Open access Protocol Cost–utility analysis of a multicomponent intervention for fibromyalgia syndrome in primary care versus usual clinical practice: study protocol for an economic evaluation of a randomised control trial Victoria Mailen Arfuch ‍ ‍,1,2 Carina Aguilar Martín,1,3 Anna Berenguera ‍ ‍,4,2 Rosa Caballol Angelats,5,6 Noèlia Carrasco-­Querol,1 Gemma González Serra,1,6 Maria Cinta Sancho Sol,1,6 Immaculada Fusté Anguera,5,6 José Fernández Sáez,1 Alessandra Queiroga Gonçalves,1,7 Marc Casajuana4 To cite: Arfuch VM, Aguilar ABSTRACT Martín C, Berenguera A, et al. Strengths and limitations of this study Introduction Fibromyalgia syndrome (FMS) imposes a Cost–utility analysis of a high cost on society. The significant economic burden from multicomponent intervention ►► This study will produce important and accurate in- the use of healthcare and, especially, social resources for fibromyalgia syndrome formation about the economic impact and health in primary care versus is a spur to revising the usual clinical care (UCC) and to benefits of a new treatment strategy for fibromyalgia usual clinical practice: study improving treatment strategies. FMS has a deleterious syndrome. protocol for an economic effect on the quality of life (QOL) and productivity, which ►► The results of the analysis will help decision-­makers evaluation of a randomised considerably increase the indirect costs to society. This to provide the best healthcare options and to consid- control trial. BMJ Open study reports an economic evaluation comparing the cost er stakeholders’ opinions. 2021;11:e043562. doi:10.1136/ and health benefits in a multicomponent intervention ►► The design of this study protocol is linked to a ran- bmjopen-2020-043562 programme and UCC of patients with FMS who attend domised control trial; it includes a broad perspective ►► Prepublication history for primary healthcare centres of the Gerència Territorial from society, and a 1-­year horizon, which will enable this paper is available online. Terres de L’Ebre region of Catalonia, Spain. This article is long-­term changes to be assessed. To view these files, please visit linked to the pre-­results of a randomised control trial study ►► Although cost–utility analysis is a popular measure- the journal online (http://​dx.​doi.​ on the implementation of this intervention programme (​ ment tool, its methodological limitations make it org/​10.​1136/​bmjopen-​2020-​ ClinicalTrials.​gov: NCT04049006). 043562). controversial among some experts. Method and analysis A cost–utility analysis will be ►► The indirect-­cost data source only includes patients Received 07 August 2020 conducted from a societal perspective. Quality-­adjusted who are linked to the social security system, which Revised 19 November 2020 life years will be calculated from the results of the SF-36 excludes self-­ employed and unemployed people, Accepted 27 November 2020 questionnaire, a QOL measurement instrument. Direct homemakers, and workers in the informal economy. and indirect healthcare costs will be obtained from official prices and reports published by the Spanish Public Health Administration and the National Statistics Institute. The incremental cost–utility ratio will be estimated to compare INTRODUCTION the two healthcare practices. Deterministic sensitivity Fibromyalgia is a chronic, medically unex- analysis will also be used to compare different cost plained syndrome that is characterised by scenarios, modifying the items with the highest weight in persistent and widespread musculoskeletal the cost composition. pain, and that is also associated with psycho- © Author(s) (or their Ethics and dissemination The Clinical Research Ethics logical and social factors.1–4 Disability is one employer(s)) 2021. Re-­use Committee of the IDIAPJGol Institute approved this of the main consequences of its impact on permitted under CC BY-­NC. No commercial re-­use. See rights study on 25 April 2018 (code P18/068) in accordance daily functioning, quality of life (QOL) and and permissions. Published by with the Helsinki/Tokyo Declaration. Information will be loss of productivity.5 The prevalence of fibro- BMJ. provided orally and in writing to participants, and their myalgia syndrome (FMS) is significant in For numbered affiliations see informed consent will be required. Participant anonymity adults. A recent review suggests its prevalence end of article. will be guaranteed. The dissemination strategy includes in the general population of many countries publications in scientific journals and presentations in local Correspondence to ranges between 0.2% and 6.6%, and it is and national media and at academic conferences. Mr Marc Casajuana; more frequent in women.6 Specifically, it is Trial registration number: NCT04049006; Pre-­results. ​mcasajuana@​idiapjgol.​org present in 2.45% of the Spanish population.7 Arfuch VM, et al. BMJ Open 2021;11:e043562. doi:10.1136/bmjopen-2020-043562 1 Open access Therefore, healthcare for patients with this diagnosis is outcomes and costs. This technique is a useful tool for not only complicated from a clinical point of view but also comparing intervention strategies, especially those with costly from an economic perspective for both the health quite different health outcomes because a standard utility and social security systems.5 8–13 unit is commonly used to measure all of them: the quality-­ Available evidence has shown that FMS imposes a adjusted life year (QALY).23 Despite its limitations, espe- considerable cost on society, especially those associated cially in measuring the value that society attaches to with comorbidity and incapacity.8 14–18 Among European different health status, CUA is better than other economic countries, the estimated total annual costs of FMS were evaluation strategies and provides useful information for €7900 (direct €910, indirect €6990) for France, €7256 resource allocation processes.24 (direct €1765, indirect €5491) for Germany and €7814 The economic evaluation of intervention programmes (direct €5241, indirect €2573) for the Netherlands.17 18 for FMS has been little studied. According to the published Additionally, FMS is responsible for the highest direct findings, non-­ pharmacological strategies, especially healthcare costs of all musculoskeletal conditions and psychology-­based therapies, have yielded positive results chronic pain-­related illnesses,14 and higher rates of unem- in terms of reducing the economic burden of FMS.19 25–31 ployment and number of days sick leave.19 In Spain, some cost–utility studies comparing alternative In the Spanish context, the overall economic burden interventions (ie, psychoeducational therapy, acceptance of FMS is considerable and has been estimated at more and commitment therapy, internet-­ delivered exposure than €12 993 million annually.20 According to the most therapy, and mindfulness-­ based stress reduction) with recent data published by the Spanish National Institute usual drug treatment have demonstrated the cost–utility of Social Security, the number of assigned temporary from a healthcare and social perspective.19 26–28 30 However, disabilities (short-­term absenteeism because of days off only the FibroQoL study has included a multicomponent sick) due to FMS has increased in recent years, as well as intervention (MI) modality, and it had significant tech- the average number of days of absence.21 A cross-­sectional nical and methodological differences compared with the and multicentre study involving a retrospective review of current proposal.26 32 medical outpatient records in Catalonia between 2006 This study aims to perform a CUA on an MI consisting and 2007 showed that patients with FMS had considerably of health education, physical activity, and cognitive-­ higher annual total costs of healthcare (including drugs, behavioural therapy, for patients with FMS compared complementary tests, all types of medical visits, referrals with their treatment under usual clinical care (UCC),33 and hospitalisations) and non-­healthcare resource utilisa- provided within the 11 primary care centres of the tion (sick leave days, and early retirement), under routine Gerència Territorial Terres de L’Ebre of the Institut medical practice in the primary care setting, compared Català de la Salut, Spain. The results of this economic with a reference population. The study obtained an incre- assessment are expected to support the evidence of the mental adjusted per-­patient per-­year total cost of €5010 randomised clinical trial (RCT) related to this project34 for patients with FMS, being €614 (12.3%) for direct (​ClinicalTrials.​gov: NCT04049006).35 It is hoped that costs and €4394 (87.7%) for indirect costs.10 this new proposed intervention will reinforce the UCC, In line with these findings, another cross-­sectional study enhance patients’ QOL, and promote the efficient alloca- conducted in Spain, based on face-­to-­face patient inter- tion of health and social resources. views, encountered a mean total cost per patient per year of €9982, comprising €3245.8 (32.5%) of direct health- care costs and €6736.2 (67.5%) of indirect costs attrib- METHOD utable to productivity losses.11 This study also showed Design that: (1) non-­pharmacological therapies accounted for This study protocol has been drafted based on a litera- the highest costs of direct healthcare resources, involving ture review and following the recommendations of the three times more than the cost of drug treatments; (2) Consolidated Health Economic Evaluation Reporting there was a significant direct association between disease Standards36 about preliminary results. The UK Medical severity and total costs; and (3) patients with a perma- Research Council guidance37 for complex interventions nent working disability made the most extensive use of has been taken into account in planning the RCT study. resources.11 However, these findings were collated over a The design of this economic evaluation study requires a decade ago, and are in need of updating with reference CUA to be conducted from a societal perspective so that to the Spanish public health system. indirect non-­medical cost variables are included. Health Health economic evaluation is essential in policy outcomes and costs will be assessed over a 12-­month dura- decision-­making since it provides evidence enabling the tion to ensure that long-­term outcomes are measured. efficiency of an intervention, programme, or project to This methodological decision is based on the clinical be determined, thereby making it possible to optimise symptoms of FMS, its consequences, its tendency to chro- the benefits from limited resources.22 Of the economic nicity, and the fact that its treatment is associated with evaluation techniques, cost–utility analysis (CUA) esti- ongoing clinical management. mates how much well-­being is achieved for each mone- The human capital approach has been judged the most tary unit invested, taking into account both health suitable method for this study due to the limitations of 2 Arfuch VM, et al. BMJ Open 2021;11:e043562. doi:10.1136/bmjopen-2020-043562 Open access the data source, given that only full sick days, prescribed Direct costs include visits to primary care services, by the general practitioner (GP), and the period with a other professional referrals, and emergency services, medical disability can be extracted from the computer- clinical tests for diagnosis and medical follow-­up, phar- ised medical history programme (eCAP). macological treatments, and hospitalisations. Costs will The elements to be compared in this study are the be calculated based on unit service prices, which will be UCC21 33 38 39 for patients with FMS, and the UCC plus obtained from the DOGC. Additionally, drug prices will an MI provided in primary care centres. The MI consists be obtained from the Council of Pharmaceutical Colleges of a 12-­week group programme of 2 hours per week of Catalonia. combining: 7 health education instructions, 11 items of Indirect non-­ medical costs include temporary and physical activity and physical health training, and 7 inter- permanent disability. As stated in the Spanish General ventions of psychological therapy based on cognitive-­ Law of Social Security (Law 20/2014; Royal Legislative behavioural strategies and pain management. Group Decree 8/2015),42 the term ‘temporary disability’ refers therapy is being delivered by the GP specialised in FMS, to sick leave days due to short-­term common or profes- the physiotherapist, and the psychologist, with the support sional illness, whereas ‘permanent disability’ refers to the of the head nurses of each health centre involved. impossibility of working due to the permanent and total or partial loss of working capacity in the long-­term. In the Study population former case, a GP determines whether a patient is unable The patients recruited for the study sample are shortlisted to work in the short term. In the latter case, a medical from the electronic medical records system eCAP of the board conducts an in-­depth assessment of the medical Catalan Health Service (CatSalut) and the Institut Català background, including the physical and mental condition de la Salut. Only the medical records of the 11 primary of the person, in order to determine whether a perma- care centres of the Gerència Territorial Terres de L’Ebre nent disability should be declared. These measurements in Catalonia, Spain, are included. Patients are allocated at will be estimated from the number of full sick leave days random to study groups from lists provided by the health and the months spent with a disability, respectively. centres in order to obtain a representative sample giving We will not collect data on other non-­medical costs, patient’s sociodemographic diversity throughout the such as presenteeism and unpaid lost time, because of territory. The inclusion criteria are set out in detail in the the limitations of the data available from our data source RCT protocol study.34 (eCap). The weighted price of the social costs will be determined Patient and public involvement by calculating a total annual average salary (including Neither patients nor the public will be involved in the regular and extra payments) for the Catalonia region, design or execution of our research, or the reporting and based on the official records of the NSI.43 This estimate dissemination of its results. will take into account part-­time and full-­time working schedules, and all activity sectors (industry, construction, Outcomes measures and data collection and all services except housework). Health outcomes Data collection is expected to be completed by April The utilities will be obtained based on the results of 2021. the health-­related QOL SF-36 questionnaire40 (Optum, license number QM048943) and the QALY estimates. Sample size This measurement instrument is administered to the In order to detect a score difference of at least five points study sample at baseline, immediately after the interven- in the SF-36 questionnaire, it has been calculated that tion, and at 6 and 12 months of follow-­up. Sociodemo- 260 participants (130 subjects per study arm) are needed graphic and clinical variables are registered at baseline to ensure an adequate sample size, assuming an α error and are fully described in the RCT study protocol.35 A of 0.05, a β error of 0.05 in a bilateral contrast, and a software application, specially designed for the study and dropout rate of 20%.34 Consequently, between 10 and 13 linked to digital medical records, is employed to register MI groups, with their respective control groups (UCC), the collected data. including 10–12 patients per group, are required. Cost outcomes Statistical analysis Direct and indirect costs, related to the use of health and SPSS V.25 and Stata V.15 for Windows will be used for social resources, will be estimated in euros (€) based the statistical analyses. First, a descriptive analysis of the on the official prices for the public sector, which are sample will be carried out that will compare the charac- published in the Diari Oficial de la Generalitat de Cata- teristics of the two study arms. lunya (DOGC)41 (updated in 2019), and in the Spanish As an economic evaluation outcome measure, the incre- National Statistics Institute (NSI), respectively. Table 1 mental ratio of the cost–utility will be estimated, dividing shows the cost variables and data sources that will be the difference in total mean costs in both UCC and MI by collected retrospectively, 12 months before the start date, the differences in QALYs of each study arm. 95% CIs will and 12 months after the end of the MI. be calculated for all parameter estimates. Arfuch VM, et al. BMJ Open 2021;11:e043562. doi:10.1136/bmjopen-2020-043562 3 Open access Table 1 Cost outcome measurements and data collection Cost outcomes Cost outcome Cost outcome description Data source Cost data source Cost calculation Direct healthcare costs Primary care visits ►► General practitioner eCAP DOGC Number of visits×price ►► Nurse ►► Physiotherapist ►► Psychologists Professional referral visits ►► Traumatology eCAP DOGC Number of visits×price ►► Psychiatry ►► Rehabilitation ►► Other specialities Clinical tests ►► Blood test eCAP DOGC Test performed x price ►► Diagnostic imaging techniques ►► Other tests Pharmacological ►► Muscle relaxants eCAP  Council of Pharmaceutical Medicines bought ×price prescriptions -Analgesics Colleges of Catalonia ►► Corticoids ►► Antidepressants ►► Anxiolytics ►► Antiseizure -Gastric protectors ►► Other drugs Emergency visits eCAP DOGC Number of visits×price Hospitalizations eCAP DOGC Number of hospitalisation days×price Indirect non-­medical costs Temporary disability (TD) eCAP NS Number of full sick leave days×salary Permanent disability (PD) eCAP NSI Number of months with PD×salary DOGC, Diario Oficial de la Generalitat de Catalunya; eCAP, computerised medical history programme; NSI, Spanish National Statistics Institute. To avoid possible biases as far as possible, the intention-­ study is expected to support the inclusion of an MI for to-­treat principle will be applied in order not to affect FMS in primary care settings in order to improve patient the random distribution. In addition, to address the QOL and to reduce its economic burden. loss of follow-­ up and non-­ response, multiple imputa- The literature review indicates that the indirect costs tion approaches to substitute missing values will be attributable to sick leave and permanent work disability implemented. exceed the direct costs of healthcare.8–11 14–20 Therefore, preventing productivity loss should be prioritised since Sensitivity analysis this imposes the highest cost on the community. This A deterministic sensitivity analysis will be performed to study adopts a societal perspective, including indirect assess the robustness of the results.44 Items with a higher non-­medical cost variables that will allow us to assess the cost will be modified in order to compare them with the impact of the burden of FMS on the social security system. initial results. More accurate methods, such as the friction cost approach, have been acknowledged as being effective for DISCUSSION estimating productivity costs. However, the human capital This study aims to address FMS as a public health problem approach has been considered the most suitable for this with economic repercussions.10 FMS compromises the study, given the data available. However, a sensitivity anal- health status of a considerable number of people, who ysis will be performed to assess alternative cost scenarios consequently consume substantial health and social that take into account the limitations of this methodolog- resources in the short and long terms. Therefore, this ical approach. It will include different direct healthcare 4 Arfuch VM, et al. BMJ Open 2021;11:e043562. doi:10.1136/bmjopen-2020-043562 Open access costs and, if necessary, the weighted price of the social time since it assumes that the utility of a health state is cost, considering that the salary rate will be an overall independent of the time the patient has experienced annual average estimate without distinction between the it, and the influence of previous and subsequent health type of activity or the working schedule. conditions.24 Although all these factors pose methodolog- Additionally, another economic concern involves the ical challenges, CUA is still a valid and effective strategy costs of the diagnostic process since it is purely clinical.45 for carrying out health economic evaluations and collab- Before FMS is diagnosed, other possible diseases must be orating with decision-­makers in choosing between inter- ruled out with objective tests and by a variety of medical vention alternatives.24 specialists. This process is often long and exhausting Another limitation related to the instruments and the for patients, frustrating for doctors, and expensive from data collection stems from the QOL being a multifactorial the perspective of the health system.46 Furthermore, the variable that could be influenced by non-­medical circum- presence of comorbidities can hinder and delay the diag- stances such as family dynamics, working conditions, and nosis, as well as complicating the choice of a treatment economic and political contexts, among others.57 Socio- strategy.47 Hence, the study sample could show differences demographic variables will therefore be analysed in the in the use of resources between patients depending on models in order to control for these possible effects. the year of diagnosis and the medical records. However, This health region covers a wide and varied territory. it is expected that the randomised allocation will balance However, all the primary care centres participating in these differences between the study arms. the study are run by the public health administration, Given the evidence about the economic burden of meaning that clinical care protocols and direct medical FMS,8 14–21 particularly related to the loss of productivity, costs are both standardised according to official regula- UCC does not seem to be entirely helpful for reducing tions and will be homogeneous for the entire sample. the effects of chronicity or for preventing disability. Regarding the indirect costs, only those people who are Thus, FMS treatment should not be limited to short-­ linked to the social security system and who have access term pain relief. It should also promote the acceptance to its benefits will be able to provide data about produc- of the condition, the self-­ management of symptoms, tivity costs. The study sample, therefore, excludes self-­ and empowering patients to deal with FMS in their daily employed and unemployed people, homemakers, and lives. Non-­pharmacological approaches could address the workers in the informal economy. In this sense, although consequences of chronicity, reducing healthcare over- the human capital approach could overestimate produc- provision and overmedication. Indeed, the proposed MI tivity costs, it could be offset by the missed data of these aims to address these challenges by combining physical, population subgroups that contribute to the productivity psychological, and health educational methods. loss to society due to the side effects of their illness. Findings regarding the efficacy of MI for patients Finally, this study could be affected by sample loss to with this condition have proved helpful for improving follow-­up given the 1-­year time horizon. This method- QOL, physical function, psychological variables, and or ological characteristic is also a strength of the study since pain after 3–12 months of follow-­up.48–53 However, more it will allow long-­term changes to be assessed. In order studies are required to address the economic efficiency of to minimise the number of participants abandoning the this type of intervention, particularly in the context of the study, reminders of upcoming interviews will be sent, and Spanish public health system. different data collection methods, such as telephone calls Evidence of efficiency is essential for decision-­making and online survey platforms, may even be used. in order to allow budgets to be prioritised for those treat- If the results indicate that the intervention is utility ment options that prove to be cost-­efficient and to fulfil cost effective, this study will support, through efficiency patients’ health needs. Economic evaluation is key to over- evidence, the inclusion of an MI as part of the usual prac- coming the obstacles arising from the uncertainty about tice for FMS in primary care centres in Catalonia, Spain. the real costs and the sustainability of particular inter- Additionally, enhancements of patient QOL and cost ventions.54 The CUA is a popular measurement tool that reductions for health and social resources are expected. combines quantity data and QOL, based on the opinions We hope that this new proposed intervention could be of the healthcare users, associated with a monetary cost. replicated throughout the rest of Catalonia and Spain, It involves a participatory and economic evidence-­based and used more extensively as a guide within other Euro- decision-­ making strategy that considers stakeholders’ pean health systems. preferences.55 However, this methodology is controver- sial,56 the main points of contention being: (1) the lack of transparency about data collection and analysis regarding ETHICS AND DISSEMINATION the measurement of the value that society assigns to a This study was designed in accordance with the Helsinki/ state of health; (2) that the gain in health depends on Tokyo Declaration. It was approved by the Clinical the severity of the condition, so the value is affected by Research Ethics Committee of the Fundació Institut patients’ perception of their pain and health status; (3) Universitari per a la recerca a l’Atenció Primària de Salut the limited value of this measurement tool for long-­term Jordi Gol i Gurina (IDIAPJGol), on 25 April 2018 (code diseases such as FMS, where disability accumulates over P18/068). Information is delivered to participants orally Arfuch VM, et al. BMJ Open 2021;11:e043562. doi:10.1136/bmjopen-2020-043562 5 Open access and in writing before their necessary informed consent a modification of the ACR preliminary diagnostic criteria for fibromyalgia. J Rheumatol 2011;38:1113–22. is obtained. This project respects the data protection 3 Wolfe F, Clauw DJ, Fitzcharles M-­A, et al. 2016 revisions to the laws guaranteeing participant anonymity. Dissemination 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum strategy includes publications in scientific journals and 2016;46:319–29. 4 Helfenstein M, Goldenfum MA, Siena CAF. Fibromyalgia: clinical and through presentations in the local and national media occupational aspects. Rev Assoc Med Bras 2012;58:358–65. and at academic conferences. 5 Skaer TL. Fibromyalgia: disease synopsis, medication cost effectiveness and economic burden. Pharmacoeconomics 2014;32:457–66. Author affiliations 6 Marques AP, Santo AdeSdoE, Berssaneti AA, et al. Prevalence of 1 Unitat de Suport a la Recerca Terres de l’Ebre, IDIAP Jordi Gol, Barcelona, fibromyalgia: literature review update. Rev Bras Reumatol Engl Ed Catalunya, Spain 2017;57:356–63. 2 Department of Pediatrics, Obstetrics and Gynecology, and Preventive Medicine, 7 Seoane-­Mato D, Sánchez-­Piedra C, Silva-­Fernández L, et al. Universitat Autonoma de Barcelona, Barcelona, Catalunya, Spain Prevalence of rheumatic diseases in adult population in Spain 3 Unitat d’Avaluació, Direcció d’Atenció Primària Terres de l’Ebre, Institut Català de la (EPISER 2016 study): aims and methodology. Reumatol Clin 2019;15:90–6. Salut, Tortosa, Catalunya, Spain 8 Robinson RL, Birnbaum HG, Morley MA, et al. Economic cost and 4 Central Research Unit, IDIAP Jordi Gol, Barcelona, Catalunya, Spain epidemiological characteristics of patients with fibromyalgia claims. J 5 Equip d’Atenció Primària Tortosa Est, Institut Català de la Salut, Tortosa, Catalonia, Rheumatol 2003;30:1318–25. Spain 9 Epidemiology SM. Costs, and the economic burden of fibromyalgia. 6 Unitat d’Expertesa en Sindromes de Sensibilització Central Terres de l’Ebre, Institut Arthritis Res Ther 2009;11:2–3. Català de la Salut, Tortosa, Catalonia, Spain 10 Sicras-­Mainar A, Rejas J, Navarro R, et al. Treating patients with 7 fibromyalgia in primary care settings under routine medical practice: Unitat Docent de Medicina de Família i Comunitària Tortosa-­Terres de L‘Ebre, a claim database cost and burden of illness study. Arthritis Res Ther Institut Català de la Salut, Tortosa, Catalonia, Spain 2009;11:1–14. 11 Rivera J, Rejas J, Esteve-­Vives J, et al. Resource utilisation and Twitter Anna Berenguera @ABerenguera health care costs in patients diagnosed with fibromyalgia in Spain. Clin Exp Rheumatol 2009;27:S39–45. Acknowledgements All authors thank the contributions of the Institut Català de 12 Thompson JM, Luedtke CA, Oh TH, et al. Direct medical costs la Salut, especially those of the Gerència Territorial Institut Catalá de la Salut Terres in patients with fibromyalgia: cost of illness and impact of a brief de l’Ebre, the Direcció d’Atenció Primària de Terres de l’Ebre, and the Unitat de multidisciplinary treatment program. Am J Phys Med Rehabil Sistemes d’informació de la Gerència Territorial Terres de l’Ebre. The participation 2011;90:40–6. and support of all the healthcare and non-­healthcare professionals involved in 13 Vervoort VM, Vriezekolk JE, Olde Hartman TC, et al. Cost of illness implementing this study and collecting the data are appreciated. and illness perceptions in patients with fibromyalgia. Clin Exp Rheumatol 2016;34:S74–82. Contributors VMA, MC, CAM, AB, JFS and AQG designed the study. VMA wrote the 14 White KP, Speechley M, Harth M, et al. The London fibromyalgia draft versions, which all the other authors reviewed. RCA, NC-­Q, GGS, MCSS, IFA, epidemiology study: direct health care costs of fibromyalgia AQG, AB, CAM, JFS and VMA are involved in the development of the general project syndrome in London, Canada. J Rheumatol 1999;26:885–9. and the RCT study from which this qualitative study is related. 15 Berger A, Dukes E, Martin S, et al. Characteristics and healthcare costs of patients with fibromyalgia syndrome. Int J Clin Pract Funding This project was funded by a research grant from the Instituto de Salud 2007;61:1498–508. Carlos III (ISCIII), awarded in 2018, with reference PI1800943, as part of the Health 16 Berger A, Sadosky A, Dukes EM, et al. Patterns of healthcare Strategy Action 2017–2020 within the National Research ProgramProgramme; utilization and cost in patients with newly diagnosed fibromyalgia. the Technical, Scientific and Innovation Research National Plan 2017–2020. It is Am J Manag Care 2010;16:S126–37. also co-­funded by the European Union ERDF (European Regional Development 17 Boonen A, van den Heuvel R, van Tubergen A, et al. Large Fund). VMA received a predoctoral grant for training in health research from the differences in cost of illness and wellbeing between patients with ISCIII (2019; reference FI19/00254). This project also received funding through fibromyalgia, chronic low back pain, or ankylosing spondylitis. Ann a scholarship from the Dr Ferran Foundation in 2017. The funders financed the Rheum Dis 2005;64:396–402. 18 Winkelmann A, Perrot S, Schaefer C, et al. Impact of fibromyalgia project but will not participate in any phase of the research, and will have no severity on health economic costs. Appl Health Econ Health Policy authority over any of the project’s activities. 2011;9:125–36. Competing interests None declared. 19 Feliu-­Soler A, Borràs X, Peñarrubia-­María MT, et al. Cost-­Utility and biological underpinnings of Mindfulness-­Based stress reduction Patient and public involvement Patients and/or the public were not involved in (MBSR) versus a psychoeducational programme (FibroQoL) for the design, or conduct, or reporting, or dissemination plans of this research. fibromyalgia: a 12-­month randomised controlled trial (EUDAIMON study). BMC Complement Altern Med 2016;16:1–16. Patient consent for publication Not required. 20 Cabo-­Meseguer A, Cerdá-Olmedo G, Trillo-­Mata JL. Fibromyalgia: Open access This is an open access article distributed in accordance with the prevalence, epidemiologic profiles and economic costs. Med Clin Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which 2017;149:441–8. permits others to distribute, remix, adapt, build upon this work non-­commercially, 21 Instituto Nacional de la Seguridad social. Guia de actualización en La and license their derivative works on different terms, provided the original work is valoración de fibromialgia, sÍndrome de fatiga crónica, sensibilidad química múltiple Y electrosensibilidad. Segunda Edición 2019 properly cited, appropriate credit is given, any changes made indicated, and the use https://www.​semg.​es/​images/​documentos/​guia_​fibromialgia_​2019.​ is non-­commercial. See: http://​creativecommons.​org/​licenses/​by-​nc/​4.​0/. pdf (Accessed 25 May 2020). 22 Chisholm D, Evans DB. Economic evaluation in health: saving money ORCID iDs or improving care? J Med Econ 2007;10:325–37. Victoria Mailen Arfuch http://​orcid.​org/​0000-​0001-​5935-​6907 23 Franklin M. Cost utility analysis. in: mental health economics: the Anna Berenguera http://​orcid.​org/​0000-​0002-​0889-​2002 costs and benefits of psychiatric care. Cham. Springer International Publishing 2017:89–119. 24 Mccabe C. What is cost-­utility analysis? Hayward Med Commun 2009:1–6 http://www.​bandolier.​org.​uk/​painres/​download/​whatis/​ What_​is_​cost-​util.​pdf (Accessed 25 May 2020). REFERENCES 25 Goossens ME, Rutten-­van Mölken MP, Leidl RM, et al. Cognitive-­ 1 Wolfe F, Smythe HA, Yunus MB, et al. The American College of educational treatment of fibromyalgia: a randomized clinical trial. II. rheumatology 1990 criteria for the classification of fibromyalgia. economic evaluation. J Rheumatol 1996;23:1246–54. Report of the multicenter criteria Committee. Arthritis Rheum 26 Luciano JV, Sabes-­Figuera R, Cardeñosa E, et al. Cost-­Utility of a 1990;33:160–72. psychoeducational intervention in fibromyalgia patients compared 2 Wolfe F, Clauw DJ, Fitzcharles M-­A, et al. Fibromyalgia criteria with usual care: an economic evaluation alongside a 12-­month and severity scales for clinical and epidemiological studies: randomized controlled trial. Clin J Pain 2013;29:702–11. 6 Arfuch VM, et al. BMJ Open 2021;11:e043562. doi:10.1136/bmjopen-2020-043562 Open access 27 Luciano JV, D’Amico F, Cerdà-Lafont M, et al. Cost-­Utility of cognitive AEMPPI Ecuador 2017 https://www.​elsevier.​com/​es-​es/​connect/​ behavioral therapy versus U.S. food and drug administration actualidad-​sanitaria/​dia-​mundial-​de-​la-​fibromialgia-​y-​el-​sindrome-​ recommended drugs and usual care in the treatment of patients de-​fatiga-​cronica?​aaref=​https%​3A%​2F%​2Fwww.​google.​com%​2F with fibromyalgia: an economic evaluation alongside a 6-­month (Accessed 27 Feb 2020). randomized controlled trial. Arthritis Res Ther 2014;16:1–17. 40 Alonso Jet al. Versión española de SF-­36v2TM health survey © 1996, 28 Luciano JV, D'Amico F, Feliu-­Soler A, et al. Cost-­Utility of group 2000, adapted by J. Alonso, et al. Heal Surv 2003:1–8 http://www.​ acceptance and commitment therapy for fibromyalgia versus ser.​es/​wp-​content/​uploads/​2015/​03/​SF36_​CUESTIONARIOpdf.​pdf recommended drugs: an economic analysis alongside a 6-­month (Accessed 1 Mar 2020). randomized controlled trial conducted in Spain (EFFIGACT study). J 41 Catalunya Gde. Diari Oficial de la Generalitat de Catalunya. Available: Pain 2017;18:868–80. https://​dogc.​gencat.​cat/​es 29 Hedman-­Lagerlöf M, Hedman-­Lagerlöf E, Ljótsson B, et al. Cost-­ 42 España Gde. Real Decreto 8/2015 POR El que se aprueba El texto Effectiveness and cost-­utility of internet-­delivered exposure therapy refundido de la Ley General de la Seguridad social. Boletín Oficial del for fibromyalgia: results from a randomized, controlled trial. J Pain Estado 2015:1–157 http://www.​boe.​es/​boe/​dias/​1994/​06/​29/​pdfs/​ 2019;20:47–59. A20658-​20708.​pdf (Accessed 1 Mar 2020). 30 Pérez-­Aranda A, D’Amico F, Feliu-­Soler A, et al. Cost–Utility of 43 Estadística INde. (ine). Coste laboral POR trabajador, comunidad Mindfulness-­Based stress reduction for fibromyalgia versus a autónoma, sectores de actividad. Available: https://www.​ine.​es/​ multicomponent intervention and usual care: a 12-­month randomized jaxiT3/​Tabla.​htm?​t=​6061 [Accessed 20 Mar 2020]. controlled trial (EUDAIMON study). JCM 2019;8:1068. 44 Andronis L, Barton P, Bryan S. Sensitivity analysis in economic 31 D'Amico F, Feliu-­Soler A, Montero-­Marín J, et al. Cost-­Utility of evaluation: an audit of NICE current practice and a review of its use Attachment-­Based compassion therapy (ABCT) for fibromyalgia and value in decision-­making. Health Technol Assess 2009;13. compared to relaxation: a pilot randomized controlled trial. J Clin 45 Wang S-­M, Han C, Lee S-­J, et al. Fibromyalgia diagnosis: a review of Med 2020;9:726. the past, present and future. Expert Rev Neurother 2015;15:667–79. 32 Luciano JV, Martínez N, Peñarrubia-­María MT, et al. Effectiveness 46 Briones-­Vozmediano E. The social construction of fibromyalgia as a of a psychoeducational treatment program implemented in general health problem from the perspective of policies, professionals, and practice for fibromyalgia patients: a randomized controlled trial. Clin patients. Glob Health Action 2017;10:1275191. J Pain 2011;27:383–91. 47 Lichtenstein A, Tiosano S, Amital H. The complexities of fibromyalgia 33 Celaya M, Ibáñez D, Laseca N. Guia per a l'avaluació de la fibromi and its comorbidities. Curr Opin Rheumatol 2018;30:94–100. lgia i de la síndrome de fatiga crònica. Generalitat de Catalunya, 48 Giusti EM, Castelnuovo G, Molinari E. Differences in multidisciplinary 2017. Available: https://​canalsalut.​gencat.​cat/​web/.​content/_​A-​Z/​F/​ and interdisciplinary treatment programs for fibromyalgia: a mapping fibromialgia/​documents/​guia_​avaluacio_​fibromialgia_​fatiga_​cronica.​ review. Pain Res Manag 2017;2017:1–19. pdf [Accessed 20 Feb 2020]. 49 Bourgault P, Lacasse A, Marchand S, et al. Multicomponent 34 Caballol Angelats R, Gonçalves AQ, Aguilar Martín C, et al. interdisciplinary group intervention for self-­management of Effectiveness, cost-­utility, and benefits of a multicomponent therapy fibromyalgia: a mixed-­methods randomized controlled trial. PLoS to improve the quality of life of patients with fibromyalgia in primary One 2015;10:e0126324. care. Medicine2019;98:e17289. 50 Ollevier A, Vanneuville I, Carron P. A 12-­week multicomponent 35 Caballol Angelats R, Gonçalves AQ, Aguilar Martín C, et al. therapy in fibromyalgia improves health but not in concomitant Effectiveness, cost-­utility, and benefits of a multicomponent therapy moderate depression, an exploratory pilot study. Disabil Rehabil to improve the quality of life of patients with fibromyalgia in primary 2019;0:1–8. care: a mixed methods study protocol. Medicine 2019;98:e17289. 51 Martín J, Torre F, Padierna A, et al. Six-­and 12-­month follow-­up of 36 Husereau D, Drummond M, Petrou S, et al. Consolidated Health an interdisciplinary fibromyalgia treatment programme: results of a Economic Evaluation Reporting Standards (CHEERS)--explanation randomised trial. Clin Exp Rheumatol 2012;30:103–11. and elaboration: a report of the ISPOR Health Economic Evaluation 52 Saral I, Sindel D, Esmaeilzadeh S, et al. The effects of long- and Publication Guidelines Good Reporting Practices Task Force. Value short-­term interdisciplinary treatment approaches in women Health 2013;16:231–50. with fibromyalgia: a randomized controlled trial. Rheumatol Int 37 Craig P, Dieppe P, Macintyre S, et al. Developing and evaluating 2016;36:1379–89. complex interventions: the new medical Research Council guidance. 53 Stein KF, Miclescu A. Effectiveness of multidisciplinary rehabilitation Int J Nurs Stud 2013;50:587–92. treatment for patients with chronic pain in a primary health care unit. 38 Nishishinya Aquino B, Requeijo Lorenzo C, Roqué Fíguls M. Scand J Pain 2013;4:190–7. Evaluación Y abordaje de la fibromialgia. Actualización de las 54 Eisman AB, Kilbourne AM, Dopp AR, et al. Economic evaluation evidencias científicas. Barcelona. Ministerio de Sanidad, Servicios in implementation science: making the business case for Sociales e Igualdad. Agència de Qualitat i Avaluació Sanit ries implementation strategies. Psychiatry Res 2020;283:112433. de Catalunya. Departament de Salut. Generalitat de Catalunya 55 Anneliese P, Hoch J. Understanding cost-­utility analysis in health 2017. (Informes de Evaluación de Tecnologías Sanitarias) https://​ care. Univ Toronto Med J 2006;83(2 http://​utmj.​org/​index.​php/​UTMJ/​ aquas.​gencat.​cat/​web/.​content/​minisite/​aquas/​publicacions/​2017/​ article/​view/​734 Fibromialgia_​actualizacion_​RedETS2017.​pdf (Accessed 27 Feb 56 McGregor M. Cost-­Utility analysis: use QALYs only with great 2020). caution. CMAJ 2003;168:433–4. 39 Gándara M, Muñoz G. Evaluación Y abordaje de la fibromialgia Y 57 Tarter T, Johnson G, Johnson R. Neuropsychology of Cancer and El síndrome de fatiga crónica. Día Mundial de la Fibromialgia Y El Oncology.. In: Noggle CA, Dean RS, eds. New York: Springer Síndrome de Fatiga Crónica. Oficial Nacional de Salud Pública-­ Publishing Company, 2013: 3–5. Arfuch VM, et al. BMJ Open 2021;11:e043562. doi:10.1136/bmjopen-2020-043562 7