EPIDEMIOLOGY of CHRONIC NON-MALIGNANT PAIN in SPAIN Lions of Adults Suffer in the USA from Mild to Moderate Non-Malignant Pain

EPIDEMIOLOGY OF CHRONIC Karla Soares Weiser Ivan Sola NON-MALIGNANT Ed Aromataris Jesús Tornero Concepción Pérez César Margarit PAIN IN SPAIN Jos Kleijnen May 2010

Kleijnen Systematic Reviews Ltd Escrick, York, YO19 6FD, United Kingdom www.systematic-reviews.com

Promoted by Fundación Grünenthal Design and Layout by Underbau ISBN: 978-84-694-4108-4 © of the Edition and content: Fundación Grünenthal The symptom of pain is very frequent in the medical practice. It has been estimated that 34 million adults suffer in the USA from mild to moderate non-malignant pain. Studies made with people over 65 years additionally inform us that 80-85% of them suffer from diseases that are related to pain: 25-50% of them have a moderate pain, amount that increases up to 45-80% for those who live in nursery homes. In Spain, a study made during the year 2000 demonstrated that each Spanish physician attends an average of 181 patients with pain per month, most of them with chronic moderate pain (51.3 persons per month). Table of contents 4 Table of contents

6 List of figures

8 List of tables

11 Introduction to the Epidemiological Review

14 Executive Summary 21 Conclusions

24 Introduction

27 Methods 28 Objective of project

28 Questions to be addressed

29 Inclusion criteria

31 Literature searches

33 Methods of study selection, quality assessment and data extraction 34 Study selection

34 Assessment of methodological quality

37 Data extraction and presentation

39 Results 40 Search, selection and allocation of studies

44 Q1 what are the population and demographics of Spain? TABLE OF CONTENTS / EPIDEMIOLOGY OF 48 Q2 What is the prevalence of chronic pain conditions in Spain? CHRONIC NON-MALIGNANT PAIN IN SPAIN 56 Q3 What is the incidence of chronic pain conditions in Spain?

57 Q4 What percentage of chronic pain patients are (a) untreated and (b) inadequately treated

64 Q5 How many chronic pain patients present themselves for treatment?

69 Q6 How many chronic pain patients get treated broken down by treatment?

76 Q7&20: What is the compliance of treated chronic pain patients and what are the determinants of compliance / adherence to drug treatments?

82 Q8 What are the severity and duration of chronic pain conditions?

91 Q9 What are the demographics of pain sufferers?

97 Q10 What are the underlying diseases of pain sufferers?

102 Q11 How many sufferers have inadequate pain control?

107 Q12a What is the impact of chronic pain on quality of life?

113 Q12b What is the impact of chronic pain on activities of daily living?

120 Q12c and d: What is the impact of chronic pain on c. Depression and other mental illness and d. Isolation, helplessness?

132 Q12e&f: What is the impact of chronic pain one) days of work and f) Incapacity benefits?

140 Q13. What are the costs of chronic pain from a) Societal perspective, b) Health care system perspective and c) Patient perspective?

149 Q14 What are issues/determinants of patients’ awareness of chronic pain?

157 Q15 what are issues/determinants of health care professionals’ awareness of chronic pain?

160 Q16. What are the main symptoms and complaints with which patients present themselves to health care professionals?

166 Q17 and Q19: What are the frequencies of drug (per WHO class), non-drug, and combined treatments and what are determinants of treatment choice within drug treatments?

176 Q18 What are the determinants of treatment choice between drug and non-drug treatments?

176 Q21 What is patients’ satisfaction about drug treatments?

181 Overallsummary table

195 References List of figures 23 Figure 1: Spain epidemiology flow for moderate to severe chronic pain

40 Figure 2: From Spain, 112 studies were found relevant

41 Figure 3: Epidemiology flow for Spain – number of studies located per question

42 Figure 4: What is the impact of chronic pain – number of studies located per question

42 Figure 5: What are the costs of chronic pain from different perspectives – number of studies located per question

43 Figure 6: Symptoms and awareness – number of studies located per question

43 Figure 7: Treatment – number of studies located per question

44 Figure 8: Age distribution of Spain 2008 45 Figure 9: Weight of the adult Spanish population 2006

46 Figure 10: Percentage of the active population of Spain in employment and unemployed

55 Figure 11: Overview of the prevalence of chronic pain disorders in Spain

67 Figure 12: Proportion of FM patients who had seen a physician for musculoskeletal symptoms in the last year LIST OF FIGURES / EPIDEMIOLOGY OF CHRONIC 68 Figure 13: Proportion of non-FM patients who had seen a physician NON-MALIGNANT PAIN IN SPAIN for musculoskeletal symptoms in the last year

75 Figure 14: Percentage of pain patients broken down by treatment

81 Figure 15: Determinants of compliance/adherence to therapy

90 Figure 16: Duration in years of chronic pain from the included studies

95 Figure 17: Demographics of patients with chronic pain in included studies

96 Figure 18: Average age of chronic pain patients

101 Figure 19: Comorbidities in the EPISER study

106 Figure 20: Control of pain

118 Figure 21: Functional capacity Collantes-Estevez (2003)

119 Figure 22: Pain interference with job or house work

138 Figure 23: Sick leave due to pain

146 Figure 24: Disability compensations Carmona et al. (2001)

165 Figure 25: Reasons for consultation List of tables 47 Table 1. Population characteristics for Spain

49 Table 2. Characteristics of studies relevant to Question 2: prevalence of chronic pain

53 Table 3. Prevalence data for chronic pain in general, and for different pain disorders

56 Table 4. Characteristics of studies relevant to question 3: incidence of chronic pain

59 Table 5. Characteristics of studies relevant to Question 4a and b: % untreated and % inadequately treated

60 Table 6. Definitions of treated, untreated, inadequately treated and inadequate pain control

61 Table 7. Summary of results for Question 4: % untreated and % inadequately treated

65 Table 8. Characteristics and results of included studies for Question 5: How many chronic pain patients present themselves for treatment

70 Table 9. Study characteristics and results of included studies relevant to Question 6: pain patients broken down by treatment LIST OF TABLES / EPIDEMIOLOGY OF CHRONIC 77 Table 10. Characteristics of two studies relevant to Questions 7 NON-MALIGNANT PAIN IN SPAIN and 20: adherence to treatment

84 Table 11. Study characteristics and results for Q8: severity and duration of chronic pain conditions

92 Table 12: Study characteristics and results of studies relevant to Question 9: what are the demographics of pain sufferers?

98 Table 13: Study characteristics of included studies for Q10: underlying diseases of pain sufferers

103 Table 14. Study characteristics of included studies for Q11: how many sufferers have inadequate pain control?

108 Table 15: Characteristics and results of the studies relevant to Question 12: the impact of chronic pain on quality of life

112 Table 16. Results for SF-36 for no pain, pain, acute pain and chronic pain

114 Table 17. Study characteristics and results of included studies for Question 12b: impact on activities of daily living

122 Table 18. Characteristics and results of relevant studies for Q12c&d: impact of pain on depression and other mental illness, isolation and helplessness

128 Table 19. Prevalence of mood disorders in patients with neck and back pain LIST OF TABLES / EPIDEMIOLOGY OF CHRONIC 133 Table 20. Characteristics and results of relevant studies for Q12e&f: NON-MALIGNANT PAIN IN SPAIN impact of pain on days off work and incapacity benefits

141 Table 21. Characteristics and results of studies relevant to question 13a, b, c: economic impact of chronic pain

151 Table 22: study characteristics and results of studies relevant to Question 14: issues/determinants of patients’ awareness of chronic pain

158 Table 23: Study characteristics and results of studies relevant to Question 15: issues /determinants of health care professionals’ awareness of chronic pain

162 Table 24: Characteristics and results of studies relevant to Question 16: the main symptoms and complaints with which patients present themselves to health care professionals

168 Table 25. Characteristics and results of studies relevant to Questions 17 and 19: frequency of treatments and determinants of drug treatments

174 Table 26. Percentages of drug type used for different diagnosis for patients newly diagnosed and patients for revision

177 Table 27. Table: Characteristics of the studies relevant to Question 21

182 Table 28. Summary of study quality, results and concluding statements for project questions 2 through 21 Introduction to the Epidemiological Review INTRODUCTION TO THE EPIDEMIOLOGICAL The symptom of pain is very frequent in medical practice. It has been estimated that 34 mil- REVIEW / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN lions of adults suffer in the USA from mild to moderate non-malignant pain. Studies made with people over 65 years of age additionally inform us that 80-85% of them suffer from diseases that are related to pain: 25-50% of them have moderate pain, which increases up to 45-80% for those who live in nursery homes. In Spain, a study from the year 2000 demonstrated that each Spanish physician attends an average of 181 patients with pain per month, most of them with chronic moderate pain (51.3 persons per month).

Chronic pain has a significant impact on those who suffer it, in the individual, psychological, familiar and social sphere: anxiety, depression, sleep disorders, frustration, reduction of the libido, reduction of the self-esteem, inactivity and less interest for the social activities, alteration on familiar dynamics, notable implications on the labour sphere with a possible decrease in the level of economic income.

Due to this high influence of pain and its health care, its individual and group impact, the present review on the epidemiology of pain is very useful and attractive in the international context, and more specifically for our country. Through detailed and exhaustive work, it has been tried to consider the whole spectrum of available scientific literature, putting empha- sis on the works done in Spain. The reader will find in this text broad information that covers not only the frequency of the incidence of this symptom, its effect and its causes, but also the risk profiles of the potential sufferers as well as important data on the suffering, the expenses and costs of attending it, as a reflection of the high socio-sanitary impact it causes.

Therefore, we believe that this text might be useful for the epidemiological researcher and the clinicians, as well as resource planners and managers and, in general, any professional, 12 sanitary or not, that has to deal with this huge problem. Its structure with analyzed themes INTRODUCTION TO THE EPIDEMIOLOGICAL and the exhaustive revision of the literature make this document an easy to use handbook REVIEW / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN and reference source about the epidemiology of pain. Therefore, from the reading of this review – unique as far as our knowledge on Spanish scientific literature is concerned – you will for sure find some points of interest and knowledge to improve your actuation and daily professional work.

We would like to thank Grünenthal for the initiative taken to do this review and for its support for this work to be published, with the layout the reader holds in his hands. This generos- ity is a statement, once again, of their firm interest in supporting any initiative that improves the sensibility of the physicians towards pain and towards the patient who suffers it.

As a conclusion, we might say that this review is the first step to identify in which areas of chronic pain there is currently little information and what we would need to focus on for deepening that knowledge. A profound knowledge of these data is a priority in order to be able to have an insight of the situation of pain and their patients in our country; all of this JESÚS TORNERO is crucial in order to manage the unmet medical needs in the management and treatment Chief of Section, Rheumatology, Hospital Universitario de Guadalajara, Associate of pain, and to understand how this is impacting the social and labour life of the patients. Professor of Medicine, Universidad de Alcalá

CONCEPCIÓN PÉREZ Pain Unit, Hospital de La Princesa de Madrid We hope that with projects like this one the reader is holding in his hands we will be able to CÉSAR MARGARIT increase our qualification and interest for the study, evaluation, diagnostic evaluation and Pain Unit, Hospital General de Alicante therapy of pain. If this would be so, the effort invested in this work would have achieved its Members of the Spanish CHANGE PAIN Advisory Board entire objective.

13 Executive Summary EXECUTIVE SUMARY / EPIDEMIOLOGY OF CHRONIC Chronic pain is very common but good data are scarce about the prevalence, incidence, diagnosis, NON-MALIGNANT PAIN IN SPAIN severity, treatment, utilization of health care, and the impact of chronic pain on society, health care systems and the patient. Information about the epidemiology of chronic pain can help health care professionals as well as decision and policy makers decide about health budgets and prioritization, patient segmenting and budget fencing, and therapy budgets, including behavioural therapy and drug budgets. This report aims to provide epidemiological information about chronic pain in Spain using the most representative, recent, comprehensive and valid studies.

Out of 112 retrieved titles and abstracts, we selected 52 studies from Spain that were relevant to the project questions. From these, we selected at least three studies per question that provided the most recent, representative and valid data. A summary of the results for each project question follows:

Q1 – what are the population and demographics of Spain? Spain in Figures 2009, the latest edition of Spain in figures, presented by the National Statistics Institute and the CIA World Factbook for Spain were used to obtain population estimates for Spain: Total population 46.16 million, 50.5% female, median age 41.1 years. Life expectancy is 80 years, 38% of adults are overweight, 16% obese. 98% are literate and 88.7% of the active population are employed.

Q2 – what is the prevalence of chronic pain conditions in Spain? Ten studies out of 19 relevant were selected, and study quality was variable. Half the studies were representative of the Spanish population. General chronic pain prevalence was estimated at 12%, back pain 14.7%, fibromyalgia (FM) 1.4-2.4%, rheumatoid arthritis (RA) 0.5% and neuropathic pain 3.9%.

Q3 – what is the incidence of chronic pain conditions in Spain? 15 Only one study was found and the value is of limited applicability to the general population. EXECUTIVE SUMARY / EPIDEMIOLOGY OF CHRONIC The incidence of neuropathic pain is 77.2% in a 6 month period in patients attending NON-MALIGNANT PAIN IN SPAIN neurology clinics.

Q4 – what percentage of chronic pain patients from Spain are untreated or inadequately treated Only Perez (2009) was representative of the Spanish population and reports a low percentage of non-cancer chronic pain patients as untreated, 0.9%. The other 2 studies report much higher levels (15% for osteoarthiris [OA] and RA, 39% for osteomuscular pain) but are low quality.

Q5 – how many chronic pain patients from Spain present themselves for treatment? Only 1 study was high quality, for FM, which found that 79% of patients had visited a physician in the last year. All studies were representative of the Spanish population, but the other two were low quality, and did not directly address the question.

Q6 – how many chronic pain patients from Spain get treated, broken down by treatment? The results from Nunez (2007), the highest quality study, were from a very specific pain population – people with knee OA on a waiting list for a total knee transplant. The only study that was representative of the population, Medina (1999) was of low quality.

Q7&20 – what is the compliance of treated chronic pain patients in Spain and what are the determinants of compliance/adherence to drug treatment? Three studies were located that addressed these questions, but due to the lack of high quality studies and the relatively small sample sizes of the available studies it is unlikely these results can be viewed as indicative of the Spanish population.

Q8 – what is the duration and severity of chronic pain conditions in Spain? 16 7 studies out of 42 were selected all of which were medium to high quality. For general EXECUTIVE SUMARY / EPIDEMIOLOGY OF CHRONIC non-cancer chronic pain the mean duration was 6.6 to 9 years, and 44% reported severe NON-MALIGNANT PAIN IN SPAIN pain; FM had a mean duration of 9 to 13 years and severity of 5.7 to 6.0 on a VAS scale; OA and RA had a mean duration of 6 to 14 years and 23-80% had moderate or intense pain.

Q9 – what are the demographics of chronic pain sufferers in Spain? Fifty five studies were relevant and 4 were selected that were medium or high quality and representative of the Spanish population. For general non-cancer pain: 52-66% were women, mean age 51-57 years, 93% lived with their family, 74.5% lived in an urban setting, 42% were overweight and 29% obese; back pain: mean age of 47.6 years, women 60.7%, manual workers 54.9% and the less educated 71.1%; OA: more frequent in women, the elderly, in people with less than 8 years of formal education, from a low social class, in obese and in those with a physically demanding job.

Q10 – what are the co-morbidities of Spanish chronic pain sufferers? 4 relevant studies were selected from 51, all of which were representative of the Spanish pain population and were generally of high quality. Hypertension was the most prevalent co-morbidity for all types of pain. For pain patients with rheumatic and osteoarthritic pain the other most common comorbidities were cardio-vascular diseases and diabetes, and in FM patients, psychiatric disease, neurologic diseases and depression.

Q11 – how many sufferers have inadequate pain control? Soucase (2005) and Rodriguez (2006) only indirectly address this question. Breivik (2006) was representative of the population and found that for people with chronic pain 67% of respondents did not have adequate pain control and 70% had changed drug prescription due to inadequate pain control.

Q12a and b – in Spain, what is the impact of chronic pain on quality of life and activities of daily living? 17 Three of the included studies (Carmona (2001), Nunez (2007) and Fernandez-Lopez (2008)) EXECUTIVE SUMARY / EPIDEMIOLOGY OF CHRONIC were of high quality and representative of the Spanish pain population. Chronic pain can NON-MALIGNANT PAIN IN SPAIN affect all areas of quality of life for sufferers, although the affects can vary on the specific dimensions of quality of life depending on the type of pain, gender, age, disease duration and satisfaction with treatment. Chronic pain sufferers report a lower quality of life than acute pain patients. For patients aged over 65 years with general non-cancer pain, the prevalence of pain interference with activities daily living was 48.6%. For patients with back pain, 36.7% were limited in their daily activities, 23% needed bed rest and 17% had to stop working due to their pain.

Q12c and d – what is the impact on depression and other mental illnesses, and on isolation and helplessness? Three of the included studies were representative of the population (Gamero (2005), Galvez (2006) and Breivik (2006)) and all included studies had large sample sizes. Levels of depression in pain patients ranged from 7% to 29%, and levels of anxiety from 8.2% to 12.9%. Both depression and anxiety were found to be higher in women and depression higher in patients with FM. Women also showed higher levels of social isolation than men, but this is related to their lower functional capacity than men as they have more chronic conditions.

Q12e and f – what is the impact of chronic pain on days off work in Spain and on incapacity benefits? All studies were of medium quality and had large sample sizes, although it was not clear that all of them were representative of the Spanish population. The mean number of days lost for general non-cancer chronic pain was 8.4 and pain led to time off work for 10% of the sample. Rheumatic conditions led to 6970 work disabilities cases during the 5 years study period, equivalent to 364 624 work off days, at a cost of 1,397,258,172 pesetas (839,769,074 euros) and the mean annual value for work disability was equivalent to 279.451.634 pesetas 18 (167,953,815 euros). EXECUTIVE SUMARY / EPIDEMIOLOGY OF CHRONIC Q13a-c – in Spain, what are the costs of chronic pain from NON-MALIGNANT PAIN IN SPAIN societal, health care system and patient perspective? All studies were either of medium or high quality and 5 represented the Spanish population. However, it is difficult to estimate the total economic costs of chronic pain as the majority of the studies reported on specific pain conditions in specific settings.

Q14 – what are the issues/determinants of patients’ awareness of chronic pain in Spain? Overall, study quality was medium to high. However, it was not clear whether any of the studies were representative of the Spanish population. For patients attending pain clinics, the higher their stress levels, the higher the level of interference of their pain. The variables that predict more stress in patients were intensity of pain, activity reduction and emotional affectation. Pain often exceeded their coping resources and became disabling and the most frequently used strategies for coping with pain: self-assertion, search for information, religion. For patients with FM those with tiredness and paraesthesia felt more of an impact of disease and the symptoms that most affect daily living are tiredness, bone and joint pain and a depressed mood.

Q15 – what are the issues/determinants of health care professionals’ awareness of chronic pain in Spain? These studies were not representative and one was rated as low quality. Little information was found in answer to this question, and it is difficult to draw conclusions from the included studies.

Q16 – what are the main symptoms and complaints with which patients present themselves to health care professionals in Spain? 19 Only one of the studies was representative of the Spanish population, however this study EXECUTIVE SUMARY / EPIDEMIOLOGY OF CHRONIC reported the most painful locations that patients present with, and not symptoms directly. NON-MALIGNANT PAIN IN SPAIN For patients visiting pain clinics, the most frequent symptoms associated with chronic pain: were sleeping disorder 50%, depression 48%, anxiety 47% and irritability 30%.

Q17 and 19 – what are the frequencies of drug, non-drug and combined treatments in Spain and what are the determinants of treatment choice between drug treatment and non-drug treatment? The quality of the included studies was varied, and only one of these was representative of the Spanish population (Breivik (2006)). For patients with general non-cancer pain, the frequencies of drug treatments were NSAID 49%, weak opioid 13%, strong opioid 1%, paracetamol 8% and COX-2 inhibitor 2%.

Q18 – what are the determinants of treatment choice between drug treatment and non-drug treatment in Spain? No studies were found that addressed this question.

Q21 – what is patients’ satisfaction about drug treatments? The study quality was varied, with studies low to high quality, only one of which was representative of the Spanish population. For patients with OA, 46% of patients and physicians were not satisfied with OA treatment, 15.5% of patients and 8.5% of physicians were highly dissatisfied. Elderly patients in primary care described their treatment as very good in 2.5%, good in 27.8%, regular in 46.2% and bad/very bad in 23.5%. For patients in nursing homes their satisfaction with analgesic treatment: 18% were “unsatisfied” or “very much unsatisfied”; the rest, 82%, were from “low satisfaction” to “high satisfaction”.

20 EXECUTIVE SUMARY / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Conclusions

Pain is a common condition that is a major source of suffering and disability in patients worldwide and has a considerable impact on quality of life (Bonica (1990)). This condition has direct social repercussions and also direct work related and economic costs.

To our knowledge this is the most comprehensive literature review on epidemiological Spanish data in this field. We have focused our attention on the identification and appraisal of the most representative, recent and valid studies published about chronic pain in Spain, including data from the main collaborative research projects (EPISER, EPIDOR, Miro (2007), PREVADOL).

Prevalence of chronic pain in Spain is estimated at 12% (Breivik (2006)), and data suggest that prevalence increases with increasing age (Miro (2007)). Analysis of the results from studies located and assessed in this review can be used to draw a profile of chronic non- malignant pain sufferers in Spain (Casals (2004), ITACA, Breivick (2006), Bassols (2003), EPISER). Those most commonly afflicted by the condition are women between the age of 51 to 57 years, live with their families in an urban setting, and are often also overweight. The duration of chronic non-malignant pain ranges from 6 to 14 years.

Chronic pain has an enormous impact on patients. The literature shows that chronic pain affects all the areas of patients’ quality of life, with variations depending on type of pain, gender, age, or disease duration. It is important to note that this condition interferes in half of all patients older than 65 years (Miro (2005)).

Although the majority of patients with chronic pain in Spain are treated, a significant per- 21 centage of patients appear to be inadequately treated. Often patients perceived that their EXECUTIVE SUMARY / EPIDEMIOLOGY OF CHRONIC treatments had no effect (EPIDOR). The paucity of data on satisfaction and/or compliance NON-MALIGNANT PAIN IN SPAIN with treatment is worrying. Some studies have shown that up to 60% of patients are dissatisfied or highly dissatisfied with the treatment received (VIOXX study).

Our review has identified some gaps that are relevant for providing an accurate estimate of the burden of chronic non-malignant pain in Spain. Although most studies identified hypertension as the main co-morbidity in patients with chronic pain, followed by other cardiovascular conditions, diabetes and mental health problems in the case of fibromyalgia, there is a need for more accurate data about the main co-morbidities and risk factors to allow physicians to identify the patients that are more prone to suffer from chronic pain.

The variability in the collected data (notable in data related to prevalence, unavailable for incidence) reflects an inconsistency in the definition of the condition, and the measurement approach to assess its impact. To have feasible and reliable epidemiological data about chronic pain, researchers should join efforts to define minimum standards to approach the research in this field. Research should also encourage and promote studies designed with a multidisciplinary approach, including different healthcare professionals and specialities responsible for pain management. These studies should be based on common and standardised diagnostic criteria, focusing on the treatments used, the social impact of chronic pain, and its related costs. Only studies with a broad approach will provide healthcare professionals and Spanish society with a clear image of the implications derived from a complex problem such as chronic pain, and will contribute to identify the gaps and neglected needs related to this condition.

22 EXECUTIVE SUMARY / EPIDEMIOLOGY OF CHRONIC Figure 1: Spain epidemiology flow for moderate to severe chronic pain NON-MALIGNANT PAIN IN SPAIN

Epidemiology Epidemiological data on Numbers on chronic pain:

1. Prevalence Population 46 160 000 (38,207,800 adults)

2. Diagnosis Prevalence 4 584 936 (12% of adults)

3. Treatment choice Patient awareness WHO class I – 8% took paracetamol; Patient presentation 49% took NSAID; 2% took Cox2 inhibitor Disease diagnosis WHO class II – 13% took a weak opioid with or without paracetamol WHO class III – 1% of chronic pain patients took a strong opioid

4. Brand choice Brand choice No data

5. Compliance Compliance – Pharmacy Rx fill Compliance with NSAIDs medium Compliance – Patient persistence score of 12 (range 4-22) on 0-70 scale (0 = perfect compliance) in patients with osteoarthritis; Compliance with rofecoxib medium score of 8 (range 1.5-16.5) in patients with osteoarthritis; Compliance in chronic pain patients treated with tramadol was poor in 12%

23 Introduction INTRODUCTION / EPIDEMIOLOGY OF CHRONIC Estimates of the prevalence of chronic pain vary widely and typically range between 10-30% NON-MALIGNANT PAIN IN SPAIN of the adult population, although studies exist reporting prevalence as low as 2% or as high as 50% (IASP (2003), Breivik (2006)). This wide variation may reflect true differences between populations, but also the use of different definitions of chronic pain in epidemiological studies. Most definitions include continuous or intermittent pain, persisting for more than 3 months. Also, assessment methods vary, mostly involving a survey either by telephone or with data collection in person, using a range of different questionnaires and rating scales.

Typical locations of chronic pain include upper and lower back, head and neck, and joints. Surveys of the location of chronic pain also report sometimes considerable variations. Chronic pain is often reported to be more common among women, in older age groups and in lower income groups.

Severity of chronic pain is another element which is not straightforward to assess, both in terms of definitions of various grades of severity, and in terms of which measurement instruments are used. Compared with chronic pain of mild intensity and minimal disability, individuals with severely disabling chronic pain are more likely to have co-morbid health conditions, poorer self-rated health, problems with mental well-being and social functioning, activities of daily living, work loss, isolation, helplessness, and high health care costs and utilization.

Chronic pain is very common but good data about prevalence, incidence, diagnosis, severity, treatment and utilization of health care are scarce. National statistics in Europe do not tend to focus on chronic pain as a discrete entity, but rather see pain as part of other underlying diseases, a symptom. This approach ignores the insight of clinicians specialised in pain 25 treatment that chronic pain is considered a discrete entity in itself, with clear characteristics INTRODUCTION / EPIDEMIOLOGY OF CHRONIC of symptoms, disability and mental health aspects which are largely independent of the NON-MALIGNANT PAIN IN SPAIN underlying disease or trauma [Ref to be added]. Many studies of chronic pain prevalence have been based in particular care settings, such as pain clinics, or in particular subgroups with certain underlying diseases.

Information about the epidemiology of chronic pain can be important for decision and policy makers, so that they can decide about health budgets and prioritization, patient segmenting and budget fencing, and therapy budgets, including behavioural therapy and drug budgets. Compared with cardiovascular disease, oncology, diabetes and mental health there often seems to be limited appreciation by decisions makers about the importance of chronic pain, so data about all aspects of the epidemiology of chronic pain from prevalence to cost impacts will be useful for proper information. Chronic pain is an important and frequent medical and public health issue, and there seems to be a need for better understanding of the burden of disease and current treatment practice of chronic pain.

This report aims to provide information about chronic pain in Spain. It is a part of a larger project addressing chronic pain in a range of European countries and Europe as a whole. Our method is a review of the available published and unpublished data, using the prin- ciples of systematic reviews in searching and identifying relevant studies, and summarizing their findings. Given the types of questions to be addressed, we aimed to use the most representative, recent, comprehensive and valid studies, rather than summarizing the results of all studies that were found.

26 Methods METHODS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Objective of project

To undertake a literature review on the most recent epidemiological data on chronic non- malignant pain in Spain.

Questions to be addressed

Epidemiology flow 1) What are the population and demographics of Spain? 2) What is the prevalence of chronic pain conditions? 3) What is the incidence of chronic pain conditions? 4) What percentage of chronic pain patients are untreated or inadequately treated? 5) How many chronic pain patients present themselves for treatment? 6) How many chronic pain patients get treated broken down by treatment? 7) What is the compliance of treated chronic pain patients?

Questions leading to in depth information to the numbers mentioned in the Epidemiology flow 1) What is the disease duration of chronic pain conditions? 2) What are the demographics of pain sufferers? 3) What are the co-morbidities of pain sufferers? 4) How many sufferers have inadequate pain control? 5) What is the impact of chronic pain on: a) Quality of life 28 b) Activities of daily living METHODS / EPIDEMIOLOGY OF CHRONIC c) Depression and other mental illness NON-MALIGNANT PAIN IN SPAIN d) Isolation, helplessness e) Days off work f) Incapacity benefits 6) What are the costs of chronic pain from a a) Societal perspective? b) Health care system perspective? c) Patient perspective? 7) What are issues/determinants of patients’ awareness of chronic pain? 8) What are issues/determinants of health care professionals’ awareness of chronic pain? 9) What are the main symptoms and complaints with which patients present themselves to health care professionals? 10) What are the frequencies of drug (per WHO class), non-drug, and combined treatments? 11) What are determinants of treatment choice between drug treatment and non-drug treatment? 12) What are determinants of treatment choice within drug treatments? 13) What are determinants of compliance / adherence to drug treatments? 14) What is patients’ satisfaction about drug treatments?

Inclusion criteria

Study characteristics Primary studies (epidemiologic, qualitative, cost analyses etc.) or systematic reviews of primary studies published 1995 onwards. Only relevant primary data used in any systematic 29 reviews identified and fulfilling the inclusion criteria were used in the data analysis. METHODS / EPIDEMIOLOGY OF CHRONIC Exclusions: non-systematic reviews, studies examining the effectiveness of treatments, com- NON-MALIGNANT PAIN IN SPAIN ments, letters, editorials; any studies not showing any original data but just expressing opinions.

We expected to use the following types of data: national statistics (question 1), data from national health surveys (questions 2, 3), epidemiological studies (cohort, cross-sectional etc.) (questions 2 to 21), insurance data (data on early retirement, service use, prescriptions etc.) (questions 2, 12, 17), qualitative studies (questions 12, 13, 14, 15, 16, 18, 19, 20, 21), economic analyses (question 13), RCTs (e.g. of specific interventions to increase awareness, adherence with awareness/adherence as main outcome, possibly treatment satisfaction) (questions 14, 15, 20, 21)

Patients Patients with chronic non-malignant moderate and/or severe pain from Spain.

Chronic pain includes: ®® musculo-skeletal pain: back pain / low back pain / shoulder pain / neck pain ®® neuropathic pain (e.g. diabetic, post herpetic) ®® fibromyalgia (FM) ®® osteoarthritis (OA) ®® rheumatoid arthritis (RA)

Exclusions: ®® children and adolescents ®® patients with mild pain ®® patients with headache / migraine 30 ®® patients with angina pectoris METHODS / EPIDEMIOLOGY OF CHRONIC ®® pain associated with very specific medical conditions, e.g. Parkinson’s disease, multiple NON-MALIGNANT PAIN IN SPAIN sclerosis etc. ®® studies of non-European participants – unless European data or data for relevant Euro- pean countries are given separately ®® studies including cancer patients – unless data for non-cancer patients are given separately (or 10% or less of cancer patients)

Literature searches

We aimed to identify all relevant studies regardless of publication status (published, unpublished, in press, and in progress), or language.

The search strategies (keywords) were developed specifically for each database (appendix).

We searched the following databases: ®® MEDLINE (1995 to August 2009) ®® EMBASE (1995 to August 2009) ®® CDSR (Cochrane Library issue 2 2009) ®® CENTRAL (Cochrane Library issue 2 2009) ®® DARE (August 2009, CRD website) ®® HTA (August 2009, CRD website) ®® Guidelines International Network database (August 2009, GIN website)

Furthermore, references in retrieved articles and systematic reviews were checked. Sup- 31 plementary searches were undertaken as appropriate. Relevant websites were searched for METHODS / EPIDEMIOLOGY OF CHRONIC national statistics, insurance data, health surveys and other relevant data. Relevant sites are NON-MALIGNANT PAIN IN SPAIN shown in the appendix. Identified references were downloaded in Reference Manager soft- ware for further assessment and handling.

The proposed search strategies (Ovid) are shown in the appendix.

32 Methods of study selection, quality assessment and data extraction METHODS OF STUDY SELECTION, QUALITY This literature review followed the methods and processes recommended in the Centre for Reviews ASSESSMENT AND DATA EXTRACTION / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN and Dissemination (CRD) “Systematic Reviews: Guidance for undertaking reviews in health care”.

Study selection

Two reviewers independently inspected the title and abstract of each reference identified by the search and determine the potential relevance of each article. For potentially relevant articles, or in cases of disagreement, the full article was obtained, independently inspected, and inclusion criteria will be applied. Any disagreement will be resolved through discussion. Justification for excluding studies from the review (after having retrieved potentially relevant articles) was documented.

Included studies were categorised in order to get a list of relevant studies per question. Where there were more than three studies addressing a single aspect of any question, then for each question the most relevant studies were extracted using the following criteria: size (large preferred), recency (most recent preferred), quality (highest quality preferred), repre- sentativeness (populations representative of the general target population preferred). Studies were ranked by these criteria and the three or four highest ranking studies were extracted.

Assessment of methodological quality

Quality assessment was carried out by one reviewer and checked by a second, using check- 34 lists as outlined below. Any disagreements were resolved by consensus. The results of the METHODS OF STUDY SELECTION, QUALITY quality assessment have been used for descriptive purposes to provide an evaluation of the ASSESSMENT AND DATA EXTRACTION / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN overall quality of the included studies and to provide a transparent method of recommenda- tion for design of any future studies. Based on the findings of the quality assessment, recommendations have been be made for the conduct of future studies.

The following quality criteria were used for the assessment of the different study types: (criteria to be answered with yes / no / unclear)

Observational studies: ®® Adequate description of study design and setting ®® Adequate description of eligibility criteria (incl. description of diagnostic criteria for chronic pain condition) ®® Study population is representative of target population (sample size, sample selection, demographics) ®® Adequate description of outcomes (and how / how often measured), exposures, predictors ®® Adequate description of statistical methods (incl. description of potential confounders and effect modifiers and how they were dealt with) ®® Adequate description of study participants ®® Adequate description of losses to follow-up (for longitudinal studies), loss to follow-up less than 10% at 12 months or less than 25% for longer follow-up ®® Results reported as unadjusted and confounder-adjusted including precision

RCTs: ®® Adequate method of randomisation ®® Adequate allocation concealment ®® Adequate blinding (if appropriate) 35 ®® Adequate handling of losses to follow-up METHODS OF STUDY SELECTION, QUALITY ®® Adequate description of eligibility criteria (incl. description of diagnostic criteria for ASSESSMENT AND DATA EXTRACTION / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN chronic pain condition), interventions and outcome measurement ®® Study population representative of target population (sample size, sample selection, demographics) ®® Groups comparable at baseline

Qualitative studies: ®® Adequate description / justification of study design and setting ®® Adequate description of eligibility criteria (incl. description of diagnostic criteria for chronic pain condition) ®® Study population representative of target population (sample size, sample selection, demographics) ®® Adequate description of outcomes / questions / procedures ®® Adequate description of study participants ®® Methods of data summary described and sound (quotes used, data categorisations, theory)

SRs of observational studies: ®® Adequate description of inclusion criteria (study design, participants, interventions / exposure, outcomes) ®® Adequate description of search strategy (sources, keywords, time period, limits) ®® Adequate description of study selection ®® Adequate description of assessment of confounding ®® Adequate description of quality assessment ®® Adequate description of data analysis and heterogeneity assessment ®® Description of study flow 36 ®® Study characteristics of each study included METHODS OF STUDY SELECTION, QUALITY ®® Quality of each study included ASSESSMENT AND DATA EXTRACTION / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN ®® Results of each study included and overall

SRs of RCTs: ®® Adequate description of inclusion criteria (study design, participants, interventions, outcomes) ®® Adequate description of search strategy (sources, keywords, time period, limits) ®® Adequate description of study selection ®® Adequate description of quality assessment of included studies ®® Description of trial flow ®® Description of data analysis / summary (including heterogeneity) ®® Description of study characteristics of the included studies ®® Quality of each study included ®® Results of each study included and overall

Data extraction and presentation

For each study, data were extracted by one reviewer and checked by a second reviewer. Any disagreements were resolved by consensus.

We employed a narrative method to present the data and for any synthesis. Typically, narrative synthesis involves the use of narrative text and tables to summarise data in order to allow the reader to consider outcomes in the light of differences in study designs and potential sources of bias for each of the studies being reviewed. This involves organising the 37 studies by (as appropriate) intervention, population, or outcomes assessed, summarising METHODS OF STUDY SELECTION, QUALITY the results of the studies, summarising the range and size of the associations these studies ASSESSMENT AND DATA EXTRACTION / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN report, and describing the most important characteristics and the quality of the included studies.

Study characteristics and quality were presented in tables. Tables of results (including basic demographics of the populations assessed) are presented in tables subdivided by questions.

38 Results RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Search, selection and allocation of studies

We retrieved and selected 112 studies from Spain that were relevant to the project questions and they can be viewed in Figure 2. The allocation and number of studies for specific project questions can be viewed in Figures 3-7.

Figure 2: From Spain, 112 studies were found relevant

Europe: 47

Denmark: 65

Germany: 169 Main search: 16 619 hits

Selected for retrieval of France: 60 17 027 hits full text articles: 1056 Dutch search including cancer pain: 408 hits Italy: 51

Clearly not Unclear – keep relevant (titles, for later: 997 Spain: 112 abstracts): 14 974 Netherlands: 155 Unclear – keep for later: 997 Sweden: 157

UK: 236 40 RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 3: Epidemiology flow for Spain – number of studies located per question NON-MALIGNANT PAIN IN SPAIN

Q1 What are the population and demographics of each Q8 What is the disease country? 2 sources duration of chronic pain conditions? 42 studies

Q2 What is the prevalence of chronic pain conditions? Q9 What are the demographics 19 studies of pain sufferers? 55 studies

Q3 What is the incidence of chronic pain condition? Q10 What are the 1 study co-morbidities of pain sufferers? 51 studies

Q5 How many chronic pain patients present themselves Q4 What percentage of chronic for treatment? 16 studies pain patients are untreated or inadequately treated? 5 studies

Q7 What is the Q6 How many chronic pain compliance of patients get treated broken down treated chronic by treatment? 17 studies pain conditions? 3 studies

Q11 How many sufferers have inadequate pain control? 41 3 studies RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 4: What is the impact of chronic pain – Figure 5: What are the costs of chronic NON-MALIGNANT PAIN IN SPAIN number of studies located per question pain from different perspectives – number of studies located per question

Q12a Quality of Life Q13 33 studies Societal perspective? Q12f Q12b 5 studies Incapacity Activities of Benefits daily living 2 studies 15 studies

Impact of Q13c chronic pain on: Patient perspective? Q12c 2 study Q12e Depression Days off Work and other 5 studies mental Illness 12 studies Q13b Q12d Health care system Isolation, perspective? Helplessness 3 studies 5 studies

42 RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 6: Symptoms and awareness – number of studies located per question NON-MALIGNANT PAIN IN SPAIN

Q14 What are issues/determinants of patients’ awareness of chronic pain? 13 studies

Q15 What are issues/determinants of health Q16 What are the main symptoms and complaints care professionals’ awareness of chronic pain? with which patients present themselves to 3 studies health care professionals? 19 studies

Figure 7: Treatment – number of studies located per question

Q17 What are the frequencies of drug (per WHO class), non-drug and combined treatments? Q18 What are the determinants of 33 studies treatment choice between drug treatment and non-drug treatment? 2 studies

Q18 What are the determinants of treatment choice between drug treatment Q18 What are the determinants of and non-drug treatment? 2 studies treatment choice between drug treatment and non-drug treatment? 2 studies

Q18 What are the determinants of treatment choice between drug treatment and non-drug treatment? 2 studies 43 RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Q1 what are the population and demographics of Spain?

To answer this question two resources were used: Spain in Figures 2009, the latest edition of Spain in figures, presented by the National Statistics Institute, corresponding to the year 2009 (http://www.ine.es/en/prodyser/pubweb/espcif/espcif_en.htm), and the CIA World Factbook for Spain (https://www.cia.gov/library/publications/the-world-factbook/geos/sp.html), which gives 2009 estimates.

The total population resident in Spain at 1 January 2008 was 46.16 million inhabitants, and 49.5% of total registered voters are male and 50.5% are women. The sex ratio at birth is 1.07 males to each female, decreasing to 0.96 males for the total population (2009 estimate). The median age of the country in total is 41.1 years, and 39.7 years for males and 42.5 years for women (2009 estimate). The population by age range is as follows: aged 0-14 years=14.5%; 15-64 years=67.4%; and over 65 years=18.1%.

Figure 8: Age distribution of Spain 2008

67% AGE 15-64 YEARS

18% AGE over 65

15% AGE 0-14 YEARS 44 RESULTS / EPIDEMIOLOGY OF CHRONIC The life expectancy at birth for the total population is 80.05 years, 76.74 years for males and NON-MALIGNANT PAIN IN SPAIN 83.57 years for females (2009 estimate). Life expectancy at birth in 2007 was 82.2 years for females and 77.8 years for males. According to the National Health Survey of 2006, 37.8% of the population 18 years of age and over is overweight and 15.6% is obese. 27.6% of the population 2 years to 17 years of age is overweight or obese.

Figure 9: Weight of the adult Spanish population 2006

38% OVERWEIGHT

16% OBESE

46% HEALTHY OR UNDERWEIGHT

97.9% of the total population is literate (defined as age 15 and over who can read and write) 98.7% of males and 97.2% of females. The forecast of the number of students in the non-university General Education System for 2008-09 is 7,419,989 and the total�� in University Educa- tion was 1,410,440 in the 2006-07 academic year.

The total population aged 16 and over in 2008 was 38 207 800 (59.8%) and of these 22 848 45 200 made up the active population, 20 257 600 were employed, 2 590 600 were unemployed RESULTS / EPIDEMIOLOGY OF CHRONIC (11.3%) and 15 359 600 made up the inactive population. The female activity rate was 50.5%, NON-MALIGNANT PAIN IN SPAIN and the male activity rate was 69.5%. The Living Conditions Survey registered an average net annual income per household of 24,525 euros in 2006.

Figure 10: Percentage of the active population of Spain in employment and unemployed

25,00 88,7% 20,00

15,00

MILLION 10,00

5,00 11,3%

0,00

EMPLOYED UNEMPLOYED

Data for the ethnic breakdown of Spain is not given on the Spanish National�� Statistics Insti- tute website. However, 11.4% of the population resident in Spain in 2008 were foreign, with Romania, Morocco, Ecuador, United Kingdom and Colombia making up the highest proportions of foreigners (13.9%, 12.4%, 8.1%, 6.7% and 5.4% respectively).

46 RESULTS / EPIDEMIOLOGY OF CHRONIC Table 1. Population characteristics for Spain NON-MALIGNANT PAIN IN SPAIN

POPULATION CHARACTERISTICS SPAIN DATA SOURCE OF DATA COLLECTION

GENERAL POPULATION DATA

Median Age (years) 41.1 Spain in Figures 2009, National Statistics Institute Sex ratio (male:female) 0.96:1

POPULATION BY AGE RANGE

0-14 yrs (%) 14.5

15 to 64 yrs (%) 67.4 CIA World Factbook for Spain

65 yrs and over (%) 18.1

AVERAGE NET ANNUAL INCOME PER HOUSEHOLD (EUROS) 24,525 Living Conditions Survey, Spain in Figures 2009, National Statistics Institute

EMPLOYMENT (2008)

Employment rate (N) 20.26 million

Unemployment rate (N) 2.59 million Spain in Figures 2009, National Statistics Institute % 11.3

Inactivity rate (N) 15.36 million

OCCUPATION

Services (%) 61.8

Industry (%) 15.8

Construction (%) 12.1 Spain in Figures 2009, National Statistics Institute Agriculture (%) 4.0

Self-employed workers (N) 3.56 million

Employed workers (N) 16.68 million 47 POPULATION CHARACTERISTICS SPAIN DATA SOURCE OF DATA COLLECTION RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN EDUCATION

Literacy rate (%) 97.9

In non-university education (N) 7.42 million Spain in Figures 2009, National Statistics Institute

In university education (N) 1.41 million

ETHNICITY – DATA NOT FOUND

Foreign (%) 11.4 Spain in Figures 2009, National Statistics Institute

BMI

Population aged 18 yrs and over Overweight (%) 37.8 Obese (%) 15.6 National Health Survey of 2006, in Spain in Figures 2009, National Statistics Institute Population aged 2 to 17 years Overweight or obese (%) 27.6

Q2 What is the prevalence of chronic pain conditions in Spain?

To answer the different aspects of this question, 10 studies were chosen for inclusion. Most studies were population-based studies investigating the prevalence of different pain disorders. In some cases the sample from which the prevalence data was determined did not represent the general adult population, but rather specific subgroups, for example the elderly (Miro et al. (2007)), or those who used a specific type of health service related to their pain/disorder (Montero Homs et al. (2005)). There was limited information available that reflected the severity of pain in those individuals identified as suffering a chronic pain condition in the included 48 studies. These details of the individual studies are shown in Table 2. Study quality was variable. Table 2. Characteristics of studies relevant to Question 2: prevalence of chronic pain

Study details Population

General chronic pain

Breivik et al. (2006) Type of chronic pain Non-cancer long-lasting pain: suffered from pain for ≥6 months, had Study Design experienced pain in the last month, at ≥2 times per week, and rated their Computer-assisted telephone survey in two parts: first persons (aged ≥18 years) were pain intensity when they last experienced pain as ≥5 on a 10-point Numeric screened for chronic pain; those who qualified received an in-depth structured interview Rating Scale (NRS; 1 = no pain at all and 10 = the worst pain imaginable)

Quality Confirmation of diagnosis Medium: representative population survey but limited information on Not reported methodology and participant characteristics for individual countries Sample size and demographics N = 4839 across Europe, n = 3801 in Spain for question on prevalence, n = 301 for severity, mean age 50.7 years in Spain; 52% female in Spain

Miro et al. (2007) Type of chronic pain Non-cancer pain: at least one day in last 3 months, of those with pain 89.9% Study Design was chronic (>3 months duration). Severity measured by Chronic Pain Cross sectional. Representative sample of older adults 65+ randomly Grade questionnaire: 40.4% at least severe (CPG: Grade selected from population and interviewed about their pain. I); 14.3% from most severe (CPG: Grade IV).

Quality Confirmation of diagnosis Medium: representative population survey but no description Not reported of statistical methods and reporting of outcomes. Sample size and demographics N = 592, 53.7% women, Mean age 74.9(6.5) years.

49 Study details Population

Multiple conditions

Carmona et al. (2001) Type of chronic pain Non-cancer pain including low back pain, symptomatic knee osteoarthritis Study Design (OA), hand OA and fibromyalgia (FM). Severity not reported. Subjects 20+ years randomly selected by stratified multistage cluster sampling from the censuses of 20 municipalities (EPISER Study). Interviews Confirmation of diagnosis and standardised physical examination by trained rheumatologists. Low back pain was defined by self-report. Symptomatic knee and hand OA, as well as FM, were defined by the respective ACR criteria. RA cases were defined by the ACR Quality classification criteria adapted to epidemiological surveys and laboratory/diagnostic testing. High: Good quality fulfilled all criteria Sample size and demographics N = 2192, 53.7% women.

Back pain

Bassols et al. (2003) Type of chronic pain Back pain: any suffered in last 6 months, of those with pain 69.2% >3 years duration. Study Design Severity measured by Verbal scale; rate intensity - light, moderate, intense, very Telephone survey of sample of adults (18+) from Catalonia stratified for age, intense, unbearable. 85.7% ≥ moderate. Also Numerical Scale; 1 - very little sex and residency, asked about their back pain, its effects and treatment. pain, 10 - unbearable. Mean 6.0 (1.6).

Quality Confirmation of diagnosis Medium: representative population survey but reporting Not reported of statistics and diagnostic criteria unclear. Sample size and demographics N = 1964, 50.3% women, Mean age 47.5(17) years.

50 Study details Population

Pinto-Meza et al. (2006) Type of chronic pain Back pain: suffered ever and if so, in last 12 months. Severity not reported. Study Design Survey of 18+ year olds. Pain and comorbidities by self-report. Mental Confirmation of diagnosis disorders by Composite International Diagnostic Interview and global Patient reported if previously diagnosed by doctor. functioning with the WHO Disability assessment schedule. Sample size and demographics Quality N = 2121, 1302 women, 819 men. Low: Eligibility criteria and sample characteristics unclear.

Fibromyalgia

Sicras-Mainar et al. (2009) Type of chronic pain Fibromyalgia. Generalised, continuous pain > 3 months duration. Severity not reported. Study Design Adults (18+) from 5 primary care centres. Retrospective analysis of Confirmation of diagnosis patient records. Comparison made between reference group without ACR criteria for musculoskeletal disorders. Fibromyalgia or Generalised Anxiety Disorder and groups with. Sample size and demographics Quality N = 63 349, 54.1% women, Mean (SD) age, 49.2 ± 17.8 yrs. Reference group, N = 59 060, Medium: Representative of population, description and reporting of outcomes unclear. 52.5% women, 48.7 ± 17.9 yrs. Fibromyalgia group, N = 904, 96.5% women, 54.3 ± 9.8 yrs.

Mas et al. (2008) Type of chronic pain Fibromyalgia. Generalised, widespread pain > 3 months duration. Study Design Severity not reported, must be greater than 1 on 0-10 VAS. Cross-sectional study of adults (20+), selected by cluster sampling (EPISER study). Subjects invited to a structured interview carried out by trained Confirmation of diagnosis rheumatologists to ascertain various musculoskeletal disorders. ACR criteria for musculoskeletal disorders.

Quality Sample size and demographics High: Good quality fulfilled all criteria N = 2192.

51 Study details Population

Osteoarthritis

Espallargues et al. (1996) Type of chronic pain Osteoarthritis and rheumatic disorders. 81.7% moderate/severe. Study Design Barcelona 1986 Health Interview Survey, a cross-sectional study of non- Confirmation of diagnosis institutionalised population aged 65+. Information was collected about Patient self-report. Not confirmed. chronic conditions, perceived morbidity, perceived health status, use of health services and questionnaire of functional capacity was administered. Sample size and demographics N = 1287. 63.3% women Quality Medium: outcomes of interest poorly described, unclear adjustment for confounders.

Knee Osteoarthritis

Fernandez-Lopez et al. (2008) Type of chronic pain Knee pain, continuous pain at least 1 month duration. Severity not reported. Study Design Cross-sectional study of adults (20+), selected by cluster sampling (EPISER Confirmation of diagnosis study). Subjects invited to a structured interview carried out by trained ACR criteria for knee osteoarthritis. rheumatologists to ascertain various musculoskeletal disorders. Sample size and demographics Quality N = 2192. High: Good quality fulfilled all criteria

Neuropathic Pain

Montero Homs et al. (2005) Type of chronic pain Neuropathic pain. 77.2% > 6 months duration. Study Design Severity not reported. Cross sectional study of adults (18+) attending neurology clinics (PREVADOL Study). Prevalence and incidence data collected by Confirmation of diagnosis neurologist diagnosis for 20 consecutive days up to 30/day. According to International Association for the Study of Pain (IASP) criteria.

Quality Sample size and demographics Medium: Well described sampling criteria and characteristics, N = 12 688. 59.4% women, Mean(SD) age, 62.84(13.9) description of outcomes and reporting unclear.

52 RESULTS / EPIDEMIOLOGY OF CHRONIC Q2 Results NON-MALIGNANT PAIN IN SPAIN Table 3 shows the prevalence data for chronic pain in general, and for different pain disorders where available. Where the sample used in the study has appeared generally representative of that of the general adult population of Spain, projections to the population have been attempted using the comparable adult population data described in Question 1 (16 years and over, 2008). These values should be treated with caution.

Table 3. Prevalence data for chronic pain in general, and for different pain disorders

Projected to adult Study Pain characteristics Prevalence population (38,207,800)

General chronic pain

Breivik et al. (2006) Moderate/severe chronic pain 12% 4,584,936

Miro et al. (2007) Chronic pain lasting >3 months 65-74yrs 70.8% 75-84yrs 71.9% ≥85yrs 72.1%

Back pain

Bassols et al. (2003) Back pain (6 month) 50.9% 19,103,900

Pinto Meza et al. (2006) Back pain (1 year) 14.7% 5,616,546 (SE 1.2)

Back pain (lifetime) 23.7% 9,055,248 (SE 1.4)

Carmona et al. (2001) Low Back Pain 14.8% 5,654,754 (95%CI 12.2-17.4) 53 Projected to adult RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Study Pain characteristics Prevalence population (38,207,800)

Fibromyalgia

Sicras-Mainar et al. (2009) ACR criteria 1.4% 534,909 (95%CI 0.6-2.2)

EPISER Study ACR criteria, widespread pain > 3 months 2.37% 905,524 Mas et al. (2008) (95%CI 1.53-3.21) Carmona et al. (2001)

Osteoarthritis (general)

Espallargues et al. (1996) Self-reported arthrosis or rheumatism 51.0% (95%CI 48.3-53.7)

Hand osteoarthritis

Carmona et al. (2001) ACR criteria 6.2% 2,368,883 (95%CI 5.9-6.5)

Knee osteoarthritis

EPISER Study ACR criteria, Knee pain most 10.2% 3,897,195 Carmona et al. (2001) of time for 1 month (95%CI 7.9-12.5) Fernandez-Lopez et al. (2008)

Rheumatoid arthritis

Carmona et al. (2001) Physical examination/testing 0.5% 191,039 (95%CI 0.3-0.9)

Neuropathic Pain

Montero Homs et al. (2005) IASP clinical criteria 3.88% (95%CI 3.54-4.22)

54 RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 11: Overview of the prevalence of chronic pain disorders in Spain NON-MALIGNANT PAIN IN SPAIN

Population 46,160,000 (38,207,800 adults)

Chronic pain (patient awareness) Moderate/severe: 4,584,936 (adults)

Back pain Neuropathic Arthritis Chronic Post- Chronic (diagnosed) pain (diagnosed) regional pain thoracotomy visceral pain 15-51% (diagnosed) no data syndromes pain, post syndromes 4% (CRPS) mastectomy no data no data pain no data

Low back Herpes zoster Osteoar- pain 14.8% & post-herpetic- thritis 51% neuralgia no data

Rheumatoid Shoulder/ Trigeminal arthritis 0.5% neck pain neuralgia no data no data

Diabetic Back pain neuropathy no data without radiculopathy no data Stump and phantom limb pain no data

Back pain with 55 radiculopathy no data RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Q3 What is the incidence of chronic pain conditions in Spain?

Only one study was located relevant to this question for Spain. Montero Homs et al. (2005) surveyed neurology clinics across Spain to estimate the prevalence and incidence of neuropathic pain. Diagnosis was made by the attending neurologist. Underlying causes and treatments of the neuropathic pain were also reported on in adult patients; however it was unclear in the publication if the prevalence/incidence data was restricted to adults alone (likely). No measure of pain severity was reported. Of the cases of neuropathic pain diagnosed in adults, 77.2% were identified as chronic (> 6 months duration). Further details of the study are in Table 4.

Table 4. Characteristics of studies relevant to question 3: incidence of chronic pain

Study details Population Outcomes and analysis

Montero Homs Type of chronic pain Outcomes measured et al. (2005) Neuropathic pain. 77.2% > 6 months duration. Incidence of neuropathic pain, underlying cause. Study Design Confirmation of diagnosis Cross-sectional study. According to International Association for the Study of Pain (IASP) criteria. Pain severity PREVADOL Study. Severity not reported. Sample size and demographics Study Method N = 12 688. Of those diagnosed with neuropathic pain; 59.4% women, Analyses Neurologists recorded Mean(SD) age, 62.84(13.9) years. Descriptive analysis only. diagnosis of attending patients for 20 consecutive Patient selection days. Reported on Diagnoses of all attending patients up to 30/day. The first 20 clinical profile and consecutive adult patients (18+) with neuropathic pain were further treatment in those with characterised. neuropathic pain. 56 RESULTS / EPIDEMIOLOGY OF CHRONIC Q3 Study quality NON-MALIGNANT PAIN IN SPAIN Montero Homs et al. (2005) The study provided a good description of the study design, setting, sampling criteria and eligibility characteristics for patients. Reporting of outcome data and any adjustment were unclear as was full description of study participants.

Q3 Results Incidence of neuropathic pain Montero Homs et al. (2005) In patients attending neurology clinics in hospital neurology units and primary care centres in Spain the daily incidence of neuropathic pain was 1.24 (1.05-1.53).

Q3 Summary The available study presented daily incidence data for neuropathic pain across Spain. This value is of limited applicability to the general population however, but rather represents the specific subset of the adult population attending neurology units for any reason.

Q4 What percentage of chronic pain patients are (a) untreated and (b) inadequately treated

We selected three studies that were relevant to this question, one of which was for general pain (Perez et al. (2009)) and two for specific types of pain, osteomuscular and ostearticular (Noceda et al. (2007) and Medina et al. (1999) respectively). Both Perez et al. (2009) and Noceda et al. (2007) may have included mild pain as well as moderate to severe. 57 RESULTS / EPIDEMIOLOGY OF CHRONIC Perez et al. (2009) was a cross-sectional, one-day, multicentre, non-interventional epide- NON-MALIGNANT PAIN IN SPAIN miological study. Patients were recruited by 623 primary-care physicians (PCPs) from across Spain, representing approximately 2% of the total number of PCPs in the country. The data were collected during a single visit carried out on 20 July 2005. The study aimed to gain epidemiological insight into neuropathic pain in the Spanish primary-care setting.

The aim of Noceda et al. (2007) was to describe the prevalence of use of the 3 analgesic steps of the WHO in patients with chronic osteomuscular pain at 2 primary care centres in Puerto de Sagunto (Valencia) and Alto Palancia (Castellón), Spain, by means of personal interviews during the second semester of 2003 and first of 2004.

Medina et al. (1999) was a three month long descriptive study of all patients with osteoarticular pain referred for the first time to a Department of Rheumatology. The aim of the study was to evaluate whether the pharmacological treatment of pain prescribed by General Practitioners to patients who were referred to a Rheumatology Department was adequate.

58 Table 5. Characteristics of studies relevant to Question 4a and b: % untreated and % inadequately treated

Study details Population Outcomes and analysis

Perez (2009) Type of chronic pain Outcomes measured General non-cancer pain location, duration, aetiology and current treatment Study Design of pain (pharmacological and otherwise). Cross-sectional survey Confirmation of diagnosis PCPs or specialists. Classification of pain aetiology into pure Pain severity Study Method NP, mixed NP or nociceptive pain was carried out at a later Not reported cross-sectional, one- stage prior to statistical analysis by a single expert in pain. day, multicentre, Analyses non-interventional Sample size and demographics Measures of central tendency and dispersion, absolute epidemiological study N = 9604 and relative frequencies. Chi-squared test for qualitative 61.7% female variables, and ANOVA for quantitative variables. Mean age not reported Pure neuropathic pain (NP) = 11.8% Mixed neuropathic pain = 13.4% Nociceptive pain = 74.9%

Patient selection Patients seeking primary care because of pain

Noceda (2007) Type of chronic pain Outcomes measured Osteomuscular Use of analgesics for pain according to age, sex, level of education. Study Design Cross-sectional, Confirmation of diagnosis Pain severity observational, Not reported Intensity of pain measured using the VAS descriptive study Sample size and demographics Analyses Study Method N = 320 ANOVA and chi squared test Personal interviews No further demographic information reported

Patient selection Patients with osteomuscular pain using analgesics according to WHO classes

59 Study details Population Outcomes and analysis

Medina (1999) Type of chronic pain Outcomes measured Osteoarthritis pain, Rheumatoid arthritis pain Whether they received treatment or not, type of drug used and via Study Design of administration of drug, influence of age, cardiovascular disease, Cross-sectional survey Confirmation of diagnosis gastrointestinal diseases and type of disease (inflammatory or not). Definition of rheumatological disease by Spanish Rheumatological Society. Study Method Pain severity Data collected from a Sample size and demographics Not reported Department of Rheumatology N = 207 in Soria, Spain. Method of 63% female Analyses collection not reported. 33% had comorbidities that could make treatment risky – Chi squared, exact Fisher test cardiovascular disease (CVD) and gastrointestinal disease (GI)

Patient selection Patients with osteoarticular pain, that were evaluated by a family physician and visiting a department of rheumatology for the first time

Table 6. Definitions of treated, untreated, inadequately treated and inadequate pain control

Definition

Study Treated Untreated Inadequately treated

Perez (2009) Receiving any kind of treatment Not receiving treatment of some kind Receiving non-pharmacological treatment alone for their (pharmacological and otherwise) pain or receiving pharmacological treatment alone

Noceda (2007) Not reported Did not receive any medication to control Combined with untreated pain or received inadequate dose.

Medina (1999) Not reported Did not receive treatment Excessive dose when quantity above maximum dose. Insufficient when max dose not used and treatment was not efficacious.

60 RESULTS / EPIDEMIOLOGY OF CHRONIC Q4 Study quality NON-MALIGNANT PAIN IN SPAIN Perez (2009) The study was representative of the target population and had adequate descriptions of the study design and setting and the statistical analyses. However, it did not have an adequate description of the eligibility criteria or the study participants. The study was rated overall as being of medium quality.

Nocedo (2007) This study was rated as low quality. There was not an adequate description of the study design and setting, the eligibility criteria, the outcomes and the study participants. There was an adequate description of the statistical methods. It was unclear whether the study population represented the target population.

Medina (1999) This study was also rated as low quality. Although there was an adequate description of the statistical methods and study participants, the study design and setting and eligibility criteria were not adequately described. It was also unclear whether the study was representative of the target population.

Table 7. Summary of results for Question 4: % untreated and % inadequately treated

Study Treated Untreated Inadequately treated

Perez (2009) 99.1% overall 0.9% overall Pharmacological treatment only: General non- 66.1% overall cancer pain 84.6% with pure NP

61 Non-pharmacological treatment only: 3.1% overall Study Treated Untreated Inadequately treated RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Noceda (2007) Not reported 38.7% overall Not reported Osteomuscular Level of education: High school or university degree = 45% Elementary school = 37.8%

Work: 52% of employed

Type of pain: Arthrosis = 41% Arthritis = 22% Chronic back pain = 43% Osteoporosis = 30%

Duration of symptoms: < 2 years = 53% > 2 years = 35%

Sex: Males = 54.7% Females = 33.9%

Medina (1999) 87% (174/200) overall 15.1% (31/207) overall Short acting NSAIDS: (96 patients) OA and RA (unclear in 7 patients) 45.8% had insufficient doses Comorbidities: 3.1% had excessive doses Comorbidities: With CVD = 12% With CVD = 88% Without CVD = 15.7% Long acting NSAIDS: (68 patients) 16.1% Without CVD = 84% had insufficient doses 11.8% had excessive With GI = 23% With GI = 77% Without GI = 14% Without GI = 87%

62 RESULTS / EPIDEMIOLOGY OF CHRONIC Q4 Results NON-MALIGNANT PAIN IN SPAIN Perez (2009) Overall 99.1% of patients were treated using either drug or non-drug treatment for their pain and 0.9% were not treated at all. Inadequate treatment as defined as receiving either only drug treatment or non-drug treatment. Overall, 61% of pain patients received only drug treatment and 3.1% received only non-drug treatment. For pure NP, 84.6% were only treated with drug treatment.

Noceda (2007) Overall 38.7% did not receive any medication to control pain or received inadequate dose. When broken down by disease, the percentage untreated ranged from 22% for arthritis to 43% for chronic back pain. A higher proportion of men than women were untreated for their pain (54.7% and 33.9% respectively) and more patients whose symptoms had a duration of less than 2 years were untreated than those whose symptoms had lasted longer than 2 years (53% and 35% respectively).

Medina (1999) Overall 15.1% patients did not receive treatment for their pain. In patients with comorbidities, the proportion untreated ranged from 12% for those with CVD to 23% of those with GI. For patients using NSAIDS to treat their pain, 45.8% had insufficient doses and 3.1% had excessive doses when using short acting NSAIDS, and of those patients using long acting NSAIDS, 16.1% had insufficient doses 11.8% had excessive doses.

Q4 Summary For general non-cancer pain 99.1% received treatment for their pain (Perez et al. (2009)). This study was representative of the general pain population in Spain. However, it did not present clear data on the proportion of pain patients receiving inadequate treatment, and 63 only gave details on the percentage of pain patients receiving either drug treatment only RESULTS / EPIDEMIOLOGY OF CHRONIC or non-drug treatment only. Far more patients received drug treatment only (66.1%) than NON-MALIGNANT PAIN IN SPAIN non-drug treatment only (3.1%) for their pain (Perez et al. (2009)). For osteomuscular pain, overall 38.7% of patients are untreated, ranging from 22% for those with arthritis to 54.7% for men (Noceda et al. (2007)). For osteoarticular pain 15.1% of patients are untreated and for those using NSAIDS 45.8% are insufficiently treated when using short acting NSAIDS.

Perez et al. (2009) and Noceda et al. (2007) may both have included mild pain patients as well as moderate to severe pain patients, and Noceda et al. (2007) and Medina et al. (1999) were of very poor quality so it is difficult to draw firm conclusions about the proportions of chronic pain patients untreated and inadequately treated in Spain.

Q5 How many chronic pain patients present themselves for treatment?

We selected 3 studies that address this question. Carneado-Ruiz et al. (2001) is a study on neuropathic pain, Gil Gregorio et al. (2007) is on pain in the elderly and Mas et al. (2008) reports on FM.

Gil Gregorio et al. (2007) aimed to obtain information concerning type, clinical evaluation and therapeutic management of pain in elderly people in a primary care setting, and recruited elderly people through their GPs across Spain.

Mas et al. (2008) reports on the EPISER study, specifically at people suffering from FM. The study is cross-sectional study of 2192 Spaniards aged 20 or above, selected by cluster sampling. Subjects were invited to a structured interview carried out by trained rheumatologists 64 to ascertain various musculoskeletal disorders. RESULTS / EPIDEMIOLOGY OF CHRONIC The aim of Carneado-Ruiz (2005) was to evaluate how often patients visit Neurology as NON-MALIGNANT PAIN IN SPAIN outpatients with neuropathic pain (NP) as the main reason for referral. A descriptive, cross sectional study was carried out on the use of the health care services; patients attended for the first time in a Neurology Screening visit were included consecutively.

Table 8. Characteristics and results of included studies for Question 5: How many chronic pain patients present themselves for treatment

Study details Population Outcomes and analysis Results

Carneado-Ruiz (2005) Type of chronic pain Outcomes measured In 81 days of consultation 1422 patients Neuropathic pain (NP) the number of first visits and the total presented themselves. 113 were Study Design number of patients attended per visiting diagnosed with neuropathic pain 8%. Cross sectional survey Diagnostic criteria session, rate of patients with NP per According to symptoms or visiting day, the topography and probable From January to April people presented Study Method provoked pain typical of NP causation of the NP, and the rate of patients themselves more frequently. Least 81 consultation sessions. referred to the monographic NP clinic frequently from July to October. Patient data systematically Sample size and demographics registered by one of the authors N = 1,972 Pain severity The most common causes of NP were found With NP n = 113 Not reported to be trigeminal neuralgia, post-herpes neuralgia and diabetic polyneuropathy. Patient selection Analyses All patients consecutively entering the Descriptive clinic for a 1 year period, sent from GP or emergency center of hospital. Included if had pain with dysesthesia, paresthesia, sharp pain, burning pain and hyperalgesia thermic. Topographic distribution synonymous with NP. Spontaneous and constant pain.

65 Study details Population Outcomes and analysis Results

Gil Gregorio et al. (2007) Type of chronic pain Outcomes measured Pain was the main reason for General chronic pain (includes cancer 2.1%) Demographic and clinical data, consultation in 86.1% of the cases. Study Design diagnosis of pain pathology, treatment 74.7% of patients had already made Cross-sectional survey Diagnostic criteria used and its effectiveness/satisfaction consultations for the same reason Diagnosis of pathology of pain made and use of healthcare resources before. In 67.7% of the patients Study Method by GP. Criteria not reported. pain was classified as chronic. Data recorded by GPs Pain severity Sample size and demographics Mean VAS 7.1 SD1.3 N = 1120 Mean age >70 years Analyses Descriptive. Comparison between Patient selection and within groups. Age over 65 years, present with pain as main reason for visit to GP

Mas et al. (2008) Type of chronic pain Outcomes measured Prevalence of FM estimated at FM Prevalence of FM 2.37% (95%CI: 1.53-3.21) Study Design Demographics of sufferers Cross-sectional survey Confirmation of diagnosis Quality of life 79% of FM patients had visited at least one ACR classification criteria Prevalence of comorbidities in FM subjects physician for musculoskeletal symptoms Study Method in the last year, compared to 32.1% of Interviews Sample size and demographics Pain severity non-FM individuals, and FM patients Total N = 2192 had a median of 2 visits per year. FM n = 52 Analyses 50 women, 2 men Chi-squared, Fisher’s exact test, adjusted ANOVA, logistic regression. Patient selection Over 20 years

66 RESULTS / EPIDEMIOLOGY OF CHRONIC Q5 Study Quality NON-MALIGNANT PAIN IN SPAIN Mas et al. (2008) fulfilled all the criteria and was rated as high quality. Gil Gregorio et al. (2007) did not have an adequate description of the study participants and the study setting and design were not clear, it was rated as low. Carneado-Ruiz (2005) was rated as low. Although it was representative of the Spanish population and had adequate descriptions of the study population, eligibility criteria and study design, it did not have an adequate description of the study participants and the statistical methods and outcomes were unclear.

Q5 Results Mas et al. (2008) The prevalence of FM in the general Spanish population is estimated at 2.37% (95%CI: 1.53-3.21), 79% of FM patients had visited at least one physician for musculoskeletal symptoms in the last year, compared to 32.1% of non-FM individuals. FM patients had a median of 2 visits per year.

Figure 12: Proportion of FM patients who had seen a physician for musculoskeletal symptoms in the last year

20,90% Patients not presenting for treatment

79,10% Patients presenting for treatment

67 RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 13: Proportion of non-FM patients who had seen a physician NON-MALIGNANT PAIN IN SPAIN for musculoskeletal symptoms in the last year

67.90% Patients not presenting for treatment

32.10% Patients presenting for treatment

Gil Gregorio (2007) In elderly patients visiting their GP, pain was the main reason for consultation in 86.1% of the cases. 74.7% of patients had already made consultations for the same reason before. In 67.7% of the patients pain was classified as chronic.

Carneado-Ruiz (2005) In 81 days of consultation 1422 patients presented themselves. 113 were diagnosed with neuropathic pain, representing 8% of all the pain patients seen. From January to April people presented themselves more frequently, and least frequently from July to October. The most common causes of NP were found to be trigeminal neuralgia, post-herpes neuralgia and diabetic polyneuropathy.

Q5 Summary Only Mas (2008) was high quality, the others were low quality, although all studies were rep- 68 resentative of the Spanish population. However, each study deals with a specific type of pain RESULTS / EPIDEMIOLOGY OF CHRONIC and only Mas (2008) directly answers the question: 79% of patients with FM had visited a NON-MALIGNANT PAIN IN SPAIN physician in the last year. In elderly patients, 86.1% of cases presented to GPs had pain, and neuropathic pain represents 8% of patients seen in a neurology clinic.

Q6 How many chronic pain patients get treated broken down by treatment?

We located 17 studies that addressed this question, 3 of which are presented here: Bassols et al. (2003) on back pain, Medina et al. (1999) on general pain patients and Nunez et al. (2007) on knee OA.

Bassols et al. (2003) conducted a survey to establish the prevalence of back pain in the general population in Catalonia. Among those suffering back pain, additional information was obtained concerning its characteristics, the relationship with socio-demographic variables, the therapeutic behaviours used by patients, and the personal, social and work impairment and disabilities.

Medina et al. (1999) conducted a descriptive study of the adequacy of the pharmacological consumption in relation to pain management, among patients referred their first time from General Practitioners to a Rheumatology Department.

Study details Population Outcomes and analysis Results

Bassols et al. (2003) Type of chronic pain Outcomes Measured Visit to the physician 71.9% Back pain Prevalence of back pain, characteristics, Use of alternative medical treatments 24.7% Study Design 82% chronic relationship to socio demographic variables, Physical therapy 22.7% (physical Descriptive cross- 41.2% osteoarticular (rheumatic, therapeutic behaviour and associated- exercises and electrotherapy) sectional arthrosis, arthritis) impairments and disabilities. Self-medication 14.6% (acetylsalicylic 19.1% professional (work accident, work disease) acid the most employed) Study Method Pain Severity Telephone interview Confirmation of diagnosis Intensity measured by verbal scale (mild, 13.9% of those with back pain Referred by patients moderate, intense, very intense, unbearable) received no treatment.

Sample Size and Demographics Analyses N = 1964 interviewed Descriptive - females 60.3%. Student t test and Mann-Whitney U for - mean age 47.5 years; range 20-91) means comparison 378 persons with chronic back pain (>1 year) X2

Patient Selection Random sample stratified by sex, age and place of residence, of general population, older than 18 years, enrolled in the Census in Catalonia. Excluded people in nursing homes, prisons or hospital in-patients.

70 Study details Population Outcomes and analysis Results

Medina (1999) Type of chronic pain Outcomes measured 15% of patients did not receive any Osteoarthritis pain, Rheumatoid arthritis pain Whether they received treatment or not, pharmacological treatment. Study Design type of drug used and via of administration Non-steroidal anti-inflammatory drugs Descriptive analysis Diagnostic criteria of drug, influence of age, cardiovascular (NSAID) were the most used (67.3%) even case series Definition of rheumatological disease by disease, gastrointestinal diseases and in non-inflammatory diseases (63.5%) Spanish Rheumatological Society. type of disease (inflammatory or not). and in patients with risk factors. Study Method Analysis of adequacy Sample size and demographics Pain severity In inflammatory diseases among treated: 85.7% of pharmacological N = 207 Not reported NSAID, 22.9% analgesics (usually combined therapy in patients with 63% female with NSAIDs), 5.7% gluco-corticoids. In non- osteoarticular pain Mean Age = 55 years. Analyses inflammatory diseases among treated: 63.5% Range: 14-84. Descriptive, X2 test, exact Fisher test NSAID, 24.7% analgesics, 17% glucocorticoids. 25.1% ≥ 65 years 33% had comorbidities that could make treatment risky – cardiovascular disease (CVD) and gastrointestinal disease (GI)

Patient selection Patients with osteoarticular pain, that were evaluated by a family physician and visiting a department of rheumatology for the first time

71 Study details Population Outcomes and analysis Results

Nunez et al. (2007) Type of chronic pain Outcomes measured 69% of patients visited a general practitioner, Knee OA grade IV Socio-demographic, disease characteristics, 40% a specialist, Study Design pharmacological treatment, use and 26% other health care professionals Cross-sectional survey Confirmation of diagnosis cost of economic resources related 5% alternative Kellgren and Lawrence criteria to knee OA in last 6 months. practitioners Study Method 13% of patients made no medical visits. Interviews and Sample size and demographics Pain severity medical records N = 104 Not reported 71% female Mean age = 71.2% (SD = 6.9) Analyses Mutliple linear regression, Spearman’s Patient selection correlation coefficient, Mann-Whitney outpatients diagnosed with knee OA grade test, Kruskall Wallis test IV (according to Kellgren and Lawrence criteria), on a waiting list for total knee transplant, for less than 6 months Excluded: functional illiteracy; inflammatory or other severe musculoskeletal conditions, metabolic or neoplastic disease and severe psychopathology or comorbidity

72 RESULTS / EPIDEMIOLOGY OF CHRONIC Q6 Study quality NON-MALIGNANT PAIN IN SPAIN Nunez et al. (2007) were rated as high quality, fulfilling all the study quality criteria.

Medina (1999) was rated as low quality. Although there was an adequate description of the statistical methods and study participants, the study design and setting and eligibility criteria were not adequately described. It was also unclear whether the study was representative of the target population.

Bassols (2003) was rated as medium quality, although it was representative of the Spanish population, the eligibility criteria, description of outcomes and statistical methods were unclear.

Q6 Results Bassols et al. (2003) Overall, patients with back pain, including chronic and those with acute pain, the therapeutic behaviours most commonly used were: visit to the physician (71.9%), the use of alternative medical treatments (24.7%), physical therapy (22.7%) and self-medication (14.6%). 13.9% of those with back pain received no treatment.

Visit to the physician: All patients were prescribed pharmacological treatment. 33.1% were also prescribed physical rehabilitation and 3.6% surgical treatment. Most prescribed drugs were diclofenac (32.2%), paracetamol (11.0%), piketoprofen (4.8%), acetyl salicylic acid (3.6%), metamizol (3.0%). 27.4% of the patients described small or no improvement in pain control.

Physical rehabilitation: Most used technique were physical exercises (47.2%), electrotherapy (25.0%), heat (10.8%), massage (10.8%), rest(3.4%). 73 RESULTS / EPIDEMIOLOGY OF CHRONIC Non-conventional treatments: Most used were local heat (24.7%), massage (23.2%), acupunc- NON-MALIGNANT PAIN IN SPAIN ture (1.8%); infusions (8.5%), healer (5.6%), homeopathy (4.9%), natural treatments (4.2%), home remedies (4.2%), arm-rests (3.5%), posture (3.5%), relaxation (2.8%).

Self-medication: Most used drugs were acetyl salicylic acid (49.2%), paracetamol (22.2%), diclofenac (9.5%), piketoprofen (7.9%), metamizol (6.3%).

Nunez et al. (2007) For patients with knee OA on a waiting list for a total knee transplant, in the 6 months previous to the study, 69% of patients visited a general practitioner, 40% a specialist, 26% other health care professionals, 5% alternative practitioners and 13% of patients made no medical visits.

Medina et al. (1999) 15% of patients with OA and RA did not receive any pharmacological treatment. Non- steroidal anti-inflammatory drugs (NSAID) were the most used (67.3%) even in non-inflammatory diseases (63.5%) and in patients with risk factors. In inflammatory diseases among treated: 85.7% NSAID, 22.9% analgesics (usually combined with NSAIDs), 5.7% gluco-corticoids. In non-inflammatory diseases among treated: 63.5% NSAID, 24.7% analgesics, 17% glucocorticoids.

74 RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 14: Percentage of pain patients broken down by treatment NON-MALIGNANT PAIN IN SPAIN

Nunez (2007) Bassol (2003) Medina (1999) 120,00%

100,00%

80,00%

60,00%

40,00%

20,00%

0,00% Received no Self-medication Physical Alternative Pharmalogi- Visited treatment/ made therapy treatment cal physician no medical visits treatment

Q6 Summary Around 70% of those with chronic pain (OA, RA and back pain) had visited a physician due to their pain. 85% to 100% of these patients were prescribed pharmacological treatment. 22.7% of patients received physical therapy and 14.6% self-medicated. 13% received no treatment for their pain. Medina (1999) reported on general pain patients, however, only reported on pharmacological treatments. The results from Bassols (2003) and Nunez (2007) refer to specific types of pain patients and only represent a subsection of pain patients in 75 Spain. RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Q7&20: What is the compliance of treated chronic pain patients and what are the determinants of compliance / adherence to drug treatments?

Three studies were selected that had information relevant to Questions 7 and 20. These questions have been combined as both aim to establish information related to adherence/ compliance to treatment in chronic pain patients. Furthermore, information directly perti- nent to Question 7 for Spain was only found for chronic pain patients receiving drug therapy as opposed to other treatments identified in Question 6.

The first study formed part (phase 2) of the VICOXX Study investigating patient and physician attitudes to osteoarthritis treatment with rofecoxib compared to traditional NSAIDS (tNSAID) (Arboleya et al. (2003b)). All patients were taking traditional NSAID treatment; half way through the 6-month prospective study patients were eligible to switch to rofecoxib. Outcomes reported included patient and physician satisfaction with treatment and assessment of general health, adherence to therapy, efficacy of treatment, use of medication and reasons for treatment discontinuation. Please note that some details presented in Table X below and used for assessing study quality were determined by referring to the associated publication reporting on phase 1 of the VICOXX study (Arboleya et al. (2003a)).

The second study was a prospective observational study of participants with non-cancer chronic pain commencing once-daily sustained-release tramadol treatment (Zytram™) with follow up after 1 week and then again at 1 month (Casals & Samper (2004)). Type and intensity of pain, quality of life and sleep, and effectiveness and tolerability of treatment over the study period were reported on. The publication reported on results of the ITACA study – Impacto del Tratamiento Analgesico sobre la Calidad de vida en 76 las Algias. RESULTS / EPIDEMIOLOGY OF CHRONIC The final study was also a prospective observational study of patients administered transder- NON-MALIGNANT PAIN IN SPAIN mal fentanyl patches for management of their chronic pain (Rodriguez et al. (2001)). Out- comes reported on included pain severity, the required dose of fentanyl, side effects and concomitant drug use, dropouts, tolerance and patient satisfaction. Details of the included studies are provided in Table 10.

Table 10. Characteristics of two studies relevant to Questions 7 and 20: adherence to treatment

Study details Population Outcomes and analysis

Arboleya et al. (2003b) Type of chronic pain Outcomes measured Osteoarthritis pain Adherence to therapy, efficacy of treatment, use Study Design of analgesics and gastro protective medication, Prospective cohort. VICOXX study Diagnostic criteria reasons for treatment discontinuation. Radiologically confirmed diagnosis of osteoarthritis at any Study Method time or clinical history documented at participating centres. Pain Severity Osteoarthritis patients from 29 primary care centres. WOMAC scale. WOMAC. 20 pt scale. Before 6-month prospective analysis of 562 participants of phase Sample size and demographics rofecoxib = 7.5, after rofecoxib = 6.25 (p = 0.001) 1 of the study. Participants continued with traditional N = 562. 76% female. Mean age 67 ± 9 years. NSAID treatment, after 3 months switched to rofecoxib if Analyses tNSAID inefficacious, adverse effects, or patient decision. Patient selection Descriptive. Comparison pre- and post rofecoxib treatment. Details not reported. Phase 2 participants selected from those who participated in phase 1 (Arboleya et al. 2003a).

77 Study details Population Outcomes and analysis

Casals & Samper (2004) Type of chronic pain Outcomes measured Non-cancer chronic pain. Included patients Analgesic effect of tramadol (pain intensity). Study Design with osteoarthritis, arthrosis, back pain, Patient satisfaction with treatment, side Prospective cohort. osteoporosis, visceral and ischaemic pain. effects/tolerability of treatment.

Study Method Diagnostic criteria Pain severity Baseline visit pre-test details recorded and Not reported. VAS scale (0 = none, 10 = most pain imaginable). tramadol dose determined and commenced. Moderate considered > 5cm. Follow up at 1 week and 1 month. Sample size and demographics Lattinen Test. 5 dimensions: pain intensity, frequency, N = 907 (66% women, 34% men). Mean analgesic use, activity, night rest on 20 pt scale. Women age 57.43 ± 11.34 (SD?) years. significantly greater than men VAS 7.41(1.31) vs 7.09(1.22) and Lattinen Test 12.21(2.64) vs 11.62(2.63) (p<0.05). Patient selection From 100 Pain Units across Spain Analyses with moderate severe pain. Descriptive Logistic regression to predict tolerability

Rodríguez et al. (2001) Type of chronic pain Outcomes measured Non-cancer chronic pain. Included patients with nociceptive Pain severity, side effects, dropouts, Study Design pain, neuropathic pain and a combination of both. tolerance and patient satisfaction. Prospective cohort. Diagnostic criteria Pain severity Study Method Not reported. VAS scale (0 = none, 10 = most pain imaginable). At start of Patients already on opiate therapy (tramadol) given treatment 8.1cm; 7 days, 4.7cm; 30 days, 2.4cm; 90 days, 72 hr release patch of 25ug/hr fentanyl. Maintained Sample size and demographics 2.5cm; 180 days, 1.9cm; 270 days, 1.8cm; 1 year, 1.6cm. tramadol for first week. Outcomes (pain intensity) N = 50 (40 women, 10 men). Mean age 62.5 years. measured prior to patch, 1 week, 1, 3, 6, 9, 12 months. Analyses Patient selection Descriptive. Not reported.

78 RESULTS / EPIDEMIOLOGY OF CHRONIC Q7 & Q20 Study quality NON-MALIGNANT PAIN IN SPAIN Arboleya et al. (2003b) The VICOXX Study was generally well reported. Most details that were adequately described related to the study setting, participants and eligibilty criteria were determined by reference to the associated publication (Arboleya et al. (2003a)). It remained unclear if the study population was representative of the target population. Reporting of results was not adjusted and deemed inadequate, as were losses to follow up of greater than 10%. Overall this study was rated as medium quality.

Casals & Samper (2004) Description of study design and setting was considered to be adequate as was the description of the statistical methods used and reporting of outcomes. Eligibility criteria were unclear with no description of confirmation of diagnosis. There was inadequate description of how the sample was recruited and the study participants involved. Over 30% Losses to follow up were reported, with no details as to why. Overall this study was considered to be low quality.

Rodriguez et al. (2001) This study was considered to be of low quality. Study setting was not described, nor were diagnostic criteria or criteria for selection. Although outcomes were defined and described not measures of precision were reported with the data. No statistical analysis was performed and figures presented appeared unrelated to the study reported on.

Q7 & Q20 Results Arboleya et al. (2003b) At the beginning of phase 2 of the VICOXX study, 562 of the 653 courses of treatment with traditional NSAIDS ceased before treatment with rofecoxib commenced. The most common 79 reason (47.7%) was due to expiration of the current prescription. The other major specified RESULTS / EPIDEMIOLOGY OF CHRONIC reasons for termination were lack of efficacy (21.1%) and GI adverse events (5.3%). The type NON-MALIGNANT PAIN IN SPAIN of drug used also appeared to be a determinant of adherence to therapy. Amongst the traditional NSAIDS, ibuprofen, meloxicam and naproxen were more likely to be associated with course terminations due to lack of efficacy, whereas diclofenac and piroxicam were more likely to be associated with discontinuation due to adverse events. Twenty-three of the 612 courses of rofecoxib therapy were discontinued due to lack of efficacy and a further 10 were stopped due to GI adverse events.

These authors also employed the Medication Adherence Scale (MAS; 0=perfect compliance, 70=total non-compliance) and reported a median score of 8 (interquartile range 1.5-16.5) during the period of rofecoxib compared to 12 (interquartile range 4-22) during the first 3 months with traditional NSAID therapy (p<0.001). Discontinuations due to lack of efficacy during rofecoxib treatment occurred at less than one-fifth of the rate reported with the tNSAID (3.8% vs 20.1% of courses, p<0.001).

Casals & Samper (2004) In subjects administered sustained release tramadol tablets some 119 or 21.1% of the sample had treatment modified after 1 month. In 61 of these subjects (51.3%) this was due to lack of analgesic efficacy and in 24 (20.2%) due to secondary or adverse effects. Tramadol was withdrawn in 29 cases (24.4%). Overall the authors report that 12.14% of patients displayed an irregular or poor adherence to therapy after the first week of treatment.

Rodriguez et al. (2001) Over the course of the 1-year study, of the 50 patients administered the transdermal fentanyl patch, 2 abandoned the treatment after 90 days and another 2 abandoned the treatment after 180 days. Side effects of the medication were the reasons for ceasing therapy for fenta- 80 nyl. The side effects that led to cessation were constipation and sedation. RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 15: Determinants of compliance/adherence to therapy NON-MALIGNANT PAIN IN SPAIN

60,00% adverse/side effec

lack efficacy 50,00% expired prescription

40,00%

30,00%

20,00%

10,00%

0,00% Rodriguez Casals & Samper Arboleya et al. et al. (2001) (2004) (2003b)

Q7 & Q20 Summary All of the prospective studies located for these questions related to compliance and adherence to treatment would suggest that lack of any analgesic effect primarily, and adverse events or side effects are major reasons for cessation or modification of NSAID and opiate therapy for chronic pain patients. The study by Arboleya et al. (2003b) also reported expiration of prescription as a reason for discontinuing therapy with traditional NSAIDs. These results also indicate that from 4-48% of subjects/patients are not compli- 81 ant with therapy. RESULTS / EPIDEMIOLOGY OF CHRONIC Due to the lack of high quality studies and the relatively small sample sizes of the available NON-MALIGNANT PAIN IN SPAIN studies it is unlikely these results can be viewed as indicative of the Spanish population. No data was located with respect to compliance and adherence to non-drug therapy for chronic pain.

Q8 What are the severity and duration of chronic pain conditions?

We selected 7 studies that address this question, 3 for general chronic pain (Breivik et al. (2006), Torre et al. (2008) and Rodriguez et al. (2006)), one for fibromyalgia (Boyer et al. (2009)), three for arthritis/arthrosis (Espallargues et al. (1996), and Batlle-Gualda et al. (2006) and Pastor et al. (1998)).

The first study was a large-scale computer-assisted telephone survey that explored the prevalence, severity, treatment and impact of chronic pain in 15 European countries and Israel (Breivik et al. (2006)). Screening interviews identified respondents’ aged ≥18 years with chronic pain for further, in-depth interviews. The data is reported here is specifically for Spain.

The aim of Torre (2008) was to measure health related quality of life, treatment of pain, pain intensity and levels of depression in patients with back pain, FM and neuropathic pain visiting a pain unit for the first time with a follow-up of 6 months.

Rodriguez et al. (2006) aimed to survey the degree of compliance with the WHO Analgesic Ladder recommendations for the treatment of chronic non-cancer pain in patients attending Spanish Pain Units. The study was performed by the Spanish Pain Society (STEP study). 82 RESULTS / EPIDEMIOLOGY OF CHRONIC The aim of Boyer et al. (2009) was to compare clinical symptoms, perceived health status, NON-MALIGNANT PAIN IN SPAIN health resource use and psychosocial features in Fibromyalgia (FM) patients at different health care levels. Patients were recruited from primary care (PC) and rheumatology settings (RS).

Espallargues et al. (1996) aimed to estimate the prevalence and related disability associated to the ostheoarthritis and rheumatic disorders in people aged 65 or more, using data from the 1986 Barcelona Health Interview Survey.

Batlle-Gualda et al. (2006) conducted a cross-sectional study, the ArtRoCad, on health resources utilization and socioeconomic impact of knee and hip osteoarthritis. The article presents the main characteristics of the population included.

Pastor et al. (1998) conducted a cross-sectional study that undertakes a 3 years period (July 1992-March 1995) to assess the prevalence of depression and level in 221 patients diagnosed of rheumatoid arthritis that attended specialist assistance by a Rheumatology Service.

83 Table 11. Study characteristics and results for Q8: severity and duration of chronic pain conditions

Study details Population Outcomes and analysis Results

Breivik (2006) Type of chronic pain Outcomes measured Severity General chronic pain Pain severity 44% of 301 pain patients reported severe pain Study Design Pain duration (8-10 on NRS) Cross-sectional Confirmation of diagnosis survey Not reported Pain severity Duration 10-point Numeric Rating Scale (NRS) Mean duration of pain = 9.1 years Study Method Sample size and demographics Large scale Total n = 3801 Analyses computer-assisted Chronic pain n = 301 telephone survey Mean age chronic pain 50.7 years, 52% female

Patient selection Any pain lasting at least 6 months, had experienced pain in the last month, and experienced pain at least two times per week

Torre et al. (2008) Type of chronic pain Outcomes measured Severity General non-cancer pain quality of life (SF-36), coping Mean VAS 5.13 (SD1.91) Study Design strategies (CAD-R), anxiety/depression Cross-sectional Diagnostic criteria (HAD) and intensity of pain Duration survey Mean 95 months (SD 127.21) Sample size and demographics Pain severity Study Method N = 119, 93 completed study (22% lost to follow-up) VAS Structured interview 74 women, 44 men Median age 55.12 (SD 13.28) range 26-82 Analyses 40% > 60 years Descriptive

Subject selection Had to have at least 6 months pain, seen for first time at pain unit. 18 years and over. Excluded if cognitive impairment, walking difficulties to arrive at the hospital or didn’t sign consent form.

84 Study details Population Outcomes and analysis Results

Rodriguez et Type of chronic pain Outcomes measured Severity al. (2006) General non-cancer pain treatment according to WHO ladder Mean VAS 5.82 (5.62-6.02), in demographic characteristics women 5.93 and in men 5.55. Study Design Diagnostic criteria pain history For those with sleeping disorders 5.93 Cross-sectional Not reported visual analogue scale Without sleeping disorder 5.44 (p<0.05) survey previous treatments Sample size and demographics change of treatment Duration Study Method N = 580 quality of life Median time of pain 80 months, range 72-88. Questionnaire Mean age 51 to 60 years adverse events 70% women economic impact of pain Pain self-assessed by the patients using a Visual Analogue Scale, average Subject selection Pain severity score. Average length of pain: 80 adult patients (> 18 years-old) with chronic non-cancer VAS months; range: 72-88 months. pain (> 6 months) attending Spanish Pain Units Analyses descriptive analysis (mean/median + SD and chi-square), t-student and ANOVA

Boyer et al. (2009) Type of chronic pain Outcomes measured Severity FM Clinical characteristics of FM Not significantly different in Study Design Health status PC and RS patients. Cross-sectional Confirmation of diagnosis Health resource use survey according to published ACR criteria Psychological factors Mean pain intensity PC = 5.71 (SD 1.86) Study Method Sample size and demographics Pain severity RS = 6.02 (SD 1.77) Interview Total n = 315 Patients rated the maximum, minimum, PC n = 101 and usual pain intensity during the week Duration RS n = 214 prior to the interview, and at the interview. PC = 9.8 years (SD 10.22) 10-point scale (0 = “no pain at all” and 10 RS = 12.9 years (SD 11.10) All participants female = “the worst pain you can imagine”). Range 9 and 13 years. The mean score of these four items was Mean age PC = 49.8 years (SD 10.39) used as a pain intensity measure. RS = 52.7 years (SD 9.01) Analyses Patient selection Chi-squared tests, independent t-tests At least 18 years old and had no psychiatric diagnosis

85 Study details Population Outcomes and analysis Results

Espallargues Type of chronic pain Outcomes measured Duration et al. (1996) OA and RA pain intensity 14.3years (SD12.7) pain treatment / doctor visits Study Design Diagnostic criteria other chronic diseases Severity Cross-sectional Self-reported self-evaluation of health 82% had pain frequently, 23% of these survey functional ability had moderate or intense pain. Sample size and demographics chronic limitation Study Method N = 1287 hospitalization Interview 76% female Pain severity Subject selection Asked intensity of their pain a stratified sample of all residents of Barcelona aged 65 or more Analyses Descriptive: frequencies

Batlle-Gualda Type of chronic pain Outcomes Measured Severity et al. (2006) Knee or hip osteoarthritis and a history of Clinical data, quality of life and resource 80% moderate or severe OA pain for 3 months in the previous year consumption, sick leave from work or days Study Design of disability in the previous 6 months Duration Cross-sectional Confirmation of diagnosis Outcomes not reported in the article Max time for pain in joints: study By a doctor, criteria of the American Knee 9.2 years (Sd7.4), median 8(0-40 years) College of Rheumatology Pain Severity Hip 7.7 years (SD 7.1), median 6 years (0-4.7) Study Method Measured by the Grade Chronic Pain Status, Both 11.11 (SD 8.8), median 10 years (0-55). 2 structured Sample Size and Demographics but not reported un the publication interviews N = 1071 and questionnaires Females 74%, males 26%. Analyses filled by the patient Mean age: 71 (SD 9). Range: 50-99. Descriptive analysis of the sample

Patient Selection Ambulatory patients in primary care attended by 113 General Practitioners, aged ≥50 years old, from all over Spain.

86 Study details Population Outcomes and analysis Results

Pastor et al. (1998) Type of chronic pain Outcomes Measured Pain severity Rheumatoid arthritis Depression level, assessed with the Self- Self-assessed by the patients Study Design Rating Depression Scale of Zung-Conde none/mild 30.8%, moderate 28.6%, Cross-sectional Confirmation of diagnosis (no depression, intermediate, depression) intense 29.4%, unbearable 11.8% study Medical specialist using 1988 criteria of the American College of Rheumatology Pain Severity Study Method Self-assessed by the patient using Personal interview Sample Size and Demographics a Likert type scale (none/mild, with the patient done N = 221. moderate, intense, unbearable) by doctor specialist Mean age = 55.4 (SD 12.4), range 17-82 years. in rheumatology Females 84.2%, males 15.8% Analyses X2 test and multivariate analysis type Patient Selection Automatic Interaction Detection, Patients attended in a specialist Rheumatology Service. based on the statistic r2.

87 RESULTS / EPIDEMIOLOGY OF CHRONIC Q8 Study Quality NON-MALIGNANT PAIN IN SPAIN Breivik et al. (2006) was rated as medium quality. Most criteria were met, however, the description of study participants was not clear enough. There was also no description of the statistical methods used.

Boyer et al. (2009) and Pastor (1998) were also medium quality, they fulfil all criteria but are not representative of the target population.

Rodriguez et al. (2006) was rated as medium quality as it was unclear whether it was representative of the target population, and the descriptions of the eligibility criteria and outcomes were also unclear.

Espallargues et al. (1996) was rated as medium quality, as the description of the outcomes was unclear and it was not clear if the results were unadjusted or confounder adjusted.

Torre (2008) was rated as medium, it was unclear if it was representative of the target population and whether the results were confounder adjusted.

Battle-Guarda (2006) was rated as high quality as it fulfilled all the criteria.

Q8 Results General non-cancer pain: Breivik (2006) Forty four percent of the 301 Spanish pain patients reported severe pain having severe pain (a score of 8-10 on the NRS) and the mean duration of pain for patients with general chronic pain was 9.1 years.

88 Rodriguez (2006) Patients with general non-cancer pain attending pain clinics was RESULTS / EPIDEMIOLOGY OF CHRONIC self- assessed using a Visual Analogue Scale, the mean score was 5.82 (5.62-6.02), in women 5.93 NON-MALIGNANT PAIN IN SPAIN and in men 5.55. Pain severity was higher in those with sleeping disorders (5.93) than those without (5.44, p<0.05). The median time of pain was 80 months, with a range 72-88 months.

Torre (2008) also reported the severity and duration of pain in patients with general non- cancer chronic pain. They found that the mean severity measured on the VAS was 5.13 (SD 1.91), and the mean duration was 95 months (SD 127.21).

FM: Boyer (2009) The pain severity in FM patients was measured on a 10 point scale, with 0 representing “no pain at all” and 10 “the worst pain you can imagine”. No statistical difference was found between primary care and rheumatology patients. The mean pain intensity for primary care patients was 5.71 (SD 1.86) and for rheumatology patients was 6.02 (SD 1.77). The mean duration was also not significantly different and ranged between 9 and 13 years. The mean duration for primary care patients was 9.8 years (SD 10.22) and for rheumatology patients 12.9 years (SD 11.10).

Arthritis/arthrosis: Pastor (1998) In patients with RA, pain severity self-assessed by the patients was: none/mild 30.8%, moderate 28.6%, intense 29.4%, unbearable 11.8%.

Espallargues (1996) The mean duration of pain was 14.3years (SD12.7), 82% had pain frequently and 23% of these had moderate or intense pain.

Battle-Gualda (2006) The mean maximum time for pain in joints was 9.2 years (SD 7.4) for the knee, with a median of 8years (0-40 years); the hip mean time was 7.7 years (SD 7.1), median 6 years (0-4.7); for both was 11.11 years(SD 8.8), median 10 years (0-55). 80% had mod- 89 erate or severe OA. RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 16: Duration in years of chronic pain from the included studies NON-MALIGNANT PAIN IN SPAIN

16 DURATION YEARS 14.3% 14

12 11.3%

10 9.1% 8.3% 8 7.9% 6.7%

0 Battle-Gualda Espallargues Boyer Torre Rodriguez Breivik (2006) (1996) (2009) (2008) (2006) (2006)

Q8 Summary The mean duration of general non-cancer pain ranged from 6.6 years to 9.1 years, 44% of respondents reported severe pain, with a mean VAS score ranging from 5.13 to 5.82. For FM, the mean duration of pain ranged from 9 to 13 years, and the severity was 5.71 to 6.02 on the VAS score. For OA and RA, the mean duration ranged between 6 years and 14.3 years, 23-80% had moderate or intense pain. Study quality was medium or high, and three of the 90 studies were representative of the Spanish population and had large sample sizes. RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Q9 What are the demographics of pain sufferers?

The EPISER study (Fernandez-Lopez et al. (2008)) was a population survey was conducted in year 2000 for which participants were selected by stratified poly-stage cluster sampling from the censuses of 20 towns in Spain. The aim was to estimate the point prevalence of knee pain suggesting OA in the adult Spanish population and to examine the distribution of associated factors.

Casals et al. (2004) reports on data gathered in the ITACA study (Impacto del Tratamiento Analgesico sobre la calidad de vida en las Algias). Its aim is to assess the effectiveness and tolerability of the management of chronic pain unrelated to cancer with controlled and sustained release tramadol administered in a single daily dose.

Bassols et al. (2003) conducted a survey to establish the prevalence of back pain in the general population in Catalonia. Among those suffering back pain, additional information was obtained concerning its characteristics, the relationship with socio-demographic variables, the therapeutic behaviours used by patients, and the personal, social and work impairment and disabilities.

Breivik et al. (2006) was a large-scale computer-assisted telephone survey that explored the prevalence, severity, treatment and impact of chronic pain in 15 European countries and Israel. Screening interviews identified respondents’ aged ≥18 years with chronic pain for further, in-depth interviews. The data is reported here is specifically for Spain.

91 Table 12: Study characteristics and results of studies relevant to Question 9: what are the demographics of pain sufferers?

Study details Population Outcomes and analysis Results

Casals et al. (2004) Type of chronic pain Outcomes measured 66% women, 34% men General non-cancer pain pain intensity (VAS, Lattinen Test, QoSleep), Average age 57.43 ± 11.34 years Study Design use of analgesics, analgesic effect of tramadol, 48% aged 55-70 years. Longitudinal/ Diagnostic criteria QoL (physical and mental dimensions), 93% lived with their family cohort study Not reported patient satisfaction with treatment, side 74.5% lived in an urban setting effects/tolerability of treatment, 42% overweight, 29% obese. Study Method Sample size and demographics prospective, N = 907 Pain severity observational, Mean age 51 to 60 years VAS scale (0 = none, 10 = most pain multicentric 66.03% female imaginable). Moderate>5 pharmaco- Lattinen Test. 5 dimensions: pain epidemiological study Patient selection intensity, frequency, analgesic use, 18-80 years, started taking tramadol tablet 150-200mg for activity, night rest on 20 point scale. moderate-severe non cancer chronic pain for new indications, poor tolerability of lack of effectiveness of previous treatment. Analyses Descriptive. Logistic regression to predict tolerability

Breivik (2006) Type of chronic pain Outcomes measured Mean age of pain General chronic pain Pain severity suffers 50.7 years Study Design Pain duration 52% female Cross-sectional Confirmation of diagnosis survey Not reported Pain severity 10-point Numeric Rating Scale (NRS) Study Method Sample size and demographics Large scale Total n = 3801 Analyses computer-assisted Chronic pain n = 301 Descriptive telephone survey Mean age chronic pain 50.7 years, 52% female

Patient selection Any pain lasting at least 6 months, had experienced pain in the last month, and experienced pain at least two times per week

92 Study details Population Outcomes and analysis Results

Bassols et al. (2003) Type of chronic pain Outcomes Measured Back pain was highly Back pain Prevalence of back pain, characteristics, prevalent (50.9%), Study Design 82% chronic relationship to socio demographic variables, appeared in all ages (mean Descriptive cross- 41.2 % osteoarticular (reumathic, arthosis, arthritis) therapeutic behaviour and associated- age of 47.6 years) sectional 19.1% professional (work accident, work disease) impairments and disabilities. highest in women (60.7%), manual workers (54.9%) and in Study Method Confirmation of diagnosis Pain Severity those less educated (71.1%). Telephone interview Referred by patients Intensity measured by verbal scale (mild, moderate, intense, very intense, unbearable) Sample Size and Demographics N = 1964 interviewed Analyses - females 60.3%. Descriptive - mean age 47.5 years; range 20-91) Student t test and Mann-Whitney U for 378 persons with chronic back pain (>1 year) means comparison X2 Patient Selection Random sample stratified by sex, age and place of residence, of general population, older than 18 years, enrolled in the Census in Catalonia. Excluded people in nursing homes, prisons or hospital in-patients.

Fernandez-Lopez Type of chronic pain Outcomes measured Determinants of knee pain et al. (2008) Knee OA Prevalence estimates of knee OA suggesting OA, Odds ratio knee OA determinants before adjustment (95%CI): Study Design Diagnostic criteria Disability – percentage receiving Cross-sectional ACR criteria disability compensations, Health Women 2.64 (1.93-3.60) survey assessment questionnaire (HAQ) Age over 50 years 18.95 Sample size and demographics Quality of life – SF12 questionnaire (11.74-30.59) Study Method N = 2192 With less than 8 years of formal Interviews and Pain severity education 6.88 (4.25-10.45) standardised Subject selection Not reported Low social class 2.72 (1.92-3.83) physical examination Aged 20 years and over Obese 3.46 (2.59-4.62) by trained Analyses Physically demanding rheumatologists Chi-squared test, odds ratio from job 2.92 (1.94-4.40) multivariate logistic regression models.

93 RESULTS / EPIDEMIOLOGY OF CHRONIC Q9 Study Quality NON-MALIGNANT PAIN IN SPAIN Fernandez-Lopez et al. (2008) was rated as high quality, it fulfilled all criteria and was representative of the Spanish population. Breivik et al. (2006) was rated as medium quality. Most criteria were met, however, the description of study participants was not clear enough. There was also no description of the statistical methods used. Bassols (2003) was rated as medium quality, although it was representative of the Spanish population, the eligibility criteria, description of outcomes and statistical methods were unclear. Casals (2004) was rated as medium, it was not representative of the target population and it did not give an adequate description of the outcome measured.

Q9 Results Casals (2004) The demographic of patients with non-cancer chronic pain are as follows: 66% were women, 34% men; the average age was 57.4 (± 11.34 years), with 48% aged 55-70 years; 93% lived with their family and 74.5% lived in an urban setting; 42% were overweight and 29% obese.

Breivik et al. (2006) was a representative sample from the Spanish population. It found that the mean age of pain suffers was 50.7 years and 52% were female.

Bassols (2003) Back pain was highly prevalent (50.9%), appeared in all ages (mean age of 47.6 years) and was the highest in women (60.7%), in manual workers (54.9%) and in those less educated (71.1%).

Fernandez-Lopez et al. (2008) Knee pain suggesting OA appears more frequently in women, the elderly, in people with less than 8 years of formal education, from a low social class, in obese and in those with a physically demanding job. After adjustment by confounders, the determinants of knee OA were female sex (OR 2.14, 95%CI 1.41-3.26), age over 50 years (OR 10.71 95%CI 94 5.94-19.30), urban residence (OR 1.74 95%CI 1.09-2.77) and obesity (OR 2.18 95%CI 1.47-3.24). RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 17: Demographics of patients with chronic pain in included studies NON-MALIGNANT PAIN IN SPAIN

80,00% Casals (2004) 71% Breivik (2006) 70,00% 66% Bassols (2003) 61% 60,00% 55% 52% 50,00% 42% 40,00%

30,00% 29%

20,00%

10,00%

0,00% Female Overweight OBESE Manual LESS EDUCATED workers

95 RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 18: Average age of chronic pain patients NON-MALIGNANT PAIN IN SPAIN

60 57% 51% 50 48%

Casals (2004) Breivik (2006) Bassols (2003)

Q9 Summary The overall quality of these studies were medium to high, and three were representative of the Spanish population and are summarised as follows: for general non-cancer pain the mean age was 50.7 years and 52% were female, back pain showed a similar mean age of 47.6 years, but back pain and OA was higher in women, manual workers and the less educated, and OA more prevalent in those from a low social class and obese. The results can be consid- 96 ered as representative of the Spanish pain population. RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Q10 What are the underlying diseases of pain sufferers?

We selected 4 studies that address this question: one study report on general non-cancer pain, 2 report specifically on FM, and one on hip and knee OA.

Loza et al. (2008) and Mas et al. (2008) both report on the EPISER study. Loza et al. (2008) focuses on the co-existence of rheumatic diseases with other chronic diseases and Mas et al. (2008) on comorbidities with fibromyalgia (FM). EPISER is a cross-sectional study of 2192 Spaniards aged 20 or above, selected by cluster sampling.

The aim of Sicras-Mainar et al. (2009) was to determine the use of services and costs in patients with fibromyalgia (FM) or generalised anxiety disorder (GAD) followed up in primary care.

97 Table 13: Study characteristics of included studies for Q10: underlying diseases of pain sufferers

Study details Population Outcomes and analysis Results

EPISER study Type of chronic pain Outcomes measured Rheumatic disease comorbidities Loza (2008) and Rheumatic diseases (Loza (2008)) Loza (2008): Observed prevalence: Mas (2008) FM (Mas (2008)) Prevalence of rheumatic disease. Arterial hypertension 7.21% Prevalence of co-existence of RD Hypercholesterolemia 5.74% Study Design Diagnostic criteria with other chronic diseases Digestive diseases 4.61% Cross-sectional survey ACR classification criteria Diabetes mellitus 2.55% Mas (2008): Cardiologic diseases 2.51% Study Method Sample size and demographics Prevalence of FM Pulmonary diseases 2.01% Interview N = 2192 Demographics of sufferers Allergies 1.96% 54% female Quality of life Prevalence of comorbidities in FM subjects FM comorbidities Patient selection Observed prevalence: Aged 20 years or over Pain severity Hypertension 36.5% Not reported Psychiatric disease 32.0% Hypercholesterolemia 21.2% Analyses Neurologic diseases 16.0% Loza (2008): Depression 11.5% Prevalence of co-occurrence was calculated Diabetes 9.6% as the product of the separate prevalences Pulmonary diseases 9.6%

Mas (2008): Chi-squared, Fisher’s exact test, adjusted. ANOVA, logistic regression.

98 Study details Population Outcomes and analysis Results

Sicras-Mainar Type of chronic pain Outcomes measured From a total of 63,349 patients, 904 (1.4%) et al. (2009) FM comorbidities, health care use, had a diagnosis of fibromyalgia and primary care cost. Study Design Diagnostic criteria Comorbidities: Cross-sectional survey ACR criteria for musculoskeletal disorders Pain severity 27.8% hypertension Not reported 8.5% diabetes Study Method Sample size and demographics 36.8% Hypercholesterolemia Retrospective analysis N = 904 Analyses 42% Obesity of patient records Mean age 41 to 50 years descriptive, Logistic regression, ANCOVA 17% Smoking 96.5% female 2% Ischemic cardiopathy 3.3% CVA Patient selection 1% COPD Adults 18+ who needed medical attention 42.4% Depression from 1 of 5 primary care centres in 2006 Conditions correlated with FM: Hypercholesterolemia OR 1.5 (CI1.3-1.08, p<0.001) Depression OR 3.9 (CI 3.4-4.6, p<0.001).

Batlle-Gualda Type of chronic pain Outcomes Measured The distribution of the main affected joint et al. (2006) Knee or hip osteoarthritis and a history of Clinical data, quality of life and resource was as follows: knee 710 (66.3%), hip 252 pain for 3 months in the previous year consumption, sick leave from work or days (23.5%) and both knee and hip 109 (10.2%). Study Design of disability in the previous 6 months Cross-sectional study Confirmation of diagnosis Outcomes not reported in the article 74% had another joint (other than By a doctor, criteria of the American hip or knee) that was painful. Study Method College of Rheumatology Pain Severity 2 structured interviews Measured by the Grade Chronic Pain Status, Comorbidities of total population: and questionnaires Sample Size and Demographics but not reported un the publication N = 1071 filled by the patient N = 1071 Hypertension 57% Females 74%, males 26%. Analyses Myocardial infarction 3% Mean age: 71 (SD 9). Range: 50-99. Descriptive analysis of the sample Cardiac failure 7% Vascular disease 15% Patient Selection Cerebral vascular disease 5.4% Ambulatory patients in primary care Diabetes 19% attended by 113 General Practitioners, aged Dementia 1.4% ≥50 years old, from all over Spain. COPD 8%

99 RESULTS / EPIDEMIOLOGY OF CHRONIC Q10 Study Quality NON-MALIGNANT PAIN IN SPAIN The EPISER study (Loza et al. (2008) and Mas et al. (2008)) and Battle-Gualda (2006) were rated as high quality, meeting all the criteria. Sicras-Mainar et al. (2009) was rated as medium quality as the description of the study design and setting and the outcomes were not clearly described.

Q10 Results EPISER Study The most common comorbidities with rheumatic diseases are arterial hypertension, with a prevalence of 7.21%, hypercholesterolemia 5.74%, digestive diseases 4.61%, diabetes mellitus 2.55%, cardiologic diseases 2.51%, pulmonary diseases 2.01% and allergies 1.96% (Loza et al. (2008)). For patients suffering specifically from FM, the most prevalent comorbidity was hypertension in 36.5%, followed by psychiatric disease 32.0%, hypercholesterolemia 21.2%, neurologic diseases 16.0%, depression 11.5%, diabetes 9.6% and pulmonary diseases 9.6%.

100 RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 19: Comorbidities in the EPISER study NON-MALIGNANT PAIN IN SPAIN

40,00%

35,00%

30,00%

25,00%

20,00%

15,00%

10,00%

5,00%

0,00% RHEUMATIC DISEASES FIBROMYALGIA

Arterial Hypertension DIABETES MELLITUS ALLERGIES

HYPERCHOLESTEROLEMIA CARDIOLOGIC DISEASES PSYCHIATRIC DISEASES

DIGESTIVE DISEASES PULMONARY DISEASES NEUROLOGIC DISEASES

101 RESULTS / EPIDEMIOLOGY OF CHRONIC Sicras-Mainar (2009) This study also looked at patients with FM and found that 27.8% also NON-MALIGNANT PAIN IN SPAIN suffered from hypertension, 8.5% diabetes, 36.8% high levels of cholesterol, 2% ischemic cardiopathy, 3.3% CVA, 1% COPD and 42.4% depression.

Battle-Gualda (2006) The comorbidities of people suffering from knee and hip OA were as follows: hypertension 57%, myocardial infarction 3%, cardiac failure 7%, vascular disease 15%, cerebral vascular disease 5.4%, diabetes 19%, dementia 1.4% and COPD 8%.

Q10 Summary Hypertension was the most prevalent comorbidity for all types of pain reported here. For pain patients with rheumatic and osteoarthritic pain the other most common comorbidities were cardio-vascular diseases and diabetes, and in FM psychiatric disease, neurologic diseases and depression. All the studies were representative of the Spanish pain population and were generally of high quality, the data can therefore be considered as representing the Spanish pain population.

Q11 How many sufferers have inadequate pain control?

We selected 4 studies that addressed this question. Breivik et al. (2006), Rodriguez et al. (2006) and Soucase et al. (2005) report on general non-cancer pain, Soucase et al. (2004) on fibromyalgia (FM).

Breivik (2006) was a large-scale computer-assisted telephone survey that explored the prevalence, severity, treatment and impact of chronic pain in 15 European countries and Israel. Screening interviews identified respondents’ aged ≥18 years with chronic pain for further, 102 in-depth interviews. The data is reported here is specifically for Spain. RESULTS / EPIDEMIOLOGY OF CHRONIC Rodriguez (2006) aimed to survey the degree of compliance with the WHO Analgesic Ladder NON-MALIGNANT PAIN IN SPAIN recommendations for the treatment of chronic non-cancer pain in patients attending Span- ish Pain Units. The study was performed by the Spanish Pain Society (STEP study).

Soucase (2005) conducted a survey on 168 patients with chronic pain attending a Multidis- ciplinary Pain Unit to study the relations and interactions between cognitive assessment procedures and coping strategies in order to determine variables and coping strategies that predict a better adaptation to chronic pain.

Table 14. Study characteristics of included studies for Q11: how many sufferers have inadequate pain control?

Study details Population Outcomes and analysis Results

Breivik (2006) Type of chronic pain Outcomes measured “Are there ever times when your pain medicines General chronic pain Percentage of inadequate pain control from are not adequate to control your pain?” Study Design medication and of chronic pain sufferers who 58% of respondents (N = 181) answered yes. Cross-sectional survey Confirmation of diagnosis report that their pain is inadequately controlled. Not reported “Would you say your pain is being Study Method Pain severity adequately controlled?” Large scale computer- Sample size and demographics 10-point Numeric Rating Scale (NRS) 33% of respondents (N = 294) answered yes assisted telephone survey Total n = 3801 Chronic pain n = 301 Analyses Mean age chronic pain 50.7 years, 52% female Descriptive

Patient selection Any pain lasting at least 6 months, had experienced pain in the last month, and experienced pain at least two times per week

103 Study details Population Outcomes and analysis Results

Rodriguez (2006) Type of chronic pain Outcomes measured In 70% of the patients drug prescription was General non-cancer pain treatment according to WHO ladder changed due to inadequate pain control. Study Design demographic characteristics Cross-sectional survey Diagnostic criteria pain history Not reported visual analogue scale Study Method previous treatments Questionnaire Sample size and demographics change of treatment N = 580 quality of life Mean age 51 to 60 years adverse events 70% women economic impact of pain

Subject selection Pain severity adult patients (> 18 years-old) with VAS chronic non-cancer pain (> 6 months) attending Spanish Pain Units Analyses descriptive analysis (mean/median + SD and chi-square), t-student and ANOVA

Soucase (2005) Type of chronic pain Outcomes Measured Patients were asked questions and Somatic 54.4% Pain valuation, pain coping strategies answered on a 1-5 Likert scale (1 = Study Design Neuropathic 41.4% (pain coping questionnaire - PCQ), level of never, 5 = completely agree) Cross-sectional study anxiety (STAI/R) and depression (BDI). Confirmation of diagnosis Medication never decrease their Study Method Referred by patients Pain Severity pain: mean 1.8 (SD 0.97) Questionnaires Visual Analogue Scale answered by patients Sample Size and Demographics Baseline level of pain 7.91 (SD 1.74) Medication never can change their N = 168 level of pain: mean = 1.57 (SD 0.93) Females: 71% Analyses Mean Age: 52.6 years; range: 20-77. Descriptive Rarely medication they take reduces X2 their pain: mean = 2.29 (SD 1.09) Patient Selection Student t-test People attended in a Pain clinic Stepwise multiple regression Medication Rarely can control pain: mean 2.07 (SD1.11)

104 RESULTS / EPIDEMIOLOGY OF CHRONIC Q11 Study Quality NON-MALIGNANT PAIN IN SPAIN Breivik (2006) was rated as medium quality. Most criteria were met, however, the description of study participants was not clear enough. There was also no description of the statistical methods used. Rodriguez (2006) was rated as medium quality as it was unclear whether it was representative of the target population, and the descriptions of the eligibility criteria and outcomes were also unclear.

Soucase (2005) was rated as medium quality. It did not include an adequate description of eligibility criteria (including description of diagnostic criteria for chronic pain condition). It is unclear whether the study population is representative of the target population. There was not an adequate description of the study participants. Results were not presented as unadjusted and confounder-adjusted including precision.

Q11 Results Breivik (2006) In a representative sample of the Spanish population with general non- cancer pain, 58% of respondents (N=181) had times when their pain medications were not adequate to control their pain, and only 33% of respondents (N=294) said that their pain was adequately controlled.

Rodriguez (2006) In 70% of patients with general non-cancer pain, their medication was changed due to inadequate pain control.

Soucase (2005) Patients were answered questions on a 5-point Likert scale (1=never, 5=completely agree): whether their medication never decreased their pain: mean 1.8 (SD 0.97), their medication never can change their level of pain: mean=1.57 (SD 0.93), rarely the medication they take reduces their pain: mean=2.29 (SD 1.09), and their medication rarely 105 can control pain: mean 2.07 (SD1.11). RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 20: Control of pain NON-MALIGNANT PAIN IN SPAIN

60 ADEQUATELY CONTROLLED PAIN

ARE THERE TIMES WHEN MEDICINES DO 50 NOT ADEQUATELY CONTROL PAIN?

CHANGE OF DRUG THERAPY DUE 40 TO INADEQUATE PAIN CONTROL?

Breivik (2006) RODRIGUEZ (2006)

Q11 Summary Rodriguez (2006) only indirectly addressed this question, reporting on the percentage of patients that had their medication changed due to inadequate pain control. However, their results reflect those found for Breivik (2006), which did directly answer the question and was also representative of the Spanish population. Soucase (2005) also indirectly answers the question, finding that pain patients agreed more that their pain medication rarely 106 reduced or controlled their pain than never reduced or controlled their pain. No results RESULTS / EPIDEMIOLOGY OF CHRONIC were given for positive statements about their pain medication. From there results, we can NON-MALIGNANT PAIN IN SPAIN conclude that pain medication does not always control patients’ pain.

Q12a What is the impact of chronic pain on quality of life?

We selected four studies that address this question. One reports on musculoskeletal pain (Carmona (2001)), two on knee OA (Fernandez-Lopez (2008) and Nunez (2007)), and one on spine osteoarthritis and low back pain (Lopez-Silva (2007)).

The EPISER study was a cross-sectional survey that used stratified multistage cluster sampling from the censuses of 20 municipalities in Spain. The survey involved interviews and standardised physical examination by trained rheumatologists and the objective was to estimate the prevalence of rheumatoid arthritis (RA), low back pain, hand and knee osteoarthritis (OA), and fibromyalgia (FM) in the adult Spanish population, and to assess the impact of these diseases on function and quality of life, and use of health and social resources (Carmona et al. (2001)). Fernandez-Lopez et al. (2008) reported specifically on the point prevalence of knee pain suggesting OA in the adult Spanish population and examined the distribution of associated factors.

Nunez et al. (2007) was carried out in the Rheumatology Service and the Knee Unit of the Orthopaedic Surgery Service of the Hospital Clinic Provincial (HCP), Barcelona (Spain), a public tertiary care centre. Included were consecutive outpatients of all ages diagnosed with knee OA and that were on a waiting list for total knee surgery. The aim of the study was to determine the health-related quality of life (HRQL) in patients with severe osteoarthritis (OA) 107 and the use and cost of resources related to knee OA. RESULTS / EPIDEMIOLOGY OF CHRONIC Lopez Silva (2007) conducted a descriptive study to compare quality of life in primary care NON-MALIGNANT PAIN IN SPAIN patients that presented pain related conditions with those with non-pain conditions. The patients were interviewed in 10 primary care centres in a rural area in northern Spain (Lugo – Galicia). The study collected demographic data (age, sex, anamnesis), and specific data for pain sufferers (chronic and acute pain, diagnosis, treatment received, and VAS score. All participants completed a validated Spanish version of SF36.

Table 15: Characteristics and results of the studies relevant to Question 12: the impact of chronic pain on quality of life

Study details Population Outcomes and analysis Results

EPISER study Type of chronic pain Outcomes measured Musculoskeletal diseases (Carmona (2001)) (Carmona et al. (2001) Musculoskeletal diseases (RA, low back Health related quality of life Effect on Functional capacity (HAQ scores): and Fernandez- pain, OA (knee and hand), FM) - Short Form 12 (SF-12) RA (1.75) Lopez et al. (2008)) Functional capacity - Health FM (1.30), Symptomatic knee OA (1.29) Confirmation of diagnosis Assessment Questionnaire (HAQ) Low back pain (1.27) Study Design Low back pain – self-report Rheumatic symptoms Cross-sectional survey OA and FM – ACR criteria Health related QoL (SF-12 scores): RA – ACR classification criteria and physical Pain severity Physical aspects Study Method examination, x ray and latex agglutination test Not reported RA (29.1) Symptomatic knee OA (31.7) Interviews and if suspected RA not confirmed by ACR criteria Low back pain (32.4) standardised physical Analyses Psychological component examination by trained Sample size and demographics Subjects weighted with respect FM (39.0) rheumatologist N = 2998 to the sampling scheme. ANOVA, parametric tests. Knee pain suggesting OA (Fernandez-Lopez (2008)) Patient selection 66.8% of respondents rated their health as poor or just fair. Subjects aged 20 years or above were randomly SF-12 physical score was 38.7 (significantly selected by stratified multistage cluster sampling different from those without knee pain, 51.5). from the censuses of 20 municipalities in Spain SF-12 mental score was also lower, 46.1 compared to 50.1.

108 Study details Population Outcomes and analysis Results

Nunez et al. (2007) Type of chronic pain Outcomes measured Factors associated with a worse HRQL: Knee OA grade IV HRQL - self-reported Spanish Female gender Study Design version of SF-36 and knee-specific Disease duration Cross-sectional survey Confirmation of diagnosis questionnaire WOMAC LK 3.0. Number of comorbidities Kellgren and Lawrence criteria Consumption of NSAIDS Study Method Pain severity Dissatisfaction with current treatment Interviews and Sample size and demographics WOMAC questionnaire medical records N = 104 Factors associated with an increased HRQL: 71% female Analyses Older age Mean age = 71.2% (SD = 6.9) Mean SF-36 scores were Higher education level compared with age sex- Heavy lifting Patient selection matched Spanish Reference Higher family income outpatients diagnosed with knee OA grade Population Values. No previous prostheses IV (according to Kellgren and Lawrence criteria), on a waiting list for total knee Multiple linear regression, transplant, for less than 6 months Spearman’s correlation Excluded: functional illiteracy; inflammatory coefficient, Mann-Whitney or other severe musculoskeletal conditions, test, Kruskall Wallis test metabolic or neoplastic disease and severe psychopathology or comorbidity

Lopez Silva (2007) Type of chronic pain Outcomes Measured Patients with chronic pain scored worse than non Spine osteoarthritis (20.9%), low back pain (15.4%) Working disability related pain sufferers in all the SF36 domains. Study Design to rheumatic diseases Cross-sectional Confirmation of diagnosis Work off days Those with chronic pain scored worse than those Criteria not specified Costs with acute pain in all the SF36 domains, except for Study Method Impact of pain on quality physical function and body pain (not significant). Questionnaire to Sample Size and Demographics of life (SF-36) patients with pain N = 170 patients (347 participants) and other conditions Females: 70%, Pain Severity in primary care Age: 63 ( ± 31) yr Not measured

Patient Selection Analyses Consecutive visits in two days selected Descriptive randomly each study week.

109 RESULTS / EPIDEMIOLOGY OF CHRONIC Q12a Study quality NON-MALIGNANT PAIN IN SPAIN Carmona et al. (2001), Nunez et al. (2007) and Fernandez-Lopez et al. (2008) were rated as high quality as they fulfilled all the study quality criteria.

Lopez Silva (2007) was rated as low quality. Most of the important features about the design were incompletely described, and did not provided a description of the eligibility criteria. The form to collect data was not described, and it is not possible to know how the main conditions (diagnostic criteria for chronic or acute pain condition) were described. It is unclear whether the study population is representative of the target population: participants were recruited consecutively in two random days each study week (winter months in 2005). The outcomes of interest were listed, but not described in detail (just a mention for the SF36 domains), as in the case of the statistical methods (t Student for mean comparisons). Adjustments for confounders were inexistent.

Q12a Results EPISER Study Carmona et al. (2001) All the conditions except hand OA significantly impaired the functional ability (measured by the HAQ) in the following order of magnitude: RA (HAQ score 1.75), FM (1.30), symptomatic knee OA (1.29), and low back pain (1.27). With regard to quality of life, FM was the only condition independently associated with a low score in the mental component of SF-12 (score 39.0). The diseases that affected the physical aspects of the quality of life in order of magnitude were: RA (29.1), symptomatic knee OA (31.7), and low back pain (32.4).

Fernandez-Lopez et al. (2008) 110 Knee pain suggesting OA 66.8% (of respondents) rated their health as poor or just fair. SF-12 RESULTS / EPIDEMIOLOGY OF CHRONIC physical score was 38.7 (significantly different from those without knee pain, 51.5). SF-12 NON-MALIGNANT PAIN IN SPAIN mental score was also lower, 46.1% compared to 50.1

Nunez et al. (2007) In outpatients diagnosed with knee OA grade IV on a waiting list for total knee transplant, factors that had a negative impact on HRQL were: female gender, disease duration, number of comorbidities, consumption of NSAIDS and dissatisfaction with current treatment. Con- versely, factors that had a positive impact on HRQL were: older age, higher education level, heavy lifting, higher family income and no previous prostheses.

Lopez Silva (2007) The study included 347 patients, 170 of which consulted for a pain condition. Within the patients that presented pain, the 74% (117) had chronic pain. Women (75%) and aged >65 years (83%) reported chronic pain more frequently than men (24%) and younger participants (59%). Most of patients reported musculo skeletal pain (37.7%). Pain and non-pain patients reported similar comorbidities (arterial hypertension, diabetes, COPD, dyslipemia, and mood disorders).

Patients with pain scored worse than non-pain sufferers in all the SF36 domains. This difference was also observed when compared chronic pain patients with non-pain patients (p<0.005 for all comparisons). Within patients with pain, those with chronic pain scored worse than those with acute pain in all the SF36 domains, except for physical function and body pain (not significant).

111 RESULTS / EPIDEMIOLOGY OF CHRONIC Table 16. Results for SF-36 for no pain, pain, acute pain and chronic pain NON-MALIGNANT PAIN IN SPAIN

SF36 Physical Social Physical Emotional Mental Body Global domains function function role role health Vitality dimension health

Mean (SD)

Non pain 78,1 – 22.2 85,7 – 23,2 85,1 – 32,5 92,3 – 23,7 69,5 – 20 64,8 – 23,4 81,0 – 23,3 48,9 – 18,9

Pain 52,8 – 30,6 57,4 – 30 41,0 – 43 73,6 – 40,3 57,0 – 23,3 43,5 – 24,7 34,5 – 23,5 34,7 – 21,1

Acute 73, 9 – 28,1 64,4 – 29,3 55,3 – 45 84,0 – 31,1 68,9 – 20,3 59,6 – 25,3 38,3 – 25,6 50,1 – 21,4

Chronic 44,8 – 28,1 54,6 – 29,3 35,5 – 45 69,6 – 31,1 52,5 – 20,3 37,4 – 25,3 33,0 – 25,6 28,8 – 21,4

Q12a Summary Three of the included studies (Carmona (2001), Nunez (2007) and Fernandez-Lopez (2008)) were of high quality and representative of the Spanish pain population. Chronic pain can affect all areas of quality of life for sufferers, although the affects can vary on the specific dimensions of quality of life depending on the type of pain, gender, age, disease duration and satisfaction with treatment. Chronic pain sufferers report a lower quality of life than acute pain patients.

112 RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Q12b What is the impact of chronic pain on activities of daily living?

We located 15 studies that addressed this question, and selected 4 of them here. Miro et al. (2007) report on chronic pain in people aged over 65 years and Espallargues et al. (1996) on OA in the same age range. Bassols et al. (2003) report on back pain in the general population and Collantes-Estevez et al. (2003) on patients in primary care with OA.

Miro et al. (2007) is based on a representative sample of older adults 65 years and over randomly selected from population and interviewed about their pain. The aim of the study is to gather information on the prevalence of pain and chronic pain in older adults in Catalonia, North East of Spain.

Collantes-Estevez et al. (2003) is a multi-centre study conducted by primary care physicians across Spain to investigate the effect of a switch from celecoxib to rofecoxib in patients with osteoarthritis. Both patients and physicians filled out questionnaires before and after the switch, which measured patients OA related health status and satisfaction with therapy, use 113 of gastroprotective medications and physicians’ impressions of patients’ status. Table 17. Study characteristics and results of included studies for Question 12b: impact on activities of daily living

Study details Population Outcomes and analysis Results

Miro et al. (2007) Type of chronic pain Outcomes measured Prevalence of pain interference = 48.6% General non-cancer pain Pain prevalence, number and location of greater in females than males, higher Study Design pain sites, onset, intensity of pain, number incidence as more pain locations. Cross-sectional survey Diagnostic criteria of days of pain, pain severity, interference Not reported with everyday life, level of expressed need (“During the past four weeks, how much did Study Method pain interfere with your normal work (including Interviews Sample size and demographics Pain severity both work outside the home and housework)”) N = 592 Chronic pain grade questionnaire Men = 274 Women = 318 Analyses Mean age over 70 years Descriptive

Patient selection Age 65 years and over, living in Catalonia. Excluded if Severe cognitive deterioration

114 Study details Population Outcomes and analysis Results

Bassols et al. (2003) Type of chronic pain Outcomes Measured Limitation of daily activity (N = 171) Back pain Prevalence of back pain, characteristics, 36.7% were limited. Study Design 82% chronic relationship to socio demographic variables, 1 day 21% Descriptive cross- 41.2 % osteoarticular (rheumatic, therapeutic behaviour and associated- 2-7 days 40% sectional arthrosis, arthritis) impairments and disabilities. 1-4 weeks 18% 19.1% professional (work accident, work disease) 1-12 months 14% Study Method Pain Severity Above 1 year 7% Telephone interview Confirmation of diagnosis Intensity measured by verbal scale (mild, Referred by patients moderate, intense, very intense, unbearable) 23% needed bed rest (N = 108) 1 day 18% Sample Size and Demographics Analyses 2-7 days 51% N = 1964 interviewed Descriptive 1-4 weeks 22% - females 60.3%. Student t test and Mann-Whitney U for 1-6 months 8% - mean age 47.5 years; range 20-91) means comparison 378 persons with chronic back pain (>1 year) X2 Stopped working N = 62 17% Patient Selection Lees than 1 week 26% Random sample stratified by sex, age and 1-4 weeks 28% place of residence, of general population, 1-6 months 26% older than 18 years, enrolled in the Census 6-12 months 5% in Catalonia. Excluded people in nursing Above 1 year 15% homes, prisons or hospital in-patients. Permanent incapacity N = 29, 6.5%

115 Study details Population Outcomes and analysis Results

Espallargues Type of chronic pain Outcomes measured 45% were independent without difficulties, 36% et al. (1996) OA and RA pain intensity independent with difficulties, 19% dependent. pain treatment / doctor visits Chronic limitation of activity 23%, those Study Design Diagnostic criteria other chronic diseases regularly using type of mechanic help 19% Cross-sectional survey Self-reported self- evaluation of health functional ability Study Method Sample size and demographics chronic limitation Interview N = 1287 hospitalization 76% female Pain severity Subject selection Asked intensity of their pain a stratified sample of all residents of Barcelona aged 65 or more Analyses Descriptive: frequencies

Collantes-Estevez Type of chronic pain Outcomes measured Before the switch to rofecoxib, mean et al. (2003) OA OA related health status and functional capacity (ACR criteria) was: satisfaction with therapy. Fully able to perform usual Study Design Diagnostic criteria Perception of stiffness, night pain, activities n = 347 (15.6%) Longitudinal NR anxiety, depression, use of concomitant Limited in work activities n = 642 (28.9%) gastroprotective medications (GPMs). Limited in work & non-work Study Method Sample size and demographics Physicians’ impressions of patients’ status. activities n = 989 (44.6%) Questionnaires N = 2228 Limited capacity to perform usual at baseline and 66.5% women Pain severity activities n = 240 (10.8%) at follow-up visit NR within 3 months Subject selection The authors do not report functional If physician thought they would benefit Analyses capacity after the switch to rofexcoxib. from a change in therapy McNemar test, Fisher exact tests, logistic regression

Q12b Study Quality Miro et al. (2007) was rated as medium quality as there was not an adequate description 116 of the eligibility criteria or the statistical methods. Espallargues et al. (1996) was rated RESULTS / EPIDEMIOLOGY OF CHRONIC as medium quality, as the description of the outcomes was unclear and it was not clear if NON-MALIGNANT PAIN IN SPAIN the results were unadjusted or confounder adjusted. Collantes-Estevez (2003) was rated as medium quality. It did not have an adequate description of the eligibility criteria or of losses to follow-up, and it is unclear if the participants were representative of the target population. Bassols (2003) was rated as medium quality, although it was representative of the Spanish population, the eligibility criteria, description of outcomes and statistical methods were unclear.

Q12b Results Miro (2007) Based on a single question taken from the SF-12 (Gandek et al. (1998)): “Dur- ing the past four weeks, how much did pain interfere with your normal work (including both work outside the home and housework)”, the prevalence of pain interference in the participants with general non-cancer chronic pain who reported some pain was 48.6%. The prevalence of pain interference was not affected by age, but it was greater in females than in males, the prevalence of pain interference increased with the number of painful areas.

Espallargues (1996) Older people with OA or RA: 45% were independent without difficulties, 36% independent with difficulties, 19% dependent. In 23% there was a chronic limitation of activity and 19% were regularly using some type of mechanic help.

Collantes-Estevez (2003) For patients with OA taking celecoxibs (before the switch to rofecoxib), the number of patients with functional capacity according to ACR criteria were as follows: 347 (15.6%) were fully able to perform usual activities, 642 (28.9%) were limited in work activities, 989 (44.6%) were limited in work & non-work activities and 240 (10.8%) had limited capacity to perform usual activities n=240 (10.8%). The authors do not report functional capacity after the switch to rofexcoxib. 117 RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 21: Functional capacity Collantes-Estevez (2003) NON-MALIGNANT PAIN IN SPAIN

45% LIMITED IN WORK AND NON-WORK ACTIVITIES

11% LIMITED CAPACITY FOR USUAL ACTIVITIES

15% FULLY ABLE

29% Patients presenting for treatment

Bassols (2003) In a representative sample of adults with back pain, 36.7% were limited in their daily activities, with the majority limited between 1 and 7 days (61%) and a fifth between 1 and 4 weeks. 23% needed bed rest for their pain, 17% had to stop working due to their pain and 6.5% had permanent incapacity.

118 RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 22: Pain interference with job or house work NON-MALIGNANT PAIN IN SPAIN

90,00%

80,00%

70,00% PAIN INTERFERENCE WITH JOB OR HOUSE WORK

60,00%

50,00%

40,00%

30,00%

20,00%

10,00%

0,00%

MIRO (2007) Bassols (2003) COLLANTE- GENERAL NON- ADULTS WITH ESTEREZ (2003) CANCER PAIN BACK PAIN PATIENTS WITH OA TAKING CELE- COXIBS

119 RESULTS / EPIDEMIOLOGY OF CHRONIC Q12 b Summary NON-MALIGNANT PAIN IN SPAIN The studies were all of medium quality and three were representative of the target population. Around half of over 65 year olds with general non-cancer pain and with OA had their pain interfere with their activities of daily living. In those with back pain, just over a third were limited in their daily activities. Although this study is representative, it may have included people with acute back pain.

Q12c and d: What is the impact of chronic pain on c. Depression and other mental illness and d. Isolation, helplessness?

We selected 6 studies that address these questions. Breivik (2006) is on general chronic pain, Pinto-Meza (2006) on back and neck pain, Gamero (2005) on rheumatologic pain, Galvez (2006) on neuropathic pain, Torre (2008) on back pain, FM and neuropathic pain and Orfila (2006) on chronic pain in the elderly.

Pinto-Meza et al. (2006) was a survey of adults aged 18 years and older, and aimed to estimate chronic back pain and chronic neck pain prevalence among the Spanish population, its co-morbidity with other mental and physical conditions and its impact on global functioning. 120 RESULTS / EPIDEMIOLOGY OF CHRONIC Gamero et al. (2005) conducted a cross sectional study to establish the prevalence and char- NON-MALIGNANT PAIN IN SPAIN acteristics of rheumatologic pain in a random sample of 1,134 adult outpatients in waiting list to be attended in specialized rheumatology offices of public Spanish hospitals.

Galvez (2006), the goal of this cross-sectional evaluation was to assess pain impact on sleep and symptoms of depression and anxiety in patients with neuropathic pain (NP). Partici- pants in an observational, prospective and multi-centre study (DONEGA study) with NP of broad aetiologies, completed the Short Form-McGill Pain Questionnaire (SFMPQ), the COVI Anxiety Scale, the RASKIN Depression Scale, and the MOS Sleep Scale at baseline.

The aim of Orfila (2006) was to evaluate to what extent gender differences in HRQL among the elderly might be explained by differences in performance-based functional capacity and chronic conditions, using the conceptual model of health outcomes as proposed by Wilson and Cleary. Data are from a cross-sectional home survey of 872 surviving individuals from an elderly cohort representative of Barcelona’s general population. A cohort of non-insti- tutionalized residents aged 65 and older included in the 1986 “Health Interview Survey of Barcelona”, Spain, (population ¼ 1.5 million inhabitants) was followed.

121 Table 18. Characteristics and results of relevant studies for Q12c&d: impact of pain on depression and other mental illness, isolation and helplessness

Study details Population Outcomes and analysis Results

Breivik (2006) Type of chronic pain Outcomes measured 29% (n = 225) diagnosed with depression General chronic pain Impact of pain on emotional status Study Design Cross-sectional Confirmation of diagnosis Pain severity survey Not reported 10-point Numeric Rating Scale (NRS)

Study Method Sample size and demographics Analyses Large scale Total n = 3801 Descriptive computer-assisted Chronic pain n = 301 telephone survey Mean age chronic pain 50.7 years, 52% female

Patient selection Any pain lasting at least 6 months, had experienced pain in the last month, and experienced pain at least two times per week

122 Study details Population Outcomes and analysis Results

Pinto-Meza et Type of chronic pain Outcomes measured (Response rate 78.6%) al. (2006) Neck and back pain 1 yr and lifetime prevalence of One year prevalence: back pain and neck pain. Study Design Diagnostic criteria Depression and anxiety: Composite Major depression 7.2% (SE 1.2) Cross-sectional Not reported international diagnostic interview (CIDI). OR 1.19 (95%CI 1.3-2.9) survey Global functioning: WHO disability Dysthymia Sample size and demographics assessment schedule 0.7% (SE 0.3) OR 1.6 (95%CI 0.6-4.2) Study Method N = 2121 Mood disorders 7.9% (SE 1.3), Questionnaire Pain severity OR 1.19 (95%CI 1.3-2.9) Patient selection Not reported 18+ yrs old, subset of earlier study, data Anxiety: derived from those subjects identified by 1st Analyses Generalised 1.4 (SE 0.4), OR 2.9 (95%CI 1.3-6.2) part of being at risk of mental illness. Descriptive, logistic and linear regression to Panic disorder 1.3% (SE 0.4) OR 3.2 (95%CI 1.4-7.2) calculate association between pain and mental Agoraphobia 0.4% (SE 0.2) No OR given illness. logistic regression to calculate ORs PTSD 1.5 (SE0.5) OR 4.1 (95%CI 1.5-11.3) Social phobia 0.8% (SE 0.3) OR 1.3 (95%CI 0.4-3.8) Other phobias 4.5% (SE 1) OR 1.1 (95%CI 0.6-2.3) Any anxiety disorder 8.2% (SE 1.6) OR 1.5 (95%CI 0.8-2.7)

Any mental disorder 12.2% (SE 1.9) OR 1.4 (95%CI 0.9-2.3)

123 Study details Population Outcomes and analysis Results

Torre et al. (2008) Type of chronic pain Outcomes measured 92 respondents, General non-cancer pain quality of life (SF-36), coping strategies (CAD-R), A significant correlation with intensity of Study Design anxiety/depression (HAD) and intensity of pain pain both for the anxiety and depression Cross-sectional Diagnostic criteria components of HAD were found. survey Pain severity Sample size and demographics VAS After 6 months, the change in the HAD Study Method N = 119, 93 completed study (22% lost to follow-up) depression scores showed improvement Structured 74 women, 44 men Analyses for back and neuropathic pain, but interview Median age 55.12 (SD 13.28) range 26-82 Descriptive reduced for FM and were as follows: 40% > 60 years –0.77 (SD 5.05) for back pain, 0.65 (SD 4) for FM, –0.82 (SD 4.61) for neuropathic pain. Subject selection Had to have at least 6 months pain, seen for first Mean change in the HAD anxiety score showed time at pain unit. 18 years and over. Excluded if an improvement in all types of pain: 0.26 cognitive impairment, walking difficulties to arrive (SD 3.99) for back pain, 1.55 (SD 5.46) for at the hospital or didn’t sign consent form. FM, 0.91 (SD 2.71) for neuropathic pain.

Gamero et Type of chronic pain Outcomes Measured 14.4% depression, 13.4% anxiety. al. (2005) Musculoskeletal pain fibromyalgia Reason for consultation characteristics of the patient, location, type, intensity, Depression N = 163, 14.4% Study Design Confirmation of diagnosis duration, tolerance and management of pain; Anxiety N = 147, 13% Cross-sectional By the doctor treatment; satisfaction with the treatment; (no confirmation of diagnoses) study and association with fibromyalgia. 3% had no symptoms of depression Sample Size and Demographics (according to scale) Study Method N = 1,134 Depression (ZUENG scale for depression, 42% mild symptoms Clinical interview New patients: 368 3 questionnaires, self-administered, 40% moderate Patients for revision: 782 measures how patient is doing and how 15% severe. Females: 71.6%, well they can perform daily activites. Age: the bigger group 45-65 years Gender: 80% chronic pain Pain Severity Women with more mod to severe depression. Visual Analogue Scale Patient Selection Brief Questionnaire for Pain Evaluation (BPI) Those with no physical activity had 1,134 adult outpatients in waiting list to higher levels of depression. be attended in specialized rheumatology Analyses offices of public Spanish hospitals Descriptive Patients with FM had more sever X2 for comparing qualitative variables forms of depression. and Student t-test and analysis of variance for quantitative variables. Data for anxiety not very reliable (no 124 explanation of how diagnosis confirmed). Study details Population Outcomes and analysis Results

Galvez (2006) Type of chronic pain Outcomes Measured 19.7% patients had symptoms of Neuropathic pain (NP) Effectiveness of analgesic treatment depression and 12.9% of anxiety. Study Design 1519 with NP: (gabapentin for 3 months) Cross-section of 603 pure NP Depression (RASKIN) 3 items – subjective Prevalence of anxiety and depression: DONEGA study, 856 mixed NP experience of depression, primary signs of BMI <27: 10.6% anxiety, 18.2% depression which was an depression, secondary signs (appetite, sleep and BMI >27 – 30 13%, 20% observational, 61.2% severe cognitive changes), (1 = not present, 5 = extreme) BMI >30 18%, 24% prospective and 32.6% moderate Scale 3-15. Cut off for presence of depression = 9. multicenter 6.2% mild Previous analgesic treatment study Anxiety (COVI) 3 items – verbal communication, Yes: 14.4%, 20.8% Pure NP, 11% diabetic, 10% trigeminal behaviour, secondary complaints (1 = No: 9.1%, 17.1% Study Method neuralgia, 13% complex pain syndrome, 15% no anxiety, 5 = extreme) Scale 3-15. Cut Evaluated post-herpetic neuralgia, 19.1% syndrome of off for presence of anxiety = 9. Intensity of pain subsection entrapment, 3% phantom limb, others. Mild: 8.5%, 9.1% of DONEGA Sleep (MOS) 12 items, including: Moderate: 5.2%, 6.8% participants Mixed NP, 29% radiculopathy, 22% back Quantity and quality of sleep, abrupt wake-up Severe: 17.2%, 27.1% pain, 70% compressed vertebrae, 8% in night, light sleep, somnolence. Scale 0-100 stenosis of spinal channel, other e.g. Gender: surgical trauma and osteoporosis. Pain Severity Male: 7.5%, 12% McGill (SF/MPQ) Likert scale (0-5) Female: 16.4%, 24.5% Confirmation of diagnosis VAS (0-100) Scales used to measure symptoms Type of pain: Analyses Pure NP: 11.2%, 20.4% Sample Size and Demographics descriptive analyses of all symptoms Mixed: 14.1%, 19.2% N = 1,519 Multiple regression (type of pain NP or mixed, Mean age ± SD = 56.9 ± 13.6 years old age, gender, duration of pain, existing analgesic Sleep disorders (0-100) 61.2% female treatment, BMI, pain intensity, punctuation <10: 0%, 0% 1.1 years (SD 2.8) pain duration of sleeping scale, medical condition of pain, >90: 34.9%, 49.8% punctuation of anxiety and depression) analysed Patient Selection with WAD test, significance level p<0.10), ANCOVA Depression increased significantly with Over 18 years, in specialist pain clinics, age, no association with anxiety. participants in the DONEGA study, Without mental incapacity, clinical diagnosis of NP. Excluded – hypersensitive to gabapentin, pregnant/breast feeding women

125 Study details Population Outcomes and analysis Results

Orfila (2006) Type of chronic pain Outcomes Measured NHP total score: the crude difference Arthritis, back problems HRQL using the Nottingham Health Profile (NHP) between elderly men and women was Study Design Functional capacity using the Established 11.5 points. Men had a total NHP score of Cross-sectional Confirmation of diagnosis Populations for the Epidemiological 16.7, compared with 28.3 for women. survey Self-reported (asked if a doctor had Study of the Elderly (EPESE) Gender difference diagnosed their chronic condition) for was 4.4 for Social Isolation. Study Method Pain Severity Interviews and Sample Size and Demographics B and p values for Social Isolation in performance tests N = 544 Analyses the multiple linear regression: 356 were women Chi-squared test Arthritis: 4.8 (2.0) 0.021 (65.4%) multiple linear regression models Back problems: 14.2 (2.2) <0.001 mean age of 78.4 (SD ¼ 4.8) for women and Path Analysis to test the Wilson and Cleary model a mean age of 78.8 (SD ¼ 5.2) for men Elderly women’s worse HRQL is due to A quarter of the study sample was living alone, a worse health status than men rather 54.2% belonged to social classes IV or V (manual, than to differences in reporting. semi-skilled or unqualified workers), and 54.0% had had fewer than 8 years of education

Patient Selection Elderly people aged over 65 years who had participated in the 1986 Health Interview Survey of Barcelona and were still living in the community

Q12c and d Study Quality Breivik et al. (2006) was rated as medium quality. Most criteria were met, however, the description of study participants was not clear enough. There was also no description of the statistical methods used.

Pinto-Meza et al. (2006) was rated as low quality, it did not have an adequate description of the eligibility criteria, there was not a clear description of the study participants and it was 126 unclear if it was representative of the target population. RESULTS / EPIDEMIOLOGY OF CHRONIC Gamero (2005) was rated as medium quality. There was not an adequate description of the NON-MALIGNANT PAIN IN SPAIN how the outcomes were measure.

Torre (2008) was rated as medium. It was unclear if it was representative of the target population and whether the results were confounder adjusted.

Galvez (2006) was rated as low quality. There is a high risk of reporting bias. Authors reported all the results dichotomizing all the scores in the scales used to measure the outcomes of interest (Covi for anxiety, Raskin for depression, MOS-sleep for sleep disturbance). Moreover, in the tables that present the results related to multivariate analyses some assessed outcomes are not reported, and some correlation coefficients are lacking (anxiety- pain for example).

Q12c and d Results Breivik (2006) In a representative sample of the Spanish population, those with chronic pain (n=225) 29% had been diagnosed with depression due to pain.

Torre (2008) Depression and anxiety was measured using the HAD scale. For 92 respondents, there was a significant correlation with intensity of pain both for the anxiety and depression components of HAD. The HAD also correlated with some aspects of the SF-36: physical function, body pain, emotional status, social function, vitality and mental health. After 6 months, the change in the HAD depression scores showed improvement for back and neuropathic pain, but reduced for FM and were as follows: –0.77 (SD 5.05) for back pain, 0.65 (SD 4) for FM, –0.82 (SD 4.61) for neuropathic pain. The mean change in the HAD anxiety score showed an improvement in all types of pain: 0.26 (SD 3.99) for back pain, 1.55 (SD 5.46) for 127 FM, 0.91 (SD 2.71) for neuropathic pain. RESULTS / EPIDEMIOLOGY OF CHRONIC Pinto-Meza (2006) NON-MALIGNANT PAIN IN SPAIN Depression and anxiety were measured using the Composite International Diagnostic Interview (CIDI 3.0), which was designed to be administered by non-psychiatry raters and provides a diagnosis of mental disorders according to the ICD diagnostic criteria. The main disorder they considered was mood disorders – depression and dysthymia, anxiety disorder, generalised anxiety, agoraphobia, PTSD, other phobias, panic attacks. The scale has a high level of concordance with actual diagnoses and is more conservative than a clinician would be. There was a response rate 78.6%, and the one year prevalence of mood disorders were as follows in table 19. The study showed that people with chronic neck and back pain had higher risk of suffering the following mental health diseases: any mood disorder, major depression, generalized anxiety, anxiety, and PTSD. All these risks were significant p<0.05, and were adjusted by sex, age, educational level, and employment.

Table 19. Prevalence of mood disorders in patients with neck and back pain

Mood disorder 1 year prevalence Odds Ratio

Major depression 7.2% (SE 1.2) 1.19 (95%CI 1.3-2.9)

Dysthymia 0.7% (SE 0.3) 1.6 (95%CI 0.6-4.2)

Mood disorders 7.9% (SE 1.3) 1.19 (95%CI 1.3-2.9)

Generalised anxiety 1.4% (SE 0.4) 2.9 (95%CI 1.3-6.2)

Panic disorder 1.3% (SE 0.4) 3.2 (95%CI 1.4-7.2)

Agoraphobia 0.4% (SE 0.2) No OR given 128 Mood disorder 1 year prevalence Odds Ratio RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN PTSD 1.5% (SE0.5) O4.1 (95%CI 1.5-11.3)

Social phobia 0.8% (SE 0.3) 1.3 (95%CI 0.4-3.8)

Other phobias 4.5% (SE 1) 1.1 (95%CI 0.6-2.3)

Any anxiety disorder 8.2% (SE 1.6) 1.5 (95%CI 0.8-2.7)

Any mental disorder 12.2% (SE 1.9) 1.4 (95%CI 0.9-2. 3)

Gamero (2005) This study assessed depression levels through the self-reported Zung scale. 14.4% of the sample had depressive symptoms. Only 3% of patients did not report depressive symptoms, 42% reported low to moderate levels, and 15% had severe depressive symptoms. The study reported significant differences in symptoms by sex (p<0.0001), with women reporting severe symptomatology in more cases than men. Women in this study were the participants with higher rates of chronic pain (81.2%). Patients with fibromyalgia (12% of the sample, 95% of whom were women) reported severe depressive symptoms. Within these patients, the most common co-morbidities were depression (patients with FM 35.5% vs patients without FM 11.4%) and anxiety (patients with FM 38,4% vs patients without FM 9,4%; p<0,0001 for both comparisons). Anxiety was observed in the 13% of the study sample. However, the data for anxiety is not very reliable as no explanation of how the diagnosis was confirmed is given.

Galvez (2006) This study measured the levels of depression, anxiety and sleep disorders in patients with neuropathic pain. Depression was measured using the RASKIN test, which has 129 3 items – subjective experience of depression, primary signs of depression and secondary RESULTS / EPIDEMIOLOGY OF CHRONIC signs (appetite, sleep and cognitive changes), where 1=not present, 5=extremely present. The NON-MALIGNANT PAIN IN SPAIN results are on a scale of 3 to 15 and the cut off for the presence of depression is a score of 9. Anxiety was measured using the COVI test, which also has 3 items – verbal communication, behaviour, secondary complaints (1=no anxiety, 5=extreme) and the results are a scale of 3 to 15. Cut off for presence of anxiety is 9. Sleep was measured with MOS, with 12 items, including: quantity and quality of sleep, abrupt wake-up in night, light sleep, somnolence and the scale is 0 to 100.

The study found that 19.7% patients had symptoms of depression and 12.9% of anxiety. The prevalence of anxiety and depression for people with BMI <27 was 10.6% anxiety, 18.2% depression, BMI >27 – 30 was 13% and 20%, BMI >30 was 18% and 24% (anxiety and depression respectively). For those who had previous analgesic treatment 14.4% reported anxiety and 20.8% depression, and who hadn’t, 9.1% and 17.1% and according to intensity of pain: mild pain 8.5% anxiety and 9.1% depression, moderate pain 5.2% and 6.8%, and severe pain 17.2% and 27.1%. Males reported 7.5% and 12% anxiety and depression, and females 16.4% and 24.5%. Those with pure NP 11.2% had anxiety and 20.4% depression, mixed NP 14.1% and 19.2%. In sleep disorders, with a score <10 there was no anxiety or depression, but in those with a score >90 34.9% had anxiety and 49.8% depression. Depression increased significantly with age, but there was no association with anxiety.

Orfila (2006) HRQL was measured using the Nottingham Health Profile (NHP), which con- tains 38 items divided into six dimensions: Energy, Sleep, Pain, Social Isolation, Emotional Reactions, and Physical Mobility and gives a score on a scale on 0-100. Functional capacity was measured using the Established Populations for the Epidemiological Study of the Elderly (EPESE), which are three tests to assess lower extremity function. B and p values for Social Isolation in the multiple linear regression were as follows: arthritis: 4.8 (2.0), p=0.021; 130 back problems: 14.2 (2.2), p <0.001. RESULTS / EPIDEMIOLOGY OF CHRONIC For chronic conditions, the study found that elderly women showed worse total NHP NON-MALIGNANT PAIN IN SPAIN score than men and in all of the dimension scores. For the NHP total score, the crude difference between elderly men and women was 11.5 points. Men had a total NHP score of 16.7, compared with 28.3 for women. The gender differences for all the other dimensions ranged from 0.5 for Sleep to 4.4 for Social Isolation. Gender differences in the total NHP score were largely explained by the higher prevalence of reported chronic conditions and worse performance-based functional capacity of elderly women, compared to men. Elderly women’s worse HRQL is due to a worse health status than men rather than to differences in reporting.

Q12c and d summary Three of the included studies were representative of the population (Gamero (2005), Galvez (2006) and Breivik (2006)) and all included studies had large sample sizes. Levels of depression in pain patients ranged from 7% to 29%, and levels of anxiety from 8.2% to 12.9%. Both depression and anxiety were found to be higher in women and depression higher in patients with FM. Women also showed higher levels of social isolation than men, but this is related to their lower functional capacity than men as they have more chronic conditions (including arthritis and chronic back problems) (Orfila (2006)). Although Orfila (2006) was rated as high quality and was representative of the Spanish population, caution needs to be taken over the conclusions as they were related to chronic conditions and not only chronic pain.

131 RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Q12e&f: What is the impact of chronic pain on e) days of work and f) Incapacity benefits?

We selected 5 studies that address this question, Breivik (2006) and Bassols (1999) on non- cancer pain, Kovacs (2007) on low back pain, Ubago (2005) on FM and Tornero (1998) on rheumatic conditions.

The aim of Bassols et al. (1999) was to characterise the prevalence of pain in the Spanish region of Catalonia, and to distinguish its relationship with socio-demographic variables and the resulting disabilities to pain sufferers.

Kovacs et al. (2007) aimed to estimate the influence of fear avoidance beliefs (FAB) on 1-year low back pain (LBP)-related sick leave in 165 workers who visited the National Health Service for LBP in Spain.

Ubago et al. (2005) was a cross-sectional, descriptive telephone survey was conducted during June, July and August 2004 on all patients diagnosed with FM during 2003 at three offices in the rheumatology department of a university hospital Virgen de las Nieves (Gra- nada, Spain) and the objective of this study was to analyse the impact of FM on the functional capacity of patients and disease impact.

132 Tornero (1998) conducted a retrospective descriptive study to account for the temporal RESULTS / EPIDEMIOLOGY OF CHRONIC work disabilities related to rheumatic conditions registered in an urban metropolitan area NON-MALIGNANT PAIN IN SPAIN in the central Spain (Guadalajara) during the period 1991-1995. The study described accu- rately the working population and surveyed the work disability through a University Hospi- tal records and the data from the National Healthcare Services and the National Institutes of Statistics. The study collected age, number of patients with a temporal work disability, days off of work, and the main rheumatic condition for the work disability.

Table 20. Characteristics and results of relevant studies for Q12e&f: impact of pain on days off work and incapacity benefits

Study details Population Outcomes and analysis Results

Breivik (2006) Type of chronic pain Outcomes measured Days of work General chronic pain Mean number of days lost during the last 6 Mean number of days lost 8.4 (n = 116) Study Design months of full or part time employment Cross-sectional Confirmation of diagnosis Lost job 22% survey Not reported Pain severity Changed job responsibilities 8% 10-point Numeric Rating Scale (NRS) Changed jobs 4% Study Method Sample size and demographics (n = 225) Large scale Total n = 3801 Analyses computer-assisted Chronic pain n = 301 Descriptive telephone survey Mean age chronic pain 50.7 years, 52% female

Patient selection Any pain lasting at least 6 months, had experienced pain in the last month, and experienced pain at least two times per week

133 Study details Population Outcomes and analysis Results

Bassols et Type of chronic pain Outcomes measured Days of work al. (1999) General non-cancer pain Pain prevalence, pain characteristics, personal, For those with chronic pain that are employed social and work disabilities due to pain. (n = 787), 123 (15.6%) needed bed rest Study Design Diagnostic criteria with a mean duration of 5.7 (SD 10.2). Cross-sectional Self-reported Pain severity survey Measured on a 5-point Likert scale and VAS Pain resulted in time off work in 10.2% of Sample size and demographics employed individuals. 41.2% of these cases Study Method N = 1964 Analyses meant less than a week away from work but Questionnaire 50.3% female Student’s t-test, ANOVA, chi-squared test, 33.8% needed a week to a month off from multivariate analysis of unconditional logistic work, with an average of 47 days in total. Patient selection regression, odd ratio (crude and adjusted) Aged 18 and over

Kovacs et Type of chronic pain Outcomes measured Baseline duration median (P25, P75) al. (2007) Back pain and low back pain LPB intensity, functional disability (Roland- number of days sick leave: Morris questionnaire), fear avoidance beliefs Study Design Diagnostic criteria (fear avoidance beliefs questionnaire), Total 7.5 (0.0, 26.75) Longitudinal / Not reported health related quality of life. With no sick leave 4.5 (0.0, 19) cohort study Short/medium sick leave 2.0 (0.0, 10.25) Sample size and demographics Pain severity Long sick leave 22.5 (4.0, 151.5) Study Method N = 165 VAS Questionnaire 53.9% female During 1 year follow-up: Analyses 77 patients did not go on sick leave, 46 were on sick Patient selection Chi-squared test, Kruskal-Wallis, multivariate leave for less than 2 months, 42 were on sick leave Workers who consulted their physician for LBP ordinal logistic regression model for a period ranging between 2 and 12 months.

134 Study details Population Outcomes and analysis Results

Ubago et al. (2008) Type of chronic pain Outcomes measured 39.3% (N = 84) unemployed due to the following FM FM impact -alteration in the functional reasons: 31.4% for sick leave (N = 67), Study Design capacity of patients diagnosed with FM 5.6% were unemployed (N = 12), Cross-sectional Diagnostic criteria Socio-demographic characteristics retired (2.3%; N = 5). survey ACR criteria Job characteristics - present job situation Clinical characteristics Within the 67 cases of sick leave, 52.2% were Study Method Sample size and demographics Health characteristics temporal (N = 35) derived in the majority Telephone N = 214 Psycho-social characteristics of cases from osteoarticular pain (74.6%, interview 92.1% female N = 50), or fibromyalgia (16.4%, N = 11). 60.7% working Pain severity Most of the patients with a sick leave had 39.3% not working Not reported manual occupations (64.8%; N = 43).

Patient selection Analyses Diagnosis of FM contingency tables and the chi-square test, Student’s t test, analysis of variance (ANOVA), Mann–Whitney and Kruskal–Wallis tests Multivariate linear regression model

Tornero (1998) Type of chronic pain Outcomes Measured 6970 work disabilities cases during the 5 years Low back pain (60.4%), soft tissue rheumatic Working disability related to rheumatic diseases study period, equivalent to 364 624 work off days. Study Design pain (18.4%), knee derangement (14.7%) Work off days Cross-sectional Costs By sex, 4639 were registered in men Confirmation of diagnosis (227 075 work off days) and 2 329 in Study Method Conditions were coded through CIE9 criteria Pain Severity women (137 522 work off days). Data obtained from Not measured medical records Sample Size and Demographics Most of the work disability periods were registered and institutional N = 145.593 inhabitants in the study area Analyses for people aged 25 to 50 (189 508 work off data from National (urban-metropolitan), 47.037 working Descriptive days). Work disabilities periods in older than 50 Statistics Institute population, 6.264 work disabilities cases. were considered more severe due to a greater Females: 71.889 inhabitants in the study number of work off days (132837). The most area, 12.226 working population. common condition that produced work disability Age: not reported periods was low back pain (60.4%; 4 212 cases, 206 932 work off days), followed of soft tissue Patient Selection rheumatic conditions (18.4%; 1285 cases, 57 All the working population reporting a working 727 work off days), and knee derangement disability period related to rheumatic conditions (14.7%; 1031 cases, 52 952 work off days).

Reported costs related to work disability periods 135 equivalent to 1.397.258.172 pesetas (that would be equal to 8.397.690,74 euros). The mean annual value for work disability was equivalent to 279.451.634 pesetas (1.679.538,15 euros). RESULTS / EPIDEMIOLOGY OF CHRONIC Q12e and f Study quality NON-MALIGNANT PAIN IN SPAIN Breivik et al. (2006) was rated as medium quality. Most criteria were met, however, the description of study participants was not clear enough. There was also no description of the statistical methods used.

Bassols et al. (1999) and Kovacs et al. (2007) were also rated as medium quality as it was unclear whether the sample populations was representative of the target population and Kovacs et al. (2007) did not have a clear description of eligibility criteria.

Ubago et al. (2005) was rated as medium quality as it did not have clear eligibility criteria and it was unclear whether it was representative of the target population.

Tornero (1998) was rated as moderate quality. Although the data was collected retrospec- tively, the population was representative of the target population mainly because the researchers collected data on all the population that reported a work disability related to rheumatic conditions in the area of the study during the study period. All the conditions were coded following CIE 9 criteria or adapted criteria of the Rheumatology Spanish Society. Costs were obtained directly from National Healthcare Services data.

Q12e and f Results Breivik (2006) In a representative sample of the Spanish population, people with chronic pain had a mean number of days lost due to pain of 8.4 (n=116). Furthermore, 22% had lost their job due to their pain, 8% had changed job responsibilities and 4% had changed jobs entirely due to their pain (n=225).

Bassols (1999) In Catalonia, for those with chronic pain that were employed (n=787), 123 136 (15.6%) needed bed rest with a mean duration of 5.7 (SD 10.2). Pain resulted in time off work RESULTS / EPIDEMIOLOGY OF CHRONIC in 10.2% of employed individuals. 41.2% of these cases meant less than a week away from NON-MALIGNANT PAIN IN SPAIN work, but 33.8% needed a week to a month off from work, with an average of 47 days in total.

Kovacs (2007) For workers who visited the National Health Service for LBP, the duration of sick leave when entering the study of the 66 participants was a median (P25, P75) number of sick days of 7.5 days (0.0, 26.75), for those taking no sick leave the median was 4.5 days (0.0, 19), those with short to medium sick leave was 2.0 days (0.0, 10.25) and those with long sick leave was 22.5 days (4.0, 151.5). In the one year of follow-up of the study 77 patients did not go on sick leave, 46 were on sick leave for less than 2 months, 42 were on sick leave for a period ranging between 2 and 12 months.

137 RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 23: Sick leave due to pain NON-MALIGNANT PAIN IN SPAIN

7 NUMBER OF WORK DAYS LOST

6 NUMBER OF DAYS WITH BED REST

BREIVIK (2006) BASSOLS (1999) KOVACKS (2007)

Tornero (1998) The researchers reported 6970 work disabilities cases during the 5 years study period (1991-1995), equivalent to 364 624 work off days. By sex, 4639 were registered in men (227 075 work off days) and 2 329 in women (137 522 work off days). Data classification by sex was missing for two work disability cases (27 work off days). Most of the work 138 disability periods were registered for people aged 25 to 50 (189 508 work off days). Work RESULTS / EPIDEMIOLOGY OF CHRONIC disabilities periods in older than 50 were considered more severe due to a greater number NON-MALIGNANT PAIN IN SPAIN of work off days (132 837). The most common condition that produced work disability periods was low back pain (60.4%; 4 212 cases, 206 932 work off days), followed of soft tissue rheumatic conditions (18.4%; 1285 cases, 57 727 work off days), and knee derangement (14.7%; 1031 cases, 52 952 work off days).

Reported costs related to work disability periods equivalent to 1,397,258,172 pesetas (that would be equal to 8,397,690 euros). The mean annual value for work disability was equivalent to 279.451.634 pesetas (1,679,538 euros).

Ubago (2005) At the moment of the interview 39.3% (N=84) of the study sample was unemployed due to the following reasons: 31.4% for a sick leave (N=67), 5.6% were unemployed (N=12), and the rest were retired (2.3%; N=5). Within the 67 cases of sick leave, 52.2% were temporal (N=35) derived in the majority of cases from osteoarticular pain (74.6%, N=50), or fibromyalgia (16.4%, N=11). Most of the patients with a sick leave had manual occupations (64.8%; N=43). Ubago (2005) did not quantify the days off of work due to sick leave.

Q12e and f Summary All studies were of medium quality and had large sample sizes, although it was not clear that all of them were representative of the Spanish population. It is clear from these studies that for people suffering from chronic pain, the impact on the number of work days lost due to their pain is great. Many pain sufferers are either unemployed or on sick leave due to their pain.

139 RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Q13. What are the costs of chronic pain from a) Societal perspective, b) Health care system perspective and c) Patient perspective?

We selected 6 studies that were relevant to this question. Four gave data for specific chronic pain conditions: Carmona et al. (2001) on musculoskeletal diseases (MES) including rheumatoid arthritis, knee and hand osteoarthritis, low back pain and fibromyalgia, Gonzalez et al. (1999) on non-specific low back pain, Sicras-Mainar (2009) on FM, Nunez et al. (2007) gives data on patients with knee osteoarthritis before and after undergoing surgery for their condition and Rodriguez et al. (2007a) and (2007b) on patients with neuropathic pain attending pain clinics.

Carmona et al. (2001) reported on the EPISER study, which was a cross-sectional survey that used stratified multistage cluster sampling from the censuses of 20 municipalities to get a sample of 2998 adults aged 20 years and above. The survey involved interviews and standardised physical examination by trained rheumatologists and the objective was to estimate the prevalence of rheumatoid arthritis (RA), low back pain, hand and knee osteoarthritis (OA), and fibromyalgia (FM) in the adult Spanish population, and to assess the impact of these diseases on function and quality of life, and use of health and social resources.

Gonzalez et al. (1999) conducted a study to assess the cost of worker’s salary compensation from absenteeism due to non-specific low back pain (LBP).

Nunez et al. (2007) was carried out in the Rheumatology Service and the Knee Unit of the Orthopaedic Surgery Service of the Hospital Clinic Provincial (HCP), Barcelona (Spain), a public tertiary care centre. Included were consecutive outpatients of all ages diagnosed with knee OA and that were on a waiting list for total knee surgery. The aim of the study was to determine the health-related quality of life (HRQL) in patients with severe osteoarthritis (OA) 140 and the use and cost of resources related to knee OA. RESULTS / EPIDEMIOLOGY OF CHRONIC Sicras-Mainar et al. (2009) was a retrospective analysis of patient records of adults aged NON-MALIGNANT PAIN IN SPAIN 18 and over from 5 primary care centres. The aim was to determine the use of services and costs in patients with fibromyalgia (FM) or generalised anxiety disorder (GAD).

The aim of Rodriguez (2007a) and (2007b) was to determine health resource consumption and costs in patients with neuropathic pain managed in pain clinics in Spain.

Table 21. Characteristics and results of studies relevant to question 13a, b, c: economic impact of chronic pain

Study details Population Outcomes and analysis Results

Sicras-Mainar Type of chronic pain Outcomes measured Costs to healthcare system et al. (2009) FM comorbidities, health care use, Detailed total costs fro primary care as more and primary care cost. than 35 million Euros per year, 25% fixed costs, Study Design Confirmation of diagnosis 75% variable, of these 12% on specialists, Cross-sectional survey ACR criteria for musculoskeletal disorders. Pain severity 60% to pharmaceutical industry (of 75%). Not reported Cost per patient per year 1063 Euros. Study Method Sample size and demographics Retrospective analysis N = 63349 Analyses of patient records With FM n = 904, 96.5% female descriptive, Logistic regression, ANCOVA

Patient selection Adults 18+ who needed medical attention from 1 of 5 primary care centres in 2006

141 Study details Population Outcomes and analysis Results

Carmona (2001) Type of chronic pain Outcomes measured Costs to society: Musculoskeletal symptoms (MES) (RA, low Received disability compensations: Study Design back pain, OA (knee and hand), FM) Costs to society: RA 9.1% Cross-sectional survey Proportion of respondents receiving Low back pain 8.0%, knee OA 5.4% Confirmation of diagnosis disability compensations. Hand OA 2.2% Study Method Low back pain – self-report FM 7.7% Interviews and OA and FM – ACR criteria Costs to healthcare system: standardised physical RA – ACR classification criteria and physical Visits to a physician because of musculoskeletal Costs to healthcare system: examination by trained examination, x ray and latex agglutination test symptoms in the preceding year. Consulted a physician for MES in past year: rheumatologist if suspected RA not confirmed by ACR criteria RA 72.2% Pain severity Low back pain 61.2%, knee OA 66.4% Sample size and demographics NR Hand OA 58.8% N = 2998 FM 76.9% Analyses Patient selection Subjects weighted with respect to the sampling Subjects aged 20 years or above were randomly scheme. ANOVA, parametric tests. selected by stratified multistage cluster sampling from the censuses of 20 municipalities in Spain

Gonzalez et al. (1999) Type of chronic pain Outcomes Measured Costs to society Non-specific low back pain The cost of worker’s salary compensation The total cost of worker’s compensation LBP Study Design claims was 11,000 million pesetas/year, and the Cost analysis Confirmation of diagnosis Pain Severity mean cost by worker was 209,666 pesetas/year. By the doctor Not reported Study Method Societal perspective: Sample Size and Demographics Analyses cost of worker’s salary Mean number of people affected Descriptive analysis compensation 55,388 per year (SD 9,230) Data from the Registry of the Ministry for Work Patient Selection and Social Affairs Workers on disability leave

142 Study details Population Outcomes and analysis Results

Nunez et al. (2007) Type of chronic pain Outcomes measured All results are for the previous 6 months Knee OA grade IV The use and cost of resources related to Study Design knee OA. Self-reported use of economic Costs to society Cross-sectional survey Confirmation of diagnosis resources during the previous 6 Months. Mean hours of informal help = 129.82 Kellgren and Lawrence criteria (909 Euros) Study Method Costs to society Interviews and Sample size and demographics Weekly number of hours of formal or informal Mean hours of formal help = 43.20 (302 Euros) medical records N = 104 home care by paid private household help 71% female or unpaid help from family or relatives Costs to patients Mean age = 71.2% (SD = 6.9) Out of pocket expenses = 23.71 Euros Costs to patients Patient selection Out-of-pocket expenses Total direct non-medical costs per outpatients diagnosed with knee OA grade (prescriptions or taxis to attend medical visits) patient = 1234.87 Euros IV (according to Kellgren and Lawrence criteria), on a waiting list for total knee Costs to healthcare system Costs to healthcare system transplant, for less than 6 months Number of visits to general practitioners Number of visits to: Excluded: functional illiteracy; inflammatory (GP), specialist, other health care GP = 2.42 (79.8Euros) or other severe musculoskeletal conditions, professionals (e.g., physiotherapist, Specialist = 0.62 (20.46 Euros) metabolic or neoplastic disease and nurse practitioner, psychotherapist and Nurse practitioner = 1.57 (23.11 Euros) severe psychopathology or comorbidity other) and alternative practitioners. Alternative practitioners = 0.09 (2.16 Euros)

Pain severity Number of technical procedures: WOMAC questionnaire includes a section on pain Conventional radiographic examinations = 0.46 (10.34 Euros) Analyses Magnetic resonance imaging = 0.13 (27.35 Euros) Costs: Other technical procedures = 0.08 (6.09 Euros) Unit prices for direct medical costs Blood test = 0.12 (2.52 Euros) according to 2001 Catalan Health Service tariffs, pharmacological treatments Pharmacological treatment: (tablets/ according to the Spanish National week) = 15.38 (31.34 Euros) Pharmacotherapeutical Catalogue. Out-of-pocket expenses self-reported. Total direct medical costs per patient = 200.24 Euros

143 Study details Population Outcomes and analysis Results

Rodríguez et al. (2007) Type of chronic pain Outcomes measured Patients with NP attended the physicians’ offices Neuropathic (NP) per month a mean of 0.8 times (95% CI 0.72, 0.89) Study Design Costs to healthcare system: Most commonly used healthcare resources Retrospective cross- Confirmation of diagnosis Utilisation of health care resources were drugs (100%), followed by diagnostic sectional study By trained pain management specialists for neuropathic pain: medical visits, procedures (93%), non-drug therapies hospital admissions and length of (58%) and hospitalization (25%). Study Method Sample size and demographics stay, diagnostic procedures, non-drug Medical visits: 77% attended pain clinics, Medical records of N = 504 treatments, drug treatments. 46% hospital specialist, 44% emergency pain patients attending 57.6% women room, 36% community specialist. pain clinics in 2004 Only costs financed by the Spanish were analysed Patient selection public healthcare are considered. Mean monthly per-patient unadjusted Outpatients, aged 18 and over, with neuropathic total direct cost was 422 Euros. Most pain diagnosed at least 30 days before Pain severity costs due to hospitalizations (45%), drug Not reported therapies to control the pain (29%). Medical visits and diagnostic procedures each Analyses represented 10% of total direct costs. Descriptive, ANCOVA models Adjusted costs were: 376 Euros for primary care setting patients 344 Euros for patients referred to pain clinics

144 RESULTS / EPIDEMIOLOGY OF CHRONIC Q13 Study Quality NON-MALIGNANT PAIN IN SPAIN Both Carmona et al. (2001) and Nunez et al. (2007) were rated as high quality as they fulfilled all the study quality criteria. Sicras-Mainar et al. (2009) was rated as medium, there was not a clear description of the study design and setting, or the outcomes measured. Gonzalez (1999) was also rated medium, as there was an inadequate description of the study participants. Rodriguez (2006) was rated as high quality although it was unclear it represented the target population.

Q13a Results: Costs to society Carmona et al. (2001) The proportion of respondents who had musculoskeletal symptoms and received disability compensations for their condition ranged from 2.2% to 9.1%. The percentage of those with RA that received disability compensations was 9.1%, 8.0% for low back pain, 5.4% for knee OA, 2.2% for hand OA and 7.7% for FM. The proportion of people receiving disability compensations was significantly greater in those classified as having any of the target conditions than in those without.

145 RESULTS / EPIDEMIOLOGY OF CHRONIC Figure 24: Disability compensations Carmona et al. (2001) NON-MALIGNANT PAIN IN SPAIN

10,00% RHEUMATOID ARTTHRITIS

9,00% loW BACK PAIN

KNEE OA 8,00% HAND OA

FIBROMYALGIA 7,00%

6,00%

5,00%

4,00%

3,00%

2,00%

1,00%

0,00%

DISABILITY COMPENSATIONS

146 RESULTS / EPIDEMIOLOGY OF CHRONIC Gonzalez (1999) NON-MALIGNANT PAIN IN SPAIN The total cost of worker’s salary compensation from absenteeism due to non-specific low back pain (LBP) was 11,000 million pesetas/year, and the mean cost by worker was 209,666 pesetas/year. The mean number of people affected 55,388 per year (SD 9,230). The mean length of LBP disability leave was 21.9 days, with a range between 19.7 and 24.2 days.

Nunez et al. 83% of patients with knee OA on a waiting list for a total knee transplant had some hours of help, but only 3% received formal help. The mean number of hours of informal help in previous 6 months was 129.82, and the mean number of hours of formal help was 43.20. The cost of this help was 909 Euros for informal help and 302 Euros for formal help.

Q13b Results: Costs to the health care system Nunez et al. (2007) For patients with knee OA, the mean number of visits to a GP in the last 6 months was 2.42, which was estimated to cost 79.8 Euros; mean number of visits to a specialist was 0.62, at a cost of 20.46 Euros; to a nurse practitioner was 1.57 visits, 23.11 Euros; and to alternative practitioners was 0.09 visits, 2.16 Euros.

The mean number of conventional radiographic examinations was 0.46, estimated as 10.34 Euros, magnetic resonance imaging 0.13 times, cost 27.35 Euros, other technical procedures 0.08 times, cost 6.09 Euros, and blood test 0.12 times, 2.52 Euros. The mean pharmacological treatment (number of tablets/week) was 15.38, at an estimated cost of 31.34 Euros. In total the mean direct medical costs per patient in the previous 6 months was 200.24 Euros.

Rodriguez (2007a) Patients with neuropathic pain attended the physicians office a mean 147 of 0.8 times (95% CI 0.72, 0.89) per month. The most commonly used healthcare resources RESULTS / EPIDEMIOLOGY OF CHRONIC were drugs (100%), followed by diagnostic procedures (93%), non-drug therapies (58%) and NON-MALIGNANT PAIN IN SPAIN hospitalization (25%). 77% attended pain clinics, 46% hospital specialist, 44% emergency room, and 36% visited a community specialist. The mean monthly per-patient unadjusted total direct cost was 422 Euros. Most costs were due to hospitalizations (45%) and drug therapies to control the pain (29%). Medical visits and diagnostic procedures each represented 10% of total direct costs. The total adjusted costs were: 376 Euros for primary care setting patients and 344 Euros for patients referred to pain clinics.

Carmona et al. (2001) In the past year, 58.8% to 76.9% of respondents with MES had consulted a physician for MES. 72.7% of those with RA, 61.2% of those with low back pain, 66.4% with knee OA, 58.8% with hand OA and 76.9% with FM. The proportion that had seen more than two physicians was lowest in those with hand OA (22.8%) and highest for those suffering from FM (42.3%). In total, 33.3% of the subjects in the sample had visited a physician for musculoskeletal problems in the past year. Subjects classified as having any of the target conditions consulted more frequently.

Q13c Results: Costs to patients Nunez et al. (2007) The mean out of pocket expenses costs (prescriptions or taxis to attend medical visits) for patients with knee OA was 23.71 Euros in the previous 6 months. In total direct non-medical costs per patient was 1234.87 Euros, which includes the costs of formal and informal help and out of pocket expenses.

Sicras-Mainar (2009) The mean annual direct ambulatory cost for patients with FM was 908.67 Euros.

Q13 Summary a) Costs to society 148 The proportion of people with chronic pain claiming disability allowance ranged from 2.2% RESULTS / EPIDEMIOLOGY OF CHRONIC of those with hand OA to 9.1% of those with RA. The yearly cost of paying disability com- NON-MALIGNANT PAIN IN SPAIN pensation for people with LBP was estimated at 209 666 pesetas. However, no studies were found that estimated the total costs for other chronic pain conditions.

b) Costs to healthcare system The percentage of patients with severe pain who had visited physician for their pain was high, ranging from 58.8% of patients with hand OA to 75.9% of patients with FM. The estimated cost of a visit to a GP was 79.8 Euros. The costs of technical procedures involved in treating their pain ranged from 2.52 Euros for blood tests to 27.35 Euros for an MRI scan. The mean annual direct ambulatory cost for patients with FM was 908.67Euros. For neuropathic pain the direct monthly total costs to the health care system was between 344 Euros and 376 Euros. These studies focused on specific pain conditions, and it is not possible to estimate the total costs to healthcare of chronic pain or other chronic pain conditions.

c) Costs to patients In general pain patients, the majority of people had out of pocket costs 1 to 100 Euros per month. For patients with knee OA, the mean out of pocket expenses costs 23.71 Euros in the previous 6 months and the costs for FM patients annually was 908.67Euros. Again, no studies were found addressing other chronic pain conditions, so it is not possible to estimate costs for these conditions.

Q14 What are issues/determinants of patients’ awareness of chronic pain?

We selected 5 studies that address this question: 3 studies in relation to patients attending pain clinics (Torre (2008), Fernandez (2007) and Soucase (2005)), and 2 studies on FM 149 (Ubago (2008), Garcia (2004)). RESULTS / EPIDEMIOLOGY OF CHRONIC Fernandez (2007) conducted a cross-sectional study on a sample of 92 patients attended in a NON-MALIGNANT PAIN IN SPAIN Pain Clinic, to investigate whether emotional alteration, and specifically stress, is associated with activity reduction and impact on the lives of people with chronic pain. Average score of pain level 67.7 in Visual Analogue Scale and 41.35 in Perceived Stress Scale.

Ubago (2008) was a telephone survey of people with FM in Granada, Spain. The objective of this study is to analyse the impact of FM on the functional capacity of patients suffering this syndrome and to identify factors that are associated with greater disease impact. FM impact was measured using the Fibromyalgia Impact Questionnaire (FIQ), in which FM patients typically score around 50, and 70 is considered a severe case.

Garcia (2004) conducted a small qualitative exploratory study on the experience of sexuality in 25 women affected by fibromyalgia, based on in-depth interviews to patients and focus groups.

150 Table 22: study characteristics and results of studies relevant to Question 14: issues/determinants of patients’ awareness of chronic pain

Study details Population Outcomes and analysis Results

Fernandez (2007) Type of chronic pain Outcomes Measured Patients with medium and high Not specified Association between emotional level of stress due to pain had very Study Design alteration and stress with activity much higher interference with Cross-sectional study Confirmation of diagnosis reduction and impact on the lives activity and daily functioning. Not specified of people with chronic pain Study Method Variables that predict more stress in Questionnaires answered by patients Sample Size and Demographics Pain Severity patients were intensity of pain, activity N = 92 Visual Analogue Scale (0-100) reduction and emotional affectation. Females: 59.8% West Have-Yale Multidimensional Mean Age: 53.8 years; range: 26-87. Pain Inventory

Patient Selection Analyses Random selection among people Descriptive attended in a Pain clinic Student t-test ANOVA Regression analysis

Soucase (2005) Type of chronic pain Outcomes Measured Patients perceived their pain as Somatic 54.4% Pain valuation, pain coping strategies exceeding their own coping resources Study Design Neuropathic 41.4% (pain coping questionnaire - PCQ), level and rated low their self-effectiveness Cross-sectional study of anxiety (STAI/R) and depression (BDI). in order to manage, control or relieve Confirmation of diagnosis pain, this being a disabling and Study Method Referred by patients Pain Severity limiting factor in their everyday life. Questionnaires answered by patients Visual Analogue Scale Sample Size and Demographics Most frequently used strategies for N = 168 Analyses coping with pain: self-assertion, Females: 71% Descriptive search for information Mean Age: 52.6 years; range: 20-77. X2 Religion. Student t-test Patient Selection Stepwise multiple regression Anxiety and depression scores People attended in a Pain clinic were moderate or high.

151 Study details Population Outcomes and analysis Results

Torre et al. (2008) Type of chronic pain Changes in health-related quality of life Improvement in the following domains Backbone pain ≈60%, fibromyalgia (HRQL), pain intensity, coping strategies (SF-36): physical role, corporal Study Design ≈20%, osteo-articular pain ≈10%, and anxiety/depression after six months. pain, vitality, mental health and the Cross-sectional survey neuropathic pain ≈3% Relation between HRQL, coping strategies, standard physical component. anxiety/depression and pain intensity HAD: anxiety values increased and Study Method Confirmation of diagnosis depression values decreased Questionnaire Referred by patients Pain Severity Negative association between Visual Analogue Scale quality of life with anxiety and Sample Size and Demographics Pain level: mean score in VAS depression and pain intensity N = 119 (93 completed questionnaires (0-10): 5.1 (SD. 1.9) Worst response to treatment at the beginning and 6 months later) was fibromyalgia patients Females: 62.2%, Analyses Mean Age: 55.1 years; range: 26-82. Descriptive X2 Patient Selection Student t-test Patients who go for the first Wilcoxon time to a Pain clinic Pearson correlation Older than 18 years, duration of pain longer than six months, non- cancer pain

152 Study details Population Outcomes and analysis Results

Ubago et al. (2008) Type of chronic pain Outcomes measured Average FIQ score for the sample was 63.6 FM FM impact -alteration in the functional Study Design capacity of patients diagnosed FIQ scores for clinical characteristics Cross-sectional survey Diagnostic criteria with FM, measured by (FIQ) Initial symptom: ACR criteria Bone and joint pain 61.42 Study Method Socio-demographic characteristics Tiredness 68.25 Telephone interview Sample size and demographics Job characteristics - present job situation Paraesthesia 67.81 N = 214 Clinical characteristics 92.1% female Health characteristics Symptom that most affects daily living: Mean age 46.9 (SD 9.5) Psycho-social characteristics Tiredness 67.51 Bone and joint pain 61.57 Subject selection Pain severity Depressed mood 68.11 Patients with FM. Not reported Excluded if had other health problems Self-rated health: Good 35.32 that affected their activities of Analyses Fair 58.22 daily living in the last week. contingency tables and the chi- Poor 67.81 square test, Student’s t test, analysis Very poor 71.07 of variance (ANOVA), Mann–Whitney and Kruskal–Wallis tests. Multivariate linear regression model.

Garcia (2004) Type of chronic pain Outcomes Measured Main disturbance is decrease of libido Fibromyalgia Experiences and opinions on due to fear of osteomuscular pain Study Design the experience of sexuality during the following days following Qualitative Confirmation of diagnosis sexual intercourse. Sexual activity Exploratory study By doctors, using American College Pain Severity was scarce and unsatisfactory. of Rheumatology criteria Not reported Study Method in-depth interviews to patients Sample Size and Demographics Analyses and focus groups N = 25 Descriptive Females: 100% Mean age: 49 years; range 28-67

Patient Selection Patients diagnosed of fibromyalgia in Aragon

153 RESULTS / EPIDEMIOLOGY OF CHRONIC Q14 Study quality NON-MALIGNANT PAIN IN SPAIN Fernandez (2007) was rated as medium quality. It did have a clear description of the study design and setting but did not included adequate description of eligibility criteria (including description of diagnostic criteria for chronic pain condition). It is unclear whether the study population is representative of the target population. There was an adequate description of outcomes and the study participants. It was unclear the description of statistical methods (including the description of potential confounders and effect modifiers and how they were dealt with). Results were not presented as unadjusted and confounder-adjusted including precision.

Soucase (2005) was rated as medium quality. It did have a clear description of the study design and setting but did not included adequate description of eligibility criteria (including description of diagnostic criteria for chronic pain condition). It is unclear whether the study population is representative of the target population. There was an adequate description of outcomes and of statistical methods, but not of the study participants. Results were not presented as unadjusted and confounder-adjusted including precision

Torre (2008) was rated as medium quality. It did have a clear description of the study design and setting, but did not included adequate description of eligibility criteria (including description of diagnostic criteria for chronic pain condition). It is unclear whether the study population is representative of the target population. There was an adequate description of outcomes, of statistical methods, and of the study participants. Loss to follow-up was bigger than 10% at 6 months (21.8%). Results were not presented as unadjusted and confounder- adjusted including precision.

Ubago (2008) was rated as medium quality, it was unclear if the population was representative 154 of the target population and there was not an adequate description of the eligibility criteria. RESULTS / EPIDEMIOLOGY OF CHRONIC Garcia (2004) was rated as high quality. It did have a clear description of the study design NON-MALIGNANT PAIN IN SPAIN and setting, and eligibility criteria. It is unclear whether the study population is representative of the target population. There was an adequate description of outcomes and the study participants. Methods of data summary were described and sound.

Q14 Results Fernandez (2007) Compared with patients with low levels of stress, patients with medium and high level of stress due to pain had very much higher interference with activity and daily functioning; however, there were not significant differences on activity and daily functioning between patients with medium or high level of stress. Variables that predict more stress in patients were intensity of pain, activity reduction and emotional affectation.

Soucase (2005) On a descriptive level, patients perceived their pain as exceeding their own coping resources and rated low their self-effectiveness in order to manage, control or relieve pain, this being a disabling and limiting factor in their everyday life. The most frequently used strategies for coping with pain were self-assertion, search of information and religion, and their anxiety and depression scores were moderate or high. On a predictive level, the emotional repression was the most relevant variable for predicting anxiety and the feeling of loss was the most relevant variable for predicting depression (things that could be done and enjoyed in the past, but not anymore).

Torre (2008) 93 patients completed the questionnaires, at the beginning and 6 months later. As measured by SF-36 there was significant improvement in following domains: physical role, corporal pain, vitality, mental health and the standard physical component. In the HAD, anxiety values increased and depression values decreased in a no significant mode. Pain intensity was moderate, and decreased in a no significant mode. At the first visit, cop- 155 ing strategies more used were self-affirmation and the look for information; 6 months later, RESULTS / EPIDEMIOLOGY OF CHRONIC active coping strategies were more used. There was a negative association between quality NON-MALIGNANT PAIN IN SPAIN of life with anxiety and depression and pain intensity. The group with worst response to treatment was fibromyalgia patients.

Ubago (2008) found that FM had a greater impact on patients with initial symptoms of tiredness and paraesthesia (FIQ scores of 68.25 and 67.81 respectively) than on those with bone and joint pain (FIQ score 61.42, p<0.01). Similarly, patients who complained that tiredness and depressed mood (FIQ 68.11) were the symptoms that most affected their daily life (p<0.01) and those that had a poor perception of their health (poor health FIQ score 67.81 and very poor health FIQ score 71.07) had higher FIQ scores.

Garcia (2004) The main disturbance is decrease of libido due to fear of osteomuscular pain during the following days following sexual intercourse. Sexual activity was scarce and unsatisfactory. The problem affects couple relationships at the beginning but not at medium-long term. This subject is not spoken with doctors at consultation.

Q14 Summary For patients attending pain clinics, the higher their stress levels, the higher the level of interference of their pain in their lives. They also felt that their pain exceeded their coping resources and became disabling for them. After 6 months treatment, patients used more active coping mechanisms. For patients with FM, the impact of the disease depended on their symptoms, those with tiredness and paraesthesia felt more of an impact. FM patients also experience a decrease in libido, an issue that it seldom discussed with their doctors. Overall, study quality was medium to high. However, it was not clear whether any of the studies were representative of the Spanish population.

156 RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Q15 what are issues/determinants of health care professionals’ awareness of chronic pain?

Two studies were found that addressed this question, one reviews chronic pain management and the other is a study of patients with OA.

Garcia-Martinez (2000) conducted a survey to review chronic pain management in primary health care (PHC), to assess coordination between the Pain Management Units (PMU) and PHC, and to identify barriers to such coordination, to make proposals to eliminate such barriers and enable coordination in order to ensure an appropriate home care follow-up for the management of chronic pain.

Collantes-Estevez et al. (2003) is a multicentre study conducted by primary care physicians across Spain to investigate the effect of a switch from celecoxib to rofecoxib in patients with osteoarthritis. Both patients and physicians filled out questionnaires before and after the switch, which measured patients OA related health status and satisfaction with therapy, use of gastroprotective medications and physicians’ impressions of patients’ status.

157 Table 23: Study characteristics and results of studies relevant to Question 15: issues / determinants of health care professionals’ awareness of chronic pain

Study details Population Outcomes and analysis Results

Garcia-Martinez 2000 Type of chronic pain Outcomes Measured PHC: Not applicable Chronic pain management in There was a lack of knowledge about the Study Design primary health care (PHC) functioning and, sometimes even about Qualitative Confirmation of diagnosis Lack of coordination between the the existence of the Pain Management Unit Cross-sectional survey Not applicable Pain Management Units (PMU) (PMU), as well as a poor training of the and PHC and identification of PHC physicians in pain-related issues. Study Method Sample Size and Demographics barriers to such coordination. Questionnaire to general practitioners, N= 96 general practitioners Issues with diagnoses due to: managers of hospital Pain Units, 3 managers of hospital Pain Units, Pain Severity further explorations are not allowed or and managers of GP teams. and 3 managers of GP teams Not applicable make the visit too lengthy and long waiting Analysis of results and discussion of Demographic data not presented lists for the access to different specialties discordant results among groups and Analyses elaboration of proposals for improvement Patient Selection Descriptive Not applicable Study on GPs and managers opinions

Collantes-Esterez et al. (2003) Type of chronic pain Outcomes Measured Aspects of the clinical effect of rofecoxib OA OA related health status and remarked upon by physicians: Study Design satisfaction with therapy. Pain control for 24 hours, increased Longitudinal Diagnostic criteria Perception of stiffness, night pain, functional capacity, reduced morning NR anxiety, depression, use of concomitant stiffness, control of night pain, satisfaction Study Method gastroprotective medications (GPMs). with treatment expressed by the patient. Questionnaires answered by patients Sample size and demographics Physicians' impressions of patients' status. Subject selection N=2228 Pain Severity 66.5% women NR

Analyses McNemar test, Fisher exact tests, logistic regression

158 RESULTS / EPIDEMIOLOGY OF CHRONIC Q15 Study Quality NON-MALIGNANT PAIN IN SPAIN Garcia-Martinez (2000) was rated as low quality. It did have a clear description of the study design and setting. There was neither adequate description of eligibility criteria (incl. description of diagnostic criteria for chronic pain condition) nor of the study participants. It is unclear whether the study population is representative of the target population. It is also unclear whether there was an adequate description of outcomes and the study participants. It is unclear the way methods of data summary were described and if they were sound.

Collantes-Estevez (2003) was rated as medium quality. It did not have an adequate description of the eligibility criteria or of losses to follow-up, and it is unclear if the participants were representative of the target population.

Q15 Results Garcia-Martinez (2000) The survey found a high prevalence of patients with pain at the primary health care (PHC) centres, and great difficulties for the establishment of etiological diagnosis, since further explorations are not allowed or make the visit too lengthy and long waiting lists for the access to different specialties. It was reported a lack of knowledge about the functioning and, sometimes even about the existence of the Pain Management Unit (PMU) itself at the PHC level, as well as a poor training of the PHC physicians in pain-related issues, despite their interest in their own training and the coordination of their work with the PMU. Responses of PHC physicians contrast with those of PMU managers and district managers, who offer easy access to their PMU for the PHC physicians and the possibility to organize and participate in training and on-the-job training courses, and provide support for a coordinated health care.

Collantes-Estevez (2003) This study reported aspects of the clinical effect of rofecoxib 159 remarked upon by physicians during the trial period. These include pain control for 24 RESULTS / EPIDEMIOLOGY OF CHRONIC hours, increased functional capacity, reduced morning stiffness, control of night pain, and NON-MALIGNANT PAIN IN SPAIN satisfaction with treatment expressed by the patient. However, the results are specific to the trial, which investigates the effects of a switch from celecoxib to rofecoxib and it is unclear whether they can be extrapolated to other pain patients.

Q15 Summary In Spanish primary healthcare it was found that there was generally a lack of knowledge about pain management units, a lack of training for physicians in pain-related issues and issues with diagnosis of pain conditions. Although physicians may be aware of chronic pain, its diagnosis and treatment were found to be lacking. Some aspects that may be relevant to physicians in the treatment and management of chronic pain were reported in a trial of pain medications, but this was not representative of the Spanish population. The first paper was also not representative and was rated as low quality. Little information was found in answer to this question, and it is difficult to draw conclusions from the included studies.

Q16. What are the main symptoms and complaints with which patients present themselves to health care professionals?

We selected 4 studies that addressed this question. Rodriguez et al. (2006) reports on patients attending Spain Pain Units with chronic non-cancer pain. Gamero et al. (2004) focuses on rheumatologic pain, Miro et al. (2007) on older adults and Arboleya et al. (2003a) on osteoarthritis.

Rodriguez et al. (2006) aimed to survey the degree of compliance with the WHO Anal- 160 gesic Ladder recommendations for the treatment of chronic non-cancer pain in patients RESULTS / EPIDEMIOLOGY OF CHRONIC attending Spanish Pain Units. The study was performed by the Spanish Pain Society (STEP NON-MALIGNANT PAIN IN SPAIN study).

Gamero et al. (2005) conducted a cross sectional study to establish the prevalence and characteristics of rheumatologic pain in a random sample of 1,134 adult outpatients in waiting list to be attended in specialized rheumatology offices of public Spanish hospitals.

The aim of Miro et al. (2007) was to gather information on the prevalence of pain and chronic pain in older adults in Catalonia, Spain, a representative sample of adults aged 65 years and over were interviewed about their pain.

Arboleya et al. (2003a) reports on phase 1 of the VICOXX study, which aimed to investigate the use of traditional non-steroidal anti-inflammatory drugs (tNSAIDs) in the management of osteoarthritis (OA) in primary care in Spain and to quantify patient and physician satisfaction with tNSAID therapy using data from the medical records of OA patients in primary care centres across Spain for the previous 6 months.

161 Table 24: Characteristics and results of studies relevant to Question 16: the main symptoms and complaints with which patients present themselves to health care professionals

Study details Population Outcomes and analysis Results

Rodriguez et Type of chronic pain Outcomes measured Most frequent symptoms associated al. (2006) General non-cancer pain treatment according to WHO ladder with chronic pain: demographic characteristics sleeping disorder 50%, Study Design Diagnostic criteria pain history depression 48%, anxiety 47% Cross-sectional Not reported visual analogue scale irritability 30% survey previous treatments Sample size and demographics change of treatment Study Method N = 580 quality of life Questionnaire Mean age 51 to 60 years adverse events 70% women economic impact of pain

162 Study details Population Outcomes and analysis Results

Gamero et al. (2005) Type of chronic pain Outcomes Measured Most frequent Musculoskeletal pain, fibromyalgia Reason for consultation (new patient or patient pathologies that caused consultation: Study Design for revision), characteristics of the patient (sex, New patients, arthrosis 31.2% Cross-sectional study Confirmation of diagnosis age, habits [alcohol/tobacco], marital status), extra-articular rheumatism 19.9% vertebral By the doctor location, type, intensity, duration, tolerance and pains 18.8% fibromyalgia 17.7% Study Method management of pain; treatment; satisfaction with Clinical interview Sample Size and Demographics the treatment; and association with fibromyalgia. Patients for revision, arthrosis 29.1% N = 1,134 inflammatory arthropaty 20.9% extra-articular New patients: 368 Pain Severity rheumatism 14% vertebral pains 12.4%. Patients for revision: 782 Visual Analogue Scale Females: 71.6%, Brief Questionnaire for Pain Evaluation (BPI) In males, Age: the bigger group 45-65 years chronic inflammatory arthropathy 26.9% Analyses arthrosis 20% ankylosing spondylitis 15.1% Patient Selection Descriptive extra-articular rheumatism 14.4% 1,134 adult outpatients in waiting list to X2 for comparing qualitative variables be attended in specialized rheumatology and Student t-test and analysis of In women, offices of public Spanish hospitals variance for quantitative variables. arthrosis 33.9% fibromyalgia 16.4% inflammatory arthropathy 21.9% extra- articular rheumatism 16.8%

Miro et al. (2007) Type of chronic pain Outcomes measured % of patients reporting most General non-cancer pain Pain prevalence, number and location of bothersome painful region: Study Design pain sites, onset, intensity of pain, number Head 3.8% Cross-sectional Diagnostic criteria of days of pain, pain severity, interference Cervical region 6.1% survey Not reported with everyday life, level of expressed need Upper limbs 4.2% Thoracic region 2.4% Study Method Sample size and demographics Pain severity Abdominal region 2.8% Interviews N = 592 Chronic pain grade questionnaire Lower back 23.8% 274 men, 318 women Hip 9% Analyses Foot 4.5% Patient selection Descriptive statistics Joints 24.1% Aged over 65 years, living in Catalonia Lower limbs 14.6%

163 Study details Population Outcomes and analysis Results

Arboleya et Type of chronic pain Outcomes measured Symptoms n (%) al. (2003a) OA tNSAID treatment and discontinuation, Men: other treatments for OA, satisfaction with Pain 210 (99.5) Study Design Diagnostic criteria OA treatment, GI adverse effects and Joint stiffness 147 (69.7) Cross-sectional Radiologically confirmed gastroprotective medication used. Joint effusion 23 (10.9) survey Other 10 (4.7) Sample size and demographics Pain severity Study Method N = 897 NR Women: Retrospective, Mean age 66 years (SD = 9) Pain 680 (99.4) observational, 76% women Analyses Joint stiffness 523 (76.5) multicentre Descriptive statistics, Fisher’s Joint effusion 86 (12.6) study conducted Patient selection exact test, chi-squared test. Other 42 (6.1) by interview. Adults over 18 years with radiologically confirmed OA, using tNSAIDS

Q16 Study Quality Arboleya et al. (2003a) was rated as medium quality as it was unclear whether the population represented the target population. Gamero (2005) was rated as high quality, fulfilling all the criteria. Miro et al. (2007) was rated as medium quality, as the eligibility criteria were not clearly stated and the description of the statistical analyses was inadequate. Rodriguez et al. (2006) was also rated as medium; the eligibility criteria and outcomes were not clearly described, and it was unclear whether the study population represents the target population.

Q16 Results Rodiguez et al. (2006) The most frequent symptoms associated with chronic pain reported by patients visiting pain units were sleeping disorder 50%, depression 48%, anxiety 47% and 164 irritability 30%. RESULTS / EPIDEMIOLOGY OF CHRONIC Gamero (2005) The most frequent pathologies that caused consultation in new patients, NON-MALIGNANT PAIN IN SPAIN was arthrosis (31.2%), extra-articular rheumatism (19.9%), vertebral pains (18.8%) and fibromyalgia (17.7%); in patients for revision, arthrosis (29.1%), inflammatory arthropaty (20.9%), extra-articular rheumatism (14%) and vertebral pains (12.4%). In males, the most frequent pathologies were chronic inflammatory arthropathy (26.9%), arthrosis (20%), ankylosing spondylitis (15.1%) and extra-articular rheumatism (14.4%; in women, arthrosis (33.9%), fibromyalgia (16.4%), inflammatory arthropathy (21.9%) and extra-articular rheumatism (16.8%).

Figure 25: Reasons for consultation

ArtHROSIS 35,00% EXTRA-AURICULAR RHEUMATISM

30,00% VERTEBRAL PAINS

FIBROMYALGIA 25,00% INFLAMMATORY ARTHROPATHY

20,00%

15,00%

10,00%

5,00%

0,00% new patients repeat visits 165 RESULTS / EPIDEMIOLOGY OF CHRONIC Miro et al. (2007) Overall, older adults reported that joint and back regions were the most NON-MALIGNANT PAIN IN SPAIN bothersome pain sites. 23.8% reported the lower back as their most painful region and 24.1% their joints. 14.6% reported their lower limbs as the most painful, 9% their hip region and 6.1% their cervical region.

Arboleya et al. (2003a) For OA patients, the main symptom for almost all men and women was pain (99.5% and 99.4% respectively). The next most common symptom was joint stiffness, which 76.5% of women presented with, but slightly less men, 69.7%. Joint effusion was less common for both men and women (10.9% and 12.6% respectively).

Q16 Summary Only one of the studies was representative of the Spanish population, however this study reported the most painful locations that patients present with, and not symptoms directly. The other studies focused on different types of chronic pain and were not representative, so it is difficult to generalise the results to the general Spanish pain population. For OA sufferers and elderly people, pain was the main symptom, as well as joint stiffness. Patients at a pain unit in Spain had sleeping and mood disorders reported as their main symptoms.

Q17 and Q19: What are the frequencies of drug (per WHO class), non-drug, and combined treatments and what are determinants of treatment choice within drug treatments?

We selected 5 studies that address these questions and present them together as there is some overlap between the questions. 2 studies refer to general non-cancer pain, one for 166 osteomuscular pain, one is set in a rheumatological clinic and another in a pain clinic. RESULTS / EPIDEMIOLOGY OF CHRONIC The first study was a large-scale computer-assisted telephone survey that explored the NON-MALIGNANT PAIN IN SPAIN prevalence, severity, treatment and impact of chronic pain in 15 European countries and Israel (Breivik et al. (2006)). Screening interviews identified respondents’ aged ≥18 years with chronic pain for further, in-depth interviews. The data is reported here is specifically for Spain.

Gamero et al. (2005) conducted a cross sectional study to establish the prevalence and characteristics of rheumatologic pain in a random sample of 1,134 adult outpatients on a waiting list to attend specialized rheumatology offices of public Spanish hospitals.

Ribera (2007) conducted a descriptive study on patients with pain that could be amenable of treatment with opioids, attended by 107 specialists from Pain Units all over Spain. The study collected demographic data, reason for consultation, background disease, time elapsed from diagnosis, treatment and pain intensity, as scored by a visual analogue scale (VAS).

167 Table 25. Characteristics and results of studies relevant to Questions 17 and 19: frequency of treatments and determinants of drug treatments

Study details Population Outcomes and analysis Results

Breivik (2006) Type of chronic pain Outcomes measured Frequencies of treatments: General chronic pain Treatments including prescription Answers to question: “Which prescription Study Design and non-prescription medicines and pain medicines are you currently taking for Cross-sectional survey Confirmation of diagnosis non-medication strategies. the specific pain we have been discussing?” Not reported (164 respondents) Study Method Pain severity Large scale Sample size and demographics 10-point Numeric Rating Scale (NRS) NSAID 49% computer-assisted Total n = 3801 Weak opioid 13% telephone survey Chronic pain n = 301 Analyses Strong opioid 1% Mean age chronic pain 50.7 years, 52% female Descriptive statistics Paracetamol 8% COX-2 inhibitor 2% Patient selection Any pain lasting at least 6 months, had experienced pain in the last month, and experienced pain at least two times per week

168 Study details Population Outcomes and analysis Results

Rodriguez et al. (2006) Type of chronic pain Outcomes measured Frequencies of treatments: General non-cancer pain treatment according to WHO ladder Level I non-opioid analgesics: Study Design demographic characteristics NSAIDs 76% of the patients, paracetamol Cross-sectional survey Diagnostic criteria pain history 53% and metamizol 36%. Not reported visual analogue scale Level II: tramadol 89% of patients Study Method previous treatments using weak opioids. Questionnaire Sample size and demographics change of treatment Level III fentanyl (63% of patients using N = 580 quality of life strong opioids), buprenorphine (27%), oral Mean age 51 to 60 years adverse events morphine (19%) and oxycodone (3%). 70% women economic impact of pain Level III drug were used in 28% of the patients.

Subject selection Pain severity 70% of the patients drug prescription was adult patients (> 18 years-old) with VAS changed due to inadequate pain control. 93% chronic non-cancer pain (> 6 months) received pharmacological treatment and in attending Spanish Pain Units Analyses 51% of them also another treatment (blocks descriptive analysis (mean/median + SD 33%, rehabilitation 27% and TENS 24%). and chi-square), t-student and ANOVA Coadjutant medication: antidepressants (52%), anticonvulsants (50%) and anxiolytics (47%).

Noceda et al. (2007) Type of chronic pain Outcomes measured Frequencies of treatments: Osteomuscular Use of analgesics for pain according WHO level 1: 54.7% Study Design to age, sex, level of education. Level 2: 6.6% Cross-sectional, Diagnostic criteria observational, Not reported Pain severity Determinants of drug treatment descriptive study VAS Sex: women: 61.2% first step drugs, Sample size and demographics 4.9% second step drugs Study Method N = 320 Analyses 33.9% no drug; Personal interviews ANOVA and chi-squared Subject selection men: 33.3% first step drugs, 12% Patients with osteomuscular pain using second step drugs 54.7% no drug analgesics according to WHO classes educational background: higher educational level: 32.5% first step drugs,22.5% second step drugs, 45% no drug;

lower educational level: 57.9% first step drugs, 4.3% second step drugs and 37.8%no drug

169 patients’ activity among active workers 47.5% was taking first level drugs and 52.5% no drug Study details Population Outcomes and analysis Results

Gamero et al. (2005) Type of chronic pain Outcomes Measured Frequencies of treatments: Musculoskeletal pain, fibromyalgia Reason for consultation (new patient or patient Overall 57.6% of patients were Study Design for revision), characteristics of the patient, receiving NSAIDs; 6.4% opioids Cross-sectional study Confirmation of diagnosis location, type, intensity, duration, tolerance and By the doctor management of pain; treatment; satisfaction with In new patients: Study Method the treatment; and association with fibromyalgia. NSAIDs 51.1% paracetamol 31.8% opioids 3.0% Clinical interview Sample Size and Demographics Non-pharmalogical treatments overall 34.9% N = 1,134 Pain Severity Massage 14.9% New patients: 368 Visual Analogue Scale Rehabilitation 7.5% Patients for revision: 782 Brief Questionnaire for Pain Evaluation (BPI) Females: 71.6%, Patients for review: Age: the bigger group 45-65 years Analyses NSAIDs 60.6% Descriptive Paracetamol 29.4% Patient Selection X2 for comparing qualitative variables Opioids 7.1% 1,134 adult outpatients in waiting list to and Student t-test and analysis of Non-pharmalogical treatments overall 33.1% be attended in specialized rheumatology variance for quantitative variables. Massage 8.9% offices of public Spanish hospitals Rehabilitation 7.9%

Ribera (2007) Type of chronic pain Outcomes Measured Frequencies of treatments: General non-cancer pain Reason for consultation, the background disease Analgesics 96%: Study Design of pain, time elapsed from diagnosis, treatment. Level 1 28.6% Cross-sectional Confirmation of diagnosis Demographic variables. Minor opioids 43.6% By the doctors Major opioids 36.9% Study Method Criteria not specified Pain Severity Questionnaire Measured by a visual analogue scale (VAS). Determinants of drug treatment to specialists of Sample Size and Demographics In 61.9% of cases, the reason for the change in Pain Units N = 1077 Analyses opioid was inefficacy of the previous treatment Females: 57.8%, Descriptive Age: 74.5% older than 50 years

Patient Selection Patients attended by 107 specialists of Pain Units all over Spain. Each specialist included an average of 10.1 patients that could be amenable of treatment with opioids.

170 RESULTS / EPIDEMIOLOGY OF CHRONIC Q17 Study Quality NON-MALIGNANT PAIN IN SPAIN Breivik (2006) was rated as medium quality. Most criteria were met, however, the description of study participants was not clear enough. There was also no description of the statistical methods used.

Rodriguez (2006) was also rated as medium; it did have an adequate description of study design and setting, statistical methods and study participants. It was unclear the description of eligibility criteria and whether study population is representative of target population and the description of outcomes (and how / how often measured), exposures, predictors. Results were not reported as unadjusted and confounder-adjusted including precision.

Gamero (2005) This cross-sectional study was rated as high quality. It did have an adequate description in almost all areas assessed: study design and setting, eligibility criteria, description of outcomes, statistical methods and study participants. The study population is representative of target population. Results were not reported as unadjusted and confounder-adjusted including precision.

Ribera (2007) was rated as low quality. It did have a clear description of the study design and setting but did not included adequate description of eligibility criteria (including description of diagnostic criteria for chronic pain condition). It is unclear whether the study population is representative of the target population. There was adequate description of out- 171 comes and study participants. There was no adequate description of statistical methods (incl. RESULTS / EPIDEMIOLOGY OF CHRONIC the description of potential confounders and effect modifiers and how they were dealt with). NON-MALIGNANT PAIN IN SPAIN Results were not presented as unadjusted and confounder-adjusted including precision.

Q17 Results Breivil (2006) In response to the question “Which prescription pain medicines are you currently taking for the specific pain we have been discussing?” 49% of the 164 respondents were using NSAIDS, 13% weak opioids, 1% strong opioids, 8% paracetamol and 2% COX-2 inhibitors.

Gamero (2005) In patients with musculoskeletal pain and FM, overall 57.6% of patients were receiving NSAIDs and opioids were used in 6.4% of patients. Most used pharmacological treatments (new patients/patients for revision) which were NSAIDs (51.1%/60.6%), paracetamol (31.8%/29.4%) and opioids (3.0%/7.1%).

Rodriguez (2006) 96% of the patients had received analgesic treatment. Drugs used: Level I non-opioids analgesics: NSAIDs 76% of the patients, paracetamol 53% and metamizol 36%. Level II: tramadol 89% of patients using weak opioids. Level III fentanyl (63% of patients using strong opioids), buprenorphine (27%), oral morphine (19%) and oxycodone (3%). Level III drug were used in 28% of the patients.

In 70% of the patients drug prescription was changed due to inadequate pain control. After those changes, 93% received pharmacological treatment and in 51% of them also another treatment (blocks 33%, rehabilitation 27% and TENS 24%). Coadjutant medication: antidepressants (52%), anticonvulsants (50%) and anxiolytics (47%).

Ribera (2007) 96.1% of the patients received analgesics. Of these, 28.6% were using first step 172 of the ladder analgesics, 43.6% were prescribed minor opioids (95.5% tramadol), while 36.9% RESULTS / EPIDEMIOLOGY OF CHRONIC were receiving major opioids. A total of 77.3% of the patients receiving tramadol used doses NON-MALIGNANT PAIN IN SPAIN in excess of 150 mg/day.

Noceda (2007) 38.7% percent of the patients did not take medication to control pain or did at insufficient doses; 54.7% used drugs of the first step of the WHO and 6.6%, of the second. There were no patients in treatment with strong opioids.

Gamero (2005) Most used treatment was pharmacological; overall 57.6% of patients were receiving NSAIDs; opioids were used in 6.4% of patients. Most used pharmacological treatments (new patients/patients for revision) were NSAIDs (51.1%/60.6%), paracetamol (31.8%/29.4%) and opioids (3.0%/7.1%). Non-pharmacological treatments: overall (34.9%/33.1%), massage (14.9%/8.9%), and rehabilitation (7.5%/7.9%). Percentages of drug type used for different diagnosis are presented in table 25, both for patients newly diagnosed and for patients for revision.

173 Table 26. Percentages of drug type used for different diagnosis for patients newly diagnosed and patients for revision

Patients with new diagnosis Patients for revision

Disease NSAIDs Paracetamol Metamizol Opioids NSAIDs Paracetamol Metamizol Opioids

Inflamatory 53.3 36.7 13.3 - 72.4 18.8 5 6.7 arthropaty

Espondilitis 65.2 13 8.7 - 79.7 15.6 1.6 6.2

Arthrosis 55.4 36.6 6.2 3.6 68.2 39.8 5.6 6.9

Methabolic 68.2 27.7 4.6 4.6 48.9 23.4 6.4 3.1 disease

Vertebral pain 44.8 41.8 6 4,5 35.2 61.5 11 4.4

Extraarticular 53.5 26.8 26.8 - 33.6 51 6.7 1.9 pathologies

Vertebral fracture 50 45 5 - 53.3 50 6.7 16.7

Fibromyalgia 33.3 42.9 4.8 6.3 41.3 46.7 16 20

Q19 Results Ribera (2007) In this study, 47.2% of the patients presented a pain VAS score of over 7. In those situations where a change in opioid proved necessary, fentanyl TTS was introduced in 75.3% of cases. In 61.9% of cases, the reason for the change was inefficacy of the previous 174 treatment. RESULTS / EPIDEMIOLOGY OF CHRONIC Noceda (2007) Significant differences of type of different analgesic treatment prescribed NON-MALIGNANT PAIN IN SPAIN depending on sex (women: 61.2% first step drugs, 4.9% second step drugs and 33.9%no drug; men: 33.3% first step drugs, 12% second step drugs and 54.7%no drug), educational background (higher educational level: 32.5% first step drugs, 22.5% second step drugs and 45%no drug; lower educational level: 57.9% first step drugs, 4.3% second step drugs and 37.8%no drug) and patients’ activity (among active workers 47.5% was taking first level drugs and 52.5% no drug).

The characteristics of chronic pain (aetiology and duration of symptoms) also affected the therapy decision. Among patients with arthrosis 40.8% did not take any analgesic, 52.7% uses first step drugs and 6.5% second step drugs. Among patients with osteoporosis 29.6% did not take any analgesic, 63% uses first step drugs and 7.4% second step drugs. Among patients with rheumatoid arthritis 22.2% did not take any analgesic, and the rest used only first step drugs. Among patients with lumbalgia 42.6% did not take any analgesic, 48.9% uses first step drugs and 8.5% second step drugs.

Q17 and 19 Summary The quality of the included studies was varied, and only one of these was representative of the Spanish population (Breivik (2006)). The results here should be considered with caution. The included studies cover most types of chronic pain: general non-cancer pain, patients in pain clinics, osteomuscular, rheumatic and musculoskeletal pain. The proportion of patients taking each WHO level of drugs varies across studies and type of pain. Only 2 studies give results relevant to Q19, and only one of these directly addresses the question.

175 RESULTS / EPIDEMIOLOGY OF CHRONIC NON-MALIGNANT PAIN IN SPAIN Q18 What are the determinants of treatment choice between drug and non-drug treatments?

No studies were found that addressed this question.

Q21 What is patients’ satisfaction about drug treatments?

We located 4 studies that addressed this question. Of these, 2 gave results for general pain patients, Canellas et al. (1996) reported on general pain in nursing home residents and Gil Gregorio et al. (2007) on elderly patients in a primary care setting. One study reports on a specific pain condition: osteoarthritis, in the VICOXX study (Arboleya et al. (2003a) and (2003b)).

Cañellas et al. (1996) conducted a cross-sectional study on 74 patients institutionalised in nursing homes to determine the characteristics of pain complaints and analgesic treatment, as well as the satisfaction degree of patients with their treatment.

The aim of Gil Gregorio et al. (1996) was to obtain information concerning type, clinical evaluation and therapeutic management of pain in elderly people in a primary care setting. Participants aged over 65 years were recruited by 213 GPs across Spain.

The aim of the VICOXX study was to provide insights into the management of OA in primary care throughout mainland Spain. Arboleya et al. (2003a) reports on phase 1, which investigated the use of traditional non-steroidal anti-inflammatory drugs (tNSAIDs) in the 176 management of osteoarthritis (OA) in primary care in Spain and to quantify patient and RESULTS / EPIDEMIOLOGY OF CHRONIC physician satisfaction with tNSAID therapy using data from the medical records of OA NON-MALIGNANT PAIN IN SPAIN patients in primary care centres across Spain for the previous 6 months. Phase 2 compared patient and physician attitudes to osteoarthritis treatment with rofecoxib to NSAIDS and was a 6 month prospective analysis of a sample of patients from phase 1.

Table 27. Table: Characteristics of the studies relevant to Question 21

Study details Population Outcomes and analysis Results

Gil Gregorio (1996) Type of chronic pain Outcomes measured The level of patient satisfaction with pain was General chronic pain. Overall main types: Demographic and clinical data, diagnosis control was: very good in 2.5%, good in 27.8%, Study Design degenerative (71.8%), inflammatory of pain pathology, treatment used and regular in 46.2% and bad/very bad in 23.5%. Cross-sectional (20.0%) and traumatism (11.9%). its effectiveness/satisfaction and use of survey healthcare resources all recorded by GPs. Diagnostic criteria Study Method Diagnosis of pathology of pain made Pain severity Data recorded by GPs by GP. Criteria not reported. VAS Scale Mean VAS 7.1 ± 1.3 Sample size and demographics N = 1120 Analyses Females 59.7% Descriptive. Comparison between Mean age: 74.5 ± 6.2 in women, 73.2 ± 5.9 in men and within groups.

Patient selection Elderly patients, attended in primary care by 312 general practitioners, with pain as main or secondary symptom

177 Study details Population Outcomes and analysis Results

Type of chronic pain Outcomes Measured Satisfaction with the analgesic treatment, Cañellas (1996) 56.8% longer than 1 month Pain (intensity, location, duration, and aetiology), 18% were “unsatisfied” or “very much Pain in limbs (70.1%), neuralgia treatment (type of drug, way of administration, unsatisfied”; the rest, 82%, were from “low Study Design (4.1%), traumatism (2.7%) doses prescribed and taken, compliance) satisfaction” to high satisfaction”. Observational and patient satisfaction with treatment. cross-sectional Confirmation of diagnosis By the doctor Pain Severity Study Method Measured by Visual Analogical Scale (0-10), by Sample Size and Demographics verbal scale (no pain, mild, moderate, intense, A researcher N = 74 unbearable) and by a scale of facial expressions. Interviewed the Females: 70.3% patients and Mean age: 75.5 ± 13.9 years; range 25-97. Analyses collected information Descriptive from medical records Patient Selection Random sample of patients taking analgesics in nursing homes in Barcelona

Arboleya (2003a) Type of chronic pain Outcomes measured 46% of patients and physicians were OA tNSAID treatment and discontinuation, not satisfied with OA treatment. Study Design other treatments for OA, satisfaction with Cross-sectional Diagnostic criteria OA treatment, GI adverse effects and 15.5% of patients and 8.5% of physicians survey Radiologically confirmed gastroprotective medication used. were highly dissatisfied

Study Method Sample size and demographics Pain severity Retrospective, N = 897 NR observational, Mean age 66 years (SD = 9) multicentre 76% women Analyses study conducted Descriptive statistics, Fisher’s by interview. Patient selection exact test, chi-squared test. Adults over 18 years with radiologically confirmed OA, using tNSAIDS

178 Study details Population Outcomes and analysis Results

Arboleya (2003b) Type of chronic pain Outcomes measured After switch to rofecoxib OA Patient and physician satisfaction with treatment, Substantial increase in proportion of Study Design Adherence to therapy patients who reported themselves as Longitudinal Diagnostic criteria Efficacy of treatment, patient and physician ‘somewhat satisfied’ and very satisfied. NR assessment of general health Study Method Use of analgesics and gastro-protective medication Approximately 66% of patients thought switch Patients at 29 Sample size and demographics Reasons for treatment discontinuation had increased satisfaction with treatment, primary-care N = 562 30% reported no change in satisfaction centres, from phase 67% women Pain severity and 7% preferred tNSAIDS to rofecoxib. 1 who were followed Mean age 67 ± 9 years WOMAC scale, which includes a pain dimension prospectively for a further 6 months Patient selection Analyses Radiologically confirmed diagnosis of OA, history Comparison pre- and post rofecoxib treatment. of OA at participating centre, using, or indication Chi-squared or Fisher’s exact test. Wilcoxon to use, oral tNSAIDs for OA at time of enrolment. signed-rank test and McNemar tests.

Q21 Study Quality The VICOXX study (Arboleya (2003a) and (2003b)) was rated as medium quality. It was unclear whether the population represented the target population and there was not an adequate description of the losses to follow-up in Phase 2. Gil Gregorio (2007) did not have an adequate description of the study participants and the study setting and design were not clear, it was rated as low. Canellas (1996) was rated as high quality.

Q21 Results VICOXX Study Phase 1 (Arboleya et al. (2003a)) reported patient and physician satisfaction with traditional NSAIDs treatment for OA in the 6 months previous to the study. 46% of patients and physicians were not satisfied with OA treatment, and 15.5% of patients and 179 8.5% of physicians were highly dissatisfied with treatment. RESULTS / EPIDEMIOLOGY OF CHRONIC Phase 2 compared patient satisfaction before and after a switch to rofecoxib from t NSAIDs. NON-MALIGNANT PAIN IN SPAIN The switch to rofecoxib led to a substantial increase in proportion of patients who reported themselves as ‘somewhat satisfied’ and ‘very satisfied’. Approximately 66% of patients thought switch had increased satisfaction with treatment, 30% reported no change in satisfaction and 7% preferred tNSAIDS to rofecoxib.

Gil Gregorio (2007) For elderly patients who attended primary care with pain as main or secondary symptom, the level of patient satisfaction with pain was control was: very good in 2.5%, good in 27.8%, regular in 46.2% and bad/very bad in 23.5%.

Canellas (1996) For patients in nursing homes, regarding satisfaction with the analgesic treatment, 18% were “unsatisfied” or “very much unsatisfied”; the rest, 82%, were from “low satisfaction” to “high satisfaction”.

Q21 Summary Overall, the majority of pain patients are either unsatisfied or highly unsatisfied with the treatment they receive to control their pain. For NSAID use in OA patients, 46% of patients and physicians were unsatisfied with the treatment, and 15.5% of patients were highly dissatisfied. In elderly patients with pain, most were patients reported their satisfaction as regular or bad/very bad. However, for patients in nursing homes using analgesics it is unclear the actual level of satisfaction as most respondents report low satisfaction to high satisfaction (and the rest unsatisfied or very much unsatisfied). The study quality was varied, with studies low to high quality, only one of which was representative of the Spanish population.

180 Overall summary table OVERALL SUMMARY TABLE / EPIDEMIOLOGY OF The study quality and results for each project question can be viewed in Table 28 along with CHRONIC NON-MALIGNANT PAIN IN SPAIN our concluding statements.

Table 28. Summary of study quality, results and concluding statements for project questions 2 through 21

Results Number of studies and Question quality (low, med, high) Chronic pain Moderate or severe chronic pain Moderate or severe chronic pain

2 – 19 studies relevant General chronic pain FM The study quality was varied for prevalence 12% 1.4 – 2.4% this question. Half the studies were of chronic 10 studies selected 65-74yrs 70.8% representative of the Spanish population, pain Breivik (2006) - med 75-84yrs 71.9% Osteoarthritis but estimates of the projected to the adult Miro (2007) - med ≥85yrs 72.1% Over 65 years 51% population should be treated with caution. Carmona (2001) – high Hand OA: 6.2% Bassols (2003) – med Back pain Knee OA: 10.2% Pinto-Meza (2006) – low Any in past 6 months (may Sicras-Mainar include acute pain) 50.9% RA (2009) – med 1 year 14.7% 0.5% Mas (2008) – high Lifetime 23.7% Espallargues Low back pain 14.8% Neuropathic pain (1996) – med 3.9% Fernandez-Lopez (2008) – high Montero Homs (2005) – med

3- incidence 1 study located Neuropathic pain Value is of limited applicability of chronic 77.2% > 6 months duration: to the general population. pain Montero Homs In patients attending neurology clinics, (2005) - med incidence was 1.24 (1.05-1.53).

182 Results Number of studies and Question quality (low, med, high) Chronic pain Moderate or severe chronic pain Moderate or severe chronic pain

4 - % 5 studies relevant Osteomuscular pain Non-cancer chronic pain: Only Perez (2009) was representative untreated Untreated:38.7% overall Untreated: 0.9% overall untreated of the Spanish population and reports 3 studies selected a low percentage of pain patients as Perez (2009) - med OA and RA: Inadequately treated: untreated. The other 2 studies report Nocedo (2007) – low Untreated: 15.1% (31/207) overall Pharmacological treatment only: much higher levels, but are low quality. Medina (1999) - low 66.1% overall Inadequately treated: 84.6% with pure NP Short acting NSAIDS: (96 patients) Non-pharmacological treatment only: 45.8% had insufficient doses 3.1% overall 3.1% had excessive doses

Long acting NSAIDS: (68 patients) 16.1% had insufficient doses 11.8% had excessive

5 - % who 16 studies relevant General chronic pain (includes cancer 2.1%) FM Only 1 study was high quality, for present Prevalence of FM estimated at FM. All studies were representative for pain 3 studies selected Elderly patients attending GP: 2.37% (95%CI: 1.53-3.21) of the Spanish population, but the treatment Mas (2008) - high Pain was the main reason for other two were low quality, and did Gil Gregorio (2007) – low consultation in 86.1% of the cases. 79% of FM patients had visited at least one not directly address the question. Carneado-Ruiz 74.7% of patients had already made physician for musculoskeletal symptoms (2005) – low consultations for the same reason before. in the last year, compared to 32.1% of In 67.7% of the patients pain non-FM individuals, and FM patients was classified as chronic had a median of 2 visits per year.

Neuropathic pain –patients visiting neurology department 1422 patients presented themselves. 113 were diagnosed with neuropathic pain 8%. The most common causes of NP were found to be trigeminal neuralgia, post-herpes neuralgia and diabetic polyneuropathy.

183 Results Number of studies and Question quality (low, med, high) Chronic pain Moderate or severe chronic pain Moderate or severe chronic pain

6 - % who 17 studies relevant Back pain (82% chronic): Osteoarthritis pain, Rheumatoid The results from Nunez, the highest gets treated, Visit to the physician 71.9% arthritis pain: quality study, were from a very specific broken down 3 studies selected Use of alternative medical treatments 24.7% 85.7% NSAID, 22.9% analgesics (usually pain population, and the only study that by treatment Bassols (2003) - med Physical therapy 22.7% (physical combined with NSAIDs), 5.7% gluco- was representative of the population, Medina (1999) - low exercises and electrotherapy) corticoids. In non-inflammatory diseases Medina (1999) was of low quality. It is Nunez (2007) - high Self-medication 14.6% (acetylsalicylic among treated: 63.5% NSAID, 24.7% therefore hard to draw conclusions. acid the most employed) analgesics, 17% glucocorticoids.

13.9% of those with back pain Knee OA grade IV: received no treatment 69% of patients visited a general practitioner, 40% a specialist, 26% other health care professionals 5% alternative Practitioners

13% of patients made no medical visits

7- % who 3 studies located: Non-cancer chronic pain OA pain: Due to the lack of high quality studies comply Arboleya (2003b) - med Tramadol treatment modified: Termination of tNSAID treatment: and the relatively small sample sizes with their Casals & Samper 51.3% due to lack of analgesic efficacy 47.7% was expiration of the current of the available studies it is unlikely treatment (2004) - low 24 (20.2%) due to secondary prescription, lack of efficacy (21.1%) these results can be viewed as 20 - Rodríguez (2001) - low or adverse effects and GI adverse events (5.3%). indicative of the Spanish population. compliance Tramadol was withdrawn in 24.4% / adherence to drug Transdermal fentanyl patch: treatments Side effects reasons for ceasing fentanyl therapy

184 Results Number of studies and Question quality (low, med, high) Chronic pain Moderate or severe chronic pain Moderate or severe chronic pain

8 – disease 42 studies relevant FM: General non-cancer pain: Study quality was medium or high, and duration of Duration: mean 9 to 13 years, Duration; mean 6.6 to 9.1 years, three of the studies were representative chronic pain 7 studies selected: Severity: 5.71 to 6.02 on the VAS score Severity: 44% of respondents reported of the Spanish population with had large conditions Breivik (2006) - med severe pain, with a mean VAS score sample sizes, the results can be viewed Torre (2008) - med OA and RA: ranging from 5.13 to 5.82 as representing the Spanish population. Rodriguez (2006) - Duration: mean 6 to 14.3 years Boyer (2009) - med Severity: 23-80% had moderate Espallargues or intense pain (1996) - med Battle-Gualda (2006) - high Pastor (1998) - med

9 – 55 studies relevant. Back pain: General non-cancer pain: The overall quality of these studies demographics mean age of 47.6 years 52-66% were women was medium to high and results of chronic women 60.7%, Mean age 51-57 years can be considered as representative pain 4 studies selected: manual workers 54.9% 93% lived with their family of the Spanish pain population. sufferers Casals (2004) – med less educated 71.1% 74.5% lived in an urban setting; Breivik (2006) – med 42% were overweight Bassols (2003) – med OA: 29% obese. Fernandez-Lopez more frequent in women, the elderly, in (2008) – high people with less than 8 years of formal education, from a low social class, in obese and in those with a physically demanding job.

185 Results Number of studies and Question quality (low, med, high) Chronic pain Moderate or severe chronic pain Moderate or severe chronic pain

10 – 51 studies relevant. Rheumatic: Hypertension was the most prevalent All the studies were representative of co-morbidities arterial hypertension7.21%, co-morbidity for all types of pain the Spanish pain population and were of chronic 4 studies selected: hypercholesterolemia 5.74%, digestive generally of high quality, the data can pain Loza (2008) - high diseases 4.61%, diabetes mellitus 2.55%, FM: therefore be considered as representing sufferers Mas (2008) – high cardiologic diseases 2.51%, pulmonary hypertension in 27.8-36.5%, the Spanish pain population. Battle-Gualda diseases 2.01% and allergies 1.96% psychiatric disease 32.0%, (2006) – high hypercholesterolemia 21.2-36.8%, neurologic Sicras-Mainar Osteoarthritus: diseases 16.0%, depression 11.5-42.4%, (2009) – med hypertension 57%, diabetes 8.5-9.6% myocardial infarction 3%, pulmonary diseases 9.6%. cardiac failure 7%, vascular disease 15%, cerebral vascular disease 5.4%, diabetes 19%, dementia 1.4% COPD 8%.

11 - 3 studies located Pain patients attending a pain clinic General non-cancer pain Soucase (2005) and Rodriguez (2006) inadequate Breivik (2006) – med Pain patients agreed more with the 67% of respondents did not have only indirectly address this question, pain control Rodriguez (2006) – med statements that their pain medication adequate pain control however, their results support the results Soucase (2005) – med rarely reduced or controlled their pain than 70% had changed drug prescription given by Breivik (2006), which was never reduced or controlled their pain. due to inadequate pain control also representative of the population. All studies are medium quality.

186 Results Number of studies and Question quality (low, med, high) Chronic pain Moderate or severe chronic pain Moderate or severe chronic pain

12 a – a - 33 studies relevant General chronic pain Knee OA Three of the included studies (Carmona impact of Patients with chronic pain scored worse than Factors associated with a worse HRQL: (2001), Nunez (2007) and Fernandez- chronic pain, 4 studies selected: non pain sufferers in all the SF36 domains. Female gender Lopez (2008)) were of high quality and quality of life EPISER study: Carmona Those with chronic pain scored worse Disease duration representative of the Spanish pain (2001) and Fernandez- than those with acute pain in all the SF36 Number of comorbidities population. Chronic pain can affect all Lopez (2008) – high domains, except for physical function Consumption of NSAIDS areas of quality of life for sufferers, Nunez (2007) – high and body pain (not significant). Dissatisfaction with current treatment although the affects can vary on the specific Lopez-Silva (2007) – low dimensions of quality of life depending Musculoskeletal diseases (Carmona (2001)) Factors associated with an increased HRQL: on the type of pain, gender, age, disease Effect on Functional capacity (HAQ Older age duration and satisfaction with treatment. scores): RA (1.75) FM (1.30), Symptomatic Higher education level Chronic pain sufferers report a lower knee OA (1.29) Low back pain (1.27) Heavy lifting quality of life than acute pain patients. Health related QoL (SF-12 scores): Higher family income Physical aspects: RA (29.1) Symptomatic No previous prostheses knee OA (31.7) Low back pain (32.4) Psychological component: FM (39.0)

Knee pain suggesting OA (Fernandez- Lopez (2008)) 66.8% of respondents rated their health as poor or just fair. SF-12 physical score was 38.7 (significantly different from those without knee pain, 51.5). SF-12 mental score was also lower, 46.1 compared to 50.1.

187 Results Number of studies and Question quality (low, med, high) Chronic pain Moderate or severe chronic pain Moderate or severe chronic pain

12 b – 15 studies relevant. OA and RA General non-cancer pain The studies were all of medium quality activities of Over 65s: 45% were independent Over 65s: Prevalence of pain interference and three were representative of the target daily living 4 studies selected: without difficulties, 36% independent with activities daily living was 48.6% population. However, although the results Miro (2007) - med with difficulties, 19% dependent. for back pain are representative, they may Espallargues Chronic limitation of activity 23%, those have included some cases of acute pain. (1996) – med regularly using type of mechanic help 19% The results for over 65s are representative Collantes-Estevez of the elderly Spanish population. (2003) – med Patients with OA taking celecoxibs: Bassols (2003) – med Fully able to perform usual activities 15.6% Limited in work activities 28.9% Limited in work & non-work activities 44.6% Limited capacity to perform usual activities 10.8%

Back pain: 36.7% were limited in their daily activities 23% needed bed rest 17% stopped working 6.5% had permanent incapacity

188 Results Number of studies and Question quality (low, med, high) Chronic pain Moderate or severe chronic pain Moderate or severe chronic pain

12 c and d – 17 studies relevant General non-cancer pain FM Three of the included studies were depression 29% (n = 225) diagnosed with depression 14.4% depressive symptoms. 3% of representative of the population (Gamero or other 5 studies selected patients did not report depressive (2005), Galvez (2006) and Breivik mental Breivik (2006) – med Neck and back pain symptoms, 42% reported low to (2006)) and all included studies had illness and Pinto-Meza (2006) – low Major depression 7.2% (SE 1.2) moderate levels, and 15% had severe large sample sizes. Although Orfila isolation / Gamero (2005) – med OR 1.19 (95%CI 1.3-2.9) depressive symptoms. 13.4% anxiety (2006) was rated as high quality and was helplessness Torre (2008) – med Dysthymia representative of the Spanish population, Galvez (2006) – low 0.7% (SE 0.3) OR 1.6 (95%CI 0.6-4.2) Neuropathic pain caution needs to be taken over the Mood disorders 7.9% (SE 1.3), 19.7% patients had symptoms of conclusions as they were related to chronic OR 1.19 (95%CI 1.3-2.9) depression and 12.9% of anxiety. conditions and not only chronic pain. Generalised anxiety 1.4 (SE 0.4), Prevalence of anxiety and depression: OR 2.9 (95%CI 1.3-6.2) BMI <27: 10.6% anxiety, 18.2% Panic disorder 1.3% (SE 0.4) depression, BMI >27 – 30 13%, 20% OR 3.2 (95%CI 1.4-7.2) BMI >30 18%, 24% Agoraphobia 0.4% (SE 0.2) No OR given Previous analgesic treatment PTSD 1.5 (SE0.5) OR 4.1 (95%CI 1.5-11.3) Yes: 14.4%, 20.8%, No: 9.1%, 17.1% Social phobia 0.8% (SE 0.3) Intensity of pain OR 1.3 (95%CI 0.4-3.8) Mild: 8.5%, 9.1% Other phobias 4.5% (SE 1) Moderate: 5.2%, 6.8% OR 1.1 (95%CI 0.6-2.3) Severe: 17.2%, 27.1% Any anxiety disorder 8.2% (SE Gender: Male: 7.5%, 12%, 1.6) OR 1.5 (95%CI 0.8-2.7) Female: 16.4%, 24.5% Any mental disorder 12.2% (SE Type of pain:Pure NP: 11.2%, 20.4% 1.9) OR 1.4 (95%CI 0.9-2.3) Mixed: 14.1%, 19.2% Sleep disorders (0-100) Elderly patients <10: 0%, 0% B and p values for Social Isolation in >90: 34.9%, 49.8% the multiple linear regression: Depression increased significantly with Arthritis: 4.8 (2.0) 0.021 age, no association with anxiety. Back problems: 14.2 (2.2) <0.001

189 Results Number of studies and Question quality (low, med, high) Chronic pain Moderate or severe chronic pain Moderate or severe chronic pain

12 e and 11 studies relevant General chronic pain FM All studies were of medium quality and had f – days of Mean number of days lost 8.4 (n = 116) 39.3% (N = 84) unemployed due large sample sizes, although it was not work and 5 studies selected: Lost job 22% to the following reasons: 31.4% clear that all of them were representative of incapacity Breivik (2006) – med Changed job responsibilities 8% for sick leave (N = 67), the Spanish population. However, It is clear benefits Bassols (1999) – med Changed jobs 4% (n = 225) 5.6% were unemployed (N = that for people suffering from chronic pain, Tornero (1998) – med 12), retired (2.3%; N = 5). the impact on the number of work days Ubago (2005) – med For those with chronic pain that are lost due to their pain is great. Furthermore, Kovacs (2007) – med employed (n = 787), 123 (15.6%) needed bed Rheumatic conditions (1995-1999) many pain sufferers are either unemployed rest with a mean duration of 5.7 (SD 10.2). 6970 work disabilities cases during or on sick leave due to their pain. the 5 years study period, equivalent Pain resulted in time off work in 10.2% of to 364 624 work off days. employed individuals. 41.2% of these cases Reported costs related to work disability meant less than a week away periods equivalent to 1,397,258,172 pesetas from work but 33.8% needed (that would be equal to 839,769,074 a week to a month off from work, euros). The mean annual value for work with an average of 47 days disability was equivalent to 279.451.634 in total. pesetas (167,953,815 euros).

Back pain and low back pain During 1 year follow-up: 77 patients did not go on sick leave, 46 were on sick leave for less than 2 months, 42 were on sick leave for a period ranging between 2 and 12 months.

190 Results Number of studies and Question quality (low, med, high) Chronic pain Moderate or severe chronic pain Moderate or severe chronic pain

13a-c – 7 studies located: Costs to society: Costs to healthcare system: All studies were either of medium or economic EU NHWS (2008) – med Musculoskeletal symptoms (LBP, OA, FM): Knee OA: visits to GP in last 6 months high quality and 5 represented the costs Carmona (2001) – high 2.2% to 9.1% received cost 79.8 Euros, specialist 20.46 Euros, Spanish population. However, it is Nunez (2007) – high disability compensation nurse practitioner 23.11 Euros, alternative difficult to estimate the total economic Sicras Mainar LBP: total cost of worker’s salary practitioner 2.16 Euros. In total the mean costs of chronic pain as the majority (2009) – med compensation from absenteeism was direct medical costs per patient in the of the studies reported on specific Gonzalez (2000) – med 11,000 million pesetas/year, and the mean previous 6 months was 200.24 Euros pain conditions in specific settings. Rodriguez (2007a) cost by worker was 209,666 pesetas/year Neuropathic pain: total adjusted costs and (2007b) – med were: 376 Euros for primary care Costs to patients setting patients and 344 Euros for Moderate to severe general non-cancer patients referred to pain clinics pain: 59% had costs of 1-100Euros knee OA: mean out-of-pocket costs was 23.71 Euros in the previous 6 months FM: mean annual direct ambulatory cost for patients was 908.67Euros

14- 13 studies relevant Patients attending pain clinic: FM: Overall, study quality was medium to determinants Higher stress levels, the higher the Symptoms - those with tiredness high. However, it was not clear whether of patient 5 studies selected: level of interference of their pain. and paraesthesia felt more of any of the studies were representative awareness Fernandez (2007) – med Variables that predict more stress in an impact of disease of the Spanish population. of chronic Soucase (2005) – med patients were intensity of pain, activity Symptom that most affects daily living: pain Torre (2008) – med reduction and emotional affectation. Tiredness, bone and joint pain Ubago (2008) – med depressed mood Garcia (2004) – high Pain exceeded their coping resources and became disabling Decrease in libido experienced

Most frequently used strategies for coping with pain: self-assertion, search for information, religion.

After 6 months treatment, patients used more active coping mechanisms

191 Results Number of studies and Question quality (low, med, high) Chronic pain Moderate or severe chronic pain Moderate or severe chronic pain

15 – 2 studies located: Aspects of pain remarked upon by Primary healthcare (PHC) and pain These studies were not representative determinants Collantes-Estevez physicians during rofecoxib trial: management units (PMU): and one was rated as low quality. Little of health (2003) – med functional capacity, morning stiffness, There was a lack of knowledge about the information was found in answer to care Garcia-Martinez control of night pain, and satisfaction with functioning and, sometimes even about the this question, and it is difficult to draw professional (2000) – low treatment expressed by the patient existence PMUs, as well as a poor training of conclusions from the included studies. awareness the PHC physicians in pain-related issues. of chronic pain Issues with diagnoses due to: further explorations are not allowed or make the visit too lengthy and long waiting lists for the access to different specialties

16 – main 19 studies relevant Patients visiting pain units OA Symptoms n (%) Only one of the studies was representative presenting Most frequent symptoms associated Men: Pain 210 (99.5) of the Spanish population, however symptoms 4 studies selected with chronic pain: sleeping disorder Joint stiffness 147 (69.7) this study reported the most painful and Arboleya (2003a) – med 50%, depression 48%, anxiety Joint effusion 23 (10.9) locations that patients present with, and complaints Gamero (2005) – high 47% and irritability 30%. Other 10 (4.7) not symptoms directly. The other studies Rodriguez (2006) – med focused on different types of chronic Miro (2007) – med General non-cancer pain: Women: Pain 680 (99.4) pain and were not representative, so it % of patients reporting most Joint stiffness 523 (76.5) is difficult to generalise the results to bothersome painful region: Joint effusion 86 (12.6) the general Spanish pain population. Head 3.8% Other 42 (6.1) Cervical region 6.1% Upper limbs 4.2% Muskuloskeletal pain and FM: Thoracic region 2.4% most frequent pathologies that caused Abdominal region 2.8% consultation in new patients, was Lower back 23.8% arthrosis (31.2%), extra-articular Hip 9% rheumatism (19.9%), vertebral pains Foot 4.5% (18.8%) and fibromyalgia (17.7%); Joints 24.1% Lower limbs 14.6% In patients for revision, arthrosis (29.1%), inflammatory arthropaty (20.9%), extra-articular rheumatism (14%) and vertebral pains (12.4%).

192 Results Number of studies and Question quality (low, med, high) Chronic pain Moderate or severe chronic pain Moderate or severe chronic pain

17 – fre- 23 studies relevant General non-cancer pain Osteomuscular pain: The quality of the included studies quency of Frequencies of treatments: WHO level 1: 54.7% was varied, and only one of these was drug, non- 5 studies selected NSAID 49% Level 2: 6.6% representative of the Spanish population drug and Breivik (2006) – med Weak opioid 13% Determinants of drug treatments: (Breivik (2006)). The results here combined Rodriguez (2006) – med Strong opioid 1% Sex, educational background, cannot be considered representative treatments Gamero (2005) – high Paracetamol 8% patients’ activity. (Noceda (2007)) of the pain population in Spain. And 19– Noceda (2007) – low COX-2 inhibitor 2% (Breivik (2006)) determi- Ribera (2007) – low Musculoskeletal pain: nants of Level I non-opioid analgesics: Overall 57.6% of patients were treatment NSAIDs 76% of the patients, paracetamol receiving NSAIDs; 6.4% opioids choice 53% and metamizol 36%. In new patients: within drug Level II: tramadol 89% of patients NSAIDs 51.1% paracetamol treatments using weak opioids. 31.8% opioids 3.0% Level III fentanyl (63% of patients using Non-pharmalogical treatments overall 34.9% strong opioids), buprenorphine (27%), oral Massage 14.9% morphine (19%) and oxycodone (3%). Rehabilitation 7.5% Level III drug were used in 28% of Patients for review: the patients. (Rodriguez (2006)) NSAIDs 60.6% Paracetamol 29.4% Analgesics 96%: Opiods 7.1% Level 1 28.6% Non-pharmalogical treatments overall 33.1% Minor opioids 43.6% Massage 8.9% Major opioids 36.9% Rehabilitation 7.9% (Gamero (2005))

In 61.9% of cases, the reason for the change in opioid was inefficacy of the previous treatment (Ribera (2007))

18 – determinants of treatment choice No relevant studies found between drug and non-drug treatments

193 Results Number of studies and Question quality (low, med, high) Chronic pain Moderate or severe chronic pain Moderate or severe chronic pain

21 – patient 8 studies relevant: Patients in nursing homes OA The study quality was varied, with studies satisfaction Satisfaction with the analgesic treatment, 46% of patients and physicians were low to high quality, only one of which was with drug 3 studies selected 18% were “unsatisfied” or “very much not satisfied with OA treatment. representative of the Spanish population. treatment VICOXX study unsatisfied”; the rest, 82%, were from (Arboleya (2003a) “low satisfaction” to high satisfaction”. 15.5% of patients and 8.5% of and (2003b)) – med physicians were highly dissatisfied Gil Gregorio (2007) – low Elderly patients in primary care Canellas (1996) – high Very good in 2.5%, good in 27.8%, regular After switch to rofecoxib in 46.2% and bad/very bad in 23.5%. Substantial increase in proportion of patients who reported themselves as ‘somewhat satisfied’ and very satisfied.

Approximately 66% of patients thought switch had increased satisfaction with treatment, 30% reported no change in satisfaction and 7% preferred tNSAIDS to rofecoxib.

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