HTA in European countries
The use of Comparative Effectiveness Research and Health Technology Assessment in
European countries: current situation and prospects for the future
Author: David Epstein
Affiliation: Department of Applied Economics, University of Granada
20 March 2014
Email: davidepstein@ugr.es
Contenido
Glossary ......................................................................................................................................... 2
Introduction .................................................................................................................................. 3
EBM, CER and HTA and their relation to the decision making process ........................................ 3
The regulatory framework in European countries. ....................................................................... 4
Pharmaceuticals ........................................................................................................................ 4
Treatment and diagnostic devices ............................................................................................ 4
Coverage and reimbursement decisions in European countries .................................................. 4
Decision making in practice .......................................................................................................... 5
Principles of HTA ........................................................................................................................... 6
Application of principles of HTA .................................................................................................... 6
Organization and administration of HTA .................................................................................... 18
Comparison of positive and negative outcomes of HTA across countries.................................. 18
Case study 1: Atypical antipsychotic for the treatment of Schizophrenia (Paliperidone) ...... 19
Case study 2: MAO inhibitor for the treatment of Parkinson’s disease (Rasagiline mesylate)
................................................................................................................................................. 19
Case Study 3: Orphan drug idursulfase ................................................................................... 19
Decision pricing and spillover effects.......................................................................................... 21
Comparison of methodologies and processes across HTA bodies .............................................. 21
Collaboration across agencies and HTA core model: EUnetHTA Project ................................ 21
Key methodology trends and issues ........................................................................................... 22
Bibliography ................................................................................................................................ 22
1
HTA in European countries
Glossary
English
Comparative effectiveness research
Cost benefit analysis
Cost effectiveness analysis
Cost minimization analysis
Cost utility analysis
Coverage
Evidence Based Medicine
Evidence synthesis
Health policy
Health Technology Assessment
Incremental cost effectiveness ratio
Marketing authorization
Markov model
National Health Service
Orphan drug
Personal and social services
Quality adjusted life year
Abbreviation
CER
CBA
CEA
CMA
CUA
Randomized controlled trial
Regulatory framework
Reimbursement and Pricing
Stakeholder groups
Therapeutic value / Added
therapeutic value
Value Based Pricing
RCT
EBM
HTA
ICER
NHS
PSS
QALY
R&P
ATV
VBP
2
Spanish equivalent
Estudios para comparar la efectividad
Análisis coste-beneficio
Análisis de coste efectividad
Análisis de minimización de costes
Análisis de coste utilidad
cobertura
Medicina basada en la evidencia
Síntesis de evidencia
Política sanitaria
Evaluación de tecnologías sanitarias
Ratio coste efectividad incremental
Autorización de comercialización
Modelo de Markov
Sistema Nacional de Salud
Medicamento huérfano
Servicios personales y sociales
Años de vida ajustados por calidad
(AVAC)
Ensayo clínico aleatorizado
Marco normativo
Reembolso y fijación de precios
Grupos de interés
Valor terapéutico/ Valor terapéutico
añadido
Precios basados en el valor
HTA in European countries
Introduction
Since the establishment of the first national HTA agency in Sweden in the 1980s, the number of
institutions involved in the assessment of health technologies has multiplied in Europe. Most
European Member States have established a formal HTA programme or are considering the
feasibility of establishing HTA intelligence to inform health policy-making (Eldessouki 2012,
http://www.ispor.org/htaroadmaps). This paper:

Examines the regulatory and decision making framework for health technologies in
European countries

Discusses the theoretical justification and principles of HTA

Compares European HTA practice against the principles

Describes the organization and administration of HTA in European countries

Compares positive and negative outcomes of decision for pharmaceuticals

Discusses key challenges and trends for the future
EBM, CER and HTA and their relation to the decision making
process
Following the definitions of Luce et al (2010)
1. Evidence-based medicine (EBM) is an evidence synthesis and decision process used to
assist patients’ and/or physicians’ decisions. It considers evidence regarding the
efficacy (“can it work?”) and effectiveness of interventions (“does it work?”) and
patients’ values and is mainly concerned with individual patients’ decisions, but is also
useful for developing clinical guidelines as they pertain to individual patients.
2. Comparative effectiveness research (CER) includes both evidence generation and
evidence synthesis. It is concerned with the comparative assessment of interventions in
routine practice settings. The outputs of CER activities do not directly feed into a
decision making process but are useful for clinical guideline development, evidencebased medicine, and the broader social and economic assessment of health technologies
(i.e., HTA).
3. Health technology assessment (HTA) is a method of evidence synthesis that considers
evidence regarding clinical effectiveness, safety, cost-effectiveness and, when broadly
applied, includes social, ethical, and legal aspects of the use of health technologies. The
precise balance of these inputs depends on the purpose of each individual HTA. A
major use of HTAs is in informing reimbursement and coverage decisions (“is it worth
it?”), in which case HTAs should include benefit-harm assessment and economic
evaluation.
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HTA in European countries
The regulatory framework in European countries.
Pharmaceuticals
The regulatory body for pharmaceuticals is the EMA (http://www.ema.europa.eu). The decision
focuses on whether the product does more good than harm for patients with defined indications.
The evidence considered is usually pre-launch, typically evidence on efficacy from randomized
controlled trials (RCTs), usually placebo-controlled, although active controls may be required
particularly when placebo control would not be ethical. Post-launch, evidence on relative
efficacy, effectiveness and/or relative effectiveness may also be considered when reviewing a
product’s ongoing benefit-risk profile (Henshall 2011)
Treatment and diagnostic devices
The regulatory body is the EU Commission and Notify Body
(http://ec.europa.eu/health/medical-devices/). The European Commission Medical Devices
Directive (93/42/EEC and subsequent Directive 2007/47/EC) defines four categories of devices,
graded according to the risk assessment considering the following four dimensions: (i) duration
of contact with the patient; (ii) the invasiveness; (iii) the intended use and dependence on an
external source of energy; (iv) the location of the anatomical area affected. The regulatory
process for diagnostics, medical devices, and medical equipment typically focuses on product
safety and function (e.g., reliably detecting specified biomarkers in the case of a diagnostic).
The extent to which regulators require evidence of clinical benefit for patients typically depends
on the level of risk to which patients are exposed, and for many products, trials to establish
efficacy or clinical benefit are not required by regulators or undertaken by manufacturers
(Henshall 2011).
Coverage and reimbursement decisions in European countries
Coverage and reimbursement decisions are informed by HTA. HTA is a multidisciplinary
process that summarizes information about the medical, social, economic and ethical issues
related to the use of a health technology in a systematic, transparent, unbiased robust manner. It
aims to inform the formulation of safe, effective, health policies that are patient-focused and
seek to achieve best value. Despite its policy goals, HTA must always be firmly rooted in
research and the scientific method (www. eunethta.net).
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HTA in European countries
HTA primarily aims to support policy-makers in making evidence-informed decisions on the
application of health technologies. It can be regarded as a flexible, ongoing process, guiding
technology from its future status to the phase of obsolescence (Drummond 2008). HTA seeks to
support decisions on whether an intervention offers useful, appropriate, and affordable benefits
for patients in a particular healthcare system (Henshall 2011). It considers evidence on relative
effectiveness/efficacy (and costs and opportunity costs across the system) as can be assembled
from all relevant trials (of the product and alternatives) with placebo or active controls, and
where necessary other study designs and/or analytic techniques such as modeling
Decision making in practice
The practice of HTA within this definition varies considerably across national settings. It
informs policy- and decision-making in specific political, economic and institutional contexts.
In order to be useful HTA has to be designed with processes and outputs that fit the relevant
context. It is recognized that HTA provides only one input for decision-making. It is usually not
the only source, nor is it always the most important input. For this reason an HTA (or its
recommendations) should not be confused with the actual decision taken (Figure 1) (Velasco
Garrido et al 2008).
Figure 1. Role of HTA in policy making (Velasco Garrido et al 2008).
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HTA in European countries
Principles of HTA
Drummond (2008) proposes 10 principles to guide HTA. These are:
1. The Goal and Scope of the HTA Should Be Explicit and Relevant to Its Use
2. HTA Should Be an Unbiased and Transparent Exercise
3. HTA Should Include All Relevant Technologies
4. A Clear System for Setting Priorities for HTA Should Exist
5. HTA Should Incorporate Appropriate Methods for Assessing Costs and Benefits
6. HTAs Should Consider a Wide Range of Evidence and Outcomes
7. A Full Societal Perspective Should Be Considered When Undertaking HTA
8. HTAs Should Explicitly Characterize Uncertainty Surrounding Estimates
9. HTAs Should Consider and Address Issues of Generalizability and Transferability
10. Those Conducting HTAs Should Actively Engage All Key Stakeholder Groups
Application of principles of HTA
Principle 1: The Goal and Scope of the HTA Should Be Explicit and Relevant to Its Use
A detailed scoping document should be developed before initiation of the HTA process, with
broad, multidisciplinary, stakeholder involvement. The document should focus on defining the
questions to be addressed by the HTA, plus the link between the HTA and any decisions about
the use of the technology.
In some jurisdictions there is resistance to explicitly including considerations of cost in HTAs.
In a diverse, decentralized system with multiple payers, insurers, healthcare organizations, and
other providers, costs and perspectives may differ widely. More importantly, inclusion of cost
into HTAs raises explicit questions of rationing of care, which is controversial and has limited
public support in some countries. For example, economic evaluation in France is still in the
development phase (HAS 2012).
Table 1.The goal and scope of HTA in European countries (Adapted from Paris and Belloni
2013)
France
Therapeutic relevance
Economic considerations
Safety, effectiveness, severity
Budget impact. New products
of disease, curative nature of
with added therapeutic value
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HTA in European countries
Germany
product, interest in terms of
will be subject to economic
public health
evaluation from Oct 2013
Yes, but the drug must not
Efficiency frontier method
belong to one of the
(Caro 2010)
categories excluded from
reimbursement by Federal
Law
Italy
Clinical effectiveness, disease
No
relevance
Belgium
Efficacy, disease relevance
Cost-effectiveness for
innovative products, budget
impact
Denmark
Yes
Reasonable price in relation
to therapeutic value
Netherlands
Added therapeutic value
Cost-effectiveness, budget
impact
Spain
Therapeutic value
Reasonable price in relation
to therapeutic value, costeffectiveness, budget impact
Sweden
Yes
Cost-effectiveness, need and
solidarity, human values
principles
UK
NICE does not grade products Cost-effectiveness
according to therapeutic value
Principle 2: HTA Should Be an Unbiased and Transparent Exercise
Given the inherently complicated and controversial nature of HTA-based decisions and their
importance to multiple decision makers and stakeholders, the HTA process is best conducted
independently of the body that ultimately will be responsible for adopting, paying and
implementing the HTA decisions. Furthermore, the HTA process and the detailed basis on
which recommendations and decisions are made must be transparent.
HTA bodies differ widely in the amount of information which is made available to the public
regarding the technology and the decision making process. Most jurisdictions publish official
prices of pharmaceutical products. However, the actual price negotiated with the manufacturer
is usually considered commercial-in-confidence (Gimenez 2013).
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HTA in European countries
Table 2.Bodies responsible for HTA process, for reimbursement decisions and price negotiation
in European countries (Adapted from Paris and Belloni 2013)
Belgium
Body responsible for
Body responsible for
Body responsible for
HTA process
decision on
price negotiation /
reimbursement
decision
National Institute for
Ministry of social
Ministry of economic
Sickness and Invalidity
affairs
affairs, with advice of
Insurance
the committee for
(INAMI)/Commission
price setting (inter-
for Reimbursement of
ministry body)
Medicines [Institut
National d’Assurance
MaladieInvalidité/Commission
de Remboursement des
Médicaments]
Denmark
Reimbursement
Outpatient drugs:
For hospital drugs,
Committee/Danish
Danish health and
purchasing agency
Centre for Evaluation
medicines authority.
carries out tenders
and Health Technology Hospital drugs: KRIS
Assessment (CEMTV)
France
Germany
Economic Committee
Ministry of Health
Committee on health
on Health Products
decides on listing and
products(inter-
(CEPS)/Transparency
Union of social
ministry body)
Commission
health insurance
[Commission de la
funds decides on
Transparence]
reimbursement rate
Federal Joint
Federal Joint
Prices negotiated
Committee/Institute
Committee (G-BA)
after G-BA
for Quality and
assessment
Efficiency in Health
Care (IQWiG)/German
Agency for Health
Technology
Assessment
(DAHTA).
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HTA in European countries
Italy
Committee on
AIFA technical
AIFA pricing and
Pharmaceuticals/Italian scientific committee
reimbursement
Medicines Agency
committee (inter-
(AIFA) [CIP
ministry body)
Farmaci/Agenzia
Italiana del Farmaco]
Netherlands
Pharmaceutical Care
Ministry of health,
Ministry of health,
Committee (CFH)
welfare and sport
welfare and sport
Pharmaceuticals
NoMA, MOH when
NoMA
Pricing Board
budget impact is high
/Health Care Insurance
Board (CVZ)
Norway
(PPB)/Norwegian
Medicines Agency
(NoMA)
Spain
Spanish Agency for
MOH
Health Technology
Inter ministerial
pricing committee
Assessment (AETS)
Sweden
Pharmaceutical
TLV
TLV
Benefits Board (LFN /
TLV)/Swedish Council
on Technology
Assessment in Health
Care (SBU)
UK (England and
NICE/National
There is no
In general,
Wales)
Coordinating Centre
systematic
manufacturers are
for Health Technology
assessment of new
free to set list prices.
Assessment
medicines, NICE
The government
(NCCHTA)
assesses on request.
controls profit levels
All medicines with
of the industry. The
marketing licences
MOH may negotiate
are automatically
Patient Access
reimbursed unless
Schemes with
NICE says no.
manufacturers if
NICE rejects a drug.
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HTA in European countries
Principle 3: HTA Should Include All Relevant Technologies
Because potential inefficiencies exist in all forms of healthcare, all health technologies should
be potential candidates for HTA. Otherwise, decision making concerning the use of resources is
likely to be distorted.
While in some HTA programs all new technologies are candidates for formal, rigorous
assessment (e.g. NICE in the United Kingdom, IQWiG and DAHTA@DIMDI in Germany,
CMS and AHRQ in the United States), in practice a disproportionate amount of HTA activity is
still directed toward drugs. The other common inappropriate focus of HTA is concentration on
assessing new technologies (Drummond 2008).
Table 3. Decision making criteria used in countries that systematically assess all new medicines
or cover all medicines at market entry by default (Adapted from Paris and Belloni 2013)
Systematically use economic
Reimbursement conditions
evaluation to make decisions
mainly based on clinical
and consider cost-
criteria related to efficacy or
effectiveness as the primary
effectiveness of new product,
condition for listing
type of disease or therapeutic
alternatives
Systematic assessment of all
Belgium, Netherlands,
new drugs or new indications
Norway and Sweden. France
of existing products before
(after Oct 2013)
France (before 2013), Italy
market entry
All medicines are covered as
UK: NICE provides advice on Germany: new drugs are
soon as they enter the market,
HTA, on request, on the
assessed 3 months after
unless they belong to a
coverage of NHS services,
market entry, to make sure
category a-priori excluded
generally after market entry.
their price represents an
from reimbursement
efficient use of resources and
set a maximum price if
needed
Principle 4: A Clear System for Setting Priorities for HTA Should Exist
A clear process for prioritizing and selecting topics needs to be established, because in
situations where not all technologies are assessed, there will be distortions in decision making
about the investment and use of resources.
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HTA in European countries
In situations where only some technologies are assessed, selection priorities need to be set. In
the United Kingdom, NICE sets priorities based on six criteria: (i) burden of disease; (ii)
resource impact; (iii) clinical and policy importance; (iv) presence of inappropriate variation in
practice; (v) potential factors affecting the timeliness of guidance; and (vi) likelihood of the
guidance having an impact. A similar approach is followed by DAHTA@DIMDI (Germany),
where a board of trustees uses similar criteria to derive priorities for future HTA projects.
The other common approach to determining priority for assessment is essentially a procedural
one. For example, in the Netherlands an HTA is conducted if there is an a priori case that a new
drug should not be clustered with other, existing drugs in the nation’s therapeutic reference
price system. The HTA is used to assess the incremental value (if any) a drug provides over
existing medicines, so as to determine whether a price premium is justified (and, if so, how
much). A similar approach is being followed in Germany, where the G-BA can ask IQWiG to
assess whether a new drug has sufficient incremental benefit to be excluded from the reference
price system (Drummond 2008).
Several studies have highlighted a lack of transparency in the topic selection process (Sorenson
et al 2008). Many HTA organizations lack explicit processes for prioritization, including
selection methods and stakeholder involvement.
There are wide differences in the number and type of drugs appraised across agencies (Kanavos
2010). These differences, in part, are a result of the selection criteria for HTA appraisals
established by each agency, as well as each country’s national priorities. Table 4 summarizes
these selection criteria for each agency. For example, when considering that France (HAS)
appraises all drugs, the fact that they have appraised the highest number of drugs is more easily
understandable. Similarly, England and Wales (NICE), having appraised the lowest number of
drugs, focuses only on those which are deemed to fulfill the highest need. National priorities
may be reflected to some extent in the ICD codes of the appraised drugs. For example, in
England the majority of cancer treatments (C00–D48) have been appraised as this is a priority
because of the need, the severity of illnesses they treat and the cost implications for the National
Health Service. In contrast, TLV (Sweden), which selects all out-patient drugs for HTA
appraisals, has a more balanced amount of appraisals across indications, which may suggest that
all drugs are considered equally important, regardless of the price, need, or severity of disease.
Table 4. Selection criteria for HTA appraisals per agency, based on the literature (Kanavos
2010)
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HTA in European countries
Principle 5: HTA Should Incorporate Appropriate Methods for Assessing Costs and Benefits
Development and consistent implementation of rigorous, analytical methods is required to
engender stakeholder and public trust in the process and its findings. This requires clarity of
HTA process and methods, as well as access to experts with appropriate clinical and
multidisciplinary methodological training.
A common approach in HTAs incorporating an economic evaluation is to propose a baseline
analysis, or “reference case,” using a standardized approach with the best available data, with
additional analyses conducted that examine the impact of alternative estimates on findings
(sensitivity analyses) and the impact in specific clinically relevant subpopulations. The goal is
to ensure consistency across different studies without stifling methodological developments and
to examine the robustness of findings and results within the range of data uncertainty,
methodological biases and limitations, and clinical populations. Given the need to use HTA
resources in a cost-effective manner, it is important that the methods used are “fit-for-purpose.”
A comprehensive, well-conducted, EBM review is a necessary first step in the HTA appraisal
process. EBM methods should be specified in advance of conducting the review and should use
the best available evidence for the questions to be addressed. Thus, while well-conducted RCTs
provide high quality evidence of efficacy, evidence from rigorous quasi- and nonexperimental
studies will usually be required to address issues of effectiveness (benefit under typical clinical
conditions), comparative effectiveness (incremental benefit versus the best available alternative
interventions) and differential effects in specific clinical populations (e.g., subgroups defined by
patient age, gender, ethnic, comorbidity).
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HTA in European countries
However, new analyses or re-analyses of existing data may be required to inform the HTA,
considering its intended purposes and resultant decisions. Typically, these analyses will be
conducted to populate economic decision-analytic or simulation models, for example to project
health and economic consequences over an adequate time horizon. In particular situations, it
may be difficult to have meaningful RCT data at all and short-term clinical trial data must be
linked with data on patient-relevant health outcomes and long-term costs. Typical examples
include the evaluation of health promotion programs, screening programs, diagnostic
procedures, or treatment of chronic diseases with a relatively slow disease progression.
Modeling techniques include decision tree analysis, Markov models, discrete-event simulation,
and others (Drummond 2008)
Principle 6: HTAs Should Consider a Wide Range of Evidence and Outcomes
HTAs require use of data from experimental, quasiexperimental, observational, and qualitative
studies, integration of both endpoint and validated surrogate data, and assessment of the
incremental impact of and trade-offs among multiple clinical, economic and social outcomes in
clinically relevant populations.
Clinical benefits, risks, and costs must be defined broadly to include all relevant outcomes of
interest. Thus, in addition to mortality and morbidity, outcomes assessed and integrated into the
decision process should include impact on patient functional status and quality of life and
economic outcomes (direct and indirect medical costs, productivity effects) not only for patients
but also for other relevant parties (e.g. family, employer, and the broader society).
Table 6. Definition of therapeutic value used in HTA processes in European countries (adapted
from Paris and Belloni 2013)
Assesement / classification of
Implication
added therapeutic value
(ATV)
Belgium
Class 1: ATV
Class 1 allowed a price above
Class 2: similar TV
the comparators price
Class 3: Generics /copies
Denmark
Health gains in natural units
France
ASMR 1: major improvement
ASMR 1-3 allowed a price
ASMR2: significant
above the comparators price
improvement
ASMR3: Modest
improvement
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HTA in European countries
ASMR 4: Minor
improvement
ASMR 5: No improvement
Germany
Considerable improvement
Medicines with some
Significant improvement
additional benefit are not
Small improvement
clustered in reference price
Additional benefit not
groups and allowed a price
quantifiable
above comparators. The
No improvement
degree of innovation is
Less benefit than comparator
referred to in the negotiation
process
Netherlands
Annex 1A: similar TV
Annex 1B allowed a price
Annex 1B: ATV
above the comparators price
Norway
Number of QALY gained
ICER compared to threshold
Spain
Classification of TV:
Price premium of 10-20% if
Significant
drug has moderate or
Moderate
significant TV
Low
No interest
Sweden
Number of QALY gained
Price premium allowed based
on ICER
UK
Number of QALY gained
ICER compared to threshold
Table 7 . Thresholds used to establish cost-effectiveness in European countries (Adapted from
Paris and Belloni 2013)
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HTA in European countries
Belgium
Threshold
Comments / exceptions
No explicit threshold.
Rarely consider
No economic evaluation
ICER>EUR 80,000.
required for orphan medicines
Bevacuzimab listed for
breast cancer with an
ICER > EUR 100,000
Netherlands
Norway
Suggested maximum of EUR
Orphan medicines have
80,000 / QALY for severe
been accepted at higher
diseases
thresholds
No explicit threshold
Sunitinib was rejected for
GIST with ICER of USD
52,000, but accepted for
renal cancer with an ICER
of USD 54,000
Sweden
No explicit threshold
Medicines for severe
diseases have been
accepted with ICER
around EUR 100,000 per
QALY
England and Wales
Threshold ICER range around
Higher thresholds for
GBP 20,000-30,000 / QALY
ultra-orphan drugs
(200,000-300,000 per
QALY) and end-of-life
(about 40.000 per QALY)
Figure 2 . Relative importance of attributes evaluated for drugs and medical devices (results of a
survey of HTA agencies). Note: Proportion of respondents reporting attribute as “high”
importance. (Stephens et al 2012)
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HTA in European countries
Principle 7: A Full Societal Perspective Should Be Considered When Undertaking
HTAs
HTAs should adopt a broad societal perspective to optimize efficiency and societal benefit and
to avoid and identify potentially distorted clinical decisions and health policies resulting from
adoption of narrower perspectives used by various healthcare system stakeholders.
Table 8. Perspective used in HTA in European countries (adapted from Paris and Belloni 2013)
Belgium
Author of guideline
Perspective
Analytic method
KCE
Social insurance
CEA or CUA
and patient
Italy
No guidelines
Norway
NoMA
Limited societal
CMA, CEA, CUA,
perspective
CBA accepted but
must be justified
Sweden
TLV
Societal
CEA or CUA. CBA
or CMA also accepted
if justified
Netherlands
Foundation for Health
Societal
CEA or CUA
NHS and patients
CMA, CEA, CUA,
care and University
Scotland
SMC
CBA accepted but
must be justified
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HTA in European countries
England and Wales
NICE
NHS or PSS
CEA or CUA
France
HAS
All financing agents
CEA or CUA
Germany
IQWIG
No
Form of CEA in
pharmacoeconomics which costs and
systematically used
health benefits are
in R&P process but
only compared within
HTA includes
a given therapeutic
information on
area (efficiency
additional cost of
frontier) (Caro 2010).
treatment
Principle 8: HTAs Should Explicitly Characterize Uncertainty Surrounding Estimates
All data are imperfect point estimates of underlying distributions that incorporate a variety of
errors. All analytical methods are subject to biases and limitations. Thus, extensive sensitivity
analyses are required to determine the robustness of HTA findings and conclusions. The
limitations of the analysis should always be acknowledged.
Principle 9: HTAs Should Consider and Address Issues of Generalizability and Transferability
Examination of the generalizability and transferability of HTA findings across clinical
populations and policy relevant perspectives is required, given the inherent variability of
disease, intervention responses, and outcomes across patients, populations, providers,
healthcare delivery sites and healthcare systems
.
Principle 10: Those Conducting HTAs Should Actively Engage All Key Stakeholder Groups
HTA programs should actively engage all key stakeholders in all stages of the HTA process, as
this is likely to result in technology assessments of higher quality that are more widely accepted
and stand a greater chance of being implemented. Moreover, such an open process will
enhance transparency and trust in the process as stakeholders develop a greater understanding
of the criteria and standards used
HTA organizations differ widely in the degree to which stakeholders are allowed to participate
in the HTA process and interact with the decision makers. However, few jurisdictions have yet
taken the step of holding all HTA deliberations and committee meetings in public (Paris and
Belloni 2013). In Germany, IQWiG has introduced a procedure where stakeholders are invited
to participate in a formally structured manner, in hearings and by written comments. All
comments and discussions are reported in the supplements of the reports (Drummond et al
2008)
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HTA in European countries
Organization and administration of HTA
Figure 3. Organization, application, and use of HTA (European respondents, Stephens 2012).
Comparison of positive and negative outcomes of HTA across
countries
Kanavos et al (2010) collected data on all appraisals between 2007–2009 from six HTA
agencies. The data were collected from the public websites of each agency. Appraisals for all
drugs and specific indications that were completed during the study period were considered,
together with their corresponding recommendations, even if the latter were made outside the
study period. In total, appraisals on 293 drugs were conducted.
Only 7% of the drugs were appraised by all six agencies, 19% by five agencies, 18% by four
agencies, 26% by three agencies, 17% by two agencies, and 13% by only one of the agencies.
This shows that, surprisingly, HTA agencies do not necessarily appraise the same drugs, or the
same drug for the same indication. HTA outcomes between agencies differed in more than half
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HTA in European countries
of the cases, whereby some agencies accepted these drugs in most cases, while others rejected
them in almost 50% of cases.
Case study 1: Atypical antipsychotic for the treatment of Schizophrenia
(Paliperidone)
Paliperidone was rejected by HAS and SMC because of insufficient evidence of a clinical
advantage compared to other antipsychotics. In contrast, TLV recommended paliperidone on the
basis that it was deemed similar in terms of efficacy and price to olanzapine and risperidone
respectively.
Case study 2: MAO inhibitor for the treatment of Parkinson’s disease
(Rasagiline mesylate)
TLV accepted to list rasagiline because it was considered cost-effective in comparison with
entecapone and tolcapone, but was restricted to the treatment of ‘on-off’ syndrome since its
therapeutic alternative (selegiline) was deemed inappropriate for this sub-population. SMC
rejected the application because no comparison with a less expensive therapeutic alternative was
presented. Similarly, HAS’s rating (ASMR V) was mainly due to the conclusion that the
treatment did not have additional benefit compared to existing alternatives. NICE did not
appraise either drug, but instead issued guidance for the treatment and management of
Schizophrenia (March 2009) and Parkinson’s disease (June 2006). In these guidelines, all
antipsychotics are considered to have equal effects, and similarly MAO-inhibitors are
one of the accepted treatment options for early Parkinson’s disease. In both cases, the choice of
treatment depends on patient tolerability and preferences.
Case Study 3: Orphan drug idursulfase
In the case of idursulfase, all appraising agencies focused on the same Phase III placebocontrolled random controlled trial (RCT). HAS concluded that, in the absence of alternative
treatment, it demonstrated “significant superiority” compared to placebo on 6MWD** and all
other secondary endpoints. SMC also concluded that the drug was “significantly more effective”
than placebo, but rejected it based on insufficiently robust economic evidence.
Figure 4. Number of appraisals and HTA outcomes (N=293 appraisals) across 6 HTA agencies
(Kanavos 2010)
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HTA in European countries
Figure 5 Appraisals by agency and outcome
Key: L (list / positive recommendations); LWC (list with criteria or restrictions); DNL (do not
list / negative recommendation)
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HTA in European countries
Decision pricing and spillover effects
Kanavos (2010) examined the effect of HTA recommendations on the prices of drugs in that
market. The trend effect of positive recommendations by both NICE and SMC was an
immediate increase in price which moderated after 6–9 months. Prices in Sweden exhibited
some volatility in either direction following a TLV recommendation, which is surprising given
that prices for reimbursement are fixed during the recommendation process. Positive and
negative recommendations by HAS had little or no visible effect on French prices.
Comparison of methodologies and processes across HTA bodies
Mathes (2013) compared the methodologies of 14 HTA agencies, examining published
documents. Most of the recommendations are in accordance with described key principles of
HTA. These concern methods for assessing cost and benefits, the range of evidence and
outcomes, the perspective of analysis and uncertainty of estimates. Differences in
recommendations are often explainable by differences in the structure and regulation of health
care systems and, therefore, different premises and goals. However there are considerable
unexplainable differences in methodological recommendations for economic evaluations. The
results of HTAs always have generalizability and transferability restrictions for different
populations and settings. However, there are process steps for the preparation of economic
evaluations that are not at all, or only marginally, affected by transferability problems (e.g.,
literature search, model structure).
Collaboration across agencies and HTA core model: EUnetHTA Project
There is a challenge of avoiding duplication of work and obtaining a more effective use of
national HTA. There is a need to find more standardized approaches in order to provide tools
that help HTA actors to reuse the work of others. For this reason the EUnetHTA Project aimed
at developing a core model and tools that help to adapt existing reports/core HTAs by defining
and standardizing the elements of an HTA (Velasco-Garrido 2008). The strategic objectives of
the EUnetHTA Project were to reduce duplication of effort to promote more effective use of
resources, increase HTA input to decision making in European countries and the EU, to increase
the impact of HTA at all levels of healthcare, strengthen the link between HTA and healthcare
policy making in the EU and its Member States, and support countries with limited experience
in HTA (Børlum Kristensen 2012)
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HTA in European countries
Key methodology trends and issues
Table 9. Key methodology trends and issues facing health technology assessment (HTA) bodies
(Stephens et al 2012)
Austria
Need for observational studies/real-life data (monitoring, registries, etc);
development of “acceptable” thresholds and methods for resource allocation
Denmark
Lack of good studies/data as inputs to the assessments
France
Early assessment of technologies with mechanism for conditional coverage,
lack of evidence for emerging technologies
Germany
Development/use of methodologies for health economic evaluations
Italy
HTA moving as a priority to regional health-care agendas
Portugal
Selection of comparators, identification and quantification of costs, uncertainty
analysis
Sweden
Link between theory and practice in HTA, uniform analyses for comparative
purposes, assessment of diagnostics, timeliness, selection of topics/comparators
Spain
Transparence, rigor, quality assessments, collaboration with other HTA
agencies nationally and internationally, improved methods, training of new
researchers
Switzerland
Horizon scanning, implementation of regular reassessments
The
Netherlands
Selection of comparators/study populations, model structure, and assumptions
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