Lee et al. Health Economics Review 2014, 4:6 http://www.healtheconomicsreview.com/content/4/1/6
RESEARCH
Open Access
A comparison of the cost-effectiveness of treatment of prolonged acute convulsive epileptic seizures in children across Europe Dawn C Lee1*, Daniel Gladwell1, Anthony J Hatswell1, Joshua Porter1, Nic Brereton1, Elaine Tate1 and Alison L Saunders2
Abstract In the majority of children and adolescents with epilepsy, optimal drug therapy adequately controls their condition. However, among the remaining patients who are still uncontrolled despite mono-, bi- or tri-therapy with chronic anti-epileptic treatment, a rescue medication is required. In Western Europe, the licensed medications available for first-line treatment of prolonged acute convulsive seizures (PACS) vary widely, and so comparators for clinical and economic evaluation are not consistent. No European guidelines currently exist for the treatment of PACS in children and adolescents and limited evidence is available for the effectiveness of treatments in the community setting. The authors present cost-effectiveness data for BUCCOLAM® (midazolam oromucosal solution) for the treatment of PACS in children and adolescents in the context of the treatment pathway in seven European countries in patients from 6 months to 18 years. For each country, the health economic model consisted of a decision tree, with decision nodes informed by clinical data and expert opinion obtained via a Delphi methodology. The events modelled are those associated with a patient experiencing a seizure in the community setting. The model assessed the likelihood of medication being administered successfully and of seizure cessation. The associated resource use was also modelled, and ambulance call-outs and hospitalisations were considered. The patient’s quality of life was estimated by clinicians, who completed a five-level EuroQol five dimensions questionnaire from the perspective of a child or adolescent suffering a seizure. Despite differences in current therapy, treatment patterns and healthcare costs in all countries assessed, BUCCOLAM was shown to be cost saving and offered increased health-related benefits for patients in the treatment of PACS compared with the current local standard of care. Keywords: Epilepsy; Cost–utility modelling; BUCCOLAM; Health technology assessment
Background Even in a relatively homogeneous region such as Western Europe, with similar population demographics and state-provided healthcare systems, differences in culture, legislation and financial incentives can mean that the treatment of patients with the same condition varies between countries. In some disease areas, the pathway of care (even the healthcare setting; that is, primary versus secondary care) may, therefore, differ between countries, and some drugs may be used routinely in one country but not be available in another. A consequence of these variations is that pharmaceutical companies are faced * Correspondence: [email protected] 1 BresMed, North Church House, 84 Queen Street, Sheffield S1 2DW, UK Full list of author information is available at the end of the article
with different challenges in persuading health technology assessment (HTA) agencies in each country of the value of their product. In this paper, we consider the example of BUCCOLAM (midazolam oromucosal solution; available from ViroPharma SPRL – BVBA, Belgium) in the treatment of prolonged, acute, convulsive seizures (PACS) in children and adolescents [1]. Across Europe, 130,000 new cases of epilepsy are recorded each year among children and adolescents (an incidence rate of 70–80 per 100,000) [2,3]. The incidence is particularly high during the first year of life, and the likelihood of developing the condition then decreases during childhood [3]. Anti-epileptic drug therapy is the primary treatment for children with epilepsy, with the aim of preventing seizures [4], and approximately 70% of
© 2014 Lee et al.; licensee Springer. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Lee et al. Health Economics Review 2014, 4:6 http://www.healtheconomicsreview.com/content/4/1/6
patients become seizure-free with optimal drug therapy [3,5]. However, patients do not always receive optimal drug therapy and approximately 50–60% of patients with epilepsy experience breakthrough seizures during the course of a year, some of whom will require a prescription for rescue medication [2]. Children who have severe, symptomatic epilepsy are those who are most commonly prescribed rescue medication [6]. The longer a seizure continues, the greater the likelihood of pharmacoresistance to termination and a worse health outcome for the patient, including increased risks of subsequent prolonged seizure activity, memory deficits and learning difficulties [7,8]. In addition, the impact on health resources is greater because these patients require more intensive medical assistance [6,9-11]. The costs of direct medical care for children with epilepsy can be very high – a recent study in Germany, for example, showed that the mean direct medical cost over three months was €1,940 for children with non-drugresistant seizures and €3,464 for those with drugresistant seizures [12]. Prompt treatment with rescue medication is an important aspect of care for children experiencing PACS; however, such treatment provides a particular challenge because these seizures occur predominantly in the community setting where rescue medication and trained carers may not always be available. A recent study by Anderson et al. noted that the ideal drug for the treatment of convulsive seizures in paediatric patients would have the following characteristics [8]: A rapid onset of action. A broad spectrum of efficacy; that is, not restricted
to a particular seizure type or underlying cause. A prolonged duration of action. Minimal adverse effects. A simple and socially acceptable administration route for both patient and caregiver. Easy storage and portability.
In most European countries, no clear guidance is available for the treatment of PACS outside of the hospital setting and no clear guidance is provided for caregivers [13,14]. In Western Europe, the treatment pathways for the use of rescue medication in the management of PACS can be broadly categorised into two groups: many continental European countries primarily advocate the use of licensed treatments, whereas a number of other countries primarily employ unlicensed treatments. More specifically, in Denmark, France, Germany, Italy and Spain the mainstay of rescue treatment is rectal diazepam, which was the only licensed treatment for PACS in children until recently. In Switzerland and Germany, there
Page 2 of 15
is frequent off-label buccal use of fast dissolving lorazepam tablets (as well as rectal diazepam). Countries that most commonly use unlicensed buccal midazolam include the UK, Sweden and Norway [13]. A significant body of evidence now supports buccal midazolam as an effective and safe first-line therapy for prolonged seizures [8], which avoids the social stigma of rectal administration. In September 2011, BUCCOLAM was granted a Paediatric-Use Marketing Authorisation (PUMA) by the European Medicines Agency (EMA) [1]. The PUMA initiative aims to ensure that medicines used to treat children are subject to high-quality, ethical research and are appropriately authorised without subjecting the paediatric population to unnecessary clinical trials [15]. In most European countries, BUCCOLAM is indicated for the treatment of PACS in infants, toddlers, children and adolescents (from three months to
RESEARCH
Open Access
A comparison of the cost-effectiveness of treatment of prolonged acute convulsive epileptic seizures in children across Europe Dawn C Lee1*, Daniel Gladwell1, Anthony J Hatswell1, Joshua Porter1, Nic Brereton1, Elaine Tate1 and Alison L Saunders2
Abstract In the majority of children and adolescents with epilepsy, optimal drug therapy adequately controls their condition. However, among the remaining patients who are still uncontrolled despite mono-, bi- or tri-therapy with chronic anti-epileptic treatment, a rescue medication is required. In Western Europe, the licensed medications available for first-line treatment of prolonged acute convulsive seizures (PACS) vary widely, and so comparators for clinical and economic evaluation are not consistent. No European guidelines currently exist for the treatment of PACS in children and adolescents and limited evidence is available for the effectiveness of treatments in the community setting. The authors present cost-effectiveness data for BUCCOLAM® (midazolam oromucosal solution) for the treatment of PACS in children and adolescents in the context of the treatment pathway in seven European countries in patients from 6 months to 18 years. For each country, the health economic model consisted of a decision tree, with decision nodes informed by clinical data and expert opinion obtained via a Delphi methodology. The events modelled are those associated with a patient experiencing a seizure in the community setting. The model assessed the likelihood of medication being administered successfully and of seizure cessation. The associated resource use was also modelled, and ambulance call-outs and hospitalisations were considered. The patient’s quality of life was estimated by clinicians, who completed a five-level EuroQol five dimensions questionnaire from the perspective of a child or adolescent suffering a seizure. Despite differences in current therapy, treatment patterns and healthcare costs in all countries assessed, BUCCOLAM was shown to be cost saving and offered increased health-related benefits for patients in the treatment of PACS compared with the current local standard of care. Keywords: Epilepsy; Cost–utility modelling; BUCCOLAM; Health technology assessment
Background Even in a relatively homogeneous region such as Western Europe, with similar population demographics and state-provided healthcare systems, differences in culture, legislation and financial incentives can mean that the treatment of patients with the same condition varies between countries. In some disease areas, the pathway of care (even the healthcare setting; that is, primary versus secondary care) may, therefore, differ between countries, and some drugs may be used routinely in one country but not be available in another. A consequence of these variations is that pharmaceutical companies are faced * Correspondence: [email protected] 1 BresMed, North Church House, 84 Queen Street, Sheffield S1 2DW, UK Full list of author information is available at the end of the article
with different challenges in persuading health technology assessment (HTA) agencies in each country of the value of their product. In this paper, we consider the example of BUCCOLAM (midazolam oromucosal solution; available from ViroPharma SPRL – BVBA, Belgium) in the treatment of prolonged, acute, convulsive seizures (PACS) in children and adolescents [1]. Across Europe, 130,000 new cases of epilepsy are recorded each year among children and adolescents (an incidence rate of 70–80 per 100,000) [2,3]. The incidence is particularly high during the first year of life, and the likelihood of developing the condition then decreases during childhood [3]. Anti-epileptic drug therapy is the primary treatment for children with epilepsy, with the aim of preventing seizures [4], and approximately 70% of
© 2014 Lee et al.; licensee Springer. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Lee et al. Health Economics Review 2014, 4:6 http://www.healtheconomicsreview.com/content/4/1/6
patients become seizure-free with optimal drug therapy [3,5]. However, patients do not always receive optimal drug therapy and approximately 50–60% of patients with epilepsy experience breakthrough seizures during the course of a year, some of whom will require a prescription for rescue medication [2]. Children who have severe, symptomatic epilepsy are those who are most commonly prescribed rescue medication [6]. The longer a seizure continues, the greater the likelihood of pharmacoresistance to termination and a worse health outcome for the patient, including increased risks of subsequent prolonged seizure activity, memory deficits and learning difficulties [7,8]. In addition, the impact on health resources is greater because these patients require more intensive medical assistance [6,9-11]. The costs of direct medical care for children with epilepsy can be very high – a recent study in Germany, for example, showed that the mean direct medical cost over three months was €1,940 for children with non-drugresistant seizures and €3,464 for those with drugresistant seizures [12]. Prompt treatment with rescue medication is an important aspect of care for children experiencing PACS; however, such treatment provides a particular challenge because these seizures occur predominantly in the community setting where rescue medication and trained carers may not always be available. A recent study by Anderson et al. noted that the ideal drug for the treatment of convulsive seizures in paediatric patients would have the following characteristics [8]: A rapid onset of action. A broad spectrum of efficacy; that is, not restricted
to a particular seizure type or underlying cause. A prolonged duration of action. Minimal adverse effects. A simple and socially acceptable administration route for both patient and caregiver. Easy storage and portability.
In most European countries, no clear guidance is available for the treatment of PACS outside of the hospital setting and no clear guidance is provided for caregivers [13,14]. In Western Europe, the treatment pathways for the use of rescue medication in the management of PACS can be broadly categorised into two groups: many continental European countries primarily advocate the use of licensed treatments, whereas a number of other countries primarily employ unlicensed treatments. More specifically, in Denmark, France, Germany, Italy and Spain the mainstay of rescue treatment is rectal diazepam, which was the only licensed treatment for PACS in children until recently. In Switzerland and Germany, there
Page 2 of 15
is frequent off-label buccal use of fast dissolving lorazepam tablets (as well as rectal diazepam). Countries that most commonly use unlicensed buccal midazolam include the UK, Sweden and Norway [13]. A significant body of evidence now supports buccal midazolam as an effective and safe first-line therapy for prolonged seizures [8], which avoids the social stigma of rectal administration. In September 2011, BUCCOLAM was granted a Paediatric-Use Marketing Authorisation (PUMA) by the European Medicines Agency (EMA) [1]. The PUMA initiative aims to ensure that medicines used to treat children are subject to high-quality, ethical research and are appropriately authorised without subjecting the paediatric population to unnecessary clinical trials [15]. In most European countries, BUCCOLAM is indicated for the treatment of PACS in infants, toddlers, children and adolescents (from three months to
![[Prolonged convulsive seizures in children: how are they managed outside the hospital?].](/assets/img/hold.png)
