FITNET trial

FITNET (or Fatigue In Teenagers on the interNET) consists of a series of research trials for teenagers with Chronic Fatigue Syndrome (or CFS/ME). The FITNET clinical trials involve children aged 12 to 19 in the Netherlands, with the UK arm FITNET-NHS, involving children aged 11 to 17.

FITNET-NHS

FITNET-NHS "will investigate whether FITNET-NHS (online CBT) is effective in treating ME/CFS in the NHS, and whether it offers value for money compared to Activity Management." FITNET-NHS plans to continue recruiting children until 2021, and recruits only children from an area without a specialist CFS service. The trial is run by Professor Esther Crawley, with the research team based in Bath, UK.

FITNET-NHS was planned with input from the charity Association of Young People with ME (AYME) and Professor Stephen Holgate supported the FITNET trial. However, AYME later merged with Action for ME, who are not providing input to the trial.

Funding

National Institute for Health Research (NIHR) and Health Technology Assessment (HTA) Programme are funding the UK research.

Total funding for the FITNET-NHS pilot and full trial: £994,430.

Controversy

David Tuller has written that although the PACE trial has been publicly discredited when a court-ordered release of key trial data which confirmed PACE authors "weakened their outcome criteria mid-stream in ways that allowed them to report dramatically better results for “improvement” (in The Lancet in 2011) and "recovery" (In Psychological Medicine in 2013)" they "continue to defend the indefensible study" and push forward with CBT with Dr. Esther Crawley promoting FITNET and wants to enroll more than 700 adolescents.

Tuller wrote in Trial By Error, Continued: A Follow-Up Post on FITNET-NHS

"As part of her media blitz for the FITNET-NHS launch, Dr. Crawley was interviewed on a BBC radio program by a colleague, Dr. Phil Hammond. In this interview, she made some statements that demonstrate one of two things: Either she doesn’t know what she’s talking about and her misrepresentations are genuine mistakes, or she’s lying. So either she’s incompetent, or she lacks integrity. Not a great choice." Dr. Crawley either made an "unfortunate mistake" or a "deliberate untruth" when she convoluted two comparison groups in the study; one group went on with FITNET and the other did not yet she put the groups together as all going on with FITNET. She also stated: "Now, you know, you can pick and choose how you redefine recovery, and that’s all very important research, but the message from the PACE Trial is not contested; the message is, if you want to get better, you’re much more likely to get better if you get specialist treatment." Dr. Tuller notes this is at serious odds with the facts.

Excerpt of Dr. Tuller explaining facts of PACE trial data

In reporting their findings in The Lancet in 2011, the PACE authors presented “improvement” results for the two primary outcomes of fatigue and physical function. They reported that about 60 percent of participants in the CBT and GET arms reached the selected thresholds for “improvement” on both measures. In a 2013 paper in the journal Psychological Medicine, they presented “recovery” results based on a composite “recovery” definition that included the two primary outcomes and two additional measures. In this paper, they reported “recovery” rates for the favored intervention groups of 22 percent.

Using the raw trial data that the court ordered them to release earlier this year, the PACE authors themselves reanalyzed the Lancet improvement findings, based on their own initial, more stringent definition of “improvement” in the protocol. In this analysis, the authors reported that only about 20 percent “improved” on both measures, using the methods for assessing “improvement” outlined in the protocol. In other words, only a third as many “improved,” according to the authors’ own original definition, compared to the 60 percent they reported in The Lancet. Moreover, in the reanalysis, ten percent “improved” in the comparison group, meaning that CBT and GET led to “improvements” in only one in ten participants—a pretty sad result for a five-million-pound trial.

The Countess of Mar wrote a November 3, 2016 open letter to the BBC in reference to its media coverage with Esther Crawley and FITNET. The BBC responded on November 21, 2016 and the Countess again wrote to the BBC on December 8, 2016 finding their response unsatisfactory.

• Nov 3, 2016, the Countess wrote to the BBC to complain about the coverage of the FITNET ME/CFS paediatric trial run by Esther Crawley. She said the reporting was "was neither accurate nor impartial" and that information on the BBC website, news bulletins & news channel were misleading.

• Nov 21, 2016, The BBC replied to the Countess's letter stating that "We are aware that research about CFS has been controversial and we try to ensure that this is reflected in our coverage....I accept that the original headline for the article by James Gallagher which referred to people being ‘cured’ was incorrect. In fact it was published in error and was corrected very shortly after the original version was first posted....we decided to make reference to [the controversy] by including a clip of Jane Colby from the Tymes Trust."

• Dec 8, 2016, the Countess wrote again to the BBC about the FITNET coverage where she stated "I regret that I find your response far from satisfactory." She referenced David Tuller's Trial By Error articles on FITNET, FITNET and the NHS, flawed Dutch studies of GET/CBT and Esther Crawley.

STOP criteria

The STOP criteria define the conditions under which the research will be halted. FITNET-NHS' STOP criteria does not include any measures of adverse experiences to participation in the trial or harm to children taking part. It does include drop-out rates from treatment.

Adverse experiences

The following events are to be recorded as adverse experiences:

Informed consent

The participant information leaflets are available on the FITNET-NHS website, along with the informed consent forms for both teenagers and parents/carers. Previous trials involving cognitive behavioral therapy and graded exercise therapy have been criticized for not informing participants of potential risks of harm.

The participant information leaflets were last updated in 2018 and does not mention:

• that the NICE treatment guidelines for CFS/ME are currently being updated
• what kind of adverse experiences may be expected from cognitive behavioral therapy (CBT)
• what medical or professional qualifications the therapists have
• rates of harm or improvement reported by adults who have undergone forms of CBT
• that CBT of a form of psychotherapy
• the term graded exercise therapy or graded activity is not mentioned, although the Activity Management description does state the children will be expected to increase their activity in steps of 10-20%

GP and pediatrician flyer information

FITNET-NHS provide information to GPs and pediatricians about how to refer children with ME/CFS to the FITNET-NHS trial, and some general information about the research trial.

Most recover with specialist treatment claim

Both the FITNET-NHS posters for GPs and pediatricians include the unreferenced claim that "most" children recover within 6 months after "specialist treatment", but that "less than 10%" of children who did not attend a specialist center recovered in that time. However, this claim may be based on a single study of FITNET in the Netherlands, so the figures many not be accurate for children in the UK being treated by the NHS.

Recovery did not mean a return to their previous level of health

Recovery in the FITNET trial was not the rate of returning to full health; and the rate of over 60% recovery in the Dutch FITNET trial has been disputed. FITNET's trial "recovery" standard was met when the child's health was within 2 standard deviations of the norm for healthy children, this dropped to 36% of children if recovery was being within one standard deviation of the norm. FITNET's 6 month assessment period was also criticized as being too short, given that some patients have a relapsing and remitting course of illness, in which there may be some periods without symptoms before the illness returns; however longer term follow up studies have since been published.

Patient flyer

The flyer for patients did not mention any likely rates for recovery from "specialist treatment" or without treatment.

Treatment available without joining the research trial

All these flyers mentioned that home based treatment was available for ages 11-17 "as part of a research study", none mentioned that some out of area or home based support was already able without needing to join a research trial.

Protocols

The FITNET and FITNET-NHS trial protocols describe how the trial will to be conducted. The FITNET-NHS (UK) protocol has been updated a number of times, with the fifth version of the protocol published in 2019.

FITNET - Netherlands

• 2011, Fatigue In Teenagers on the interNET - The FITNET Trial. A randomized clinical trial of web-based cognitive behavioural therapy for adolescents with chronic fatigue syndrome: study protocol. - ISRCTN59878666

FITNET-NHS - UK

• 2018, Investigating the effectiveness and cost-effectiveness of FITNET-NHS (Fatigue In Teenagers on the interNET in the NHS) compared to Activity Management to treat paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME): protocol for a randomised controlled trial - ISRCTN18020851

Results

FITNET - Netherlands

• 2012, Effectiveness of internet-based cognitive behavioural treatment for adolescents with chronic fatigue syndrome (FITNET): a randomised controlled trial
• 2013, Internet-Based Therapy for Adolescents With Chronic Fatigue Syndrome: Long-term Follow-up
• 2013, Functional Improvement is Accompanied by Reduced Pain in Adolescent Chronic Fatigue Syndrome

FITNET - UK

Criticism

• 2017, FITNET’s Internet-Based Cognitive Behavioural Therapy Is Ineffective and May Impede Natural Recovery in Adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. A Review by Simin Ghatineh and Mark Vink

  Abstract: The Dutch Fatigue In Teenagers on the interNET (FITNET) study claimed that after 6 months, internet based cognitive behaviour therapy in adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), led to a 63% recovery rate compared to 8% after usual care, and that this was maintained at long term follow up (LTFU). Our reanalysis shows that their post-hoc definition of recovery included the severely ill, the unblinded trial had no adequate control group and it used lax selection criteria as well as outcomes assessed via quqqestionnaires rather than objective outcomes, further contributing to exaggerated recovery figures. Their decision not to publish the actometer results might suggest that these did not back their recovery claims. Despite these bias creating methodological faults, the trial still found no significant difference in recovery rates (“~60%”) at LTFU, the trial’s primary goal. This is similar to or worse than the documented 54–94% spontaneous recovery rates within 3–4 years, suggesting that both FITNET and usual care (consisting of cognitive behaviour and graded exercise therapies) are ineffective and might even impede natural recovery in adolescents with ME/CFS. This has implications for the upcoming costly NHS FITNET trial which is a blueprint of the Dutch study, exposing it to similar biases.

• 2018, Investigating the effectiveness and cost-effectiveness of FITNET-NHS (Fatigue In Teenagers on the interNET in the NHS) compared to Activity Management to treat paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME): protocol for a randomised controlled trial

Investigators

FITNET-NHS (UK)

• Chief investigator: Esther Crawley

• Co-investigators: Hans Knoop, David Kessler, Elise Van de Putte, Nicola Mills, Sanne Nijhof, Harriet Downing, Chris Metcalfe, Gijs Bleijenberg, John Macleod, Paul Stallard, William Hollingworth.

Learn more

• FITNET-NHS trial - Bristol University

See also

• CMRC
• Biopsychosocial model
• Cognitive behavioral therapy
• Graded exercise therapy
• Outcome switching