Curr Pain Headache Rep (2014) 18:385 DOI 10.1007/s11916-013-0385-0
CHRONIC DAILY HEADACHE (SJ WANG, SECTION EDITOR)
Economic Burden and Costs of Chronic Migraine Michel Lanteri-Minet
Published online: 13 December 2013 # Springer Science+Business Media New York 2013
Abstract Chronic migraine (CM) is a subtype of migraine broadly defined by the presence of headache at least 15 days per month. Emerging evidence suggests that CM and episodic migraine (EM) differ not only in headache frequency, but that they are distinct clinical entities. Because individuals with CM are more disabled, they demonstrate higher societal burden than those with EM. There have been three important surveys published within the last five years that have focused on the societal burden associated with CM. The first is the American Migraine Prevalence and Prevention (AMPP) study, a longitudinal population-based survey performed in the U.S. The second, the International Burden Migraine Study (IBMS), is a Web-based survey conducted in North America, Western Europe, Asia/Pacific, and Brazil. The third is a clinic-based survey performed in Taiwan. This review discusses results of these studies with regard to healthcare resource use (and related direct costs) and loss of productivity (and related indirect costs) from the perspective of cost-effectiveness of new therapeutic approaches to CM. Keywords Chronic migraine . Episodic migraine . Epidemiology . Burden . Healthresourceuse . Lostproductivity time . MIDAS . Direct costs . Indirect costs . Cost-effectiveness
Introduction Chronic daily headache (CDH) related to migraine was first described as transformed migraine (TM) by Mathew et al. [1], This article is part of the Topical Collection on Chronic Daily Headache M. Lanteri-Minet (*) Département d’Evaluation et Traitement de la Douleur, Pôle Neurosciences Cliniques CHU de Nice, Hôpital de Cimiez, 4 avenue Reine Victoria, 06000 Nice, France e-mail: [email protected]
with diagnostic criteria proposed by Silberstein et al. [2, 3]. This concept of transformed migraine was widely adopted, particularly in the United States, but the term chronic migraine (CM) was preferred by the International Headache Society. In 2004, CM was added to the second edition of the International Classification of Headache Disorders [4] as a complication of migraine. The criteria (ICHD-II criteria) required migraine without aura on 15 or more days per month for at least 3 months in the absence of medication overuse. The International Headache Society determined that these ICHD-II criteria were too restrictive, and in 2006 proposed revised criteria (ICHD-IIR criteria) for a broader concept of CM [5] ICHD-IIR criteria required 15 or more days with headache per month for at least 3 months, and migraine, or a response to migraine-specific treatment, at least 8 days per month, and again required the absence of medication overuse. These ICHD-IIR criteria were controversial due to the fact that medication overuse associated with CM is very common, and if headache frequency increases with the overuse of medication, medication overuse itself may be a response to frequent headache. As a result, modified criteria were proposed in the third edition (ICHD-3 beta version) of the International Classification of Headache Disorders [6••] in 2013. The ICHD-3 criteria allow CM diagnosis in the presence of medication overuse such that, after drug withdrawal, migraine will either revert to the episodic subtype or remain chronic and be re-diagnosed accordingly. Moreover, the ICHD-3 CM criteria distinguishes attacks of either type (without and with aura) from complication of migraine. In an update of the literature on worldwide migraine epidemiology studies including ICHD-II criteria, the aggregate weighted estimate of 12-month prevalence of CM was 0.5 %, with a range of 0.2–2.7 % [7]. In a more inclusive review of studies using both ICHD-II and TM criteria, the prevalence of CM ranged from 0.9 % to 5.1 % in the general population, with estimates typically in the range of 1.4 % to 2.2 % [8].
385, Page 2 of 6
Emerging evidence suggests that if CM and EM are part of the spectrum of migraine disorders, CM is a distinct disorder with a clinico-epidemiological profile different from that of EM (review in 9, with an update in 10). Additionally, although expert opinion has suggested that conventional preventive therapy for EM may also be useful in managing CM [11•], CM and EM each have unique therapeutic response patterns. This has led to new evidence-based treatment options specifically for the management of CM, including botulinum toxin type A [12, 13] and occipital nerve stimulation [14]. Although these new therapeutic treatments are more expensive than conventional preventive treatment, the cost of these alternatives should be considered in the context of the societal and economic burden of CM. With regard to prevalence studies, the evolution of diagnostic criteria over time has been a challenge in epidemiological studies focused on economic burden of CM. Previous data showed that burden of CDH was strongly associated with migraine features and suggested that CM was the more disabling form of CDH [15]. These data have been confirmed in more recent studies comparing the economic impact of EM and CM. This review will provide an update on these recent studies. We will begin by focusing on methodological key elements. Based on the results of the studies, we will describe societal economic burden of CM and provide estimates of the total direct (healthcare resource use) and indirect (headache-related disability) costs associated with CM. Finally, we will discuss the implications of the economic data in cost-effectiveness analysis for new treatments for CM.
Studies Presentation The first of these studies focusing on economic burden of CM was the American Migraine Prevalence and Prevention (AMPP) study [16] that was begun in 2004. This study involved the screening of 120,000 U.S. households to determine a representative population of individuals with self-reporting headache. In 2005, after the initial screening phase, these individuals were included in an initial baseline study in which a survey was conducted to identify headache symptoms and impact. Individuals were then included in a 3-year follow-up phase during which annual questionnaires were utilized to survey changes in symptoms, impairment, and health resource utilization . The AMPP economic burden evaluation utilized data from the 2006 follow-up survey based on an initial sample of 14,544 adults identified as having migraine, aaccording to ICHD-II criteria, in either the 2004 screening or 2005 baseline survey. Among them, a total of 7,796 completed the 2006 follow-up survey. Based on TM criteria, those who developed CM (n=359) were compared with those who did not develop CM (n=7437) in the 1- and 2-year intervals between screening/baseline and follow-up. Data were
Curr Pain Headache Rep (2014) 18:385
collected from self-administered, validated questionnaires on headache frequency (number of headache days in the prior month and past 12 months), resource use (number of visits to a primary care doctor’s office, hospital emergency room, urgent care center, neurologist or headache specialist’s office, or pain clinic in the past 12 months; number of nights spent in the hospital in the past 12 months); medication use (number of months of use of any of 29 identified potential migrainepreventive medications, number of days/month of the use of any of 31 identified non-prescription and prescription acute medications) and productivity loss (number of days of work/ school missed or productivity was reduced by 50 % or greater from the previous 3 months, based on MIDAS questionnaire). Resource use-related costs were estimated using unit cost assumptions from the PharMetrics Patient-Centric database. Medication use-related costs were estimated using wholesale acquisition costs, which were assumed to be equal to published average wholesale drug prices, discounted by 20 %. Annual average productivity estimate was calculated from the MIDAS score, multiplied by 4, and weighted with the national average number of hours worked by women and productivity loss-related costs were estimated by multiplying hours of productivity loss by the national U.S. hourly wage for women aged 25 and older. All unit costs were calculated in 2006 U.S dollars. The study was sponsored by the National Headache Foundation through a grant from OrthoMcNeil Janssen Scientific Affairs, LLC. The second study was the International Burden of Migraine Study (IBMS) [17, 18••]. IBMS was a worldwide study conducted in 2009–2010 in North America (U.S. and Canada), Western Europe (Germany, France, Italy, Spain, and UK), Asia/Pacific (Australia, Taiwan), and Brazil, with detailed data available for North America [19••] and Western Europe [20••]. IBMS utilized a Web-based methodology to recruit individuals with EM (according to ICHD-II criteria) and CM (according to TM criteria). The enrollment target was a minimum of 100 CM subjects in the U.S. and 50 in each of the remaining nine countries. IBMS involved 23,312 participants among 72,059 panelists invited via e-mail to participate (32.4 % response rate). Participants were included in a screening phase from which were selected 9,160 eligible individuals with EM and 555 eligible individuals with CM (enrollment target not reached in Taiwan). All data were collected directly from EM and CM eligible individuals via Web-based survey. Data largely overlapped those from the AMPP study. For each country, the medication list employed in IBMS was adapted to the local market by a key opinion leader or local affiliate familiar with available medications and country practices. In North America and Europe, unit costs unique to each country were collected from detailed data in publicly available sources and were applied to healthcare resource use parameters. Cost estimates were from a direct medical care perspective and calculated in 2010 U.S. or Canadian dollars for
Curr Pain Headache Rep (2014) 18:385
North America, and standardized to 2010 euros for Europe and the UK. The study was funded by Allergan, Inc. With regard to the IBMS-recruited Taiwanese sample, which was too small for meaningful analysis, Wang et al. conducted a study to evaluate economic burden of CM in Taiwan [21••]. This was a cross-sectional clinic-based observational survey performed in two headache clinics from February to April 2011. A total of 331 migraine patients (164 with EM according to ICHD-II criteria and 167 with CM according to TM criteria) completed the survey. Data collected were similar to those collected in IBMS. For healthcare resource use and productivity loss, only descriptive data (without cost estimates) were available. The study was supported, in part, by the Taiwan Headache Society and Allergan Singapore Pte Ltd.
Healthcare Resource Use – Direct Costs Healthcare resource use associated with CM was best presented in the IBMS data, which provided a worldwide comparison of different national health systems [18••, 19••, 20••]. The confirmed that healthcare resource associated with CM was significantly higher than that of EM. In univariate analyses (adjusted for sociodemographic variables and comorbidities) of the entire IBMS population sample, the odds ratio for experiencing primary care physician (PCP) visits during the preceding 3 months was 2.32 (95 % CI: 2.15–2.51) for CM vs. EM; 3.23 (2.78–3.75) for neurologist/headache specialist visits; 3.01 (2.56–3.55) for emergency department visits; and 2.84 (1.99–4.06) for hospitalizations [18••]. Significant differences in healthcare resource use between CM and EM individuals were found in all North American and European countries for PCP visits (Europe: 54.5 % vs. 29.8 %, with p
CHRONIC DAILY HEADACHE (SJ WANG, SECTION EDITOR)
Economic Burden and Costs of Chronic Migraine Michel Lanteri-Minet
Published online: 13 December 2013 # Springer Science+Business Media New York 2013
Abstract Chronic migraine (CM) is a subtype of migraine broadly defined by the presence of headache at least 15 days per month. Emerging evidence suggests that CM and episodic migraine (EM) differ not only in headache frequency, but that they are distinct clinical entities. Because individuals with CM are more disabled, they demonstrate higher societal burden than those with EM. There have been three important surveys published within the last five years that have focused on the societal burden associated with CM. The first is the American Migraine Prevalence and Prevention (AMPP) study, a longitudinal population-based survey performed in the U.S. The second, the International Burden Migraine Study (IBMS), is a Web-based survey conducted in North America, Western Europe, Asia/Pacific, and Brazil. The third is a clinic-based survey performed in Taiwan. This review discusses results of these studies with regard to healthcare resource use (and related direct costs) and loss of productivity (and related indirect costs) from the perspective of cost-effectiveness of new therapeutic approaches to CM. Keywords Chronic migraine . Episodic migraine . Epidemiology . Burden . Healthresourceuse . Lostproductivity time . MIDAS . Direct costs . Indirect costs . Cost-effectiveness
Introduction Chronic daily headache (CDH) related to migraine was first described as transformed migraine (TM) by Mathew et al. [1], This article is part of the Topical Collection on Chronic Daily Headache M. Lanteri-Minet (*) Département d’Evaluation et Traitement de la Douleur, Pôle Neurosciences Cliniques CHU de Nice, Hôpital de Cimiez, 4 avenue Reine Victoria, 06000 Nice, France e-mail: [email protected]
with diagnostic criteria proposed by Silberstein et al. [2, 3]. This concept of transformed migraine was widely adopted, particularly in the United States, but the term chronic migraine (CM) was preferred by the International Headache Society. In 2004, CM was added to the second edition of the International Classification of Headache Disorders [4] as a complication of migraine. The criteria (ICHD-II criteria) required migraine without aura on 15 or more days per month for at least 3 months in the absence of medication overuse. The International Headache Society determined that these ICHD-II criteria were too restrictive, and in 2006 proposed revised criteria (ICHD-IIR criteria) for a broader concept of CM [5] ICHD-IIR criteria required 15 or more days with headache per month for at least 3 months, and migraine, or a response to migraine-specific treatment, at least 8 days per month, and again required the absence of medication overuse. These ICHD-IIR criteria were controversial due to the fact that medication overuse associated with CM is very common, and if headache frequency increases with the overuse of medication, medication overuse itself may be a response to frequent headache. As a result, modified criteria were proposed in the third edition (ICHD-3 beta version) of the International Classification of Headache Disorders [6••] in 2013. The ICHD-3 criteria allow CM diagnosis in the presence of medication overuse such that, after drug withdrawal, migraine will either revert to the episodic subtype or remain chronic and be re-diagnosed accordingly. Moreover, the ICHD-3 CM criteria distinguishes attacks of either type (without and with aura) from complication of migraine. In an update of the literature on worldwide migraine epidemiology studies including ICHD-II criteria, the aggregate weighted estimate of 12-month prevalence of CM was 0.5 %, with a range of 0.2–2.7 % [7]. In a more inclusive review of studies using both ICHD-II and TM criteria, the prevalence of CM ranged from 0.9 % to 5.1 % in the general population, with estimates typically in the range of 1.4 % to 2.2 % [8].
385, Page 2 of 6
Emerging evidence suggests that if CM and EM are part of the spectrum of migraine disorders, CM is a distinct disorder with a clinico-epidemiological profile different from that of EM (review in 9, with an update in 10). Additionally, although expert opinion has suggested that conventional preventive therapy for EM may also be useful in managing CM [11•], CM and EM each have unique therapeutic response patterns. This has led to new evidence-based treatment options specifically for the management of CM, including botulinum toxin type A [12, 13] and occipital nerve stimulation [14]. Although these new therapeutic treatments are more expensive than conventional preventive treatment, the cost of these alternatives should be considered in the context of the societal and economic burden of CM. With regard to prevalence studies, the evolution of diagnostic criteria over time has been a challenge in epidemiological studies focused on economic burden of CM. Previous data showed that burden of CDH was strongly associated with migraine features and suggested that CM was the more disabling form of CDH [15]. These data have been confirmed in more recent studies comparing the economic impact of EM and CM. This review will provide an update on these recent studies. We will begin by focusing on methodological key elements. Based on the results of the studies, we will describe societal economic burden of CM and provide estimates of the total direct (healthcare resource use) and indirect (headache-related disability) costs associated with CM. Finally, we will discuss the implications of the economic data in cost-effectiveness analysis for new treatments for CM.
Studies Presentation The first of these studies focusing on economic burden of CM was the American Migraine Prevalence and Prevention (AMPP) study [16] that was begun in 2004. This study involved the screening of 120,000 U.S. households to determine a representative population of individuals with self-reporting headache. In 2005, after the initial screening phase, these individuals were included in an initial baseline study in which a survey was conducted to identify headache symptoms and impact. Individuals were then included in a 3-year follow-up phase during which annual questionnaires were utilized to survey changes in symptoms, impairment, and health resource utilization . The AMPP economic burden evaluation utilized data from the 2006 follow-up survey based on an initial sample of 14,544 adults identified as having migraine, aaccording to ICHD-II criteria, in either the 2004 screening or 2005 baseline survey. Among them, a total of 7,796 completed the 2006 follow-up survey. Based on TM criteria, those who developed CM (n=359) were compared with those who did not develop CM (n=7437) in the 1- and 2-year intervals between screening/baseline and follow-up. Data were
Curr Pain Headache Rep (2014) 18:385
collected from self-administered, validated questionnaires on headache frequency (number of headache days in the prior month and past 12 months), resource use (number of visits to a primary care doctor’s office, hospital emergency room, urgent care center, neurologist or headache specialist’s office, or pain clinic in the past 12 months; number of nights spent in the hospital in the past 12 months); medication use (number of months of use of any of 29 identified potential migrainepreventive medications, number of days/month of the use of any of 31 identified non-prescription and prescription acute medications) and productivity loss (number of days of work/ school missed or productivity was reduced by 50 % or greater from the previous 3 months, based on MIDAS questionnaire). Resource use-related costs were estimated using unit cost assumptions from the PharMetrics Patient-Centric database. Medication use-related costs were estimated using wholesale acquisition costs, which were assumed to be equal to published average wholesale drug prices, discounted by 20 %. Annual average productivity estimate was calculated from the MIDAS score, multiplied by 4, and weighted with the national average number of hours worked by women and productivity loss-related costs were estimated by multiplying hours of productivity loss by the national U.S. hourly wage for women aged 25 and older. All unit costs were calculated in 2006 U.S dollars. The study was sponsored by the National Headache Foundation through a grant from OrthoMcNeil Janssen Scientific Affairs, LLC. The second study was the International Burden of Migraine Study (IBMS) [17, 18••]. IBMS was a worldwide study conducted in 2009–2010 in North America (U.S. and Canada), Western Europe (Germany, France, Italy, Spain, and UK), Asia/Pacific (Australia, Taiwan), and Brazil, with detailed data available for North America [19••] and Western Europe [20••]. IBMS utilized a Web-based methodology to recruit individuals with EM (according to ICHD-II criteria) and CM (according to TM criteria). The enrollment target was a minimum of 100 CM subjects in the U.S. and 50 in each of the remaining nine countries. IBMS involved 23,312 participants among 72,059 panelists invited via e-mail to participate (32.4 % response rate). Participants were included in a screening phase from which were selected 9,160 eligible individuals with EM and 555 eligible individuals with CM (enrollment target not reached in Taiwan). All data were collected directly from EM and CM eligible individuals via Web-based survey. Data largely overlapped those from the AMPP study. For each country, the medication list employed in IBMS was adapted to the local market by a key opinion leader or local affiliate familiar with available medications and country practices. In North America and Europe, unit costs unique to each country were collected from detailed data in publicly available sources and were applied to healthcare resource use parameters. Cost estimates were from a direct medical care perspective and calculated in 2010 U.S. or Canadian dollars for
Curr Pain Headache Rep (2014) 18:385
North America, and standardized to 2010 euros for Europe and the UK. The study was funded by Allergan, Inc. With regard to the IBMS-recruited Taiwanese sample, which was too small for meaningful analysis, Wang et al. conducted a study to evaluate economic burden of CM in Taiwan [21••]. This was a cross-sectional clinic-based observational survey performed in two headache clinics from February to April 2011. A total of 331 migraine patients (164 with EM according to ICHD-II criteria and 167 with CM according to TM criteria) completed the survey. Data collected were similar to those collected in IBMS. For healthcare resource use and productivity loss, only descriptive data (without cost estimates) were available. The study was supported, in part, by the Taiwan Headache Society and Allergan Singapore Pte Ltd.
Healthcare Resource Use – Direct Costs Healthcare resource use associated with CM was best presented in the IBMS data, which provided a worldwide comparison of different national health systems [18••, 19••, 20••]. The confirmed that healthcare resource associated with CM was significantly higher than that of EM. In univariate analyses (adjusted for sociodemographic variables and comorbidities) of the entire IBMS population sample, the odds ratio for experiencing primary care physician (PCP) visits during the preceding 3 months was 2.32 (95 % CI: 2.15–2.51) for CM vs. EM; 3.23 (2.78–3.75) for neurologist/headache specialist visits; 3.01 (2.56–3.55) for emergency department visits; and 2.84 (1.99–4.06) for hospitalizations [18••]. Significant differences in healthcare resource use between CM and EM individuals were found in all North American and European countries for PCP visits (Europe: 54.5 % vs. 29.8 %, with p
