EuroScan Newsletter Web: http://www.euroscan.org.uk December 2012 Number 13

A note from the editor

Early awareness and alert activities

Welcome to issue 13 of the

EuroScan newsletter. In this

bumper issue you can read about

the work of eight EuroScan

member agencies, with articles

on emerging health technologies;

methods employed by agencies

and their networks; an evaluation

of an early awareness and alert

system; and research utilizing the

EuroScan database of emerging

technologies. There is also an

overview of the views of other

organisations on recent important

technological developments and

predictions for 2013.

This issue, we have invited

organisations who Euroscan has

a MoU with or collaborates with

to contribute to the newsletter.

The WHO has recently put out a

call to encourage the

development of innovative

technologies for use in low

resource settings, HTAi is

getting ready for its annual

meeting which is in Seoul in

2013 and you can read about

the recently funded AdHopHTA

project.

In addition to the work of

individual agencies the EuroScan

network has been busy. In

2012, the EuroScan executive

committee and members have

finalised a work programme for

the next 3 years. This will be

published on the Euroscan

website early in 2013 but work

is already ongoing to improve

the exchange of information and

share skills and experiences in

Early Awareness and Alert

activities. The year ahead

promises to be very productive.

Sue Simpson EuroScan Newsletter Editor

EuroScan’s goals include

strengthening activities for the

development of methodological

approaches to the identification,

description and assessment of

emerging technologies; and

increasing the impact of EuroScan

International Network’s output.

So it was with great enthusiasm

and pleasure that a number of

members of EuroScan accepted

the opportunity to be associate

editors for an early awareness

and alert (EAA) themed section in

the International Journal

Technology Assessment in Health

Care.

The themed section was

published in the July 2012 edition

of the journal (Volume 28 /

Issue 03) and gave a great

opportunity to disseminate the

work of EuroScan member

agencies and others working in

the field. Articles featured

covered methods employed by

EuroScan member agencies;

implementation of an EAA; an

analysis of 10 years of EAA

activities; a description of EAA

activities in Latin America,

Canada and Israel; and the use

of best-worst scaling to help

predict impact of emerging

technologies. The editorial

allowed reflection on how EAA

methods and systems had

evolved over the last decade

(and more!) and the opportunity

to present some of the

methodological challenges that

may face EAA systems with the

advent of emerging health

technologies such as

regenerative medicines,

information and communication

technologies, and personalized

health care.

EuroScan International Network

will continue to collaborate to

share and develop appropriate

methods that address the

challenges created by an ever

changing health care sector and

though our website, conference

presence and this newsletter will

share the work of the network.

In this edition

Member Profile:

Institut national

d’excellence en santé et

en services sociaux

(INESSS)

Horizon Scanning

Second Generation

Transcatheter Aortic

Valve Replacement

(TAVR) Devices

Personalised therapies

and in vitro companion

diagnostic tests for

melanoma

Methods and Evaluation

Impact evaluation of

“Horizon Scanning in

Oncology”

Providing evidence and

recommendations to

renew the benefit

package of the Basque

Health System

Evolution of the Italian

EAA system through

the RIHTA network

Horizon scanning and

burden of disease:

Does innovation in

healthcare reflect

need?

Collaboration

HTAi

WHO Call for

Innovative

Technologies

AdHopHTA

2 EUROSCAN NEWSLETTER

Member Profile: INESSS

Institut national d’excellence en santé et services sociaux Pierre Dagenais, directeur du Soutien à la qualité et à la méthode, INESSS

Since its creation, in January 2011,

the Institut national d’excellence en

santé et en services sociaux

(INESSS), a para-governmental

organization for the Province of

Québec in Canada, has been in

charge of assessing a wide range of

health technologies including drugs

and medical devices, as well as

health services and social care

delivery systems. The Institute has

also the mandate to develop

guidelines for clinical and social care

practices and to guide the optimal

use of specific technologies such as

drugs and devices.

INESSS mission is to promote

clinical excellence and efficient use

of resources in the health and social

care sectors by supporting decision

making at every level in the system.

For each technology, it may assess

various dimensions according to

decision needs including; efficacy,

effectiveness, safety, efficiency and

costs, organizational, professional,

psychosocial, ethical and legal

aspects. Based on systematic

reviews and contextual information

from stakeholders, including health

and social care professionals,

managers as well as patients and

beneficiaries, it usually issues

recommendations for adoption, use

and coverage of the technologies by

the public system. In order to

ensure that our products are up to

date, the Institute has implemented

an environmental scanning

procedure for detecting

information that could change our

recommendations and guidelines.

In regards to horizon scanning,

INESSS is a member of CNESH,

the first Canadian collaboration

dedicated to identifying new and

emerging technologies. Mainly,

our organization is involved in

horizon scanning on assistive

devices for physical disabilities.

This early awareness and alert

activity was requested by the

Ministry of Health and Social

Services for improving its

awareness of emerging

technologies in the pipeline that

may have an impact for patients

and the system in terms of

disability management, efficacy

and costs.

A provincial steering committee

consisting of the Ministry of

Health and Social Services,

INESSS, a Laval University

affiliated rehabilitation institute

(IRDPQ, Institut de réadaptation

en deficiencies physiques de

Québec), the Association of

Québec physical rehabilitation

centers (AERDPQ) and the

Health Insurance Board (RAMQ)

was set up 6 months ago. It’s

remit is to establish technological

priorities for a pilot horizon

scanning project that will be

chosen from four categories of

assistive devices: mobility,

hearing, communication and

visual aids. IRDPQ will be in

charge of the horizon scanning

activities in collaboration with

INESSS, which will finance and

coordinate these activities, as

well as provide methodological

support for horizon scanning and

knowledge translation strategies.

The EuroScan International

Network welcomed INESSS to be

a member of the collaboration in

August 2012. It is anticipated

that EuroScan membership will

contribute to the general

development of Horizon

Scanning at INESSS and enable

INESSS to contribute specific

information on Horizon Scanning

for Assistive Devices to

EuroScan.

DECEMBER 2012 3

Second Generation Transcatheter Aortic Valve Replacement (TAVR) Devices Andra Morrison, CADTH

Aortic stenosis (AS) occurs when

there is the narrowing of the

aortic valve opening. Prognosis in

the absence of treatment is poor;

most patients will die within five

years. Up until recently, surgical

aortic valve replacement was the

only treatment for severe aortic

stenosis (SAS) other than medical

therapy with drugs. However,

transcatheter aortic valve

replacement (TAVR) has emerged

as a potential alternative

treatment for some patients with

SAS. Current TAVR devices are

used on SAS patients who are

inoperable or at high surgical risk,

a population that represents

approximately 10% of patients

with SAS. Second generation

TAVR devices may expand the

existing SAS population to

younger and healthier patients.

There are at least eight

transcatheter aortic valves in

clinical development that are

intended to address challenges

associated with first generation

devices:

EngagerTM(Medtronic): In

September 2011, Medtronic

announced the start of a

European non-randomized single

arm trial to pursue a CE Mark for

EngagerTM. The trial will evaluate

the safety and clinical

performance of the valve in high

risk SAS patients.

Acurate TATM(Symetis): CE Mark

approval was received in September

2011, and the transapical valve was

commercial launched in October

2011. A post market surveillance

study for its continued safety

monitoring is currently enrolling

patients. Symetis is also expected

to start a study of its transfemoral

system the Acurate TFTM by the end

of 2012.

Direct Flow Medical Aortic Valve

(Direct Flow Medical): A European

CE Mark safety and performance

trial is expected to be completed by

the end of 2012.

Sadra Medical Lotus TM (Boston

Scientific): A prospective single arm

safety and performance study,

REPRISE I, in patients with SAS was

initiated in 2012. Enrollment in

REPRISE II is anticipated next year.

Portico THV TM (St Jude Medical): A

2011 study evaluated the technical

feasibility, safety and device

deployment characteristics of this

valve in high risk SAS patients. A

multicenter observational cohort

study is currently recruiting patients

for the investigation of the safety

and effectiveness of the valve in

patients at high surgical risk.

JenaValveTM (JenaValve): CE Mark

approval was received in September

2011. The CE Mark pivotal study

was a multicentre, prospective,

single-arm study of 67 patients who

were at high risk for surgery. A new

observational cohort study is

currently recruiting patients with

SAS at increased risk of surgery

for the evaluation of the long

term performance and safety of

JenaValve.

SAPIEN 3 and CENTERA

(Edwards Lifescience): Edwards

has conducted two first-in-

human trials for these two

second generation valves. Both

are investigational devices that

are not yet commercially

available in any country.

Vitality™ and Vanguard™:

(ValvXchange): ValvXchanage

completed first-in-man clinical

studies in 2011 for its valve, and

will be pursuing clinical trials in

Europe in 2012. ValveXchange is

also developing the Vanguard™

series of valves for non-surgical

patients.

Heart Leaflet Technology valve

(Bracco Diagnostic): In 2008, a

non-randomized single arm

study was initiated to confirm

whether the dimensions of the

Heart Leaflet valve are

appropriate for patients with

aortic stenosis.

CADTH are producing an

environmental scan on TAVR.

Environmental Scans are short

reports on current or emerging

issues in health care

technology. Each report

provides information to support

health care decision-making

and policy development in

Canada.

http://www.cadth.ca/en/produc

ts/environmental-

scanning/environmental-scans

4 EUROSCAN NEWSLETTER

Impact evaluation of “Horizon Scanning in Oncology” Anna Nachtnebel, LBI-HTA, Austria

Since 2009, “Horizon Scanning

in Oncology” (HSO) is a

permanent work programme at

the Austrian Ludwig Boltzmann

Institute for Health Technology

Assessment. This programme

was set up to inform decision-

makers, foremost hospital-

based decision-makers, on

emerging and new oncologic

drugs. The underlying rationale

was to facilitate the evidence-

based use of new oncologic

drugs but also to foster the

estimation of the financial

impact on hospital budgets.

Since its implementation, 33

reports and 3 updates have

been published and were

distributed by different means.

Besides e-mail notifications via

a mailing-list for HTA-interested

persons in general, e-mail

alerts are also specifically sent

to decision-makers at Austrian

hospitals (e.g. head of

pharmacies, medical directors)

with oncologic wards as soon

as new reports are published

on the LBI’s homepage.

Furthermore, all reports are

entered to the EuroScan

database, they are freely

available on our institute’s

homepage, and short

summaries of the reports are

irregularly published in our

newsletter.

Despite these various

dissemination methods, it

remained unclear whether

reports had been used at all

and if, for what purposes.

Given that considerable

resources, mostly in terms of

staff, are dedicated to the HSO

programme, the question arose

whether pursuing this

programme line proofed

worthwhile. Thus, an impact

analysis consisting of a

download analysis and an

online-questionnaire was

conducted.

The download analysis yielded

that HSO reports had been

viewed about 14,000 times

(from October 2009 – February

2012) and had been

downloaded about 7,000 times.

Huge differences exist between

individual reports as, for

example, the most popular

report (bendamustine for non-

Hodgkin’s lymphoma , chronic

lymphocytic leukaemia and

multiple myeloma) had been

downloaded approximately 900

times, whereas axitinib for

renal cell carcinoma ranged

with only 37 downloads at the

other side of the spectrum.

However, these numbers have

to be interpreted against the

background that the temporal

availability of reports differed

substantially; bendamustine

had been online for about two

years and axitinib had been

published only one month

prior to the download

analysis. Besides overall

downloads, the average

monthly download rates per

year were calculated. Starting

with an average of 11

downloads per month in 2009,

this number increased to 40 in

2012. Despite this trend, one

has to bear in mind that also

the number of published

reports rose from 7 in 2009 to

24 in 2012. Thus, the sheer

availability of an ever

increasing number of reports

has definitely contributed to

this gain.

“According to the download

rates and the satisfaction of

the primary target audience,

continuation of our HSO

programme is justified”

Table 1: Satisfaction with HSO reports

completely satisfied

satisfied fairly satisfied

somewhat dissatisfied

very dissatisfied

not able to judge

structure of the

reports44% 50% - 6% - -

breadth of the reports

59% 35% 6% - - -

quality of the reports

50% 50% - - - -

timing of the publication

47% 35% 18% - - -

type of notification

56% 39% - - - 6%

DECEMBER 2012 5

To investigate whether the

actual target audience of the

HSO programme used the

reports and how quality and

content was perceived, an

online questionnaire was sent to

those Austrian decision-makers

who also receive the e-mail

notifications on new reports -

approximately 120 individuals.

Despite repeated reminders, the

response rate did not exceed

30% with the majority of

respondents being pharmacists.

Interestingly, only a little over

50% knew the programme.

Nonetheless, respondents were

overall satisfied with the quality,

structure and depth of

information provided within the

reports (see table 1). Only with

the timing of the reports, about

20% were “fairly satisfied” but

it is unclear whether earlier or

later reports, for example closer

to actual reimbursement

decisions, would have been

appreciated. When questioned

about the usage of the reports,

most respondents valued them

as an information source rather

than as decision documents (see

figure 1). However, this may be

a result of the rather low

response rate as well as of the

fact that survey participants

came mainly from the same

professional background.

According to the download rates

and the satisfaction of the

primary target audience,

continuation of our HSO

programme is justified.

Nonetheless, several issues

remain unresolved. For one, it is

unclear who the actual users of

our reports are, because the

download analysis did not allow

identification of the users’

professional backgrounds. Also

the international impact, for

example usage within the

EuroScan database, is unknown.

Lastly but foremost, whether

HSO reports are used for those

purposes set out in the

programme’s objectives is,

due to the low survey

response rates, uncertain.

However, based on this

impact analysis a couple of

actions arose. Besides

improved methods for a more

detailed analysis of the usage,

efforts for further increasing

the awareness of the HSO

programme are clearly

needed. In addition, adaption

of the underlying processes as

well as of the outputs of our

horizon scanning project

might be in order to better

meet our target audience’s

needs. Out of a broader

scientific perspective and in

absence of commonly

accepted frameworks more

refined methods for fully

capturing the impact of policy-

oriented research activities

need to be developed.

Figure 1: Reasons for using HSO reports

6 EUROSCAN NEWSLETTER

Personalised therapies and in vitro companion diagnostic tests for melanoma C. Poggiani, D. Pase, R. Joppi – Italian Horizon Scanning Project

Background

In the oncology setting, the

need of drugs associated with a

lower incidence of side effects

together with a well-

demonstrated efficacy is

leading to an increased move

to develop personalised

therapies. These treatments

are directed to a specific

molecular target or mutation of

tumour cells that become a

predictor of therapy response.

In this context, molecular

diagnosis is fundamental to

select patients who are most

likely to respond to the

therapy, thus rendering it

necessary to co-develop with

each new personalised therapy,

for which a specific diagnostic

test does not already exist, the

matching companion in vitro

diagnostic test1.

Molecularly targeted assays are

usually specific for DNA

mutations, for expression of

transcripts or protein or to

determine functional properties

of molecular complexes. Two

early examples of companion

diagnostic tests are the HER2-

directed therapy in breast

cancer with trastuzumab and

EGFR-targeted therapy in

colorectal cancer with

cetuximab or panitumumab1.

Aim

This article will describe new

oncology personalised therapies

co-developed with related in

vitro companion diagnostic

tests for melanoma and will

evaluate regulatory aspects

concerning in vitro companion

diagnostic tests.

Method

Medical literature, websites of

early awareness and alert

systems, company websites

and regulatory agencies were

searched.

Results

Recently, in the EU2 and US3,

vemurafenib was approved with

its companion diagnostic test

for the treatment of BRAFV600-

positive metastatic melanoma.

Vemurafenib is a first-in-class

inhibitor of oncogenic BRAF

kinase and, according to

European guidelines, it is

considered an optimal first-line

choice for metastatic melanoma

in a subset of patients with

mutated BRAF4. In the pivotal

phase III trial, 675 patients

with untreated stage IIIc-IV

metastatic melanoma

presenting the BRAF V600E

mutation, as detected by the

companion cobas 4800 BRAF

V600 Mutation Test, were

treated with vemurafenib or

dacarbazine. Vemurafenib

significantly prolonged both

overall survival (value not reached

after a median follow-up of 6.21

months for vemurafenib vs. 7.89

months with dacarbazine,

p<0.0001) and progression-free

survival (5.3 vs. 1.6 months,

p<0.001)5.

Both US and EMA labels indicate

that before taking vemurafenib,

patients must have undergone a

molecular diagnosis with the

companion cobas 4800 BRAF

V600 Mutation Test. This test,

which is CE marked, was

designed to detect the

predominant BRAF V600E

mutation with high sensitivity

(down to 5% V600E sequence in

a background of wild-type

sequence from FFPE-derived

DNA) and it is used to assess the

BRAF mutation status of DNA

isolated from formalin-fixed,

paraffin-embedded (FFPE) tumour

tissue. The test was co-developed

with vemurafenib and it was used

to select patients eligible for

phase II and III trials at

designated laboratories in the US,

Europe and Australia2,3,6.

During vemurafenib’s

development program, the cobas

test was validated through

retrospective sequencing analyses

with the Sanger method. Four

hundred and sixty seven

specimens were positive with the

DECEMBER 2012 7

cobas test in non-clinical and

clinical studies. The BRAF V600-

mutation positive status was

further confirmed with “deep”

sequencing of 454 out of all

those selected specimens2,3.

Recently, two other BRAF-

targeted therapies are being

developed with companion tests,

the BRAF inhibitor dabrafenib

and the MEK kinase inhibitor

trametinib. In phase III studies,

both trametinib and dabrafenib

significantly prolonged

progression-free survival (PFS)

vs control (trametinib vs

paclitaxel or dacarbazine: 4.8 vs

1.5 months, p<0.0017;

dabrafenib vs dacarbazine: 5.1

vs 2.7 months, p<0.00018). In

parallel, in a phase I/II trial in

247 patients with metastatic

melanoma and BRAF V600

mutations, the combination

dabrafenib+trametinib

prolonged PFS vs dabrafenib

monotherapy (9.4 vs 5.8

months, p<0.001). For both

drugs a companion test for BRAF

mutation detection is being co-

developed and was used to

select patients in the phase III

trials. One of the secondary

objectives of both trials was the

validation of the tests9,10.

Clinical validation of companion

tests co-developed with

personalised therapies is

required for regulatory approval

by the FDA11. However, it is not

mandatory for CE marking12. On

the other hand, the validation

process in clinical setting is

recommended by the EMA. This

is in order to collect all the

information necessary to

describe the companion test in

both the assessment report

and in the summary of product

characteristics of the related

matching drug. This helps to

prepare for and facilitate the

transition of testing

methodology in post-approval

clinical use13.

Conclusions

BRAF-directed therapies are

new treatment options for a

subset of patients with

metastatic melanoma, for

which other specific treatments

do not exist4. The use and the

possible efficacy of these

therapies is strictly related to

the selection of patients with

mutated BRAF, as detected by

companion diagnostic tests.

Global definition and

harmonisation of regulatory

requirements for the co-

development of companion

tests with matching therapies

is necessary to introduce in

clinical practice rigorously

validated companion tests, that

are able to support the

appropriate utilisation of the

related personalised therapies.

References 1Zieba A et al. Molecular tools for companion diagnostics. N Biotechnol 29(6):634‐640 2http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002409/human_med_001544.jsp&mid=WC0b01ac058001d124. Accessed on 04/12/2012 3http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed on 04/12/2012 4Dummer R et al. Cutaneous 

melanoma: ESMO clinical practice guidelines for diagnosis, treatment and follow‐up. Annals of Oncology 23 (Supplement 7): vii86–vii91, 2012 5Chapman PB et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011, 364:2507‐2516 6Cheng S et al. Co‐development of a companion diagnostic for targeted cancer therapy. N Biotechnol 2012, 29(6):682‐688 7Flaherty KT et al. Improved survival with MEK inhibition in BRAF‐mutated melanoma. N Engl J Med 2012, 67:107‐114 8Hauschild A et al. Dabrafenib in BRAF‐mutated metastatic melanoma: a multicenter, open‐label, phase 3 randomised controlled trial. Lancet 2012, 380:358‐365 9Protocol for: Flaherty KT, Robert C, Hersey P, et al. Improved survival with MEK inhibition in BRAF‐mutated melanoma. N Engl J Med 2012;367:107‐14. DOI: 10.1056/NEJMoa1203421. 10Supplement to: Hauschild A, Grob 

J‐J, Demidov LV, et al. Dabrafenib in BRAF‐mutated metastatic melanoma: a multicentre, open‐label, phase 3 randomised controlled trial. Lancet 2012; published online June 25. http://dx.doi.org/10.1016/S0140‐6736(12)60868‐X. 11http://www.fda.gov/medicaldevic

es/deviceregulationandguidance/guidancedocuments/ucm262292.htm. Accessed on 04/12/2012 12http://ec.europa.eu/enterprise/p

olicies/european‐standards/harmonised‐standards/iv‐diagnostic‐medical‐devices/index_en.htm. Accessed on 04/12/2012 13Refelection paper on co‐

development of pharmacogenomic biomarkers and assays in the context of drug development. EMA/CHMP/641298/2008, 24/06/2010 

The Italian Horizon Scanning

Centre (IHSP) is an Early

Warning System for

identification and assessment of

emerging medicines and medical

devices with medicated coating.

http://horizon.cineca.it/

 

8 EUROSCAN NEWSLETTER

Providing evidence and recommendations to renew the benefit package of the Basque Health System Iñaki Gutiérrez-Ibarluzea, Gaizka Benguria-Arrate, Rosa Rico-Iturrioz and Marta López de Argumedo Osteba, Basque Office for HTA. Department of Health and Consumer Affairs. Basque Government.

One of the main goals of Early

Awareness and Alert Systems is to

improve the implementation /

diffusion processes of new and

emerging technologies by providing

evidence and recommendations to

decision-makers at the different

levels of decision. Osteba started its

early awareness and alert system

(EAAS) 14 years ago when it was

invited to a meeting where

EuroScan was founded. Since then,

Osteba has updated its methods

including the concept of Life cycle of

Health Technologies that led to the

analysis of not only new but low-

added value technologies.

Osteba has recently started a new

initiative to improve its impact in the

benefit basket or package of the

Basque Health System. To this end,

a new unit has been created called

the Comparative Effectiveness Unit,

Osteba-EKU. EKU is an advice or

consultation body that aims to

provide information on both

emerging and low added-value

health technologies. The aim is to

include in the benefit package of

health services, those technologies

with maximum benefit for health to

make better use of available

resources.

EKU has started a process this year

to identify technologies that could

be included or delisted in the benefit

package. The project started with a

transparent identification process

followed by a prioritisation

scheme that resulted in the final

list. The following sources were

used to identify technologies:

GenTecS, EuroScan, Cochrane,

INAHTA, NICE, ECRI and

Cleveland Clinic Databases for

new and emerging technologies;

the Spanish National Guidelines

Clearing House and NICE

databases for low-added value

technologies. In terms of the

prioritisation process, we used

PriTec software coordinated by

the Galician HTA Agency Avalia-T

which is available at:

http://pritectools.es/index.php?idi

oma=en.

We identified 910 new and

emerging health technologies

initially that were reduced after

different cycles of prioritisation to

a total of 11. In the case of low

added value technologies, 375

technologies were identified and

finally 9 were included for the

assessment. This prioritisation

process was conducted by the

advisory board of EKU involving

clinicians, medical directors,

hospital managers, decision-

makers and health care service

managers.

Osteba-EKU is currently

conducting a process of

assessment that will provide

evidence, including an analysis of

variability of health care services

in the case of low-added value

technologies, and

recommendations and a plan for

the implementation of the

promising technologies in clinical

practice. Some preliminary

results are already available at

the Osteba webpage

http://www.osakidetza.euskadi.n

et/osteba .

Osteba has designed different

type of documents and diffusion

processes, tailoring them to the

needs of various stakeholders.

http://www.osakidetza.euskadi.n

et/r85-

pkoste13/en/contenidos/informa

cion/osteba_eku/en_osteba/oste

ba_eku.html

Further studies will be required

to analyse the impact of this

initiative in health services

provision and resources

allocation.

DECEMBER 2012 9

Evolution of the Italian EAA system through the RIHTA network

Antonio Migliore and Marina Cerbo, , Agenas, Italy

According to its core mission,

supporting Regional

Governments to establish,

improve and maintain HTA

activities, in 2009 Agenas

created RIHTA: the Italian

Network for HTA. RIHTA is a

collaborative network among

Regions and Regional

Healthcare Agencies aimed at

spreading the HTA/EAA culture

across Italy, promoting the

launch of new HTA/EAA

programmes and improving the

ones already running, and

facilitating collaboration among

Regions on common issues.

In 2012, Agenas focused on the

evolution of the EAA system

created within the research

project named COTE (concluded

in 2011) [1]. The new

framework, proposed by Agenas

and discussed with RIHTA

members, was aimed at

promoting a more active

participation of members in EAA

activities. The agreed workflow

was then tested in real-life.

The new features are related to

the prioritisation and

assessment phases. As the EAA

became a regular Agenas

activity (reports are not

committed anymore by the

Ministry of Health but produced

with Agenas’s own budget) the

prioritisation is carried out by

RIHTA members. Every 2

months all the members receive

a list of the new and emerging

technologies that have been

identified and are asked to

prioritise 3 technologies of

interest. The criteria used for the

choice are internal to each Region

(a range of different methods,

qualitative/quantitative, has been

observed; see EuroScan

Newsletter n.12 [2]).

On the basis of the number of

preferences obtained by the single

technology, working groups are

defined to perform the

assessment. The multi-regional

teams are then coordinated by

Agenas.

The first assessment experience

with this new model was the

Agenas HS report n.10 [3]. Two

Regions were asked to collaborate:

Liguria (with one epidemiologist)

and Piemonte (one clinical

engineer and one librarian).

Logistically, e-mails and e-

meetings have been utilised

instead of face-to-face meetings to

avoid travel costs. Agenas

coordination work consisted of:

general project management,

interaction with external clinical

experts, interaction with

manufacturers, internal review,

translation of the final document

(from English to Italian), upload of

the document on the EuroScan

database and Agenas website.

The report was produced within

the expected deadline and

without relevant organisational

problems. Thanks to the internal

review by Agenas experts and

extra support by the Agenas

coordinator, the final document

was produced according to the

previous quality standard. A new

assessment is ongoing.

SUGGESTED READING

[1] Migliore A, Perrini MR,

Jefferson T, Cerbo M.

Implementing a national early

awareness and alert system for

new and emerging health

technologies in Italy: the COTE

Project. Int J of Technol Assess

Health Care. 2012 Jul, 28(3):

321-326.

[2] Migliore A. “Prioritisation in

the Italian Regions”. EuroScan

Newsletter. June 2012 Issue 12.

http://euroscan.org.uk/mmlib/inc

ludes/sendfile.php?id=130

[3] Migliore A, Bonelli L, Giani E,

Romano V. Raman spectroscopy

for early detection of skin cancer.

Agenas, Agenzia nazionale per i

servizi sanitari regionali. Rome,

July 2012.

http://www.agenas.it/agenas_pdf/spectroscopy_english.pdf

10 EUROSCAN NEWSLETTER

Health Technology Assessment International (HTAi) Chris Sargent, Managing Director, HTAi

HTAi is a global society focused on

supporting those involved with and

practicing health technology

assessment in every part of the

world. HTAi Annual Meetings, held

in May-June each year, attract

thousands of researchers from

around the globe, with the most

recent meeting in Bilbao, Spain

providing an opportunity for

members to share the latest

thinking and cutting-edge

techniques in HTA.

HTAi’s up-coming Annual Meeting in

Seoul, in June 2013 offers a

thought-provoking agenda that

examines the balance between art

and science in the practice of HTA

and will bring together the brightest

minds in HTA from Asia and around

the world. The call for abstracts is

now out; more information can be

found on the HTAi website at

www.htai.org.

HTAi also continues to serve the

needs of its growing membership in

emerging markets in Asia and Latin

America and convenes the HTAi

Policy Forum. A clear example of

HTAi supporting its members is

HTAi’s second Latin America

regional meeting that took place in

early December in Bogota,

Colombia, which brought together

over 200 HTA experts from across

Latin America. The meeting focused

on topics ranging from good

practice principles for HTA agencies

to methodological challenges when

conducting HTA to looking at

managed entry schemes and

disinvestment. It was also an

exciting moment for HTA as this

meeting coincided with the

establishment of Colombia’s HTA

agency, IETS.

The continued growth and

success of HTAi in these regions

is one of Dr. Clifford Goodman’s

main area of focus on during his

tenure as President of the HTAi

Board. Dr. Goodman says, “as in

other parts of the world with a

range of rapidly evolving

economies, the need for HTA in

Latin America is driven by greater

health care demand of an

expanding middle class, rapidly

rising prevalence of chronic

disease, and ongoing

technological innovation and

marketing. Many decision makers,

including those at ministries of

health, hospitals, and private

insurers increasingly see the need

for making transparent, evidence-

based, and accountable policies

and guidelines. Although there is

great diversity in the roles,

resources, and maturity of HTA

programs in Latin America, they

are very involved in regional and

global HTA networks, and they

are making strong contributions

to advancing the field.”

HTAi will soon return to Spain for

its annual Policy Forum meeting

in Barcelona in February 2013.

The HTAi Policy Forum provides a

venue for senior leaders from the

not-for-profit and for-profit

sectors to discuss issues of

emerging global importance and

to share the findings of those

discussions with the wider HTA

community. This year’s topic is

HTA and Value, and discussions

will examine the various

dimensions of value, including

innovation, how these are

viewed and prioritised by

different stakeholders, and how

this information can best be

factored into decision making in

health care systems. A paper will

be published on the main

themes discussed at the meeting

in IJTAHC, HTAi’s peer-reviewed

journal. All papers of the HTAi

Policy Forum are available on

the HTAi website.

As a global society, HTAi

continues to ensure it stays the

course as a neutral forum for

diverse stakeholders engaging in

multidisciplinary, multi-sector

collaboration. This requires

remaining responsive to the

needs and priorities of our

individual and organizational

members across the globe. As

always, Dr. Clifford Goodman

and his colleagues on the HTAi

Board, look forward to continued

collaboration with EuroScan and

its members to support and

promote health technology

assessment.

EuroScan signed a Memorandum

of Understanding with HTAi in

June 2011.

DECEMBER 2012 11

Horizon scanning and burden of disease: Does innovation in healthcare reflect need? Orsolina Martino, NIHR-HSC

Studies that have used research

funding to estimate the amount of

innovation in healthcare have

raised concerns that some disease

areas are neglected despite

having a high burden on society.

A study carried out within the

NIHR Horizon Scanning Centre in

England used data from the

EuroScan network as a novel way

to measure innovation.1

Technologies reported on the

EuroScan database between 2000

and 2009 by 21 agencies were

compared with the burden of

related diseases among their

respective countries. 17 countries

were represented in all, but the

data were combined to give

figures for EuroScan as a whole.

Burden of disease was measured

as deaths and disability-adjusted

life years (DALYs), taken from the

WHO’s 2004 Global Burden of

Disease estimates.2 These were

grouped by 21 main disease

areas, which were split further

into 102 specific causes. Each

technology entered onto the

EuroScan database was given a

code so that it could be matched

to the relevant disease.

The results showed only a weak

relationship between technologies

reported by EuroScan members

and the burden of related

diseases. Most notably, there

was more innovation than

expected for cancer and less for

neuropsychiatric conditions.

Dividing the main groups into

specific diseases weakened the

association further, as illustrated

in Figure 1.

It was concluded that outputs

from horizon scanning activity do

not always reflect areas of the

greatest need, as factors other

than disease burden drive

innovation.

  References: 1. Martino OI, Ward DJ, Packer C, Simpson S, Stevens AJ. Innovation and the burden of disease: Retrospective observational study of new and emerging health technologies reported by the EuroScan network from 2000 to 2009. Value in Health 2012;15:376-80. 2. World Health Organization. The Global Burden of Disease: 2004 Update. Geneva: WHO, 2008.

Figure 1- Relationship between DALYs and technologies for 102 specific causes.

12 EUROSCAN NEWSLETTER

Contact person:

Laura Sampietro-Colom

(lsampiet@clinic.ub.es)

Hospital Clinic Barcelona

(Coordinator)

AdHopHTA: a new European Project on Hospital Based Health Technology Assessment

The EU has provided a grant for the

AdHopHTA (Adopting Hospital

Based Health Technology

Assessment in EU) project under the

7th Framework Research

Programme. AdHopHTA aims to

strengthen the use and impact of

excellent quality HTA-results in

hospital settings, making available

pragmatic knowledge and tools to

facilitate adoption of hospital based

HTA-initiatives. As a secondary aim,

the project will build an adequate

ecosystem where formal

coordination amongst existing

hospital based HTA-initiatives and

liaisons with national and regional

agencies will flourish.

AdHopHTA has 10 partners with

different, but complementary,

backgrounds: five hospitals with

HTA-programs (Hospital Clinic

Barcelona/FCRB-Spain

[Coordinator]; Odense University

Hospital-Denmark; Hospital District

of Helsinki and Uusimaa-Finland;

Hospices Cantonaux CHUV-

Switzerland; Università Catolica

del Sacro Cuore-Italy), two

hospitals without a HTA program

(Ankara Numune Training and

Research Hospital-Turkey; Tartu

Univeristy Hospital-Estonia), two

national HTA agencies/institutes

(The National Health Center for

Health Services-Norway; Ludwig

Boltzmann Institute for HTA-

Austria) and one business school

(IESE-Spain). It also has an

advisory board where

international societies and key

institutions are represented

(HTAi, INAHTA, EuroScan,

EUnetHTA, ISQua, CEDIT-

Assistance Publique Hôpitaux

Paris, HTA Centrum at

Sahlgenska University Hospital).

The final output of the project will

be a handbook on best practices

for hospital based HTA as well as

a hospital based HTA deployment

toolkit. Another relevant output will

be the design and creation of a

pilot repository on hospital based

HTA-products which aims to be

aligned as much as possible with

the EUnetHTA-POP Database, in

order to ensure that the

AdHopHTA-repository

complements it. These outputs will

be built through five main technical

work packages supported by

dissemination and management

work packages. Figure 1 shows the

PERT diagram of the project.

It is intended that the results of

AdHopHTA will be applied across

the EU and worldwide, and will

facilitate the start of hospital based

HTA-programmes, make improved

tools available for hospital based

HTA (e.g. mini-HTA 2.0), improve

the quality and efficiency of current

hospital based HTA-programmes,

improve the liaison with

national/regional HTA-programmes

and set up the basis for a

European network of hospital

based HTA. AdHopHTA is a

complementary initiative for

EUnetHTA Joint Action, bringing

forward a more comprehensive

HTA-strategy across health system

levels in Europe.

EuroScan looks forward to

supporting the AdHopHTA Project

as a member of the advisory

board.

Fig. 1. Graphical presentation of the interdependencies of work packages and project components (Pert diagram).

DECEMBER 2012 13

The Israeli Center for Emerging Technologies Orna Tal and Nina Hakak, ICET

Technology advances in 2012 & predictions for 2013

The Israeli Center for Emerging

Technologies (ICET), formerly

known as DMTP, is currently

concentrating on 2 major trends:

A) Hospital-based HTA

1. An in-depth assessment of

hospital technologies in Israel is

required since the annual

updating process of the National

List of Health Services focuses

mainly on technologies provided

within the framework of the

community.

2. Hospitals are considered to be

technology promoters due to

several factors:

a) Hospitals have additional

sources of funding for research

and invest in developing

specialists who concentrate on

very specific issues.

b) The existence of competition

between hospitals is a powerful

tool to encourage innovation. This

entails the capacity of each

hospital to develop services

according to staff members

especially specialists in fields such

as genetics, imaging and

nanotechnology procedures.

c) Hospitals encourage specialists

to focus on rare diseases such as

genetic disorders e.g. Fabry

disease.

3. Hospitals are challenged by

unique populations such as ethnic

subgroups e.g. specific groups of

immigrants from Africa or highly

orthodox populations requiring

sensitive ethical approaches.

Thus, specific elements of HTA

are used to identify emerging

technologies.

B) Personalized Medicine

The current trend throughout

the world and in Israel involves

focusing on the identification and

adoption of genetic markers to

diagnose and treat different

diseases. This can be

demonstrated in:

• BRAF & CTLA4 for identifying

a treatment response for

malignant melanoma

• MLH1, PMS2, MSH2 and MSH6

for Lynch Syndrome.

Nature Medicine recently

summarized notable advances in

biomedicine in 2012 (Vol 18, No.

12 p 1732-3). These included the

discovery of new candidate genes

for autism spectrum disorders

offering new directions for autism

research; research showing how

the plant–derived compound

resveratrol might imitate the

benefits of caloric restriction; the

identification of the novel

hormone irisin which is thought to

turn white fat ‘beige’ , thus

burning energy rather than

storing it; and the findings of 2

studies of the inhibitory co-

receptor PD-1 (protein cell death

protein 1) that further validated

immune modulation of T cell

activity as a therapeutic approach

to cancer treatment.

The Lancet reviewed 2012 (Vol

380, Dec 8 p1979-80) and

highlighted the Encyclopedia Of

DNE Elements (ENCODE) project,

which has assigned biochemical

functions to 80% of our genome

and will transform the future of

medical research.

At the end of October 2012

Cleveland Clinic announced its list

of Top 10 Medical Innovations

that will have a major impact on

improving patient care in 2013.

The Top 10 Medical Innovations

for 2013 selected by a panel of

Cleveland Clinic physicians and

scientists are:

1. Bariatric Surgery for Control of Diabetes

2. Neuromodulation Device for Cluster and Migraine Headaches

3. Mass Spectrometry for Bacterial Identification

4. Drugs for Advanced Prostate Cancer

5. Hand-held Optical Scan for Melanoma

6. Femtosecond Laser Cataract Surgery

7. Ex Vivo Lung Perfusion

8. Modular Devices for Treating Complex Aneurysms

9. Digital Breast Tomosynthesis (DBT)

10. Health Insurance / Medicare Program / Rewards for Better Health

http://www.clevelandclinic.org/INN

OVATIONS/SUMMIT/topten.html

14 EUROSCAN NEWSLETTER

WHO Call for Innovative Health Technologies

EuroScan Executive Committee

Do you have a new technology

solution to a well-known health

problem?

Do you have a technology

solution to a health problem not

yet addressed?

Medical devices and eHealth

solutions have the potential to

improve lives. However, too

many people worldwide suffer

because they don’t have access

to the appropriate health

technologies. The Medical

Devices and eHealth units of the

World Health Organization invite

you to submit your solution to

the Call for innovative health

technologies for low-

resource settings.

Deadline for submission is

March 15th, 2013. Selected

submissions will be published in

the WHO Compendium of

innovative health technologies

2013.

WHO aims to raise awareness of

the pressing need for appropriate

design solutions. The Compendium

series specifically focuses on

showcasing innovative medical

devices and eHealth solutions that

are not yet widely available in

under-resourced regions. The

annual publication serves as a

neutral platform to introduce

health technologies that have the

potential to improve health

outcomes or to offer a solution to

an unmet medical need. It is

designed to help developing

countries to become aware of

appropriate health technologies in

support of their environment. The

Compendium 2012 can be viewed

at:

www.who.int/medical_devices/inn

ovation/compendium202

About EuroScan

EuroScan - the International Information Network on New and Emerging Health Technologies - is a collaborative network of member agencies for the exchange of information on important new and emerging health technologies.

Mission

EuroScan International Network is the leading global collaborative network that collects and shares information on innovative technologies in healthcare in order to support decision-making and the adoption and use of effective, useful and safe health-related technologies. We are also the principal global forum for the sharing and development of methods for the early identification and early assessment of new and emerging health-related technologies and their potential impact on health services and existing technologies.

EuroScan International Network is committed to work with a high level of transparency and professionalism, and in partnership with researchers, research centres, governments and international organisations to produce high quality information and effective early awareness and alert systems for our respective constituencies. We are also committed to support the development of existing and new not-for-profit public agencies working in the early awareness and alert field.

Position Current Post Holder End of termChair Professor Brendon Kearney, HPACT 31/12/13 Vice Chair Dr Marianne Klemp, NOKC 31/12/13 Registrar Dr Kees Groeneveld, GR 31/12/12 Dr Roberta Joppi, IHSP From 1/1/13-31/12/14Treasurer Christoph Künzli, SFOPH 31/12/12 Dr Anna Nachtnebel, LBI-HTA From 1/1/13-31/12/14Head of Secretariat Dr Claire Packer, NIHR HSC n/a

Visit http://www.euroscan.org.uk to find out more about EuroScan, its work and how to become a

member.

If you have any feedback, questions, would like to know more or have any articles that would be of interest for the next edition of the newsletter please contact Dr Sue Simpson, EuroScan Network Co-ordinator, NIHR HSC, Department of Public Health, Epidemiology and Biostatistics, University of Birmingham, B15 2SP S.L.Simpson.20@bham.ac.uk +44 121 414 7496

Views of individual authors are not necessarily the views of the editor or EuroScan members

EuroScan has a Memorandum of

Understanding with the World

Health Organisation and has an

agreed collaboration plan. As such

EuroScan members have

contributed to the previous

Compendiums by evaluating

submissions using agreed criteria.