Coverage with evidence development schemes for medical ...
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Vol.:(0123456789) 1 3 The European Journal of Health Economics (2021) 22:1253–1273 https://doi.org/10.1007/s10198-021-01334-9 ORIGINAL PAPER Coverage with evidence development schemes for medical devices in Europe: characteristics and challenges Carlo Federici 1,2 · Vivian Reckers‑Droog 3 · Oriana Ciani 1,6 · Florian Dams 4,5 · Bogdan Grigore 6 · Zoltán Kaló 7 · Sándor Kovács 7 · Kosta Shatrov 4,5 · Werner Brouwer 3,8 · Michael Drummond 9 Received: 29 November 2020 / Accepted: 2 June 2021 / Published online: 12 June 2021 © The Author(s) 2021 Abstract Objectives Medical devices are potentially good candidates for coverage with evidence development (CED) schemes, as clinical data at market entry are often sparse and (cost-)effectiveness depends on real-world use. The objective of this research was to explore the diffusion of CED schemes for devices in Europe, and the factors that favour or hamper their utilization. Methods We conducted structured interviews with 25 decision-makers from 22 European countries to explore the charac- teristics of existing CED programmes for devices, and how decision makers perceived 13 pre-identified challenges associ- ated with initiating and operating CED schemes for devices. We also collected data on individual schemes that were either initiated or still ongoing in the last 5 years. Results We identified seven countries with CED programmes for devices and 78 ongoing schemes. The characteristics of CED programmes varied across countries, including eligibility criteria, roles and responsibilities of stakeholders, funding arrangements, and type of decisions being contemplated at the outset of each scheme. We observed a high variability in how decision makers perceived CED-related challenges possibly reflecting country-specific arrangements and different experi- ences with CED. One general finding across all countries was that relatively little attention was paid to the evaluation of schemes, both during and at their completion. Conclusions CED programmes for devices with different characteristics exist in Europe. Decision-makers’ perceptions differ on the challenges associated with these schemes. More exchange of knowledge and experience will help decision makers anticipate the likely challenges in CED schemes for devices, and to learn from good practices existing elsewhere. Keywords Coverage with evidence development · Medical devices · European HTA policies · Value of information · Adoption and reimbursement of medical devices JEL Classification I18 * Carlo Federici [email protected] 1 Centre for Research On Health and Social Care Management, SDA Bocconi School of Management, Bocconi University, Via Roberto Sarfatti 25, 20100 Milan, Italy 2 School of Engineering, Warwick University, Coventry, UK 3 Erasmus School of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, The Netherlands 4 KPM Center for Public Management, University of Bern, Bern, Switzerland 5 Swiss Institute of Translational and Entrepreneurial Medicine (Sitem-Insel AG), Bern, Switzerland 6 Evidence Synthesis and Modelling for Health Improvement, Institute of Health Research, College of Medicine and Health, University of Exeter, Exeter, UK 7 Syreon Research Institute, Budapest, Hungary 8 Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, The Netherlands 9 Centre for Health Economics, University of York, York, UK
Transcript of Coverage with evidence development schemes for medical ...
Vol.:(0123456789)1 3
The European Journal of Health Economics (2021) 22:1253–1273 https://doi.org/10.1007/s10198-021-01334-9
ORIGINAL PAPER
Coverage with evidence development schemes for medical devices in Europe: characteristics and challenges
Carlo Federici1,2 · Vivian Reckers‑Droog3 · Oriana Ciani1,6 · Florian Dams4,5 · Bogdan Grigore6 · Zoltán Kaló7 · Sándor Kovács7 · Kosta Shatrov4,5 · Werner Brouwer3,8 · Michael Drummond9
Received: 29 November 2020 / Accepted: 2 June 2021 / Published online: 12 June 2021 © The Author(s) 2021
AbstractObjectives Medical devices are potentially good candidates for coverage with evidence development (CED) schemes, as clinical data at market entry are often sparse and (cost-)effectiveness depends on real-world use. The objective of this research was to explore the diffusion of CED schemes for devices in Europe, and the factors that favour or hamper their utilization.Methods We conducted structured interviews with 25 decision-makers from 22 European countries to explore the charac-teristics of existing CED programmes for devices, and how decision makers perceived 13 pre-identified challenges associ-ated with initiating and operating CED schemes for devices. We also collected data on individual schemes that were either initiated or still ongoing in the last 5 years.Results We identified seven countries with CED programmes for devices and 78 ongoing schemes. The characteristics of CED programmes varied across countries, including eligibility criteria, roles and responsibilities of stakeholders, funding arrangements, and type of decisions being contemplated at the outset of each scheme. We observed a high variability in how decision makers perceived CED-related challenges possibly reflecting country-specific arrangements and different experi-ences with CED. One general finding across all countries was that relatively little attention was paid to the evaluation of schemes, both during and at their completion.Conclusions CED programmes for devices with different characteristics exist in Europe. Decision-makers’ perceptions differ on the challenges associated with these schemes. More exchange of knowledge and experience will help decision makers anticipate the likely challenges in CED schemes for devices, and to learn from good practices existing elsewhere.
Keywords Coverage with evidence development · Medical devices · European HTA policies · Value of information · Adoption and reimbursement of medical devices
JEL Classification I18
* Carlo Federici [email protected]
1 Centre for Research On Health and Social Care Management, SDA Bocconi School of Management, Bocconi University, Via Roberto Sarfatti 25, 20100 Milan, Italy
2 School of Engineering, Warwick University, Coventry, UK3 Erasmus School of Health Policy and Management, Erasmus
University Rotterdam, Rotterdam, The Netherlands4 KPM Center for Public Management, University of Bern,
Bern, Switzerland
5 Swiss Institute of Translational and Entrepreneurial Medicine (Sitem-Insel AG), Bern, Switzerland
6 Evidence Synthesis and Modelling for Health Improvement, Institute of Health Research, College of Medicine and Health, University of Exeter, Exeter, UK
7 Syreon Research Institute, Budapest, Hungary8 Erasmus School of Economics, Erasmus University
Rotterdam, Rotterdam, The Netherlands9 Centre for Health Economics, University of York, York, UK
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Introduction
At the time of the publication of the ISPOR ‘Good Practices for Performance-Based Risk-Sharing Arrangements (PBR-SAs) Task Force’ report [1], it was acknowledged that there were two types of arrangements to aid the market entry of new technologies; finance-based and performance-based agreements. Briefly, in finance-based arrangements, agree-ments between payers and manufacturers are purely finan-cial and may involve for example price–volume agreements, price discounts or budget caps. In PBRSAs one of the key elements is that the price, or reimbursement of a technol-ogy is linked to its performance which is assessed through a purposeful, prospective data collection.. Indeed, some of the earliest examples of PBRSAs concern coverage with evi-dence development (CED) schemes that were initiated by the Centres for Medicare & Medicaid Services in the US and the Ontario Ministry of Health in Canada for medical proce-dures and devices [2, 3]. In CED schemes, data are collected with the objective of reducing uncertainty concerning the clinical or cost-effectiveness of a health technology and to assist in future decisions about its reimbursement, coverage, or recommendations for its use. Typically, these schemes are centrally coordinated and require substantial data collection.
Since the publication of the Task Force’s report, two trends can be observed. Firstly, there has been a growth in the popularity of finance-based agreements, or simple price reductions, as compared with performance-based schemes. In a recent review of managed entry agreements in Europe, Dabbous et al. [4] note that ‘despite the interests in CED schemes, European countries have moved towards finance-based agreements due to the complexities and burdens associated with PBRSAs’. The lack of appetite for complex agreements among policy-makers was also noted by Karls-berg Schaffer et al. [5], who concluded that ‘there is a mis-match between the enthusiasm in the academic literature for developing new approaches and the scepticism of payers that they can work, or are necessary for the foreseeable future’. Secondly, there has been a growth in the application of financed-based and performance-based agreements to drugs rather than to other types of technologies, which could be a response to the growing number of transformational, but highly expensive new drugs entering the market [6]. Many recent reviews of PBRSAs discuss issues that apply to health technologies in general but draw almost exclusively on drugs for their examples [4, 7–9].
In principle, medical devices are good candidates for PBRSAs, particularly for CED schemes, since there are often considerable uncertainties concerning their (cost-)effectiveness. This is mainly because the data requirements to obtain market access are often less stringent than those for drugs, and therefore devices are generally adopted
in clinical practice with relatively little clinical or eco-nomic evidence [10, 11].. In contrast to pharmaceuticals where the market authorization and supervision is cen-trally managed by the European Medicine Agency (EMA) (Regulation (EC) No 726/2004), the conformity assess-ment procedures for medical devices of risk class II or higher in Europe are decentralized and operated by public or private notified bodies (NBs) which are designated by the EU member states. Evidence requirements for market authorization are regulated by the medical device regula-tion (MDR), which also defines when a clinical investiga-tion of the new device is required or when conformity assessment can be based on the equivalence principle with a previously marketed device. However, notwithstanding the requirements for clinical investigations, a controlled clinical trial, which demonstrates the relative effective-ness compared to alternative treatments, is generally not mandatory for MDs. Besides the differences in the regula-tory approaches compared with pharmaceuticals, certain sources of uncertainty around a medical device are rela-tively less easy to explore by means of pre-market studies. Many devices are part of complex interventions, consisting of multiple behavioural, technological, and organizational components, and therefore their actual (cost-)effectiveness profile usually depends on a series of context-specific fac-tors that are difficult to assess before their adoption in the real-world. For example, device performance in regu-lar clinical practice often depends not only on the device itself, but also on the skills of the user [12, 13]. In addi-tion, while finance-based agreements are also possible, the cost of adopting a new device depends not only on its price, but also the cost of any new procedures or other organizational changes that might be required for its use. Therefore, a price reduction for the device itself may have less of an impact on overall costs. Moreover, finance-based agreements do not resolve potential issues about uncer-tainty in the effectiveness of the device, which both payers and patients may feel is important.
The pace of innovation in medical devices is consider-able, with many new products entering the market every year. For example, in 2017, the number of patents in the field of medical technologies filed with the European Patent Office (EPO) was more than double compared to the number concerning pharmaceuticals (13,000 versus 6300), and the total expenditure on medical technologies in Europe was roughly estimated as €115 billion [14]. Given the relevance of the market and the above-mentioned challenges with evi-dence generation at market launch, any policy tool such as CED, which foresees a controlled introduction of a technol-ogy while collecting further post-market evidence, is highly relevant in the context of medical devices. However, despite the possible advantages of CED schemes for aiding coverage decisions regarding new devices, little is known about the
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extent to which these schemes are used in Europe and the detailed perceptions of decision-makers regarding their utili-zation [15–17]. Therefore, the objective of this research was to contribute to filling this gap by exploring the character-istics and diffusion of CED schemes for devices in Europe, and the challenges that decision-makers face during the dif-ferent phases of a scheme [1, 14]. Our aim was to assist those considering the implementation of CED schemes for medical devices and to increase the understanding of both how schemes are currently being applied in Europe and how the challenges associated with them are being addressed.
Methods
This study is part of the EU Horizon 2020 COMED pro-ject that has been reviewed and approved by the Bocconi University Ethics Committee (protocol number: 0068538, approved on May 8, 2018).
The research was conducted in three consecutive steps: (1) development of a structured interview guide (2) inter-views with decision-makers from a sample of European countries, (3) synthesis and qualitative content analysis of the interview data, the data made available by the deci-sion-makers during or following the interview, and data on scheme characteristics previously obtained [17]. The steps are described in more detail below.
Development of the interview guide
We developed a structured interview guide (Online Resource 1) that consisted of three sections. Section A
included general questions on whether CED programmes underpinning the individual schemes existed in the deci-sion-maker’s country and for which type of technology they were used. Section B included questions on 13 chal-lenges for CED schemes for devices (Table 1). This list was derived from a recent systematic review that identi-fied 20 challenges for CED schemes for devices [17]. To reduce the participants’ burden, we reduced the original list of 20 challenges to 13, by grouping different aspects of the same general challenge. The final list of challenges was discussed and agreed among all authors to ensure that all relevant aspects originally identified were covered in the interview guide (see the Online resource 2 for more details).
We asked the decision-makers to assess how they per-ceived the 13 challenges to apply to CED schemes for devices on a six-point Likert scale (ranging from 0 “not a challenge” to 5 “a major challenge”). Where CED schemes for devices existed, we also asked respondents how the challenges were met in their country, and the interview pro-ceeded to Section C. Otherwise, the interview ended here. Section C included questions on the detailed characteristics of individual CED schemes for devices that had been either initiated or still ongoing in the past five years. These ques-tions concerned a description of the device under evalua-tion, its clinical application, the objective of the scheme, key sources of uncertainty, funding of the scheme, its design, the decision rule, and outcome (if re-assessment was done), and any public source of information on the scheme.
Table 1 phases of CED schemes
Assessing the desirability of a schemeThis initial phase relates to the way candidate technologies for CED schemes are identified and selected. It also concerns the criteria used to
assess whether a scheme is a good policy option, compared with other available options such as, for example, fully adopting the technology despite the residual uncertainties; refusing to adopt the technology until better evidence becomes available; or negotiating/mandating a lower price for the technology.
Designing the scheme This phase is about deciding on the specific features of the scheme design. These include, for example, the categories of patients who will
have access to the technology during the scheme (e.g., Only in Research or Only With Research schemes), and the characteristics of the data collection plan, such as the study design (e.g., registry-based studies versus randomized controlled studies), the duration of the data collection, and the types of outcomes to be measured.
Implementing the scheme Reflecting the previous design phase, this phase is about the different ways schemes are operated and how roles and responsibilities are dis-
tributed among the stakeholders involved (e.g., the national/regional HTA agencies, the manufacturers, or the providers collecting the data). Relevant aspects are, for example, who will initially design the study protocol, who will coordinate and/or perform the data collection, monitoring and analysis, and who will fund the provision of care and the extra costs of collecting the new evidence.
Evaluating the scheme This phase relates to the types of decisions/policy updates that are made at the end of the scheme once the data collection is concluded and
the new evidence has been assessed along with other evidence that has become available. It also concerns the way data collection is moni-tored during the scheme and the definition of any stopping rule or intermediate assessment of the evidence being collected
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Interviews with decision‑makers
A first draft of the interview guide was circulated for com-ments among the COMED project partners. Subsequently the final draft of the interview guide was pilot tested during interviews with one Italian policy maker and two academic experts with extensive experience of CED in Canada and the USA, two countries with a substantial number of schemes.
The interviews were conducted face-to-face or by tel-ephone between June and December 2019. Decision-mak-ers from decision bodies at the central (or in two cases regional) level were identified from the professional net-works of the members of the COMED project team or the websites of relevant decision bodies in the following European countries: Austria, Belgium, Bulgaria, Croa-tia, Czech Republic, Denmark, England, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, the Netherlands, Norway, Poland, Portugal, Romania, Scot-land, Slovakia, Slovenia, Spain, Sweden, and Switzer-land. Other countries from the EU/EEA were excluded because it was not possible to identify a relevant decision-making body for the technology assessment of medical devices. We invited decision-makers to participate in the study by sending them an email with information on the COMED project and the objective of our study. When we were unable to identify a decision-maker from the networks or websites, we sent the information and invita-tion to the relevant decision bodies. In three cases where no relevant decision-maker could be identified (i.e. Bul-garia, Czech Republic, and Sweden), we invited academic researchers with relevant expertise to participate. None of these countries had however any CED programme for devices in place. We interviewed more than one decision maker from a given country in cases where schemes were
operated in more than one jurisdiction (i.e., Italy), where more than one decision body was involved in operating schemes (i.e., France), or where more than one decision-maker, from different parts of the relevant organization, agreed to participate (i.e., England). We excluded Croatia, Iceland, Romania, and Slovenia from our sample after repeated attempts to schedule an interview by December 2019 were unsuccessful. Information on the individual CED schemes provided by decision-makers during or fol-lowing the interview was supplemented with information on individual schemes previously obtained [17], compiled in tabular form, and sent to the participants for a validity check.
Data analysis
The transcripts were subjected to qualitative content analysis using deductive coding to meet the objective of this research. The results of each interview were reported in a table by one author (CF) and assessed by two authors (CF and VRD) who independently extracted the relevant information. Agree-ment on the data to be reported was then reached through discussion and further analysis of the original transcripts. The data obtained from Sections A and C of the interview guide, together with the data obtained prior to and follow-ing the interviews were used to identify and classify the characteristics of the existing CED programmes for devices according to the four phases of CED schemes: 1) assessing the desirability of the scheme; 2) designing the scheme; 3) implementing the scheme, and 4) evaluating it (1). These phases are described in more detail in Table 2. The informa-tion collected was then synthesised in a narrative review.
The data obtained from Section B of the interview guide were used to obtain insight into the participants’ perceptions
Table 2 Challenges with CED schemes for medical devicesa
CED coverage with evidence developmenta Derived from Reckers-Droog et al. 2020 17
Challenge
1 Deciding which medical devices are candidates for CED schemes2 Obtaining stakeholder agreement on the scheme3 Securing funding for the scheme4 Determining the appropriate study design for data collection5 Determining the relevant outcome measure(s) on which data are collected6 Dealing with data collection and monitoring7 Dealing with data analysis8 Ex-ante definition of decision rule, based on possible outcomes of the scheme9 Reaching an agreement on price, reimbursement or use of the device at the end of the scheme10 Withdrawing a device from the market when evidence indicates the device is not (cost-) effective11 Obtaining agreements about the duration of the scheme and the stopping rule12 Adapting the scheme to account for product modifications or a learning curve13 Dealing with the market entry of similar devices
1257Coverage with evidence development schemes for medical devices in Europe: characteristics…
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of the 13 challenges and into the factors that influenced their score for a particular challenge. The quantitative data obtained from Section B were used to calculate the mean (SD) and median (IQR) Likert scores for the 13 challenges (excluding the challenges that were marked as ‘not applica-ble’ by the participants). Then, we calculated these statis-tics separately for participants from countries with and from countries without a CED programme for medical devices. Because of the small sample sizes, we did not examine the differences in scores by performing statistical tests, but all factors which were perceived as having a positive or nega-tive influence on each challenge were synthetized in tabular form.
Results
We interviewed 25 participants from 23 jurisdictions. Respondents were from national or regional health authorities (n = 15); national health insurance bodies (n = 2); hospitals (n = 3); and universities (n = 3) (see Online Resource 3 for details). Eighteen participants had high-level managerial roles related to the HTA of medi-cal devices or services, or were responsible for the CED programme in their jurisdiction; four participants were technical advisers directly involved in the assessment of medical devices, and three were academics with an exper-tise in conditional reimbursement schemes. In seven out of the 23 jurisdictions (30.4%), CED programmes existed that included (or were specific to) schemes for medical devices (i.e., Belgium, England, France, Germany, the Netherlands, Spain, and Switzerland). In France, two dif-ferent programmes were identified: Post Registration Stud-ies (PRS) for devices submitting for registration into the positive list of reimbursable products and services (LPPR list); and Forfait innovation (FI) for highly innovative tech-nologies early in their development phase. Of the remain-ing jurisdictions, 5 (21.7%) operated CED programmes for drugs only (i.e., Bulgaria, Hungary, Portugal, Scotland, and Slovakia), and 11 (47.8%) did not operate any CED programmes (i.e., Austria, Czech Republic, Denmark, Fin-land, Greece, Ireland, Italy-Emilia Romagna Region, Italy-national level, Norway, Poland and Sweden), although some of these may have other types of PBRSAs such as performance linked reimbursement schemes (e.g., payment by results schemes). In addition, single ‘one-off’ expe-riences with schemes for specific devices were reported by participants from Emilia Romagna Region in Italy and Ireland, in the absence of formal programmes for CED schemes for devices.
Overall, we identified 78 CED schemes for devices which were ongoing in the last 5 years in Europe. A full overview of the characteristics of these schemes is
included in Online Resource 4. Table 3 and Fig. 1 pre-sent an overview of how the existing national CED pro-grammes underpinning the individual schemes address the different phases of CED schemes. Our main findings are highlighted below.
Assessing the desirability of a CED scheme
We identified three main ways in which devices are selected for a scheme (Table 3). Firstly, a device can be selected as the direct result of a formal health tech-nology assessment (HTA), if the decision body making the assessment identifies remaining uncertainties on the device (cost-)effectiveness and therefore propose initia-tion of a scheme. Such HTAs can be conducted for exam-ple, in the context of i) a request from a manufacturer to include the device on a positive reimbursement list (e.g., Belgium, France—PRS, the Netherlands and Switzerland); ii) a request from a provider for an extra remuneration of the procedure involving the device, for example on top of an existing diagnosis-related group -DRG tariff (e.g., in Germany); or iii) a request for an evaluation of a proce-dure or device already in use in clinical practice (e.g., in Belgium, Germany, Spain and Switzerland). Secondly, a device could be selected following an active screening of potential candidates for CED schemes conducted by the decision body or by a committee specifically appointed for this task (e.g., in England or Spain). Finally, a device could be selected following a direct application to initiate a CED scheme by manufacturers or other stakeholders, such as care providers and health insurers with an interest in the device (e.g., in Belgium, France—FI studies, the Netherlands and Switzerland).
In all jurisdictions criteria are used to select and/or pri-oritize devices for inclusion in a scheme, and decisions are made either through a deliberative process or using an explicit scoring system or checklist. However, a formal assessment of the pros and cons of initiating a scheme, as opposed to other policy decisions, such as providing uncon-ditional coverage, or refusing to adopt the device until better evidence becomes available, was never clearly defined.
Designing a CED scheme
We identified differences in the design of schemes between countries. For example, Spain and Switzerland mainly operated schemes in which a device is reimbursed for all indicated patients while data are collected in a subset of patients (i.e., only with research—OWR), whereas England, the Netherlands and Belgium mainly operated schemes in which a device is reimbursed only for patients who enrol
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Tabl
e 3
Ove
rvie
w o
f the
cha
ract
erist
ics o
f CED
pro
gram
mes
for m
edic
al d
evic
es in
Eur
ope
Engl
and
Fran
ceG
erm
any
Net
herla
nds
Spai
nSw
itzer
land
Bel
gium
Nam
e of
the
CED
Po
licy
Com
mis
sion
ing
thro
ugh
Eval
u-at
ion
Forfe
it In
nova
tion
(FI)
/Po
st-Re
gistr
atio
n St
udie
s (PR
S)
(étu
des p
ost-i
nscr
ip-
tion
sur l
este
chno
logi
es d
e sa
nté)
Eval
uatio
n of
med
ical
exa
min
a-tio
n an
d tre
atm
ent m
etho
ds (§
13
7e S
GB
V)
Con
ditio
nal a
dmis
-si
on (V
oorw
aard
elijk
e to
elat
ing)
a
Postl
aunc
h ev
i-de
nce-
gene
ratio
n stu
dies
(Estu
dios
de
Mon
itori-
zaci
ón”)
Serv
ices
in e
valu
-at
ion
(Lei
stun-
gen
in E
valu
a-tio
n)
Lim
ited
clin
i-ca
l app
licat
ion
(Bep
erkt
e kl
inis
che
toep
assi
ng)
Des
irabi
lity
of sc
hem
es T
echn
olog
y se
lect
ion
Prop
osal
s for
new
sc
hem
es a
re
co-o
rdin
ated
by
NH
S En
glan
d’s
CRG
s dur
ing
a ‘T
opic
Sel
ec-
tion’
pha
se a
nd
asse
ssed
by
the
Clin
ical
Pan
el
that
det
erm
ines
w
hich
sche
mes
go
forw
ard
for
impl
emen
tatio
n
FI p
acka
ge: p
ropo
s-al
s are
subm
itted
by
man
ufac
ture
rs
alon
e or
in p
artn
er-
ship
with
phy
sici
an’s
as
soci
atio
nsPR
S: if
, dur
ing
the
asse
ssm
ent o
f a
requ
est f
or in
scrip
-tio
n in
the
LPPR
, th
e C
NED
iMTS
id
entifi
es re
mai
ning
un
certa
intie
s on
the
tech
nolo
gy’s
shor
t or
long
-term
out
com
es,
it ca
n re
quire
col
-le
ctio
n of
new
dat
a th
roug
h a
PRS
Dur
ing
the
eval
uatio
n pr
oced
ure
of a
dia
gnos
tic a
nd th
erap
eutic
m
etho
d, if
the
opin
ion
of th
e IQ
WIG
repo
rts th
at th
e be
nefit
ha
s not
bee
n co
nfirm
ed, b
ut
the
met
hod
offer
s the
pot
entia
l of
bei
ng a
trea
tmen
t alte
rna-
tive.
Req
uests
for t
he e
valu
-at
ion
of m
etho
ds m
ay b
e pu
t fo
rwar
d by
1) s
take
hold
ers
orga
niza
tions
for i
npat
ient
(§
137c
, SG
B V
) and
out
pa-
tient
(§ 1
35 S
GB
V) c
are,
2)
dire
ctly
by
man
ufac
ture
rs (§
13
7e S
GB
V) o
r 3) b
y ho
spi-
tals
, sub
mitt
ing
a fir
st re
ques
t fo
r NU
B p
aym
ent t
o th
e In
EK
(§ 1
37 h
SG
B V
)
Tech
nolo
gies
can
be
iden
tified
in 2
way
s: 1
) a
botto
m-u
p pr
oces
s whe
re
parti
es c
an su
bmit
thei
r ow
n ap
plic
atio
n on
ce a
ye
ar; a
nd 2
) a to
p do
wn
proc
ess,
whe
re th
e ZI
N
reco
mm
ends
, in
any
nega
tive
view
follo
win
g an
ass
essm
ent,
whe
ther
an
inte
rven
tion
can
be
elig
ible
for c
ondi
tiona
l ad
mis
sion
Tech
nolo
gies
are
id
entifi
ed b
y th
e N
atio
nal
Com
mis
sion
of
Prov
isio
n, In
sur-
ance
and
Fin
anc-
ing
(CPA
F) o
f th
e M
inist
ry
of H
ealth
and
se
lect
ed b
y th
e D
irect
orat
e G
en-
eral
of t
he c
om-
mon
por
tfolio
of
serv
ices
of t
he
Nat
iona
l Hea
lth
Syste
m (N
HS)
an
d Ph
arm
acy
(DG
PSPh
). To
p-ic
s are
usu
ally
id
entifi
ed fr
om
prev
ious
HTA
re
ports
from
the
Span
ish
Net
wor
k fo
r Hea
lth
Tech
nolo
gy
Ass
essm
ent a
nd
Serv
ices
of t
he
NH
S (R
edET
S)
Tech
nolo
gies
can
be
iden
tified
in
2 w
ays:
1) f
ol-
low
ing
a re
ques
t fo
r ver
ifica
tion
that
a m
edic
al
serv
ice
is e
ffec-
tive,
app
ropr
iate
an
d effi
cien
t (W
ZW c
riter
ia),
if du
ring
the
asse
ssm
ent
the
EAM
GK
/C
FAM
A is
sues
a
“Yes
in e
valu
-at
ion”
reco
m-
men
datio
n; 2
) fo
llow
ing
a di
rect
requ
est
from
man
u-fa
ctur
ers o
r pr
ovid
ers f
or
med
ical
dev
ices
th
at n
eed
to b
e lis
ted
unde
r the
m
edic
al d
evic
e ai
d lis
t
CED
sche
mes
can
be
initi
ated
top-
dow
n fo
llow
ing
a te
ch-
nolo
gy a
ppra
isal
by
the
CTI
IMH
of
the
RIZ
IV. B
ot-
tom
-up
requ
ests
fo
r the
initi
atio
n of
CED
sche
mes
ca
n be
subm
it-te
d by
scie
ntist
or
par
ticip
atin
g ho
spita
ls; h
owev
er,
thes
e sc
hem
es c
an
form
ally
onl
y be
in
itiat
ed b
y th
e C
TIIM
H o
f the
R
IZIV
1259Coverage with evidence development schemes for medical devices in Europe: characteristics…
1 3
Tabl
e 3
(con
tinue
d)
Engl
and
Fran
ceG
erm
any
Net
herla
nds
Spai
nSw
itzer
land
Bel
gium
Crit
eria
for
elig
ibili
ty a
nd
prio
ritiz
atio
n
The
follo
win
g el
igib
ility
crit
eria
m
ust b
e m
et:
1) T
echn
olog
y fa
lls w
ithin
NH
S En
glan
d’s d
irect
co
mm
issi
onin
g re
spon
sibi
litie
s 2)
The
trea
tmen
t or
car
e pa
thw
ay
show
s sig
nific
ant
prom
ise;
3) a
cl
inic
al c
omm
is-
sion
ing
polic
y is
pub
lishe
d co
nfirm
ing
that
th
e te
chno
logy
is
not
rout
inel
y co
mm
issi
oned
, or
ther
e ar
e si
gnifi
-ca
nt re
mai
ning
qu
estio
ns o
f cl
inic
al o
r cos
t-eff
ectiv
enes
s, an
d/or
out
com
es
in th
e ro
utin
e cl
inic
al se
tting
. 4)
exi
sting
un
certa
intie
s will
no
t be
answ
ered
by
cur
rent
or
plan
ned
clin
ical
tri
als.
5) M
ean-
ingf
ul n
ew o
ut-
com
e da
ta c
an b
e ga
ther
ed w
ithin
th
e lik
ely
time-
scal
e of
a sc
hem
e (1
–2 y
ears
)
FI: r
eque
sts a
re
acce
pted
if th
e de
vice
is e
xpec
ted
to b
e in
nova
tive
(4
crite
ria: 1
) the
nov
-el
ty o
f the
dev
ice,
2)
early
dis
sem
inat
ion
phas
e, 3
) acc
epta
ble
risk
for p
atie
nts,
and
4) p
rom
ise
of si
gnifi
-ca
nt h
ealth
impr
ove-
men
ts o
r red
uctio
n in
he
alth
care
cos
ts; a
nd
the
prot
ocol
is c
on-
side
red
adeq
uate
to
answ
er th
e id
entifi
ed
rese
arch
que
stion
s (a
rticl
e 16
5.1.
1 of
th
e Fr
ench
soci
al
secu
rity
code
)PR
S: A
requ
est f
or a
PR
S is
don
e w
hen-
ever
the
CN
EDiM
TS
outli
nes r
elev
ant
rem
aini
ng u
ncer
tain
-tie
s (no
prio
ritiz
a-tio
n)
The
new
met
hod
mus
t hav
e po
sitiv
e pr
omis
e of
ben
efit,
as
defin
ed in
the
Ger
man
cod
e of
pro
cedu
res:
1) p
oten
tial
repl
acem
ent o
f mor
e co
mpl
ex
met
hods
; 2) f
ewer
exp
ecte
d si
de e
ffect
s, 3)
hig
her e
xpec
ted
clin
ical
ben
efits
10 p
rimar
y cr
iteria
for
adm
issi
bilit
y to
a sc
hem
e (y
es/n
o an
swer
s, al
l to
be
satis
fied)
, and
5 se
cond
-ar
y cr
iteria
for p
riorit
iza-
tion
(sco
re fr
om 1
to 1
0).
Prio
ritiz
atio
n cr
iteria
in
clud
e: 1
) Dis
ease
bur
-de
n, 2
) exi
stenc
e of
clin
i-ca
l alte
rnat
ives
, 3) t
he
expe
cted
add
ed v
alue
of
the
inte
rven
tion
(hea
lth
bene
fits/
eco
nom
ic/
orga
niza
tiona
l/soc
ial/e
th-
ical
impa
ct) 4
) exi
stenc
e of
oth
er (s
imila
r) st
udie
s on
goin
g or
pla
nned
and
5)
The
leve
l of e
vide
nce
of th
e pr
opos
ed st
udy
(RC
Ts, o
bser
vatio
nal
desi
gn, c
ompa
rativ
e or
no
t-com
para
tive
studi
es)
A q
uant
itativ
e pr
i-or
itiza
tion
tool
is
used
. Crit
eria
are
de
fined
acr
oss
4 do
mai
ns: 1
) Po
pula
tion/
end
user
s (e.
g., d
is-
ease
bur
den,
fre-
quen
cy o
f use
); 2)
Tec
hnol
ogy
(inno
vativ
enes
s, di
ffere
nt e
xpec
-ta
tions
of u
se);
3) S
afet
y/ad
vers
e eff
ects
(e.g
., sa
fety
issu
es,
unde
tect
ed
adve
rse
effec
ts);
4) o
rgan
izat
ion/
costs
and
oth
er
impl
icat
ions
(e
.g.,
lear
ning
cu
rve,
fina
ncia
l im
pact
, org
ani-
zatio
nal o
r stru
c-tu
ral i
mpa
ct)
An
expl
icit
chec
klist
is u
sed
for t
echn
olog
y se
lect
ion
and
prio
ritiz
atio
n.
Mai
n cr
iteria
ar
e: 1
) exi
stenc
e of
a re
leva
nt
evid
ence
gap
re
gard
ing
effi-
cien
cy, s
afet
y,
cost-
effec
tive-
ness
and
con
di-
tions
of u
se; 2
) in
tere
st fo
r the
te
chno
logy
(e.g
., di
seas
e bu
rden
, ex
isten
ce o
f tre
atm
ent
alte
rnat
ives
, si
gnifi
cant
eco
-no
mic
impa
ct);
3) e
xiste
nce
of
ongo
ing
studi
es
4) th
e re
sear
ch
prop
osal
can
an
swer
the
evid
ence
gap
s 5)
feas
ibili
ty o
f a
CED
sche
me
for
the
tech
nolo
gy
6) e
xpec
ted
pos-
itive
cos
t–be
n-efi
t rat
io; a
nd 7
) ca
paci
ty o
f the
ne
w fi
ndin
gs to
aff
ect c
over
age
deci
sion
s
Mai
n cr
iteria
us
ed a
re: 1
) the
in
nova
tiven
ess o
f th
e te
chno
logy
; 2)
feas
ibili
ty o
f an
swer
ing
the
iden
tified
rese
arch
qu
estio
ns w
ithin
th
e tim
efra
me
of
the
study
Rese
arch
des
ign
1260 C. Federici et al.
1 3
Tabl
e 3
(con
tinue
d)
Engl
and
Fran
ceG
erm
any
Net
herla
nds
Spai
nSw
itzer
land
Bel
gium
Typ
e of
CED
sc
hem
ebO
nly
in re
sear
chFI
: Onl
y in
rese
arch
, PR
S: O
nly
with
re
sear
ch
Onl
y w
ith re
sear
ch fo
r Inp
atie
nt
care
, Onl
y in
rese
arch
for
outp
atie
nt c
are
Onl
y in
rese
arch
cO
nly
with
rese
arch
(in
sele
cted
he
alth
care
ce
ntre
s ide
ntifi
ed
at th
e re
gion
al
leve
l)
Onl
y w
ith
rese
arch
Onl
y in
rese
arch
Typ
es o
f stu
dy
desi
gnM
ainl
y pr
ospe
ctiv
e ob
serv
atio
nal
studi
es u
sing
dat
a co
llect
ed fr
om
exist
ing
clin
ical
da
taba
ses,
or b
y se
tting
up
a ne
w
regi
stry
FI: H
ighe
st le
vel o
f ev
iden
ce p
refe
rred
(e
.g.,
RCTs
)PR
S: M
ainl
y si
ngle
-ar
m, r
egist
ry b
ased
, ob
serv
atio
nal s
tudi
es
Hig
hest
leve
l of e
vide
nce
pre-
ferr
ed (e
.g.,
RCTs
)H
ighe
st le
vel o
f evi
denc
e pr
efer
red
(e.g
., RC
Ts).
Furth
erm
ore,
a su
pple
-m
enta
ry (o
bser
vatio
nal)
study
may
be
initi
ated
af
ter t
he e
nrol
men
t of
the
pref
erre
d stu
dy is
co
mpl
eted
Pros
pect
ive,
si
ngle
-arm
ob
serv
atio
nal
studi
es; f
ocus
on
desi
gns w
hich
m
inim
ize
data
co
llect
ion
effor
t
Pref
erab
ly R
CTs
, ot
her d
esig
ns
may
be
also
co
nsid
ered
(b
efor
e-an
d-af
ter c
ompa
ri-so
ns, c
ase
serie
s or
com
paris
ons
with
hist
oric
al
cont
rols
)
Pros
pect
ive
obse
r-va
tiona
l stu
dies
, ba
sed
on re
gistr
y da
ta
Impl
emen
tatio
n F
undi
ng o
f the
re
sear
chN
HS
Engl
and
pro-
vide
s fun
ds fo
r se
rvic
e pr
ovis
ion
to th
e pa
rtici
pat-
ing
cent
res a
nd
NIC
E to
ove
rsee
th
e sc
hem
e.
NIC
E di
rect
ly
com
mis
sion
s an
Exte
rnal
Ass
ess-
men
t Cen
tre fo
r da
ta c
olle
ctio
n an
d da
ta a
naly
sis
FI: a
forfe
it pa
ymen
t fo
r the
pro
cedu
re a
nd
the
asso
ciat
ed h
ospi
-ta
l cos
ts is
est
ab-
lishe
d at
the
star
t of
the
sche
me.
Cos
ts o
f da
ta c
olle
ctio
n an
d an
alys
is fa
ll on
the
sche
me
appl
ican
tPR
S: F
ollo
win
g th
e C
NED
iMTS
ap
prai
sal,
the
devi
ce
is te
mpo
raril
y lis
ted
in L
PPR
and
cov
ered
by
the
soci
al h
ealth
in
sura
nce.
Cos
ts o
f da
ta c
olle
ctio
n an
d an
alys
is fa
ll on
the
man
ufac
ture
rs
G-B
A c
oord
inat
es a
ll ph
ases
of
the
desi
gn a
nd im
plem
enta
tion
of th
e sc
hem
e. T
he d
iagn
ostic
an
d th
erap
eutic
met
hod
unde
r ev
alua
tion
is c
over
ed b
y th
e he
alth
insu
ranc
e. O
verh
eads
of
the
study
can
be
finan
ced
by th
e m
anuf
actu
rer o
f the
de
vice
bei
ng e
valu
ated
or a
re
finan
ced
by st
atut
ory
heal
th
insu
ranc
e vi
a G
-BA
The
care
pro
vide
d is
co
vere
d by
the
basi
c in
sura
nce
pack
age.
The
re
imbu
rsem
ent r
ate
is
nego
tiate
d be
twee
n th
e he
alth
insu
ranc
e co
mpa
-ni
es a
nd th
e pa
rtici
patin
g ho
spita
ls a
nd in
clud
ed
in a
cov
enan
t agr
eem
ent
sign
ed b
y al
l par
ties
invo
lved
in th
e sc
hem
e.
The
costs
of d
ata
col-
lect
ion
and
anal
ysis
are
co
vere
d by
the
sche
me
appl
ican
ts. H
owev
er,
ther
e is
the
poss
ibili
ty to
ap
ply
for a
rese
arch
gra
nt
at Z
onM
w
Regi
onal
HTA
ag
enci
es re
ceiv
e fu
ndin
g fo
r da
ta c
olle
ctio
n,
anal
ysis
and
re
porti
ng fr
om
the
cent
ral M
in-
istry
of H
ealth
. Th
e pr
ice
of th
e de
vice
is n
egot
i-at
ed in
divi
dual
ly
by th
e re
gion
s pa
rtici
patin
g in
the
sche
me.
Pa
rtici
patin
g ho
spita
ls d
o no
t re
ceiv
e ex
tra
fund
ing
for d
ata
colle
ctio
n
The
reim
burs
e-m
ent o
f the
pr
oced
ure
is
cove
red
by th
e he
alth
insu
r-an
ce. C
osts
of
data
col
lect
ion
and
anal
ysis
fa
lls o
n th
e m
anuf
actu
rer
Follo
win
g th
e re
com
men
datio
n of
the
CTI
IMH
to
initi
ate
a sc
hem
e,
the
min
ister
of
heal
th ta
kes a
de
cisi
on re
gard
-in
g th
e te
mpo
rary
re
imbu
rsem
ent o
f th
e ca
re se
rvic
e an
d th
e re
imbu
rse-
men
t met
hods
to
be a
pplie
d. P
ar-
ticip
atin
g ho
spita
ls
do n
ot re
ceiv
e an
y fu
ndin
g fo
r dat
a co
llect
ion
and
anal
ysis
1261Coverage with evidence development schemes for medical devices in Europe: characteristics…
1 3
Tabl
e 3
(con
tinue
d)
Engl
and
Fran
ceG
erm
any
Net
herla
nds
Spai
nSw
itzer
land
Bel
gium
Defi
nitio
n of
stu
dy p
roto
col
The
study
pro
toco
l is
dev
elop
ed
by th
e Ex
tern
al
Ass
essm
ent C
en-
tre in
par
tner
ship
w
ith N
ICE
FI: T
he st
udy
prot
ocol
is
dire
ctly
subm
itted
by
the
sche
me
appl
i-ca
nt a
nd e
valu
ated
by
the
HA
SPR
S: T
he re
spon
sibi
l-ity
of d
efini
ng th
e pr
otoc
ol fa
lls o
n th
e sc
hem
e ap
plic
ants
. A
utho
ritie
s onl
y pr
ovid
e br
oad
indi
ca-
tions
on
the
type
of
unce
rtain
ties t
hat
mus
t be
addr
esse
d by
the
sche
me,
and
ap
prov
e th
e fin
al
vers
ion
of th
e stu
dy
prot
ocol
The
key
aspe
cts o
f the
stud
y ar
e de
fined
in th
e di
rect
ive
appr
ovin
g th
e sc
hem
e. T
he
prot
ocol
is th
en re
fined
by
the
rese
arch
insti
tutio
n th
at
cond
ucts
the
study
Dev
elop
men
t of t
he
study
pro
toco
l is a
di
rect
resp
onsi
bilit
y of
th
e sc
hem
e ap
plic
ant.
ZIN
ass
esse
s the
stud
y pr
opos
al in
col
labo
ra-
tion
with
the
Scie
ntifi
c A
dvis
ory
Cou
ncil
(WA
R)
and
ZonM
w
The
study
pro
toco
l is
defi
ned
by th
e re
gion
al H
TA
agen
cies
par
tici-
patin
g in
the
data
co
llect
ion
The
desi
gn o
f the
pr
otoc
ol is
a
resp
onsi
bilit
y of
the
sche
me
appl
ican
t. Th
e pr
opos
al is
then
ev
alua
ted
and
appr
oved
by
the
FOPH
The
rele
vant
qu
estio
ns to
be
answ
ered
in th
e sc
hem
e an
d th
e se
t-up
of th
e re
g-ist
ry a
re p
ropo
sed
by th
e C
TIIM
H
and
disc
usse
d w
ith
the
stak
ehol
ders
in
volv
ed, t
o ob
tain
an
agr
eem
ent.
Out
com
es to
be
cons
ider
ed a
re d
is-
cuss
ed b
etw
een
the
expe
rt sc
ient
ific
com
mun
ity a
nd
the
CTI
IMH
whi
ch
also
app
rove
s the
fin
al v
ersi
on o
f the
pr
otoc
ol
1262 C. Federici et al.
1 3
Tabl
e 3
(con
tinue
d)
Engl
and
Fran
ceG
erm
any
Net
herla
nds
Spai
nSw
itzer
land
Bel
gium
Dat
a co
llect
ion,
m
onito
ring.
an
d an
alys
is
The
data
col
lec-
tion
is o
vers
een
by th
e ap
poin
ted
steer
ing
grou
p,
and
supp
orte
d by
the
Exte
rnal
A
sses
smen
t C
entre
. Per
iodi
c ch
ecks
and
fol-
low
ups
are
don
e on
the
qual
ity
and
valid
ity o
f da
ta su
bmitt
ed to
en
sure
mea
n-in
gful
dat
a is
be
ing
colle
cted
. A
naly
sis o
f the
da
ta is
don
e by
the
exte
rnal
as
sess
men
t cen
tre
and
revi
ewed
by
NIC
E
FI a
nd P
RS:
The
re
spon
sibi
lity
for
both
the
data
col
lec-
tion
and
anal
ysis
falls
on
the
man
ufac
ture
r on
ly. F
or P
RS
stud-
ies,
the
CN
eDM
Ts
eval
uate
the
qual
ity
of th
e ne
w e
vide
nce
prov
ided
at t
he
time
of th
e pl
anne
d re
-app
rais
al o
f the
te
chno
logy
Dat
a co
llect
ion
and
anal
ysis
are
do
ne b
y an
ext
erna
l res
earc
h in
stitu
tion
whi
ch h
as b
een
appo
inte
d by
G-B
A th
roug
h a
publ
ic te
nder
, if t
he o
verh
eads
ar
e fin
ance
d vi
a G
-BA
The
sche
me
appl
ican
t has
th
e m
ain
resp
onsi
bilit
y fo
r dat
a co
llect
ion
and
mon
itorin
g. T
he Z
IN
mon
itors
the
cour
se o
f th
e sc
hem
e an
d re
ports
it
annu
ally
to th
e M
inist
er
of H
ealth
. ZIN
ass
esse
s th
e ne
w e
vide
nce
pro-
vide
d at
the
time
of th
e pl
anne
d as
sess
men
t of
the
tech
nolo
gy
Dat
a co
llect
ion
and
anal
ysis
is
coor
dina
ted
by
the
Regi
onal
H
TA a
genc
ies
parti
cipa
ting
in th
e sc
hem
e.
Task
s inc
lude
ch
ecki
ng d
ata
com
plet
enes
s an
d qu
ality
, sa
fety
surv
eil-
lanc
e, a
nd y
early
re
porti
ng to
the
CPA
F on
the
prog
ress
of t
he
sche
me
The
appl
ican
t (p
rovi
der a
nd/
or m
anuf
actu
rer)
ar
e th
e so
le
resp
onsi
ble
for
data
col
lect
ion
and
anal
ysis
. Ye
arly
repo
rts
have
to b
e re
porte
d to
the
FOPH
, sho
win
g ho
w th
e stu
dy
is p
roce
edin
g.
Thes
e re
ports
m
ay in
form
ch
ange
s to
the
sche
me
or e
ven
caus
e ea
rly
term
inat
ion,
if
issu
es a
rise
with
da
ta c
olle
ctio
n (e
.g.,
poor
qua
l-ity
of t
he d
ata,
sl
ow re
crui
t-m
ent)
Dat
a co
llect
ion
is
a re
spon
sibi
lity
of th
e ho
spita
ls
that
hav
e si
gned
th
e ag
reem
ent t
o pa
rtici
pate
in th
e sc
hem
e. D
epen
d-in
g on
the
agre
e-m
ent,
the
hosp
itals
or
an
exte
rnal
pee
r-re
view
gro
up/s
ci-
entifi
c as
soci
atio
n ar
e re
spon
sibl
e fo
r th
e sc
ient
ific
repo
rt
Eval
uatio
n E
xiste
nce
of e
x-an
te d
ecis
ion
rule
s for
the
sche
me
linki
ng
the
resu
lts o
f th
e sc
hem
e to
a d
eci-
sion
on
pric
e,
reim
burs
emen
t or
use
No
No
(bot
h FI
and
PR
S)N
oA
gree
men
ts re
gard
ing
the
upta
ke o
f the
inte
rven
-tio
n, in
cas
e of
a p
ositi
ve
cove
rage
dec
isio
n at
the
end
of th
e sc
hem
e, o
r ex
it str
ateg
ies i
n ca
se o
f a
nega
tive
opin
ion
(e.g
., be
caus
e th
e in
terv
entio
n is
not
effe
ctiv
e, o
r the
da
ta q
ualit
y is
con
side
red
insu
ffici
ent t
o ta
ke a
de
cisi
on) a
re d
efine
d in
th
e co
nven
ant a
gree
men
t pr
ior t
o th
e st
art o
f the
sc
hem
e
No
No
No
1263Coverage with evidence development schemes for medical devices in Europe: characteristics…
1 3
Tabl
e 3
(con
tinue
d)
Engl
and
Fran
ceG
erm
any
Net
herla
nds
Spai
nSw
itzer
land
Bel
gium
Typ
es o
f dec
i-si
ons i
nfor
med
by
the
sche
me
Resu
lts o
f the
sc
hem
e ar
e us
ed
for t
he d
evel
op-
men
t of C
linic
al
Com
mis
sion
-in
g po
licy
for
NH
S En
glan
d’s
dire
ctly
com
mis
-si
oned
spec
ial-
ised
serv
ices
FI: C
ondi
tiona
l re
imbu
rsem
ent i
s pr
ovid
ed o
nly
for
the
dura
tion
of th
e sc
hem
e, th
en d
evic
es
ente
r usu
al e
valu
a-tio
n pa
thw
ays (
e.g.
, a
new
requ
est b
y th
e m
anuf
actu
rer f
or
insc
riptio
n in
the
LPPR
)PR
S: c
onfir
ma-
tion
of th
e de
vice
in
the
LPPR
and
re
finem
ents
of t
he
cond
ition
s of u
se.
Fina
ncia
l pen
al-
ties o
n th
e pr
ice
of
the
devi
ce m
ay b
e ap
plie
d in
cas
e of
po
or d
ata
qual
ity a
t re
asse
ssm
ent
Con
firm
atio
n of
the
reim
burs
e-m
ent s
tatu
sC
onfir
mat
ion
of th
e re
im-
burs
emen
t sta
tus
Con
firm
atio
n of
re
imbu
rsem
ent
stat
us u
nder
the
sam
e co
nditi
ons
of u
se, c
hang
es
to th
e co
ndi-
tions
of u
se o
r w
ithdr
awal
of
the
tech
nolo
gy
from
the
bene
fit
pack
age
Con
firm
atio
n of
th
e re
imbu
rse-
men
t sta
tus,
refin
emen
ts o
f co
nditi
ons o
f us
e, a
nd c
hang
es
in th
e m
axim
um
reim
burs
emen
t ra
te fo
r the
te
chno
logy
or
proc
edur
e
Con
firm
atio
n of
the
reim
burs
emen
t st
atus
a Star
ting
from
201
9, c
ondi
tiona
l adm
issio
n sc
hem
es h
ave
starte
d to
be
grad
ually
repl
aced
by
sche
mes
with
in th
e ne
w P
rom
ising
Car
e Su
bsid
y Fu
nd (P
CSF)
. The
mai
n di
ffere
nce
betw
een
the
two
pro-
gram
mes
conc
erns
the w
ay ca
re p
rovi
sion
is re
imbu
rsed
dur
ing
a sch
eme,
i.e.,
dire
ctly
subs
idiz
ed in
the P
CSF
rath
er th
an co
vere
d by
the s
tatu
tory
hea
lth in
sura
nce a
s in
cond
ition
al ad
miss
ion
sche
mes
. The
sc
hem
es al
read
y on
goin
g w
ill b
e com
plet
ed ac
cord
ing
to th
e VT
prog
ram
me d
escr
ibed
in th
e Tab
leb
“ Onl
y in
rese
arch
” ar
e de
fined
as s
chem
es in
whi
ch a
dev
ice
or p
roce
dure
is re
imbu
rsed
onl
y fo
r pat
ient
s who
enr
ol in
a c
linic
al st
udy,
whe
reas
“O
nly
with
rese
arch
” sc
hem
es a
re d
efine
d as
sche
mes
in
whi
ch a
devi
ce o
r pro
cedu
re is
reim
burs
ed fo
r all
indi
cate
d pa
tient
s whi
le d
ata a
re co
llect
ed in
a su
bset
of p
atie
nts
c Cond
ition
ally
app
rove
d ca
re is
onl
y co
vere
d if
the
patie
nt p
artic
ipat
es in
the
mai
n stu
dy. H
owev
er, p
atie
nts w
ho a
re n
ot a
ble
to p
artic
ipat
e ca
n cl
aim
the
cond
ition
ally
app
rove
d ca
re if
they
par
ticip
ate
in
a su
pple
men
tary
anc
illar
y stu
dy. C
NED
iMTS
, Fre
nch
Med
ical
Dev
ice
and
Hea
lth T
echn
olog
y Ev
alua
tion
Com
mitt
ee; C
RGs,
Clin
ical
Ref
eren
ce G
roup
s (En
glan
d); C
TIIM
H, B
elgi
um Im
plan
t and
Inva
-siv
e M
edic
al D
evic
e Re
imbu
rsem
ent C
omm
ittee
;; FO
PH, S
wiss
Fed
eral
Offi
ce o
f Pub
lic H
ealth
; G-B
A, G
erm
an F
eder
al Jo
int C
omm
ittee
; InE
K, G
erm
an In
stitu
te fo
r the
Hos
pita
l Rem
uner
atio
n Sy
stem
; IQ
WiG
, Ger
man
Insti
tute
for t
he H
ospi
tal R
emun
erat
ion
Syste
m; L
PPR,
List
of P
rodu
cts a
nd S
ervi
ces q
ualif
ying
for R
eim
burs
emen
t (Fr
ance
); RC
Ts, R
ando
miz
ed C
ontro
lled
Tria
ls; R
IZIV
, Bel
gian
Med
i-ci
nes
Verifi
catio
n O
rgan
isatio
n; Z
IN, N
ethe
rland
s N
atio
nal H
ealth
Car
e In
stitu
te; Z
onM
W, N
ethe
rland
s or
gani
satio
n fo
r Hea
lth R
esea
rch
and
Dev
elop
men
t, Im
plan
t and
Inva
sive
Med
ical
Dev
ice
Reim
-bu
rsem
ent C
omm
ittee
1264 C. Federici et al.
1 3
in a clinical study (i.e., only in research—OIR). In France schemes were either OIR in the FI programme or OWR in the PRS, whereas in Germany the type of schemes depended on whether the technology was intended for inpatient use (OWR) or outpatient use (OIR).
It is worth noting, however, that within countries, the designs were relatively similar between schemes and appeared not to be tailored to (the specific characteristics of) the device under evaluation or to key sources of uncertainty. Moreover, the study designs were similar between schemes
Fig. 1 Overview of the main characteristics of CED programmes in Europe
1265Coverage with evidence development schemes for medical devices in Europe: characteristics…
1 3
in each country and mainly concerned either observational designs utilizing real-world data, or experimental designs to ensure a high level of evidence (e.g., randomized controlled trials).
Implementing a CED scheme
We observed differences in the governance of CED schemes as well as in the roles and responsibilities of the stakeholders involved, regarding the development of the research protocol and the subsequent monitoring of the scheme. Overall, we identified two main approaches. In the first approach (e.g., in France, the Netherlands and Switzerland), the responsibility for the development of the study protocol, the monitoring of the scheme and the quality of the generated data relies entirely on the scheme applicants (e.g., the manufacturer or care providers). However, in defining the study protocol the applicants typically must follow the recommendations of the relevant decision body. Usually, the protocol requires formal approval before study initiation, to make sure that it is suitable for addressing the identified uncertainties regard-ing the device. In the second approach, the responsibility for the development of the study protocol and the quality of the generated data are coordinated centrally (e.g., by HTA agencies), and managed either directly or through third-party research centres (e.g., in Belgium, England, Germany and Spain).
Patient representatives may be involved in the initial assessment phase on the desirability of the scheme (e.g., in Spain or France) or later during the recruitment phase of the study (e.g., in England), but their involvement in the design phase and the development of the protocol was generally limited.
During the scheme, the costs of care provision (includ-ing utilization of the device) are usually funded through the public health care system. Specific funding arrangements may be defined at the onset to cover the additional costs of the device or procedure, by either establishing a forfeit or negotiating an add-on to an already existing DRG tariff. However, different arrangements exist for covering the addi-tional costs associated with the research, including the costs of developing the study protocol, scientific monitoring, data collection and analysis. These costs may be either entirely financed with public funds (e.g., in Belgium, England and Spain) or they may be partially or entirely covered by the scheme applicant (e.g., in France, Germany, the Netherlands and Switzerland). Notably, in some cases, funding arrange-ments also include resources for data collection. In other cases, health care providers are required to perform this task without any additional funding, for example, as a condition of participating in the scheme and gaining market access for the device (e.g., in Spain or Belgium).
Evaluating a CED scheme
Decisions at the end of schemes mainly concerned the con-firmation of the reimbursement status of the device, the refinement of clinical indications or conditions of use. For most of the identified schemes, no ex-ante decision rules that explicitly linked the scheme results to future decisions were defined. In most countries the schemes solely concerned the collection of additional evidence to reduce the identified uncertainties, while the final decision on the reimbursement, coverage or use of the device was integrated in the routine decision-making framework. A notable exception was the Netherlands, where the level of effectiveness that must be demonstrated during the scheme to obtain unconditional reimbursement was predefined at the onset of the scheme, in a covenant agreement signed by all stakeholders. Moreover, the covenant also addressed how to manage the withdrawal of a device in case it proved to be insufficiently effective or the data did not allow an informed decision (e.g., due to poor data quality or inconclusive results).
Notably, all participants reported having no, or only very little experience, with schemes that led to a negative cov-erage decision. Indeed, of the 24 CED schemes for which information on final decisions were available, coverage was confirmed (or conditional coverage prolonged due to data quality issues) in 22 cases.
Challenges associated with CED schemes for medical devices
Of the 25 participants, 18 scored the 13 challenges on the six-point Likert scales. Of these, nine were from jurisdic-tions with CED programmes involving devices, and nine were from jurisdictions with CED programmes involving drugs only. The seven participants who did not score the challenges were from countries without CED programmes.
For most of the assessed challenges, scores were observed across the full range of the Likert scales, indicating no clear patterns in the decision-makers’ perceptions. Table 4 pre-sents the mean and median scores for each challenge. Over-all respondents from jurisdictions with CED programme for medical devices tended to give lower scores to most of the challenges as opposed to respondents from jurisdictions without such programmes. However, the low sample size and the variability in responses within each challenge ham-pered any firm conclusion.
Table 5 presents the main factors that, according to the participants, positively or negatively influenced the chal-lenges. Many of the factors identified are common to all technologies and consistent with the existing literature on CED schemes. However, some elements specific to devices could be identified.
1266 C. Federici et al.
1 3
Devices were generally considered to be more difficult to identify and monitor than pharmaceuticals, given that their routes to market are often less clear and may not be observed by those who are responsible for selecting potential candidates for CED schemes. The intrinsic characteristics of devices were also reported to pose additional challenges in the design and implementation of schemes. For exam-ple, device-user interactions and the context-specific factors which may affect device performance in the real-world were considered as challenges for the identification of all relevant uncertainty at the time of scheme initiation, and for the defi-nition of the study protocol. In addition, devices may be associated with uncertainties that cannot be easily resolved within a feasible time frame for a scheme, such as uncer-tainties over the devices’ durability or their long-term per-formance in patients with different clinical conditions and physiologies. This in turn may increase the tension between the need to pragmatically rely on surrogate endpoints, which are rarely validated for MD procedures, and the relevance of the data collected to inform decision-making at the end of the scheme. In addition, routinely collected data, such as administrative datasets or electronic health records were expected to be less often available, or relevant, for devices, as compared with pharmaceuticals.
Relating to the possibility of product modifications dur-ing the timeframe of the scheme, one of the main concerns related to the fact that such modifications could bias the results of the study or compromise the relevance of the new evidence collected. In this respect, being able to anticipate product modifications by means of dialogues with manufac-turers and sharing of information was considered a poten-tially mitigating factor. However, the possibility of product modifications was not perceived by most of the respondents as a major challenge, or something which is likely to occur during the duration of a scheme.
Similarly, about half of the respondents did not consider the possibility that similar products would enter the market during the period of the scheme to be an important chal-lenge. Possible reasons related to the fact that most of the schemes evaluate a class of devices or a procedure rather than a single branded device, or that, even if focussed on a single product, they collected mainly non-comparative data. However, other respondents emphasised the difficulty of anticipating which products would enter the market dur-ing the schemes and the possibility that relative effectiveness estimates may not be meaningful anymore by the end of the scheme, as clinical practice changes more rapidly in the context of devices compared to pharmaceuticals.
Table 4 Assessment of challenges by participantsa
a Assessed on a six-point Likert scale (ranging from 0 “not a challenge” to 5 “a major challenge”)b Two participants scored the challenges for this country
Challenge Participants from countries with CED programmes for medical devices (Belgium, Englandb, Franceb, Germany, Netherlands, Spain, Switzer-land)
Participants from countries without CED programmes for medical devices (Bulgaria, Hungary, Ireland, Italyb, Poland, Portugal, Scotland, Slovakia)
n Mean (SD) Median (IQR) n Mean (SD) Median (IQR)
1 Deciding which medical devices are candidates for CED schemes 9 2.5 (1.17) 2 (2.25) 9 3.78 (1.48) 4 (2.5)2 Obtaining stakeholder agreement on the scheme 9 2.17 (1.46) 2 (2.75) 8 2.75 (1.83) 2.5 (3.5)3 Securing funding for the scheme 9 0.89 (1.05) 1 (1.50) 8 3 (1.69) 3 (3.5)4 Determining the appropriate study design for data collection 9 2.39 (1.45) 2 (2.75) 9 3.33 (1.32) 4 (2)5 Determining the relevant outcome measure(s) on which data are collected 9 2.61 (1.27) 2 (2.50) 9 2.78 (1.72) 2 (3.5)6 Dealing with data collection and monitoring 8 2.13 (1.64) 2.5 (3.5) 9 3.78 (1.2) 4 (2.5)7 Dealing with data analysis 9 1.61 (1.22) 1.5 (2.5) 8 3 (1.51) 3.5 (2.75)8 Ex-ante definition of decision rule, based on possible outcomes of the
scheme3 3 (1) 3 (2) 8 3.75 (1.58) 4.5 (2.75)
9 Reaching an agreement on price, reimbursement or use of the device at the end of the scheme
5 2.1 (2.13) 2 (4.25) 7 3.57 (1.27) 4 (3)
10 Withdrawing a device from the market when evidence indicates the device is not (cost-) effective
6 3 (0.89) 3 (2) 8 4.5 (1.07) 5 (0.75)
11 Obtaining agreements about the duration of the scheme and the stopping rule
9 1.94 (1.13) 2 (1.25) 8 1.75 (1.49) 1.5 (2.75)
12 Adapting the scheme to account for product modifications or a learning curve
8 1.44 (1.45) 1.5 (2.38) 8 3.25 (1.49) 3.5 (2.75)
13 Dealing with the market entry of similar devices 9 1.83 (1.73) 1 (2.75) 8 2.25 (1.67) 2 (3)
1267Coverage with evidence development schemes for medical devices in Europe: characteristics…
1 3
Tabl
e 5
Fac
tors
with
pos
itive
and
neg
ativ
e in
fluen
ce o
n ch
alle
nges
with
CED
sche
mes
for d
evic
es
Cha
lleng
eFa
ctor
s with
pos
itive
influ
ence
Fact
ors w
ith n
egat
ive
influ
ence
1D
ecid
ing
whi
ch m
edic
al d
evic
es a
re c
andi
date
s for
CED
sc
hem
esTh
ere
is a
stru
ctur
ed p
roce
ss le
adin
g to
the
iden
tifica
tion
of
pote
ntia
l can
dida
tes f
or C
ED sc
hem
esPr
iorit
izat
ion
and
incl
usio
n of
tech
nolo
gies
into
a sc
hem
e is
m
ade
acco
rdin
g to
exp
licit
and
shar
ed c
riter
iaTh
e su
itabi
lity
of th
e pr
opos
ed st
udy
prot
ocol
is a
pre
-con
di-
tion
to in
clus
ion
of a
tech
nolo
gy in
a sc
hem
eTh
e re
ques
t to
prov
ide
addi
tiona
l dat
a is
app
lied
to a
ll te
ch-
nolo
gies
for w
hich
rele
vant
evi
denc
e ga
ps a
re id
entifi
ed
durin
g an
ass
essm
ent a
nd th
e m
ain
resp
onsi
bilit
y of
dat
a co
llect
ion
falls
on
the
man
ufac
ture
rs/a
pplic
ants
HTA
pro
cess
es fo
r dev
ices
are
less
form
aliz
ed, c
omm
issi
on-
ing
mai
nly
occu
rs a
t the
loca
l lev
elA
hig
h nu
mbe
r of d
evic
es a
nd la
ck o
f hor
izon
scan
ning
pr
oces
ses t
o in
form
can
dida
tes f
or C
ED sc
hem
es o
f med
ical
de
vice
sO
ptim
al a
lloca
tion
of th
e fu
nds f
or C
ED sc
hem
es is
ham
pere
d by
the
fact
that
pro
posa
ls a
re e
valu
ated
at d
iffer
ent t
imes
ov
er th
e ye
arIt
is n
ot e
asy
to e
stab
lish
whe
ther
the
avai
labl
e ev
iden
ce is
su
ffici
ent t
o in
itiat
e C
ED sc
hem
e or
whe
ther
it is
too
early
fo
r rei
mbu
rsem
ent
2O
btai
ning
stak
ehol
der a
gree
men
t on
the
sche
me
Ther
e ex
ists a
wel
l-defi
ned
and
struc
ture
d pr
oces
ses f
or
stak
ehol
der e
ngag
emen
tA
ll de
tails
of t
he sc
hem
e, in
clud
ing
the
role
s and
obl
igat
ions
of
the
stak
ehol
ders
invo
lved
are
defi
ned
in a
con
tract
ual
agre
emen
t bef
ore
sche
me
initi
atio
nRe
latio
nshi
ps w
ith c
linic
ians
and
man
ufac
ture
rs a
re fa
cili-
tate
d if
CED
sche
mes
are
per
ceiv
ed a
s the
onl
y m
eans
to
use
the
tech
nolo
gyTh
e re
spon
sibi
lity
to c
olle
ct th
e da
ta (a
nd c
oord
inat
e w
ith
parti
cipa
ting
cent
res a
nd o
ther
stak
ehol
ders
) fal
l on
man
u-fa
ctur
ers/
appl
ican
ts
The
com
plex
ity o
f CED
sche
mes
and
the
diffe
rent
exp
ecta
-tio
ns o
f the
stak
ehol
ders
invo
lved
requ
ire a
stro
ng a
nd ti
me-
cons
umin
g co
ordi
natin
g eff
ort
For d
evic
es, i
t is m
ore
diffi
cult
to fi
nd p
atie
nts t
o pa
rtici
pate
in
pub
lic c
onsu
ltatio
ns d
urin
g th
e sc
hem
e (e
.g.,
com
pare
d to
ph
arm
aceu
tical
s)In
cou
ntrie
s with
smal
l mar
kets
man
ufac
ture
rs m
ay h
ave
a hi
gh b
arga
inin
g po
wer
whe
n di
scus
sing
the
cond
ition
s for
th
e sc
hem
es
3Se
curin
g fu
ndin
g fo
r the
sche
me
Fixe
d bu
dget
s for
CED
sche
mes
are
gra
nted
on
a pe
riodi
c ba
sis
The
addi
tiona
l cos
ts o
f run
ning
a sc
hem
e fa
ll up
on th
e m
anuf
actu
rers
/app
lican
ts
Lack
of a
d ho
c fu
nds a
nd/o
r hum
an re
sour
ces t
o ru
n th
e sc
hem
es
4D
eter
min
ing
the
appr
opria
te st
udy
desi
gn fo
r dat
a co
llect
ion
The
heal
th a
utho
rity
can
expl
icitl
y or
impl
icitl
y m
anda
te th
e ty
pe o
f stu
dy to
be
cond
ucte
dSt
udy
desi
gn is
defi
ned
by a
third
-par
ty re
sear
ch in
stitu
tion
CED
sche
mes
are
mos
tly re
lyin
g on
rout
inel
y co
llect
ed d
ata
A re
gistr
y on
the
dise
ase/
devi
ce is
alre
ady
in p
lace
and
suit-
able
to a
nsw
er th
e re
sear
ch q
uesti
ons
Setti
ng u
p th
e re
sear
ch g
over
nanc
e is
usu
ally
com
plex
, with
se
vera
l org
aniz
atio
ns in
volv
ed a
nd m
any
prac
tical
que
stion
s to
ans
wer
Ther
e m
ay b
e di
sagr
eem
ent o
n stu
dy d
esig
n be
twee
n th
e go
vern
men
t, th
e m
anuf
actu
rers
and
the
prov
ider
sSe
lect
ing
the
cent
res t
hat w
ill c
olle
ct d
ata
for t
he sc
hem
es
may
be
prob
lem
atic
and
tim
e co
nsum
ing
Orig
inal
pat
ient
s’ in
form
ed c
onse
nt fo
r reg
istrie
s may
not
al
low
subs
eque
nt a
naly
ses o
f dat
a
1268 C. Federici et al.
1 3
Tabl
e 5
(con
tinue
d)
Cha
lleng
eFa
ctor
s with
pos
itive
influ
ence
Fact
ors w
ith n
egat
ive
influ
ence
5D
eter
min
ing
the
rele
vant
out
com
e m
easu
re(s
) on
whi
ch d
ata
are
colle
cted
The
heal
th a
utho
rity
defin
es th
e pr
imar
y an
d se
cond
ary
outc
omes
. Tho
se re
spon
sibl
e fo
r car
ryin
g ou
t the
rese
arch
m
ust j
ustif
y if
they
do
not f
ollo
w th
e in
dica
tion
Clin
icia
ns a
nd e
xper
ts a
re in
volv
ed fr
om th
e on
set i
n th
e de
finiti
on o
f the
out
com
esPr
evio
us e
vide
nce
from
the
liter
atur
e or
inte
rnat
iona
l col
-la
bora
tions
(e.g
., Eu
netH
TA re
ports
) alre
ady
outli
ned
the
mos
t rel
evan
t out
com
es
Rele
vant
safe
ty a
nd e
ffect
iven
ess i
ssue
s are
mor
e di
fficu
lt to
id
entif
y fo
r dev
ices
com
pare
d to
dru
gs a
t the
tim
e of
the
eval
uatio
nPa
tient
Rep
orte
d O
utco
mes
dat
a ar
e ge
nera
lly d
ifficu
lt to
co
llect
A b
alan
ce is
requ
ired
betw
een
wha
t out
com
es w
ould
be
desi
rabl
e an
d w
hat c
an b
e pr
agm
atic
ally
col
lect
ed b
y th
e pa
rtici
patin
g ce
ntre
sD
iffer
ent s
take
hold
ers m
ay d
isag
ree
on th
e re
lativ
e im
por-
tanc
e of
the
outc
omes
to b
e co
llect
ed (e
.g. s
urro
gate
ver
sus
patie
nt re
leva
nt o
utco
mes
)6
Dea
ling
with
dat
a co
llect
ion
and
mon
itorin
gD
ata
colle
ctio
n is
bas
ed o
n ro
utin
ely
colle
cted
dat
a fro
m
elec
troni
c so
urce
s (e.
g., e
lect
roni
c he
alth
reco
rds)
Feas
ibili
ty o
f the
dat
a co
llect
ion
burd
en is
dis
cuss
ed a
nd
agre
ed a
mon
g al
l act
ors i
nvol
ved
at th
e be
ginn
ing
of th
e sc
hem
eTh
ere
is in
tero
pera
bilit
y of
dat
a ac
ross
dat
a so
urce
s and
re
sear
ch c
entre
s/pr
ovid
ers
Con
tinuo
us fo
llow
-up
is d
one
to c
heck
the
qual
ity a
nd
valid
ity o
f dat
a su
bmitt
ed a
nd to
ens
ure
mea
ning
ful d
ata
is
bein
g co
llect
ed
Ther
e is
less
ava
ilabi
lity
of ro
utin
ely
colle
cted
out
com
es d
ata
for d
evic
es c
ompa
red
to p
harm
aceu
tical
sU
ncer
tain
ties o
n de
vice
s may
requ
ire th
e co
llect
ion
of lo
ng-
term
out
com
e da
ta, i
ncom
patib
le w
ith th
e le
ngth
of t
he
sche
me
Hav
ing
to d
eal w
ith m
any
low
-vol
ume
cent
res w
ith d
iffer
ent
expe
rienc
e m
ay a
ffect
dat
a qu
ality
, and
incr
ease
the
colle
c-tio
n eff
ort
Hos
pita
ls/p
artic
ipat
ing
cent
res m
ay la
ck in
cent
ives
to p
rovi
de
timel
y an
d hi
gh q
ualit
y da
ta if
they
do
not r
ecei
ve sp
ecifi
c fu
ndin
g fo
r thi
s tas
kRe
crui
tmen
t may
be
slow
er th
an e
xpec
ted
affec
ting
the
time
whe
n th
e sc
hem
e re
ports
its r
esul
ts7
Dea
ling
with
dat
a an
alys
isA
n in
depe
nden
t res
earc
h bo
dy is
app
oint
ed fo
r dat
a an
alys
is,
incl
udin
g qu
ality
and
risk
of b
ias a
sses
smen
tTh
ere
is a
n es
tabl
ishe
d ex
perie
nce
with
dat
a an
alys
is
Diffi
cult
to fi
nd a
dequ
ate
cont
rols
with
obs
erva
tiona
l stu
dies
Get
ting
the
anal
ysis
don
e an
d tim
ely
deliv
ered
may
be
diffi
cult
if no
add
ition
al fu
nds a
re p
rovi
ded
for t
his t
ask
8Ex
-ant
e de
finiti
on o
f dec
isio
n ru
le, b
ased
on
poss
ible
out
-co
mes
of t
he sc
hem
eSc
hem
es a
re o
nly
abou
t col
lect
ion
of n
ew d
ata
Dec
isio
n ru
les,
incl
udin
g sto
ppin
g ru
les d
urin
g th
e sc
hem
es,
and
man
agem
ent o
f spe
cific
cas
es a
t the
end
of t
he d
ata
colle
ctio
n (e
.g.,
insu
ffici
ent q
ualit
y of
dat
a, te
chno
logy
not
eff
ectiv
e) a
re d
efine
d in
a c
ontra
ct a
gree
d am
ong
all p
artie
s in
volv
ed
Fixe
d de
cisi
on ru
les a
t the
ons
et m
ay b
e aff
ecte
d by
unf
ore-
seen
cha
nges
in th
e de
vice
s or m
arke
t dyn
amic
s
9Re
achi
ng a
n ag
reem
ent o
n pr
ice,
reim
burs
emen
t or u
se o
f th
e de
vice
at t
he e
nd o
f the
sche
me
At t
he e
nd o
f the
sche
me,
tech
nolo
gies
are
re-e
valu
ated
ac
cord
ing
to b
usin
ess a
s usu
al e
valu
atio
n pr
oced
ures
The
sche
me
may
not
hav
e co
llect
ed th
e pl
anne
d da
ta b
y th
e tim
e of
the
reas
sess
men
t, or
dat
a m
ay b
e un
-con
clus
ory
Rele
vant
diff
eren
ces i
n (c
ost)
effec
tiven
ess l
ess c
lear
am
ong
sim
ilar d
evic
es c
ompa
red
to p
harm
aceu
tical
s10
With
draw
ing
a de
vice
from
the
mar
ket w
hen
evid
ence
indi
-ca
tes t
he d
evic
e is
not
(cos
t-) e
ffect
ive
An
exit
strat
egy
in c
ase
the
tech
nolo
gy is
not
(cos
t) eff
ectiv
e is
defi
ned
at th
e on
set i
n a
cont
ract
agr
eed
betw
een
all
stak
ehol
ders
invo
lved
Hav
ing
a w
ell-d
esig
ned
sche
me
whi
ch p
rodu
ces s
cien
tifi-
cally
robu
st re
sults
Patie
nts a
nd m
anuf
actu
rers
may
cha
lleng
e th
e w
ithdr
awal
de
cisi
on a
nd ta
ke a
ctio
ns a
gain
st it
The
man
agem
ent o
f exp
lant
s for
impl
anta
ble
devi
ces i
n ca
se
the
study
out
lines
safe
ty is
sues
is c
ompl
ex
1269Coverage with evidence development schemes for medical devices in Europe: characteristics…
1 3
Tabl
e 5
(con
tinue
d)
Cha
lleng
eFa
ctor
s with
pos
itive
influ
ence
Fact
ors w
ith n
egat
ive
influ
ence
11O
btai
ning
agr
eem
ents
abo
ut th
e du
ratio
n of
the
sche
me
and
the
stopp
ing
rule
The
dura
tion
of th
e sc
hem
e is
agr
eed
base
d on
the
time
that
is
nee
ded
to c
olle
ct th
e re
quire
d da
ta a
nd th
e ch
arac
teris
-tic
s of t
he d
isea
se/te
chno
logy
Con
tinua
tion
of th
e sc
hem
e is
link
ed to
per
iodi
c m
onito
ring
on it
s pro
gres
ses
Ado
ptin
g th
e sto
ppin
g ru
les d
efine
d at
the
onse
t of t
he sc
hem
e m
ay b
e di
fficu
lt w
hen
the
sche
me
is o
ngoi
ngTh
ere
is a
tens
ion
betw
een
the
shor
t life
-cyc
le o
f dev
ices
and
th
e ne
ed fo
r lon
g-te
rm o
utco
mes
Diff
eren
t per
spec
tives
am
ong
invo
lved
stak
ehol
ders
(e.g
. clin
i-ci
ans,
man
ufac
ture
rs, N
HS
and
HTA
bod
ies)
Slow
recr
uitin
g m
ay im
pact
on
the
time
whe
n th
e stu
dy
repo
rts it
s res
ults
12A
dapt
ing
the
sche
me
to a
ccou
nt fo
r pro
duct
mod
ifica
tions
or
a le
arni
ng c
urve
The
time
fram
e of
the
sche
me
is re
lativ
ely
shor
t to
avoi
d pr
oduc
t mod
ifica
tions
Con
side
ratio
ns o
n th
e el
igib
ility
of a
dev
ice
to a
sche
me
also
con
side
r if n
ewer
gen
erat
ions
of t
he sa
me
devi
ces a
re
expe
cted
in th
e sh
ort-t
erm
The
com
pany
shar
es in
adv
ance
avai
labl
e in
form
atio
n on
po
tent
ial e
volu
tions
of t
he d
evic
e an
d th
ese
are
cons
ider
ed
whe
n di
scus
sing
the
study
pro
toco
lD
ata
on th
e eff
ect o
f the
lear
ning
cur
ve is
pub
licly
avai
labl
e
Ther
e is
littl
e po
licy
expe
rienc
e w
ith h
ow to
dea
l with
pro
duct
m
odifi
catio
ns a
nd/o
r lea
rnin
g cu
rves
Inte
rpre
tatio
n of
resu
lts a
re c
onfo
unde
d by
pro
duct
mod
ifica
-tio
ns th
at o
ccur
dur
ing
the
time-
fram
e of
the
study
Exist
ence
of a
lear
ning
cur
ve m
ay c
ompl
icat
e th
e se
lect
ion
proc
ess o
f par
ticip
atin
g ce
ntre
s in
the
sche
me
13D
ealin
g w
ith th
e m
arke
t ent
ry o
f sim
ilar d
evic
esSc
hem
es e
valu
ate
the
clas
s of d
evic
es o
r the
pro
cedu
re, n
ot
indi
vidu
al d
evic
esA
sche
me
can
invo
lve
mul
tiple
dev
ices
from
diff
eren
t man
u-fa
ctur
ers
Sche
mes
are
not
com
para
tive
in n
atur
e. A
ny si
mila
r pro
duct
en
terin
g th
e m
arke
t may
be
requ
este
d to
pro
vide
add
ition
al
data
or n
ot b
ased
on
thei
r lev
el o
f evi
denc
eM
anuf
actu
rers
of s
imila
r dev
ices
ent
erin
g th
e m
arke
t afte
r sc
hem
e is
initi
ated
may
be
requ
ired
to p
rovi
de d
ata
to th
e sa
me
natio
nally
-wid
e re
gistr
y
Iden
tifyi
ng si
mila
r dev
ices
ent
erin
g th
e m
arke
t is h
ampe
red
by th
e di
fficu
lty to
do
horiz
on sc
anni
ng fo
r dev
ices
Mor
e ra
pid
chan
ges i
n cl
inic
al p
ract
ice
with
dev
ices
com
pare
d to
pha
rmac
eutic
als
Incl
usio
n of
a n
ew d
evic
e en
terin
g th
e m
arke
t whe
n th
e sc
hem
e is
ong
oing
may
be
mor
e di
fficu
lt th
an in
clud
ing
it fro
m th
e be
ginn
ing
CED
cov
erag
e w
ith e
vide
nce
deve
lopm
en
1270 C. Federici et al.
1 3
Finally, with respect to the existence of a learning curve, interviewees acknowledged it as a challenge which affects both the collection and analysis of data, as well as the design of the study, such as deciding on the number of clinical cen-tres authorized to use the device as part of the scheme. How-ever, direct experience with this aspect was generally limited across all respondents.
Discussion
CED schemes and their application to medical devices are important items on the policy and research agendas. The objectives of this research were to explore the characteris-tics and use of CED schemes for devices in Europe, as well as the challenges that decision-makers face when designing and operating these schemes. Our study importantly adds to the existing knowledge base by providing a comprehensive and multi-country overview, which was directly informed by surveys with European decision/makers.
We found that 78 device-related CED schemes have been operated over the last 5 years in European countries. How-ever, only seven countries had CED programmes in place for medical devices. To a large extent, this result may reflect the uneven application of HTA within Europe, since it may be difficult to develop a policy for CED schemes without having an established HTA capacity. For example, deciding that more data are required post-launch implies that some form of assessment of clinical or cost-effectiveness has been made. Nevertheless, HTA capacity cannot fully explain these differences, since CED schemes seem to be less frequently used for devices than for drugs [15].
The characteristics of the identified CED programmes underpinning the individual schemes for devices varied between countries, which may reflect local differences in how HTA is organised and practised. For example, schemes were either initiated by the authorities (i.e., Ministry of Health), often as a consequence of the findings of an HTA for the technology, or as a response to a request from a man-ufacturer. We found similar patterns in the relative respon-sibilities for the funding of schemes and the design of study protocols although the authorities always played some role in study design, either by outlining a general specification or recommending that an independent research centre be involved. These differences in roles were also found in the aspects of the implementation of schemes, including the collection and analysis of data, which was sometimes the responsibility of the manufacturer and sometimes an inde-pendent party.
One aspect that deserves attention is how devices are selected for a scheme. Indeed, CED is not a costless activ-ity and its (opportunity) costs and benefits should be con-sidered alongside other policy options, such as adopting
or refusing adoption of the technology, based on currently available data, or negotiating a lower price. Aspects to be considered should include: 1) the expected value of research option(s) in terms of reduced uncertainty; 2) the direct costs of collecting evidence; 3) the opportunity costs of any delay in providing access to the technology because of the scheme; and 4) the existence of any irreversibility in the process (e.g. difficulty to subsequently withdrawal the technology, or difficulty to conduct further research after conditional approval) [1, 13]. However, while all the identified programmes used criteria to identify and pri-oritize technologies for a scheme, a formal assessment of these aspects was generally missing. Related to the previ-ous point. In many jurisdictions, there does not seem to be an option for choosing among different types of CED schemes, such as OWR and OIR schemes. Nonetheless, also depending on characteristics that are specific to, or particularly relevant for devices (e.g., the existence of irreversible upfront investment costs), there may be cases where either one or the other type of CED scheme would be optimal [13, 18]. As reported in the recent report from the ISPOR good practice Task Force, Value of Information (VOI) analysis may be used to support formal assessments on the opportunity to initiate a CED scheme and the type of scheme which maximizes optimal allocation of health-care and research funds [19].
In addition, one general finding across all countries was that relatively little attention seemed to be paid to the evalu-ation of schemes, both in itinere during data collection and at the time of the reassessment of the technology once the scheme reported its results. This mirrors the findings of other studies of CED and market access schemes more generally [1, 20, 21] and is obviously an area that requires further attention by policy makers and researchers. Indeed, issues with the quality and timely reporting of data have been mentioned as a factor hampering CED schemes (see e.g., Table 5). For example, in France, where manufacturers are solely responsible for the collection of additional data, the lack of the requested evidence from post-registration studies was often reported in the technology re-appraisals.
The policy responses at the end of a CED scheme for devices may be more complicated than, for example, decid-ing on whether to include a drug on a formulary or to deter-mine prescribing guidelines, since the reimbursement of devices, and the policies to determine their use, are often linked to the use of broader surgical, or other treatment, interventions. Therefore, policies probably involve adjust-ments to DRG tariffs, or changes to clinical guidelines, and/or hospital practice more generally. Hence, decision rules and policies for discontinuing the use of devices require attention in this context.
Notably, all participants reported to have no or little expe-rience with refusing to confirm reimbursement at the end
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of the schemes. While this may reflect the degree and type of uncertainties existing at the beginning of the schemes, it may also signal a certain difficulty in reversing the prelimi-nary reimbursement decision once a technology has entered a scheme [17, 22, 23]. This aspect may be even more rel-evant if no ex-ante criteria for evaluating the schemes were defined, as was the case for almost all schemes for devices in Europe.
Based on our observations of variation in the characteris-tics of schemes, it is difficult to prescribe a single preferred approach to CED of devices in Europe. Each country has specific local differences in HTA practices, although knowl-edge on how CED schemes have been used elsewhere can be used to develop local guidance. However, ideally a primary driver of the initiation of CED schemes would be the out-come of HTAs for the technologies concerned, since this can help identify the uncertainties in (cost-) effectiveness that (in principle) could be resolved through CED.
The participants’ perceptions of the various challenges in initiating, designing, implementing, and evaluating CED schemes were varied and did not indicate that, in general, some challenges were substantially more important than oth-ers. The reasons for this are unclear, although in some cases the participant’s perception of a given challenge reflected local circumstances. For example, funding was not perceived as a major challenge in settings where public funding was made available, but a major challenge in settings where it was not. In addition, the scores obtained for those challenges that were ‘device specific’ did not differ substantially from those for the other, more generic challenges. While this aspect requires further investigation, our general impression was that some of the low scores given for ‘device specific’ challenges are attributable to a lack of direct experience with addressing these issues, given that the use of CED schemes for medical devices in some European countries is generally quite recent. For example, it has been argued that manufac-turers may be reluctant to engage in a scheme and generate new evidence if other competitors entering the market with fast-follower products could also benefit from it [24]. So, one option would be to require that each manufacturer generates the same clinical evidence as for devices already on the mar-ket, unless there is compelling evidence of ‘equivalence’ for the new device [24, 25]. However, this option risks a waste of (public) resources in conducting clinical studies that are not strictly necessary. Moreover, the consequences of such a strategy in terms of competitiveness, market prices and eventually access of potentially valuable devices to patients remain largely unexplored.
We observed that the scores for the challenges were lower for respondents in countries where there was direct experi-ence in CED for devices, as compared with those having experience with CED for drugs only. However, although the numerical differences in the scores were substantial, the
small sample size means that no firm conclusions can be drawn. This could be explored in further research by com-paring decision-makers’ perceptions before and after oper-ating CED schemes and relating these perceptions to the general (HTA) infrastructure in a country.
We used a combination of methods to obtain insights in the use of and challenges related to CED schemes in the relatively understudied context of devices, including a large set of European countries. The insights obtained allow learning from experiences across countries and increase the chances of having successful CED schemes in the future, by highlighting how decision makers perceive and deal with specific challenges. Nonetheless, some limitations also need highlighting. First, although we studied experiences in many European countries, we cannot be sure that our overview is complete as some countries were not included in the study. Moreover, although in each country we interviewed the per-son we considered to be most knowledgeable about CED schemes, we cannot be sure that the views of the participants are representative of the views of decision-makers more generally. Additionally, we focussed on the detailed percep-tions of decision-makers, with a focus on HTA agencies at the national or regional level and (some) national payers because recent research suggests that decision-makers may be hesitant to engage in CED schemes [5]. This makes them not only a relevant source for the current study in terms of knowledge, but also in articulating (potential) challenges and difficulties with applying such schemes. Future studies could nonetheless supplement this with information on the perceptions of other stakeholders, such as clinical profes-sionals, patient organisations, local payers/decision mak-ers, and manufacturers. Finally, our focus was on schemes initiated at the national or regional level. In addition, some schemes involving devices may be negotiated at the local level directly between providers and manufacturers. Many of these may be ‘pay for performance’ schemes, but some could be characterized as CED schemes. These schemes were out-side the scope of our current study, but their characteristics and performance are nonetheless important to investigate further.
Conclusions
CED schemes for medical devices offer a promising tool to increase value for money in health care. While they are cur-rently used in Europe, this study has shown experience with these schemes to be limited to a relatively small number of countries. Moreover, considerable variation exists between countries in how schemes are initiated, designed, imple-mented, and evaluated.
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While the identified challenges in using CED schemes were perceived differently, none of them was unanimously considered insignificant. Hence, all challenges should be considered when initiating CED schemes in a given coun-try. Our recommendation is that each jurisdiction embarking on CED schemes for devices should undertake its own ‘risk assessment’, using our list of challenges as a starting point, and considering for each of them the factors that decision-makers in this study outlined as having either a positive or negative influence. If a given challenge is considered to be important locally, the highlighted experiences of other countries in this study can help in addressing or overcoming them. That way, this study directly contributes to making CED schemes for devices a more effective policy option in the future.
Supplementary Information The online version contains supplemen-tary material available at https:// doi. org/ 10. 1007/ s10198- 021- 01334-9.
Acknowledgements The authors thank all COMED project members, and particularly the project leader Aleksandra Torbica, for their helpful comments on an earlier version of this paper. The authors also want to thank the participants to the survey for their thoughtful answers dur-ing the interview and their continuous support following any further request for clarification and/or validation.
Author contribution Conceptualization: CF, VR-D, WB, MD; Meth-odology: CF, VR-D; Formal analysis and investigation: CF; Writing—original draft preparation: FC, VR-D, MD; Writing—review and edit-ing: OC, FD, BG, ZK, SK, KS, WB, MD; Supervision: WB, MD.
Funding Open access funding provided by Università Commerciale Luigi Bocconi within the CRUI-CARE Agreement. This study has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 779306 for the project “Pushing the boundaries of cost and outcome analysis of medi-cal technologies—COMED”.
Availability of data and material The full database with information on the 78 CED schemes collected is provided in Online Resource 4.
Declarations
Conflict of interest The authors have no relevant financial or non-fi-nancial interests to disclose.
Ethics approval This study is part of the EU Horizon 2020 COMED project that has been reviewed and approved by the Bocconi Univer-sity Ethics Committee (protocol number: 0068538, approved on May 8, 2018).
Open Access This article is licensed under a Creative Commons Attri-bution 4.0 International License, which permits use, sharing, adapta-tion, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in
the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/.
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