessely and the Principal Investigator of the PACE trial, Peter White, were given free rein to dramatize their predicament posed by the protest. Much later, in the 2016 Lower Tribunal Hearing, testimony would be given by PACE

Co-Investigator Trudie Chalder would much later (2016) cast doubt on whether the harassment was as severe or violent as it was portrayed. Before that, the financial conflicts of interest of Peter White that were denied in the article would be exposed.

In response to her testimony, the UK Information Officer stated:

Professor Chalder’s evidence when she accepts that unpleasant things have been said to and about PACE researchers only, but that no threats have been made either to researchers or participants.

But in 2012, a pamphlet celebrating the success of The Science Media Centre started by Wessely would be rich in indiscreet quotes from Esther Crawley. The article in BMJ was revealed to be part of a much larger orchestrated campaign to smear, discredit and silence patients, parents, advocates and their allies.

Dr. Esther Crawley’s participation in a campaign organized by the Science Media Center to discredit patients, parents, advocates and supporters.

 The SMC would later organize a letter writing campaign to Parliament in support of Peter White and his refusal to release the PACE data to Alem Mattheees who had made a requestunder the Freedom of Information Act. The letter writing campaign was an effort to get scientific data excluded from the provisions of the freedom of information act. The effort failed and the data were subsequently released.

But here is how Esther Crawley described her assistance:

The SMC organised a meeting so we could discuss what to do to protect researchers. Those who had been subject to abuse met with press officers, representatives from the GMC and, importantly, police who had dealt with the  animal rights campaign. This transformed my view of  what had been going on. I had thought those attacking us were “activists”; the police explained they were “extremists”.

And

We were told that we needed to make better use of the law and consider using the press in our favour – as had researchers harried by animal rights extremists. “Let the public know what you are trying to do and what is happening to you,” we were told. “Let the public decide.”

And

I took part in quite a few interviews that day, and have done since. I was also inundated with letters, emails and phone calls from patients with CFS/ME all over the world asking me to continue and not “give up”. The malicious, they pointed out, are in a minority. The abuse has stopped completely. I never read the activists’ blogs, but friends who did told me that they claimed to be “confused” and “upset” – possibly because their role had been switched from victim to abuser. “We never thought we were doing any harm…”

 The patient community and its allies are still burdened by the damage of this effort and are rebuilding its credibility only slowly. Only now are they beginning to get an audience as suffering human beings with significant, legitimate unmet needs. Only now are they escaping the stigmatization that occurred at this time with Esther Crawley playing a key role.

Where does this leave us?

stop posterParents are being asked to enroll in a clinical trial without clear benefit to the children but with the possibility of considerable risk from the graded exercise. They are being asked by Esther Crawley, a physician, who has previously inflicted a quack treatment on their children with CFS/ME in the guise of a clinical trial, for which he is never published the resulting data. She has played an effective role in damaging the legitimacy and capacity of patients and parents to complain.

Given this history and these factors, why would a parent possibly want to enroll their children in the MAGENTA trial? Somebody please tell me.

Special thanks to all the patient citizen-scientists who contributed to this blog post. Any inaccuracies or excesses are entirely my own, but these persons gave me substantial help. Some are named in the blog, but others prefer anonymity.

 All opinions expressed are solely those of James C Coyne. The blog post in no way conveys any official position of Mind the Brain, PLOS blogs or the larger PLOS community. I appreciate the free expression of  personal opinion that I am allowed.

 

 

 

 

 

 

Relaxing vs Stimulating Acupressure for Fatigue Among Breast Cancer Patients: Lessons to be Learned

  • A chance to test your rules of thumb for quickly evaluating clinical trials of alternative or integrative  medicine in prestigious journals.
  • A chance to increase your understanding of the importance of  well-defined control groups and blinding in evaluating the risk of bias of clinical trials.
  • A chance to understand the difference between merely evidence-based treatments versus science-based treatments.
  • Lessons learned can be readily applied to many wasteful evaluations of psychotherapy with shared characteristics.

A press release from the University of Michigan about a study of acupressure for fatigue in cancer patients was churnaled  – echoed – throughout the media. It was reproduced dozens of times, with little more than an editor’s title change from one report to the next.

Fortunately, the article that inspired all the fuss was freely available from the prestigious JAMA: Oncology. But when I gained access, I quickly saw that it was not worth my attention, based on what I already knew or, as I often say, my prior probabilities. Rules of thumb is a good enough term.

So the article became another occasion for us to practice our critical appraisal skills, including, importantly, being able to make reliable and valid judgments that some attention in the media is worth dismissing out of hand, even when tied to an article in a prestigious medical journal.

The press release is here: Acupressure reduced fatigue in breast cancer survivors: Relaxing acupressure improved sleep, quality of life.

A sampling of the coverage:

sample coverage

As we’ve come to expect, the UK Daily Mail editor added its own bit of spin:

daily mailHere is the article:

Zick SM, Sen A, Wyatt GK, Murphy SL, Arnedt J, Harris RE. Investigation of 2 Types of Self-administered Acupressure for Persistent Cancer-Related Fatigue in Breast Cancer Survivors: A Randomized Clinical Trial. JAMA Oncol. Published online July 07, 2016. doi:10.1001/jamaoncol.2016.1867.

Here is the Trial registration:

All I needed to know was contained in a succinct summary at the Journal website:

key points

This is a randomized clinical trial (RCT) in which two active treatments that

  • Lacked credible scientific mechanisms
  • Were predictably shown to be better than
  • A routine care that lacked the positive expectations and support.
  • A primary outcome assessed by  subjectiveself-report amplified the illusory effectiveness of the treatments.

But wait!

The original research appeared in a prestigious peer-reviewed journal published by the American Medical Association, not a  disreputable journal on Beall’s List of Predatory Publishers.

Maybe  this means publication in a peer-reviewed prestigious journal is insufficient to erase our doubts about the validity of claims.

The original research was performed with a $2.65 million peer-reviewed grant from the National Cancer Institute.

Maybe NIH is wasting scarce money on useless research.

What is acupressure?

 According to the article

Acupressure, a method derived from traditional Chinese medicine (TCM), is a treatment in which pressure is applied with fingers, thumbs, or a device to acupoints on the body. Acupressure has shown promise for treating fatigue in patients with cancer,23 and in a study24 of 43 cancer survivors with persistent fatigue, our group found that acupressure decreased fatigue by approximately 45% to 70%. Furthermore, acupressure points termed relaxing (for their use in TCM to treat insomnia) were significantly better at improving fatigue than another distinct set of acupressure points termed stimulating (used in TCM to increase energy).24 Despite such promise, only 5 small studies24– 28 have examined the effect of acupressure for cancer fatigue.

290px-Acupuncture_point_Hegu_(LI_4)You can learn more about acupressure here. It is a derivative of acupuncture, that does not involve needles, but the same acupuncture pressure points or acupoints as acupuncture.

Don’t be fooled by references to traditional Chinese medicine (TCM) as a basis for claiming a scientific mechanism.

See Chairman Mao Invented Traditional Chinese Medicine.

Chairman Mao is quoted as saying “Even though I believe we should promote Chinese medicine, I personally do not believe in it. I don’t take Chinese medicine.”

 

Alan Levinovitz, author of the Slate article further argues:

 

In truth, skepticism, empiricism, and logic are not uniquely Western, and we should feel free to apply them to Chinese medicine.

After all, that’s what Wang Qingren did during the Qing Dynasty when he wrote Correcting the Errors of Medical Literature. Wang’s work on the book began in 1797, when an epidemic broke out in his town and killed hundreds of children. The children were buried in shallow graves in a public cemetery, allowing stray dogs to dig them up and devour them, a custom thought to protect the next child in the family from premature death. On daily walks past the graveyard, Wang systematically studied the anatomy of the children’s corpses, discovering significant differences between what he saw and the content of Chinese classics.

And nearly 2,000 years ago, the philosopher Wang Chong mounted a devastating (and hilarious) critique of yin-yang five phases theory: “The horse is connected with wu (fire), the rat with zi (water). If water really conquers fire, [it would be much more convincing if] rats normally attacked horses and drove them away. Then the cock is connected with ya (metal) and the hare with mao (wood). If metal really conquers wood, why do cocks not devour hares?” (The translation of Wang Chong and the account of Wang Qingren come from Paul Unschuld’s Medicine in China: A History of Ideas.)

Trial design

A 10-week randomized, single-blind trial comparing self-administered relaxing acupressure with stimulating acupressure once daily for 6 weeks vs usual care with a 4-week follow-up was conducted. There were 5 research visits: at screening, baseline, 3 weeks, 6 weeks (end of treatment), and 10 weeks (end of washout phase). The Pittsburgh Sleep Quality Index (PSQI) and Long-Term Quality of Life Instrument (LTQL) were administered at baseline and weeks 6 and 10. The Brief Fatigue Inventory (BFI) score was collected at baseline and weeks 1 through 10.

Note that the trial was “single-blind.” It compared two forms of acupressure, relaxing versus stimulating. Only the patient was blinded to which of these two treatments was being provided, except patients clearly knew whether or not they were randomized to usual care. The providers were not blinded and were carefully supervised by the investigators and provided feedback on their performance.

The combination of providers not being blinded, patients knowing whether they were randomized to routine care, and subjective self-report outcomes together are the makings of a highly biased trial.

Interventions

Usual care was defined as any treatment women were receiving from health care professionals for fatigue. At baseline, women were taught to self-administer acupressure by a trained acupressure educator.29 The 13 acupressure educators were taught by one of the study’s principal investigators (R.E.H.), an acupuncturist with National Certification Commission for Acupuncture and Oriental Medicine training. This training included a 30-minute session in which educators were taught point location, stimulation techniques, and pressure intensity.

Relaxing acupressure points consisted of yin tang, anmian, heart 7, spleen 6, and liver 3. Four acupoints were performed bilaterally, with yin tang done centrally. Stimulating acupressure points consisted of du 20, conception vessel 6, large intestine 4, stomach 36, spleen 6, and kidney 3. Points were administered bilaterally except for du 20 and conception vessel 6, which were done centrally (eFigure in Supplement 2). Women were told to perform acupressure once per day and to stimulate each point in a circular motion for 3 minutes.

Note that the control/comparison condition was an ill-defined usual care in which it is not clear that patients received any attention and support for their fatigue. As I have discussed before, we need to ask just what was being controlled by this condition. There is no evidence presented that patients had similar positive expectations and felt similar support in this condition to what was provided in the two active treatment conditions. There is no evidence of equivalence of time with a provider devoted exclusively to the patients’ fatigue. Unlike patients assigned to usual care, patients assigned to one of the acupressure conditions received a ritual delivered with enthusiasm by a supervised educator.

Note the absurdity of the  naming of the acupressure points,  for which the authority of traditional Chinese medicine is invoked, not evidence. This absurdity is reinforced by a look at a diagram of acupressure points provided as a supplement to the article.

relaxation acupuncture pointsstimulation acupressure points

 

Among the many problems with “acupuncture pressure points” is that sham stimulation generally works as well as actual stimulation, especially when the sham is delivered with appropriate blinding of both providers and patients. Another is that targeting places of the body that are not defined as acupuncture pressure points can produce the same results. For more elaborate discussion see Can we finally just say that acupuncture is nothing more than an elaborate placebo?

 Worth looking back at credible placebo versus weak control condition

In a recent blog post   I discussed an unusual study in the New England Journal of Medicine  that compared an established active treatment for asthma to two credible control conditions, one, an inert spray that was indistinguishable from the active treatment and the other, acupuncture. Additionally, the study involved a no-treatment control. For subjective self-report outcomes, the active treatment, the inert spray and acupuncture were indistinguishable, but all were superior to the no treatment control condition. However, for the objective outcome measure, the active treatment was more effective than all of the three comparison conditions. The message is that credible placebo control conditions are superior to control conditions lacking and positive expectations, including no treatment and, I would argue, ill-defined usual care that lacks positive expectations. A further message is ‘beware of relying on subjective self-report measures to distinguish between active treatments and placebo control conditions’.

Results

At week 6, the change in BFI score from baseline was significantly greater in relaxing acupressure and stimulating acupressure compared with usual care (mean [SD], −2.6 [1.5] for relaxing acupressure, −2.0 [1.5] for stimulating acupressure, and −1.1 [1.6] for usual care; P < .001 for both acupressure arms vs usual care), and there was no significant difference between acupressure arms (P  = .29). At week 10, the change in BFI score from baseline was greater in relaxing acupressure and stimulating acupressure compared with usual care (mean [SD], −2.3 [1.4] for relaxing acupressure, −2.0 [1.5] for stimulating acupressure, and −1.0 [1.5] for usual care; P < .001 for both acupressure arms vs usual care), and there was no significant difference between acupressure arms (P > .99) (Figure 2). The mean percentage fatigue reductions at 6 weeks were 34%, 27%, and −1% in relaxing acupressure, stimulating acupressure, and usual care, respectively.

These are entirely expectable results. Nothing new was learned in this study.

The bottom line for this study is that there was absolutely nothing to be gained by comparing an inert placebo condition to another inert placebo condition to an uninformative condition without clear evidence the control condition offered control of nonspecific factors – positive expectations, support, and attention. This was a waste of patient time and effort, as well as government funds, and produced results that were potentially misleading to patients. Namely, results are likely to be misinterpreted the acupressure is an effective, evidence-based treatment for cancer-related fatigue.

How the authors explained their results

Why might both acupressure arms significantly improve fatigue? In our group’s previous work, we had seen that cancer fatigue may arise through multiple distinct mechanisms.15 Similarly, it is also known in the acupuncture literature that true and sham acupuncture can improve symptoms equally, but they appear to work via different mechanisms.40 Therefore, relaxing acupressure and stimulating acupressure could elicit improvements in symptoms through distinct mechanisms, including both specific and nonspecific effects. These results are also consistent with TCM theory for these 2 acupoint formulas, whereby the relaxing acupressure acupoints were selected to treat insomnia by providing more restorative sleep and improving fatigue and the stimulating acupressure acupoints were chosen to improve daytime activity levels by targeting alertness.

How could acupressure lead to improvements in fatigue? The etiology of persistent fatigue in cancer survivors is related to elevations in brain glutamate levels, as well as total creatine levels in the insula.15 Studies in acupuncture research have demonstrated that brain physiology,41 chemistry,42 and function43 can also be altered with acupoint stimulation. We posit that self-administered acupressure may have similar effects.

Among the fallacies of the authors’ explanation is the key assumption that they are dealing with a specific, active treatment effect rather than a nonspecific placebo intervention. Supposed differences between relaxing versus stimulating acupressure arise in trials with a high risk of bias due to unblinded providers of treatment and inadequate control/comparison conditions. ‘There is no there there’ to be explained, to paraphrase a quote attributed to Gertrude Stein

How much did this project cost?

 According to the NIH Research Portfolios Online Reporting Tools website, this five-year project involved support by the federal government of $2,265,212 in direct and indirect costs. The NCI program officer for investigator-initiated  R01CA151445 is Ann O’Marawho serves ina similar role for a number of integrative medicine projects.

How can expenditure of this money be justified for determining whether so-called stimulating acupressure is better than relaxing acupressure for cancer-related fatigue?

 Consider what could otherwise have been done with these monies.

 Evidence-based versus science based medicine

Proponents of unproven “integrative cancer treatments” can claim on the basis of the study the acupressure is an evidence-based treatment. Future Cochrane Collaboration Reviews may even cite this study as evidence for this conclusion.

I normally label myself as an evidence-based skeptic. I require evidence for claims of the efficacy of treatments and am skeptical of the quality of the evidence that is typically provided, especially when it comes from enthusiasts of particular treatments. However, in other contexts, I describe myself as a science based medicine skeptic. The stricter criteria for this term is that not only do I require evidence of efficacy for treatments, I require evidence for the plausibility of the science-based claims of mechanism. Acupressure might be defined by some as an evidence-based treatment, but it is certainly not a science-based treatment.

For further discussion of this important distinction, see Why “Science”-Based Instead of “Evidence”-Based?

Broader relevance to psychotherapy research

The efficacy of psychotherapy is often overestimated because of overreliance on RCTs that involve inadequate comparison/control groups. Adequately powered studies of the comparative efficacy of psychotherapy that include active comparison/control groups are infrequent and uniformly provide lower estimates of just how efficacious psychotherapy is. Most psychotherapy research includes subjective patient self-report measures as the primary outcomes, although some RCTs provide independent, blinded interview measures. A dependence on subjective patient self-report measures amplifies the bias associated with inadequate comparison/control groups.

I have raised these issues with respect to mindfulness-based stress reduction (MBSR) for physical health problems  and for prevention of relapse in recurrence in patients being tapered from antidepressants .

However, there is a broader relevance to trials of psychotherapy provided to medically ill patients with a comparison/control condition that is inadequate in terms of positive expectations and support, along with a reliance on subjective patient self-report outcomes. The relevance is particularly important to note for conditions in which objective measures are appropriate, but not obtained, or obtained but suppressed in reports of the trial in the literature.