Quality of life and treatment satisfaction in Spanish epilepsy patients on monotherapy with lamotrigine or valproic acid

Article Outline

• Abstract
• 1. Introduction
• 2. Methods
  • 2.1. Statistical analysis
• 3. Results
  • 3.1. Sample description
  • 3.2. Overall HRQoL and treatment satisfaction
  • 3.3. Women subanalysis
  • 3.4. Women HRQoL and treatment satisfaction
• 4. Discussion
  • 4.1. Overall sample
• 5. Conclusions
• Competing interests
• Acknowledgements
• Appendix A. 
• References
• Copyright

Abstract 

Background

Patients suffering from epilepsy have an impaired health related quality of life (HRQoL) because of seizures and treatment adverse events. Epilepsy affects differently both genders, due to hormonal influence in women. The aim of this study is to assess the impact on HRQoL and treatment satisfaction in epilepsy patients treated with stable doses of lamotrigine and valproic acid.

Methods

Observational cohort prospective study was conducted in 18 Spanish neurology sites. Patients with clinically stable partial or generalized epilepsy, already receiving lamotrigine or valproic acid on monotherapy, were assessed in two visits: baseline and at 6 months. Socio-demographic and clinical variables were recorded at baseline; HRQoL (QOLIE-10) treatment satisfaction and women image self-perception were assessed at both visits. Impact on HRQoL was assessed in both treatment arms overall and in the women subgroup.

Results

A total of 107 patients were evaluated; 53 (14 men, 39 women) on lamotrigine and 54 (27 men, 27 women) on valproic acid. Mean (SD) age was 30.4 (9.1) years and mean (SD) time since epilepsy diagnosis was 8 (8.1) years. Mean (SD) QOLIE-10 score at baseline was 73.9 (15.7) points (76.6 and 71.4 for lamotrigine and valproic, respectively). At follow up, patients reported better HRQoL on both lamotrigine (78.8 points) (p<0.05) and on valproic (72.4 points) in comparison with baseline. Women's HRQoL at follow up was better on the lamotrigine arm compared with valproic acid: 78.8 (12.8) vs. 70.3 (15.9) (p<0.05). Women on the lamotrigine arm declared higher satisfaction with treatment and higher disagreement with the different statements referred to a negative image self-perception.

Conclusions

Chronic patients with epilepsy already treated with lamotrigine slightly improved HRQoL at 6 month follow up, whereas no significant changes were observed in the valproic acid group. Lamotrigine impact on patients’ HRQoL seems to be even more positive in the subgroup of women.

Keywords: Health related quality of life (HRQoL), Epilepsy, QOLIE-10, Lamotrigine, Valproic acid

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1. Introduction 

Epilepsy is a chronic neurological disorder characterized by recurrent episodes of sensory, motor or autonomic phenomena with or without loss of consciousness. It is estimated that, in the general population, 4–10 per 1000 people have active epilepsy.¹ Up to 70% of people with epilepsy could lead normal lives with adequate treatment²; thus, the choice of an antiepileptic therapy is guided both by the objectives of reducing the number of seizures and minimizing adverse events. Monotherapy is preferred to polytherapy because the risk of adverse events and drug interactions, the increasing cost of therapy, and lesser patient compliance.³

Although epilepsy is as frequent in women as it is in men,⁴ women present some gender-specific problems with regard due to a relation between hormones (oestrogen and progesterone) and seizures.⁵ Women of childbearing age also cope with many added difficulties: menstrual and fertility problems and drug–drug interactions of antiepileptic drugs (AED) with hormonal preparations including oral contraceptives. Potential teratogenicity of AED may also condition their decisions about pregnancy, as foetal malformations are doubled in women taking AED compared with the general population (7% vs. 3%).⁶

Valproic acid and lamotrigine are frequently used first-line AED. Valproic acid is effective in generalized tonic–clonic seizures and partial seizures being the drug of choice for absences and myoclonic seizures.⁷ Lamotrigine has been approved for monotherapy, and shown to be efficacious in the treatment of both generalized and focal epilepsy syndromes.^[8], ^[9] One of the main advantages of lamotrigine is that it causes little cognitive impairment or sedation compared with other treatments,¹⁰ while its main disadvantage is the risk of skin rash.^[11], ^[12]

Health related quality of life (HRQoL) is impaired in patients with epilepsy compared to people of the same age and gender in the general population.¹³ Several factors contribute to the poor HRQoL in these patients, including worry about seizures, functional impairment, educational handicap, difficulties with relationships and depression. Patients with partial or generalized epileptic seizures have reported significantly lower HRQoL compared with healthy people using the SF-36.^[14], ^[15] Several instruments are available to assess HRQoL in patients with epilepsy, including both generic questionnaires such as the SF-36¹⁶ and the different versions of the Quality of Life in Epilepsy Inventory (QOLIE), QOLIE-89, QOLIE-31,²¹ and QOLIE-10.²²

The objective of the study was to assess HRQoL and treatment satisfaction among epileptic patients already receiving lamotrigine and valproic acid in a real life practice setting.

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2. Methods 

This observational, two-cohort prospective multicentre study was carried out between January 2004 and March 2006. A total of 21 neurologists from 18 different sites all over Spain took part in the study. The main objective of the study was the validation of the Spanish version of the QOLIE-10 Questionnaire, as reported elsewhere.²²

Patients with partial or generalized epilepsy aged between 18 and 50 years old, who had been clinically controlled on monotherapy with lamotrigine or valproic acid, at stable doses, for a minimum of 1.5 months and a maximum of 4.5 months, were consecutively invited to participate. Pregnant or breastfeeding women, patients taking lamotrigine who had previously taken valproic acid or vice versa, patients with secondary epilepsy or progressive disease and patients in whom the study drugs were contraindicated, were excluded. Written informed consent was obtained from all the participants. The study was approved by the Germans Trias i Pujol Hospital Research Ethics Committee, and received administrative authorization according to the Spanish law.

All assessable patients completed the study procedures in the two scheduled visits according to the protocol: an initial visit (baseline) and a 6 month follow-up visit. At the baseline visit, general socio-demographic characteristics were collected, as well as the type of epilepsy, time since diagnosis, previous and current antiepileptic treatment. At 6 months, any changes in the antiepileptic treatment and adverse events suffered by the patient were collected. At both visits, other variables were collected by QOLIE-31 (data not shown), QOLIE-10, patient's satisfaction with treatment and women's physical image self-perception.

The QOLIE-10 is a disease specific HRQoL questionnaire for epilepsy, derived from the QOLIE-31. The QOLIE-10 is a 10-item questionnaire, with two domains: ‘daily activities and treatment impact’ and ‘mental health’. The overall score ranges from 0 to 100, the higher score the better HRQoL. The period of time to which the questions refer to is “during the last four weeks”.

A short ad hoc questionnaire with five questions especially designed for this study was used to assess patients’ treatment satisfaction (effect on general health, relief of epilepsy symptoms, adverse effects, number of tablets, overall satisfaction). Response options were collected in a 5-Likert scale response options (going from 1 “very unsatisfied” to 5 “very satisfied”). The questions addressed: global health, symptoms relief, absence of adverse events, and treatment received to treat epilepsy. The higher score the better the satisfaction with the treatment.

Self-perceived physical image was assessed in women through seven ad hoc questions (“I see myself different in the mirror”, “I feel ugly”, “I look awful in photographs”, “I don’t go out with friends because the way I look”, “I try to avoid social relationships”, “people look at me because the way I look”. “the physical changes caused by my disease and treatment are limiting my life”) with a 5-Likert scale response options (from 1 “absolutely agree” to 5 “absolutely disagree”): the higher the disagreement with the questions, the better physical image's perception.

2.1. Statistical analysis 

The sample size was calculated in order to validate the Spanish version of QOLIE-10, the primary objective of the study.²² A descriptive analysis of the socio-demographic and clinical variables (including time since diagnosis, type of seizure, and concomitant diseases), and humanistic variables was carried out for the study population, by treatment arms. For all the variables, comparisons between visits within each treatment arm were performed, as well as comparisons between both treatment arms. All comparisons were carried out using parametric tests or non-parametric tests when appropriate.

The effect size, a measure to quantify the importance of the questionnaire score changes between visits, was calculated as the mean score change in QOLIE-10 divided by the standard deviation (SD) of the baseline score.

In the subgroup of women a subanalysis was performed in order to detect differences on the HRQoL in women between both visits and between treatment arms. Self-perceived physical image was also analyzed to detect differences between both visits and between treatment arms.

All data were analyzed using the 15.0 version of the SPSS software. The probability level of 0.05 was considered statistically significant.

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3. Results 

3.1. Sample description 

A total of 116 patients were included in the study, 9 of them did not complete the follow-up period (1 patient voluntarily withdrew from the study, 2 were withdrawn due to pregnancy and 6 were lost to follow up). Thus, 107 patients were evaluable, 53 on the lamotrigine arm and 54 on the valproic acid arm.

Mean age (SD) of patients was 30.4 (9.1) years; 61.7% (n=66) were women (39 on lamotrigine and 27 on valproic acid); the predominance of women on lamotrigine was statistically significant (p<0.05). Other socio-demographic characteristics are shown in Table 1. Concomitant diseases were present in 29 patients (27.1%), most of them were allergies (6.5%) or dermatological disorders (4.7%).

Table 1. Socio-demographic and clinical patients’ characteristics by treatment arms.

Global	Lamotrigine	Valproic acid	Total
	n	n	n
Socio-demographic characteristics
Gender*
Woman	39	27	66
Total	53	54	107
Education level
None/primary	16	27	43
Secondary	22	19	41
University	14	8	22
Total	52	54	106
Working status
Self-employed	5	6	11
Salary earner	31	20	51
Unemployed	4	7	11
Housekeeping	5	5	10
Student	6	15	21
Other	1	1	2
Total	52	54	106
Clinical characteristics
Type of seizure
Generalized seizures	20	38	58
Partial seizures	29	16	45
Not specified seizures	4	-	4
Total	53	54	107
BMI [Mean (SD)]	23.6 (3.3)	26.2 (3.1)	24.9 (3.4)

¥ p<0.01; BMI: Body Mass Index (kg/m²).

Mean time elapsed since epilepsy diagnosis was 8.0 years (7.6 and 8.3 years for lamotrigine and valproic groups, respectively (p>0.05)). A relation was observed between the type of epileptic seizures and the treatment group: 54.8% of patients had partial seizures in the lamotrigine arm, whereas the majority of patients (70.4%) in the valproic acid arm had generalized seizures (p<0.01) (Table 1).

During the study, 61.3% of patients reported adverse events, 52.8% of those treated with lamotrigine and 69.8% with valproic acid (Table 2). Statistically significant differences were observed for the occurrence of tremor (p<0.05), hair loss (p<0.01), confusion (p<0.01), and weight gain (p<0.01); all of them occurred more frequently in patients on valproic acid.

Table 2. Drug adverse events by treatment arms (>10% incidence) [data shown as number and percentage of adverse events].

3.2. Overall HRQoL and treatment satisfaction 

At baseline, the mean (SD) QOLIE-10 overall score was 76.6 (14.3) points in the lamotrigine arm, while at the follow-up visit this score improved to 78.8 (13.8) points (p<0.05). Analyzing the results by domain at baseline, patients receiving lamotrigine scored 79.9 (16.3) points on ‘daily activities and treatment impact’ domain, these scores increasing to 83.8 (15.6) points at follow up (p<0.05). For the ‘mental health’ domain, the baseline score (SD) for lamotrigine arm was of 71.7 (16.7), and 71.5 (14.9) at follow up (Table 3).

Table 3. QOLIE-10 score by treatment arms [data shown as mean (SD) points].

Global	Lamotrigine (N=51)			Valproic acid (N=52)			Total (N=103)
	Baseline	Follow up	Diff	Baseline	Follow up	Diff	Baseline	Follow up	Diff
Daily activities and treatment impact	79.9 (16.3)	83.8 (15.6)	3.9 (10.3)	76.7 (20.2)	78.0 (17.7)	1.4 (10.2)	78.3 (18.4)	80.9 (16.9)	2.6 (10.3)
Mental health	71.7 (16.7)	71.5 (14.9)	−0.3 (8.8)	63.4 (17.4)	63.8 (17.3)	0.4 (8.1)	67.5 (17.5)	67.6 (16.5)	0.1 (8.4)
Total QOLIE-10	76.6 (14.3)	78.8 (13.8)	2.3 (7.4)	71.4 (16.7)	72.4 (15.3)	1.0 (7.9)	73.9 (15.7)	75.5 (14.9)	1.6 (7.6)

*Lamotrigine: daily activities and treatment impact domain between visits, p<0.05; total QOLIE-10, p<0.05.

In the valproic acid arm, the mean overall score (SD) on QOLIE-10 at baseline was 71.4 (16.7) points, increasing to 72.4 (15.3) after the follow-up visit at 6 months. The score in the ‘daily activities and treatment impact’ domain increased from 76.7 (20.2) points, at baseline, to 78.0 (17.7) at follow up; and on the ‘mental health’ domain the baseline score was 63.4 (17.4) points and it increased to 63.8 (17.3) points at follow up. Nevertheless, none of the changes between both visits on the valproic treated arm reached statistical significance (Table 3).

The effect size according to changes on overall QOLIE-10 scores between baseline and follow-up visit is shown in Fig. 1. The greater change on HRQoL due to treatment, the greater was the effect size. Effect size by treatment arm is not shown as only a few patients on each treatment group reported a worse HRQoL on the follow up than on baseline.

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• Fig. 1. 

  Effect size on QOLIE-10 of treatment intervention.

3.3. Women subanalysis 

Mean (SD) age of women (n=66) was 29.8 (8.4) years; other socio-demographic and clinical women's characteristics are shown in Table 4.

Table 4. Socio-demographic and clinical women's characteristics by treatment arms.

Women	Lamotrigine	Valproic acid	Total
	n	n	n
Socio-demographic characteristics
Education level
None/primary	11	12	23
Secondary	19	11	30
University	9	4	13
Total	39	27	66
Working status
Self-employed	2	1	3
Salary earner	23	9	32
Unemployed	3	4	7
Housekeeping	5	4	9
Student	4	9	13
Other	1	–	1
Total	38	27	65
Clinical characteristics
Type of seizure¥
Generalized seizures	11	20	31
Partial seizures	25	7	32
Not specified seizures	3	–	3
Total	39	27	66
BMI* [Mean (SD)]	23.3 (3.1)	25.7 (3.9)	24.3 (3.6)

BMI: Body Mass Index (kg/m²).

AED's adverse events were suffered by 63.6% of the women (53.8% and 77.8% of patients on lamotrigine and valproic, respectively) (Table 5). Statistical significant differences between both treatment arms were shown for confusion (p<0.05), weight gain (p<0.01), tremor (p<0.01), and hair loss (p<0.01), all of them being more frequent in women receiving valproic acid than in those receiving lamotrigine.

Table 5. Drug adverse events suffered by women by treatment arms (>10% incidence) [data shown as number and percentage of adverse event].

BMI measure experienced a change between both visits, decreasing a mean (SD) of 0.3kg/m² in women on lamotrigine and increasing by 0.4kg/m² in women on valproic acid (p<0.05).

3.4. Women HRQoL and treatment satisfaction 

The mean QOLIE-10 overall score (SD) at baseline for women treated with lamotrigine was 76.3 (12.7) points and, at the follow-up visit improved to 78.8 (12.8) points (p<0.05). Patients scored 79.6 (15.0) points at baseline on ‘daily activities and treatment impact’ domain, this increasing to 83.6 (14.6) points at follow up (p>0.05). On the ‘mental health’ domain the baseline score for lamotrigine was of 71.2 (15.1), and decreased to 70.9 (14.1) at follow up (Table 6).

Table 6. QOLIE-10 score in women by treatment arms [data shown as mean (SD) points].

Women	Lamotrigine (N=39)			Valproic acid (N=25)			Total (N=64)
	Baseline	Follow up	Diff	Baseline	Follow up	Diff	Baseline	Follow up	Diff
Daily activities and treatment impact	79.6 (15.0)	83.6 (14.6)	4.06 (11.0)	76.5 (21.1)	75.1 (19.9)	−1.4 (8.7)	78.4 (17.5)	80.3 (17.2)	1.9 (10.4)
Mental health	71.2 (15.1)	70.9 (14.1)	−0.3 (9.0)	62.5 (18.3)	63.0 (17.4)	0.5 (8.8)	67.8 (16.9)	67.8 (15.8)	0 (8.8)
Total QOLIE-10¥	76.3 (12.7)	78.8 (12.8)	2.5 (7.8)	70.8 (17.3)	70.3 (15.9)	−0.5 (7.1)	74.1 (14.8)	75.5 (14.6)	1.3 (7.6)

On the valproic acid treatment arm, the mean (SD) overall score on QOLIE-10 at baseline was 70.8 (17.3) points, and 70.3 (15.9) after 6 months. The ‘daily activities and treatment impact’ domain the score decreased from 76.5 (21.1) points at baseline to 75.1 (19.9) at follow up; and on the ‘mental health’ domain the baseline score was 62.5 (18.3) points and increased to 63.0 (17.4) points at follow up. None of the changes between both visits on the valproic acid arm reached statistical significance (Table 6). Women's HRQoL at follow up was better on the lamotrigine arm compared with valproic acid: 78.8 (12.8) points vs. 70.3 (15.9) (p<0.05).

Satisfaction with treatment was not different between treatments, although more women reported to be “satisfied” or “very satisfied” with the lamotrigine treatment than with valproic acid (Fig. 2).

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• Fig. 2. 

  Percentage of patients who rated ‘satisfied’ or ‘very satisfied’ in the two treatment arms, global and women. LTG: lamotrigine; VPA: valproic acid.

In general, women reported to disagree with the statements regarding the negative self-perceived image. At the follow-up visit more women on the lamotrigine arm disagreed than women on the valproic acid arm. On the assertion: ‘I see myself differently in front of a mirror’ more patients on the lamotrigine arm disagreed with it than patients on the valproic arm on both visits (p<0.05) (Fig. 3).

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• Fig. 3. 

  Percentage of patients who rated ‘disagree’ or ‘strongly disagree’ in the physical image self-perception in women. LTG: lamotrigine; VPA: valproic acid.

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4. Discussion 

4.1. Overall sample 

The results of this study show that even though chronic patients with epilepsy reported no significant changes on HRQoL after 6 months’ follow up, a slight improvement was observed in patients on lamotrigine. Additionally, when comparing HRQoL in women at the end of the follow-up visit, patients on lamotrigine showed a better score compared with patients on valproic acid. It is important to keep in mind that epilepsy patients receiving stable doses of antiepileptic drug are not expected to have substantial changes on their HRQoL.²³

In women receiving lamotrigine, an improvement on HRQL was observed in comparison with those receiving valproic acid. They were also more satisfied with their treatment and had a better image self-perception than those in the valproic acid group.

Lamotrigine and valproic acid have been approved in Spain for a number of years for the treatment of generalized as well as partial seizures on monotherapy.²⁴ In this study, patients with partial seizures were mainly treated with lamotrigine, while those with generalized seizures were treated with valproic acid. The different distribution of patients on treatment groups by seizure type indicates the preference of neurologists to prescribe a different AED according to the type of seizure to treat, even though both lamotrigine and valproic acid are indicated for both generalized and partial seizures. As a result of this treatment pattern, the distribution of patients between treatment arms seems biased according to type of seizure. Due to the design of our study, a purely observational study following clinical practice, the study groups are not completely homogenous, and therefore comparisons should be made with caution.

Adverse events were observed in more than 60% of patients, which is not surprising if we compare this figure with the percentages of adverse events reported in previous studies with lamotrigine (72.7%) and valproic acid (83.3%).²⁵ Despite the rate of adverse events, both drugs were well tolerated; no adverse event occurred during the study was severe, and no patient withdrew because of adverse events. Patients receiving stable doses of lamotrigine slightly improved their HRQoL during the study, despite of 60.4% of patients suffering adverse events. Patients on the valproic acid arm did not improve nor worsen their HRQoL although they suffered more adverse events (69.8%) than lamotrigine treated patients. Additionally, the HRQoL did not change significantly from the baseline to the follow-up visit, despite the percentage of patients who suffered adverse events during the study period. This fact suggests that HRQoL may not be substantially affected by adverse events on patients on monotherapy with stable doses of antiepileptic drugs.

This was an observational study, so no experimental intervention was performed on the patients groups and physicians followed their usual clinical practice. At baseline, patients had already been receiving treatment at stable doses for six weeks at least; this may explain why no significant changes were observed in patients’ HRQoL. The effect size between the scores at each visit was small because patients were on stable antiepileptic medication, hence a greater impact was only seen in those patients in whom their HRQoL worsened after the 6 month follow-up period. Lamotrigine has already demonstrated to improve several aspects of HRQoL in patients with epilepsy when compared with valproic acid (assessed by QOLIE-89).²⁶ Moreover, a recently published study found that HRQoL in patients receiving valproic acid was especially affected by the incidence of adverse events.²⁷ In contrast, Marson et al.²⁸ did not find any differences on HRQoL between treatments in a study performed comparing topiramate, valproic acid and lamotrigine. The study patients on the lamotrigine arm scored higher in their HRQoL than those on valproic acid, this confirming that lamotrigine patients were less affected by adverse events than epileptic patients on valproic.

The percentage of patients satisfied with the treatment for epilepsy was high; for patients on lamotrigine it was over 80% for all five questions in both visits; for patients on valproic acid it ranged between 50% and 80%. In a previous study with well-controlled epileptic patients, more than 90% of them scored as excellent or satisfactory different statements related to their antiepileptic treatment.²⁹ The results of this study confirm that, in general, epileptic patients under treatment are satisfied with the treatment received; there was a trend to better satisfaction in those patients receiving lamotrigine.

Women with stable doses of antiepileptic drugs on monotherapy did not change significantly their HRQoL over the time; their QOLIE-10 scores were similar at both visits, which was to be expected since women were already on stable treatment at the study inclusion. When both treatment arms were studied separately, lamotrigine treated-women, after 6 months of follow up, exhibited more improvement in the HRQoL score than those women receiving valproic acid. In general, women on valproic acid scored worse than the whole study sample, which suggests that valproic acid impacts negatively HRQoL in epileptic women. A study, previously conducted in Italy, confirmed that female gender was a strong predictor of worse HRQoL in epileptic patients on stable treatment.³⁰

Patients’ HRQoL may be affected by adverse events occurring during antiepileptic treatment. During the study period, increase in weight was observed in 16.7% of women. Weight gain was more frequent in women receiving valproic acid than in those receiving lamotrigine, this difference showing statistical significance. Despite such statistical differences, no clinical implication is foreseen as the overall absolute weight gain was less than 1kg. The results from an online survey performed during 2005 revealed that women's greatest concern related to antiepileptic drug therapy was weight gain (63% “extremely” or “very” concerned), among others, and 75% of the women participating in the survey said that antiepileptic treatment affected their weight.³¹ Weight gain is a common adverse event observed in patients receiving stable doses of valproic acid, and greater than in patients receiving lamotrigine.³² The results of these two previous studies may provide a clue to explain the trend towards better satisfaction with treatment in women receiving lamotrigine in this study, since, even if the increase in weight was small, women seem to be very concerned about this.

Physical self-perception only showed differences between study treatments, at both visits, in only one question: ‘I see myself differently in a mirror’. Despite no other differences were identified between treatments, a trend towards greater improvement could be distinguished for lamotrigine; even for those questions whose answers worsened between visits, lamotrigine remained superior to valproic acid.

Several methodological limitations should be noted. First of all, because of its non-interventional observational design, study cohorts are likely not to be balanced regarding several factors that may influence quality of life and satisfaction with treatment. Therefore, the results should be interpreted with caution. Secondly, the main objective of the original study was to assess the validity of the translated version of the epilepsy specific questionnaire, QOLIE-10, not to establish differences in HRQoL between treatments. Therefore it is reasonable to believe that with a larger sample size, larger differences intra-treatment or inter-treatments might have been found. For the gender subanalysis, the sample size was even smaller. Another reason why large differences were not found in patients’ HRQoL during the follow up is the fact that the patients included in the study were all clinically stable and had been receiving the study treatment for a certain period.

Future investigations should be specifically designed to assess long-term variations on HRQoL, to include other common antiepileptic drugs in order to compare usual clinical practice drugs on patients with stable disease. In particular, to assess those specific gender issues that showed a trend in this study, such as the improvement on women's HRQoL being treated with lamotrigine.

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5. Conclusions 

In conclusion, HRQoL in epileptic patients receiving stable doses of lamotrigine showed a slight improvement after 6 month follow up while no significant change was shown in valproic acid treated patients. More patients in the lamotrigine arm referred to be satisfied with treatment than those on the valproic acid therapy. A trend towards higher improvement on HRQoL was shown in women on lamotrigine, and they also reported higher satisfaction with the antiepileptic drug.

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Competing interests 

Dr. C. Viteri has served as consultant, advisor or speaker for the following companies: UCB. EISAI, GSK and Pfizer. Dr. M. Codina has no conflict of interests. Dr. J. Barriga, Dr. S. Barrera, and Dr. M.D. Morales have no conflict of interests. Dr. J. Lahuerta and S. Cobaleda are employees of GlaxoSmithKline, S.A.

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Acknowledgements 

The authors thank the following organisation and people for their scientific and logistic contributions to the project; Xavier Badía, Nuria Perulero y Evelyn Cadenas, IMS Health, Health Economics and Outcomes Research.

This study was funded by GlaxoSmithKline, S.A. Tres Cantos (Madrid), Spain. The sponsor GSK contributed to the design, conduct, analysis and interpretation of this study. However the final authority on the interpretation of the results was given to the first author (Dr. C. Viteri).

The authors would like to acknowledge the investigators taking part in the Spanish QOLIE-10 validation Study Group.

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Appendix A. 

The Spanish QOLIE-10 Validation Study Group: Elena López, H. de Xàtiva (Valencia), Lamberto Landete, H. Dr. Peset (Valencia), Angel Pérez, H. Vega Baja (Alicante), Mercedes Martín, H. Gregorio Marañón (Madrid), Ignacio Sarasqueta, H. de la Princesa (Madrid), Fco. Javier Barriga, H. Fundación Alcorcón (Madrid), Juan Galán, H. de Valme (Sevilla), Dolores Morales, H. Virgen de la Macarena (Sevilla), Juan Mercadé, H. Carlos Haya (Málaga), Sebastián Barrera, H. Virgen de la Macarena (Sevilla), Mª Isabel Forcadas, H. de Cruces (Bilbao), Purificación Cacabelos, H. Clínico Universitario (Salamanca), Jesús Cacho, H. Clínico Universitario (Salamanca), Alberto Mercado, H. General Yagüe (Burgos), José Ramón Lorenzo, Clínica Povisa (Pontevedra), Soledad López, H. Juan Canalejo (La Coruña) Robustiano Pego, H. Xral Calde (Lugo), Renée Ribacoba, H. Álvarez Buylla (Asturias), Alberto García, H. Central de Asturias (Asturias), Javier Martín, Hospital Virgen de la Arrixaca (Murcia), José Meca, Hospital Virgen de la Arrixaca (Murcia).

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