Qigong and Fibromyalgia circa 2017

Qigong is an internal art practice with a long history in China. It is currently characterized as meditative movement (or as movement-based embodied contemplative practice), but is also considered as complementary and alternative exercise or mind–body therapy. There are now six controlled trials and nine other reports on the effects of qigong in fibromyalgia. Outcomes are related to amount of practice so it is important to consider this factor in overview analyses. If one considers the 4 trials (201 subjects) that involve diligent practice (30–45 min daily, 6–8 weeks), there are consistent benefits in pain, sleep, impact, and physical and mental function following the regimen, with benefits maintained at 4–6 months. Effect sizes are consistently in the large range. There are also reports of even more extensive practice of qigong for 1–3 years, even up to a decade, indicating marked benefits in other health areas beyond core domains for fibromyalgia. While the latter reports involve a limited number of subjects and represent a self-selected population, the marked health benefits that occur are noteworthy. Qigong merits further study as a complementary practice for those with fibromyalgia. Current treatment guidelines do not consider amount of practice, and usually make indeterminate recommendations.


Introduction
Qigong is a traditional practice with a history of over 2500 years in China, and many forms have been developed within different contexts [1]. The health benefits of qigong are currently receiving increasing attention, and in 2009, terminology that is more familiar to Western biomedicine was proposed to facilitate further exploration of this potential [2]. Core elements of qigong practice involve movements, meditative components, attention to breathing, and promotion of a state of deep relaxation and integration. Qigong, characterized as meditative movement (MM), uses a framework of movement with unique attentional features [2,3]. A further characterization is as movement-based embodied contemplative practice in which the mind-body (mind-in-body) connection is emphasized; qualities and characteristics of movement are distinguished from conventional exercise, and contemplative aspects are considered within a framework of body awareness and somatic approaches [4]. Tai Chi, as well as several other more recently developed and contemporary somatic therapeutic techniques, are also considered under these umbrella terms [2][3][4]. MM is the more established term, and will be used throughout this report.
Fibromyalgia (FM) is a condition involving chronic pain, sleep disturbances, fatigue, and often additional co-morbidities [5]. In the 1990s, FM was recognized as a clinical entity with tender point criteria, but updated criteria proposed in 2010/2011 and 2016 emphasize the chronic and widespread nature of the pain, the lack of refreshing sleep, and the variability of additional comorbidities [5,6].
FM also has been characterized as a central sensitivity syndrome recognizing the polymodal nature of comorbidities [7] (overlapping conditions include chronic fatigue syndrome, irritable bowel syndrome, headaches, multiple chemical sensitivity, and others). Treatment of FM involves many strategies and can include forms of complementary and alternative medicine (CAM). Treatment guidelines for FM have been developed by several professional organizations, and the most recent versions of such guidelines specifically reference MM as part of CAM within a comprehensive consideration of treatment options [8]. Table 1 provides examples of dedicated terminology used to characterize qigong in recent focused reviews of treatments for FM. Further consideration of evidence for qigong in FM occurs using more general terminology, i.e., in a systematic overview of reviews of CAM [9], an umbrella systematic review of exercise [10], and a Cochrane analysis of mind-body therapies [11].  [17][18][19][20][21][22]; these originated at different sites (USA, Sweden, Canada, Italy) and reflect different forms of qigong and different regimens of practice. Four RCTs involved daily practice of qigong for 6-8 weeks [19][20][21][22]. Some reviews and analyses include a pilot study of external qigong [23], a study in children [24], and studies where qigong was part of multi-component treatment and no daily practice was involved [17,18].
This review article summarizes clinical experiences with qigong in FM in randomized controlled trials (RCTs) as well as other trial forms, and considers research challenges inherent in continued exploration of the health benefit potential of this practice.

Clinical Evidence and Observations
Clinical exploration of effects of qigong in FM to date includes RCTs (Table 2) as well as pilot studies, an observational trial, and case reports (Table 3). Both quantitative and qualitative information is available.
There are challenges to assessing effects of qigong in FM, and these have led to diverse conclusions in systematic reviews and meta-analysis, as well as other reviews ( Table 1). The most homogeneous body of data is represented by N = 4 RCTs involving 201 subjects in which qigong was practiced for 30-45 min daily for 6-8 weeks and there was encouragement to continue practice to 4-6 months [19][20][21][22]. In these trials, there were consistent medium-to-large effect sizes in all domains relevant to FM (pain, sleep, impact, physical and mental function) which were manifest after 6-8 weeks of practice, and benefits were sustained at 4-6 months ( Table 2) [15]. Two of these trials [19,21] used a design in which the wait-list group, used as a control, was subsequently offered qigong training and constituted a delayed intervention group; both trials indicate good reproducibility between the immediate and delayed training groups.  (2) Both undertook continued qigong training and practice because of health experiences with initial practice (over months) Case 1: initial improvements in pain, tension, anxiety, food sensitivities, blood pressure; 12 mos: medications and supplements discontinued; 3 yrs: minimal pain (occasional, local), headaches gone, cognition, sleep, fatigue, mood, skin and circulation all improved Case 2: initial improvements in energy and bowel and bladder function; 6-12 mos: vast improvement in pain and other symptoms (including vision); 3 yrs: resumed eating foods previously allergic to, stopped amitriptyline and supplements Limitations: unknown generalizability; retrospective selection (6) Sawynok and Lynch 2014 [29] Retrospective analysis of qualitative comments by N = 73 who completed initial 6 mo RCT [21] Note: (1) Given that benefits were shown to be related to amount of practice [21], narrative comments for extension trial completers were considered separately in a post hoc manner.
(2) Comments for those who practiced per protocol (≥5 h/wk; N = 38), minimally (≤3 h/wk; N = 13), or in between considered as blocks Narrative: There was a difference in initial experiences (over 6 mos) with qigong by those who completed the extension trial (N = 13) vs. those who did not complete (N = 7); comments recapitulate quantitative domain measures, but also cover other areas Thematic: There was a clear difference in comments on pain, sleep and quality of life by those who practiced per protocol compared to those who practiced minimally; the intermediate group also made positive comments, but these were more moderate in tone Limitations: variable depth of qualitative comments offered by different participants The relationship of amount of qigong practice to outcomes requires specific attention. Effective qigong practice involves diligence and may not be for everyone (despite good intentions), and this factor needs to be considered in analyses. The benefits of qigong in core domains of FM [21] and in chronic fatigue syndrome [31] are related to the amount of practice, providing direct support for the need to consider this factor. In the FM study that compared those who practiced per protocol (≥5 h/week) with those who practiced minimally (≤3 h/week), differences in outcomes were observed in all domains, and effect sizes in the per protocol group were uniformly large (0.95-1.67) [15].
There are several additional reports that further document effects of qigong practice in FM (Table 3). An extension trial involving the addition of further instruction in qigong (forms of meditation) further supports the observation that benefits are related to the amount of practice [27]. Qualitative information from an RCT (qigong for 6 months) [29], and the extension trial (qigong ≥ 12 months) [27], indicates that, in addition to positive comments on core domains that essentially recapitulate the quantitative information (pain, sleep, impact, physical and mental function), health benefits in other areas also are reported (e.g., food allergies, chemical sensitivities, asthma, sleep apnea, migraines, and blood pressure). In those who practiced qigong extensively via involvement in community-based venues (1-3 years), marked health benefits occurred in FM symptomology (pain absent or minimal; other core domains improved), and there were additional benefits (e.g., irritable bowels, food sensitivities, headaches, blood pressure, and skin) [28]. In those who practiced for even longer (5-10 years), health benefits were profound, with a complete resolution of FM symptoms as well as several comorbidities (sleep apnea, high cholesterol, allergies and intolerance to multiple foods, and irritable bowel syndrome); other issues (susceptibility to infections) were much improved, and there were even marked improvements in vision [30]. Benefits in different areas occurred over time and with different time courses. Practitioners that experienced health changes over the first months of practice continued, and even increased, practice over time with the desire to further explore the health potential of the practice. Each of the trials reported in Table 2 have limitations, including the retrospective nature of case selection and the unknown generalizability of observations. Nevertheless, the profound nature of the health benefits in cases with longstanding FM and other comorbidities, where many conventional medical treatments and complementary therapies had previously been used, are particularly interesting. If they are considered to provide "proof-of-concept" information, one must conclude that qigong merits further exploration in FM.
There is an additional report on the effectiveness of external qigong for FM in which participants received 5-7 sessions delivered by an experienced practitioner over three weeks [23]. That study reports good outcomes in 13 individuals, two of whom showed particularly marked and persistent benefits, and over three months, considered themselves cured. External qigong presents unique additional challenges in relation to the nature of the intervention and mechanisms by which health changes occur [1]. It should be noted that some RCTs included sessions of external qigong in addition to the self-practice or internal qigong that was the intervention under investigation [19,27] and that external qigong sessions were also involved in cases of extensive practice [29].

Methodological and Interpretational Challenges of Qigong Trials
Challenges to the conduct of trials on qigong, and other MM forms, have been indicated in several general, as well as FM-specific, reviews [1][2][3][4]15]. Some challenges relate to general experimental design and include: (1) the nature of controls (wait list with treatment as usual, sham interventions such as exercise, educational/psychological support via group processes); (2) blinding (this is not possible for participants, but is for data collection and analysis); (3) small sample size (RCTs of N = 14-128) (funding for such trials is difficult to obtain); (4) description of interventions (there is often limited descriptive information within the study; reference to the form of qigong provides specifics); (5) challenges of adherence during trials and of follow-up (this can bias results towards those who do obtain benefit). These factors lead to the designation of trial quality as "low" and the strength of evidence as "weak". Other challenges are specific to the study of qigong. These include (6) heterogeneity of types of qigong (relies on local resources; styles differ at different geographic sites); (7) diverse instruction protocols and self-practice expectations (the later varies from no home practice to daily practice of 30-45 min over 6-8 weeks and continuing to 6 months); (8) a mix of potentially active factors (exercise, meditative elements, belief and expectation, psychological support); (9) skill levels of instructors and prior experience with FM populations (only some trials are informed by pilot studies); (10) development of predictive methodology to determine who is more likely to succeed with qigong practice (e.g., using health locus of control measures). With respect to continued exploration, the introduction of contemporary terminology and identification of core domains of practice in recent years represents a major advance in this area [2][3][4]. The existence of CONSORT statement variations regarding non-pharmacological interventions provides an additional framework for enhancing reporting trial quality [32]. Overview analysis of any kind must include a consideration of the amount of practice.
In the quest to better understand and improve treatment of chronic pain, the distinction between explanatory/efficacy trials and pragmatic/effectiveness trials is being elaborated [33]. Explanatory/efficacy trials have high internal validity, use pre-determined primary outcomes, have controlled conditions, use inclusion and exclusion criteria, select for homogeneous populations, compare treatments to placebo or reference drug/treatment, and provide information on mechanisms of diseases; they are highly relevant to regulatory approval and drug development. Pragmatic/effectiveness trials exhibit different characteristics, show high external validity, examine the "entire package", use broad inclusion criteria, embed the trial within ongoing regular care, compare to usual care or standards of care, have a primary endpoint of patient care, and may be better situated for examining complex interventions such as qigong. FM is a complex chronic pain condition with multiple comorbidities, and is a challenge for patients who experience it, as well as for health practitioners who treat them [34,35]. Pragmatic trials of qigong may be more relevant than efficacy trials for providing information relating to real-world experiences of FM. Some viewpoints acknowledge pragmatic approaches to complementary therapies for FM if risk assessment indicates a low risk of harm, and within this consideration, qigong is considered potentially beneficial [36,37].

Summary and Conclusions
This manuscript summarizes beneficial effects of qigong in FM as reported in six RCTs and a further nine reports using diverse approaches. Benefits in many domains are statistically related to amount of practice [21], and this factor provides a lens through which to view the additional reports. Individual cases involving extensive practice report remarkable outcomes, both in core domains of FM as well as in other health areas. While the latter reports are limited by small numbers, selection factors, and their retrospective nature, the benefits are striking.
The study of health benefits of qigong presents unique challenges. These include challenges of representing the practice (traditional vs. contemporary terms and constructs), finding language that makes it amenable (to medical professions, as well as to those who wish to learn the practice), determining who is likely to benefit from the practice (it requires diligence and dedication, and is not for everyone), and knowing how much is needed to provide benefit for a particular condition (pain, other symptoms, comorbidities). Trials use specific protocols, but only in some instances is the protocol based on pilot studies. Benefit is related to the amount of practice, yet few studies or overview analyses stratify outcomes for this. Cases indicate that extended practice (guided by initial experiences over the first few months) is of marked benefit in many areas, but no specifics can be provided about which symptom will respond and when. The chronic pain field is now recognizing that efficacy trials and pragmatic trials have different attributes, and that pragmatic approaches can offer useful information that is relevant to the real-world experience of FM. Standard analysis of qigong trials using prescribed approaches lead to modest conclusions about merits, while a pragmatic approach, which recognizes that it is not for everyone and that multiple trial forms can provide useful information, leads to a conclusion that qigong is worthy of further exploration for FM using multiple approaches.