SMILE trial

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
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
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
The initial budget was £164,000 funded by the Linbury Trust and the Ashden Trust.

Research ethics
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."

Invest in ME in a letter to the National Research Ethics Committee (NRES) described the process as "rather like CBT but with bullying and risks of harm."

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
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."

To document the results from these threads, see here, here, and here.

Criticisms
James Coyne has criticized Crawley's work with regard to public availability of data & the involvement of Phil Parker in the SMILE study.

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'."

The study only received final ethical approval after prolonged protests from patient groups in January 2011.

Patient advocate John Peters has criticized the study.

Dr David Tuller has severely criticised the SMILE trial.

Editorial correction
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
2017, Clinical and cost-effectiveness of the Lightning Process in addition to specialist medical care for paediatric chronic fatigue syndrome: randomised controlled trial (Full text)

2019, Editor's Note on Correction to Crawley et al. 2018 (Full text)

Investigators
Esther Crawley, Daisy Gaunt, Kirsty Garfield, Nicola Mills, William Hollingworth, Zuzana Deans, Jonathan A Sterne, Jenny L Donovan, Lucy Beasant, Alan Montgomery and Simon Collin.