Clinical Trial – Page 9 – American ME and CFS Society

A randomised controlled trial of the monoaminergic stabiliser (-)-OSU6162 in treatment of myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

OBJECTIVE: The monoaminergic stabiliser (-)-OSU6162 has in previous studies shown promising effects on mental fatigue after stroke and traumatic brain injury. This study investigated the safety and effectiveness of (-)-OSU6162 in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

METHODS: A total of 62 patients were randomly assigned to placebo or (-)-OSU6162. Primary outcomes were assessment on the mental fatigue scale (MFS) and the clinical global impression of change (CGI-C) scale. Secondary outcomes were results on the FibroFatigue scale (FF), the Beck Depression Inventory (BDI), the pain visual analogue scale and neuropsychological tests. Assessments were performed at baseline, after 1 and 2 weeks of treatment and at follow-up after 6 weeks.

RESULTS: MFS and CGI-C showed significant improvements for both treatment groups after treatment but not at follow-up; a similar pattern was seen for FF and BDI. However, significant differences between groups could not be demonstrated. On the other hand, correlation analyses showed a significant correlation between (-)-OSU6162 concentration and change in MFS, FF, and BDI score within the concentration interval 0.1-0.7 µM. Exploratory subgroup analyses showed a larger treatment effect with (-)-OSU6162 in improving MFS and FF symptoms in patients on antidepressant therapy compared to those without antidepressant treatment.

CONCLUSION: (-)-OSU6162 was found to be safe and well tolerated. When analysing the entire material (-)-OSU6162 was not found to differ significantly from placebo in alleviating fatigue in ME patients but was superior to placebo in counteracting fatigue in a subgroup of ME patients who received concomitant pharmacological treatment for depression.

Source: Nilsson MKL, Zachrisson O, Gottfries CG, Matousek M, Peilot B, Forsmark S, Schuit RC, Carlsson ML, Kloberg A, Carlsson A. A randomised controlled trial of the monoaminergic stabiliser (-)-OSU6162 in treatment of myalgic encephalomyelitis/chronic fatigue syndrome. Acta Neuropsychiatr. 2017 Dec 7:1-10. doi: 10.1017/neu.2017.35. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29212562

The Young ME Sufferers Trust: No Reported Harassment at Bristol University (Information Obtained Under FOI)

There has been no reported harassment of staff at Bristol University. Yes, you read that correctly.

We have all become accustomed to the increasingly shrill ‘harassment’ accusations against ME patients
and ‘activists’, both via the media and in lectures. This campaign appears to have originated at that now
infamous meeting of the Science Media Centre, revealed by our original 2014 Freedom of Information
Report, now updated under the title Shining a Light on the CMRC Setup (http://www.tymestrust.org/pdfs/ shiningalight.pdf). Members of the UK Research Collaborative have continued to spread these allegations ever since its launch.

In Shining a Light we stated: In the records of the meeting where ‘harassment’ of researchers was discussed, no mention was made of personal threats such as have been reported in the media. Freedom of Information (FOI) requests were listed as the most damaging type of ‘harassment’. The 2016 tribunal appeal Judgement ordering QMUL to release the PACE trial data highlights that Professor Trudie Chalder accepts that “no threats have been made either to researchers or participants”.

And yet the accusations persist and have even escalated. Tymes Trust has found this constant narrative so abhorrent that we have sought some answers. We have, once again, sought evidence.

You can read the rest of this report here: http://www.tymestrust.org/pdfs/noharassmentbristol.pdf

Clinical and cost-effectiveness of the Lightning Process in addition to specialist medical care for paediatric chronic fatigue syndrome: randomised controlled trial

Editor’s Comment: Numerous critiques of the Lightning Process have been made by physicians, medical practitioners, and patient organizations. There are cases in which LP has resulted in long-lasting physical harm. (You can read about these cases here and here.) Dr. Charles Shepherd, an ME/CFS specialist, does not recommend LP for any ME/CFS patients.

Abstract:

OBJECTIVE: Investigate the effectiveness and cost-effectiveness of the Lightning Process (LP) in addition to specialist medical care (SMC) compared with SMC alone, for children with chronic fatigue syndrome (CFS)/myalgic encephalitis (ME).

DESIGN: Pragmatic randomised controlled open trial. Participants were randomly assigned to SMC or SMC+LP. Randomisation was minimised by age and gender.

SETTING: Specialist paediatric CFS/ME service.

PATIENTS: 12-18 year olds with mild/moderate CFS/ME.

MAIN OUTCOME MEASURES: The primary outcome was the the 36-Item Short-Form Health Survey Physical Function Subscale (SF-36-PFS) at 6 months. Secondary outcomes included pain, anxiety, depression, school attendance and cost-effectiveness from a health service perspective at 3, 6 and 12 months.

RESULTS: We recruited 100 participants, of whom 51 were randomised to SMC+LP. Data from 81 participants were analysed at 6 months. Physical function (SF-36-PFS) was better in those allocated SMC+LP (adjusted difference in means 12.5(95% CI 4.5 to 20.5), p=0.003) and this improved further at 12 months (15.1 (5.8 to 24.4), p=0.002). At 6 months, fatigue and anxiety were reduced, and at 12 months, fatigue, anxiety, depression and school attendance had improved in the SMC+LP arm. Results were similar following multiple imputation. SMC+LP was probably more cost-effective in the multiple imputation dataset (difference in means in net monetary benefit at 12 months £1474(95% CI £111 to £2836), p=0.034) but not for complete cases.

CONCLUSION: The LP is effective and is probably cost-effective when provided in addition to SMC for mild/moderately affected adolescents with CFS/ME.

TRIAL REGISTRATION NUMBER: ISRCTN81456207.

Source: Crawley EM, Gaunt DM, Garfield K, Hollingworth W, Sterne JAC, Beasant L, Collin SM, Mills N, Montgomery AA. Clinical and cost-effectiveness of the Lightning Process in addition to specialist medical care for paediatric chronic fatigue syndrome: randomised controlled trial. Arch Dis Child. 2017 Sep 20. pii: archdischild-2017-313375. doi: 10.1136/archdischild-2017-313375. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28931531

How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome has been a controversial diagnosis, resulting in tensions between patients and professionals providing them with care. A major constraint limiting progress has been the lack of a ‘gold standard’ for diagnosis; with a number of imperfect clinical and research criteria used, each defining different, though overlapping, groups of people with myalgic encephalomyelitis or chronic fatigue syndrome. We review basic epidemiological concepts to illustrate how the use of more specific and restrictive case definitions could improve research validity and drive progress in the field by reducing selection bias caused by diagnostic misclassification.

Source: Nacul L, Lacerda EM, Kingdon CC, Curran H, Bowman EW. How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies? J Health Psychol. 2017 Mar 1:1359105317695803. doi: 10.1177/1359105317695803. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28810428

Cognitive behaviour therapy and objective assessments in chronic fatigue syndrome

Abstract:

Most evaluations of cognitive behavioural therapy to treat people with chronic fatigue syndrome/myalgic encephalomyelitis rely exclusively on subjective self-report outcomes to evaluate whether treatment is effective. Few studies have used measures appropriate to assessing whether cognitive behavioural therapy changes in more objective measures. A review of studies incorporating objective measures suggests that there is a lack of evidence that cognitive behavioural therapy produces any improvement in a patient’s physical capabilities or other objective measures such as return to work. Future studies of chronic fatigue syndrome/myalgic encephalomyelitis should include some objective assessments as primary outcomes. If this is to include activity monitors, we first need a sound baseline dataset.

Source: McPhee G. Cognitive behaviour therapy and objective assessments in chronic fatigue syndrome. J Health Psychol. 2017 Aug;22(9):1181-1186. doi: 10.1177/1359105317707215. Epub 2017 Jun 19. https://www.ncbi.nlm.nih.gov/pubmed/28805529

PACE investigators’ response is misleading regarding patient survey results

Abstract:

The PACE investigators’ citation of a patient survey might mislead readers into thinking that the experience of people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) supports PACE findings. In fact, patient survey evidence directly contradicts the results of the PACE trial. A review of survey data published between 2001 and 2015 reveals that for most patients, graded exercise therapy leads to worsening of symptoms, cognitive behavioural therapy leads to no change in symptoms, and pacing leads to improvement. The experience of people with ME/CFS as reflected in surveys is a rich source of information, made more compelling by the consistency of results. Consequently, patient survey evidence can be used to inform practice, research and guidelines. Misrepresentation of patient experience must be vigorously challenged, to ensure that patients and health professionals make decisions about therapies based on accurate information.

Source: Kirke KD. PACE investigators’ response is misleading regarding patient survey results. J Health Psychol. 2017 Aug;22(9):1168-1176. doi: 10.1177/1359105317703787. Epub 2017 May 11. https://www.ncbi.nlm.nih.gov/pubmed/28805528

Bias, misleading information and lack of respect for alternative views have distorted perceptions of myalgic encephalomyelitis/chronic fatigue syndrome and its treatment

Abstract:

The PACE trial is one of the most recent studies evaluating cognitive behavioural therapy and graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome. These interventions are based on a model which assumes that symptoms are perpetuated by factors such as misguided beliefs and a lack of activity. Our analysis indicates that the researchers have shown significant bias in their accounts of the literature and may also have overstated the effectiveness of the above treatments. We submit that their approach to criticisms undermines the scientific process and is inconsistent with best practice.

Source: Goudsmit E, Howes S. Bias, misleading information and lack of respect for alternative views have distorted perceptions of myalgic encephalomyelitis/chronic fatigue syndrome and its treatment. J Health Psychol. 2017 Aug;22(9):1159-1167. doi: 10.1177/1359105317707216. Epub 2017 May 29. https://www.ncbi.nlm.nih.gov/pubmed/28805527

The problem of bias in behavioural intervention studies: Lessons from the PACE trial

Abstract:

Geraghty’s recent editorial on the PACE trial for chronic fatigue syndrome has stimulated a lively discussion. Here, I consider whether the published claims are justified by the data. I also discuss wider issues concerning trial procedures, researcher allegiance and participant reporting bias. Cognitive behavioural therapy and graded exercise therapy had modest, time-limited effects on self-report measures, but little effect on more objective measures such as fitness and employment status. Given that the trial was non-blinded, and the favoured treatments were promoted to participants as ‘highly effective’, these effects may reflect participant response bias. In non-blinded trials, the issue of reporting biases deserves greater attention in future.

Source: Wilshire C. The problem of bias in behavioural intervention studies: Lessons from the PACE trial. J Health Psychol. 2017 Aug;22(9):1128-1133. doi: 10.1177/1359105317700885. Epub 2017 Mar 23. https://www.ncbi.nlm.nih.gov/pubmed/28805526

PACE-GATE: An alternative view on a study with a poor trial protocol

Abstract:

The controversies surrounding the effectiveness of cognitive behavioural therapy and graded exercise therapy for chronic fatigue syndrome are explained using Cohen’s d effect sizes rather than arbitrary thresholds for ‘success’. This article shows that the treatment effects vanish when switching to objective outcomes. The preference for subjective outcomes by the PACE trial team leads to false hope. This article provides a more realistic view, which will help patients and their doctors to evaluate the pros and cons.

Source: Stouten B. PACE-GATE: An alternative view on a study with a poor trial protocol. J Health Psychol. 2017 Aug;22(9):1192-1197. doi: 10.1177/1359105317707531. Epub 2017 May 12. https://www.ncbi.nlm.nih.gov/pubmed/28805525

PACE trial authors continue to ignore their own null effect

Abstract:

Protocols and outcomes for the PACE trial were changed after the start of the trial. These changes made substantial differences, leading to exaggerated claims for the efficacy of cognitive behavior therapy and graded exercise therapy in myalgic encephalomyelitis/chronic fatigue syndrome. The small, self-reported improvements in subjective measures cannot be used to say the interventions are effective, particularly in light of the absence of objective improvement. Geraghty’s criticism of the trial was reasonable and supported by the evidence.

Source: Vink M. PACE trial authors continue to ignore their own null effect. J Health Psychol. 2017 Aug;22(9):1134-1140. doi: 10.1177/1359105317703785. Epub 2017 Apr 27. https://www.ncbi.nlm.nih.gov/pubmed/28805519