The SMILE Trial was a feasibilty study followed by a clinic trial of the controversial Lightning Process in children and adolescents with chronic fatigue syndrome. It took place at the Royal National Hospital for Rheumatic Diseases in Bath and the University of Bristol in Britain. The principle investigator was Esther Crawley. It was designed to the effects of standard medical treatment (SMC) against that of the Lightning Process & Standard Medical Care (SMC) together. The Lightning process takes place over three consecutive days in a group format. Participants were children aged between 12 and 18 drawn from the Bristol and Bath areas. Those who were housebound were excluded.
The co-applicant for the study was Fiona Finch, the Research Director at the Lightning Process company (Phil Parker Ltd).
Methodology[edit | edit source]
The trial compared patients receiving Standard Medical Care (SMC) against the Lightning Process (LP) in conjunction with SMC.
Self-assessment questionnaires were completed at the first clinical assessment and subsequently at 6 weeks, 3 months, 4.5 months.
Out of 156 children considered eligible, 56 participated, with the study beginning in September 2012. Anxious children were offered three sessions of cognitive behavioral therapy (CBT) over a six-week period.
Specialized Medical Care (SMC) consisted of graded activity with phone calls and family-based rehabilitation consultations lasting an hour at six weeks, three months & 4.5 months.
Outcome swapping[edit | edit source]
The primary outcome was initially to be based on school attendance. This was changed to the physical function short form (SF-36) questionnaire, with most secondary outcomes also being self-assessed using the following scales: the Chalder fatigue scale, pain visual analogue scale, the Spence Children’s Anxiety Scale (SCAS), the Hospital Anxiety and Depression Scale (HADS) for children aged 14 and over,, and the Euroqol (EQ-5D) a five-item quality of life inventory, plus school attendance.
Funding[edit | edit source]
The initial budget was £164,000 funded by the Linbury Trust and the Ashden Trust.
Research ethics[edit | edit source]
In a joint statement in August 2010, the ME Association and the Young ME Sufferers Trust called the SMILE study "unethical" saying, "The ME Association and The Young ME Sufferers Trust do not believe that it is ethically right to use children in trialling an unproven and controversial process such as the Lightning Process."
Professor Robin Gill, a member of the British Medical Association's medical ethics committee, wrote to the Church Times about the LP and the SMILE trial. He expressed concern about the issue of coercion of children in the trial.
Results[edit | edit source]
The results of the SMILE trial were not published until 2017, despite the trial being completed in 2013, with the print version published in 2018. Complaints to the publishing journal, Archives of Disease in Childhood, were extensively investigated in 2018 and 2019, resulting in a significant editorial correction in July 2019.
There are some selective quotes in a 2015 paper as well the final study protocol, which was published after the trial ended. James Coyne said of the quotes "(they) 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."
Criticisms[edit | edit source]
Daniel Clark has noted that the primary outcome measure was changed from school attendance to scores on a self-report questionnaire after the trial was registered, a process known as outcome swapping. Before the publication of trial, he stated, "Given that LP involves making claims to patients about their own ability to control symptoms in exactly the sort of way likely to lead to response bias, it seems very likely that this trial will now find LP to be 'effective'."
Editorial correction[edit | edit source]
An open letter was sent to the editor of Archives of Disease in Childhood in January 2018 by Dr David Tuller and over twenty other signatories for a correction to the serious issues and anomalies in the published paper. In July 2019, after an investigation by the Archives of Disease in Childhood, and significant correspondence between the study's authors, journal editor Nick Brown, and Dr David Tuller, a lengthy and detailed editorial correction to the SMILE trial was published. In the correction, Archives of Disease in Childhood published a justification for the journal's refusal to retract the SMILE publication, and a list of many of the issues with the original publication.
Notable publications[edit | edit source]
Investigators[edit | edit source]
See also[edit | edit source]
- Chalder fatigue scale
- Esther Crawley
- Lightning Process
- Cognitive behavioral model
- FITNET trial
- MAGENTA trial
- PACE trial
- Ethical issues
- Pediatric myalgic encephalomyelitis/chronic fatigue syndrome
References[edit | edit source]
- Crawley, Esther; Mills, Nicola; Beasant, Lucy; Johnson, Debbie; Collin, Simon M.; Deans, Zuzana; White, Kate; Montgomery, Alan (Dec 5, 2013). "The feasibility and acceptability of conducting a trial of specialist medical care and the Lightning Process in children with chronic fatigue syndrome: feasibility randomized controlled trial (SMILE study)". Trials. 14 (1): 415. doi:10.1186/1745-6215-14-415. ISSN 1745-6215. PMC . PMID 24304689.
- SMILE Trial Protocol - Bristol University 2013
- Final Study Protocol - Crawley et al (Dec 2013)
- Stern, Anna F. (Jul 1, 2014). "The Hospital Anxiety and Depression Scale". Occupational Medicine. 64 (5): 393–394. doi:10.1093/occmed/kqu024. ISSN 0962-7480.
- Dworkin, RH; Turk, DC; Farrar, JT; Haythornthwaite, JA; Jensen, MP; Katz, NP; Kerns, RD; Stucki, G; Allen, RR; Bellamy, N; Carr, DB (Jan 1, 2005). "Core outcome measures for chronic pain clinical trials: IMMPACT recommendations" (PDF). PAIN. 113 (1): 9–19.
- £164,000 grant for study into the Lightning Process and children with ME - ME Association (March 2010)
- "The Lightning Process and SMILE trial is an "unethical" study involving children | 20 September 2010". Retrieved Jul 16, 2019.
- Letter to National Research Ethics Committee - Invest in ME
- meagenda (Oct 14, 2010). "Children should not be used as guinea pigs: Prof Robin Gill, Church Times (LP pilot study)". ME agenda. Retrieved Jul 16, 2019.
- Brown, Nick (Jul 2019). "Editor's Note on Correction to Crawley et al 2018". Archives of Disease in Childhood.
- Crawley, Esther M; Gaunt, Daisy M; Garfield, Kirsty; Hollingworth, William; Sterne, Jonathan A C; Beasant, Lucy; Collin, Simon M; Mills, Nicola; Montgomery, Alan A (Feb 2018). "Clinical and cost-effectiveness of the Lightning Process in addition to specialist medical care for paediatric chronic fatigue syndrome: randomised controlled trial". Archives of Disease in Childhood. 103 (2): 155–164. doi:10.1136/archdischild-2017-313375. ISSN 0003-9888. PMC . PMID 28931531.
- What matters to children with CFS/ME? A conceptual model as the first stage in developing a PROM - Archives of Disease in Childhood, Crawley et al 2015
- Before you enroll your child in the MAGENTA chronic fatigue syndrome study: Issues to be considered - James Coyne (September 2015) Plos Blog
- James Coyne's criticisms of the work of Esther Crawley
- Daniel Clark''s criticism on Skepdic website
- Ethics Committee finally approves SMILE (January 2011)
- "THE SMILE TRIAL (part 1)". johnthejack. Jul 2, 2017. Retrieved Jul 16, 2019.
- "THE SMILE TRIAL (part 2)". johnthejack. Jul 5, 2017. Retrieved Jul 16, 2019.
- "THE SMILE TRIAL (part 3)". johnthejack. Jul 9, 2017. Retrieved Jul 16, 2019.
- Tuller, David (Dec 13, 2017). "Trial By Error: The SMILE Trial's Undisclosed Outcome-Swapping". Virology blog. Retrieved Jul 16, 2019.
- Tuller, David (Jan 30, 2018). "Trial By Error: A Letter to Archives of Disease in Childhood". Virology blog. Retrieved Jul 16, 2019.
chronic fatigue syndrome (CFS) - A fatigue-based illness. The term CFS was invented invented by the U.S. Centers for Disease Control as an replacement for myalgic encephalomyelitis (ME). Some view CFS as a neurological disease, others use the term for any unexplained long-term fatigue. Sometimes used as a the term as a synonym of myalgic encephalomyelitis, despite the different diagnostic criteria.
randomized controlled trial (RCT) - A trial in which participants are randomly assigned to two groups, with one group receiving the treatment being studied and a control or comparison group receiving a sham treatment, placebo, or comparison treatment.