Study Protocol Clinical Trial Medicine ® OPEN Effectiveness, cost-utility, and benefits of a multicomponent therapy to improve the quality of life of patients with fibromyalgia in primary care A mixed methods study protocol ∗ Rosa Caballol Angelats, MDa,b, Alessandra Queiroga Gonçalves, PhDc,d, Carina Aguilar Martín, MD, PhDc,e, , Maria Cinta Sancho Sol, BScb,f, Gemma González Serra, MScb,g, Marc Casajuana, MSch,i, Noèlia Carrasco-Querol, PhDc, José Fernández-Sáez, PhDc, Maria Rosa Dalmau Llorca, MD, PhDa,c, Rosa Abellana, PhDj, Anna Berenguera, PhDh,i, on behalf of SensiTEbre group Abstract Introduction: Fibromyalgia (FM) is a chronic condition characterized by chronic pain, fatigue and loss of function which significantly impairs quality of life. Although treatment of FM remains disputed, some studies point at the efficacy of interdisciplinary therapy. This study aims to analyze the effectiveness, cost-utility and benefits of a multicomponent therapy on quality of life (main variable), functional impact, mood and pain in people suffering from FM that attend primary care centers (PCCs) of the Catalan Institute of Health (ICS). Methods and analysis: A 2-phase, mixed methods study has been designed following Medical Research Council guidance. Phase 1: Pragmatic randomized clinical trial with patients diagnosed with FM that attend one of the 11 PCCs of the ICS Gerència Territorial Terres de l’Ebre. We estimate a total sample of 336 patients. The control group will receive usual clinical care, while the multicomponent therapy group (MT group) will receive usual clinical care plus group therapy (consisting of health education, exercise and cognitive-behavioural therapy) during 12 weeks in 2-hourly weekly sessions. Analysis: the standardized mean response and the standardized effect size will be assessed at 3, 9, and 15 months after the beginning of the study using multiple linear regression models. Utility measurements will be used for the economic analysis. Phase 2: Qualitative socio constructivist study to evaluate the intervention according to the results obtained and the opinions and experiences of participants (patients and professionals). We will use theoretical sampling, with 2 discussion groups of participants in the multicomponent therapy and 2 discussion groups of professionals of different PCCs. A thematic content analysis will be carried out. Ethics and dissemination: This study protocol has been approved by the Clinical Research Ethics Committee of the Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (code P18/068). Articles will be published in international, peer-reviewed scientific journals. Trial registration: Clinical-Trials.gov: NCT04049006. The project received a research grant from the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain), awarded on the 2018 call under the Health Strategy Action 2017–2020, within the National Research Program oriented to Societal Challenges, within the Technical, Scientific and Innovation Research National Plan 2017-2020, with reference PI1800943, co-funded with European Union ERDF funds (European Regional Development Fund) and with a scholarship from Dr. Ferran Foundation awarded on 2017. The funders financed the project but will not participate in any phase of the investigation. The funders will not have any authority over any of the activities of the project. The authors have no conflicts of interest to disclose. a Equip d’Atenció Primària Tortosa Est, Institut Català de la Salut, Tortosa, b Unitat d’Expertesa en Sindromes de Sensibilització Central Terres de l’Ebre, Institut Català de la Salut, Tortosa, Tarragona, c Unitat de Suport a la Recerca Terres de l’Ebre, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), d Unitat Docent de Medicina de Família i Comunitària Tortosa-Terres de L‘Ebre, Institut Català de la Salut, e Unitat d’Avaluació, Direcció d’Atenció Primària Terres de l’Ebre, Institut Català de la Salut, f Fundació Pere Mata Terres de l’Ebre, g Servei de Rehabilitació i Medicina Física, Hospital de Tortosa Verge de la Cinta, Institut Català de la Salut, Tortosa, h Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, i Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès, j Departament de Fonaments Clínics, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain. ∗ Correspondence: Carina Aguilar Martín, Unitat de Suport a la Recerca Terres de l’Ebre, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Spain (e-mail: caguilar.ebre.ics@gencat.cat). Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite this article: Angelats RC, Gonçalves AQ, Martín CA, Sol MCS, Serra GG, Casajuana M, Carrasco-Querol N, Fernández-Sáez J, Llorca MRD, Abellana R, Berenguera A. Effectiveness, cost-utility and benefits of a multicomponent therapy to improve the quality of life of patients with fibromyalgia in primary care. Medicine 2019;98:41(e17289). Received: 29 August 2019 / Accepted: 30 August 2019 http://dx.doi.org/10.1097/MD.0000000000017289 1 Angelats et al. Medicine (2019) 98:41 Medicine Abbreviations: FM = fibromyalgia, ICS = Catalan Institute of Health, MT group = multicomponent therapy group, PCCs = primary care centres. Keywords: cost utility analysis, fibromyalgia, implementation science, pragmatic clinical trials, primary health care, qualitative research, quality of life 1. Introduction achieve a better implementation of interventions adapted to the people and their environment, and greater sustainability. The Fibromyalgia (FM) is a disease characterized by chronic pain, Medical Research Council has established a methodology to fatigue, and loss of function, which physically limits the patient develop this type of interventions, which comprise various phases and consequently impacts mood, the social and working that are implemented iteratively using both quantitative and environments, generates sleep disturbances and generally impairs qualitative methodologies. The combination of methodologies quality of life.[1] FM is classified as a central sensitivity syndrome incorporates the input of patients, in order to better adapt the (CSS), and is frequently associated to other CSS such as Chronic intervention to their needs, and takes into account the character- Fatigue Syndrome and Multiple Chemical Sensitivity.[2,3] istics (social, resources, health etc.) of the environment where the The diagnosis of FM is based on clinical criteria, initially intervention takes place.[34–36] defined by the American College of Rheumatology.[4,5] New In 2016, 18 accredited units specialized in Central Sensitivity amendments added in 2016 improve the detection of the disease Syndromes (USCSS) were created throughout Catalonia,[37] with in the primary care (PC) setting, although at the cost of lower the aim to provide consistent health care to all patients with specificity.[6] Prevalence of FM in the general population ranges fibromyalgia.[38] The USCSS consist of interdisciplinary teams between 0.2% and 6.6%, and in women from 2.4% to 6.8%.[7] based both in primary care centers (PCCs) and in hospitals. In Spain, prevalence is estimated at 2.45% (D. Seoane-Mato, After reviewing the available evidence, we want to propose a personal communication, July 2019), with a female/male ratio of therapy for patients with FM to be delivered within the primary 21:1, and is usually diagnosed in middle-aged people.[1,8] health care system. The objective of this proposal is to analyze the The cost of FM for the health system is high.[9] Total annual effectiveness and cost-utility of a multicomponent therapy that costs per patient in industrialized countries are estimated between consists of health education, exercise and cognitive-behavioral 7256 and 7900 euros, and indirect costs (for instance, therapy, and to compare it with usual clinical care with regard to productivity loss) are considered higher than direct costs (such quality of life, functional impact, mood and pain in patients with as medical visits and multiple prescriptions).[10–12] In addition, FM that attend Primary Health Care Centers (PCCs) of the when comparing with other conditions that cause chronic pain, Gerència Territorial Terres de L’Ebre of the Catalan Institute of FM is associated with higher rates of unemployment and a higher Health (ICS). Based on the data collected about the opinion and number of sick leave days.[13] experience of patients and professionals, the following aspects of The best treatment for FM is currently disputed. Some studies the implementation of the intervention will also be evaluated: have shown clinical improvement with non-pharmacological acceptability, adaptability, adherence, feasibility and compatibil- therapies, particularly with exercise[14] and with cognitive- ity. This intervention is founded on the transtheoretical model of behavioral therapy (CBT).[15,16] There is also some evidence change, which can be applied to multiple behaviors and risk on the effectiveness of multicomponent group therapy, which factors and is recommended in research with a multibehavioral or involves patient education, exercise and CBT[17,18], with reported multiple risk approach. Furthermore, the intervention applies the clinical improvement that lasts 3 to 12 months after the conceptual framework of the “5As” (Assess, Advise, Agree, intervention.[19,20] Interdisciplinary interventions conducted Assist, and Arrange-follow up) to standardize and facilitate the from hospitals[21–23] and PC[24–27] have obtained similar positive intervention.[39,40] results. The most recent review (2017) of the European League Against Rheumatism (EULAR)[28] on the management of FM endorsed the abovementioned therapies, and also included 2. Methods and design promising results on complementary therapies such as mindful- 2.1. Setting and participants ness, hydrotherapy and acupuncture. There is also evidence on the benefits of some drugs for the treatment of severe pain and Participants will be patients diagnosed with FM that attend 11 insomnia (amitriptyline and cyclobenzaprine, duloxetine and PCCs of the ICS Gerència Territorial Terres de l’Ebre. pregabalin).[28] Few studies on the economic evaluation of interventions for 2.1.1. Inclusion criteria (all criteria must be met). patients with FM have been published to date.[29–33] With respect  Clinical diagnosis of FM (International Classification of to cost-utility, psychology-based therapies showed better results Diseases-10 codes: M79.0, M79.7); in most studies.[30–33] A cost-utility study carried out in Spain that  Having a phone number; compared a psychoeducational intervention with usual clinical  Accepting participation in the study. care found that on average, the incremental gain in quality- adjusted life years (QALYs) per person was 0.12 (0.06 to 2.1.2. Exclusion criteria. 0.19).[30] Complex interventions, as well as interventions based on  Active psychotic episode; Health Coaching, aim to promote healthy habits. The design of  Intellectual impairment; complex, multimodal, and interdisciplinary interventions aims to  Severe depression and personality disorder; 2 Angelats et al. Medicine (2019) 98:41 www.md-journal.com  Auto/heteroaggressive behaviour; 2.3.2. Randomization, recruitment, and data collection. For  Self-reported use of psychoactive substances; each study unit a randomization list will be generated according  Having previously participated in a multicomponent therapy to Efron procedure,[41] using the IBM SPSS Statistics v.23.0. group (MT group) in the Terres de l’Ebre (pilot study); package for Windows. An appointment will be arranged with  Unable to attend the group sessions. patients who meet inclusion criteria for the first interview, where they will receive the information leaflet of the study and will sign the informed consent form. Next, patients will be allocated to a 2.2. Training of FM specialists study group according to the randomization list. Additionally, Before starting the study, a nurse or a general practitioner of each the patients will be asked to respond to the study questionnaires PCC (hereafter called “FM specialists”) will receive training on (SF-36v2 health survey questionnaire[42] (Optum, Inc. license aspects related to FM, exercise, cognitive-behavioral therapy and number QM048943), Revised Fibromyalgia Impact Question- on the methodology of data collection for the study. To guarantee naire (FIQR),[43,44] Visual Analog Scale (VAS),[45,46] tender quality and consistency, annual refresher training will be points[47] and Hospital Anxiety and Depression Scale provided. (HADS)[48,49]) and will take part in the activities planned for Following Medical Research Council guidelines[35] on the each group (see below). evaluation of complex interventions, we will conduct a mixed Control group: Patients in the control group will receive methods study consisting of 2 phases. Figure 1 shows the study regular clinical care in their PCC,[50] which consists on an flowchart. individual visit with the FM specialist, who will conduct a standardized clinical history and will inform the patient on the 2.3. Phase 1: Study of the effectiveness and cost-utility of disease using a custom designed leaflet. the intervention MT group: in addition to usual PC clinical care, participants 2.3.1. Study design and sample size. We will carry out a will receive MT consisting of health education, exercise and pragmatic randomized clinical trial (type: parallel group) with cognitive-behavioural therapy, during 12 weeks in 2-hourly patients suffering from FM to compare the effect of a weekly sessions (Fig. 2). Group therapy will be delivered by the multicomponent therapy with usual clinical care in PC. The FM specialist in each PCC, with the support of the physiothera- intervention will be structured in study units. Each study unit pist and the psychologist of the USCSS. consists of a MT group and a control group, each with 10 to 12 Patients in the control and MT groups will receive an participants. Assuming an alpha error of 0.05 and a beta error of appointment to attend their PCC at 3, 9, and 15 months after 0.05 in a bilateral contrast, and an estimated dropout rate of 20%, the beginning of the study. During these appointments they will a sample size of 130 participants in each group of the study will be be asked to respond to the study questionnaires (SF-36, FIQR, required in order to detect a score difference equal or higher than 5 VAS, tender points and HADS). units in the Short Form 36 (SF-36) health survey questionnaire. A All data will be collected in a software application that has common standard deviation of 10 is assumed. Based on these been custom designed for the treatment protocol of FM in the calculations, we will create a total of 14 MT groups, with their study sites. This application will be available in the Terres de respective control groups, between April and December 2019. The l’Ebre ICS website and will be linked to the electronic medical number of participants estimated is 336 patients. records. The application aims to standardize all information Phase 1: Clinical Trial Elegibility Assessment Follow-up Control Baseline at 3, 9, 15 group Interview months Randomizaon (SF36, FIQR, (SF36, FIQR, Stascal (n= 336) VAS, Tender VAS, Tender analysis Points and MT group Points and HADS HADS quesonnaires) quesonnaires) 2 groups Parcipants in Phase 2:Qualitave Study MT group Themac 4 discussion groups (8-12 Content parcipants/group) 2 groups analysis Professionals Figure 1. Flowdiagram of the study. FIQR = Revised Fibromyalgia Impact Questionnaire, HADS = Hospital Anxiety and Depression Scale, MT group = multicomponent therapy group, SF-36 = Short Form 36 health survey questionnaire, VAS = visual analog scale. 3 Angelats et al. Medicine (2019) 98:41 Medicine HEALTH EDUCATION COMPONENT PHYSICAL COMPONENT PSYCHOLOGICAL COMPONENT Session 1 Introduction to Multicomponent Therapy 6-min walking test Cognitive-behavioural strategies Breathing and Progressive walking exercises 6-20min (home) Session 2 Cognitive-behavioural strategies and Pain management Neurophysiology and Pharmacology of Pain Breathing and Relaxation Session 3 Breathing and Relaxation Management of Attention Session 4 Techniques of Postural Hygiene Stretching exercises Session 5 Nutrition Breathing and Relaxation Session 6 Management of Insomnia Joint exercises/ games Session 7 Memory Stretching/joint exercises Session 8 Sexuality Postural hygiene /stretching Strength/joint exercises Activities and Mood Session 9 Planning pleasant activities Session 10 Coordination exercises Breathing and Relaxation Management of Difficulties Session 11 6-min walking test Identification of Objectives Session 12 Design by Ignasi Barrera Curto Figure 2. Content of the multicomponent therapy sessions. related to patients with FM who visit the USCSS and will be used change in the control group, and the standardized effect size for research and for clinical care. (SES). The SES will be calculated as the difference of the mean of the scores of both groups divided by the combined standard 2.3.3. Masking. Due to the study characteristics (pragmatic deviation. To detect differences within each study group, the trial), it is not possible to mask the health professionals and difference of the means between baseline and each follow up participants. The data analyst will be blind to the patients’ point will be calculated, and also the effect size or standardized allocation group. mean response (SMR), in accordance with Kazis’ method.[52] The 2.3.4. Outcomes. The main result variable of the study is quality SMR will be calculated as the mean change divided by the of life (SF-36v2).[42,51] Table 1 shows the study variables, the standard deviation of change. To evaluate the SMR and the SES measurement instruments and the timing of data collection. All we will use Cohen rule, which classifies effect size as small (0.2 to variables will be collected for both study groups. The cost-utility 0.5), medium (0.5 to 0.8), and large (greater than 0.8). variables will be collected at 2 time points: 1 year before the Finally, multiple linear regression models will be used to beginning of the study and 1 year after the beginning of the study. explore the variables associated with the percentage change [(follow-up scores minus baseline scores)/baseline scores  100] 2.3.5. Statistical analysis. Data analysis will take place at of the scores in the SF-36 and other questionnaires. The baseline and after 3, 9, and 15 months. Intention to treat analysis multivariate models will include variables that might be clinically will be used. The quality of data collection will be periodically linked, and the variables statistically significant in the previous monitored to minimize biases due to incomplete data. The non- bivariate analyses. Models will be also adjusted by confounding response bias will be evaluated at all points of follow up. variables. Interactions and collinearity will be evaluated.[53] Descriptive analyses of variables will be carried out using the Statistical significance for all study tests will be set at a  0.05 and media (standard deviation), median (interquartile range) or 95% CI. The statistical package IBM SPSS Statistics v.23.0.for frequency (percentage), depending on the distribution of Windows will be used. variables. For comparisons between and within the 2 study groups 2.3.6. Economic evaluation. The perspective of the National (intervention and control) and the study variables, the following Health System will be used for the analysis of the economic tests will be used: Student’s t test for independent or paired data, evaluation. The use of resources and their respective costs for McNemar, Chi-square test and analysis of variance or the both groups will be described and compared. Temporal horizon corresponding non-parametric tests. will be 12 months, with a discount rate of 3%. Costs will be To evaluate the effectiveness of the intervention at each point calculated according to the most recent official prices published in of follow up, we will calculate the change in scores of the SF-36 the Diari Oficial de la Generalitat de Catalunya (DOGC)[54] for and the other questionnaires in the intervention group minus the the public sector, updated to 2019. The utilities will be calculated 4 Table 1 Study variables, measurement instruments and timing of data collection. Data collection Variables Measurement instrument Type of response Score (range/dimension) Baseline Follow-up Dependent variables 3 months 9 months 15 months Quality of life Short Form 36 (SF-36) Likert (0 = worse to 100 = better) 36 items; 8 dimensions: physical ▪ ▪ ▪ ▪ health survey questionnaire functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health (0– 100/dimension) Angelats et al. Medicine (2019) 98:41 Functional impact FM Revised Fibromyalgia Likert (0 = better to 100 = worse) 21 items; 3 dimensions: ▪ ▪ ▪ ▪ Impact Questionnaire (FIQR) function, impact, symptoms (0–10/dimension) Presence of pain Tender points Likert: 0 = better; 18 = worse 18 pain points (0–18) ▪ ▪ ▪ ▪ Intensity of pain Visual Analog Scale (VAS) Likert: 0 = absence of pain; 10 (0–10) ▪ ▪ ▪ ▪ 10 = worst possible pain Mood Hospital Anxiety and Likert (0–7 = NO anxiety/depression; 14 items; 2 dimensions: anxiety, ▪ ▪ ▪ ▪ Depression Scale (HADS) 8–10 = doubtful; >11 = probable) depression (0–3/dimension) Independent variables Socio-demographic Age, gender, civil status, educational level, Ad-hoc questionnaire Nominal ▪ social class, employment, living arrangement Clinical 5 Physical manifestations Ad-hoc questionnaire Nominal ▪ Trigger factor (physical or psychological) Ad-hoc questionnaire Nominal ▪ Perpetuating factor (physical or psychological) Ad-hoc questionnaire Nominal ▪ Family history of FM Ad-hoc questionnaire Nominal ▪ Psychological and cognitive symptoms Ad-hoc questionnaire Nominal ▪ Comorbidities electronic medical history Nominal ▪ Duration of disease in years electronic medical history Quantitative (years) ▪ Health history electronic medical history Nominal ▪ Blood tests results electronic medical history Quantitative ▪ Pharmacotherapy electronic medical history Nominal ▪ ∗ Costs-related variables Direct medical Pharmacy billing Electronic medical history Quantitative (euro) One year before the beginning of the study compared with one year after the beginning of the study Cost of visits to the GP Electronic medical history /DOGC Quantitative (euro) Cost of visits to the nurse Electronic medical history /DOGC Quantitative (euro) Cost of visits to the emergency department Electronic medical history /DRG Quantitative (euro) Cost of referrals to specialists Electronic medical history /DOGC Quantitative (euro) Indirect Medical Costs due to loss of productivity (days of sick leave) Electronic medical history /INE Quantitative (euro) ∗ One year before the beginning of the study compared with one year after the beginning of the study. DOGC = Official Journal of the Generalitat de Catalunya, DRG = diagnosis-related groups, FM = fibromyalgia, GP = general practitioner, INE = National Institute of Statistics. www.md-journal.com Angelats et al. Medicine (2019) 98:41 Medicine using the SF-36v2, to obtain the quality-adjusted life years because this intervention is devised as a long-term healthcare (QALYs) as effectiveness measure. The incremental ratio of the commitment. Confidentiality of study subjects will be guaran- cost-utility will be calculated dividing the difference in total mean teed, in agreement with the Organic Law of Personal Data costs in both groups by the differences in QALYs. To check Protection (03/2018 December 5, LOPD) and with the Regula- robustness of results we will carry out a sensitivity analysis with tion (EU) 2016/679 (April 27) of the European Parliament and various discount rates and different costs. Table 1 shows costs- Council of Data Protection (RGPD) and the national regulations related variables, measurement instruments and timing of data of application. Any alteration of the study protocol will be collection. submitted to the ethical committee of the IDIAPJGol for approval and will be published in clinical trials.gov. 2.4. Phase 2: Study of the evaluation of the intervention The results of the study will be published in scientific journals using qualitative methodology and will be presented in national and international meetings. The results will be communicated to the patients of our health region The evaluation of the intervention will be founded on the by means of a meeting and also through the local and national constructs and guidelines suggested by experts of implementation media, and will be also disseminated to the general population. research.[55,56] The objective of this Phase is to evaluate the intervention with the use of qualitative methodology, with the aim to detect improvable aspects according to the opinion and 3. Discussion experiences of participants (users and professionals). This study aims to provide evidence on the effectiveness of a multicomponent therapy implemented in the public primary care 2.4.1. Study design. Interpretive, descriptive qualitative re- setting with the objective to improve the quality of life of patients search will be carried out. diagnosed with FM. 2.4.2. Participants, sampling, and recruitment. Patients who The proposal of the study originates from a healthcare demand have participated in 95% of the MT group sessions, and PC which requires interdisciplinary collaboration between general professionals. We will use theoretical sampling to achieve practitioners, nurses, psychologists, physiotherapists, rheuma- maximum discursive variability. Informants of different gender, tologists and physical medicine, and rehabilitation doctors. The age, socioeconomic status, geographical area and progression of project will take into account the available health resources in PC, disease will be selected amongst participants. Regarding PC the perceptions of patients and professionals, and will also professionals, we will include informants of both genders, evaluate cost-utility. different age groups and disciplines (general practitioners, nurses, Since current evidence suggests that multicomponent group psychologists, physiotherapists, rheumatologists and physical therapy is the most successful treatment for FM,[58–60] the medicine and rehabilitation doctors). emerging challenge for the health system is to implement this approach effectively and sustainably in PC. We believe that PC 2.4.3. Data collection. Two discussion groups of participants constitutes the ideal setting for this type of interventions, since it and 2 discussion groups of professionals from different PCCs will provides accessibility and long-term care. However, data from be organized. These 4 groups of 8 to 12 people will follow a topic the primary care setting and data comparing the cost-effective- list. When necessary, additional discussion groups will be ness of treatments provided in PC versus hospital-based treat- conducted to achieve discourse saturation. The discussion groups ments remain scarce. will be audio and video recorded prior informed consent and will If this intervention is effective, we anticipate a swift transfer of be literally and systematically transcribed. Identifying data of the results in our setting and in other regions of Spain with similar informants in the transcripts will be anonymized. primary care systems. A common strategic national health plan 2.4.4. Data analysis. The text corpus will include the transcripts would facilitate further expansion of this program. Moreover, of the discussion groups and the field notes of the groups’ since other European nations have already implemented the observers. After successive readings of the sole text corpus and healthcare model organized in USCSS, they could also benefit the formulation of pre analytical intuitions, a thematic interpre- from our findings. A pilot study conducted in rehabilitation tive content analysis will be carried out with the support of the centers in Belgian hospitals showed an improvement regarding Atlas-Ti programme and thereafter triangulated amongst the the impact of FM, pain in tender-points and other health various members of the research team.[57] The meanings will be parameters at the end of a multicomponent therapy lasting 12 interpreted and an explanatory framework will be created with weeks that combined exercise and CBT, with the exception of the contributions of each type of informant (patients and patients with moderate depression.[18] In this study improvement professionals participating in the study). started after 6 weeks of therapy, but no information is provided on the duration of the beneficial effects. One limitation of our project is that the group leaders cannot 2.5. Ethics and dissemination be blinded to treatment allocation. However, the data analyst will This study protocol (version 1, 04/04/2018) has been approved be blinded to the participants’ allocation group. In order to by the Clinical Research Ethics Committee of the Fundació minimize follow-up variability, the group leaders will receive Institut Universitari per a la recerca a l’Atenció Primària de Salut instruction before the start of the study, and subsequent annual Jordi Gol i Gurina (IDIAPJGol), on 25/04/2018 (code P18/068), refresher training. In addition, the educational and therapeutic in agreement with the Declaration of Helsinki/Tokyo. All contents of the group sessions will be standardized. Finally, all participants will receive oral and written information about study units will consist of the same 3 professionals: the FM the study and Informed Consent will be obtained. The research specialist of the PCC, a physiotherapist and one psychologist. team undertakes to invite patients in the control group to This study will provide novel scientific evidence, since few participate in the next MT group that takes place in their PCC, randomized clinical trials in this area of knowledge include 6 Angelats et al. Medicine (2019) 98:41 www.md-journal.com qualitative methodology to evaluate multicomponent interven- Sancho Sol, Gemma González Serra, Marc Casajuana, Noèlia tions.[58] The qualitative phase of the project will contribute data Carrasco-Querol, José Fernández-Sáez, Anna Berenguera. for the evaluation of the acceptability and feasibility of the Writing – review & editing: Rosa Caballol Angelats, Alessandra intervention, in accordance with the opinion and experiences of Queiroga Gonçalves, Carina Aguilar Martín, Maria Cinta participants (patients with FM and health professionals). It will Sancho Sol, Gemma González Serra, Marc Casajuana, Noèlia also contribute information on barriers and facilitators that can Carrasco-Querol, José Fernández-Sáez, Maria Rosa Dalmau be used to design an intervention more flexible, dynamic, and Llorca, Rosa Abellana, Anna Berenguera. adapted to the needs of participants. References Acknowledgments [1] Mas AJ, Carmona L, Valverde M, et al. Prevalence and impact of The authors are grateful to the following Departments from the fibromyalgia on function and quality of life in individuals from the general population: results from a nationwide study in Spain. Clin Exp ICS for their contribution in the development and implementa- Rheumatol 2008;26:519–26. tion of the study: Gerència Territorial ICS Terres de l’Ebre, [2] Kevin C, Fleming MD, Volchek MM. Central sensitization syndrome Direcció d’Atenció Primària de Terres de l’Ebre and Unitat de and the initial evaluation of a patient with fibromyalgia: a review. Med J Sistemes d’ informació de la Gerència Territorial Terres de l’Ebre. 2015;6:1–12. [3] Fitzcharles MA, Ste-Marie PA, Pereira JX. Canadian Fibromyalgia The authors also thank the members of the Grup de recerca en Guidelines Committee. Fibromyalgia: evolving concepts over the past 2 Síndromes de Sensibilització Central a les Terres de l’Ebre decades. CMAJ 2013;185:E645–51. (SensiTEbre group) for participate in the data collection of the [4] Wolfe F, Smythe HA, Yunus MB, et al. The American college of study: Adrià Suazo Ciurana (Unitat d’informàtica, Gerència rheumatology 1990 criteria for the classification of fibromyalgia. report Territorial ICS Terres de l’Ebre), Albert Gómez Sorribes (Equip of the multicenter criteria committee. Arthritis Rheum 1990;33:160–72. [5] Wolfe F, Clauw DJ, Fitzcharles MA, et al. 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