Identifying key elements of non-pharmacological treatment package for fibromyalgia: Evidence synthesis and Delphi exercise

Kundakci, Burak (2021) Identifying key elements of non-pharmacological treatment package for fibromyalgia: Evidence synthesis and Delphi exercise. PhD thesis, University of Nottingham.

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Fibromyalgia (FM) is a common condition that manifests with chronic widespread pain, fatigue, non-restorative sleep and cognitive dysfunction. FM impacts directly on health and quality of life (QoL) and is associated with a large economic burden on health care systems. Its diagnosis and management are often challenging due to heterogeneous manifestations. Non-pharmacological interventions are recommended as first-line treatment for FM. However, there are no evidence-based recommendations for which intervention(s) to offer patients with different manifestations of FM, and, which of these should be offered as core and adjunctive treatments within a package of care.

Objectives: The overall purpose of the research project was to identify key elements of a non-pharmacological treatment package for FM. The study had the following objectives:

1. To estimate the efficacy of non-pharmacologic treatments for FM using a systematic review with conventional meta-analysis (CMA) approach.

2. To estimate the relative efficacy of non-pharmacologic interventions for FM using a Bayesian network meta-analysis (NMA) approach.

3. To select the most efficacious interventions for different outcomes of FM using a Delphi exercise (consensus building) approach.


Two meta-analytical techniques, CMA and NMA, were conducted in the first stage of the project. Following this, a Delphi exercise was undertaken.

CMA and NMA: MEDLINE, EMBASE, AMED, PsycINFO, CINAHL, Web of Science were systematically searched from their dates of inception until September 2018. In addition, the first 100 articles on Google Scholar were included. Randomised controlled trials (RCTs) comparing any non-pharmacological intervention versus another non-pharmacological intervention, usual care, no treatment, waiting list or placebo/sham treatments in patients with FM aged >16 were included without language restriction. The composite score of the FM Impact Questionnaire (FIQ) was the primary outcome of interest. Pain, fatigue, sleep and depression were assessed as secondary outcomes. Usual care/placebo controlled RCTs were pooled in random-effects conventional meta-analyses (CMA) and standardised mean difference (SMD) and 95% confidence interval (CI) were calculated. Bayesian network meta-analysis (NMA) compared the treatments using usual care as a common comparator. SMDs and 95% credible intervals (CrIs) were estimated between interventions. Direct and indirect evidence were pooled using the random effect model. Modified Cochrane‘s tool was used to assess risk of bias. Publication bias was assessed using funnel plot and Egger’s test.

Delphi exercise: A three-stage Delphi exercise was designed and potential panel members were selected from experts in FM identified from the author list of international FM guidelines (EULAR, Canadian guidelines) and local clinician advice. In the first round Delphi survey, participants were asked to confirm their professional details, select interventions that they thought should be offered to people with FM, and to rate these interventions as core or adjunctive treatment for the four key symptoms of FM (pain, fatigue, sleep disturbance and depression). They were provided a summary of current research evidence from CMA to support their decision-making. Surveys for the second and third rounds were prepared based on the items which did not achieve the consensus threshold of 70%.


16,251 studies were identified and 187 RCTs (n=13,454 participants) met all inclusion criteria for the systematic review. In total, 21 non-pharmacological interventions were evaluated.

CMA: 148 RCTs (n=9,598) were included in the CMA. Exercise was the only intervention associated with significant improvements for all five outcomes [FIQ (SMD=-0.67; 95% CI -0.89, -0.45), pain (-0.84; 95% CI -1.13, -0.55), fatigue (-0.88; 95% CI -1.39, -0.37), sleep (-0.55; 95% CI -1.04, -0.06) and depression (-0.55; 95% CI -0.82, -0.28)]. Psychological treatments including cognitive behavioural therapy (CBT) and mindfulness were significantly more efficacious than usual care for FIQ, pain and depression but showed no improvement for fatigue and sleep. All exercise types were effective at relieving pain. Mind body and strengthening exercises were effective at improving fatigue, while aerobic and strengthening exercises were effective at improving sleep. All exercise types except for aerobic exercise improved depression.

NMA: 78 studies (n = 5,639 participants) met the inclusion criteria. While multidisciplinary treatment (MDT) was the best for improving pain [-1.28 (-1.84, -0.72)], sleep [-1.14 (-2.38, 0.07)] and depression [-1.20 (-1.99, -0.46)], balneotherapy and exercise were the most effective treatments for overall FIQ [-1.06 (-1.52, -0.62)] and fatigue [-0.75 (-1.35, -0.25)] respectively. Data from 47 exercise trials (n = 3,271 participants) were also analysed to examine the relative efficacy of different exercise types. Of the different types of exercise, strengthening showed the greatest benefits for FIQ [-0.76 (-1.39, -0.15)], pain [-0.94 (-1.58, -0.29)] and depression [-0.83 (-1.53, -0.14)], whereas aerobic exercise was the best for fatigue [-0.98 (-2.33, 0.18)] and sleep disorders [-0.96 (-2.08, 0.13)].

Delphi exercise: Of 48 invitees, 17 agreed to participate. These included seven rheumatologists, two physiotherapists, one psychologist, one nurse and six people from other professional backgrounds, specifically physical medicine and rehabilitation, neurology, immunology and public health. Response and completion rates for the 17 participants were 100%. Aerobic exercise, education, sleep hygiene, CBT, mindfulness, mind-body exercise and stress management were recommended for all four outcomes. Also, all these interventions except for mindfulness were voted as core in the management of FM.


Several non-pharmacological interventions are beneficial for FM. Some interventions appear particularly efficacious for certain FM manifestations. The results of this study should be used to guide the selection of the most beneficial interventions according to the predominant symptom(s) of the individual patient. Further research is required to evaluate if such a strategy better improves outcomes in FM patients.


The protocol for the systematic review of non-pharmacological interventions for FM has been registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42017074982.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Abhishek, Abhishek
Zhang, Weiya
Doherty, Michael
Hall, Michelle
Keywords: fibromyalgia, non-pharmacological management, meta-analysis, delphi
Subjects: W Medicine and related subjects (NLM Classification) > WE Muscoskeletal system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 65549
Depositing User: KUNDAKCI, BURAK
Date Deposited: 04 Aug 2021 04:42
Last Modified: 31 Mar 2022 04:30

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