Introduction ................................................................................................................................ 2
Aims of the project ..................................................................................................................... 3
Description of the consortium composition ............................................................................... 4
Detailed work plan with detailed division of tasks .................................................................... 8
WP1- Development of protocol. .............................................................................................. 11
WP1b – Collection of evidence based information .......................................................... 11
WP1c - Literature Review ................................................................................................ 11
WP1d - Corrective feedback of prevalence measurements and sampling methods ......... 12
WP1e - Description of the protocol development ............................................................ 12
Sampling size determination and recruitment of samples ................................................ 13
WP2- Revision of protocol and development of plan for pilot phase ...................................... 15
WP3- Pilot phase ...................................................................................................................... 16
WP4- preparation of the final protocol .................................................................................... 17
CV of participants + relevant publication list .......................................................................... 18
1

Hepatitis C virus infect the liver and can silently progress to serious diseases such as cirrhosis and liver cancer.
The pravaence in Europe was recently estimated [ HCV varies between 2.4% for Western and
Central Europe and 2.9% for Eastern Europe. The global population of this area is approximately 740,000,000 persons, leading to an estimation of the HCV infected pool of more than 19,000,000 persons, a number to be adjusted in the future given the limited evidentiary support, especially for some countries in Central Europe and for the whole
Eastern European bloc. The shortcomings of this and other studies reside in the fact that evidence is based on surveys often conducted in selected groups, or including or excluding high-risk populations such as prison inmates and groups of persons living in social exclusion.
Furthermore, many studies are outdated and have failed to take into consideration the influence of some recent drivers such as migratory movements, including those regarding war refugees and illegal human trafficking.
Hepatitis C virus infection causes a large burden of disease worldwide. In the WHO European region, the attributable fractions of cirrhosis for HCV are 38% for Western and 34% for
Eastern Europe while those for hepatocellular carcinoma are, respectively, 44% and 15%
[Perz et al. . However, given the delay between infection and end-stage chronic liver diseases, the burden of disease associated with infection acquired in the past is expected to increase over the next decade.
New and extremely effective treatments became recently available for the management and elimination of HCV infections and have opened new perspectives, including the possibility to cure patients of the HCV infections. However, new treatments are expensive. Costs of the treatment may deter some policy makers from more active strategies for testing which may result in further under –ascertainment of cases and an ineffective public health response. Costeffectiveness analyses may help in pricing levels at which treatment would be cost-effective.
These delicate arguments on the cost of care need to be based on the best possible data to ensure that any decisions on priorities are as evidence based as possible.
Therefore, the available sero-prevalence data obtained from a standardized protocol can be used as a key indicator of the chronic infections and which can be used to measure the burden of disease associated with HCV infection.
On the other hand, a primary prevention of new infections can be used to prevent the burden of disease associated with HCV infection. This may for instance prevent transmission mong persons who inject drugs (PWID), and to improve infection control in healthcare settings.
Reported rates of acute hepatitis C should reflect the incidence of HCV infection but data available are of poor quality.
The prevalence of anti-HCV ranges between 0.2 % (The Netherland) and 4.4 % (Italy) in the general population (Hahne et al; BMC infectious diseases 2013;3:181). These meta data analytical approaches suffer from information gaps across countries or time periods and from heterogeneity in the method used that may limit comparison between studies. These mean that decision making is made more difficult in the following ways:
 Information is missing at the national level where policy makers need to make
 decisions around testing treatment.
Information on prevalence over time is lacking which could be used to estimate the effectiveness of primary and secondary prevention. .
2

The purpose of serological surveillance is to monitor levels of immunity to particular diseases within different age groups of the population [Osborne et al.; Euro Surveill. 1997;2:167;
Tischer et al.; Epidemiol Infect 2007;135:787-97].
This is particularly but not only relevant for vaccine-preventable diseases. In case of HCV the introduction of a new therapeutic opportunities will necessitate to measure the prevalence of this infectious disease in the general population as well as in the at risk groups i.e. PWID, migrants, prisoners… In order to introduce new drugs, cost benefit analysis will necessitate the availability of the prevalence measurements of the distribution within the population and with a geographical representativity. Serological surveys allow the identification of the susceptible cohorts and to adjust and guide preventive policies .
In future, ECDC would like to explore hepatitis C serological surveys as a supplement to existing national and international case-based surveillances. The aim of this project is therefor to recommend a standardized technical protocol for serological surveys within the different member states. These methodological elements needs to include detailed information on design and costing, to be taken into account for the member states planning their own serological surveys. In order to be used for national decision making, the protocol should allow high quality data, obtained using well defined epidemiological and laboratory methods..
National sero-prevalence data for HCV are well described in the literature allowing the rough estimation of the prevalence . However the methodology to obtain these results differ and thereby an overview of the results is difficult to make and interpret due to the wide variation of patient inclusion criteria, regional versus national studies, selected specimen under study, testmethod, inclusion or exclusion of risk groups, year of investigation, …. Nevertheless, the seroprevalence together with the incidence are however key epidemiological information at national and international level, to guide policy decisions that need to be made.
Only in the case of the use of standardized protocol for serological surveys, data will enable comparable data which can then be used for further metadata-analysis
For a selection of member states for which sero-prevalence studies are needed, a support for the actual implementation will be envisaged.
The main objectives of the availability of the standardized sero-prevalence survey protocol:
 It will help the member states that do not have any data to provide data using a
 harmonised study protocol
Allow an estimation of the proportion of infected patients in the population who are
 aware of their status.
Allow an estimation of the prevalence of infection among key risk groups (PWID, migrants, prisoners, sex-workers,…within the member states and at EU level
 Obtain more accurate estimation of the overall prevalence at the EU level
 Improved comparison of the prevalence data between countries.
Additional benefits that may result from a serological survey:

To generate information on other related issues (behavioural information,…).

This standardisation of a sero-prevalence protocol might be the drive for other infectious diseases to transpose this standardised methods to these diseases.
3

For this tender, a joint effort will be realised between the Belgian Public Health Institute
(WIV-ISP), a governmental organization experienced in epidemiology, public health and harbouring the national reference center of hepatitis, and on the other hand the University
Clinic of Antwerp (UZA), a clinical academic with experience in hepatitis (both HBV and
HCV) hepatitis, health economics, evaluation of vaccination, worldwide (sero-)prevalence studies,… (To complete)
Table 1: Overview of the different institutes and their units bringing the expertise together (To discuss)
Organisation Unit Contact
Person
City Country Member type
WIV-ISP Brussels Belgium
WIV-ISP
Epidemiology of infectious
Dr. S.
Quoilin diseases
Viral diseases Prof. St. Van Brussels Belgium
Consortium leader (to discuss
Consortium
UZA Vaccine and infectious diseases
Gucht
Prof. P. Van
Damme
UZA Dr. Th. Van
Wolleghem
Organisation of each consortium member
Antwerp
Antwerp
Belgium
Belgium member
Consortium member
Consortium member
WIV-ISP unit “Epidemiology of Infectious diseases”
Mission
The unit “ Epidemiology of Infectious diseases ” (within the WIV-ISP) gathers relevant information on infectious diseases with a view to improving public health in Belgium. The unit develops the requisite epidemiological methods to interpret this information and obtain an accurate picture of the extent of a particular health problem. It shares its knowledge and expertise with the government in establishing preventative guidelines and taking control measures in the field of public health.
Tasks
 Describe and monitor the epidemiological evolution of infectious diseases and detect possible changes based on data gathered through the indispensable and reliable voluntary participation of health partners such as microbiologists, clinicians, general

 practitioners, etc.


Study the impact of infectious diseases on the population,
Carry out evaluations of any health risk linked to a pathogen, whether for permanent or recurrent problems, or conversely, in the situation of a potential health emergency
 Interpret this information in order to enable scientifically documented decision-
 making regarding prevention
Provide epidemiological support in the case of a public health crisis, at a local as well as international level
Contribute to the development of a European health framework
Develop any reliable tool that enables the gathering, validating and analysing as well as the publishing and distributing of relevant epidemiological information, according to the needs of users
4

Collaboration
According to cooperation agreements, the major partners of the service Epidemiology of infectious diseases are the Flemish Community, the French Community, the Brussels Region, the National Institute of Sickness and Validity Insurance (INAMI-RIZIV) and the FPS Public
Health. All activities are also conducted within a European perspective, particularly through close collaboration with the European Centre for Diseases Control and Prevention (ECDC).
Team
The team within the unit “epidemiology of infectious diseases” is composed of:

10 clinical experts

8 scientific assistants

3 data managers
 pool of administrative assistants
WIV-ISP unit “Viral diseases”
Mission
The mission of the unit “Viral diseases” within the WIV-ISP is the diagnosis, detection and surveillance of viruses responsible for infectious diseases in humans. In the framework of its mission the service conducts innovative research to improve methods for prevention, diagnosis and treatment of viral diseases. In order to achieve this mission, the unit operates as a centre of expertise within three programmes: respiratory viruses, emerging viruses and encephalitis viruses. The unit of Viral diseases includes the following national reference centres (NRC): NRC Influenza virus, NRC Measles virus, Mumps and Rubella virus, NRC
Hepatitis viruses (B, C, D and E), NRC Rabies virus and NRC Papilomavirus.
Tasks
The unit of “Viral disease” within the WIV-ISP was officially recognised on July 1979 by the
WHO and as National Reference Center for Hepatitis viruses since October 2011.
The Centre is responsible of the following tasks:
 performance of analysis and confirmation tests (immunoblot and/or nucleic acid tests) on request by university laboratories, hospitals and others
 performance of tests for rare parameters which are not part of the routine testing of clinical laboratories (HDV and HEV);
 optimisation of techniques for detection of Hepatitis viruses i.e. oral fluid testing;
 collection of epidemiological data concerning hepatic viruses (A, B, C, D, E), including data relating to the number, geographical distribution, type of virus and immunity within population groups
 Organisation of surveys and studies , in collaboration with other institutions
(universities, health care organisations, etc.).
The laboratory is ISO15189 accredited.
The WHO and NRC recognition, the experience, the diagnostic capacity and the involvement in the surveillance system in the field of hepatitis viruses support the participation of this viral disease unit to the consortium team.
Current and planned research activities concerning HCV in unit viral disease of WIV-ISP
 Optimisation of assays for antiviral resistance based on the different described mutations •
5

 HCV seroprevalence study (anti-HCV) on the recently collected serum bank (2013-
2014) from the “Unit Epidemiology of Infectious Diseases” of the WIV-ISP.
 Identification of HCV genotype: INNO-LIPA assay is available but in some cases the
 result is inconclusive. For those cases we will set up a new in-house sequencing assay for the amplified 5’UTR and core regions of the viral genome.
Conduct a study on the circulating genotypes in Belgium.
Other participations to hepatitis surveillance studies (national and international surveillances)
The unit “viral diseases” participated in the European project ESEN 2 (European Sero-
Epidemiology Network 2). The aim of the ESEN2 project (2001-2005) was to coordinate and harmonise the serological surveillance of immunity to eight vaccine preventable infections
(including Hepatitis A and B) in Europe in order to improve vaccination policies and strategies. The task of the virology lab consisted of testing sera for the presence of anti- HBc, anti-HBs and HBsAg (ELISA).
The unit “viral diseases” collaborated in a study undertaken in every Belgian prison during
October - November 2006 to assess the prevalence of drug use and related risk behaviour in prisoners. ( Drug use in Belgian prisons – monitoring of health risks: final report 2006 – collaboration with Prison Health Care Service and Modus Vivendi )
The unit “viral diseases” participated in a prevalence study of HIV, HBV and HCV using oral fluid in the population of injecting drug users (IDUs) in Belgium (2012).
The virology lab developed and validated oral fluid ELISA tests for the detection of anti-HIV, anti-HCV antibodies and HBsAg antigen. The lab also performed the tests in the framework of this prevalence study.
Collaborative work between unit of epidemiology of infectious diseases and the unit of viral disease
Multiple collaborative studies between the unit “epidemiology of infectious diseases” and the unit “viral disease” demonstrates their synergistic effect:
 Yearly surveillance of Influenza virus epidemic and other respiratory infectious diseases [ http://influenza.wiv-isp.be/en/Pages/default.aspx]
 Previous sero-prevalence studies for HAV, HBV, and HCV in a the general population
 using oral fluid [Quiolin et al.;Eur J Epidemiol, 2007; 22:195-202]
Current use of a serologic bank for the national seroprevalence studies of following infectious diseases: mumps, Bordetella pertussis, Corynebacterium diphteriae and

Tetanus. [Amber et al. XXXX]
Participation of the laboratory to the network of sentinel laboratories
[ https://nrchm.wiv-isp.be/fr/labovigies/default.aspx
]
Team
The team within the unit “Viral diseases” is composed of:
 ….
UZA unit Vaccine and infectious diseases
…
Added value of each consortium member
The consortium members have a high expertise in:
6

 …
7

WP1- Development of protocol
……Signing of specific contract
A project work plan, including general methodological approach and timelines
Kick-off meeting
The report of the one ‐ day kick ‐ off meeting with ECDC staff
Produce a two ‐ page synopsis of the project
Produce a short background document in preparation for the first expert panel
Expert panel meeting (EP)
Prepare background discussions and answer scientific advice
Support ECDC in the preparations of EP meeting
Attend and produce a meeting report of the first expert panel to be hosted by
ECDC
Deliverable
DL1
DL2
DL3
DL4
DL5
Collection of evidence based information
Literature Review
Corrective feedback of prevalence measurements and sampling methods
Protocol development
Produce a first draft protocol(s) based on the desktop review, literature review,
MS survey (if conducted) and input from the first expert panel meeting
WP2- Revision of protocol and development of plan for pilot phase
……Signing of specific contract
An updated project work plan, including general methodological approach and timelines
DL6
M0
DL7
Produce a short background document in preparation for the second expert panel DL8
Timeline
Responsibility
Contributory work t=0 t= 2 w t= 1m ECDC t=6 w t=6w t=EP1-2w t= EP1 t= EP1+/-2w
ECDC t= EP1+/-2w t=EP1+2w t= 1 y t=0 t=EP2-2w
8

meeting including information on likely costs and a detailed plan of the pilot study
Expert panel meeting (EP)
Prepare background discussions and answer scientific advice
Support ECDC in the preparations of EP meeting
Attend and produce a meeting report of the second expert panel to be hosted by
ECDC (
Revise the draft protocol(s) and produce a detailed plan for the pilot phase based on input from the second expert panel meeting
DL9
DL10
WP3- Pilot phase
……Signing of specific contract
An updated project work plan, including general methodological approach and timelines
M0
DL11
Pilot the survey in three different countries and produce a report on the findings DL12
Revise the protocol(s) (including finances) according to the findings and experiences of the pilot study and draft accompanying standards DL13
Expert panel meeting (EP)
Prepare background discussions and answer scientific advice
Support ECDC in the preparations of EP meeting
Attend, facilitate, present and then produce a meeting report of the third expert panel to be hosted by ECDC in Stockholm
Produce a final summary document which includes the revised protocol(s) taking into account what is agreed in the third expert panel, the report of the pilot phase and the input of the expert panel.
Attend a dissemination meeting to be hosted by ECDC and provide an overview of the work
DL14
DL15
DL16
WP4- preparation of the final report of the CB t= EP2 t= EP2+/-2w
ECDC t= EP2+/-2w t=EP2+2w t= 18m t=0 t=2w t=EP3-2w t= EP3 t= EP3+/-2w
ECDC t= EP3+/-2w t=EP2+2w t= ?? t= 36m
9

Abbreviations
DL: deadline
EP: expert panel
A monthly review of the status of the methodology of surveillance will be sent to all participants either by email and/or conference call. Feedback sessions from the participants will also be organised.
A meeting with all participants will be organised after the kick-off meeting to fine tune the steps to take during the next months. As scheduled in the timetable, additional meetings with all participants are foreseen after all official review meetings.
10

WP1a – project plan, kick-off and expert panel meeting
A project work plan, including general methodological approach and timelines will be written as described in the tender (DL1).
Further, the expert panel will be prepared (DL3) and the representatives from the team will participate to kick-off and the expert panel meeting (DL4). Also the meeting minutes from these meetings will be written and communicated to ECDC and other participants (DL2 and
DL5)
Also a two-page synopsis of the project as described in the tasks of the tender will be written
(DL3)
A described in the ternder specifications, the expert panel meeting report will include:

Description of the detailed project work plan agreed with ECDC.

Propose a set of the benefits of and major and minor objectives for conducting sero‐ prevalence surveys for hepatitis in EU/EEA Member States. These objectives will then be used to guide the development of a survey protocol(s).

Proposed options of methods that may be appropriate to achieve each of the objectives, building upon preliminary work already undertaken by ECDC.

Paper/s on other protocol related issues that may be agreed upon with ECDC at the kick‐off meeting.
WP1b – Collection of evidence based information
Evidence based information from following items will be collected and reviewed to support the different options of the prevalence methodology.

Systematic literature review based on a set of pre-defined selection (inclusion and exclusion) criteria (see WP1b), and if possible a meta-analysis will be conducted.

Information available from the European (i.e. technical reports ECDC) and other international studies and available reports.
 …
WP1c - Literature Review
A literature review including scientific peer reviewed papers, abstracts and guidelines will be based on following pre-defined selection criteria (not limited)
Inclusion criteria Exclusion criteria
Population General population from EU member states
Non-EU member states
Infectious diseases HCV
Combination of following keywords

Prevalence studies

Surveillance analysis

HCV, transmission
Study period Primarily 2000-2016
Secondly 1990-1999
Language
Other pathogens
Before 1990
English, French, German, Spanish Other languages
11

This list might be adapted based on the outcome of the first round of literature review.
Relevant papers will be selected by screening for the inclusion criteria in the titles, followed by abstracts and the entire articles retrieved through the MEDLINE database searches.
WP1d - Corrective feedback of prevalence measurements and sampling methods
Due to the variety of the reported sero-prevalence measurements in the different member states, the calculated sampling strategy will be different per member states. However the correctness of the measurement of these data depends on the used methodology and the year of analysis as previously described. In order to improve the estimation of the available prevalence data, we will compare these data with the one form the their neighbouring countries.
In this part of the study, our main goal is to set the groundwork to describe the standardized protocol to measure the sero-prevalence. Specifically, we will determine the epidemiological and laboratory protocol providing the most accurate data.
Therefore, following partial objectives will be investigated:
 Determine the average and ranges of the available national sero-prevalence studies grouped per EU region. Previous results demonstrates that the prevalence’s are different for the different EU region (North, West, South, East and central Europe).
The grouping of the member states can thus be subdivided according to the available prevalence data.
 To exclude sampling strategies with a negative impact on the correctness of the
 prevalence data by determination of the outliers
To establish a common sampling strategy taking into account its feasibility for all member states, the representativeness of the results for the general population and the limits of the budget.
 Define the possible laboratory methods to be used to obtain comparable results taking into account the laboratory capacity of the member states
 To establish an epidemiological model with the aim of determining the validity of sampling campaigns that could be performed for the general population of the different member states.
 A consultation round could be envisaged to receive some feedback on the feasibility of the findings before writing down the conclusions.
WP1e - Description of the protocol development
The standardised sero-prevalence survey protocol will be used as a manual for the member states to perform the study. It will include following aspects: background information, rationale, objectives, , study design, methodology (i.e. sample size determination, sample collection, transport and storage, selection of testmethods, elegible criteria for study centers), cleaning and statistical evaluation of the data, and proposal organization of the serooprevalence study. It will as well include a check-list of topics to complement by the individual member states organisers i.e. sponsors, list of participants, access to data dissemination policy,….
The obtained protocol can be used for multiple purposes by the different member states.
Objectives:

Guide for a team to ensure that the methodology is clear and roles and responsibilities are well defined.
 forces the investigators to clarify their thoughts and to think about all aspects of the study
12

 as a support to plan the project and to foresee the logistic organisation
 essential document for the member states to submit as a proposal for funding
 essential document in order to get institutions ethical approval
 basic document for reporting the results when study is completed
 avoid protocol amendments or interruption of the study
The use of a standardized protocol

Will reduce inappropriate variation
 will allow to generate data that are comparable by a meta-data analysis between the different EU member states.
Sampling size determination and recruitment of samples
Estimated number of participants needed to achieve study objectives and how it was determined, including clinical and statistical assumptions supporting any sample size calculations.
Strategies for achieving adequate participant enrollment to reach target sample size
To obtain a geographically well distributed sample, public and private diagnostic laboratories will be invited to participate to the collection of samples. According to the response of the participating laboratories and their geographical distribution, a test sample will be retained to participate to the study, to allow geographical representativity and effective management..
The number of samples will further be stratified by gender, to obtain equal numbers of males and females in each age group. Age groups will be defined per single age year up to age 19 years, and in 5 year age groups for adult samples.
The sample size can be calculated according to ESEN recommendations as well as previous experience with various age-specific analyses of seroprevalence data. For sero-surveys, the
ESEN project guidelines recommend to include 100 samples per one-year age band till the age of 20, 200 samples per 5-year age band between 20 and 39 years of age and from then on
200 per 10 years (1). For the age group 0 to 19 years, where sufficient serum collection for successive analyses is more difficult to obtain, an extra 20 samples per one year age band will be collected. In total, 4000 sera will be collected, distributed over the age groups as presented in Table 1.
Table 1: Number of samples per age group
Age group Relative number
0-19
20-39
40-69
100 +20 per year
200 per 5 years
200 per 10 years
70+ 200
Specimen type
Selection of serum/saliva/dry blood spot….
Sample collection, storage and transportation
Total number
2400
800
600
200
13

A serum/saliva/dry blood spot/… bank should be constituted based on a prospective crosssectional study design. Pre-labeled tubes should be available and included into the cost analysis. Similar for the transportation cost.
Samples submitted to diagnostic laboratories should be as representative of the population
(age, gender, geographically) as possible, readily accessible and therefore cheap to collect.
…
Participating laboratories/institutes should be informed on the methodology of the study and sampling criteria, volume, storage and transportation.
Laboratory analysis method
Steven???
Data collection and data cleaning
…
This part will include:

Plans for assessment and collection of outcome, baseline, and other trial data, including any related processes to promote data quality (e.g., duplicate measurements, training of assessors) and a description of study instruments (e.g., questionnaires, laboratory tests) along with their reliability and validity, if known.

Plans for data entry, coding, security, and storage, including any related processes to promote data quality (e.g., double data entry; range checks for data values). Reference to where details of data management procedures can be found, if not in the protocol.

Statistical methods for analyzing primary and secondary outcomes. Reference methods for any additional analyses (e.g., subgroup and adjusted analyses)

Definition of analysis population relating to protocol nonadherence (e.g., asrandomized analysis), and any statistical methods to handle missing data (e.g., multiple imputation)
Data flow and management
Information from the collected samples and their obtained results should be centralized and validated for completeness and duplicates. If necessary, laboratories should be contacted to check or complete missing information or to collect a new sample. Laboratory results should be linked to the database based on the sample code. Information on date of birth and postcode will be deleted once the serum bank is completed.
All data should be protected and restricted access should be foreseen
Data analysis
For each pathogen studied, the prevalence of sero-negativity, sero-positivity and equivocal results will be standardized for age, gender and geographical distribution based on the most recent available National Registry data
Calculation of necessary resources to fulfil the survey by the meber state
A tool to calculate the necessary budget for fulfilling the sero-prevalence study will be made available for the study coordinators of the member states.
14

Ethical committee
The final protocol for the seroprevalence will contain an annex containing all necessary information to request the approval of the study from the Ethic committee in an institute of each EU member states.
WP1f - First draft protocol (DL6)
Final requirements of the daft protocol(s) for undertaking sero ‐ prevalence survey among the general population and key population groups in the EU/EEA.

Based on the inputs provided by the discussions of the key stakeholder expert panel at the first meeting, the desktop review, the literature review and if considered necessary the MS expert survey, we will produce a first draft protocol(s) for undertaking sero‐prevalence survey of hepatitis C among key population groups in the EU/EEA.

The draft protocol(s) should provide options for conducting the sero‐prevalence survey, in different settings/populations and at differing levels of resources.

The protocol(s) will include the minimum elements listed (see beyond) and elaborate the likely resources required for implementation of the different options. Methodological approaches will be described: o Selection of sites/population o Sampling and stratified sampling method options riskpopulation o Specimen/data collection, storage and transport
-representativity
-general and at
-blood, saliva, finger,dry blood o Supplementary data capture standards and forms - o Confidentiality and ethical issues -ethical committee o Laboratory testing options (including quality control) -,national labs vs virtual labs
(centralised) o Data management (including data entry, validation and analysis) double checks, Qc o Investigator training/briefing requirements o Quality assurance of the entire operations o Reporting considerations including dealing with bias and limitations of the study o Timelines and plans o Budgetary considerations, with options for differing levels of funding
WP2a – project plan and expert panel meeting
Based on the expert panel suggestions and comments and the feedback from individual member states, the protocol will be revised (DL7). It will also be used as a tool to prepare a template of protocol for the individual member states.
It will contain:
 the items as foreseen in the WP1.

The methodological approaches
15


More precise timeline based on the accurate description of the protocol, project milestones and key deliverables

Additionally it will also give a preliminary estimation of the sample size determination for a o small, medium and dense population country o an East, South, West, North and central EU member state

Similarly an estimation of the cost will be calculated.
These calculations will assist the ECDC in their choice to select a pilot country.
As described in the tender, a project work plan, including general methodological approach and timelines will be written (DL7).
Further, the second expert panel will be prepared (DL8) and the representatives from the team will participate to this expert panel meeting (DL9). Also the meeting minutes from these meetings will be written and communicated to ECDC and other participants (DL2 and DL5)
A described in the tender specifications, the second expert panel meeting report will include:

The contractor will support ECDC in the preparations of the second expert panel (as described in first expert panel of WP1).

In preparation for the second expert panel, ECDC will circulate the draft protocol(s) and a plan for the pilot phase of the project for discussion and review in advance of the meeting.

The contractor is expected to take notes of the discussions and prepare a report from the meeting.
Additionally:

Revised second draft protocol and a plan for review and approval.

Development of a draft a set of standards to accompany the protocol.

Revise the plan for piloting in accordance with feedback obtained during the second panel meeting and from liaison with pilot countries
WP2b – Revised protocol (DL10)
The draft protocol described in WP1f will be revised based on the input of the second expert panel panel meeting. Also a detailed plan will be presented as described in the tender specifications.
WP3a – project plan and expert panel meeting
Based on the expert panel suggestions and comments and the feedback from individual member states, the protocol will be revised (DL11)
In this third work package, the protocol as described in WP2 will be executed for the 3 pilot countries selected by ECDC. The entire pilot phase will beforehand be described and planned with timelines including project milestones and key deliverables and roles and responsibilities
(DL11). Since the will cover the funding of the sample collection, transport and storage and of the sample analysis, this section should not be described.
WP3b - Pilot the sero ‐ prevalence survey for hepatitis C (DL12)
16

Finalization of the protocol for the 3 pilot countries
Search for the partners of the study
Approval of necessary documents
Pilot phase
Including sample collection, transportation, storage, analysing of samples, data cleaning an data analysis, data reporting
Lessons learned
WP3c – Third expert panel meeting (DL14)
The third expert panel will be prepared and the representatives from the team will participate to this expert panel meeting. Also the meeting minutes from these meetings will be written and communicated to ECDC and other participants.
A described in the tender specifications, the third expert panel meeting report will include:

The contractor will support ECDC in the preparations of the third expert panel meeting as previously.

In preparation for the third expert panel, ECDC will circulate two weeks in advance the report on the piloting of the survey (see 2.2.2.10 IV. of the tender specification).

The contractor will present the findings, experiences and lessons learnt to the third expert panel meeting and this presentation will be supported by the key investigators of the pilot countries.

The contractor will moderate the discussions and take note of all the changes, amendments and improvements to the protocol, as well as their comments on the standards to be applied in the conduct of the surveys, as raised by the participants.

The contractor is expected to prepare a meeting report.
Based on the expert panel suggestions and comments and the feedback from individual member states, the protocol will be finalized (DL15) and dissiminated (DL16).
17

18