ORIGINAL ARTICLE
Changes in Quality of Life after 3 months of Usual Care in a Large Sample of Patients with Noncancer Pain: The “QOOL: Quality of Life and Pain” Study Ignacio Vel azquez Rivera, BMBS*; Modesto Garcıa Escobar, BMBS†; Jorge Juan Moya Riera, BMBS‡; Javier Manuel del Saz de la Torre, BMBS§; Pedro Fenollosa V azquez, BMBS¶; Jose´ Manuel Gonzalez Mesa, BM, FIPP**; Alfonso Casado, PhD Medicine & Surgery††; Mayte Martın Fuentes, BSc in Pharmacy‡‡; Javier de Andres Ares, BMBS§§ *Pain Unit, Alta Resoluci on de Guadix Hospital, Granada; †Pain Unit, San Juan de Alicante University Hospital, Alicante; ‡Pain Unit, Instituto Clınico del Dolor, Menorca, Illes Balears; § Pain Unit, Puerta de Hierro Majadahonda University Hospital, Madrid; ¶Pain Unit, Quir on Clinic, Valencia; **Pain Unit, Virgen de la Victoria University Hospital, M alaga; ††Faculty of Medicine, Autonomous University of Madrid, Madrid; ‡‡Medical Department, Mundipharma Pharmaceuticals, Madrid, Spain; §§Pain Unit, Virgen de la Salud Hospital, Toledo, Spain
& Abstract: Large-scale observational studies can provide useful information on changes in health outcomes over time. The aim of this study was to investigate the effect of 3 months of usual care on quality of life (QOL) and pain outcomes in noncancer chronic pain patients managed by pain specialists and to examine factors associated with changes in QOL. This was assessed using the EQ-5D and pain outcomes using the Brief Pain Inventory (BPI). Changes in
zquez Address correspondence and reprint requests to: Ignacio Vela n de Guadix; Pain Unit, Avda. Rivera, BMBS, Hospital de Alta Resolucio Mariana Pineda, s/n, 18500 Guadix (Granada), Spain. E-mail: [email protected]. Conflict of interests: Mayte is employed by Mundipharma Pharmaceuticals. No other conflicts of interest have been declared. Submitted: December 14, 2013; Revised March 27, 2014; Revision accepted: May 17, 2014 DOI. 10.1111/papr.12231
© 2014 World Institute of Pain, 1530-7085/14/$15.00 Pain Practice, Volume 15, Issue 7, 2015 633–642
QOL and pain were studied for the overall sample and in subgroups defined by baseline pain severity. Multivariate regression was used to investigate factors associated with change on EQ-5D. Three thousand and twenty-nine patients were included for analysis. After 3 months of usual care, a mean of 40.9% of patients showed improvement on individual EQ-5D dimensions, with the highest rates of improvement seen on the pain/discomfort (50.8%) and anxiety/depression (48.3%) dimensions. The EQ-5D Index increased from a mean (SD) of 0.35 (0.2) to 0.58 (0.21) points between baseline and month 3, and the thermometer from 41.5 (19.4) to 58.7 (17.8), indicating a large effect. Improvements in QOL were larger in those with severe baseline pain. The BPI severity summary score improved from a mean (SD) of 6.5 (1.4) to 4.1 (1.7) and the interference summary score from 6.6 (1.5) to 4.2 (1.9). Changes on the BPI severity and interference scores were associated with changes in the EQ-5D Index and thermometer. In conclusion, 3 months of usual care in noncancer pain patients led to substantial improvements in QOL and pain outcomes. &
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Key Words: pain, quality of life, cohort study, pain clinics, usual care, Spain
INTRODUCTION Chronic pain, a frequent and increasing health problem in Europe, has been estimated to occur in approximately 20% of the European general population.1 The average duration of chronic pain is 7 years, and pain is severe in 1/3 of sufferers. In Spain, the prevalence is somewhat lower, at 12% to 17%, but average duration is 9.1 years and pain is reported as severe in just under half of patients (44%).1,2 Chronic pain has a significant impact on patient quality of life (QOL).3,4 A pan-European study found that chronic pain led to problems with sleeping, exercising, walking, doing housework, and maintaining an independent lifestyle in half or more of patients.1,5 Social relationships, sexual life, and the ability to work are affected.5 There is also evidence that levels of anxiety and depression are higher in patients with pain.1,6 In Spain, 29% of patients with chronic pain had depressive symptoms.1 Adequate pain control should lead to improvements not just in the symptom itself but also in QOL. However, data suggest that chronic pain is not adequately controlled. One study showed that 81% of primary care physicians believe pain to be inadequately controlled in significant numbers of noncancer chronic pain patients, with fewer than half of patients achieving optimal symptom control.7 Another recent study showed that up to 79% of patients believe their pain to be inadequately treated.8 One obstacle to better control appears to be treatment side effects.7 Large-scale, observational studies in conditions of usual clinical care can provide useful information on how QOL and pain outcomes evolve over time in patients treated with the typical approach to pain management. These studies can also help to identify at risk groups of patients or subgroups showing below average improvement or even deterioration in their pain. They can therefore indicate where improvements in treatment are required or where additional resources are needed. The “QOOL: Quality of Life and Pain” study was a large, multicenter, observational study in which the primary objective was to evaluate change in QOL and pain outcomes over 3 months in patients suffering moderate-to-severe noncancer-related pain treated in pain units. Further objectives were to validate the short
form of the Brief Pain Inventory in Spanish, investigate the influence of intestinal functioning on QOL, and analyze the evolution of sleep and overall functioning. In this article, we report QOL outcomes after 3 months of usual care in these patients. The analysis was performed for the sample as a whole and in subgroups defined by baseline pain severity. We also examined patient characteristics associated with changes in QOL using multivariate regression models.
METHODS Study Design and Patient Population The QOOL study was a descriptive, observational, multicenter, prospective study carried out in pain units throughout Spain between February 2010 and September 2010. A total of 133 pain units participated. The study was carried out in accordance with the principles of the Declaration of Helsinki (2004) and local legislation on data protection for this type of study. The study protocol was approved by Ethics Committees in the study coordinators’ hospitals, and all participating centers were free to submit the protocol to their own review board. All patients provided written informed consent to participate in the study. Patients were followed for a period of 3 months and made a total of three study visits (baseline, 1 month, and 3 months). HRQOL data were collected at baseline and 3 months. Data were collected using a validated electronic data capture system, which included audit trails and data security systems. Consecutive patients aged 18 years or older with moderate to severe chronic noncancer pain making their first visit to a pain clinic were eligible for inclusion in the study. Patients considered by the investigator to be cognitively unable to participate were excluded. Participating centers were requested to follow their usual approach to pain management, which in this case involved only treatment with medication or minimally invasive treatments. The sample size was calculated to be able to detect a minimal clinically important difference (MCID) in the EQ-5D Index between the first and last study visits and for comparisons across a maximum of three equivalently sized groups. The MCID is defined as the smallest difference in score in the domain (or scale) of interest which patients perceive as beneficial.9 In this study, it was defined as a change of 0.06 points on the EQ-5D Index.10
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Assessments At baseline, investigators collected demographic and clinical data including patient age and sex, pain origin (somatic, visceral, or neuropathic), and pain management (WHO pain ladder). Intensity of pain on the day of the visit was measured using a 0 to 10 (0 = no pain; 10 = worst imaginable pain) numeric rating scale (NRS). Only patients with a rating of > 4 points were included. HRQOL was measured using the EQ-5D questionnaire, and pain severity and impact were assessed using the short form of the Brief Pain Inventory (BPI). The EQ-5D is a standardized measure of health status developed to provide a simple, self-completed, generic measure of health for clinical and economic appraisal.11 It has been used in a wide range of health conditions and treatments and provides a simple descriptive profile and a single index value for health status that can be used in the clinical and economic evaluation of health care as well as in health surveys. The descriptive system of the EQ-5D measures HRQOL in five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/ depression), each of which has three response levels (no problems, some problems, extreme problems). The respondent is asked to indicate his/her health state on the day of the interview. In this way, respondents selfclassify themselves in one of 243 (3^5) unique health states defined by the instrument. These EQ-5D health states may be converted into a single summary score (EQ-5D Index) by applying a formula that attaches societal values or weights to each level in each dimension.12 In this study, Spanish general population weights were used to calculate Index scores.13 These range from 0.0757 to 1, with the former corresponding to the worst possible health state defined by the EQ-5D descriptive system (scoring 3 in all dimensions: 3,3,3,3,3) and the latter corresponding to perfect health state (1,1,1,1,1). Respondents also rated their overall health status on a 0 to 100 hash-marked, vertical visual analog scale (EQ-VAS, or thermometer), on which 0 represents the worst imaginable health state and 100 represents the best possible imaginable health state. A previously validated Spanish version of the EQ-5D was used in this study.14 The BPI is one of the most widely used tools to assess clinical pain and allows patients to rate the severity of pain and the degree to which it interferes with common dimensions of well-being and function. Although it was originally developed to assess pain related to cancer, it
has been used in other conditions.15,16 Both long and short forms of the BPI are available; the short form (BPISF) was used in this study. The BPI-SF measures patient perceptions of pain severity and degree of interference on daily functioning and allows patients to record pain location, pain medication, and the degree of pain relief in the last 24 hours. Pain severity items assess pain “at its worst”, “at its least,” and “on average” over the previous 24 hours as well as pain at the time of completing the questionnaire. The pain interference scale assesses the degree to which pain interferes with enjoyment of life, general activity, walking ability, mood, sleep, normal work, and relations with other people. Items in the pain severity scale are answered on four 0-to-10 NRS where 0 = “no pain” and 10 = “pain as bad as you can imagine”. Numerical rating scales used to assess pain interference are anchored by 0 = “does not interfere” and 10 = “interferes completely”. Subscale scores are available for the pain severity and pain interference scales.17 The long version of the BPI has been validated for use in Spanish,18 and we used an adapted short form version in this study.19 Both the EQ-5D and BPI were self-administered, although healthcare personnel were on hand to help with completion when necessary. Statistical Analysis Continuous variables were described using means (standard deviation—SD) and medians (interquartile range—IQR), as appropriate. Categorical variables were described using frequencies and percentages. Student’s t-test or the nonparametric Mann–Whitney U-test was used for bivariate analysis of continuous variables. Change over time was assessed using paired t-tests or Wilcoxon or Mann–Whitney U-tests as appropriate. In all comparisons, results were considered statistically significant when P < 0.05. To help interpret the magnitude of change, effect sizes (ES) were calculated by dividing mean change on the variable of interest by the standard deviation for that variable at baseline.20 An ES of 0.20 was considered to represent a small change, 0.50 a moderate change, and 0.80 a large change.21 Multivariate analysis was used to assess the effect of different parameters on changes in the EQ-5D Index and VAS. Dependent variables were the EQ-5D Index and VAS and independent variables tested in different combinations were age, sex, BPI scores (baseline and change scores), pain origin, and bowel function, among others. The Mallow Cp criterion (Homer and
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Lemeshow) was used to select the optimal model in each case. All analyses were performed using version 17 of SPSS. (SPSS Inc., Released 2008. SPSS Statistics for Windows, Version 17.0, Chicago, IL, USA)
RESULTS A total of 3,526 patients were initially included in the study. However, 497 patients were excluded from the final analysis: three were excluded because they failed to meet one of the inclusion criteria, 19 were excluded because they had a visual numerical pain scale < 4 at baseline, 178 were excluded because of missing data in at least one of the study visits, which meant that we Table 1. Demographic and Clinical Characteristics of the Study Population at Baseline: Overall Sample and by Subgroup
Variable
Overall Sample (n = 3,029)
Age, years, 61.6 (14.0) mean (SD) Sex, female, n 2,032 (67.1) (%) Origin of pain, n (%) Somatic 2,412 (79.6) Visceral 64 (2.1) Neuropathic 1,667 (55.0) Treatment, n (%) 1st step 391 (12.9) 2nd step 423 (14.0) 3rd step 2,514 (83.0) BPI, mean (SD) Least 5.0 (2.1) Average 6.6 (1.4) Worst 7.8 (1.3) Now 6.6 (1.9) 6.5 (1.9) Severity summary score, mean (SD) 6.6 (1.5) BPI interference, mean (SD) EQ-5D dimensions (% reporting Mobility 83.3 Self-care 71.7 Usual 93.9 activities Pain/ 99.4 discomfort Anxiety/ 83.2 depression 0.35 (0.20) EQ-5D Index score, mean (SD) EQ-5D VAS, 41.5 (19.4) mean (SD)
Pain Intensity Moderate ≤ 7 (n = 1,802)
Severe > 7 (n = 1,227)
61.6 (14.8)
61.6 (14.3)
—
1,185 (65.8)
847 (69.0)
—
1,465 (81.3) 42 (2.3) 962 (53.4)
947 (77.2) 22 (1.8) 705 (57.5)
— — —
267 (14.8) 296 (16.4) 1,422 (78.9)
124 (10.1) 127 (10.4) 1,092 (89.0)
— — —
3.8 5.8 7.3 5.7 5.6
(1.5) (1.4) (1.2) (1.7) (0.9)
6.0 (1.5)
P Values*
(1.3) (0.9) (0.9) (1.0) (0.8)
< 0.001 < 0.001 < 0.001
7.5 (1.2)
< 0.001
6.8 7.8 8.6 8.0 7.8
problems in EQ dimensions) 80.7 87.1 82.2 64.5 91.8 97.0
< 0.001
< 0.001 < 0.001 < 0.001
99.7
99.2
< 0.001
77.9
91.0
< 0.001
0.40 (0.20)
0.27 (0.19)
< 0.001
45.0 (17.4)
36.5 (21.1)
< 0.001
BPI, brief pain inventory. *Differences between subgroups defined by pain severity.
could not calculate BPI and/or EQ-5D scores, and 297 were excluded because no data were available at month 3. Therefore, a total of 3,029 patients with data from the baseline and 3 month visits were available for analysis. Table 1 shows the demographic and clinical characteristics of the study population at baseline, for the overall sample and by pain severity subgroup. Mean (SD) age was 61.6 years (14.0), and 67.1% of the overall sample were female. Origin of pain was predominantly somatic (79.6%) and/or neuropathic (55.0%), and most (83%) patients were on the third step of the WHO pain ladder. Mean (SD) EQ-5D Index and VAS scores at baseline indicated very poor QOL, with values of 0.35 (0.20) and 41.5 (19.4), respectively. At baseline, only seven patients (0.2%) reported being in the best possible EQ-5D health state (1,1,1,1,1). Table 2 shows the change in BPI scores from baseline to 3 months, for the overall sample and for subgroups defined by pain severity. All of the measures showed considerable improvement (large effect sizes); the severity summary score improved from a mean (SD) of 6.5 (1.4) to 4.1 (1.7) and the interference summary score from 6.6 (1.5) to 4.2 (1.9). Patients with more severe baseline pain (BPI severity subscale score of > 7) showed more marked improvement on both the pain severity and pain interference subscales (change of 3.4 points in severe patients compared with 1.7 points in moderate patients on the interference scale, and of three compared with 2 points on the interference subscale). Figure 1 shows the results on the BPI severity and interference subscales for the overall study population and for patients with severe and less severe pain at baseline. Table 3 shows the changes over the study period on EQ-5D dimensions for the overall sample. A considerable reduction in the number and proportion of patients reporting moderate or extreme problems could be seen on all dimensions. The improvements were particularly noticeable on the dimensions of pain discomfort (53.8% reporting extreme problems at baseline, compared with 12.1% at 3 months), anxiety/depression (27% reporting extreme problems at baseline, compared with 7.8% at 3 months), and usual activities (23.4% reporting extreme problems at baseline, compared with 6% at 3 months). Table 4 shows the number and percentage of patients who improved, worsened, or remained unchanged at month 3 in each EQ-5D dimension, both overall and by subgroup. The percentage of patients who worsened was small in all dimensions. In the sample as a whole, the
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Table 2. Scores on BPI at Baseline and 3 Months: Overall Sample and Severity Subgroups, Means and Standard Deviations Overall Sample Variable Pain severity items Minimum pain intensity in last 24 hours Average pain intensity in last 24 hours Maximum pain intensity in last 24 hours Pain intensity at the time of completion Severity summary score Pain interference items General activities Mood Walking Usual work Relations with others Sleep Enjoyment Interference summary score
Moderate (< 7)
Baseline
3 Months
Baseline
5.0 (2.1) 6.6 (1.4) 7.8 (1.3) 6.6 (1.9) 6.5 (1.4)
2.9 (1.8) 4.2 (1.8) 5.4 (2.0) 4.0 (2.0) 4.1 (1.7)
3.8 5.8 7.3 5.7 5.6
(1.5) (1.4) (1.2) (1.7) (0.9)
2.6 4.0 5.3 3.7 3.9
7.2 (1.7) 6.8 (2.1) 6.4 (2.5) 7.2 (1.9) 5.9 (2.4) 5.9 (2.6) 6.9 (2.1) 6.6 (1.5)
4.7 (2.1) 4.2 (2.4) 4.1 (2.4) 4.7 (2.3) 3.7 (2.3) 3.5 (2.3) 4.4 (2.3) 4.2 (1.9)
6.6 6.2 5.9 6.7 5.2 5.2 6.3 6.0
(1.7) (2.1) (2.5) (2.0) (2.3) (2.5) (2.1) (1.5)
4.6 4.0 3.9 4.6 3.5 3.3 4.3 4.0
Severe (> 7)
3 Months
Baseline
3 Months
(1.7) (1.6) (1.8) (1.9) (1.6)
6.8 (1.3) 7.8 (0.9) 8.6 (0.9) 8.0 (1.0) 7.8 (0.8)
3.5 (1.9) 4.4 (2.0) 5.4 (2.2) 4.4 (2.1) 4.4 (1.9)
(2.0) (2.3) (2.4) (2.2) (2.2) (2.3) (2.3) (1.8)
8.0 (1.7) 7.8 (1.6) 7.1 (2.3) 7.9 (1.5) 6.9 (2.0) 6.9 (2.3) 7.9 (1.7) 7.5 (1.2)
5.5 (2.2) 4.6 (2.4) 4.3 (2.5) 4.9 (2.4) 4.0 (2.3) 3.8 (2.3) 4.5 (2.0) 4.5 (2.0)
All between-group comparisons were significant at < 0.001.
greatest improvement was seen in pain/discomfort and anxiety/depression (50.8% and 48.3% improved, respectively). The lowest rate of improvement was in the mobility dimension (27.7%). The subgroup with the highest level of baseline pain also had the highest proportion of patients reporting improvement at 3 months. At the final visit, 213 patients (7.0% of the total) reported being in the best possible health state of 1,1,1,1,1, a 10-fold increase over the number at baseline. Table 5 shows the EQ-5D Index and EQ-5D VAS scores at baseline and 3 months, as well as their corresponding effect sizes. Improvements in QOL were observed in both the overall sample and the two study subgroups. Effect sizes showed that improvements were large in all cases, although they were larger in the group with worse baseline pain. Figure 2 shows the results on the EQ-5D Index and VAS for the overall study population and for patients with severe and less severe pain at baseline. Table 6 shows the variables associated with changes in EQ-5D VAS and Index scores. Changes on the BPI severity and interference subscales were significantly associated with changes on both of the EQ-5D measures. Improvements in pain interference had a greater impact on overall health status measured by the EQ-5D VAS than changes in pain severity; for each 1 point increase on the interference subscale, the EQ-VAS score increased by 3.8 points. A 1 point improvement on the severity subscale led to only a 1.4 point increase on the EQ-5D VAS. A similar effect was seen on the EQ-5D Index, where a 1 point increase on the BPI interference
subscale was associated with a 0.051 increase on the EQ-5D Index, compared with an increase of 0.034 points for a 1 point increase on the severity subscale. The final EQ-VAS and EQ-Index models explained 22% (R2a = 0.222) and 39% (R2a = 0.397) of the variance in scores, respectively.
DISCUSSION This is one of relatively few large-scale studies to have examined the evolution of chronic noncancer pain patients managed with usual care. Other large-scale studies 22 in similar patients have looked at the impact of specific therapies, although they did not use QOL as a primary endpoint. Some authors have recently pointed out the need for more large-scale studies on chronic noncancer pain in Europe.5 This type of study can help to highlight areas of healthcare needs and to suggest where resources and further investigation are required. In the present study, substantial improvements in both QOL and pain outcomes were observed over the 3-month study period, both in the sample as a whole and in the two study subgroups defined by pain severity. Nevertheless, a considerable proportion of patients still reported some pain at the final visit. The very low scores on the EQ-5D Index and VAS at baseline indicate the severe impact of pain on QOL, with all dimensions of QOL measured by EQ-5D being substantially affected. At baseline, over 70% of patients reported at least “some” problems on each EQ-5D dimension. Even on the dimension of self-care, which was the least affected dimension, only 28.3% of patients
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BPI severity score p
Changes in Quality of Life after 3 months of Usual Care in a Large Sample of Patients with Noncancer Pain: The “QOOL: Quality of Life and Pain” Study Ignacio Vel azquez Rivera, BMBS*; Modesto Garcıa Escobar, BMBS†; Jorge Juan Moya Riera, BMBS‡; Javier Manuel del Saz de la Torre, BMBS§; Pedro Fenollosa V azquez, BMBS¶; Jose´ Manuel Gonzalez Mesa, BM, FIPP**; Alfonso Casado, PhD Medicine & Surgery††; Mayte Martın Fuentes, BSc in Pharmacy‡‡; Javier de Andres Ares, BMBS§§ *Pain Unit, Alta Resoluci on de Guadix Hospital, Granada; †Pain Unit, San Juan de Alicante University Hospital, Alicante; ‡Pain Unit, Instituto Clınico del Dolor, Menorca, Illes Balears; § Pain Unit, Puerta de Hierro Majadahonda University Hospital, Madrid; ¶Pain Unit, Quir on Clinic, Valencia; **Pain Unit, Virgen de la Victoria University Hospital, M alaga; ††Faculty of Medicine, Autonomous University of Madrid, Madrid; ‡‡Medical Department, Mundipharma Pharmaceuticals, Madrid, Spain; §§Pain Unit, Virgen de la Salud Hospital, Toledo, Spain
& Abstract: Large-scale observational studies can provide useful information on changes in health outcomes over time. The aim of this study was to investigate the effect of 3 months of usual care on quality of life (QOL) and pain outcomes in noncancer chronic pain patients managed by pain specialists and to examine factors associated with changes in QOL. This was assessed using the EQ-5D and pain outcomes using the Brief Pain Inventory (BPI). Changes in
zquez Address correspondence and reprint requests to: Ignacio Vela n de Guadix; Pain Unit, Avda. Rivera, BMBS, Hospital de Alta Resolucio Mariana Pineda, s/n, 18500 Guadix (Granada), Spain. E-mail: [email protected]. Conflict of interests: Mayte is employed by Mundipharma Pharmaceuticals. No other conflicts of interest have been declared. Submitted: December 14, 2013; Revised March 27, 2014; Revision accepted: May 17, 2014 DOI. 10.1111/papr.12231
© 2014 World Institute of Pain, 1530-7085/14/$15.00 Pain Practice, Volume 15, Issue 7, 2015 633–642
QOL and pain were studied for the overall sample and in subgroups defined by baseline pain severity. Multivariate regression was used to investigate factors associated with change on EQ-5D. Three thousand and twenty-nine patients were included for analysis. After 3 months of usual care, a mean of 40.9% of patients showed improvement on individual EQ-5D dimensions, with the highest rates of improvement seen on the pain/discomfort (50.8%) and anxiety/depression (48.3%) dimensions. The EQ-5D Index increased from a mean (SD) of 0.35 (0.2) to 0.58 (0.21) points between baseline and month 3, and the thermometer from 41.5 (19.4) to 58.7 (17.8), indicating a large effect. Improvements in QOL were larger in those with severe baseline pain. The BPI severity summary score improved from a mean (SD) of 6.5 (1.4) to 4.1 (1.7) and the interference summary score from 6.6 (1.5) to 4.2 (1.9). Changes on the BPI severity and interference scores were associated with changes in the EQ-5D Index and thermometer. In conclusion, 3 months of usual care in noncancer pain patients led to substantial improvements in QOL and pain outcomes. &
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Key Words: pain, quality of life, cohort study, pain clinics, usual care, Spain
INTRODUCTION Chronic pain, a frequent and increasing health problem in Europe, has been estimated to occur in approximately 20% of the European general population.1 The average duration of chronic pain is 7 years, and pain is severe in 1/3 of sufferers. In Spain, the prevalence is somewhat lower, at 12% to 17%, but average duration is 9.1 years and pain is reported as severe in just under half of patients (44%).1,2 Chronic pain has a significant impact on patient quality of life (QOL).3,4 A pan-European study found that chronic pain led to problems with sleeping, exercising, walking, doing housework, and maintaining an independent lifestyle in half or more of patients.1,5 Social relationships, sexual life, and the ability to work are affected.5 There is also evidence that levels of anxiety and depression are higher in patients with pain.1,6 In Spain, 29% of patients with chronic pain had depressive symptoms.1 Adequate pain control should lead to improvements not just in the symptom itself but also in QOL. However, data suggest that chronic pain is not adequately controlled. One study showed that 81% of primary care physicians believe pain to be inadequately controlled in significant numbers of noncancer chronic pain patients, with fewer than half of patients achieving optimal symptom control.7 Another recent study showed that up to 79% of patients believe their pain to be inadequately treated.8 One obstacle to better control appears to be treatment side effects.7 Large-scale, observational studies in conditions of usual clinical care can provide useful information on how QOL and pain outcomes evolve over time in patients treated with the typical approach to pain management. These studies can also help to identify at risk groups of patients or subgroups showing below average improvement or even deterioration in their pain. They can therefore indicate where improvements in treatment are required or where additional resources are needed. The “QOOL: Quality of Life and Pain” study was a large, multicenter, observational study in which the primary objective was to evaluate change in QOL and pain outcomes over 3 months in patients suffering moderate-to-severe noncancer-related pain treated in pain units. Further objectives were to validate the short
form of the Brief Pain Inventory in Spanish, investigate the influence of intestinal functioning on QOL, and analyze the evolution of sleep and overall functioning. In this article, we report QOL outcomes after 3 months of usual care in these patients. The analysis was performed for the sample as a whole and in subgroups defined by baseline pain severity. We also examined patient characteristics associated with changes in QOL using multivariate regression models.
METHODS Study Design and Patient Population The QOOL study was a descriptive, observational, multicenter, prospective study carried out in pain units throughout Spain between February 2010 and September 2010. A total of 133 pain units participated. The study was carried out in accordance with the principles of the Declaration of Helsinki (2004) and local legislation on data protection for this type of study. The study protocol was approved by Ethics Committees in the study coordinators’ hospitals, and all participating centers were free to submit the protocol to their own review board. All patients provided written informed consent to participate in the study. Patients were followed for a period of 3 months and made a total of three study visits (baseline, 1 month, and 3 months). HRQOL data were collected at baseline and 3 months. Data were collected using a validated electronic data capture system, which included audit trails and data security systems. Consecutive patients aged 18 years or older with moderate to severe chronic noncancer pain making their first visit to a pain clinic were eligible for inclusion in the study. Patients considered by the investigator to be cognitively unable to participate were excluded. Participating centers were requested to follow their usual approach to pain management, which in this case involved only treatment with medication or minimally invasive treatments. The sample size was calculated to be able to detect a minimal clinically important difference (MCID) in the EQ-5D Index between the first and last study visits and for comparisons across a maximum of three equivalently sized groups. The MCID is defined as the smallest difference in score in the domain (or scale) of interest which patients perceive as beneficial.9 In this study, it was defined as a change of 0.06 points on the EQ-5D Index.10
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Assessments At baseline, investigators collected demographic and clinical data including patient age and sex, pain origin (somatic, visceral, or neuropathic), and pain management (WHO pain ladder). Intensity of pain on the day of the visit was measured using a 0 to 10 (0 = no pain; 10 = worst imaginable pain) numeric rating scale (NRS). Only patients with a rating of > 4 points were included. HRQOL was measured using the EQ-5D questionnaire, and pain severity and impact were assessed using the short form of the Brief Pain Inventory (BPI). The EQ-5D is a standardized measure of health status developed to provide a simple, self-completed, generic measure of health for clinical and economic appraisal.11 It has been used in a wide range of health conditions and treatments and provides a simple descriptive profile and a single index value for health status that can be used in the clinical and economic evaluation of health care as well as in health surveys. The descriptive system of the EQ-5D measures HRQOL in five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/ depression), each of which has three response levels (no problems, some problems, extreme problems). The respondent is asked to indicate his/her health state on the day of the interview. In this way, respondents selfclassify themselves in one of 243 (3^5) unique health states defined by the instrument. These EQ-5D health states may be converted into a single summary score (EQ-5D Index) by applying a formula that attaches societal values or weights to each level in each dimension.12 In this study, Spanish general population weights were used to calculate Index scores.13 These range from 0.0757 to 1, with the former corresponding to the worst possible health state defined by the EQ-5D descriptive system (scoring 3 in all dimensions: 3,3,3,3,3) and the latter corresponding to perfect health state (1,1,1,1,1). Respondents also rated their overall health status on a 0 to 100 hash-marked, vertical visual analog scale (EQ-VAS, or thermometer), on which 0 represents the worst imaginable health state and 100 represents the best possible imaginable health state. A previously validated Spanish version of the EQ-5D was used in this study.14 The BPI is one of the most widely used tools to assess clinical pain and allows patients to rate the severity of pain and the degree to which it interferes with common dimensions of well-being and function. Although it was originally developed to assess pain related to cancer, it
has been used in other conditions.15,16 Both long and short forms of the BPI are available; the short form (BPISF) was used in this study. The BPI-SF measures patient perceptions of pain severity and degree of interference on daily functioning and allows patients to record pain location, pain medication, and the degree of pain relief in the last 24 hours. Pain severity items assess pain “at its worst”, “at its least,” and “on average” over the previous 24 hours as well as pain at the time of completing the questionnaire. The pain interference scale assesses the degree to which pain interferes with enjoyment of life, general activity, walking ability, mood, sleep, normal work, and relations with other people. Items in the pain severity scale are answered on four 0-to-10 NRS where 0 = “no pain” and 10 = “pain as bad as you can imagine”. Numerical rating scales used to assess pain interference are anchored by 0 = “does not interfere” and 10 = “interferes completely”. Subscale scores are available for the pain severity and pain interference scales.17 The long version of the BPI has been validated for use in Spanish,18 and we used an adapted short form version in this study.19 Both the EQ-5D and BPI were self-administered, although healthcare personnel were on hand to help with completion when necessary. Statistical Analysis Continuous variables were described using means (standard deviation—SD) and medians (interquartile range—IQR), as appropriate. Categorical variables were described using frequencies and percentages. Student’s t-test or the nonparametric Mann–Whitney U-test was used for bivariate analysis of continuous variables. Change over time was assessed using paired t-tests or Wilcoxon or Mann–Whitney U-tests as appropriate. In all comparisons, results were considered statistically significant when P < 0.05. To help interpret the magnitude of change, effect sizes (ES) were calculated by dividing mean change on the variable of interest by the standard deviation for that variable at baseline.20 An ES of 0.20 was considered to represent a small change, 0.50 a moderate change, and 0.80 a large change.21 Multivariate analysis was used to assess the effect of different parameters on changes in the EQ-5D Index and VAS. Dependent variables were the EQ-5D Index and VAS and independent variables tested in different combinations were age, sex, BPI scores (baseline and change scores), pain origin, and bowel function, among others. The Mallow Cp criterion (Homer and
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Lemeshow) was used to select the optimal model in each case. All analyses were performed using version 17 of SPSS. (SPSS Inc., Released 2008. SPSS Statistics for Windows, Version 17.0, Chicago, IL, USA)
RESULTS A total of 3,526 patients were initially included in the study. However, 497 patients were excluded from the final analysis: three were excluded because they failed to meet one of the inclusion criteria, 19 were excluded because they had a visual numerical pain scale < 4 at baseline, 178 were excluded because of missing data in at least one of the study visits, which meant that we Table 1. Demographic and Clinical Characteristics of the Study Population at Baseline: Overall Sample and by Subgroup
Variable
Overall Sample (n = 3,029)
Age, years, 61.6 (14.0) mean (SD) Sex, female, n 2,032 (67.1) (%) Origin of pain, n (%) Somatic 2,412 (79.6) Visceral 64 (2.1) Neuropathic 1,667 (55.0) Treatment, n (%) 1st step 391 (12.9) 2nd step 423 (14.0) 3rd step 2,514 (83.0) BPI, mean (SD) Least 5.0 (2.1) Average 6.6 (1.4) Worst 7.8 (1.3) Now 6.6 (1.9) 6.5 (1.9) Severity summary score, mean (SD) 6.6 (1.5) BPI interference, mean (SD) EQ-5D dimensions (% reporting Mobility 83.3 Self-care 71.7 Usual 93.9 activities Pain/ 99.4 discomfort Anxiety/ 83.2 depression 0.35 (0.20) EQ-5D Index score, mean (SD) EQ-5D VAS, 41.5 (19.4) mean (SD)
Pain Intensity Moderate ≤ 7 (n = 1,802)
Severe > 7 (n = 1,227)
61.6 (14.8)
61.6 (14.3)
—
1,185 (65.8)
847 (69.0)
—
1,465 (81.3) 42 (2.3) 962 (53.4)
947 (77.2) 22 (1.8) 705 (57.5)
— — —
267 (14.8) 296 (16.4) 1,422 (78.9)
124 (10.1) 127 (10.4) 1,092 (89.0)
— — —
3.8 5.8 7.3 5.7 5.6
(1.5) (1.4) (1.2) (1.7) (0.9)
6.0 (1.5)
P Values*
(1.3) (0.9) (0.9) (1.0) (0.8)
< 0.001 < 0.001 < 0.001
7.5 (1.2)
< 0.001
6.8 7.8 8.6 8.0 7.8
problems in EQ dimensions) 80.7 87.1 82.2 64.5 91.8 97.0
< 0.001
< 0.001 < 0.001 < 0.001
99.7
99.2
< 0.001
77.9
91.0
< 0.001
0.40 (0.20)
0.27 (0.19)
< 0.001
45.0 (17.4)
36.5 (21.1)
< 0.001
BPI, brief pain inventory. *Differences between subgroups defined by pain severity.
could not calculate BPI and/or EQ-5D scores, and 297 were excluded because no data were available at month 3. Therefore, a total of 3,029 patients with data from the baseline and 3 month visits were available for analysis. Table 1 shows the demographic and clinical characteristics of the study population at baseline, for the overall sample and by pain severity subgroup. Mean (SD) age was 61.6 years (14.0), and 67.1% of the overall sample were female. Origin of pain was predominantly somatic (79.6%) and/or neuropathic (55.0%), and most (83%) patients were on the third step of the WHO pain ladder. Mean (SD) EQ-5D Index and VAS scores at baseline indicated very poor QOL, with values of 0.35 (0.20) and 41.5 (19.4), respectively. At baseline, only seven patients (0.2%) reported being in the best possible EQ-5D health state (1,1,1,1,1). Table 2 shows the change in BPI scores from baseline to 3 months, for the overall sample and for subgroups defined by pain severity. All of the measures showed considerable improvement (large effect sizes); the severity summary score improved from a mean (SD) of 6.5 (1.4) to 4.1 (1.7) and the interference summary score from 6.6 (1.5) to 4.2 (1.9). Patients with more severe baseline pain (BPI severity subscale score of > 7) showed more marked improvement on both the pain severity and pain interference subscales (change of 3.4 points in severe patients compared with 1.7 points in moderate patients on the interference scale, and of three compared with 2 points on the interference subscale). Figure 1 shows the results on the BPI severity and interference subscales for the overall study population and for patients with severe and less severe pain at baseline. Table 3 shows the changes over the study period on EQ-5D dimensions for the overall sample. A considerable reduction in the number and proportion of patients reporting moderate or extreme problems could be seen on all dimensions. The improvements were particularly noticeable on the dimensions of pain discomfort (53.8% reporting extreme problems at baseline, compared with 12.1% at 3 months), anxiety/depression (27% reporting extreme problems at baseline, compared with 7.8% at 3 months), and usual activities (23.4% reporting extreme problems at baseline, compared with 6% at 3 months). Table 4 shows the number and percentage of patients who improved, worsened, or remained unchanged at month 3 in each EQ-5D dimension, both overall and by subgroup. The percentage of patients who worsened was small in all dimensions. In the sample as a whole, the
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Table 2. Scores on BPI at Baseline and 3 Months: Overall Sample and Severity Subgroups, Means and Standard Deviations Overall Sample Variable Pain severity items Minimum pain intensity in last 24 hours Average pain intensity in last 24 hours Maximum pain intensity in last 24 hours Pain intensity at the time of completion Severity summary score Pain interference items General activities Mood Walking Usual work Relations with others Sleep Enjoyment Interference summary score
Moderate (< 7)
Baseline
3 Months
Baseline
5.0 (2.1) 6.6 (1.4) 7.8 (1.3) 6.6 (1.9) 6.5 (1.4)
2.9 (1.8) 4.2 (1.8) 5.4 (2.0) 4.0 (2.0) 4.1 (1.7)
3.8 5.8 7.3 5.7 5.6
(1.5) (1.4) (1.2) (1.7) (0.9)
2.6 4.0 5.3 3.7 3.9
7.2 (1.7) 6.8 (2.1) 6.4 (2.5) 7.2 (1.9) 5.9 (2.4) 5.9 (2.6) 6.9 (2.1) 6.6 (1.5)
4.7 (2.1) 4.2 (2.4) 4.1 (2.4) 4.7 (2.3) 3.7 (2.3) 3.5 (2.3) 4.4 (2.3) 4.2 (1.9)
6.6 6.2 5.9 6.7 5.2 5.2 6.3 6.0
(1.7) (2.1) (2.5) (2.0) (2.3) (2.5) (2.1) (1.5)
4.6 4.0 3.9 4.6 3.5 3.3 4.3 4.0
Severe (> 7)
3 Months
Baseline
3 Months
(1.7) (1.6) (1.8) (1.9) (1.6)
6.8 (1.3) 7.8 (0.9) 8.6 (0.9) 8.0 (1.0) 7.8 (0.8)
3.5 (1.9) 4.4 (2.0) 5.4 (2.2) 4.4 (2.1) 4.4 (1.9)
(2.0) (2.3) (2.4) (2.2) (2.2) (2.3) (2.3) (1.8)
8.0 (1.7) 7.8 (1.6) 7.1 (2.3) 7.9 (1.5) 6.9 (2.0) 6.9 (2.3) 7.9 (1.7) 7.5 (1.2)
5.5 (2.2) 4.6 (2.4) 4.3 (2.5) 4.9 (2.4) 4.0 (2.3) 3.8 (2.3) 4.5 (2.0) 4.5 (2.0)
All between-group comparisons were significant at < 0.001.
greatest improvement was seen in pain/discomfort and anxiety/depression (50.8% and 48.3% improved, respectively). The lowest rate of improvement was in the mobility dimension (27.7%). The subgroup with the highest level of baseline pain also had the highest proportion of patients reporting improvement at 3 months. At the final visit, 213 patients (7.0% of the total) reported being in the best possible health state of 1,1,1,1,1, a 10-fold increase over the number at baseline. Table 5 shows the EQ-5D Index and EQ-5D VAS scores at baseline and 3 months, as well as their corresponding effect sizes. Improvements in QOL were observed in both the overall sample and the two study subgroups. Effect sizes showed that improvements were large in all cases, although they were larger in the group with worse baseline pain. Figure 2 shows the results on the EQ-5D Index and VAS for the overall study population and for patients with severe and less severe pain at baseline. Table 6 shows the variables associated with changes in EQ-5D VAS and Index scores. Changes on the BPI severity and interference subscales were significantly associated with changes on both of the EQ-5D measures. Improvements in pain interference had a greater impact on overall health status measured by the EQ-5D VAS than changes in pain severity; for each 1 point increase on the interference subscale, the EQ-VAS score increased by 3.8 points. A 1 point improvement on the severity subscale led to only a 1.4 point increase on the EQ-5D VAS. A similar effect was seen on the EQ-5D Index, where a 1 point increase on the BPI interference
subscale was associated with a 0.051 increase on the EQ-5D Index, compared with an increase of 0.034 points for a 1 point increase on the severity subscale. The final EQ-VAS and EQ-Index models explained 22% (R2a = 0.222) and 39% (R2a = 0.397) of the variance in scores, respectively.
DISCUSSION This is one of relatively few large-scale studies to have examined the evolution of chronic noncancer pain patients managed with usual care. Other large-scale studies 22 in similar patients have looked at the impact of specific therapies, although they did not use QOL as a primary endpoint. Some authors have recently pointed out the need for more large-scale studies on chronic noncancer pain in Europe.5 This type of study can help to highlight areas of healthcare needs and to suggest where resources and further investigation are required. In the present study, substantial improvements in both QOL and pain outcomes were observed over the 3-month study period, both in the sample as a whole and in the two study subgroups defined by pain severity. Nevertheless, a considerable proportion of patients still reported some pain at the final visit. The very low scores on the EQ-5D Index and VAS at baseline indicate the severe impact of pain on QOL, with all dimensions of QOL measured by EQ-5D being substantially affected. At baseline, over 70% of patients reported at least “some” problems on each EQ-5D dimension. Even on the dimension of self-care, which was the least affected dimension, only 28.3% of patients
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BPI severity score p
