HE380.0.1 Managed Healthcare Assignment 4
nmbeytrickrtts
RequiredReadingChapter2.2.pdf
Economic evaluations in European reimbursement submission guidelines: current status and comparisons Expert Rev. Pharmacoecon. Outcomes Res. 13(5), 579–595 (2013)
Andrea Bracco*1 and Marieke Krol2,3
1 AMGEN Europe GmbH, Dammstrasse
23, Zug, Switzerland 2 Department of Health Policy and
Management, Erasmus University,
Rotterdam, The Netherlands 3 Institute for Medical Technology
Assessment, Erasmus University,
Rotterdam, The Netherlands
*Author for correspondence:
Tel.: + 41 413 692 590
Fax: + 41 413 690 400
This study aimed to review European national health-economic (HE) guidelines and to identify recent developments in guideline recommendations by comparing the findings with those of a review published in 2001. Guidelines were identified by searching websites of the Internal Society for Pharmacoeconomics and Outcomes Research (ISPOR) and government health insurance agencies, and by a literature review. National guidelines showed broad consistency in ranking clinical data sources and choice of comparators for HE analysis, but varied in recommended costs to be included, methods related to cost calculation and discounting. Many European countries have developed or revised national HE guidelines. The recommendations in these guidelines differ in some key aspects, limiting transferability of outcomes of HE evaluations.
KEYWORDS: health economics • health technology assessment • pharmacoeconomic guidelines • reimbursement • societal perspective
The past decade has seen considerable expan- sion of the use of health-economic (HE) anal- ysis to inform decision makers when considering reimbursement of new health interventions in Europe. Although in some European nations HE analysis has been incor- porated in the decision-making process since the 1990s [1,2], in other countries HE analysis began to play a formal role much later. In Belgium, for example, the application of Health Technology Assessment (HTA) in reim- bursement decisions was introduced in 2001, and since 2003 the Belgian Health Care Knowledge Centre (Federaal Kenniscentrum voor de Gezondheidszorg/Centre fédéral d’expertise des soins de santé; KCE) has been charged with advising policy makers on effi- cient allocation of healthcare resources, includ- ing evaluation of drug cost–effectiveness [3]. Similarly, submission of a HE analysis has been mandatory for pharmaceutical companies seeking reimbursement in The Netherlands only since 2005 [4]. In France, the National
Authority for Health (Haute Autorité de Santé; HAS) was established in 2005 to assist health- care decision-making, but was not charged with conducting HE assessments prior to 2008 [5]. In eastern Europe the use of HE anal- ysis in reimbursement processes has also been increasing [6]; HTA agencies in the region now play a key role in applying HE analysis to reimbursement decision making [7]. Beyond new guidelines emerging in countries previ- ously lacking HE guidelines, existing guidelines are regularly updated, sometimes with major changes (e.g., the German guidelines [8]).
A seminal review of national HE guidelines by Hjelmgren et al. (2001) identified a lack of consensus on key aspects of HE analysis [9]. Although most European guidelines seemed in fairly good agreement regarding recommenda- tions on type of HE analysis, use of incremen- tal rather than average cost–effectiveness ratios, use of modeling and choice of time horizon, the review identified important differences among guidelines on topics such as HE study
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perspective, inclusion of resources and costs and the valuation of resources. Moreover, the review reported on some inconsis- tencies within guidelines. For instance, several guidelines rec- ommended using a societal perspective while simultaneously insisting on focusing on direct healthcare costs. Similarly, a 2005 review by Jacobs et al. reported large variation among national guidelines in recommendations on costing and valua- tion [10]. More recently, Knies et al. focused on recommenda- tions in different countries on study perspective and methods for valuing lost productivity, and revealed ongoing differences regarding the inclusion of the societal perspective and, among guidelines advocating this perspective, how to value loss of productivity [11].
Reviewing variation among HE guidelines from different agencies, Sculpher and Drummond pointed out that some dif- ferences are to be expected given legitimate diversity among healthcare systems [12]. Other differences may be attributable to a lack of theoretical consensus regarding specific HE topics for which variation exists among available HE methods and there is no clear basis to select a preferred approach. However, other differences are more difficult to justify because they are incon- sistent with healthcare system objectives and constraints, or do not reflect good methodological practice [12].
Given the evolving state of HE guidelines in Europe in the past decade, and the discrepancies in previous guideline recom- mendations from different nations, we set out to comprehen- sively review current European HE guidelines. The main goals were to update the 2001 review of HE guidelines by Hjelmgren et al. in order to highlight new developments of European national health economic guidelines over the past decade, and to identify whether there has been any convergence on recommendations for those aspects of HE studies where previous reviews found discordance. Moreover, we summarized the guidelines’ content on key topics (e.g., recommendations regarding perspective, discounting and comparator) and we assessed the categorization of the guidelines regarding their role in reimbursement applications.
Methods Complementary methods were applied to identify the most current HE guidelines for European nations. Websites of the Internal Society for Pharmacoeconomics and Outcomes Research (ISPOR), primarily ISPOR’s ‘Pharmacoeconomic Guidelines Around The World’ database [101] and government health insurance agencies were searched. Members of national HE organizations were also contacted to request relevant guide- lines for countries whose guidelines could not be readily retrieved from the internet.
Additionally, a literature search was conducted using online search engines. Primary searches used PubMed, with supplementary searches for citing articles using Google Scholar. PubMed literature searches used the following search terms: ‘health economic’, ‘pharmacoeconomic’, ‘reimburs*’ or ‘health technology assessment’; combined with ‘guideline’ or ‘guidelines’, ‘recommendation’ or
‘recommendations’; combined with ‘Europe’ or ‘European’. To increase sensitivity of searches, additional searches were performed without the terms ‘Europe’ or ‘European’. The last search update was conducted on 27 March 2011.
Identified guidelines were summarized according to their intended use and main recommendations. Retrieved guidelines were analyzed according to the following framework:
• Identifying the status of HE guidelines for each country since the 2001 Hjelmgren et al. review:
– Which guidelines were new? – Which guidelines were updated? – Which guidelines remained unchanged?
• Reviewing the guideline recommendations
– Summarize the guideline’s key recommendations. – Identify similarities and differences.
Information from guidelines was summarized into tables. Guidelines were categorized into one of three types according to their role in national reimbursement processes, adapting defini- tions used by Hjelmgren et al. (2001) based on prior work by Drummond (1994) [9,13]. Formalized guidelines were defined as those whose recommendations were required for reimbursement submissions. Informal guidelines were those intended to guide reimbursement submissions, but not considered by payers to be mandatory. Finally, guidelines for economic evaluations were defined as general recommendations intended for use in discus- sing and improving methodology in HE evaluations.
Additionally, the guidelines’ content was tabulated on the following topics: the type of analysis recommended by the guidelines, the recommended study perspective, information on the direct costs to include, information on indirect costs, if any, to include in the economic evaluation and which method should be used for quantification of productivity loss, the method and the rate to use for discounting, recommended data sources for evidence of comparative efficacy, and finally recom- mendations on choice of comparators.
Results The current status of national HE guidelines in Europe is pre- sented in (TABLE 1). New guidelines are now available for ten European countries that were not included in the 2001 review by Hjelmgren et al. [9]. These were primarily in eastern Europe, but also included Scotland, Austria and Swe- den. Of the 13 countries included in the 2001 review, 12 had updated versions of HE guidelines; the exception was Portugal, for which the 1998 HE guidelines remain current [102]. The UK NICE updated and published new guidelines in April 2013.
As shown in (TABLE 2), most national HE guidelines were for- malized, prescribing HE methods for reimbursement submis- sions. Although Portugal’s guidelines were identified by Hjelmgren et al. as being formalized, the guidelines themselves state that they were not be intended to be considered administra- tive (i.e., mandatory), but rather were a guide of good practice
Review Bracco & Krol
580 Expert Rev. Pharmacoecon. Outcomes Res. 13(5), (2013)
that was sufficiently general to be used in any institutional con- text [102]; accordingly, we have categorized them as informal. Guidelines for Spain were also considered to be informal, though they may become mandatory to follow in reimbursement submis- sions in the near future [14]. Similarly, ISPOR notes that follow- ing the methodology of Poland’s informal guidelines is recommended for sponsors requesting reimbursement there [102,103]. The only other countries with non-formalized guidelines were Austria and France, which have general methodo- logical guidelines for conducting HE studies [15,104].
Cost–utility (CUA), cost–effectiveness (CEA) and cost–mini- mization (CMA) studies were the types of analysis most often identified as acceptable methods (TABLE 2). Most guidelines expressed a preference for CUA, but acknowledged that there would be cases where CEA or CMA would be more appropri- ate (specifically, scenarios in which quality-adjusted life years (QALYs) were not the most relevant outcome measure). Cost- benefit analysis (CBA) was generally discouraged, although some guidelines considered it acceptable under limited circum- stances. Notable exceptions were Switzerland, in which CBA was considered to be the preferred reference case method to use, if data on economic valuation of outcomes permitted [16], and Germany, where CBA was prescribed using the efficiency frontier approach [105–107]. Some of the guidelines where CUA was recommended also indicated methods to measure utilities. Time-Trade-Off (TTO), Standard Gamble and the Visual Ana- logue scales were the preferred methods to determine individual utility values as recommended in the guidelines from France, Sweden, Portugal and Italy [17,101,104,108], whereas the EQ-5D (Euro QoL), the SF-36 and Health Utility Index were the health-related quality of life (HRQoL) instruments mentioned in the guidelines from UK, Hungary, Poland, Norway, The Netherlands and Belgium [18,19,102,109,110,111].
Despite some formalized HE guidelines recommended a healthcare payer perspective (TABLE 2) the majority of these also accepted presentation of a societal perspective as an additional analysis. A societal perspective was more often the primary rec- ommendation of academic HE methods guidelines or informal guidelines, as in France and Portugal [101,104].
Generally speaking, current national HE guidelines identified similar resources to include in direct costs: primarily direct medi- cal and nonmedical costs arising as a result of the proposed treat- ment and its consequences, though there was less consensus on how to value indirect costs (TABLE 2). Guidelines that requested the societal perspective universally included lost employee productiv- ity in indirect costs, but varied in how specific they were regard- ing inclusion of both absenteeism and decreased productivity while at work, or economic losses due to premature death. There remained little agreement on methods for valuing productivity losses, indicating no movement towards standardization since the guideline versions reviewed by Knies et al. [11]. In addition there was limited guidance in how to value unpaid work. Sweden was the only country requiring the inclusion of indirect medical costs for future medical care not directly related to the proposed treatment [109].
Most HE guidelines requested discounting of both costs and benefits that accrued over more than a year into the future (TABLE 3). The most commonly requested annual discount rates were in the range from 3 to 5%. Although most guidelines advocated using the same discount rate for costs and benefits, lower discount rates for benefits compared with costs were advo- cated in Belgium, The Netherlands and Poland [18,102,109]. The majority of guidelines called for sensitivity analyses in which dis- count rates were varied to assess the sensitivity of results to this parameter.
Table 1. Versions of European Health Economic guidelines cited in published reviews.
Country Date of national guideline version
Hjelmgren et al. (2001) [9]
Current version
Austria NA 2006
Baltic States NA 2002
Belgium 1995 2008 †
Croatia NA 2009
Denmark 1995 2008
England & Wales 2001 2008/2009 ‡
Finland 1999 2009
France 1997 2003/2004 §
Germany 1995 2009
Hungary NA 2002
Ireland 1999 2010
Italy 1995 2001
The Netherlands 1999 2006
Norway 1999 2005
Poland NA 2009
Portugal 1998 1998
Russia NA 2002
Scotland NA 2011
Slovak Republic NA 2009
Spain 1995 2010
Sweden NA 2003/2008 {
Switzerland 1995 2000
† Guidelines in the published paper [18] are identical to those in the 2008 report [117] by the same authors. ‡The 2008 Technology Appraisal Methods guidelines are still current, but an implementation guide for manufacturers was updated in 2009 and the NICE guide to technology appraisal was updated in April 2013. § 2004 is the date of the English translation, but the original French version is from 2003. {The 2003 pharmacoeconomic guidelines are still current, but an implementation guide for manufacturers was updated in 2008. NA: Not included.
Economic evaluations in reimbursement guidelines Review
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T a b le
2 . R e co
m m e n d a ti o n s o n a n a ly ti c m e th o d s,
p e rs p e ct iv e s a n d co
st s in
E u ro p e a n H e a lt h E co
n o m ic s g u id e li n e s.
C o u n tr y
T y p e o f
g u id e li n e s
T y p e o f a n a ly si s
P e rs p e ct iv e
D ir e ct
co st s
In d ir e ct
co st s
R e f.
A u st ri a
G u id e lin e s fo r
e co n o m ic
e va lu a ti o n s
C E A , C U A , C M A o r C B A ,
d e p e n d in g o n th e
re se a rc h q u e st io n ; c h o ic e
m u st
b e ju st if ie d
C h o ic e o f p e rs p e c ti ve
m u st
d e ri ve
lo g ic a lly
fr o m
re se a rc h q u e st io n a n d b e
ju st if ie d . P re se n t re su lt s fo r
d if fe re n t p e rs p e ct iv e s
se p a ra te ly
A ll c o n su m p ti o n o f
re so u rc e s re su lt in g fr o m
tr e a tm
e n t: d ir e ct
m e d ic a l
a n d n o n m e d ic a l c o st s
P ro d u ct iv it y lo ss e s re su lt in g fr o m
ill n e ss
a n d p re m a tu re
d e a th . If
im p a ir m e n t o f w o rk
c a p a c it y is
c o n si d e re d to g e th e r w it h
a b se n te e is m , th is m u st
b e p re se n te d
se p a ra te ly . H C A p re fe rr e d ; u se
o f
F C M
m u st
b e ju st if ie d
[1 5]
B a lt ic st a te s
(E st o n ia , L a tv ia ,
L it h u a n ia )
F o rm
a liz e d
C E A , C U A o r C M A ;
c h o ic e m u st
b e ju st if ie d
H e a lt h c a re
p e rs p e ct iv e .
S o ci e ta l p e rs p e c ti ve
m a y
o n ly b e p re se n te d in
a d d it io n to
d ir e c t
h e a lt h c a re
p e rs p e ct iv e if
c o n si d e re d re le va n t b y
a p p lic a n t
A ll d ir e c t c o st s in si d e
h e a lt h c a re
sy st e m .
N o n m e d ic a l c o st s; e .g .,
so c ia l se rv ic e s, p a ti e n t
tr a ve l, o th e r c o st s to
th e
p a ti e n t o r fa m ily
In d ir e c t c o st s sh o u ld
b e re p o rt e d
se p a ra te ly . M e th o d s fo r c a lc u la ti n g
p ro d u c ti vi ty
c o st s n o t sp e c if ie d
[1 18 ]
B e lg iu m
F o rm
a liz e d
C E A if im
p ro v in g lif e -
e xp e ct a n cy
is m o st
im p o rt a n t o u tc o m e ; C U A
if tr e a tm
e n t h a s
si g n if ic a n t H R Q o L im
p a c t;
C M A o n ly if ju st if ie d b y
p ro o f o f id e n ti c a l
o u tc o m e v s c o m p a ra to r;
C B A n o t a c ce p te d a s
re fe re n ce
c a se
b u t m a y
b e p re se n te d in
a d d it io n
to C E A o r C U A
H e a lt h c a re
p a ye r
p e rs p e ct iv e . A d d it io n a l
a n a ly se s fr o m
b ro a d e r
p e rs p e ct iv e c a n b e
p re se n te d if c o n si d e re d
im p o rt a n t, b u t sh o u ld
b e
c le a rl y d is ti n g u is h e d fr o m
th e re fe re n c e c a se
D ir e c t h e a lt h c a re
c o st s p a id
b y h e a lt h c a re
b u d g e t a n d
p a ti e n t c o p a ym
e n ts .
N o n m e d ic a l c o st s m a y b e
p re se n te d se p a ra te ly if
c o n si d e re d im
p o rt a n t
P ro d u ct iv it y lo ss e s a n d in d ir e c t
h e a lt h c a re
c o st s m a y b e p re se n te d in
a se p a ra te
a n a ly si s. M e th o d s fo r
c a lc u la ti n g p ro d u ct iv it y c o st s n o t
sp e ci fi e d
[1 8]
C ro a ti a
F o rm
a liz e d
C E A n o t m a n d a to ry .
H o w e v e r, p re v io u sl y
p u b lis h e d C E A o r C E A
su b m it te d in
o th e r
ju ri sd ic ti o n s sh o u ld
b e
su b m it te d a s a tt a ch m e n ts
H e a lt h c a re
p a ye r
p e rs p e ct iv e
D ir e c t c o st s in cl u d e d ru g s,
p ri m a ry
c a re ,
h o sp it a liz a ti o n , sp e c ia lis t
a d v is o ry
c a re , si ck
le a ve
N A
[1 19 ]
D e n m a rk
F o rm
a liz e d
C E A , C U A o r C B A
d e p e n d in g o n th e
re se a rc h q u e st io n
S o ci e ta l p e rs p e c ti ve
re c o m m e n d e d ; a n a ly se s
w it h n a rr o w e r p e rs p e ct iv e
m u st
b e ju st if ie d
D ir e c t c o st s sp e n t o n th e
tr e a tm
e n t o r sa v e d b y
c h a n g in g th e tr e a tm
e n t
R e p o rt c o st s d u e to
p ro d u c ti o n lo ss
se p a ra te ly . H C A re c o m m e n d e d o ve r
F C M
[1 19 ,1 20 ]
A E : A d ve rs e e v e n t; C B A : C o st – b e n e fi t a n a ly si s; C C A : C o st – co n se q u e n ce
a n a ly si s; C D A : C o st -o f- d is e a se
a n a ly si s; C E A : C o st – e ff e ct iv e n e ss
a n a ly si s; C M A : C o st -m
in im
iz a ti o n a n a ly si s; C U A : C o st – u ti lit y a n a ly si s; C V A : C o st –
va lu e
a n a ly si s;
FC M : Fr ic ti o n
c o st
m e th o d ; H C A : H u m a n
ca p it a l a p p ro a c h ; H E : H e a lt h -e co n o m ic ; H R Q o L:
H e a lt h -r e la te d
q u a lit y o f lif e ; H S E : H e a lt h
S e rv ic e
E x e c u ti ve ; LY
G : Li fe -y e a r g a in e d ; N A : N o t a p p lic a b le ;
N H S : N a ti o n a l H e a lt h S e rv ic e ; Q A LY
: Q u a lit y- a d ju st e d lif e ye a r; P S S : P e rs o n a l S o ci a l S e rv ic e s; S H I: S ta tu to ry
H e a lt h In su ra n ce ; W T P : W ill in g n e ss
to p a y .
Review Bracco & Krol
582 Expert Rev. Pharmacoecon. Outcomes Res. 13(5), (2013)
T a b le
2 . R e co
m m e n d a ti o n s o n a n a ly ti c m e th o d s,
p e rs p e ct iv e s a n d co
st s in
E u ro p e a n H e a lt h E co
n o m ic s g u id e li n e s (c o n t. ).
C o u n tr y
T y p e o f
g u id e li n e s
T y p e o f a n a ly si s
P e rs p e ct iv e
D ir e ct
co st s
In d ir e ct
co st s
R e f.
E n g la n d &
W a le s
F o rm
a liz e d
C U A (C E A is
re c o m m e n d e d a s
a p p ro p ri a te
fo rm
o f
e co n o m ic e va lu a ti o n , b u t
h e a lt h e ff e c ts
sh o u ld
b e
e xp re ss e d in
Q A L Y s)
F o r th e re fe re n ce
c a se , th e
p e rs p e ct iv e o n o u tc o m e s
sh o u ld
b e a ll d ir e c t h e a lt h
e ff e ct s w h e th e r fo r p a ti e n ts
o r, w h e re
re le v a n t, o th e r
in d iv id u a ls . T h e p e rs p e c ti ve
a d o p te d o n c o st s sh o u ld
b e
th a t o f th e N H S a n d P S S
C o st s sh o u ld
re la te
to
re so u rc e s th a t a re
u n d e r
th e c o n tr o l o f th e N H S a n d
P S S . W h e re
th e a ct u a l p ri c e
p a id
fo r re so u rc e m a y d if fe r
fr o m
th e p u b lic
lis t p ri ce
(e .g ., p h a rm
a ce u ti c a ls ,
m e d ic a l d e v ic e s) , th e p u b lic
lis t p ri c e sh o u ld
b e u se d
In e xc e p ti o n a l ci rc u m st a n ce s w h e n
te ch n o lo g ie s h a ve
a su b st a n ti a l im
p a ct
o n th e co st s (o r sa vi n g s) to
o th e r
g o ve rn m e n t b o d ie s, co st s to
o th e r
g o ve rn m e n t b o d ie s m a y b e in cl u d e d if
th is h a s b e e n sp e ci fi ca lly
a g re e d w it h
th e D e p a rt m e n t o f H e a lt h . W h e n
n o n – re fe re n ce -c a se
a n a ly se s in cl u d e
th e se
b ro a d e r co st s, e xp lic it m e th o d s
o f va lu a ti o n a re
re q u ir e d . In
a ll ca se s,
th e se
co st s sh o u ld
b e re p o rt e d
se p a ra te ly fr o m
N H S /P S S co st s. T h e se
co st s sh o u ld
n o t b e co m b in e d in to
a n
in cr e m e n ta l co st – e ff e ct iv e n e ss
ra ti o
(I C E R ; w h e re
th e Q A LY
is th e
o u tc o m e m e a su re
o f in te re st )
[1 11 ]
F in la n d
F o rm
a liz e d
C E A , C U A , C M A o r C B A ,
d e p e n d in g o n h o w
th e
th e ra p ie s c o m p a re d a ff e ct
p a ti e n t h e a lt h st a te s;
c h o ic e m u st
b e ju st if ie d
S o c ie ta l p e rs p e c ti v e
e ss e n ti a l; d ir e ct
m e d ic a l
p e rs p e ct iv e in su ff ic ie n t
u n le ss
m e d ic in e c o st
is th e
o n ly d if fe re n ce
b e tw
e e n
tr e a tm
e n ts
A ll th e d ir e c t h e a lt h ca re
c o st s o f th e m e d ic a l
p ro d u c t a n d th e
c o m p a ra to r
C o st s o f p ro d u ct io n lo ss e s a tt ri b u ta b le
to th e d is e a se
b e ca u se
o f a b se n te e is m ,
th e va lu e o f le is u re
ti m e lo st , a n d th e
va lu e o f a ss is ta n ce
n e e d e d b u t n o t
re m u n e ra te d . If in d ir e ct
co st s a re
p re se n te d , th e y sh a ll b e k e p t cl e a rl y
se p a ra te
fr o m
d ir e ct
co st s a n d re su lt s
sh a ll a ls o b e p re se n te d e xc lu si ve
o f
in d ir e ct
co st s. M e th o d s fo r ca lc u la ti n g
p ro d u ct iv it y co st s n o t sp e ci fi e d
[1 22 ]
F ra n c e
G u id e lin e s fo r
e co n o m ic
e va lu a ti o n s
C E A , C U A , C M A , C C A o r
C B A , d e p e n d in g o n th e
re se a rc h q u e st io n ; c h o ic e
m u st
b e ju st if ie d
W id e st
p o ss ib le
p e rs p e ct iv e
(s o c ie ta l) p re fe rr e d .
P e rs p e c ti ve
o f o th e r a g e n ts
(e .g ., F re n ch
n a ti o n a l h e a lt h
in su ra n c e p ro g ra m ) a ls o
p o ss ib le
D ir e ct
m e d ic a l a n d
n o n m e d ic a l c o st s
a tt ri b u ta b le
to th e d is e a se
P ro d u ct io n , p ro d u ct iv it y a n d h u m a n
lif e lo ss e s. N o re c o m m e n d a ti o n
b e tw
e e n H C A a n d F C M
d u e to
lim it a ti o n s o f e a c h a p p ro a ch .
In c lu si o n o f in d ir e c t c o st s m u st
b e
sp e c if ic a lly
a n a ly z e d a n d it s im
p a c t o n
th e re su lt s o f th e e va lu a ti o n st u d ie d
in th e lig h t o f th e m e th o d a d o p te d
[1 05 ]
G e rm
a n y
F o rm
a liz e d
C B A u si n g e ff ic ie n c y
fr o n ti e r a p p ro a ch
H e a lt h c a re
p a ye r p ri m a ri ly .
If lo ss
o f p ro d u ct iv it y is
su b st a n ti a lly
a ff e c te d b y
n e w
h e a lt h te c h n o lo g y,
c o rr e sp o n d in g c o st s m a y b e
e va lu a te d se p a ra te ly
D ir e ct
m e d ic a l co st s o f
re so u rc e s re im b u rs e d b y th e
S H I o r p a ti e n t co p a ym
e n ts .
D ir e ct
n o n -m
e d ic a l co st s (e .g .,
tr a n sp o rt co st s, h o m e h e lp )
sh o u ld
b e in cl u d e d if p e rt in e n t
In c lu d e lo ss
o f p ro d u c ti vi ty
d u e to
m o rt a lit y o n th e b e n e fi t si d e . In cl u d e
lo ss
o f p ro d u c ti vi ty
d u e to
in c a p a c it y
fo r w o rk
o n th e c o st
si d e a s in d ir e c t
c o st s. P ri m a ri ly u se
H C A , b u t F C M
m a y a ls o b e u se d
[1 05 – 10 7]
A E : A d ve rs e e v e n t; C B A : C o st – b e n e fi t a n a ly si s; C C A : C o st – co n se q u e n ce
a n a ly si s; C D A : C o st -o f- d is e a se
a n a ly si s; C E A : C o st – e ff e c ti ve n e ss
a n a ly si s; C M A : C o st -m
in im
iz a ti o n a n a ly si s; C U A : C o st – u ti lit y a n a ly si s; C V A : C o st –
va lu e
a n a ly si s;
F C M : Fr ic ti o n
co st
m e th o d ; H C A : H u m a n
ca p it a l a p p ro a c h ; H E : H e a lt h -e co n o m ic ; H R Q o L:
H e a lt h -r e la te d
q u a lit y o f lif e ; H S E : H e a lt h
S e rv ic e
E xe cu ti v e ; L Y G : Li fe -y e a r g a in e d ; N A : N o t a p p lic a b le ;
N H S : N a ti o n a l H e a lt h S e rv ic e ; Q A LY
: Q u a lit y- a d ju st e d lif e ye a r; P S S : P e rs o n a l S o ci a l S e rv ic e s; S H I: S ta tu to ry
H e a lt h In su ra n ce ; W T P : W ill in g n e ss
to p a y .
Economic evaluations in reimbursement guidelines Review
www.expert-reviews.com 583
T a b le
2 . R e co
m m e n d a ti o n s o n a n a ly ti c m e th o d s,
p e rs p e ct iv e s a n d co
st s in
E u ro p e a n H e a lt h E co
n o m ic s g u id e li n e s (c o n t. ).
C o u n tr y
T y p e o f
g u id e li n e s
T y p e o f a n a ly si s
P e rs p e ct iv e
D ir e ct
co st s
In d ir e ct
co st s
R e f.
H u n g a ry
F o rm
a liz e d
C E A , C U A o r C M A
d e p e n d in g o n th e
re se a rc h q u e st io n
H e a lt h ca re
p a y e r
p e rs p e ct iv e . S o c ie ta l
p e rs p e ct iv e a ls o d e si ra b le ;
p re se n t re su lt s se p a ra te ly
fr o m
p a y e r p e rs p e c ti ve
T h e p e rs p e c ti ve
o f c o st in g
sh o u ld
b e th e sa m e a s th e
st u d y p e rs p e c ti ve . C o n si d e r
o n ly th o se
c o st s in c u rr e d
d ir e c tl y a s a c o n se q u e n c e
o f th e in te rv e n ti o n u n d e r
in v e st ig a ti o n
C a lc u la te
p ro d u ct iv it y c o st s a s g ro ss
a v e ra g e sa la ry
fo r w o rk in g a g e d
p a ti e n ts
in b a se -c a se
a n a ly si s. N o
p re fe rr e d m e th o d to
c a lc u la te
p ro d u ct iv it y c o st s; te st
d if fe re n t
a p p ro a c h e s in
se n si ti v it y a n a ly se s
[1 9]
Ir e la n d
F o rm
a liz e d
C U A p re fe rr e d fo r
re fe re n ce
ca se . In
e xc e p ti o n a l ci rc u m st a n ce s,
C E A m a y b e u se d a s
re fe re n ce
o r se co n d a ry
a n a ly si s if C U A is
co n si d e re d u n su it a b le ;
ch o ic e m u st b e ju st if ie d .
C M A m a y b e co n si d e re d if
n o m e a n in g fu l d if fe re n ce
in
im p o rt a n t o u tc o m e s e xi st s
b e tw
e e n co m p a ra to rs
F o r th e re fe re n c e c a se , th e
p e rs p e ct iv e o n o u tc o m e s
sh o u ld
b e a ll h e a lt h e ff e ct s
a cc ru in g to
in d iv id u a ls .
P e rs p e c ti ve
o n c o st s sh o u ld
b e th a t o f th e p u b lic ly -
fu n d e d h e a lt h a n d so c ia l
c a re
sy st e m . S o c ie ta l
p e rs p e ct iv e m a y b e
p re se n te d a s a se co n d a ry
a n a ly si s if e x p e ct e d to
im p a ct
re su lt s si g n if ic a n tl y
O n ly d ir e c t m e d ic a l c o st s
fo r th e H S E ; e xc lu d e n o n -
re im
b u rs a b le
c o st s b o rn e b y
p a ti e n ts
M a y in cl u d e p ro d u ct iv it y c o st s, a s
w e ll a s a d d it io n a l c o st s th a t m a y
a c cr u e to
o th e r p u b lic
se ct o r
a g e n c ie s, p a ti e n ts
o r c a re g iv e rs
a s a
re su lt o f a te c h n o lo g y.
M e th o d s fo r
c a lc u la ti n g p ro d u c ti vi ty
c o st s n o t
sp e c if ie d
[1 12 ,1 13 ]
It a ly
F o rm
a liz e d
C E A o r C U A p re fe rr e d ;
C M A c a n b e
c o m p le m e n ta ry ; C B A n o t
lik e ly to
b e h e lp fu l
S o c ie ta l p e rs p e ct iv e a n d
It a lia n N H S p e rs p e ct iv e
D ir e ct m e d ic a la n d
n o n m e d ic a lc o st s. W it h ty p e s
o f re so u rc e s. C o st s o b ta in e d
fr o m
st u d ie s ca rr ie d o u t in
m e d ic a ls tr u ct u re s a re
p re fe rr e d . U n p a id se rv ic e s
p ro vi d e d b y fa m ily
m e m b e rs
a n d vo lu n te e rs (a p p ly g ro ss
sa la ry p a id fo r si m ila r jo b s)
P ro d u ct iv it y c o st s. H C A is
re co m m e n d e d b e c a u se
It a lia n d a ta
fo r F C M
n o t a v a ila b le
[1 7]
N e th e rl a n d s
F o rm
a liz e d
C U A ; C E A if H R Q o L is n o t
a n im
p o rt a n t e ff e c t o f
d ru g b e in g a ss e ss e d ;
C M A if e q u a l c lin ic a l
e ff e c ts
o f c o m p a ra to rs
c a n b e su b st a n ti a te d
S o c ie ta l p e rs p e ct iv e
D ir e c t c o st s w it h in
a n d
o u ts id e th e h e a lt h ca re
sy st e m
E x cl u d e in d ir e c t c o st s in si d e th e
h e a lt h ca re
sy st e m
n o t re la te d to
th e
tr e a tm
e n t. C a lc u la te
p ro d u c ti vi ty
c o st s u si n g F C M . P re se n t se p a ra te
a n a ly se s w it h a n d w it h o u t
p ro d u ct iv it y c o st s
[1 10 ]
N o rw
a y
F o rm
a liz e d
C U A re c o m m e n d e d ; C V A
m a y b e p e rf o rm
e d a s a
su p p le m e n t. C E A , C M A
a n d C B A m a y b e u se d
d e p e n d in g o n th e
re se a rc h q u e st io n ; c h o ic e
m u st
b e ju st if ie d
S o c ie ta l p e rs p e ct iv e a n d
p e rs p e ct iv e o f N a ti o n a l
In su ra n c e A d m in is tr a ti o n ;
p re se n t se p a ra te ly
D ir e c t c o st s w it h in
a n d
o u ts id e th e h e a lt h ca re
sy st e m , re g a rd le ss
o f w h o
p a y s th e m
Lo ss
in p ro d u ct io n d u e to
ill n e ss
a n d
d e a th . If d e e m e d re le va n t to
in cl u d e
in d ir e ct
co st s in
in cr e m e n ta l co st s, th is
m u st b e ju st if ie d a n d in cr e m e n ta l co st s
m u st a ls o b e p re se n te d e xc lu d in g
in d ir e ct
co st s. H C A a n d FC
M b o th
a cc e p ta b le , b u t ch o ic e m u st b e ju st if ie d
[1 12 ]
A E : A d ve rs e e ve n t; C B A : C o st – b e n e fi t a n a ly si s; C C A : C o st – c o n se q u e n ce
a n a ly si s;
C D A : C o st -o f- d is e a se
a n a ly si s; C E A : C o st – e ff e c ti ve n e ss
a n a ly si s; C M A : C o st -m
in im
iz a ti o n a n a ly si s; C U A : C o st – u ti lit y a n a ly si s; C V A : C o st –
v a lu e
a n a ly si s;
FC M : F ri ct io n
co st
m e th o d ; H C A : H u m a n
c a p it a l a p p ro a ch ; H E : H e a lt h -e co n o m ic ; H R Q o L:
H e a lt h -r e la te d
q u a lit y o f lif e ; H S E : H e a lt h
S e rv ic e
E xe cu ti ve ; LY
G : L if e -y e a r g a in e d ; N A : N o t a p p lic a b le ;
N H S : N a ti o n a l H e a lt h S e rv ic e ; Q A L Y : Q u a lit y- a d ju st e d lif e y e a r; P S S : P e rs o n a l S o ci a l S e rv ic e s; S H I: S ta tu to ry
H e a lt h In su ra n c e ; W T P : W ill in g n e ss
to p a y.
Review Bracco & Krol
584 Expert Rev. Pharmacoecon. Outcomes Res. 13(5), (2013)
T a b le
2 . R e co
m m e n d a ti o n s o n a n a ly ti c m e th o d s,
p e rs p e ct iv e s a n d co
st s in
E u ro p e a n H e a lt h E co
n o m ic s g u id e li n e s (c o n t. ).
C o u n tr y
T y p e o f
g u id e li n e s
T y p e o f a n a ly si s
P e rs p e ct iv e
D ir e ct
co st s
In d ir e ct
co st s
R e f.
P o la n d
G u id e lin e s fo r
e co n o m ic
e va lu a ti o n s
S ta n d a rd
e co n o m ic a n a ly si s
sh o u ld in cl u d e b o th
a C C A
a n d e it h e r C E A o r C U A .
W h e n th e re a re
n o
d if fe re n ce s in e ff e ct iv e n e ss ,
a C M A a n a ly si s m a y re p la ce
C E A . A u th o rs m a y p re se n t
a d d it io n a la n a ly se s. C B A is
n o t re co m m e n d e d a s th e
b a si c m e th o d
H e a lt h c a re
p a y e r
p e rs p e ct iv e p ri m a ri ly .
S o c ie ta l p e rs p e c ti v e m a y b e
ju st if ie d if th e H T A re p o rt
a u th o r c o n si d e rs
it
si g n if ic a n t fo r fi n a n c in g
d e ci si o n -m
a k e rs . P re se n t
re su lt s fo r h e a lt h c a re
p a y e r
a n d so ci e ta l p e rs p e c ti ve s
se p a ra te ly
D ir e c t m e d ic a l a n d
n o n m e d ic a l c o st s
L o ss
o f p ro d u ct iv it y c a u se d b y ill n e ss
o r p re m a tu re
d e a th . H C A is
re c o m m e n d e d (e .g ., o n th e b a si s o f
a ve ra g e w a g e s)
[1 03 ]
P o rt u g a l
In fo rm
a l
C U A (p re fe rr e d ) o r C B A
a re
re c o m m e n d e d
w h e n e v e r p o ss ib le .
O th e rw
is e , u se
C M A if
e q u a l c lin ic a l e ff e c ts
o f
c o m p a ra to rs
c a n b e
sh o w n , o r C E A . C D A a n d
C C A a re
a cc e p te d to
ju st if y th e c h o ic e o f
tr e a tm
e n t a lt e rn a ti ve s
S o c ie ta l p e rs p e c ti v e ; p re se n t
o th e r re le va n t p e rs p e c ti ve s
se p a ra te ly , w it h sp e ci a l
a tt e n ti o n to
th ir d -p a rt y
p a ye rs
w h e n th e y a re
ta rg e t a u d ie n c e
C o st s o f h e a lt h c a re
p ro v id e d a s a re su lt o f th e
tr e a tm
e n t a n d it s
c o n se q u e n c e s, n o n m e d ic a l
e xp e n se s, in fo rm
a l n u rs in g
a n d o th e r se rv ic e s; o n ly
in c lu d e e xp e n se s th a t a re
d ir e c t re su lt o f tr e a tm
e n t in
q u e st io n
T h e o n ly in d ir e ct
c o st s in c lu d e d
sh o u ld
b e fo r e m p lo y e e s’ lo st
p ro d u ct iv it y.
M e th o d s fo r c a lc u la ti n g
p ro d u ct iv it y c o st s n o t sp e c if ie d
[1 01 ]
R u ss ia n
F e d e ra ti o n
F o rm
a liz e d
C E A , C U A , C M A o r C B A ,
d e p e n d in g o n th e
re se a rc h q u e st io n ; c h o ic e
m u st
b e ju st if ie d . C D A
m a y b e u se d fo r sp e c ia l
p u rp o se s a s
su p p le m e n ta ry
m e th o d
P e rs p e c ti ve
c a n b e so c ie ta l,
fe d e ra l h e a lt h c a re
sy st e m ,
in st it u ti o n a l, p a ti e n t a n d
fa m ily , o r m e d ic a l in su re rs ;
c h o ic e sh o u ld
b e c o n si st e n t
w it h st u d y’ s in te n d e d u se
A ll d ir e ct
e xp e n se s o f th e
h e a lt h c a re
sy st e m
a n d
d ir e c t n o n m e d ic a l c o st s
L o ss
o f p ro d u ct iv it y d u e to
a b se n c e
fr o m
w o rk
o f p a ti e n t o r c a re g iv e rs ,
d e c re a se d p ro d u ct iv it y a t w o rk ;
e co n o m ic lo ss e s d u e to
p re m a tu re
d e a th . M e th o d s fo r c a lc u la ti n g
p ro d u ct iv it y c o st s n o t sp e c if ie d
[1 23 ]
S co tl a n d
F o rm
a liz e d
C U A g e n e ra lly
a p p ro p ri a te ; C M A if
th e ra p e u ti c e q u iv a le n ce
c a n b e d e m o n st ra te d ;
C E A if Q A LY
is n o t m o st
a p p ro p ri a te
o u tc o m e
m e a su re
(m u st
b e
ju st if ie d )
P e rs p e ct iv e o n o u tc o m e s
sh o u ld b e a ll d ir e ct h e a lt h
e ff e ct s fo r p a ti e n ts o r o th e r
re le va n t in d iv id u a ls (p ri n ci p a lly
ca re g iv e rs ). P e rs p e ct iv e o n
co st s sh o u ld b e th a t o f th e
N H S in S co tl a n d a n d so ci a l
w o rk . If w id e r p e rs p e ct iv e s
a re e xp e ct e d to
in fl u e n ce
re su lt s si g n if ic a n tl y, th e se
sh o u ld b e re p o rt e d in a
se n si ti vi ty a n a ly si s
C o st s o f re so u rc e s u n d e r
th e c o n tr o l o f th e N H S in
S co tl a n d a n d so c ia l w o rk
N o n -N H S /s o c ia l w o rk
c o st s. C o st s o f
p ro d u ct iv it y lo ss e s a n d v a lu a ti o n
m e th o d s a re
n o t e xp lic it ly d is c u ss e d
[1 15 ]
A E : A d ve rs e e v e n t; C B A : C o st – b e n e fi t a n a ly si s; C C A : C o st – c o n se q u e n ce
a n a ly si s; C D A : C o st -o f- d is e a se
a n a ly si s; C E A : C o st – e ff e c ti ve n e ss
a n a ly si s; C M A : C o st -m
in im
iz a ti o n a n a ly si s; C U A : C o st – u ti lit y a n a ly si s; C V A : C o st –
va lu e
a n a ly si s;
F C M : Fr ic ti o n
co st
m e th o d ; H C A : H u m a n
ca p it a l a p p ro a ch ; H E : H e a lt h -e co n o m ic ; H R Q o L:
H e a lt h -r e la te d
q u a lit y o f lif e ; H S E : H e a lt h
S e rv ic e
E xe cu ti ve ; L Y G : Li fe -y e a r g a in e d ; N A : N o t a p p lic a b le ;
N H S : N a ti o n a l H e a lt h S e rv ic e ; Q A LY
: Q u a lit y- a d ju st e d lif e ye a r; P S S : P e rs o n a l S o ci a l S e rv ic e s; S H I: S ta tu to ry
H e a lt h In su ra n ce ; W T P : W ill in g n e ss
to p a y.
Economic evaluations in reimbursement guidelines Review
www.expert-reviews.com 585
T a b le
2 . R e co
m m e n d a ti o n s o n a n a ly ti c m e th o d s,
p e rs p e ct iv e s a n d co
st s in
E u ro p e a n H e a lt h E co
n o m ic s g u id e li n e s (c o n t. ).
C o u n tr y
T y p e o f
g u id e li n e s
T y p e o f a n a ly si s
P e rs p e ct iv e
D ir e ct
co st s
In d ir e ct
co st s
R e f.
S lo va k R e p u b lic
F o rm
a liz e d
C E A , C U A o r C M A
d e p e n d in g o n th e c lin ic a l
c h a ra c te ri st ic s o f th e c a se
S o c ie ta l o r h e a lt h ca re
p a y e r
p e rs p e ct iv e , d e p e n d in g o n
ta rg e t a u d ie n c e ; re p o rt
d if fe re n t p e rs p e c ti ve s
se p a ra te ly
R e p o rt se p a ra te ly d ir e c t
m e d ic a l a n d n o n m e d ic a l
c o st s a s w e ll a s c o st s
in c u rr e d b y p u b lic
a n d
p ri va te
so u rc e s
L o ss
o f p ro d u ct iv it y,
c a lc u la te d a s th e
a ve ra g e g ro ss
w a g e o f p a ti e n ts
o f
w o rk in g a g e
[1 16 ]
S p a in
In fo rm
a l
C E A , C U A , C M A o r C B A ,
d e p e n d in g o n th e
re se a rc h q u e st io n ;
d if fe re n t m e th o d s n o t
m u tu a lly
e xc lu si v e
S o c ie ta l p e rs p e ct iv e
p re fe rr e d ; in c lu d e N H S
p e rs p e ct iv e , p re se n t
se p a ra te ly
O p p o rt u n it y c o st s o f
re so u rc e s; d is ti n g u is h
b e tw
e e n h e a lt h ca re
a n d
n o n -h e a lt h c a re
c o st s
D is ti n g u is h b e tw
e e n la b o r lo ss e s,
ti m e lo ss , a n d in fo rm
a l c a re
to a vo id
d o u b le -c o u n ti n g su ch
c o st s. H C A a n d
F C M
b o th
a c ce p ta b le
[1 4]
S w e d e n
F o rm
a liz e d
C U A re c o m m e n d e d . F o r
tr e a tm
e n ts
th a t m o st ly
a ff e c t su rv iv a l, a ls o
p re se n t C E A u si n g L Y G .
C B A w it h W T P m a y b e
u se d w h e n it is d if fi cu lt to
u se
Q A LY
s. C M A m a y
su ff ic e if th e n e w
m e d ic in e h a s th e sa m e
h e a lt h e ff e c t a s th e b e st
c o m p a ra to r
S o c ie ta l p e rs p e ct iv e
A ll re le v a n t c o st s a ss o c ia te d
to th e tr e a tm
e n t a n d ill n e ss
sh o u ld
b e id e n ti fi e d ,
q u a n ti fi e d a n d e va lu a te d
P ro d u ct io n lo ss
fo r tr e a tm
e n t a n d
si c k n e ss
sh o u ld
a ls o b e in c lu d e d ; u se
H C A
[1 08 ,1 23 ]
S w it ze rl a n d
F o rm
a liz e d
C B A p re fe rr e d fo r
re fe re n ce
c a se
b u t it m a y
b e d if fi cu lt to
m e a su re
in ta n g ib le
c o st s a n d
b e n e fi ts
in m o n e ta ry
te rm
s; C E A is d e fa c to
st a n d a rd
b u t C U A is
p re fe ra b le ; C M A if
c o m p a ra to rs
h a v e sa m e
e ff ic a c y a n d si d e -e ff e ct
p ro fi le s
S o c ie ta l p e rs p e ct iv e ; h e a lt h
sy st e m
p e rs p e c ti ve
re le v a n t
fo r re im
b u rs e m e n t
d e ci si o n s; o th e r
p e rs p e ct iv e s p o ss ib le
D is ti n g u is h b e tw
e e n d ir e ct
m e d ic a l c o st s d ir e c tl y
in c u rr e d b y th e
in te rv e n ti o n , d ir e c t m e d ic a l
c o st s o f se c o n d a ry
e ff e c ts
(e .g ., A E m a n a g e m e n t) ,
a n d d ir e ct
n o n m e d ic a l c o st s
L o ss
o f p ro d u ct iv it y d u e to
a b se n ce
fr o m
w o rk , d e c re a se d p ro d u c ti vi ty
a t
w o rk , p re m a tu re
d e a th . M e th o d s fo r
c a lc u la ti n g p ro d u c ti vi ty
c o st s n o t
sp e ci fi e d
[1 6]
A E : A d ve rs e e ve n t; C B A : C o st – b e n e fi t a n a ly si s; C C A : C o st – co n se q u e n ce
a n a ly si s; C D A : C o st -o f- d is e a se
a n a ly si s; C E A : C o st – e ff e ct iv e n e ss
a n a ly si s; C M A : C o st -m
in im
iz a ti o n a n a ly si s; C U A : C o st – u ti lit y a n a ly si s; C V A : C o st –
va lu e
a n a ly si s;
FC M : Fr ic ti o n
c o st
m e th o d ; H C A : H u m a n
ca p it a l a p p ro a ch ; H E : H e a lt h -e c o n o m ic ; H R Q o L:
H e a lt h -r e la te d
q u a lit y o f lif e ; H S E : H e a lt h
S e rv ic e
E x e c u ti ve ; LY
G : L if e -y e a r g a in e d ; N A : N o t a p p lic a b le ;
N H S : N a ti o n a l H e a lt h S e rv ic e ; Q A LY
: Q u a lit y- a d ju st e d lif e ye a r; P S S : P e rs o n a l S o ci a l S e rv ic e s; S H I: S ta tu to ry
H e a lt h In su ra n ce ; W T P : W ill in g n e ss
to p a y .
Review Bracco & Krol
586 Expert Rev. Pharmacoecon. Outcomes Res. 13(5), (2013)
National guidelines showed broad consistency in advice on choice of comparators for HE analysis (TABLE 3). Standard treat- ment in current clinical practice for the relevant indication was most often identified as the reference-case alternative. To sup- plement comparisons with standard treatment, many guidelines suggested additional comparisons using the most effective alter- native treatment or the treatment recommended in clinical practice guidelines.
Few national guidelines took an explicit position on how to determine the relative efficacy of comparators; instead, most pre- sented a hierarchy of evidence quality, and advocated use of the best data available (TABLE 3). Randomized, controlled trials (RCTs) were the most commonly identified ‘gold standard’ for clinical evidence. Guidelines that provided advice on how to perform indirect comparisons in the absence of head-to-head studies between the intervention in question and its comparators were those of England and Wales, France, Germany, Hungary, Ire- land, Poland, Scotland and the Slovak Republic [19,102,104,105– 107,110,112–115]. Mixed treatment comparison was the most recom- mended method to determine relative efficacy of comparators.
TABLE 4 presents these results categorized by topic and recom- mendation, to more easily identify variation among countries in recommended HE approach.
Discussion In the past decade, many European nations have either adopted new national guidelines for HE analysis or else updated existing guidelines. Despite this opportunity to standardize recommen- dations across countries, this review has shown that guidelines continue to diverge with respect to key aspects of HE studies.
The last years, many broad health related costs and effects have received scientific attention such as the estimation of health related productivity gains and losses [20] and the meas- urement of the impact of interventions on caregivers and family members in terms of economic effects [21] and in terms of effects on their health [22,23] and HRQoL [24,25].
All costs and effects should be counted if the aim of an eco- nomic evaluation is to make a complete welfare economic trade- off and to ensure welfare enhancement in decision-making. This seems the most important reason for advocating the societal per- spective. In the other hands if an economic evaluation are aiming to aid health-care decision-makers who are concerned with a sub- goal (optimizing health care), as in the concept of local rational- ity, not all costs may be equally relevant in the decision-making context. Some costs are more relevant in terms of having an opportunity cost on health than others. The perspective could then be narrowed down to those costs and savings that represent an opportunity cost in terms of health than others [26].
In this context, compared to the international guidelines reviewed by Hjelmgren et al., a higher proportion of the current European guidelines express a preference for the healthcare payer perspective instead of a societal perspective with guidelines for England and Wales, Scotland, Ireland and Germany require ana- lysts to adopt a payer perspective only [9]. However, the other guidelines recommending the payers perspectives also accept the
inclusion of a broader societal perspective as separate analysis. The inclusion of both the payers and societal perspective should give more transparency on the cost and effect of a new interven- tion on the national healthcare system and the society as a whole. Authors of HE and reimbursement guidelines might have recog- nized different objectives of economics evaluations and different interests of decision makers.
From one side this may reflect greater representation of formal- ized guidelines than in the earlier review, since the target audience for HE studies that follow formalized guidelines – healthcare payers – may more likely be concerned with costs that they must bear than costs (or savings) falling outside their responsibility. On the other hand it may also show a trend toward a broader perspec- tive in economic evaluations in formalized guidelines. To illus- trate, the non-formalized guidelines compiled by health economists for France, Portugal and Spain all advocate the societal perspective. Where guidelines request that the primary perspective be societal this may suggest that authorities recognize that in their publicly funded programs it is important that economic evalua- tions are able to inform about the impact of decisions beyond the health care budget [27,28]. Although the societal perspective was somewhat more prevalent in countries with a National Health Service healthcare system such as the Scandinavian nations, Portu- gal and Spain. However, several other countries with this type of healthcare system required the payer perspective, notably England and Wales and Ireland. Conversely, while some countries with a social security-based (‘Bismarck’ [29]) healthcare system like Bel- gium and Germany requested the payer perspective, other coun- tries with this healthcare system called for the societal perspective, including France, The Netherlands and Switzerland.
It has long been recognized that considering only the costs and benefits within the healthcare sector lacks justification in the welfare-economics basis for cost–benefit analysis [30], since deci- sions based on a limited amount of information on costs and effect may be suboptimal for the societal as a whole. However, lack of universal recommendation of the societal perspective in reference- case analyses could be due to the fact that despite the attention to broader aspects in HE research, no consensus has emerged among academics on how to identify, measure and validate costs (and sav- ings) related to either productivity losses [2,31] or other societal costs and effects, such as those on family members [32].
Which costs to include within a given perspective are broadly similar across many guidelines and national guidelines show broad consistency in ranking clinical data sources and choice of comparators for HE analysis. However, the guidelines vary in recommended methods for cost inclusion and discount- ing there is little guidance on how exactly to include costs. Especially, the level of detail regarding cost inclusion, measure- ment and valuation differs widely between guidelines. As a result, there is much variation in methods used in economic evaluation and it subsequently seems that actual standardization remains a distant objective.
Such lack of standardization represents an ongoing challenge for researchers and the pharmaceutical industry [33]. Previous studies that have examined adherence of reimbursement
Economic evaluations in reimbursement guidelines Review
www.expert-reviews.com 587
T a b le
3 . R e co
m m e n d a ti o n s o n d is co
u n ti n g , so
u rc e s o f e ff ic a cy
e v id e n ce
a n d co
m p a ra to rs
in E u ro p e a n H e a lt h E co
n o m ic
g u id e li n e s.
C o u n tr y
D is co
u n ti n g
D a ta
so u rc e s
C o m p a ra to rs
R e f.
A u st ri a
C o st s a n d b e n e fi ts : 5 % ; 3 %
a n d 1 0 %
in se n si ti vi ty
a n a ly se s; d is co u n t
n o n m o n e ta ry
o u tc o m e s se p a ra te ly
C lin ic a l d a ta
so u rc e s ra n k e d fo r q u a lit y , b u t
n o e xp lic it p o si ti o n is ta k e n o n h o w
to
d e te rm
in e re la ti ve
e ff ic a cy
o f c o m p a ra to rs
C h o ic e o f a lt e rn a ti ve s m u st
b e a p p ro p ri a te
to th e
re se a rc h q u e st io n a n d th e st a te
o f sc ie n c e . T h e
c h o se n a lt e rn a ti ve s sh o u ld
b e d e sc ri b e d a s fu lly
a s p o ss ib le
a n d c o m p ly w it h A u st ri a n c lin ic a l
p ra ct ic e . C o m p a ri so n sh o u ld
b e m a d e fi rs t o f a ll
w it h st a n d a rd
th e ra p y in
th e c a se
o f a lt e rn a ti ve
fo rm
s o f tr e a tm
e n t. If th e st a n d a rd
th e ra p y
c a n n o t b e c le a rl y e st a b lis h e d , th e m o st
fr e q u e n t
th e ra p y o r th e m o st
e ff e c ti ve
th e ra p y c a n
lik e w is e b e c h o se n
[1 5]
B a lt ic st a te s
(E st o n ia , L a tv ia ,
L it h u a n ia )
C o st s a n d b e n e fi ts : 5 % ; ju st if y o th e r
ra te s u se d
M e ta -a n a ly si s p re fe rr e d to
si n g le
c lin ic a l tr ia l.
N o e xp lic it p o si ti o n is ta k e n o n h o w
to
d e te rm
in e re la ti ve
e ff ic a cy
o f c o m p a ra to rs
C o st s a n d o u tc o m e s o f a st a n d a rd
tr e a tm
e n t o r
th e u su a l tr e a tm
e n t in
d a ily
p ra c ti ce
in th e
re sp e c ti ve
st a te s sh o u ld
b e c o m p a re d w it h th e
c o st s a n d o u tc o m e s o f th e n e w
d ru g
[1 18 ]
B e lg iu m
C o st s: 3 % ; b e n e fi ts : 1 .5 % ; se n si ti v it y
a n a ly se s m a y b e p e rf o rm
e d
B a se
e co n o m ic e va lu a ti o n a s m u ch
a s p o ss ib le
o n d a ta
fr o m
h e a d -t o -h e a d c o m p a ri so n s
b e tw
e e n th e st u d y p ro d u c t a n d th e
c o m p a ra to r
D ru g sh o u ld
b e c o m p a re d w it h th e m o st
re le v a n t
a lt e rn a ti ve
tr e a tm
e n t fo r th e p ro p o se d in d ic a ti o n
o f th e d ru g . T h e m o st
re le v a n t a lt e rn a ti v e
tr e a tm
e n t is e it h e r th e tr e a tm
e n t th a t is m o st
lik e ly to
b e re p la c e d b y th e n e w
tr e a tm
e n t o r, in
c a se
o f a d d -o n tr e a tm
e n ts , th e c u rr e n t tr e a tm
e n t
w it h o u t th e a d d -o n p ro d u ct . If th is tr e a tm
e n t
c a n n o t b e id e n ti fi e d , th e re c o m m e n d e d
tr e a tm
e n t a c c o rd in g to
th e B e lg ia n c lin ic a l
g u id e lin e s sh o u ld
b e u se d a s a c o m p a ra to r
[1 8]
C ro a ti a
N A
N o e xp lic it p o si ti o n is ta k e n o n h o w
to
d e te rm
in e re la ti ve
e ff ic a cy
o f c o m p a ra to rs
C u rr e n t lis te d th e ra p e u ti c o p ti o n s a s w e ll a s
c lin ic a l p ra ct ic e in
th e R e p u b lic
o f C ro a ti a
[1 19 ]
D e n m a rk
N o sp e c if ic ra te
p re sc ri b e d
N o e xp lic it p o si ti o n is ta k e n o n h o w
to
d e te rm
in e re la ti ve
e ff ic a cy
o f c o m p a ra to rs
B e st
a lt e rn a ti ve
m e d ic a l d ru g
[1 19 ,1 20 ]
E n g la n d a n d
W a le s
C o st s a n d b e n e fi ts : 3 .5 %
; v a ry
0 – 6 %
in se n si ti vi ty
a n a ly se s
N IC E h a s a st ro n g p re fe re n c e fo r e vi d e n c e
fr o m
‘h e a d -t o -h e a d ’ R C T s th a t d ir e ct ly
c o m p a re
th e te ch n o lo g y w it h th e a p p ro p ri a te
c o m p a ra to r in
th e re le v a n t p a ti e n t g ro u p s. If
d a ta
fr o m
h e a d -t o -h e a d R C T s a re
n o t
a va ila b le , in d ir e ct
tr e a tm
e n t c o m p a ri so n
m e th o d s sh o u ld
b e u se d
R e le v a n t c o m p a ra to rs
a re
id e n ti fi e d , w it h
c o n si d e ra ti o n g iv e n sp e c if ic a lly
to ro u ti n e a n d
b e st
p ra ct ic e in
th e N H S (i n cl u d in g e xi st in g N IC E
g u id a n c e ) a n d to
th e n a tu ra l h is to ry
o f th e
c o n d it io n w it h o u t su it a b le
tr e a tm
e n t
[1 11 ]
H E : H e a lt h -e co n o m ic s; IQ W iG : In st it u te
fo r Q u a lit y a n d E ff ic ie n cy
in H e a lt h C a re ; M T C : M ix e d tr e a tm
e n t co m p a ri so n ; N IC E : N a ti o n a l In st it u te
fo r H e a lt h a n d C a re
E xc e lle n ce ; R C T : R a n d o m iz e d co n tr o lle d tr ia l.
Review Bracco & Krol
588 Expert Rev. Pharmacoecon. Outcomes Res. 13(5), (2013)
T a b le
3 . R e co
m m e n d a ti o n s o n d is co
u n ti n g , so
u rc e s o f e ff ic a cy
e v id e n ce
a n d co
m p a ra to rs
in E u ro p e a n H e a lt h E co
n o m ic
g u id e li n e s (c o n t. ).
C o u n tr y
D is co
u n ti n g
D a ta
so u rc e s
C o m p a ra to rs
R e f.
F in la n d
C o st s a n d b e n e fi ts : 3 % ; a ls o p re se n t
re su lt s fo r 0 %
P ri o ri ty
is g iv e n to
ra n d o m iz e d c o n tr o lle d
st u d ie s w h e re
th e tr e a tm
e n t c o m p a ra to rs
h a v e b e e n d ir e c tl y c o m p a re d w it h e a ch
o th e r
If th e m e d ic in a l p ro d u c t is d e si g n e d to
re p la c e a
sp e c if ic m e d ic in a l p ro d u c t o r tr e a tm
e n t, it sh a ll
b e c o m p a re d w it h th a t m e d ic in a l p ro d u ct
o r
tr e a tm
e n t. If th a t tr e a tm
e n t is n o t th e m o st
c o m m o n ly u se d , th e m e d ic in a l p ro d u c t sh o u ld
a ls o b e c o m p a re d w it h th e m o st
c o m m o n ly u se d
tr e a tm
e n t. T h e tr e a tm
e n t c a n a ls o b e c o m p a re d
w it h th e b e st
o r w it h th e m in im
u m
p ra ct ic e
[1 22 ]
F ra n c e
C o st s a n d b e n e fi ts : 0 % , 3 %
a n d 5 % ;
c o n d u c t se n si ti v it y a n a ly si s
D ir e c t c o m p a ri so n b e tw
e e n tw
o st ra te g ie s
p re se n ts
th e g re a te st
sc ie n ti fi c re le va n c e . It
m a y , h o w e ve r, b e n e ce ss a ry
to p e rf o rm
a n
in d ir e ct
c o m p a ri so n b a se d o n p u b lis h e d d a ta
in th e a b se n c e o f a n y o ri g in a l st u d ie s a llo w in g
fo r d ir e ct
c o m p a ri so n
T h e ra p e u ti c st ra te g ie s m o st
fr e q u e n tl y u se d
(i n c lu d in g n o n -t re a tm
e n t) o r n e w e r st ra te g ie s
w h ic h m a y le g it im
a te ly b e d e e m e d lik e ly to
b e co m e re fe re n ce
st ra te g ie s in
th e v e ry
n e a r
fu tu re
[1 05 ]
G e rm
a n y
C o st s a n d b e n e fi ts : 3 % ; 0 % , 5 % , 7 %
a n d 1 0 %
in se n si ti v it y a n a ly se s
IQ W iG
p ri m a ri ly u se s d ir e c t c o m p a ri so n s
(h e a d -t o -h e a d c o m p a ri so n s) . If n e c e ss a ry ,
IQ W iG
c a n a ls o u se
in d ir e ct
c o m p a ri so n s;
e .g ., M T C m e ta -a n a ly si s, n o t n o n -a d ju st e d
in d ir e ct
c o m p a ri so n s
A ll th e ra p e u ti c a lt e rn a ti ve s re le v a n t in
a p a rt ic u la r
th e ra p e u ti c a re a
[1 05 – 10 7]
H u n g a ry
C o st s a n d b e n e fi ts : 5 % ; v a ry
3 – 6 %
fo r
c o st s a n d 0 – 6 %
fo r b e n e fi ts
in
se n si ti vi ty
a n a ly se s
If a va ila b le , c lin ic a l tr ia ls o r sy st e m a ti c re v ie w
o f ra n d o m iz e d c lin ic a l tr ia ls d ir e ct ly c o m p a ri n g
th e n e w
h e a lt h te c h n o lo g y w it h th e
c o m p a ra to rs . If th is is n o t a va ila b le , c lin ic a l
tr ia ls in v o lv in g th e sa m e re fe re n c e h e a lt h
te c h n o lo g y (e .g ., p la c e b o )
C u rr e n tl y a cc e p te d st a n d a rd
th e ra p y (t h e ra p ie s)
th a t th e n e w
in te rv e n ti o n is in te n d e d to
re p la ce
[1 9]
Ir e la n d
C o st s a n d b e n e fi ts : 4 % ; v a ry
0 – 6 %
in
se n si ti vi ty
a n a ly se s
In th e e ve n t o f lim
it e d h e a d -t o -h e a d R C T
d a ta , m ix e d tr e a tm
e n t c o m p a ri so n s c a n b e
u se d
‘R o u ti n e c a re ’; i. e ., th e te c h n o lo g y o r
te c h n o lo g ie s m o st
w id e ly u se d in
c lin ic a l p ra c ti ce
in Ir e la n d
[1 12 ,1 13 ]
It a ly
C o st s a n d b e n e fi ts : 3 % ; a ls o p re se n t
re su lt s fo r 0 % ; v a ry
0 – 8 %
in se n si ti vi ty
a n a ly se s
N o e xp lic it p o si ti o n is ta k e n o n h o w
to
d e te rm
in e re la ti v e e ff ic a cy
o f c o m p a ra to rs
M o st
w id e sp re a d tr e a tm
e n t (p h a rm
a co lo g ic a l o r
n o n -p h a rm
a co lo g ic a l) w it h a va ila b le
c lin ic a l d a ta
[1 7]
N e th e rl a n d s
C o st s: 4 %
; b e n e fi ts : 1 .5 %
N o e xp lic it p o si ti o n is ta k e n o n h o w
to
d e te rm
in e re la ti v e e ff ic a cy
o f c o m p a ra to rs
S ta n d a rd
tr e a tm
e n t, o r if th a t d o e s n o t e xi st , th e
u su a l tr e a tm
e n t (e it h e r m e d ic in a l o r n o n -
m e d ic in a l)
[1 10 ]
N o rw
a y
C o st s a n d b e n e fi ts : fi x a ra te
fr o m
2 .5 – 5 % ; a ls o p re se n t re su lt s fo r 0 %
fo r b e n e fi ts ; v a ry
c o st
a n d b e n e fi ts
0 – 8 %
in se n si ti vi ty
a n a ly se s
D a ta
fr o m
R C T s w h e re
th e tr e a tm
e n t is
c o m p a re d d ir e c tl y w it h re le va n t re fe re n c e
a lt e rn a ti ve (s ) is re c o m m e n d e d
T h e m o st
p re va le n t tr e a tm
e n t, o r th e m o st
in e x p e n si v e tr e a tm
e n t; o th e r a lt e rn a ti v e s c a n a ls o
b e u se d
[1 12 ]
H E : H e a lt h -e co n o m ic s; IQ W iG : In st it u te
fo r Q u a lit y a n d E ff ic ie n cy
in H e a lt h C a re ; M T C : M ix e d tr e a tm
e n t c o m p a ri so n ; N IC E : N a ti o n a l In st it u te
fo r H e a lt h a n d C a re
E xc e lle n ce ; R C T : R a n d o m iz e d c o n tr o lle d tr ia l.
Economic evaluations in reimbursement guidelines Review
www.expert-reviews.com 589
T a b le
3 . R e co
m m e n d a ti o n s o n d is co
u n ti n g , so
u rc e s o f e ff ic a cy
e v id e n ce
a n d co
m p a ra to rs
in E u ro p e a n H e a lt h E co
n o m ic
g u id e li n e s (c o n t. ).
C o u n tr y
D is co
u n ti n g
D a ta
so u rc e s
C o m p a ra to rs
R e f.
P o la n d
C o st s: 5 %
; B e n e fi ts : 3 .5 % ; a p p ly 5 % /
5 %
, 0 % /0 %
a n d 5 %
/0 %
in se n si ti v it y
a n a ly se s
R C T s d ir e c tl y c o m p a ri n g th e a ss e ss e d
te c h n o lo g ie s. In d ir e ct
c o m p a ri so n in
c a se
o f
la c k o f h e a d -t o -h e a d tr ia ls
E x is ti n g p ra c ti ce
(p ro c e d u re
th a t w ill lik e ly b e
re p la ce d b y th e a ss e ss e d te c h n o lo g y in
m e d ic a l
p ra c ti ce ). It is a ls o re c o m m e n d e d to
p e rf o rm
a
c o m p a ri so n w it h th e m o st
fr e q u e n tl y u se d ,
c h e a p e st , a n d m o st
e ff ic ie n t te c h n o lo g ie s
c o m p lia n t w it h th e st a n d a rd s a n d g u id e lin e s fo r
c lin ic a l m a n a g e m e n t
[1 03 ]
P o rt u g a l
C o st s a n d b e n e fi ts : 5 % ; v a ry
in
se n si ti v it y a n a ly se s, in c lu d in g 0 %
fo r
b e n e fi ts
if n o t v a lu e d m o n e ta ri ly
C lin ic a l d a ta
so u rc e s ra n k e d fo r q u a lit y , b u t
n o e xp lic it p o si ti o n is ta k e n o n h o w
to
d e te rm
in e re la ti v e e ff ic a cy
o f c o m p a ra to rs
C u rr e n t p ra ct ic e , i. e ., th e m o st
c o m m o n
tr e a tm
e n t u se d fo r th e h e a lt h p ro b le m
in
q u e st io n . If th e m o st
c o m m o n tr e a tm
e n t is n o t
th e o n e re co g n iz e d a s th e m o st
e ff ic a c io u s, o r is
n o t th e c h e a p e st
o f th e e ff ic a c io u s tr e a tm
e n ts ,
th e se
tr e a tm
e n ts
sh o u ld
a ls o b e u se d a s
c o m p a ra to rs
[1 01 ]
R u ss ia n
F e d e ra ti o n
C o st s a n d b e n e fi ts : 5 %
C lin ic a l d a ta
so u rc e s ra n k e d fo r q u a lit y , b u t
n o e xp lic it p o si ti o n is ta k e n o n h o w
to
d e te rm
in e re la ti v e e ff ic a cy
o f c o m p a ra to rs
T y p ic a l m a n a g e m e n t p ra ct ic e fo r th e d is e a se ;
m o st
e ff e c ti ve , le a st
e xp e n si v e , o r re co m m e n d e d
in te rv e n ti o n , o r n o -i n te rv e n ti o n if th is c a n o cc u r
in c lin ic a l p ra ct ic e
[1 23 ]
S co tl a n d
C o st s a n d b e n e fi ts : 3 .5 % ; v a ry
0 – 6 %
in se n si ti v it y a n a ly se s
If n o h e a d to
h e a d e vi d e n c e is a va ila b le
a n
in d ir e ct
c o m p a ri so n is re q u ir e d
T h e m e d ic in e th a t w ill m o st
lik e ly b e re p la ce d if
th e m e d ic in e u n d e r c o n si d e ra ti o n is a cc e p te d b y
th e S M C fo r u se
in S co tl a n d .
[1 15 ]
S lo v a k
R e p u b lic
C o st s a n d b e n e fi ts : 7 %
to 3 1 st
M a y
2 0 0 9 ; 5 %
fr o m
1 st
Ju n e 2 0 0 9
R C T s o r sy st e m a ti c re v ie w s o f R C T s th a t
d ir e c tl y c o m p a re
th e n e w
te c h n o lo g y to
c u rr e n tl y a va ila b le
te c h n o lo g ie s. If th e se
a re
u n a v a ila b le , u se
c lin ic a l st u d ie s w it h th e sa m e
re fe re n c e te c h n o lo g y (e .g ., p la ce b o )
C u rr e n tl y a cc e p te d st a n d a rd
tr e a tm
e n t. If th e re
a re
se v e ra l c o m m o n ly u se d a lt e rn a ti v e tr e a tm
e n ts
w it h th e sa m e e ff e c ti ve n e ss
a s th e b e n c h m a rk
tr e a tm
e n t, u se
th e le a st
e xp e n si ve
a lt e rn a ti ve .
In cl u d e tr e a tm
e n ts
k n o w n to
b e c o st
e ff e c ti ve
(e .g ., in
o th e r c o u n tr ie s) , b u t n o t c o m m o n ly u se d
in S lo va k R e p u b lic
[1 16 ]
S p a in
C o st s a n d b e n e fi ts : 3 % ; v a ry
3 – 5 %
in
se n si ti v it y a n a ly se s; a ls o a p p ly 0 %
to
b e n e fi ts
in se n si ti v it y a n a ly si s
N o e xp lic it p o si ti o n is ta k e n o n h o w
to
d e te rm
in e re la ti v e e ff ic a cy
o f c o m p a ra to rs
S ta n d a rd
te ch n o lo g y u se d in
c u rr e n t h e a lt h ca re
p ra c ti ce ; a n y g o ld
st a n d a rd
te c h n o lo g y
[1 4]
S w e d e n
C o st s a n d b e n e fi ts : 3 % , 0 %
a n d 5 %
in se n si ti v it y a n a ly se s; a ls o a p p ly 0 %
to
b e n e fi ts
in se n si ti v it y a n a ly si s
N o e xp lic it p o si ti o n is ta k e n o n h o w
to
d e te rm
in e re la ti v e e ff ic a cy
o f c o m p a ra to rs
T h e m o st
a p p ro p ri a te
a lt e rn a ti ve
tr e a tm
e n t in
S w e d e n (e .g ., th e m o st
u se d )
[1 08 ,1 23 ]
S w it z e rl a n d
3 – 5 % , c o st s a n d m o n e ta ry
b e n e fi ts
C lin ic a l d a ta
so u rc e s ra n k e d fo r q u a lit y , b u t
n o e xp lic it p o si ti o n is ta k e n o n h o w
to
d e te rm
in e re la ti v e e ff ic a cy
o f c o m p a ra to rs
S ta n d a rd
(s ta tu s q u o ), e st a b lis h e d a n d a cc e p te d
tr e a tm
e n t, o r n o tr e a tm
e n t
[1 6]
H E : H e a lt h -e co n o m ic s; IQ W iG : In st it u te
fo r Q u a lit y a n d E ff ic ie n cy
in H e a lt h C a re ; M T C : M ix e d tr e a tm
e n t c o m p a ri so n ; N IC E : N a ti o n a l In st it u te
fo r H e a lt h a n d C a re
E xc e lle n c e ; R C T : R a n d o m iz e d c o n tr o lle d tr ia l.
Review Bracco & Krol
590 Expert Rev. Pharmacoecon. Outcomes Res. 13(5), (2013)
Table 4. Recommendations in European Health Economic guidelines, categorized by topic.
Topic Countries
Type of guidelines
Formalized Baltic states, Belgium, Croatia, Denmark, England & Wales, Finland,
Germany, Hungary, Ireland, Italy, The Netherlands, Norway, Russian Federation,
Scotland, Slovak Republic, Sweden, Switzerland
Informal Portugal, Spain
Guidelines for economic evaluations Austria, France, Poland
Type of analysis for reference case
CUA England & Wales, Ireland, The Netherlands, Norway, Portugal, Scotland, Sweden
CUA or CEA Italy
CCA and [CEA or CUA] Poland
CBA Germany, Switzerland
Depends on research question or
most important outcome
Austria, Baltic states, Belgium, Denmark, Finland, France, Hungary, Russian Federation,
Slovak Republic, Spain
Not specified Croatia
Perspective in reference case
Societal Denmark, Finland, France, The Netherlands, Portugal, Spain, Sweden, Switzerland
Healthcare payer Baltic states, Belgium, Croatia, England & Wales, Germany, Ireland, Poland, Scotland
Societal and healthcare payer Hungary, Italy, Norway
Depends on research question
or target audience
Austria, Russian Federation, Slovak Republic
Direct costs
Direct medical costs Croatia, Denmark, England & Wales, Finland, Ireland, Scotland
Direct medical + nonmedical costs Austria, Baltic states, Belgium, France, Germany, Hungary, Italy, The Netherlands,
Norway, Poland, Portugal, Russian Federation, Slovak Republic, Spain, Sweden, Switzerland
Indirect costs
Productivity losses Austria, Denmark, France, Germany, Hungary, Italy, The Netherlands, Norway,
Poland, Portugal, Russian Federation, Slovak Republic, Spain, Sweden, Switzerland
Productivity losses + indirect
healthcare costs
Belgium, Finland
Costs to other government bodies England & Wales
Productivity losses + costs to other
government bodies
Ireland, Scotland
Not specified Baltic states, Croatia
Discounting in reference case
Costs and benefits: 5% Austria, Baltic states, Hungary, Portugal, Russian Federation, Slovak Republic
Costs and benefits: 4% Ireland
Costs and benefits: 3.5% England & Wales, Scotland
Costs and benefits: 3% Finland, Germany, Italy, Spain, Sweden
Costs and benefits: 0%, 3%, and 5% France
Costs 5%; Benefits: 3.5% Poland
CBA: Cost–benefit analysis; CCA: Cost–consequence analysis; CEA: Cost–effectiveness analysis; CUA: Cost–utility analysis; RCT: Randomized controlled trial.
Economic evaluations in reimbursement guidelines Review
www.expert-reviews.com 591
submissions to HE guidelines have found incomplete compli- ance with recommended practice [34,35]. Lack of standardization across countries limits the transferability of HE expertise, and may decrease sponsors’ compliance with guideline recommenda- tions [12], since it takes considerable resources to conduct indi- vidual health economic studies for each country a company seeks reimbursement of a pharmaceutical. Moreover, many national guidelines (e.g., those for France and Austria) leave considerable scope for deviation from the primary recommenda- tions as long as choices are justified; although this within- country variability offers flexibility, it could also hamper trans- ferability and decrease comparability across studies.
In conclusion, consistency between national HE guidelines on key aspects of study conduct remains lacking. Although some of the observed variation may be attributable to legiti- mate differences between countries in clinical practice or the objectives and constraints of their healthcare systems, differen- ces may also arise from continuing debate about appropriate analytic methods [12]. Several of these methodological issues, such as valuation of costs and benefits have been identified as being of high priority to decision-makers as topics requiring further research [36]. In that sense, an important role in Europe may be played by EUnetHTA, an international collaboration
of government appointed organizations and relevant regional agencies producing HTA aiming at sharing HTA knowledge and increasing transferability of health economic data. Never- theless, until scientific consensus is reached, continuing lack of consistency among guidelines is likely to pose ongoing difficul- ties for those performing and reviewing HE analyses.
Expert commentary The lack of consistency among European guidelines has been identified as one of the limitations on reimbursement decision across European countries. However, someone may wonder whether following local HE and reimbursement guidelines really matter in the decision making process on pricing and access in each of the markets. I would personally raise the following questions:
• What are the key factors influencing reimbursement decisions? • How the economic crisis has changed pricing and reimburse- ment of new drugs in Europe?
• Is value for money still the fundamental question for access to new technologies? Or affordability to a new drug is becoming the key hurdle?
New reimbursement trends and the influence of health tech- nology assessments could help answer those questions.
Table 4. Recommendations in European Health Economic guidelines, categorized by topic (cont.).
Topic Countries
Discounting in reference case
Costs: 4%; Benefits: 1.5% The Netherlands
Costs: 3%; Benefits: 1.5% Belgium
Fixed rate within range Norway (2.5–5%), Switzerland (3–5%)
Not specified Croatia, Denmark
No discounting
Preferred data source
Meta-analysis Baltic states, Slovak Republic
Head-to-head comparisons (RCTs) Belgium, England & Wales, Finland, France, Germany, Hungary, Ireland, Norway,
Poland, Scotland
Not specified Austria, Croatia, Denmark, Italy, The Netherlands, Portugal, Russian Federation,
Spain, Sweden, Switzerland
Comparator in reference case
Current standard Austria, Baltic states, Belgium, France, Hungary, Ireland, Italy, The Netherlands,
Portugal, Russian Federation, Slovak Republic, Sweden
Best practice Croatia, Denmark
Standard and best practice England & Wales, Spain
Standard or least expensive Norway
Standard, accepted, or no treatment Switzerland
Treatment that will be replaced Finland, Poland, Scotland
All relevant therapeutic alternatives Germany
CBA: Cost–benefit analysis; CCA: Cost–consequence analysis; CEA: Cost–effectiveness analysis; CUA: Cost–utility analysis; RCT: Randomized controlled trial.
Review Bracco & Krol
592 Expert Rev. Pharmacoecon. Outcomes Res. 13(5), (2013)
Five-year view The tension between rising health care costs and budget con- straint has been magnified by the ongoing economic crisis and created the ‘perfect storm’ for payers and reimbursement authorities. In the next years the outcomes of the ‘perfect storm’ most likely will be an increased efficiency allocation of funds, unprecedented health care and reimbursement reforms and growing role of HTA type of reviews. In addition, the political turmoil in most of the European countries has changed pricing, reimbursement and HTA bodies, and increased time and uncertainty on reimbursement decisions.
The outcomes of new reimbursement trends will increasingly impact three main areas of access to new technologies:
• Price: The price of drugs has been the target of cost contain- ment measures for more than a decade. Financial and outcome- based risk sharing agreements are used more and more in sev- eral European countries and include negotiated budget caps, price/volume agreements and per/patients caps. Regular price cuts and annual reference price reviews have been implemented along with price/volume agreements re-negotiations.
• Population: Historically the National Institute of Clinical Excellence and other HTA bodies restricted their recommen-
dations/reimbursement based on higher clinical efficacy and cost–effectiveness in certain patients’ population vs label. Other European reimbursement authorities adopted this approach in order to ensure the prescription of drugs only in patients who will benefit the most and at the same time reducing the budget impact.
• Time to market: A longer time between marketing authoriza- tion and reimbursement decisions has been observed in the last few years in some markets. Reasons for lengthier proc- esses could be several. Changes in countries government and pricing and reimbursement committees, delayed publications of new drugs price to contain drugs expenditure are just some example.
Financial & competing interests disclosure
A Bracco is an employee of Amgen and holds stock. No funding was
received for this research. The author has no other relevant affiliations or
financial involvement with any organization or entity with a financial
interest in or financial conflict with the subject matter or materials dis-
cussed in the manuscript apart from those disclosed.
Medical writing and editorial support were provided by W Mark Rob-
erts, Montreal, Canada.
References
Papers of special note have been highlighted as
• of interest
•• of considerable interest
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124 Edling A, Stenberg AM.
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125 http://www.eunethta.eu/Public/
About_EUnetHTA/
Economic evaluations in reimbursement guidelines Review
www.expert-reviews.com 595
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