Health Economic Guidelines

Health Economic Guidelines—Similarities, Differences and Some Implications
Jonas Hjelmgren BSc1,

Fredrik Berggren PhD1,2,
Fredrik Andersson PhD1
Article first published online: 23 DEC 2001
DOI: 10.1046/j.1524-4733.2001.43040.x
Issue
Value in Health
Volume 4, Issue 3, pages 225–250, May/June 2001
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How to CiteAuthor InformationPublication History
How to Cite
Hjelmgren, J., Berggren, F. and Andersson, F. (2001), Health Economic Guidelines—
Similarities, Differences and Some Implications. Value in Health, 4: 225–250.
doi: 10.1046/j.1524-4733.2001.43040.x
Author Information
1
AstraZeneca R & D Lund, Clinical Science, Health Economics & Outcomes Research,
Lund, Sweden,
2
Lund University Centre for Health Economics (LUCHE), Lund, Sweden
*Correspondence: Address correspondence to: Fredrik Berggren, PhD, AstraZeneca R &
D Lund, Clinical Science, Health Economics & Outcomes Research, SE-221 87 Lund,
Sweden. E-mail: Fredrik.Berggren@astrazeneca.com
Publication History
Issue published online: 23 DEC 2001
Article first published online: 23 DEC 2001
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Keywords:
cost-effectiveness;
economic evaluations;
health economic guidelines;
reimbursement
Abstract
Top of page
Abstract
Introduction
Materials and Methods
Results
Discussion
Acknowledgments
References
Objective: To classify, summarize, and compare the health economic guidelines (HE)
issued in Europe, North America, and Australia to clarify similarities and differences
between them.
Materials and Methods: In a literature review HE guidelines were classified according to
whether they were 1) formalized, 2) informal, or 3) guidelines for health economic
methods. All the guidelines were summarized in a table format according to 15 important
methodological aspects. The aspects were compared both within and between the three
groups.
Results: A total of 25 guidelines were identified, seven formalized, eight informal, and 10
guidelines for HE methods. The levels of agreement for methodological aspects within
groups were 40% to 100%, 25% to 100% and 30% to 100% for the formalized, informal,
and HE guidelines, respectively. The formal guidelines were slightly more homogenous
than the other groups. The between-group comparison showed that the guidelines were in
agreement for about 75% of methodological aspects. Disagreement between guidelines
was found in choice of perspective, resources, and costs that should be included in the
analysis, and in methods of evaluating resources used.
Conclusion: A harmonization of methodological requirements and recommendations
exists both within and between the guideline groups. This review provides information
concerning the core of agreements that have been reached. A number of policy
implications for various parties, mainly the pharmaceutical industry, were identified.
Introduction
Top of page
Abstract
Introduction
Results
Discussion
Acknowledgments
References
In 1992, Australia became the first country to formalize and issue mandatory guidelines
for health economic evaluations of pharmaceutical products as a requirement prior to
reimbursement [1]. This document was revised in 1995 [2]. There are similar mandatory
guidelines in Canada [3], Finland [4], the Netherlands [5], and Portugal [6], as well as
from the managed care organization Regence Blue Shield (USA) [7–9]. The newly
established National Institute for Clinical Excellence (NICE) has just issued its guidelines
[10]. The function of NICE is to appraise the clinical and economic benefits of new and
existing technologies in England and Wales notified by the Department of Health and the
Assembly of Wales, and to make recommendations to the National Health System
(NHS). The impact of NICE is predicted to be significant because they have strongly
promoted implementing and disseminating their recommendations. In this respect, their
guidelines can be regarded as mandatory. Other countries that have developed principles
and recommendations for use in health economic evaluations are Denmark [11], Ireland
[12], New Zealand [13], Norway [14], the United States [15–17], and Switzerland [18],
but these guidelines are still voluntary.
The primary role of guidelines is to function as input in the pricing and reimbursement
process. Therefore, payers have an interest in scientifically consistent studies. To clarify
what is really required in undertaking economic evaluations of medical technologies,
research teams around the world have developed methodological principles and
guidelines for health economic analyses [19–29].
The objective of this review is to: 1) classify, present, and group guidelines issued in
Europe, North America, and Australia according to their purpose; 2) provide a
comprehensive and structured group-wise summary of the guidelines; and 3) generalize
and compare the guidelines according to the classifications given in 1), to clarify both
similarities and differences between them. Possible policy implications of the guidelines
will be discussed.

Top of page
Abstract
Introduction
Results
Discussion
Acknowledgments
References
This review is based on literature from various sources, such as health economic journals
and government-issued documents. Guidelines issued by governments were identified by
Internet searches; both directly via the web sites of various authorities and indirectly via
the search engine AltaVista, as well as via direct contacts with the regulatory authorities.
Guidelines published in health economic journals were identified both by a literature
search via websites (e.g., PharmacoEconomics: http://www.adis.com; newsletters) and
via AltaVista (search profile: authors, cost-effectiveness, cost-utility analysis,
pharmacoeconomic analysis, etc.).
Classification of Guidelines
Guidelines for health economic evaluations have been classified according to their
purpose by Drummond [30]. Drummond outlines three purposes of guidelines: 1) as a
requirement prior to reimbursement 2) as a statement of methodological standards, and 3)
as a statement of ethical standards. In this report we have used Drummond's first two
purposes or classifications. Good and transparent methodology, and justification for
assumptions made in evaluations, will function to some extent as protection against the
unethical conduct of studies. We have therefore disregarded the third classification.
Drummond's first classification was subdivided into two subgroups: formalized (i.e.,
mandatory) requirements prior to reimbursement, and informal (i.e., voluntary)
requirements prior to reimbursement. The first subgroup consists of national guidelines
that have been established to control expenditure for health care technologies and ensure
that funds are spent in the best possible way. The second subgroup consists of guidelines
that thus far need not be followed as a part of the reimbursement process (although health
economic data may help).
Based on these definitions, we have used the following classification: formalized
guidelines [2–10] (as a requirement prior to reimbursement), informal guidelines [11–18]
(a recommendation prior to reimbursement), and guidelines for health economic methods
[19–29] (guidelines intended for use in discussing and improving methodology in health
economic evaluations). These three groups of classifications will be used when
presenting and comparing the guidelines.
The guidelines are presented in table format, both individually and by group, under the
headings Background, Methodological Issues and Assistance/Extra Input. The
Background section presents the affiliation of authors, year of last revision, year of
implementation, purpose, and the target audience. The next section presents some
important methodological aspects that researchers ought to keep in mind when
conducting health economic evaluations. The issues in the methodological section
originate from the theoretical framework described in classical health economic
textbooks [31,32] and are presented in the following order: perspective, resource
use/costs, outcome measurement, type of analysis, incremental or average cost-
effectiveness, treatment comparator, methods of data capture, modeling, time horizon,
discounting, sensitivity analysis, reporting results, and financial implication for society.
The last section, Assistance/Extra Input, reports whether there are standardized price lists
when estimating costs, and if templates are available when compiling results.
In earlier research related to health economic guidelines, other dimensions or aspects
have also been considered, e.g., Luce and Simpson [33] discussed meta-analysis and
DeVries and Gagnon [34] discussed the issue of when studies should be performed and
by whom. Our approach considers cross-sectional variations in health economic
guidelines from the perspective of economic theory. Consequently, we do not cover all
the interesting and relevant aspects in the intersection between health economics and
other aspects of importance for the illumination of health care technologies in society.
Results
Top of page
Abstract
Introduction
Results
Discussion
Acknowledgments
References
A Tabulated Summary Of Classified Guidelines
A structured summary of the guidelines is presented in Table 1. The guidelines are
presented in the following order: formalized guidelines A–G (Table 1a), informal
guidelines H–O (Table 1b), guidelines intended to improve health economic studies P–Y
(Table 1c).
Table 1a. Formalized guidelines (A-G)
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(E) The —Guidelines
(C) Revised
(D) Dutch Portugues for the
Ministry Guideli
(A) Australia guidelines e submission
Origin (B) of Social nes for
—Common for Pharmacy of Clinical
of Canada— Affairs Manufa
Wealth pharmaco- and and
guidelin Ontario and cturers
Department economic Medicines Economic
es [3]. Health— and
[2]. research Institute Data
Finland Sponsor
[5]. (INFARM Supporting
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
QoL, quality of life; QALYs, quality of life years; WTP, willingness to pay; SG, standard
gamble; TTO, time trade off; VAS, visual analogue scale: EQ5D, EuroQoL 5
dimensions; CMA, cost-minimization analysis; CEA, cost-effectiveness analysis; CUA,
cost-utility analysis; CCA, cost-consequence analysis; CBA, cost-benefit analysis; RCT,
randomized clinical trial; CONSORT, consolidated standards of reporting trials; BMJ,
British Medical Journal.
Backgro
und
The
Ministry
Pharmaceuti MEDT
Affiliati Ontario of Social Sickness
cal Benefit Academia Academia AP
on of ministry of Affairs Funds
Advisory . and Industry. Internat
authors Health. and Council.
Committee ional.
Health.
(PBAC).
Year of
November March Nov
last — — — 1998.
1995. 1999. 2000.
revision
Year of January June July 2000. November — 2000
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making
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Institute
[10].
impleme
1993. 1999. 1998.
ntation
Purpose Provide Offer Provide Provide Present a To describe Provide
sponsors guidance a guidelines number of the process manufa
with on how to compreh which reference used by cturers
guidance address ensive together principles. Regence to and
concerning economic assessme represent Improve collect and sponsor
the issues nt of the state-of- the review s of
presentation beyond cost of the-art technical clinical, technol
of clinical unit price pharmac methodolog ability of economic ogies
effectiveness listing euticals y for the and other selected
data and the when and pharmaco- authors to health for
most submitting other economic ensure outcomes appraisa
appropriate new alternati research to high data as of the l with a
form of products. ve provide quality plan's drug basis
economic therapies reliable, studies. formulary for
evaluation. as well reproducibl adoption preparin
as the e and process. g their
related verifiable submiss
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insight into
the
benefits. therapeutic ions.
value of a
drug.
Manufacture The
Decision- Manufa
rs Minister of
makers cturers
Target (companies Manufactu Manufac Public Authors
within the and
audience preparing rers. turers. Health, of studies.
health care sponsor
submissions) Welfare
sector. s.
. and Sport.
Methodo
logical
issues
Perspect Societal Health Societal Societal Societal System wide From
ive perspective care sector perspecti perspective perspectiv perspective the
and health and/or ve. . e. including Nationa
care sector. Societal Regence l health
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system
(NHS)
and
patients Persona
perspectiv
(third party l social
e.
payer). services
(PPS)
decision
-maker.
Resourc Direct health All All All direct All All relevant All
e care costs. relevant direct health costs relevant direct costs. relevant
use/costs The use of costs health (inside and direct and direct
indirect costs (direct and care outside the indirect costs
may be indirect) costs. health care costs that incorpo
included but with Possibly sector) can be rated in
is not reference indirect must be associated the
encouraged. to the costs. included. to the NHS
Canadian Indirect treatment. and
health care costs The only PPS
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outside the perspect
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should be indirect es used
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justified. regarded patients
system. Productivit as should
y losses relevant is be
should be productivi reported
valued by ty loss. separate
the friction ly (e.g.,
cost time
approach. costs).
Outcom Effectivenes Effectiven — Effectivene Effectiven Effectiveness Long-
e s units in ess rather ss rather ess rather not efficacy. term
measure natural than than than Output clinical
ment— (patient efficacy. efficacy. efficacy measures: effectiv
Type of relevant) Effectiven Effectivene (efficacy e.g., QALYs eness;
utilities units ess units: ss units: after- (such as morbidi
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? Type s units that monetary (measurem can be McMaster mortalit
of health are related to (QALYs), ent used). Use health y. Final
status the analytic monetary methods— cardinal utilities clinical
classific method. (WTP) SG, TTO scale to index), life end-
ation Both global- and or VAS). measure years gained, points.
system and disease- natural Generic QALYs episode-free When
and specific QoL units. and (SG or days etc.. interme
preferen instruments Only non- specific TTO). Final diate
ce may be used. disease- questionnai Classificat outcomes are endpoin
scores? The selected specific res. ion preferred to ts are
QoL utility systems: intermediate used a
instrument scales Both measures. strong
should be acceptable general Intermediate associat
valid, when and endpoints ion
reliable and calculating disease need to be between
responsive to QALYs. specific justified. the final
differences The (e.g., and
in health rationale EQ5D). interme
status behind the Contingen diate
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end-
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point
valuation
chosen should
to
measurem be
measure
ent demons
WTP.
method trated.
Effectiven
(source of Utility
ess units:
between QALY measure
natural
individuals. weights or s should
units,
method of preferab
quality of
eliciting ly be
life
WTP) based
related
should be on
units or
stated. social
monetary
preferen
units.
ces.
Type of CMA, CEA CCA, CMA, CEA or CMA, No preferred CEA or
Analysis and CUA. CEA, CEA, CUA— CEA, method, e.g., CUA.
—most CUA and CUA CBA is not CUA and CMA, CEA, Subgro
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preferre CBA. No and recommend CBA. CUA or CBA up
d? single best CBA. ed. could be analysis
method is The used. Type of should
mentioned choice of analysis be
. method should be underta
must be transparent ken if
justified. with other cost-
components effectiv
in the eness is
analysis. expecte
d to
vary
between
groups
within
the
populati
on;
distingu
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between
high
risk
patients
and the
general
populati
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Increment
Incremental Increme
al cost-
Increme Increme cost- ntal
Incremental Increment effectiven Incremental
ntal or ntal cost- effectivene cost-
cost- al cost- ess cost-
average effective ss analysis. effectiv
effectiveness effectivene analysis. effectiveness
c-e ness Report eness
ratios. ss ratios. Report analysis.
ratios ratios. totals as analysis
totals as
well. .
well.
Treatme The Compariso Compari The Common Multiple Should
nt treatment n with son with treatment practice treatment be the
compara that is least the in common and/or the analysis. most
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frequent
ly used
and/or
product the
expensive which is most
prescribed
currently to be cost-
for the
available replaced, most effectiv
largest practice—
strategy the best effective e
number of the
tor and/or available or least treatme
patients (in standard
most product costly nt;
the same treatment.
commonly or treatment. could
therapeutic
used minimu be a
class).
strategy. m drug or
practice. a
surgical
procedu
re.
Method Data RCTs or RCTs or Data from Results RCTs and The
of data collected meta- Meta- clinical obtained secondary ideal is
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(meta- prospec
(in
analysis) tive
which from
where RCTs RCT
analysis RCTs RCTs are
are used— with a
(in which are used) preferred.
comparison studies naturali
only RCTs Selection Meta-
with the under stic
capture are used) criteria analysis data.
main realistic design.
to locate in the derived
comparator conditions. Data
various studies from
is the ideal. based
results. used RCTs is
The listing on
must be accepted.
of efficacy
describe
comparative .
d.
RCTs must
be complete.
Modelin Modeling Modeling Modelin Modeling Extension Each model To
g may be acceptable g is is needed if s from should bridge
(accepta needed to to acceptab the primary short to incorporate a between
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le if the
take into efficacy
treatmen long term disease-based
account and
t require treatment
patient incorporat effectiv
situation modeling. framework
conditions e future eness.
is data do not The examining (i)
that were not lifetime The
changed provide model total costs
ble? accounted costs and nature
and if sufficient populatio before the
analytic for in the effects. of any
data insight into n must be drug is
horizon? RCT. Time modelin
reflectin long term specified introduced
) Markov horizon g used
g the effects and and and (ii) after
chain should be should
normal costs. representa the drug has
process, clearly be
situation tive of the been listed
decision tree, stated. closely
are not user of (new
Monte Carlo explain
available treatment. equilibrium).
simulation. ed.
.
Time Depends on Long Should Long Must Long enough Should
horizon the treatment enough to be enough to capture all to capture all cover
pattern—the structure sufficien capture all costs and relevant the
natural all tly long relevant consequen aspects (costs period
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of
which
the
main
health
to ces
effects
capture regardless
and the
relevant all aspects of of the and effects)
history of the health
outcomes relevant costs and moment of the
disease. care
and costs. future effects. at which disease.
resourc
costs and they
es use
effects. occur.
are
expecte
d to be
experie
nced.
Discount 5% discount 5% 5% as a The base is Use 5% as Discounting Discoun
ing rate. discount standard 4%. Also a base and should be t costs
(future rate. combine use 0%, 3% in a undertaken at 6%
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discoun
t rate
and
benefits
at 1.5%
(base
case).
(both costs
In
and benefits).
costs d with a 3%, or 5% sensitivi
The choice of
and 0% in a sensitivity ty
rates(s)
outcome discount sensitivity analysis. analysis
should be
s) rate. analysis. (i) costs
given and
and
justified.
benefits
6% and
(ii)
costs
6% and
benefits
0%.
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Sensitivi Present Sensitivity If the When All Should be 95%
ty incremental analysis results or conditions uncertain undertaken to Confide
analysis ratios as must be the and parameter control the nce
95% used to underlyi assumption s should robustness of interval
confidence assess the ng data s are undergo a the results. s for
intervals. robustness are uncertain a sensitivity cost
Vary all of the uncertain sensitivity analysis. differen
main conclusion . analysis These are ces if
outcome s. must be to be data
variables in undertaken. presented originat
the At least a as limits e from
preliminary univariate (upper RCTs.
(trial based) sensitivity and Univari
analysis and analysis. lower). ate and
major multiva
assumptions riate
used in the sensitivi
model. ty
analysis
when
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modelin
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Reportin Present — In Report in Should In A clear
g results results both aggregat disaggregat follow a disaggregated presenta
in ed and ed detail. standard form to tion of
aggregated disaggre Probability form facilitate the
and in gated tree for containing comparison clinical
disaggregate form. relevant all between trial
d form. Direct alternatives relevant studies. (CONS
Direct and and . Reporting data in a ORT
indirect costs indirect must disaggreg stateme
presented costs are follow a ated nt). All
separately. to be standard fashion. costs
reported structure. and
separatel outcom
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should
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reported
in
disaggr
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detail.
The
results
for the
principa
l
outcom
es of
each
study
include
d in
submiss
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should
be
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sions to
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[10].
reported
individu
ally in
tabular
form.
The
resourc
es used
by each
treatme
nt
approac
h
should
be
reported
in
natural
units.
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making
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Resourc
e data
sources
must be
clearly
cited.
Estimat
es in
95%
confide
nce
interval
s.
Financia Estimate Products — Financial — — Budget
l financial that result analysis is impact
implicati implications in large not part of on the
ons for for the PBS expenditur pharmacoe NHS
society and for es for the conomic system.
government Ontario research. For new
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
drug
health program technol
budgets. will ogies
Calculate require the
costs much budget
(savings) as more impact
payments rigorous over a
actually economic 3-5 year
made. impact- period.
analysis.
Extra inputs/Assistance
Valuatio Manual of Unit prices Treatme Manual for Valuation Prices (unit Standar
n/Price Resource for the nt cost should costs) and d unit
list Items and resources practices research. (ideally) quantities values
available Their used must and costs Methods reflect should be based
Associated be should and opportunit reported on
Costs estimated be recommend y costs of separately. average
(Opportunity in Canada. adjusted ed prices resources Methods for costs
cost). so as to for used. the for each
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
Standard
costing is
correspo economic an resourc
nd to the evaluations appropriat e item.
estimation of
Finnish in health e Prices
both costs
treatmen care. Edited alternative in Unit
Alternatively and
t by The . Costs of
: DRG lists. quantities
practices Council for Construct health
should be
and cost Health vectors of and
given.
structure Insurance, costs and Social
. Amselveen. quantities Care.
separately
.
Templat — Worksheet — Standard Template BMJs Standar
e (a format for is checklist for d
available framework reporting available authors and reportin
of 19 pharmacoe in the referees. g form.
questions) conomic appendix.
for research
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
preparatio
n of
available in
pharmacoe
appendix.
conomic
analysis.
Table 1b. Informal guidelines (H-O)
QALYs, quality of life years; SG, standard gamble; TTO, time trade off; WTP,
willingness to pay; QoL, quality of life; CBA, cost-benefit analysis; CEA, cost-
effectiveness analysis; CMA, cost-minimization analysis; CUA, cost-utility analysis;
RCT, randomized clinical trial; BCBS, Blue Cross-Blue Shield; DRG, disease related
groups.
Origin (H) (I) Irish (J)A (K) (L) (M) FDA (N) (O)
of Danish Healthca Prescripti Norwegia Guideline Draft Swiss Academ
guidelin Ministry re on for n s for Blue Guidelines Manual y of
es of Technolo Pharmcoe guidelines Cross and — for the Manage
Health gy conomic for Blue Principles Standar d Care
—A Assessm Analysis. pharmaco Shield of for the dization Pharma
Report ent New economic Colorado Review of of cy
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
Clinical
(AMCP
of and
)—
Guidelin Econom
analysis in AMCP'
es for Guidelin ic
connectio Pharmaco s
Econom es— Evaluati
n with and economic Format
ic Draft Zealand on of
applicatio Nevada Promotion for
Evaluati version [13]. Medical
n for [15]. —USA Formul
ons of no 2. Technol
reimburse [16]. ary
Pharmac [12]. ogy
ment [14]. Submis
euticals (second
sions
[11]. draft)
[9,17].
[18].
Backgro
und
Affiliati Academ National Pharmace The University The Consult Consult
on of ia. Centre utical Norwegia of Division ed ed
authors for Managem n Colorado. of Drug experts academi
Pharmac ent Medicines Marketing from the c
o- Agency Control , Swiss experts.
(G)
Nationa
l
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for
Clinical
(F) Regence
Excelle
Blue Shields
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(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
Advertisin
Ltd/Healt g and federal
economi
h Funding Communi office of
cs in Authority.
Authority cations social
Ireland.
(HFA). (DDMAC security.
).
Year of
Dec. Nov.
last 1998. 1999. 1998. — 1995. —
1999. 1999.
revision
Year of
Oct.
impleme — — — Jan. 2002. 1994. 1995. —
2000.
ntation
Purpose Provide Provide Provide To obtain — Enumerate Support Rationa
knowled the Dept. HFA with pharmaco pharmaco ed lize the
ge on of means of economic economic decision formula
how to Health, deciding informatio reviewing -making ry
design the GMS how to n to principles. regardin decision
health payment allocate increase g process
(G)
Nationa
l
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for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
and to
support
board and (among
informe
and improve other
d
prescribe resources the things)
decision
economi rs with to those decision- reimbur
s to
c info. on activities making sement
obtain
evaluati the c-e of that are process by
value
ons. a health most concernin social
from
care desirable. g health
pharma
technolo reimburse insuranc
ceutical
gy. ment. e.
product
s.
Target Should Decision Pharmace Pharmace Industry E.g., Multiple Manufa
audience be -makers. utical utical — pharmace (e.g., cturers
mention companie companies submitting utical decision (submitt
ed. s. . companies marketers. - ing
. makers, compan
third ies).
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
party
payers,
provider
instituti
ons).
Methodo
logical
issues
The Multiple
Multiple
adopted (e.g.,
(society,
perspecti society, AMCP'
third
ve third party s health
System party
Societal should Societal Societal payer, plan
Perspect impact payer,
perspect be perspecti perspectiv patient). (AMCP
ive perspectiv patient,
ive. clearly ve. e. The 's
e. health
stated perspectiv patients
care
and e must be ).
provider
explaine stated
).
d. clearly.
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
All
relevant
All costs that
relevant can be
direct related to All Direct
All medical the important medical
All
relevant There are and utilization resource All services
relevant
costs no indirect of the utilization relevant provide
Resourc direct
associat agreed- medical drug variables direct d by the
e costs met
ed with upon costs should be consistent and health
use/costs by the
the cost (e.g., included. with the indirect plan
health
treatmen models. patient Report stated costs. (direct
system.
t. co- indirect perspectiv medical
payment, costs e. costs).
travel separately
time). from the
direct
costs.
Outcom Output The Effective Effectiven Final Physical Outcom Final
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
es measure primary ness ess outcomes. units that e outcom
measure s: outcome rather (ideally) Outcomes represent measure es.
ment— QALYs, measure( than efficacy must be in resources s: Disease
Type of life s) should efficacy. until a form utilized primary specific
utilities years be Generic effectiven which (e.g., clinical as well
accepted gained, clearly measure ess studies makes it physician outcome as
? Type episode- stated ment are possible to visits, paramet generic
of health free and instrumen available. monitor courses of ers, measure
status days, explaine ts Effectiven the impact medicatio seconda s (e.g.,
classific etc. SG, d reflecting ess unit of the new n con- ry QALYs
ation Rating (publishe societal that is product on sumed) or clinical ).
system scale d preferenc related to a clinical outcome Efficac
and and evidence es (e.g., the budgetary outcomes paramet y has to
preferen TTO are ). EuroQol). analytic period (e.g., ers and be
ce preferre Calculati method. basis. treatment interme translat
scores? d when ons of Efficacy failures, diary ed into
measuri QALYs terms changes in clinical effectiv
ng should should be QoL). A outcome eness.
QALYs. based on translated link paramet
It is actual into between ers.
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
inapprop (real-life) effectiven final and Both
riate to measures ess terms. intermedia specific
base the in a real te and
evaluati world endpoints generic
on only setting should be instrum
upon and not document ents can
WTP. on ed if be used
This artificial intermedia to elicit
method clinical te end- quality
can, trial points are of life.
however settings. used. If TTO,
, be used monetary SG and
as a units are Rating
comple used, the scales
ment. monetary can be
values used to
must be elicit
dis-closed. utilities.
QoL When a
instru- CBA is
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
ments put into
should practice
incor- in
porate all accord
relevant with
and method
important ological
domains measure
and ment
provide principl
represent- es—try
ative to get as
measures close as
of these possible
domains. to the
Evidence instrum
concern- ents
ing used in
validity of theoreti
QoL cal
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
instrument
s must be literatur
document e.
ed.
No
preferred
method.
The
CMA, CMA,
CMA, method
CEA, CEA,
Type of CEA and must be No
CUA or CUA
Analysis CEA CUA. The consistent single
CBA. and
—most and CUA. choice of with — method
Generall CBA.
preferre CUA. method meeting preferre
y CEA is CBA is
d? must be the cost- d.
preferred preferre
justified. and
. d.
outcome-
impact
requireme
nt.
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
Increme
Increment
Increme ntal
al cost- Increment
Increme Increment ntal cost-
effectiven al cost
ntal or al cost- cost- effectiv
ess analysis is
average — — effectiven — effectiv eness
analysis. of limited
c-e ess eness when
Report applicatio
ratios analysis. analysis CEA or
totals as n.
. CUA is
well.
applied.
Treatme — State the No The most The Comparat Current Relevan
nt rationale treatment commonly drug(s) ors should practice t
compara for a (doing used which the be and compar
tor chosen nothing) treatment, product is disclosed non- ators.
alternativ as well as the least expected when interven Include
e. close expensive to replace. based on tion. a
Explain comparat and/or head-to- The discussi
the ors. another head compara on of
alternativ comparato studies. tor must compar
e in r that is Difference be ator
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
s between
treat- relevant
considere ments for product
detail.
d relevant. must be clinical (s).
statisticall practice.
y proven.
Method RCTs RCT, RCT in Data from RCTs - Methods RCTs Data
of data and meta combinati RCTs in results of data and must be
capture secondar analysis, on with combinati should be capture meta- applica
y data. observati real-life on with interprete that pro- analysis ble to
onal data data to register d for the duce an . the
and capture data (real- BCBS acceptable health
modeling patients life). treatment level of plans
. with poor Meta- population precision. populati
complian analysis . Meta- Data on a on.
ce. may also analysis; drugs Prospec
be used. include effect tive
inclusion must piggy-
criteria for comply backed-
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
studies, with the ,
processes internal naturali
for and stic
extracted external compar
data and validity ative,
statistical criteria. retrospe
analysis! Studies ctive-,
All based on or
collected literature modelin
data must review g
be should studies.
relevant include all
for the relevant
BCBS studies
treatment and
environme employ
nt. systematic
and
document
ed search
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
methods.
Data must
be
applicable
to the US
environme
nt.
Modelin Modelin Details Modeling May be Modeling Models Modelin Disease
g g is should acceptabl used to acceptable should be g is -based
(accepta appropri be given e for estimate — used only appropri analytic
ble? ated about the capturing long term assumptio when it is ate to model
analytic when model long term effects ns should impossible bridge that
horizon? data is used effects of and costs. be to gather the gap depicts:
) collecte (e.g., an presented data using between disease,
d from decision interventi and well- efficacy clinical
multiple tree or on. justified. controlled and course,
sources. regressio studies. effectiv primary
n model). eness. treatme
The nt,
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
assumpti options,
ons treatme
should nt
be process,
justified. clinical
pathwa
y etc.
Transpa
rent
models;
assumpt
ions
and
calculat
ions
must be
designe
d to
allow
the
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
health
plan to
investig
ate the
results
afterwar
ds.
Long Long
Should
enough enough
be Long Long
to to
clearly enough to Long enough
capture capture
described capture enough to (depend
all Prevalenc all
and all the capture all ent on
Time relevant e period— relevant
appropria differenti relevant — the
horizon aspects maximum aspects
te to the al effects aspects of nature
(costs 3 years. (costs
disease of an costs and of the
and and
and interventi effects. disease)
effects) effects)
treatment on. .
of the of the
.
disease. disease.
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
All costs
The
and
usual
Discoun benefits
discount
Discount ting should be The
The rates are
ing should discounte discount Discounti
choice of 2.5%,
(future be d. The rate ng is of
discount 5% and
costs undertak base rate should be less —
rate(s) 10%.
and en. No is 10% (0, in the 2, importanc
should Other
outcome specific 5 and 5%–10% e.
be given. choices
s) rates are 15% in a range.
must be
given. sensitivit
justified
y
.
analysis).
Sensitivi Should Altered All At all Sensitivity Sensitivity Sensitiv
ty be variables uncertain levels of analysis analysis ity
analysis undertak and the parameter the focused should be analyse
en to ranges s (e.g., analysis on examined s on
control over discount where scenario for both pivotal
the which rate, net parameter developm the effects estimate
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
cost
baseline
health
they are
status) s and and the
robustne altered s and
should be assumptio economic
ss of the should ent. assumpt
varied in ns are parameter
results. be ions.
a uncertain. s.
justified.
sensitivit
y
analysis.
Reportin In Major Both in Report Summary Inclusion All key In
g results disaggre outcomes disaggreg results in of criteria for paramet disaggr
gated should ated and disaggreg pharmaco resource ers must egated
form to be in ated form. economic use and be detail
facilitate presented aggregate Decision evidence monetary examine (tabular
compari in d form. tree and should be valuation d in a form).
son aggregat Markov reported should be sensitivi Separat
between ed models in clearly ty e
studies. (summar may be spreadshe pre- analysis resourc
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
y form) used to et format sented. . Limits e
and visualize (disaggreg Basis for of utilizati
disaggre the ated conclusion paramet on, total
gated results. form). should be er costs,
form. presented. values total
Limitation in the effectiv
s of the analysis eness,
study should and
design and be increme
findings, justified ntal
assump- . effectiv
tions, etc. eness in
should be the
presented report
for the format.
reader. Costs
should
be
presente
d as
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
total net
costs of
introduc
tion of
the new
product.
Financia — — — — — — The System
l report wide
implicati should impact
ons for cover for the
society all health
relevant plan.
economi Impact
c issues assessm
in a ents
disaggre should
gated be
form estimate
(e.g., d for
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
cost per
case). A
discussi
on of
compara
the first
bility
three
with
budget
other
periods.
studies
should
be
included
.
Extra input/Assistance
Valuatio — Methods Prices Opportuni Average Average Second Prices
n/Price for based on ty costing wholesale Wholesale best and
list estimatio DRGs. (ideally). prices for Price opera- resourc
available n of Calculatio drug costs (AWP). tional es must
prices ns of costs and procedu be
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
and should Medicare res to applica
quantitie reflect fee determi ble to
s should Norwegia schedules ne the the
be n for costs of health
presented condition. medical a tech- plan.
. costs. nology
have to
be
applied
since
the
calculati
on of
opportu
nity
costs
requires
perfect
markets.
Accept-
(G)
Nationa
l
Institute
for
Clinical
(F) Regence
Excelle
Blue Shields
nce—
(C) Revised
Ministry Guideli
Finland Sponsor
[4]. s of
ED) [6]. Formulary
Technol
Consideratio
ogies
n [7–9].
making
Submis
sions to
the
Institute
[10].
able
cost
data:
fees,
tariffs
and
reimbur
sement
figures.
A
reportin
g Formul
Short
structur ary
Templat structure
e is submiss
e — — — of analysis — —
given ion
available is
on p. checklis
presented.
B3-B4 t.
in the
manual.
Table 1c. Guidelines intended to improve HE studies (P-Y)
(T)
Econom
(P) A ic
proposal analysis
(U)
for (R) of
Hanove (V) UK
methodolo Guidelines (S) A health
r guidance on
gical and proposal technolo
Guideli good practice in
Origin guidelines (Q) recommend for Italian gies and
nes for the conduct of
of for Canada— ations for guidelines program
Econo economic
guidelin economic CCOHTA French in s. A
mic evaluation of
es evaluation [20]. pharmacoe pharmacoe Spanish
Evaluat medicines -
of conomic conomics proposal
ion— United
pharmaceu studies [22]. for
German Kingdom [26].
ticals— [21]. method
y [25].
Belgium ological
[19]. standard
ization
[23,24].
Backgro
und
The Mario
Belgian CCOHTA,
Colleges Negri Consult
Society Departme Univers
Affiliati Des Institute ed Government/Ph
for nt of ity of
on of Économiste Centre for academi armaceutical
Pharmaco- Health, Hanove
authors s De La Health c industry.
epidemiol industry, r.
Santé. Economics experts.
ogy. academia.
(CESAV).
2nd
Year of edition
last — 1997 — — — — 1994.
revision (Novembe
r).
Year of
November January
impleme 1994. April 1997. 1995. 1995. —
1995. 1995.
ntation
Purpose Provide Provide Provide Promote Formula Improv —
guidance assistance credibility the te an e clarity
to to the doer (for the diffusion initial of
conductors of results), of a proposal health
and pharmacoe quality rational for econom
evaluators conomic (studies) approach method ic
(T)
Econom
(P) A ic
proposal analysis
(U)
for (R) of
Hanove (V) UK
r guidance on
Econo economic
mic evaluation of
Evaluat medicines -
ion— United
y [25].
Belgium ological
[19]. standard
ization
[23,24].
analyses
in
providing
standardiz ological
ed and and standard
of to health
reliable comparabil s for
pharmacoe care
info to the ity economi studies.
conomic problems
target (between c
studies. in Italy.
audience. studies). evaluati
Consistent on.
with a
variety of
purposes.
Decisio
Multiple
n-
(e.g.,
Decision- makers Decisio
decision-
Decision- makers on on n-
makers,
Target makers on different different makers
third party — —
audience different levels. levels on
payers,
levels. Researcher and in differen
provider
s. various t levels.
institution
contexts
s).
.
Methodo
logical
(T)
Econom
(P) A ic
proposal analysis
(U)
for (R) of
Hanove (V) UK
r guidance on
Econo economic
mic evaluation of
Evaluat medicines -
ion— United
y [25].
Belgium ological
[19]. standard
ization
[23,24].
issues
Depend
s on the
aim of
the
Societal study
perspectiv (e.g.,
e (ideally), Third party societal,
Depends
other Societal payer or third Societal
Perspecti on the aim Societal
perspectiv perspectiv patient party perspec
ve of the perspective.
es should e. perspective payer, tive.
study.
also be . etc.).
considered The
. perspect
ive
should
be
stated.
Resourc All All health The costs Only direct Depend All All relevant
e relevant care costs, included costs are to s on the direct direct and
use/costs costs direct and depend on be aim of and indirect costs.
should be indirect, the aim of considered. the indirect
reported. that can be the study. study. costs.
Indirect associated All costs Costs
and with the that are of side
(T)
Econom
(P) A ic
proposal analysis
(U)
for (R) of
Hanove (V) UK
r guidance on
Econo economic
mic evaluation of
Evaluat medicines -
ion— United
y [25].
Belgium ological
[19]. standard
ization
[23,24].
effects
relevant
are to
must be
be
distinguish
intangible reporte
ed and
costs treatment d with
presented
should be should be the
in detail.
reported included. probabi
Report
separately. lity of
indirect
their
costs
occurre
separately.
nce.
Outcome Effectiven Effectiven Effectivene Effectivene Effectiv Valid Outcome
measure ess rather ess rather ss rather ss rather eness and measures
ment— than than than than rather reliable should be
Type of efficacy. efficacy. efficacy. efficacy. than profilin identified and
utilities Both Effectiven The use of Only efficacy. g and the basis for
accepted specific ess units: final end- clinically The use indexin their selection
? Type and QALYs points is relevant of more g reported.
of health generic recom- preferred to end-points than one instrum Generic
status instrument mended. surrogate should be measure ents measures of
classific s can be Contingen end-points. considered ment of should QoL when
ation used to t valuation Generic (e.g., effectiv be used CUA is used.
system elicit preferred and disease survival, eness for
and quality of for specific quality of (e.g., measuri
preferen life. When assigning instruments life). life ng
(T)
Econom
(P) A ic
proposal analysis
(U)
for (R) of
Hanove (V) UK
r guidance on
Econo economic
mic evaluation of
Evaluat medicines -
ion— United
y [25].
Belgium ological
[19]. standard
ization
[23,24].
values to
outcomes
or a
in CBA.
combinatio
HrQoL
n of these
instrument years
are
s: gained
acceptable quality
eliciting Functional and
for of life.
QALYs, living QALYs
measuring Both
preference index, Surrogate ) is
quality of indicati
measures Western end-points recomm
life. on
ce are Ontario- should be ended.
QALYs and/or
scores? recommen McMaster viewed Generic
can be non-
ded (e.g., Osteo- with measure
elicited specific
TTO, SG arthritis caution. s are
through the instrum
or rating index, preferab
use of SG, ents can
scale). Sickness le when
TTO or be used.
Impact eliciting
VAS. The
Profile QoL.
use of
and
WTP must
Nottingha
be justified.
m Health
Profile.
Type of CMA, CCA, CMA, CMA, CEA CMA, CMA, CEA,
Analysis CEA, CMA, CEA, CUA CEA or and/or CEA, CUA or CBA.
—most CUA and CEA, and CBA. CUA. CEA CUA. CUA
(T)
Econom
(P) A ic
proposal analysis
(U)
for (R) of
Hanove (V) UK
r guidance on
Econo economic
mic evaluation of
Evaluat medicines -
ion— United
y [25].
Belgium ological
[19]. standard
ization
[23,24].
and
CBA.
The
CBA. The CUA and choice
The choice
choice of CBA. of
preferred of method is most
method CUA and method
? must be preferred.
must be CBA most depends
justified.
justified. preferred. on the
purpose
of the
study.
Costs and
outcomes
Increment
must be Increme
al cost- Increme
Increme reported ntal
effectiven Incrementa Incrementa ntal
ntal or as cost-
ess l cost- l cost- cost- Incremental
average increments effectiv
analysis. effectivene effectivene effectiv cost analysis.
c-e . Report eness
Reports ss analysis. ss analysis. eness
ratios totals for analysis
totals as analysis.
each .
well.
alternative
as well.
Treatme Existing, Compariso Current The Depend Most Should be
nt minimum n with and/or comparator s on the effectiv stipulated and
compara or most both most should be aim of e form justified.
(T)
Econom
(P) A ic
proposal analysis
(U)
for (R) of
Hanove (V) UK
r guidance on
Econo economic
mic evaluation of
Evaluat medicines -
ion— United
y [25].
Belgium ological
[19]. standard
ization
[23,24].
the
used both of
study.
effective recommend internation treatme
Possible
practice. ed practice ally and in nt, most
existing options
The (ideally). Italy. Can widely
practice are:
choice of Practice in be the most distribu
tor and most
comparato the same widely ted or
minimum efficient
r should pharmacoth used or the minimu
practice. , most
be erapeutic doing m
used or
justified. class. nothing practice
doing
alternative. .
nothing.
Method Primary Performan RCTs, RCTs or RCTs or Data RCTs, meta-
of data data ce and retrospectiv meta- meta- from analysis,
capture (RCTs) documenta e case- analysis analysis. clinical observational
and meta- tion of control (based on Meta- trials is data and
analysis data studies, RCTs). analysis recomm modeling. The
can be collection interventio must be ended. choice of
used. The should n trials, carried Meta- method should
quality of follow cohort out in analysis be justified.
the data well- studies, such a is also
should be defined patient way that accepte
documente procedures databases, reprodu d.
d. . modeling, cibility
etc. is
Overview guarante
(T)
Econom
(P) A ic
proposal analysis
(U)
for (R) of
Hanove (V) UK
r guidance on
Econo economic
mic evaluation of
Evaluat medicines -
ion— United
y [25].
Belgium ological
[19]. standard
ization
[23,24].
of RCTs in
a meta-
analysis is ed.
also
acceptable.
Modelin The The Modeling — When In Modeling is
g analytic structure is needed data that connect acceptable.
(accepta horizon and the when the capture ion
ble? should be nature of availability the with
analytic extended the model of data whole calculat
horizon? to capture must be concerning analytic ion of
) all presented. future horizon long
relevant events is are not term
outcomes. limited. availabl effects
To do so e, and
modeling modelin costs.
might be g is
required. suggeste
The d. The
structure underlyi
and ng
rationale assumpt
of the ion of
model the
should be model
(T)
Econom
(P) A ic
proposal analysis
(U)
for (R) of
Hanove (V) UK
r guidance on
Econo economic
mic evaluation of
Evaluat medicines -
ion— United
y [25].
Belgium ological
[19]. standard
ization
[23,24].
must be
well
explained.
describe
d.
The
time
Long Long horizon
Long
enough to enough to should
enough to
Time capture capture be the
capture all — — —
horizon long term long term entire
relevant
effects and effects and life span
outcomes.
costs. costs. of the
patients
affected.
Discount
Standard 5% as a
Use 5% as costs using
discount base -
Discount a base. 2.5-5% Use an
rate 5%. use 3%
ing Rates in rates. The initial rate
In The and
(future the 0-5% effects of 5% The
sensitivity standard 10% in
costs range are should be (3%-7% in recommended
analysis rate is a
and recommen presented a rate is 6%.
use 3% as 6%. sensitiv
outcome ded in a with and sensitivity
a base and ity
s) sensitivity without analysis).
0% as a analysis
analysis. discounting
minimum. .
.
(T)
Econom
(P) A ic
proposal analysis
(U)
for (R) of
Hanove (V) UK
r guidance on
Econo economic
mic evaluation of
Evaluat medicines -
ion— United
y [25].
Belgium ological
[19]. standard
ization
[23,24].
Must be
Should
applied
be
when the Calculat
Uncertain Both underta
To capture economic e a
parameters classical ken All uncertainty
all kinds model is central
should sensitivity when in the analysis
of determinist baseline
undergo a analyses paramet should be
uncertaint ic. and
sensitivity where ers are covered with
Sensitivi y should a Uncertain extreme
analysis. uncertain uncertai the use of
ty rigorous parameters values
The parameters n. The confidence
analysis sensitivity should be for an
ranges and are varied upper intervals and
analysis varied in interval
choice of and and appropriate
be an (2
parameters statistical lower ranges for
undertake increasing standard
should be distribution limits parameters.
n. and a de- deviatio
justified. tests. must be
creasing ns).
justified
range of
.
10%.
Reportin Reports in Standardiz Results — The use — In
g results disaggrega ed should be of disaggregated
ted and reporting presented various form.
technical structure. in a indicato
detail Reports successive rs of
following both in and effectiv
a disaggrega detailed eness in
standardiz ted and way. Costs the
(T)
Econom
(P) A ic
proposal analysis
(U)
for (R) of
Hanove (V) UK
r guidance on
Econo economic
mic evaluation of
Evaluat medicines -
ion— United
y [25].
Belgium ological
[19]. standard
ization
[23,24].
aggregated
report is
form.
recomm
Probabilit
ended
y tree for
(Cost
clinical and effects
per life
ed outcomes are to be
year
structure. should be presented
gained,
provided separately.
cost per
for the
QALY
relevant
gained,
alternative
etc.).
.
Financia — A — — — — —
l financial
implicati impact
ons for analysis
society should be
conducted
for major
organizati
ons that
would be
affected
by the
decision
(T)
Econom
(P) A ic
proposal analysis
(U)
for (R) of
Hanove (V) UK
r guidance on
Econo economic
mic evaluation of
Evaluat medicines -
ion— United
y [25].
Belgium ological
[19]. standard
ization
[23,24].
(primary
decision-
maker).
Extra inputs/Assistance
Valuatio Costs Economic — Costs Producti — Resource use
n/Price should definition borne by a on costs should (ideally)
list ideally be of costs third party from the reflect full
available valued in must be payer account opportunity
terms of used - the should be s of the cost. Average
opportunit concept of considered produce cost data is
y costs. opportunit - gross r acceptable as a
Physical y cost. prices (ideally) proxy.
units are CCOHTA including . Market
to be Guidance patient price
reported document copayment under
separately for the and conditio
from the costing charges. ns of
costs of process. Price list: perfect
the Italian competi
resources National tion
used. Tariff List. may
Resource also be
utilization used.
data must
reflect
(T)
Econom
(P) A ic
proposal analysis
(U)
for (R) of
Hanove (V) UK
r guidance on
Econo economic
mic evaluation of
Evaluat medicines -
ion— United
y [25].
Belgium ological
[19]. standard
ization
[23,24].
local
conditions
.
Ten
Standardiz questio
ed ns
reporting which
structure - should
Standardiz a be
ed framework asked
Templat reporting to ensure when
e structure that — — — designi —
available is included studies are ng
in the reported in health
appendix. an econom
adequate ic
and evaluati
consistent ons
manner. (append
ix).
QALYs, quality of life years; TTO, time trade off; WTP, willingness to pay; SG,
standard gamble; CBA, cost-benefit analysis; HrQoL, health-related quality of life; VAS,
visual analogue scale; QoL, quality of life; CUA, cost-utility analysis; CMA, cost-
minimization analysis; CEA, cost-effectiveness analysis; RCT, randomized clinical trial;
CCOHTA, Canadian Coordinating Office for Health Technology Assessment.
QALYs, quality-adjusted life years; SG, standard gamble; TTO, time trade off; HUI,
Health Utilities Index; WTP, willingness to pay; CUA, cost-utility analysis; CMA, cost-
minimization analysis; CEA, cost-effectiveness analysis; CBA, cost-benefit analysis;
RCT, randomized clinical trial.
Background
Academia (sponsored
Affiliation of University of
by the US Public Health PhRMA
authors Pennsylvania.
Service).
1996 (published Feb.
Year of last revision 1996. 1995.
1997).
Year of
— — —
implementation
Provide PhRMA
members with a set of
voluntary principles Standardization of
Purpose Academic.
for the conduct of methods.
pharmacoeconomic
research.
Reference case for
Decision-makers
Target audience analysts and PhRMA members.
on different levels.
researchers.
Methodological
issues
Depends on the aim of
the study (e.g.,
Reference case for Multiple (e.g.,
societal, third party
Perspective analysts and society, third party
payer, etc.). The
researchers. payer, patients).
perspective should be
stated.
All relevant direct and
All relevant direct and
indirect costs in All relevant direct
indirect costs that can
Resource use/costs accordance with the and indirect costs
be associated with the
perspective should be should be included.
intervention.
included.
Outcome An outcome measure A variety of different Outcome measures:
measurement - Type that incorporates both outcome measures are natural units (e.g.,
of utilities accepted? quality of life and life accepted: monetary years of life saved,
Type of health expectancy (e.g., life benefit, effectiveness, work loss days),
status classification years gained) is QoL, utility, efficacy, QALYs and WTP.
system and recommended. QALY safety, morbidity,
weights can be obtained
by SG, TTO and/or
rating scale (interval
scale). A generic health
preference score? status classification mortality.
system is recommended
- for example HUI,
EuroQoL and Quality
of Well-Being Scale.
Type of analysis - CMA, CEA, CUA, or CMA, CEA, CUA
CUA is preferred.
most preferred? CBA. or CBA.
Incremental or Incremental cost- Incremental cost-
—
average c-e ratios effectiveness analysis. effectiveness analysis.
Existing practice is the
most appropriate
Least expensive
comparator. The best
currently available
available alternative or Alternative treatment -
Treatment therapy, most
no intervention other drugs, surgical or
comparator commonly used or
alternative can also be doing nothing.
most effective
used if the existing
therapy.
practice is not cost-
effective.
RCTs (when
efficacy is of
interest). When the
A variety of data
Corrected RCT results time horizon is
sources can be used,
(deleting protocol longer, other
Method of data for example RCTs and
driven costs or methods are
capture databases. The quality
outcomes) and/or meta- appropriate: large-
of the collected data
analysis. sample trial,
must be documented.
modeling,
multivariate
analysis, etc.
Modeling (Markov,
When the time frame of decision analysis,
When modeling is
the study is too narrow regression, etc.) is
Modeling used, the
to capture all relevant appropriate to bridge
(acceptable? underlying logic of
costs and outcomes, the gap from efficacy
analytic horizon?) the model should
modeling is then a valid to effectiveness or for
be described.
form. adding long term
outcomes.
Time horizon Long enough to capture Should be stated and The selected time
all relevant aspects of based on the likely use horizon should be
justified and
sufficient
information should
the treatment. and effect of the drug.
be provided for
readers to evaluate
the time frame.
The base rate is 3%. In
The base rate is
a sensitivity analysis the Discounting should be
Discounting (future 5%. This should be
rate can be varied undertaken but no
costs and outcomes) varied in a
within the 0%-7% specific rate is given.
sensitivity analysis.
range.
Key parameters should,
at a minimum, be varied Uncertainty should be The particular
in a univariate demonstrated in a variables selected
sensitivity analysis. A sensitivity analysis for a sensitivity
Sensitivity analysis
multivariate analysis (e.g., random effects analysis should be
may also be conducted and uncertain described and
for important assumptions). justified.
parameters.
Present the results in 2
parts, a journal report The results should be Report the results
(publishable report) and presented in a in disaggregated
a technical report (a disaggregated form - form. Cost items
Reporting results
more detailed report). readers should be able should be
The results should be to reproduce the key differentiated as
reported in a results. much as possible.
disaggregated form.
Financial
implications for — — —
society
Extra
inputs/Assistance
A resource that is used
should (ideally) be The price and the
valued at its opportunity quantity of a
Valuation/Price list
cost. In case this is not — consumed resource
available
possible, Average should be described
Wholesale Price is separately.
recommended.
Template available — —
A Generalized Comparison of Different Groups Of Guidelines
Table 2 is intended to give a general overview of the groups of guidelines and their
recommendations, as presented in the previous section. As can be seen, each group has its
own column in the table. These columns show the typical guideline within each cluster at
each analytical level. A generalization has different levels of strength. If all the guidelines
within a group agree about a recommendation, the level of strength is equal to 1 (7/7 = 1,
8/8 = 1 and 10/10 = 1). When there is major disagreement between guidelines and more
than half of the guidelines have recommendations other than the typical example, the
level of strength is marked as vague.
Table 2. An overview of similarities and differences between groups of HE guidelines
Formalized A– Level of Level of HE methods Level of
Informal H–O
G Strength Strength P–Y Strength
CEA, cost-effectiveness analysis; CUA, cost-utility analysis; CBA, cost-benefit analysis;
c-e, cost-effectiveness; RCT, randomized clinical trial.
Analytical level Methodological issues
3/8
i) Societal 4/7 i) Societal
vague
Depends on
Perspective ii) Multiple the aim of the 5/10
ii) Societal
(including 2/8 study
and/or health 6/7
societal, third vague
care sector
party payer
Direct health All relevant All relevant
Resources/costs 5/7 4/8 5/10
care costs costs costs
Generic and Generic and Generic and
disease disease disease
Outcome -
specific 6/7 specific 5/8 specific 8/10
measurement
measurement measurement measurement
instruments instruments instruments
i) CEA or i) CEA or i) CEA or
7/7 5/8 9/10
CUA CUA. CUA
Type of analysis
ii) CEA, CUA ii) CEA, CUA
4/7 8/10
or CBA or CBA
Incremental or Incremental c- Incremental c- Incremental c-
7/7 4/8 9/10
average c-e e e e
Treatment Common Common 3/8 Existing 3/10
5/7
comparator practice practice vague practice vague
Methods of data RCT (and RCT (and RCT (and
7/7 7/8 5/10
capture meta analysis) other methods) other methods)
Modeling Accepted 7/7 Accepted 8/8 Accepted 9/10
Time horizon Long enough 7/7 Long enough 6/8 Long enough 5/10
Table 2. An overview of similarities and differences between groups of HE guidelines
Formalized A– Level of Level of HE methods Level of
Informal H–O
G Strength Strength P–Y Strength
5% discount 2.5-10% 2/8 5% discount
Discounting 4/7 5/10
rate discount rate vague rate
When When When
Sensitivity
uncertainty 7/7 uncertainty 8/8 uncertainty 10/10
analysis
arises arises arises
In In In
Reporting
disaggregated 6/7 disaggregated 8/8 disaggregated 8/10
results
detail detail detail
Financial
implications for Not necessary 4/7 Not necessary 6/8 Not necessary 9/10
society
Extra input/Assistance
Country
Valuation/Price No principles 2/8 Opportunity
specific cost 3/7 5/10
list available of valuation vague cost pricing
condition
Price list Fees and/or 2.8
3/7
available tariffs vague
Template Template 4/7 No template 5/8 No template 7/10
The following one-to-one comparison between groups has been made: 1) formalized
versus informal, 2) formalized versus health economic methods, and 3) informal versus
health economic methods. To be as concise as possible, the focus is on the most obvious
differences between the groups.
Formalized Guidelines versus Informal Guidelines
When the formalized guidelines are compared with the informal guidelines, it is seen that
12 out of 15 levels are fairly similar. The most obvious differences concern 1) the
resources/costs that should be included in the evaluation, 2) the choice of discount rate,
and 3) the valuation of costs.
The formalized guidelines are quite clear on which costs to include in the health
economic evaluation. Five out of seven stress that all relevant direct health care costs
should be included in the evaluation, while four out of seven of the informal guidelines
recommend that the analyst include all relevant costs, including indirect costs.
Individual time preferences are reflected in the discount rate. The standard discount rate
is 5% and is often used in health economic evaluations. The formalized guidelines have
adopted this rate in four out of seven cases. Recommendations in the informal guidelines
are vague; two out of eight recommend that the analyst adopt a discount rate between 2.5
and 10%.
The final and perhaps most important difference between these groups concerns how to
measure costs. The formalized guidelines are divided into two groups of equal size; three
out of seven suggest country-specific costing, and three out of seven can provide
researchers with price lists. Whether country-specific costing means that costs should
reflect the best use of resources (opportunity cost) is not obvious. The informal guidelines
are also divided into two groups of equal size; two out of eight suggest no principles of
valuation, or fees and tariffs, respectively. There seems to be major disagreement among
the informal guidelines as to how to value resources used; for example, Norway
advocates opportunity costing whereas Switzerland advocates fees and tariffs.
In summary, the formalized guidelines are generally more homogenous than the informal
guidelines.
Formalized Guidelines versus Guidelines for Health Economic Methods
When examining the differences between the formalized guidelines and the guidelines for
health economic methods, it is important that their respective purposes be borne in mind.
The formalized guidelines were developed to inform decision makers within the
regulatory authority as to whether a pharmaceutical product adds enough extra value to
be reimbursed. The guidelines for health economic methods were established to develop
a state-of-the-art methodology for health economic evaluation based on economic theory.
The formalized guidelines and the guidelines for health economic methods are fairly
similar in 11 of 15 levels. However, four main differences can be distinguished between
the two types of guidelines. These are: 1) the perspective of the evaluation 2) the
recommendations and requirements concerning evaluation of resource use/costs 3) the
choice of treatment comparator, and 4) the valuation of costs.
The formalized guidelines stress that the perspective of the analysis should be societal,
whereas the guidelines for health economic methods appear to be less restrictive. The
guidelines for health economic methods generally point out that the perspective is
dependent on the aim of the study. This means that the researcher has more freedom to
choose the analytical aspects he/she wants to emphasize within the scope of the
perspective. For example, the researcher has the freedom to examine the impact of two
pharmaceutical products on the utilization of inpatient care and is allowed to exclude
costs that fall outside this area. This approach is narrower than the societal or the health
sector approach. The societal perspective stipulated by the formalized guidelines does not
allow the researcher to exclude important direct costs within the health care sector, which
include utilization of both inpatient and outpatient care. In this respect the formalized
guidelines are more restrictive.
Although the guidelines for health economic methods are less restrictive in the choice of
perspective, it is interesting to note that these guidelines actually have more restrictive
inclusion criteria concerning resources used and costs. Within the societal perspective, all
costs, both direct and indirect, should ideally be included to capture the total impact of a
pharmaceutical product. This requirement is met by the guidelines for health economic
methods but not by the formalized guidelines. Consideration of direct costs outside the
health care sector, such as patients' out-of-pocket expenses and transportation costs, and
indirect costs for productivity losses, is not a general requirement in the formalized
guidelines. The reason for not also including indirect costs as a requirement could be that
the method (human capital approach) for measuring these costs is still controversial.
Agreement among the formalized guidelines to use common practice as the treatment
comparator is quite clear; the strength of this generalization is five of seven. It is difficult
to find a general rule for choice of comparator in the guidelines for health economic
methods. A variety of different comparators are suggested, such as existing practice,
minimum practice, and most effective practice, but these definitions are quite vague. The
most general recommendation is existing practice, which is stressed in 3 out of 10 cases.
If the definitions for existing practice and common practice are considered to overlap,
there is a weak relationship between the formalized guidelines and the guidelines for
health economic methods in this area.
Valuation of health care resources appears to be a difficult problem. A general rule for
decision making in formalized guidelines does not exist—both country-specific costing
and use of available price lists are recommended—however, the principle on which
valuation of resources rests is unclear. In 5 out of 10 cases the guidelines for health
economic methods stress that resources should reflect the opportunity cost of the
resources used. This principle is a cornerstone in economics, but it is difficult to apply in
practice because of imperfections in health care markets.
In summary, there appears to be more agreement among regulatory authorities than
among health economic researchers on how to guide those who perform health economic
studies.
Informal Guidelines versus Guidelines for Health Economic Methods
When the informal guidelines are compared with the guidelines for health economic
methods, it can be seen that 11 levels out of 15 are fairly similar. However, obvious
differences are noted in four areas. These are: 1) the perspective of the study 2) the
choice of treatment comparator 3) the choice of discount rate, and 4) the valuation of
costs. Differences in the choice of discount rate and in the valuation of costs were
discussed when we analyzed formalized versus informal guidelines and formalized versus
health economic methods. We shall now focus on 1) and 2).
As was already pointed out, the guidelines for health economic methods have adopted a
perspective that is dependent on the aim of the study. The informal guidelines have
adopted a societal perspective in three out of eight cases and a multiple perspective in
two out of eight cases. A logical explanation for this distribution in the informal
guidelines could be the differences in health care systems in the countries that have
issued these guidelines. For instance, the US FDA guidelines and the Swiss guidelines
are both informal guidelines. Both reflect the respective health care systems in these
countries. These health care systems are based on a free-market structure wherein a
variety of providers and payers of health care coexist as separate bodies. The private
(third-party) payers of health care, i.e., insurance companies, focus on direct health care
costs that would otherwise be borne by the patient himself/herself. This means that costs
falling outside this range are more or less ignored (e.g., costs for workdays lost). On the
other hand, in countries like Norway and Denmark that are more regulated, the
government plays a major role in governing the health care system; hence, the societal
perspective is of more interest.
As was the case when we compared the formalized guidelines and the guidelines for
health economic methods, there appears to be some confusion concerning the definitions
of alternative treatments. The informal guidelines are vague in their recommendations of
common practice as the treatment comparator (3/8), and the guidelines for health
economic methods are vague in their recommendations of existing practice (3/10). Are
these poorly defined concepts equivalent, or do they partly overlap? If they are
equivalent, agreement between the informal and the health economic guidelines is weak.
If they only partly overlap, agreement is very weak.
In summary, the informal guidelines and the guidelines for health economic methods
seem to be equally generalized.
Discussion
Top of page
Abstract
Introduction
Results
Discussion
Acknowledgments
References
This review has classified, summarized, and compared health economic guidelines issued
in Europe, North America, and Australia according to their purpose. Three classes of
guidelines were identified and compared: formalized guidelines (i.e., mandatory
guidelines prior to reimbursement), informal guidelines (i.e., voluntary guidelines prior to
reimbursement), and guidelines intended for use in improving and discussing health
economic methods.
Fairly good agreement could be found in about three quarters of the guideline
recommendations such as type of analysis (cost-effectiveness analysis and cost-utility
analysis), incremental cost-effectiveness ratios, acceptance of modeling, and adequacy of
time horizon. This indicates good harmonization among the three sets of guidelines
concerning core aspects. One possible explanation for this harmonization could be that
the formalized guidelines were generally issued earlier than the informal guidelines and
therefore could be functioning as a template.
There are some important differences among the three groups, however. For instance,
disagreement could be found in the perspective of the study, resources used and costs,
and the valuation of resources used in the analysis. The perspective of the study and the
choice of resources and costs used vary because of differences in health care systems or
in the purposes of the guidelines. The monetary valuation of resources and costs used
seems to vary because most guidelines do not have standardized recommendations for
valuation, such as price lists.
Methodological recommendations concerning guidelines have been reviewed earlier [33–
38]. However, reviews must be updated regularly as more countries continue to develop
guidelines, and the status of existing and newly issued guidelines is ambiguous. In some
countries guidelines are a formal requirement, whereas in others they are still used on a
voluntary basis.
This review contains a substantial number of health economic guidelines. It is, however,
not implausible that we have missed some guidelines, for example, guidelines published
in a non-English journal. We have also intentionally excluded literature on health
economic evaluation with textbook approaches [31,32] and guidelines specifically
intended for internal use by an organization. In addition, some early guidelines have been
withdrawn or are simply outdated.
Guidelines are likely to affect both the producers and the consumers of economic
evaluations. We will focus here on some aspects that might be important to address in the
interpretation and implementation of guidelines for the parties involved.
Most of the formal guidelines state that their view is societal, but they nevertheless insist
on focusing primarily on direct health care costs. One consequence of not recommending
that indirect costs also should be included is that they increase the potential difficulty of
proving the cost-effectiveness of certain classes of newly developed drugs. Advantages in
aspects of productivity do not bear the same weight as advantages in the health care
sector. Future research might change this, since in general economic terms changes in
productivity are constantly in focus, i.e., increases in gross domestic product are usually
major news.
The principles for monetary valuation of resources are unclear, or at least not explicit, in
most guidelines. For purposes of comparability, these need to be harmonized.
Harmonization with respect to prices, through the establishment of independent
databases, is one way to apply an external standard. Another way is to communicate with
customers (e.g., third-party payers, authorities) a priori about which prices are
appropriate to use.
The comparators in cost-effectiveness analyses ought to relate to plausible substitutes
under normal practice. However, how to implement this in multinational clinical trials is
not evident, since normal clinical practices may vary substantially even within one
country. In many cases it may be difficult to identify the treatments that ought to be
included in a study to fulfill the HE requirements of many different countries.
Most guidelines demand effectiveness data and not efficacy data. Effectiveness data
demonstrate that the evaluated treatment works in normal clinical practice, while efficacy
data show that the evaluated treatment has an impact on patients in a structured setting.
The increasing demand for effectiveness data has considerable impact on the design of
clinical studies, e.g., the number of patients needed to be able to show a significant
difference between treatments when the patient groups are somewhat heterogeneous.
Harmonization of outcomes and effectiveness is essential if studies are to be compared.
Recommendations concerning appropriate outcome measures might be necessary to
allow comparison of different studies with different treatments. One way to increase
comparability is through research on patient preferences for various indications. In
economics, preferences are treated as rather stable, and research on patient preferences
concerning different symptoms might be essential in choosing outcome and effectiveness
measures. In this way, conflicting messages could be avoided when products for the same
indication are priced or reimbursed.
Economists are not able to discuss with certainty health-related behavior based on
normative health economic evaluations. Therefore, decisions based solely on health
economic data prior to launch of a treatment cannot constitute the only foundation on
which reimbursement decisions are based. Hutton and Maynard [39] have pointed out
that “the economic result can never be definitive at that stage.” Economic evaluations
alongside closely monitored clinical trials should not be regarded as the state of the art
approach for appraisals post launch. After a drug is launched, however, the option of
analyzing real-life data becomes available. The real-life impact of a particular drug could
be assessed by conducting health econometric analyses, or other kinds of retrospective
analyses on administrative databases. This is more in line with mainstream economics
than the narrow use of health economics or pharmacoeconomic analyses alongside
clinical trials. Alternatively, clinical studies might be replicated with retrospective data
from different sorts of databases.
Providing a model has occasionally been the solution when there is a lack of information.
Models are accepted and even required in most countries. Given the chronic nature of
many diseases, it is reasonable and necessary to conduct research using long-term models
that ought to be developed over time, expanded, and disseminated. There might,
however, be a trade-off between modeling research and the implementation of
prospective health economic analyses and health econometric analyses. In the future, it
will be reasonable to expect the provider of formal guidelines to also provide guidance on
the types of analyses that are acceptable under different circumstances.
Providing detailed guidelines is cumbersome work, and if they are provided, they run the
risk of becoming a cookbook instead of a useful tool for conducting an appraisal. The
extent to which guidelines will become a useful tool for the health care sector in different
countries in working with issues such as cost-containment and cost-effectiveness,
remains to be seen. There are recent data suggesting that the studies received so far by the
reimbursement authorities in Australia and the Canadian province of British Columbia
may not be optimal [40–42]. It is clear from these data that the pharmaceutical industry
needs to work in a more long-term, strategic, and innovative way to support its products
with useful, timely, and high-quality health economic data.
Developing guidelines is a dynamic process; the number of formal health economic
guidelines is increasing, and the content of the guidelines will most likely be further
developed. The development of guidelines will hopefully be the result of the interaction
between the interested parties: patient groups, governments, the industry, third-party
payers, researchers, etc. These parties usually have conflicting interests. For instance, the
reaction of Glaxo Wellcome and the industry toward the NICE decision to not
recommend the flu drug Relenza as a treatment attracted worldwide attention. Glaxo
Wellcome was said to be considering taking legal actions if NICE refused to recommend
Relenza, and the company even threatened to move out of the UK [43,44]. In Canada and
Australia also, pharmaceutical companies have brought political and legal pressure on the
institutions responsible for judging the relative merits of their products [45,46].
From the industry's point of view it is important to take a constructive part in the
development of guidelines and to be given the opportunity to propose ways of improving
these guidelines. If not, the credibility of the result may be taxed, since many health
economic analyses are presently normative, or the results can be used normatively as a
result of the experimental setting of the clinical studies on which they are based.
In conclusion, this review has covered 25 health economic guidelines, which can be
considered as fairly homogenous. However, there are differences between guidelines to
which pharmaceutical companies should pay attention in an effort to design studies that
are as relevant and acceptable as possible. Whether or not the guidelines will be an
efficient way of regulating the market remains to be seen. Resources will unavoidably
continue to be limited, however, despite the success or failure of the guidelines in their
present form. If the guidelines turn out to be unsatisfactory, other health policy
instruments will most likely replace them.
Acknowledgments
Top of page
Abstract
Introduction
Results
Discussion
Acknowledgments
References
AstraZeneca R & D Lund, Sweden funded this study.
References
Top of page
Abstract
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Acknowledgments
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Health Economic Guidelines

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Health Economic Guidelines—Similarities, Differences and Some Implications

Jonas Hjelmgren BSc1,

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