Tuesday, 23 April 2019

Research Ethics and Conflicts of Interest

This will be a long post. There is a lot of detail and most of it is ugly. It concentrates on ethical issues - it doesn't go into great depth analysing the results (others will do that better - and this blog has a somewhat different audience). 

It involves a pilot study on children with Attention deficit hyperactivity disorder (ADHD) involving homeopathy and "nutritional therapy" and the award of grants by the Homeopathy Research Institute (HRI).

There are questions about why the trial was permitted.

Philippa Fibert
Fibert has been mentioned on this blog before. Fibert is a homeopath and member of the Society of Homeopaths (SoH). Fibert is listed on the CEASE therapy website. It is likely that she was among the homeopaths sent an enforcement notice by the Advertising Standards Authority (ASA). From what Fibert has said in various places, she has used CEASE therapy, does believe it works and has "trained" others in its use.

Fibert is a "research consultant" for the SoH and a co-author of this submission on anti-microbial resistance. It states -


We provide evidence to support our claims that:
  • Homeopathy is a demonstrably effective treatment option for a range of human infectious diseases. 
  • Homeopathic treatment can be at least equivalent in effectiveness to antibiotics for certain human infectious diseases.
  • Homeopathy can offer an effective alternative to non-essential antimicrobial usage in animal husbandry. Homeopathy has a robust track record of controlling, managing and preventing outbreaks of infectious diseases on a large scale.
  • Homeopathy provides a rich potential for the development of novel antimicrobial therapies (that are not susceptible to the problems of developing microbial resistance) which deserves adequate research funding and support.
And then goes on to do nothing of the sort. Fibert was also awarded a Fellowship by the SoH. The SoH has awarded Fellowships to some dubious characters including Jeremy Sherr and Misha Norland.

Fibert makes much of having been a teacher, home educator and aspects of her family life. This is largely irrelevant. What isn't is her belief in the efficacy of homeopathy. This video is instructive -




Clare Relton
Relton was a practicing homeopath but these days is a Senior Lecturer in Clinical Trials at Queen Mary University of London and Honorary Senior Research Fellow at the University of Sheffield. Relton was a trustee of the HRI and is currently on their Scientific Advisory CommitteeRelton was "research director" for the SoH. 

Relton is also director of Wellforce, a complementary health clinic (which is not registered with Care Quality Commission).

Case Series
As part of a MSc in Research Methods in Psychology. Fibert carried out a study of children with ADHD involving homeopathy. It's not clear if this is the same as the current Masters by Research (MRes). What homeopathy has to do with psychology is unclear. 

This was subsequently written up as A comparative consecutive case series of 20 children with a diagnosis of ADHD receiving homeopathic treatment,compared with 10 children receiving usual care ("case series").

It's not good. It shares ethical approval problems with the pilot study (no NHS ethical approval) but other problems include - 
A novel methodology based on isopathic prescriptions of parent reported environmental stressors was found to be particularly effective.
And 
Five children (25%) measured large changes. Three had additional diagnoses of autism spectrum disorders and four described environmental insults and were treated using CEASE methodology.
Fibert was using CEASE to treat "parent reported environmental stressors"? Whatever that might mean?
Homeopathic remedies were prescribed in pill or liquid form, sourced from homeopathic pharmacies ‘Helios’ or ‘Vital Homeopathics’, packaged and sent to participants by Marlow Homeopathic Clinic.
Those who have read this blog before are likely aware that the supply to lay homeopaths of unlicensed medicines is a breach of the Human Medicines Regulation 2012. For them to supply them to consumers would also be in breach. What is worse is that Vital Homeopathics is not a pharmacy and nor is the person behind a pharmacist. They have advertised remedies for CEASE therapy in the past.

The results are not compelling.

Pilot Study
Fibert's PhD thesis is called Rethinking ADHD intervention trials: the feasibility testing of two treatments and a methodology. It is 359 pages and 81,000 words long. A lot of the content is extraneous and it is difficult not to come away with the impression of attempts to justify a naive bias as well as a leaning towards conspiracy theories.

There is also the Protocol for the STAR (Sheffield Treatments for ADHD) project:an internal pilot study assessing the feasibility of the Trials within Cohorts (TwiCs) designto test the effectiveness of interventions for children with ADHD. It is not interesting in itself but does reveal a few key things.

Ethical Approval
Despite a Freedom of Information Act request, it has not be possible to obtain the materials that would have been submitted to the University of Sheffield School of Health and Related Research (ScHARR) Research Ethics committee (REC). To be blunt, experience has shown that homeopaths often do not provide clear or complete information. Sometimes out of ignorance, sometimes deliberately so.

Sheffield provides copious guidance to researchers on applying for ethical approval. And there is specialist guidance on research involving children which includes -
On commencing research, the first question to ask is: who are the gatekeepers for the research project? The school or childcare facility in question? Parents? Health and social care authorities? In many countries, access to children and young people is controlled by a range of individual and institutional gate-keepers. For example, researchers may need to obtain official government clearance, such as criminal records checks in response to child protection concerns, before research can commence. These legal/official requirements vary between countries. In addition, however, schools, social care and health authorities may place requirements on researchers in relation to the nature and conduct of their research that raise other ethical issues. For example, schools may insist that research is not carried out during lesson times and limit researchers’ access to children to playtimes. Researchers need to consider the extent to which using children’s free time at school, when they may want to play or be with their friends, raises ethical issues
The importance of this will become apparent. 

The protocol reveals -
The study was approved under the University of Sheffield’s Ethics Review Procedure by the School of Health and Related Research (ScHARR) Research Ethics committee (REC) on 30/4/15, application number 003424. 
The University of Sheffield is the Research Governance Sponsor (University Research Management System (UMRS) number: 143647). The project was classified as a ‘human-interventional study’, under the University’s quality assurance procedure for such studies, requiring it to be risk assessed, and was considered to be low risk. They confirmed that a trial measuring treatment by a homoeopath and a nutritionist did not constitute a Clinical Trial of a Medicinal Product (CTIMP); therefore, Medicines Regulatory Health Authority (MRHA) approval was not required.
It is Medicines and Healthcare products Regulatory Agency (MHRA) that approval must be applied for in the Clinical Trial of an Investigatory Medicinal Product (CTIMP). Whilst these errors may seem minor, they suggest an unfamiliarity with regulation.

This contains an explanation of the role and remit of a REC in clear language. It doesn't matter that it is NHS focused - the same principles apply across the board. It contains something very interesting - 

A REC must not give a favourable opinion where it knows the research will break the law. However, it is not the role of the REC to offer a legal opinion on research proposals, although it may advise the researcher, sponsor or host organisation whenever it considers that legal advice might be helpful to them. Researchers, sponsors and organisations where research is carried out remain responsible for making sure the research is conducted in accordance with the requirements of law, relevant regulators and guidance, e.g. the UK Policy Framework for Health and Social Care Research (or other recognised standards of good practice, as applicable), the Data Protection Act and the Codes of Practice issued under the Mental Capacity Act and Human Tissue Act.

NHS Ethical Approval and MHRA trial registration
The trial did not have NHS Ethical Approval. In fact, it was never applied for -
The decision was made not to apply for NHS ethical approval to recruit through the NHS (section 6.2) because sufficient numbers of participants were recruited outside of NHS services. Furthermore the process is lengthy and can be difficult to obtain for trials of homeopathy (Viksveen, http://etheses.whiterose.ac.uk/11875/). It is disputable whether this influenced recruitment of a representative sample. One the one hand it may have contributed to recruitment of hard-to reach participants, since those satisfactorily engaged with usual care do not look elsewhere, whilst those joining the STAR cohort may have been motivated by a feeling of unmet need. On the other hand it restricted access to specific target groups of ‘at need’ children such as the ‘looked after’ children under the care of Sheffield City council. 
The question of whether NHS ethical approval was a pre-requisite for a study of ADHD was resolved (section 8.2), but raised interesting questions and was not a clear-cut decision. The question centred on response to the Medicines Health Authority (MHA) algorithm: “Will your study involve research participants identified from, or because of their past or present use of services (adult and children’s health care within the NHS and adult social care)”. RIS stated that “the STAR study only recruited children where the carers self-reported that their child has received a diagnosis of ADHD. The diagnosis itself could have come from an NHS service, but it may have come from elsewhere (e.g. a health service in another country) and hence the participants have not be identified from, or because of, their use of the NHS specifically”. The STAR management team concurred with this. The ADHD population intersects with, and impacts on many publicly funded systems and services, of which health care is only one, such as social care, the criminal justice system and education. However, NHS clinicians maintain that all children with ADHD are under the care of the NHS and therefore NHS ethical approval is required. Furthermore, care within other services tends to include NHS care.

RIS = University of Sheffield Research and Innovation Services. NHS ethical approval should happen within 60 calendar days if there are no problems with the trial submission. To quote from the protocol -
Homoeopaths are registered with one of the four main bodies representing homoeopaths in the UK. Nutritional therapists are registered with the British Association of Applied Nutrition and Nutritional Therapy and are members of the Complementary and Natural Healthcare Council. All therapists are CRB checked, complete an on-line NSPCC child protection course (https://www.nspcc.org.uk/what-you-can-do/get-expert-training), attend a 1-day training course on risk and receive guidelines in management of ADHD and serious adverse events.
Homeopaths and nutritional therapists are not legally recognised as health professionals. They are treated as medically unqualified lay-persons.

There is more -
Application to advertise the project was made to Sheffield Parent Carers, an independent, local authority funded group of 1,000+ carers of children with disabilities including 150+ with ADHD. They agreed to post an advertisement in their newsletter and send an email to all members registering a child with ADHD. 
Sheffield city council Multi Agency Support Teams (MAST) and the research office for children’s services were applied to. MAST were too busy to consider the application, but the city council felt the trial met their concerns regarding appropriate management of safeguarding, data protection, and consenting children (Appendices 9 & 10). They requested that literature refer to ‘carers’ rather than ‘parents’ which was done. They were particularly positive about the trial design because children would not be offered the possibility of something they may not get. However, when the STAR project was presented to their ‘Looked after children’ committee (chaired by an NHS CAMHS paediatrician) the committee considered that NHS ethical approval was a pre-requisite. 
Family Action Sheffield were approached. Sheffield City council contract Family Action Sheffield to run 10-week parenting programmes and conduct home visits for newly diagnosed ADHD families. Permission was gained from national Family Action to advertise the trial to families they work with. Two weeks after the STAR project started recruiting there was a breach of protocol, whereby a Family Action worker erroneously handed out flyers within CAMHS: Family Action workers sometimes work alongside NHS staff in NHS premises, but since NHS ethical approval had not been obtained, recruitment should not have occurred during combined sessions or on NHS premises. It was made clear to Family Action workers that the study does not have NHS REC approval. 
The breach of protocol resulted in a challenge to the STAR project recruitment strategy. It was claimed that NHS approval is required for all children diagnosed with ADHD. This was refuted by ScHARR research ethics committee, University of Sheffield Research and Innovation services, and the chair of the steering committee, who all confirmed that NHS ethical approval was not a pre-requisite (see discussion section 9.1.1).
NHS ethical approval is not legally required by the Medicines for Human Use (Clinical Trials) Regulations 2004 but not seeking is poor practice at best. The ethics of paediactric trials are different from those involving adults - because children can not consent. It can be argued that the NHS should be regarded as a gatekeeper for children under their care.

This NHS guidance on trials involving children is helpful. Whilst not mandatory -
Children and young people should be involved in the decision-making process whenever possible. You should ensure that they receive information about your trial, which is understandable to them.
There is something strange in the pilot study as well -
The first version of the pilot trial conceived one arm as a trial of polyunsaturated fatty acids (PUFAs). When the University of Sheffield Research and Innovation services (RIS) were applied to, they recommended contacting the Medicines Health Regulatory Authority (MHRA) in case this arm might be considered a Clinical Trial of a Medicinal Product (CTIMP) and therefore require MHRA approval. The MRHA did indeed deem that the PUFAs were being tested as a medicinal product. Therefore to ensure that the study would not be classified as a CTIMP, with all the additional bureaucracy that would entail, the PUFA arm was substituted with ‘treatment by a nutritional therapist’.
There is guidance. A strict interpretation of the Regulations 2012 would class homeopathic remedies used in the trial as Investigational Medicinal Products. UK law treats homeopathic remedies as medicines. Thus it seems very likely that the pilot study is a CTIMP and an application to the MHRA would have been necessary.

What was the pilot study supposed to do?
This thesis addresses the question: “is the Trials within Cohorts (TwiCs) design feasible to generate evidence about the effectiveness of interventions for ADHD?”
TwiCs stands for "Trials within cohorts" - which is an invention of Relton (a more detailed explanation can be found here). It uses a comparison of nutritional therapy and homeopathy as adjunctive treatments for ADHD to test this. There was a "treatment as usual" control group.

But this is not how the study is being communicated to the homeopathic community et al. It is presented as a trial of homeopathic treatment for ADHD. 

Recruitment and retainment issues
As the section on NHS ethical approval shows, recruitment to the study was per force restricted. This is expanded on -
Recruitment from nationally-funded ADHD facilities such as special schools, secure units, NHS based facilities, and children engaged with support services was not successful. Nor was it possible to recruit from the NIHR-funded Yorkshire and Humber CLAHRC ADHD health tracker cohort. Either NHS ethical approval would have had to be obtained, or there was minimal take up from advertisement, or the process of obtaining the approvals required was too lengthy and onerous. Nor was permission received to recruit from the Newcastle University autism spectrum database (ASD-UK).
Parents were recruited by a number of other routes. As already mentioned, the Sheffield branch of Family Action were used but so where a number of other routes -
As no NHS approval was obtained, the STAR project recruited through a broad variety of non-NHS sources such as local authority based organisations, schools, university based events and listings, clinically relevant support groups, clinically relevant conferences, and social media.
There is a website and a Facebook page. A flyer was sent out that contains roughly the same information. Note that none of these are explicit in what treatments are actually being offered (although the Facebook page does a long time after initial recruitment). A questionnaire (either paper or online) was completed by carers which determined eligibility to the trial. If eligible, a letter was sent to carers for themselves and the child to sign and return - effectively this would be the consent.

Informed parental consent and at the very least assent from the children would be required to participate the pilot study. Yet -
Homeopaths reported that carers needed explanations about what to expect from a homeopathic remedy, sometimes found the different approach difficult to grasp, but were often intrigued. They reported that homeopathic remedies were well adhered to.
Difficult to grasp? The letter sent to carers who completed the questionnaire is unrevealing of what homeopathy actually is. It directs them to this on the SoH website. But it can not be expected that someone will type in that link on a computer to view the information and even if the information was read, is it possible to give informed consent based on what is essentially marketing material? To quote part of it -
Homeopathy is based on the principle that you can treat ‘like with like’, that is, a substance which causes symptoms when taken in large doses, can be used in small amounts to treat similar symptoms. For example, drinking too much coffee can cause sleeplessness and agitation, so according to this principle, when made into a homeopathic medicine, it could be used to treat people with these symptoms. This concept is sometimes used in conventional medicine, for example, the stimulant Ritalin is used to treat patients with ADHD, or small doses of allergens such as pollen are sometimes used to de-sensitise allergic patients.
False comparison, especially in the case of Ritalin and ADHD - the use of certain stimulants is to deal with attention deficit, not activity levels. Allergen immunotherapy is very different from the purported mechanism of homeopathy. No mention is made of the non-existence of any real evidence base for the efficacy of homeopathy, let alone homeopathy. This is unlikely to satisfy the requirements of the Regulations 2004. 

The nutritional therapy letter states -
Nutritional therapy is individually tailored supplements, information, and advice about nutrition to help ADHD. This means you might be given some supplements considered helpful for ADHD, some information about foods which might be aggravating your child’s ADHD, and an individually tailored plan with some menu suggestions.
Considered helpful by who? Supplements would be helpful for those with dietary deficiencies, but nutritional therapists can not diagnose them. The evidence for supplement use and dietary changes for ADHD is very poor. This is not mentioned. But at least there is some plausibility for dietary interventions for ADHD. 

This level of information would not have been acceptable in an NHS approved trial. To quote variously from the UK policy framework for health and social care research issued Health Research Authority -
Where consent is sought: a. potential research participants should be provided, normally by the research team, with the information they need to help them decide whether they wish to take part in research or not, and should be given reasonable time to reach their decision. The information should be provided in a suitable format. Unless otherwise justified (e.g. by feedback from public involvement), the information should include a concise explanation of relevant research evidence and research in progress that shows why the proposed research is justified;
And
Proportionality should be applied to the provision of information to potential research participants. The more research deviates from established practice or otherwise detrimentally affects the balance between the anticipated risks and benefits, the greater the amount of information that needs to be provided to potential participants. By the same token, the closer the research is to standard practice, the less need there is to provide patients and service users with detailed and lengthy information. For instance, pragmatic trials looking at the effectiveness of routinely used standard treatments should be facilitated so that patients can be recruited in a way that complies with the law but does not unduly burden either patients or the care professionals seeking their consent.
Schedule 1, Part 4 CONDITIONS AND PRINCIPLES WHICH APPLY IN RELATION TO A MINOR of the Regulations 2004 contains -


8.  No incentives or financial inducements are given—
(a)to the minor; or
(b)to a person with parental responsibility for that minor or, as the case may be, the minor’s legal representative,
except provision for compensation in the event of injury or loss. 
The pilot study reveals that £10 vouchers were given to certain carers -
After discussion with the steering committee and approval from the ethics committee (amendment number 4, Table 16), an incentive was added. From 28/4/16 onwards, on receipt of CQs, participants were sent a £10 Boots voucher in a card thanking them for being part of the STAR project. Vouchers were also sent to those who had previously returned CQs. This improved the return rate to 72% (section 7.4.1).
This would appear to be in breach of the Regulations 2012.

Who was involved? 
In September 2016 five homeopaths were recruited from Sheffield or nearby and saw participants at Wellforce clinic, Sheffield, Western House consulting rooms, Barnsley, or in participants own homes. Homeopaths did not have particular experience with ADHD, however, 3/5 had experience of working with challenging families. All were registered with the Society of Homeopaths. 
In January 2017 the study started recruiting participants from across the UK requiring online consultations. Since two homeopaths did not want to conduct on-line consultations and three were inexperienced in conducting on-line consultations (no experience, or just one experience), three more homeopaths, experienced in conducting on-line consultations, were recruited from a Complementary Therapies clinic in Marlow, Buckinghamshire, of whom one (myself) had experience of treating children with ADHD, whilst two had experience of working with challenging families.
It is possible narrow down the homeopaths involved. Some have been previously mentioned by this blog. The Wellforce homeopaths are -

Annie Williams (offers Emotional Freedom Technique - EFT)
Gill Upham (did offer CEASE at one point)
June Dinwoodie (offers herbalism)
Krys Chandler

The homeopath at Western House is Jackie Raw. Marlow Homeopathy are

Elizabeth Courtis (who uses the Asyra machine and unspecified allergy & food intolerance testing, likely using the machine)
Jo O'Flanagan (who offers Craniosacral Therapy - CST)
Tim Lloyd
Vicki Steedman (who offers CST)
Kay Willis (another Asyra user)

Fibert used to work there too. 

It is unknown where the nutritional therapists came from or who they are but it is reported that they were all members of BANT and thus also fall under the Complementary and Natural Healthcare Council (CNHC). Nutritional therapies sometimes offer other therapies. Some are know to use the Asyra machine for example.

There was a "management committee" consisting of just Fibert and Relton. There was a "steering committee" additionally comprised of -

Prof David Daley (Nottingham University) (Chair)
Prof Mike Campbell (Medical Statistics, ScHARR, UoS) 
Dr Tessa Peasgood (Health Economics and Decision Science (HEDS), ScHARR, UoS) 
Dr Liz Williams (Human Nutrition, Oncology, UoS) 
Catherine Witzmann (Doncaster NHS) - who is likely an occupational therapist with Doncaster CAHMS
Gill Badby (parent representative, Sheffield NHS) 
Heather Wingfield (parent representative)

Competence and Safeguarding Issues
From what can be worked out, no medical professional was involved in this pilot study. To quote from UK policy framework for health and social care research issued -
Principle 2: Competence All the people involved in managing and conducting a research project are qualified by education, training and experience, or otherwise competent under the supervision of a suitably qualified person, to perform their tasks.
This blog has long made the case that the treatment of autism is beyond the competence of any homeopath. The same would also apply to ADHD. It is also the case of some of the children also had ASD. That a homeopath is registered with the Society of Homeopaths means very little.

Nutritional therapists are not dieticians (who are regulated) or nutritionists. Nutritional therapists are notorious for bad (even dangerous) advice and selling expensive tests and supplements of little or no value.

It is questionable whether homeopaths or nutritional therapists would be able to recognise an adverse reaction, mainly because of their lack of knowledge but also because of their sometimes bizarre beliefs. Detoxification is an obvious example common to both.

Worse, there is "Adverse events in homeopathy and homeopathic aggravations" (a document found in the appendices of the pilot study) which states -
No serious adverse events [re use of homeopathy] have been reported (ECCH 2009). The adverse events most commonly reported include: headaches, tiredness, skin eruptions, dizziness, diarrhoea or loose stools, and aggravations of patients’ pre-existing symptoms (Dantas & Rampes (2000). 
Mild and transient aggravations of patients’ pre-existing symptoms, usually associated with increased feelings of wellbeing, are commonly referred to as ‘homeopathic aggravations’ in the homeopathy literature. They occur relatively soon after taking a homeopathic medicine and are normally considered favourable and part of patients’ curative process (Endrizzi et al. 2005, Thompson et al. 2004). Such aggravations occur more commonly with a particular homeopathic protocol to be used in this trial (CEASE, Smits, 2010).
"Aggravations" have been discussed before (here and here). As homeopathy has not been demonstrated to have any effect, these symptoms are caused by something other than homeopathic remedies. More worrying is that the document is couched in terms purely of reporting the incident to the management committee. No mention is made of seeking medical assistance.

Fibert may have been a Special Educational Needs (SEN) teacher but that was many years ago. Whether she has any relevant experience in training lay persons in the current best practice of management of ADHD is unknown.

The amount and type of safeguarding training required is debatable. The safeguarding document in the appendices is fairly cursory. CEASE advocates medical neglect and some homeopaths, supporters and their organisations have trouble acknowledging this (it is irrelevant that CEASE doesn't seem to have been used). It is not only the inability to recognise CEASE as neglect but not recognising other treatments as neglect or directly harmful that is a concern. In the case of the pilot study, yes, the concern is (partly) mitigated by the children receiving treatment as usual and thus being under the care of the NHS, attending school and possibly having involvement with Social Services. They are exposed to multiple professionals with extensive safeguarding training. 

What is clear is that some of the homeopaths did struggle -
Homeopaths said that on average, trial participants had more serious symptoms compared with their private clients. They expressed frustration at missed consultations, difficulty contacting participants, and the influence of life events. They felt that their intervention was at times “a drop in a turbulent ocean”. The therapist who dropped out said that “treating these children makes me feel incompetent, it’s hard not to take missed appointments personally”. 
Homeopaths commented that at times they found it difficult to identify a suitable individually-tailored homeopathic remedy. They said that separating the child’s story from the carer’s story was sometimes difficult since information was delivered by carers, some of whom had traumatic life histories themselves. They found that the symptoms of those children who were on medication were subdued, which was problematic because prescription relies on accurate observation of symptoms. They felt that the child’s behaviour was sometimes inhibited in the consultation room. 
The interaction between ADHD medication and homeopathic remedies was sometimes a concern for homeopaths, participants and/or their GPs or consultants. Several participants either stopped or didn’t start homeopathic treatment on the advice of their doctors. Some participants changed conventional medications during homeopathic treatment which homeopaths reported made analysis of change due to homeopathic remedy difficult. And two participants wanted homeopathic treatment specifically to manage the side effects of conventional medication.
That could be read in a number of ways but it is suggestive that the homeopaths were out of their depth. The implication that homeopathy can not treat when a patient is on medication (suppression of symptoms) is troubling. Would the homeopaths suggest medication is stopped?

The picture is slightly different with the nutritional therapists.
Like homeopaths, nutritional therapists expressed frustration at participants who repeatedly missed consultations, and/or didn’t follow advice, and commented on the difference between trial participants and their private clients: “frequent changes to plans (cancellations the day before or 'forgetting' appointments) can be extremely frustrating and obviously happen far more often than with my usual clients, which took some getting used to”. Another therapist said, “I feel like a supplement pharmacist or I stroke the carers”. Therapists felt that much depended on the carer’s attitude: “if mum has decided it won’t work, it does not stand a chance”. 
Participants often had poor diets consisting of junk food, sweets, fizzy drinks, and other sugary products. Children, particularly teenagers, bought sweets on the way home from school, which carers could not monitor. Some carers felt unable to implement dietary advice. 
Therapists felt that restrictive diets and sensory issues of those with co-occurring ASCs was a problem that often needed working around. They felt that the nutritional intervention was just one cog in a complex wheel with confounding factors which often interfered with treatment. One therapist said “Sometimes nutrition seems unimportant compared to what I've been hearing about (violent criminal behaviour, trouble with police etc)”.
Although initial consultations were face-to-face, subsequent ones tended to be via other media such as Skype. Whilst this isn't so much of an issue with nutritional therapy, it is with homeopathy - how does "accurate observation of symptoms" occur?

Was CEASE therapy used?
Fibert's entry on the CEASE therapy website says -
She then conducted a consecutive case series of children with ADHD as a component of an MSc at Goldsmiths, University of London where CEASE methodology made a significant difference to the outcome of these cases. She is currently running a clinical trial in the same area as part of PhD studies at Sheffield University, where again CEASE is being used in most cases.
But this was written before the trial had been given ethical approval!

The study says -
Before the trial began, all therapists who were going to deliver the therapies attended workshops run by the PI. The workshops trained them in management of ADHD and how to recognise and respond to any serious adverse events (Appendices 9 & 10). All therapists completed the on-line Sheffield safeguarding children child protection course (Safeguardingchildrentraining@sheffield.gov.uk). Homeopaths were given training in a specific homeopathic methodology for treatment of exposure to environmental toxins, which had been found to be useful in the case series (Fibert, Relton, Heirs, & Bowden, 2016).
That this is CEASE is confirmed by -
Some extra training provided in: CEASE methodology, NSPCC child protection, and ADHD management 
But then there is this - 
Homeopaths attended several workshops preceding participation in the trial concerning specific methodologies for treating ADHD cases (section 6.5). It is common for homeopaths to attend courses as part of their continuous practitioner development (CPD) so this was not necessarily a deviation from usual practice, although the courses were paid for as part of the research, which is. However, none of the homeopaths utilised the methodologies they were trained in during these courses, preferring to use the methods they normally used. Recruitment of future homeopaths will not offer this extra training as it was not cost effective and reduced the pragmatism of the intervention, but will try to recruit homeopaths who have already incorporated the techniques into their routine practice.
If CEASE was used, it would have been by Fibert. It is unknown if Upham was involved in the pilot study.

The intention to use CEASE is very clear though.

Supply of Products
This blog does labour the point that most homeopathic remedies are not registered with the MHRA. They have the status of unlicensed medicines. There are strict controls on the supply of unlicensed medicines. The direct supply to consumers is forbidden but exemptions for pharmacists do exist. These exemptions do not apply to medically unqualified homeopaths, either in terms of supply to them or supply by them to trial participants. As described above, a REC can not give approval to a trial that involves illegality. Fibert is a member of the SoH. There is an onus on her as a member to abide by their Code of Ethics which has a requirement to abide by law and there is this but it is relatively recent, wrong (supply, not sales) and totally ignored by the SoH.

Assuming the use of homeopathic products in treatment of ADHD does constitute a CTIMP, charging for them at any point in the supply is illegal under the Regulation 2004.

The situation with products used in nutritional therapy is very complicated. Some are absolutely illegal, but it is not clear if they were used in the pilot study. 

Results etc
What the trial is doing is comparing Treatment as Usual versus Treatment as Usual + homeopathy versus Treatment as Usual + Nutritional TherapyIt should be obvious why this is problematic.

Fibert says - 
This thesis addressed the research question: Is the TwiCs design suitable to assess the effectiveness of interventions to improve outcomes for ADHD? A small-scale test of the design and measures was conducted to answer the question, and the results suggest that the TwiCs approach to pragmatic trial design, with some modifications to its implementation, is feasible and appropriate for trials testing interventions for children with ADHD.
So, in reality, no, the TwiCs design was not suitable if it required modification. It becomes something else if modified. This might seem a quibble over methodology but as Fibert's thesis hinges on the validity of the TwiCs approach, it could be argued that there is a significant failure.

Forgetting the point of her thesis, do the results say anything? Are they compelling? Do they suggest a way forward via medically unqualified persons? No. Marginal parent reported results assessed by a non-clinician. With obvious bias.

Apparently, a reasonable request can obtain the raw data. It depends on who on the gatekeeper of the data is. I'll ask. For a friend. That's not going to end well.

Funding and potential conflicts of interest
The funding for the trial comes from the HRI. They are briefly discussed here. Over time, HRI have allocated £127,623 to Fibert's research - £3,113 for the case series and £124,510 for the pilot study. Where the money for the pilot study came from is unknown.
The cost of running the STAR pilot trial, excluding an investigator’s salary, was less than £50,000.
So, over the course of the study, Fibert would have received £75k or more in the way of a stipend from the HRI. It is unknown whether she was also practicing as a homeopath during this period or had any other additional income.

The allocation was funds to the pilot study was made in two parts. One in financial year 2012/13, the other in 2013/14. Clare Relton was a trustee of the HRI until 20/02/2014. This money was designated as "restricted funds" - it can only be used for the purposes it was donated for. Thing is, originally more money was allocated. Some of the funds were transferred to systematic reviews by Robert Mathie. So either the restrictions were not absolute or the donor(s) agreed to the transfer. It is also the case that the funds were allocated before ethical approval was granted for the pilot study - it would be foolish to specify restrictions on funds that were so specific as to not allow re-allocation of funds if the pilot study had not received approval. 

How much say the trustees had in the allocation of the funds is unclear but there is an obvious potential for conflict of interest. Charity Commission guidance is very clear. HRI say that there wasn't one. 

Most "therapy centres" operate on the principle of self-employed therapists renting room from the centre rather than being employees of the centre. As Relton is a director of Wellforce, unless Wellforce chose to waive/reduce rental costs for sessions conducted there, she could have received a (small) financial benefit.

Also the pilot study reveals that a small number decided to carry on with homeopathic treatment. Where is unclear. 

Intention to continue/expand
The pilot study talks about the desire to continue the study and increase the size of the cohort. This story on the SoH website states -
“We’re looking to recruit 400-500 more families to the cohort. Let us know if you can contribute or if you know anyone who might be able to help,” said Philippa, whose interest in the field was inspired by her previous work with children with special needs as a teacher and parent educator.
From above, it would seem that Fibert wants to recruit homeopaths who use CEASE.

Investigations
It will come as no surprise that the University of Sheffield when concerns were raised regarding this pilot study initiated an investigation. This is believed to be ongoing - no outcome has been as yet communicated.

The MHRA have been requested to review the trial protocol to determine whether approval was required. As yet the issue of the supply of homeopathic remedies used in and whether they are investigatory medical products has not been raised.

Both Sheffield City Council and Sheffield Children's NHS Foundation Trust have been informed. It is unlikely that either would mount investigations themselves.

Conclusion
The fundamental question is whether ethical norms apply in a situation where very low risk therapies are used as an adjunct to treat as usual? If the answer is no, then, all of the above is redundant.

If the answer is yes, violations of those norms has occurred.

Any REC really should have considered whether Fibert is qualified to be principle investigator, provided supervision and, worse, a provider in the trial given her obvious bias. The intention to use CEASE should have been considered too. Fibert's links to HRI may or may not be relevant.

It took several years to get to the point of recruiting for the pilot study. Applying for NHS approval would not have added much in the way of delay. It's difficult not to come away with the impression that it wasn't sought because of the possibility of it not being granted.

The most important thing is that no more recruitment occurs. 



Slightly amusing aside
Fibert believes that homeopathy is "under attack", etc - 
Considerable resources are employed by a small group of very effective detractors in the UK to influence public, media and government opinion against homeopathy. They largely refer to two biased documents: a meta-analysis by Shang et al. (2005) which fails sensitivity analysis (L├╝dtke & & Rutten, 2008); and a House of Commons technology report (House of Commons Science and Technology Committee, 2010) which is based on Shang et al, and was dismissed by the department of health in an early day motion. Nevertheless detractors have succeeded in creating an environment where debate and media coverage is one sided and limits the acceptability and publication of any positive homeopathy results generated.
Fibert simply repeats myths popular in UK homeopathy. The Department of Health said that commissioning of homeopathy was a matter for local NHS bodies. The Early day motion had nothing to do with them. This is touched on in this post. 
For example, I co-authored a systematic review of homeopathy for depression which was initially accepted by sub-editors of a well-known journal but then rejected by the editor. He provided a negative opinion piece and a blog to justify the journal’s stance that homeopathy is not an effective treatment for any health condition. In other words, only articles informing the journal’s interpretive stance were acceptable. In another incident, I was interviewed on BBC Oxford describing my research, whereupon a well-known sceptic blogger complained to the BBC, who responded to his complaint by assuring him that homeopathy will never again be discussed without the prior proviso that it does not work. 
It would appear this blog post upset Fibert. False balance is a difficult concept for homeopaths as is scientific/medical consensus. This blog has a tiny audience. 




Friday, 29 March 2019

More on BBC and ASA reports re CEASE therapy

A previous post discussed recent BBC reporting and an Advertising Standard Authority (ASA) regarding CEASE therapy. It also looked at the potential impacts on the Society of Homeopaths (SoH).

This post has several different perspectives.

Reach
It is difficult to gauge how many people have seen the reports. They did not just appear on the BBC but in several newspapers and on many websites. What is curious though that that both the Guardian and Daily Mail did not reference their previous reporting.

A large number of local newspaper and radio websites carried the story but they were carrying the same AP story as most of the nationals. 

Some NHS websites carry BBC health news as a feed.


National Autism Society Statement
The NAS said on Twitter - 
Autism is lifelong. It’s not a disease or an illness. And many autistic people feel that their autism is a core part of their identity. It is deeply offensive for anyone to claim that unproven and even harmful therapies and products can ‘cure’ autism – and particularly appalling where people target vulnerable families. 
We are really pleased that the @ASA_UK is taking action against the bogus claims by people pedalling CEASE therapy. This sends a strong message to all homeopaths to make sure that their practice is evidence-based and follows national guidance and that failure to do this will lead to further sanctions and potentially prosecution by Trading Standards. 
There are around 700,000 autistic people in the UK. Life can be desperately difficult for autistic people and families, particularly just before and after receiving a diagnosis, when so much is unclear and support is often hard to come by.  
We must all do everything we can to protect autistic people and their families. This means challenging myths, reporting dodgy therapies to the authorities and making sure they use their powers to stop their production, promotion, sale and use.  
The Government and its agencies, like health and education, must also make sure autistic people and families have accurate information about the support that can actually help – and this support must be available when and where it’s needed.

Reactions
The responses of homeopaths and their supporters to the reports are predictable. Generally, they seem to ignore the ASA's sending of Enforcement Notices and concentrate on "well, they didn't interview a homeopath! Bias!!!". Some also say that they did not interview any of the "hundreds" of parents whose children had been "cured" of autism. There are a couple of Youtube videos that purport to show "cured" children but their veracity can not be confirmed and at least one is highly suspect.

Something that comes across very strongly in some responses are anti-vaccination conspiracy theories. This post from Steve Scrutton that attempts to defend CEASE is a perfect example of how homeopaths are pathologically incapable of addressing the real issues - medically unqualified lay persons with no training in autism or safeguarding acting far beyond their competence who advocate neglect of autistic children. Emma Dalmayne is mis-characterised as an an "anti-homeopathy" campaigner. Dalmayne campaigns against bogus and dangerous treatments of autism full stop.  It displays not uncommon attitudes towards the ASA and the BBC. It makes the mistake of thinking all of this is about homeopathy. It isn't. It's about autistic children being put at risk.

Scrutton's attack on the National Autistic Society shows how deeply conspiracy thinking runs in some homeopaths. 
The programme also used the expert opinion of the National Autistic Society (NAS). This charity has an annual budget of almost £1 billion, and it’s an organisation funded to a significant degree by the pharmaceutical industry. Certainly, this exchange between Dr Vernon Coleman and NAS in 2007 confirms that this was the situation at that time, and I can find no evidence that this situation has changed since then. 
So perhaps unsurprisingly, NAS confirmed the view of conventional medicine that autism is a 'life-long condition’, and a "part of who people are", that it was "wrong and appalling that anyone to claim that bogus and potentially harmful therapies such as CEASE cure autism".
NAS's Annual Report tells a very different story and Vernon Coleman's "exchange" does not confirm Scrutton's assertions.

There has not been a tremendous amount of reaction from autism groups but what there is has been approving of the ASA's action. 

Implications for Individuals
What are the implications for those 150 homeopaths sent the ASA Enforcement Notice? What is going to happen to the five practitioners being investigated by Trading Standards?

Although Bucks and Surrey Trading Standards have not said that what they have done so far, what might well have gone on it is that after initial investigation they informally advised the accused of what legislation says and their obligations under it. Trading Standards have a range of options but a likely next step would be the issuing of a Compliance order. This will set a deadline for compliance. The accused will have to inform their insurer (and their membership organisation if they have one) at this point - it is a contractual obligation.  A business can appeal against such an order via the Courts. Non-compliance can result in prosecution.

Only the very foolhardy or ignorant would not seek legal advice at this point. Or perhaps a paranoid conspiracy theorist? An insurer or member organisation would very likely advise of the need to.

Trading Standards can go straight to the prosecution stage without issuing a Compliance notice. 

Any prosecution is likely under the Consumer Protection from Unfair Trading Regulations 2008. The claim to treat or cure autism with homeopathy is misleading but claims that vaccines cause autism might also be considered. There is no specific provision that relates to the use of creating undue fear in consumers it might well be considered an aggressive marketing practice. Whilst prosecution under the Human Medicines Regulations 2012 is possible, because a service is being advertised rather than named medicines, this route may not be taken. There is a seeming reluctance to act on supply of unauthorised homeopathic remedies (see this for discussion of the legislation and also this).

If they do end up in Court, it is unlikely that their insurance will cover their legal costs. Having looked at some policies, breaches of the Human Medicines Regulations 2012 and Consumer Protection from Unfair Trading Regulations 2008 are not included. Accused would have to find funding themselves.

Offences under both sets of Regulations can be tried in a Magistrates Court. If the accused pleads guilty, the prosecution will set out the facts of the case and the accused will present any mitigation. Sentence may or may not be made at this point. It must be pointed out that it would be impossible to claim ignorance of the Regulations as mitigation at this point as Trading Standards will have made them aware prior to this.

It seems unlikely that a homeopath who got to that stage would plead guilty (would have ample opportunity to comply prior to this). If a not guilty charge is entered, the court will adjourn and a date will be set for a trial. Bail may be set to prevent further offences being committed. To be explicit, the Court could forbid a homeopath from practicing. If they did, they could find themselves back in front of the Court. It would not necessarily have a direct effect on determination of guilt and sentencing but...

Any credible defence would have to deliver concrete evidence of CEASE "curing" autism and also evidence of the "hundreds" of cases claimed. Anecdotes and testimonials are unlikely to be accepted, nor are unethical and illegal medical trials. The situation with "vaccines cause autism" is worse because scientific evidence is so strong against such a link. The claim to cure vaccine injury is almost impossible to prove as it would require a diagnosis.

In some trials involving quacks, multiple witnesses have been called to testify to their "cure" and/or the good character of the accused. It would be unfortunate if the parents of autistic children were asked to appear. 

Courts often have little patience for the submission of lengthy reports, spurious "evidence" and the calling of "expert witnesses" who are nothing of the sort. Character witnesses likewise. All of these things extend the duration of a trial and increase legal costs.

A conviction is likely to result in a fine. A prison sentence is unlikely. The Court might well make a Criminal Behaviour Order (CBO). An referral to the Disclosure and Barring Service to place on the Barred List could be made. It is also likely that they will have to pay Trading Standards' legal costs as well as their own (which is why a lengthy trial is such a bad idea).  

A CBO might well force a homeopath to find employment but a criminal record/entry on Barred List will preclude some roles, especially those involving children. An offender practices homeopathy part-time and has other employment could well lose their job. 

Broader Implications
A conviction would set a legal precedent with huge implications for UK homeopathy. Not only in terms of any future prosecution. Whereas homeopaths often try to dismiss ASA rulings on the basis of "bias", a clear ruling on the illegality of certain claims and actions would be difficult to ignore.

Of course, some would paint it as the judiciary being part of a conspiracy against homeopathy and the establishment being under the thrall of Big Pharma. Of course, conviction would be impossible if legislation didn't exist. But it does. Historical deliberate misinterpretations of that legislation will be put to bed.

There would be extensive media coverage, have no doubt of that.

If homeopaths and their associations had acted responsibly and accepted the de facto limitations of homeopathy, none of the above would happen. If regulators like the Medicines and Healthcare Product Regulatory Agency and General Pharmaceutical Council had made efforts to curtail the supply of unlicensed medicines to lay homeopaths by pharmacies, CEASE therapy could have been made very difficult to practice. The media will ask why these things have not happened.

Homeopathy is not popular in the UK, whatever homeopathy associations might like you to think but it could become even less popular. 

Readers can draw their own conclusions about how bad things could get.