<table><thead><tr><td>N-group</td><td>Label N-group</td><td>Filter parameter</td></tr></thead><tbody><tr><td>N33</td><td>Transplantations</td><td>SUITABLE</td></tr><tr><td>N40</td><td>Internal medicine</td><td>SUITABLE</td></tr><tr><td>N41</td><td>Pneumology</td><td>SUITABLE</td></tr><tr><td>N42</td><td>Gastro-enterology</td><td>SUITABLE</td></tr><tr><td>N45</td><td>Radiation therapy</td><td>SUITABLE</td></tr><tr><td>N46</td><td>Nuclear medicine in vivo</td><td>SUITABLE</td></tr><tr><td>N47</td><td>Nuclear medicine in vitro</td><td>NOT SUITABLE</td></tr><tr><td>N48</td><td>Radio-isotopes</td><td>NOT SUITABLE</td></tr><tr><td>N50</td><td>Roentgen diagnose</td><td>NOT SUITABLE</td></tr><tr><td>N51</td><td>Percutaneous interventions</td><td>NOT SUITABLE</td></tr><tr><td>N53</td><td>Patient's contribution - hospitalized patients</td><td>SUITABLE</td></tr><tr><td>N54</td><td>Paediatrics</td><td>SUITABLE</td></tr><tr><td>N55</td><td>Cardiology</td><td>SUITABLE</td></tr><tr><td>N56</td><td>Neuropsychiatry</td><td>NOT SUITABLE</td></tr><tr><td>N57</td><td>Physical therapy</td><td>NOT SUITABLE</td></tr><tr><td>N59</td><td>Dermato-venereology</td><td>SUITABLE</td></tr><tr><td>N60</td><td>Clinical biology - accessible for medical specialists</td><td>NOT SUITABLE</td></tr><tr><td>N61</td><td>Outpatient lump sum fees - clinical biology</td><td>NOT SUITABLE</td></tr><tr><td>N62</td><td>Inpatient lump sum fees - clinical biology</td><td>NOT SUITABLE</td></tr><tr><td>N63</td><td>Anatomopathology</td><td>NOT SUITABLE</td></tr><tr><td>N64</td><td>Genetic testing</td><td>NOT SUITABLE</td></tr><tr><td>N70</td><td>Devices</td><td>SUITABLE</td></tr><tr><td>N73</td><td>Opticians</td><td>SUITABLE</td></tr><tr><td>N77</td><td>Urostomy, enterostomy and tracheostomy</td><td>SUITABLE</td></tr><tr><td>N80</td><td>Biosynthetics and disposables</td><td>NOT SUITABLE</td></tr><tr><td>N81</td><td>Renal dialysis</td><td>SUITABLE</td></tr><tr><td>N85</td><td>Personal share hospitalization</td><td>NOT SUITABLE</td></tr><tr><td>N86</td><td>Pharmaceuticals</td><td>NOT SUITABLE</td></tr><tr><td>N87</td><td>Hospital nursing</td><td>NOT SUITABLE</td></tr><tr><td>N88</td><td>Revalidation & re-adaptation - patient's contribution</td><td>NOT SUITABLE</td></tr><tr><td>N89</td><td>Placement & travel costs MPC - patient's contribution</td><td>NOT SUITABLE</td></tr><tr><td>N90</td><td>Smoking cessation session codes</td><td>NOT SUITABLE</td></tr><tr><td>N93</td><td>Regularisation codes</td><td>NOT SUITABLE</td></tr><tr><td>N95 - N96 - N98</td><td>Various administrative codes (non relevant for present study)</td><td>NOT SUITABLE</td></tr><tr><td>N97</td><td>Refunding of patient contributions</td><td>NOT SUITABLE</td></tr><tr><td>N99</td><td>Not elsewhere attributable regularisations</td><td>NOT SUITABLE</td></tr></tbody></table>

As a result of this scrutiny, approximately 42% of 273 stays were excluded (see addendum 2 for details): 114 stays were definitely excluded and 51 stays were affirmatively included (by finding a HBV specific intervention). However, for the remaining 108 stays no decision could be made in present level. Consequently inclusion-exclusion had to be decided solely on low level NIHDI billing codes criteria (see section below).

Stay inclusion resulted in principal acceptance of all billing records in the corresponding stay, be it with further diversification in separate cost groups (see level 3).

Stay exclusion resulted in total discarding of all billing records in the corresponding stay, exception made HOWEVER of hepatitis B attributable diagnostic testing or subsidiary interventions (Table 45) and hepatitis B specific medication (see section 3.4 beneath).
<table><caption>Table 45. Hepatitis B attributable diagnostic testing or subsidiary interventions</caption><thead><tr><td>NIHDI_codes</td><td>Label</td><td>Type</td></tr></thead><tbody><tr><td>437054_437065</td><td>Diagnosis and follow up of HBV: HBe antigen</td><td>Test</td></tr><tr><td>437091_437102</td><td>Diagnosis and follow up of HBV: HBe antibodies</td><td>Test</td></tr><tr><td>551390_551401</td><td>Diagnosis and follow up of HBV: HBs antigen</td><td>Test</td></tr><tr><td>551412_551423</td><td>Diagnosis and follow up of HBV: HBe antigen</td><td>Test</td></tr><tr><td>551434_551445</td><td>Diagnosis and follow up of HBV: anti HBs antibodies</td><td>Test</td></tr><tr><td>551456_551460</td><td>Diagnosis and follow up of HBV: anti HBe antibodies</td><td>Test</td></tr><tr><td>551471_551482</td><td>Diagnosis and follow up of HBV: anti HBc antibodies</td><td>Test</td></tr><tr><td>355751_355762</td><td>Liver punction</td><td>Intervention</td></tr><tr><td>473395_473406</td><td>Percutaneous bile duct or vena portae catheterization</td><td>Intervention</td></tr><tr><td>473410_473421</td><td>Catheterization of the venae suprahepaticae</td><td>Intervention</td></tr><tr><td>473712_473723</td><td>Fibroduodenoscopic placement of a bile duct dilatation prosthesis</td><td>Intervention</td></tr></tbody></table>

### 5.3.3.4 Low level cost sub grouping on NIHDI codes

As argued before, HBV infections frequently occur as an epiphenomenon with other pre-existing or concurrent disease(s) or treatment(s) (e.g. coagulation disorders needing multiple blood transfusions, haemodialysis, HIV ...). Therefore it certainly was crucial for this cost study to separate NIHDI code reimbursements in different 'cost sub groups' (Table 46):

1. HBV: costs indisputably or most likely attributable to HBV;

2. nHBV: costs not automatically attributable to HBV diagnosis and/or treatment (see addendum 3);

3. SOC: costs related to social security 'low income compensation' regulations;

4. EXC: cost related to hospital financing by lump sums (laboratory testing, medical imaging, inpatient pharmaceuticals) that were excluded and replaced by 100% extrapolations of fee-for service part of corresponding remunerations (see section 4 beneath);

5. PAT: costs related to 'compulsory patient contribution' regulations (paid by the patient himself).

<table><caption>Table 46. Crude NIHDI cost data 2006 for not excluded patient stays (not extrapolated)</caption><thead><tr><td>Cost_sub gr</td><td>NIHDI reimb (€ x 1000)</td></tr></thead><tbody><tr><td>HBV</td><td>749</td></tr><tr><td>nHBV</td><td>716</td></tr><tr><td>SOC</td><td>33</td></tr><tr><td>EXC</td><td>154</td></tr></tbody></table>

Frequency queries for each NIHDI code per HBV clinical phase group were obtained, including corresponding patient counts and reimbursement totals. Those three elements were considered while scrutinizing all records one by one (be it by means of strategic and consecutive filtering on the N-groups) so that sound decisions could be made on which cost class they should fit in. Results are to be found in addenda 4 to 7.
### 5.3.3.5 Low level cost sub grouping on pharmaceuticals

#### Introduction

The Federal Agency for Medicines and Health Products® (FAMHP - former Directorate-General for Medicinal Products of the FPS Public Health) is the official authority for medicines and health products in Belgium. The FAMHP ensures, from development to use, the quality, safety and efficacy of medicines for human and veterinary use, including homeopathic medicines, herbal medicines, pharmacy made and official preparations. Its authority extends to medical devices and accessories, as well as raw materials for the preparation and production of medicines. It also covers clinical trials registration, marketing authorization procedures in Belgium, pharmacovigilance - control and inspection activities - and advertising regulations.

The FAMHP Marketing Authorisation department is responsible for evaluating and overall managing of requests for marketing authorisation (or their modification) of medicines in Belgium.

Once such authorisation obtained, the Federal Public Service (FPS) Economy¹ sets a maximum price per brand and at the same time the pharmaceutical company can apply for NIHDI refunding² at the Commission for Refunding of Medicines³. Within a legally fixed delay a motivated proposal on refunding (or not) is handed over to the Minister of Social Affairs, who takes the final decision. If positive, the pharmaceutical brand is added to the 'List of refundable pharmaceuticals', which covers different 'chapters', depending on refundable indications and the pharmaceutical category, resulting sometimes in different reimbursement tariffs. The corresponding database, which is regularly updated, can be consulted online at:

* http://www.riziv.fgov.be/inami_prd/ssp/cns2/pages/SpecialityCns.asp (Dutch)
or

* http://www.inami.fgov.be/inami_prd/ssp/cns2/pages/SpecialityCns.asp (French).

Any pharmaceutical authorized for release on the Belgian market is identified by a 7 digit code, called CNK code¹, which is unique for brand name and package. This allows for unequivocal identification, ATC¹-DDD² classification and DPP¹ retrieval. Since hospital pharmaceuticals often are delivered per 'unit dose' (UD), such UD conditionings receive a different CNK code (identifiable by a leading '07' in the CNK code).

Data recordings on delivered pharmaceuticals in Belgium go through two possible channels: one for deliveries by hospital pharmacies (dispensaries accessible to inpatients as well as outpatients) and one by 'extra muros' pharmacies. The former are registered, along with all other charged health care services and medical supplies delivered, through hospital reimbursement claims sent to the health insurance company (HIC) of the patient after his/her discharge³. The latter recordings originate in a nationwide, electronic data registry system connecting all 'extra muros' pharmacies with so called legally instituted 'tarification offices', that assemble all individual claims to dispatch them to the corresponding HIC.

<footnote>e See http://www.fagg-afmgps.be/en/items-HOME/useful_information/index.jsp and http://www.fagg-afmpbs.be/en/annual_report/index.jsp</footnote>

<footnote>f See: http://economie.fgov.be/en/</footnote>

<footnote>g See: http://riziv.fgov.be/drug/nl/drugs/general-information/refunding/index.htm#p2 (Dutch) or http://riziv.fgov.be/drug/fr/drugs/general-information/refunding/index.htm#p2 (French)</footnote>

<footnote>h NIHDI Commission for refunding of medicines = Commissie tegemoetkoming geneesmiddelen (CTG) - Commission de remboursement des médicaments (CRM)</footnote>

<footnote>i Code National – Nationale Kode</footnote>

<footnote>j The Anatomical Therapeutic Chemical (ATC) Classification System used for the classification of drugs is controlled by the WHO Collaborating Centre for Drug Statistics Methodology (WHOCC), and was first published in 1976. See : http://www.whocc.no/atc/structure_and_principles/</footnote>

<footnote>k DDD = Defined Daily Dose (for an average adult weighting 70 kg.)</footnote>

<footnote>l DPP = Dosis Per Package = package quantity divided by DDD = number of DDD's per package</footnote>

<footnote>m Claims remain valid up to 1 year after discharge</footnote>
For both pathways emphasis should be laid on the fact that prescription registries only contain records on the time points of delivery of drugs and related supplies to individual patients along with information on brand code (CNK code) and amount delivered. However, those sources of data do not provide direct information on the time of initiation and discontinuation of drug treatment. In present study, being a public health cost study, this drawback is of minor importance.

### Pharmaceutical deliveries by 'extra muros' pharmacies

Extensive information about the Pharmanet circuit can be found on the official NIHDI web site (downloadable document in English, 80 pages):

http://riziv.fgov.be/drug/nl/statistics-scientific-information/pharmanet/introduction/pdf/analyticalreport_eng.pdf.

Pharmacotherapeutical information (indications, contra-indications, adverse effects, posology...) on outpatient pharmaceuticals can be found at the BCFI - CBIP<sup>n</sup> website at: http://www.bcfi.be/ (Dutch) or http://www.cbip.be/ (French). Although the online consultable database is quite comprehensive, it does not include specific hospital pharmaceuticals.

### Pharmaceutical deliveries by hospital pharmacies

Lists of hospital pharmaceuticals and their lump sum ruling inclusion or exclusion are monthly updated and web published (for download by hospital pharmacists) at:

http://riziv.fgov.be/care/nl/hospitals/specific-information/forfaitarisation/index.htm

### Inclusion - exclusion tables for pharmaceuticals

All antiviral pharmaceuticals found in the IMA data are listed in Table 47. They were flagged for 'HBV' and 'not HBV' indications i.e. their clinical indication in the present study context (tenofovir, for example, can also be used for treatment of HIV infection, but, since HIV patients were excluded at intake, his indication was not withheld for present study). Based on this table primary inclusion-exclusion decisions were straight forward.

<table><caption>Table 47. Antivirals found in database</caption><thead><tr><td>CNK-code</td><td>ATC5</td><td>ATC_label</td><td>ATC2_class</td><td>Clinical indication (*)</td></tr></thead><tbody><tr><td>1256072</td><td>J05AF05</td><td>Lamivudine</td><td>Antivirals for systemic use</td><td>HBV</td></tr><tr><td>1411354</td><td>J05AF05</td><td>Lamivudine</td><td>Antivirals for systemic use</td><td>HBV</td></tr><tr><td>1411362</td><td>J05AF05</td><td>Lamivudine</td><td>Antivirals for systemic use</td><td>HBV</td></tr><tr><td>1700608</td><td>J05AF05</td><td>Lamivudine</td><td>Antivirals for systemic use</td><td>HBV</td></tr><tr><td>1743806</td><td>J05AF07</td><td>Tenofovir disoproxil</td><td>Antivirals for systemic use</td><td>HBV</td></tr><tr><td>1784032</td><td>J05AF08</td><td>Adefovir dipivoxil</td><td>Antivirals for systemic use</td><td>HBV</td></tr><tr><td>772483</td><td>J06BB04</td><td>Hepatitis b immunoglobulin</td><td>Immune sera and immunoglobulins</td><td>HBV</td></tr><tr><td>298398</td><td>L03AB04</td><td>Interferon alfa-2a</td><td>Immunostimulants</td><td>HBV</td></tr><tr><td>227686</td><td>L03AB05</td><td>Interferon alfa-2b</td><td>Immunostimulants</td><td>HBV</td></tr><tr><td>1414564</td><td>L03AB05</td><td>Interferon alfa-2b</td><td>Immunostimulants</td><td>HBV</td></tr><tr><td>458133</td><td>J05AB01</td><td>Aciclovir</td><td>Antivirals for systemic use</td><td>Herpes viruses</td></tr><tr><td>1663939</td><td>J05AB14</td><td>Valganciclovir</td><td>Antivirals for systemic use</td><td>Herpes viruses</td></tr><tr><td>1612597</td><td>J05AE</td><td>Protease inhibitors, rotinavir + lopinavir</td><td>Antivirals for systemic use</td><td>HIV</td></tr><tr><td>1466549</td><td>J05AE03</td><td>Ritonavir</td><td>Antivirals for systemic use</td><td>HIV</td></tr><tr><td>1612597</td><td>J05AE06</td><td>Lopinavir</td><td>Antivirals for systemic use</td><td>HIV</td></tr><tr><td>1370659</td><td>J05AG01</td><td>Nevirapine</td><td>Antivirals for systemic use</td><td>HIV</td></tr><tr><td>760561</td><td>J05AR01</td><td>Zidovudine and lamivudine</td><td>Antivirals for systemic use</td><td>HIV</td></tr><tr><td>1378280</td><td>J05AR01</td><td>Zidovudine and lamivudine</td><td>Antivirals for systemic use</td><td>HIV</td></tr></tbody></table>

<footnote>(*) Clinical indication used for the purpose for inclusion/exclusion in the study.</footnote>

<footnote>n BCFI = Belgisch Centrum voor Farmacotherapeutische Informatie, CBIP = Centre Belge d'Information Pharmacothérapeutique</footnote>
### 5.3.4 Extrapolations for partial lump sum remunerations

#### 5.3.4.1 Laboratory testing

As elaborated in KCE report 121 "Feasibility study of the introduction of an all-inclusive case-based hospital financing system in Belgium" and its supplement (downloadable at http://www.kce.fgov.be/), financing of laboratory testing in Belgium partly consists of a fee-for-service system and partly of lump sum payments. Codes for billing the latter are to be found in Table 48. Both inpatient and outpatient sectors are involved and related billings are available in the IMA records.

<table><caption>**Table 48.** Lump sum codes for laboratory tests</caption><thead><tr><th>Domain</th><th>NIHDI code</th><th>Specifications - applicability</th></tr></thead><tbody><tr><td rowspan="5">Inpatient</td><td>591102</td><td>Lump sum on hospital admission - base sum</td></tr><tr><td>591124</td><td>Lump sum on hospital admission - 3 FT</td></tr><tr><td>591146</td><td>Lump sum on hospital admission - 2 FT</td></tr><tr><td>591603</td><td>Lump sum on hospital admission - accreditation certificate</td></tr><tr><td>592001</td><td>Lump sum per hospital stay day - inpatients - acute hospitals</td></tr><tr><td rowspan="3">Day care</td><td>591091</td><td>Lump sum on 'one day' admission - base sum</td></tr><tr><td>591135</td><td>Lump sum on 'one day' admission - 2 FT</td></tr><tr><td>591113</td><td>Lump sum on 'one day' admission - 3 FT</td></tr><tr><td rowspan="15">Outpatient</td><td>592874</td><td>Lump sum clinical biology art 3 - accreditation certificate - relative cumulative value &lt; B 700</td></tr><tr><td>592830</td><td>Lump sum clinical biology art 3 - no accreditation certificate - relative cumulative value &lt; B 700</td></tr><tr><td>592970</td><td>Lump sum clinical biology art 3 - accreditation certificate - relative cumulative value B 700 - B 1749</td></tr><tr><td>592933</td><td>Lump sum clinical biology art 3 - no accreditation certificate - relative cumulative value B 700 - B 1749</td></tr><tr><td>593073</td><td>Lump sum clinical biology art 3 - accreditation certificate - relative cumulative value B 1750 - B 3499</td></tr><tr><td>593036</td><td>Lump sum clinical biology art 3 - no accreditation certificate - relative cumulative value B 1750 - B 3499</td></tr><tr><td>593176</td><td>Lump sum clinical biology art 3 - accreditation certificate - relative cumulative value &gt; B 3500</td></tr><tr><td>593132</td><td>Lump sum clinical biology art 3 - no accreditation certificate - relative cumulative value &gt; B 3500</td></tr><tr><td>592852</td><td>Lump sum clinical biology art 18 &amp; 24 - accreditation certificate - relative cumulative value &lt; B 700</td></tr><tr><td>592815</td><td>Lump sum clinical biology art 18 &amp; 24 - no accreditation certificate - relative cumulative value &lt; B 700</td></tr><tr><td>592955</td><td>Lump sum clinical biology art 18 &amp; 24 - accreditation certificate - relative cumulative value B 700 - B 1749</td></tr><tr><td>592911</td><td>Lump sum clinical biology art 18 &amp; 24 - no accreditation certificate - relative cumulative value B 700 - B 1749</td></tr><tr><td>593051</td><td>Lump sum clinical biology art 18 &amp; 24 - accreditation certificate - relative cumulative value B 1750 - B 3499</td></tr><tr><td>593014</td><td>Lump sum clinical biology art 18 &amp; 24 - no accreditation certificate - relative cumulative value B 1750 - B 3499</td></tr><tr><td>593154</td><td>Lump sum clinical biology art 18 &amp; 24 - accreditation certificate - relative cumulative value &gt; B 3500</td></tr><tr><td>593110</td><td>Lump sum clinical biology art 18 &amp; 24 - no accreditation certificate - relative cumulative value &gt; B 3500</td></tr></tbody></table>
## Inpatients & day care

Hospital lump sum tariffs are dependent on (1) the type of hospital, acute versus rehabilitation hospitals, (2) the hospital case-mix based on previous linked MCR-HBR hospital records, (3) the number of laboratory specialists, counted in full time units (FTU) and (4) whether or not the performing lab physician has a (personal) accreditation certificate®, which entitles him to charge a higher priced code (591603).

Since hospitals receive lump sums per admission (only acute care hospitals) and per stay day (acute care as well as rehabilitation hospitals) for each inpatient and day care patient whether or not there was any laboratory test performed, lump sum payments to hospitals have little connection with actual services delivered. To restore the link with actual practice for inpatients, lump sum payments were substituted by fee-for-service amounts extrapolated to such an extent that 'theoretical' 100% values were obtained.

## Outpatients

For outpatients, lump sum tariffs are dependent on (1) laboratory tests actually performed, i.e. no lump sum is paid without tests, (2) their amount in terms of relative cumulative value, (3) the N-group (N08 versus N47 and N60 – see Table 48) of the laboratory tests performed, and (4) whether or not the clinical biologist has an accreditation certificate. Based on the two first conditions, and unlike inpatients, connection with actual services delivered is in a certain way maintained, albeit with some disproportionality regarding N08 group versus N60 and N47 groups (condition 3).

## Calculation of extrapolation factors

Lump sum amounts for laboratory testing were discarded (cost class 'EXC') and each fee-for-service part for laboratory tests (NIHDI N-groups N08, N47 and N60) was extrapolated to its estimated 100% level by multiplying it with a corresponding extrapolation factor (EF) calculated on full NIHDI accountancy records (doc N) for the year 2006 (Table 49). Since the Doc N registry does not include hospital identification, we could not differentiate for the number of laboratory FTU®.

<table><caption>Table 49. Total NIHDI expenses on inpatient laboratory testing in 2006</caption><thead><tr><td>Part / Domain</td><td>Outpatient & day care</td><td>Inpatient</td></tr></thead><tbody><tr><td>Fee-for-service</td><td>362.366.413,42 €</td><td>81.239.605,58 €</td></tr><tr><td>Lump sums</td><td>168.620.963,43 €</td><td>314.331.842,06 €</td></tr><tr><td>Year total</td><td>530.987.376,85 €</td><td>395.571.447,64 €</td></tr><tr><td>Extrapolation factor</td><td>3,1490</td><td>4,8692</td></tr></tbody></table>

For inpatients this method seems quite accurate, at least with reference to NIHDI annual accounts and exception made for the number of laboratory FTU's per hospital.

For day care and outpatients on the other hand we have to accept some more degree of distortion in our extrapolation: since day care services are charged with the same set of fee-for-service billing codes as those used for outpatients we could not fractionate the 2006 total of fee-for-service payments into correct outpatient and day care parts and at the same time separate N08 from N47-N60 reimbursements to calculate different extrapolation factors. This forced us to take all outpatient code reimbursements together for calculation of a common EF, even if lump sum allocation rules are quite different (see Table 48).

<footnote>o Comparable to the CME certificates in the USA.</footnote>

<footnote>p The only way to get to such differentiation would be to calculate EF's on SHA and ADH databases of the NIHDI; unfortunately we did not have those at our disposal.</footnote>
### 5.3.4.2 Medical imaging

NIHDI codes for medical imaging (MI) come in two sets: one confined to specialists in radiology (45* codes) and a second for so-called 'connected MI' i.e. allied medical imaging performed by other specialists in the field of their speciality (46* codes, e.g. coronarographies by cardiologists).

As for laboratory testing, financing of medical imaging (MI) consists of partly a fee-for-service system and partly lump sum payments. Billing codes for MI lump sums are listed in Table 50.

<table><caption>**Table 50.** Lump sum codes for medical imaging</caption><thead><tr><th>Domain</th><th>NIHDI code</th><th>Label code</th></tr></thead><tbody><tr><td rowspan="5">Outpatient</td><td>460670</td><td>Consultancy fee for specialist in radiology, outpatients (restricted to a specific set of codes – see addendum 10)</td></tr><tr><td>460795</td><td>Consultancy fee for specialist in radiology with accreditation certificate, outpatients (restricted to a specific set of codes – see addendum 10)</td></tr><tr><td>460972</td><td>Lump sum fee per prescription and per day for outpatient medical imaging listed under art. 17, §1, except if conditions under code 460994 or 461016 are met</td></tr><tr><td>460994</td><td>Lump sum fee per prescription and per day for outpatient medical imaging listed under art. 17, §1 with at least one of the codes flagged for this code in addendum 10</td></tr><tr><td>461016</td><td>Lump sum fee per prescription and per day for outpatient medical imaging listed under art. 17, §1 with at least one of the codes flagged for this code in addendum 10</td></tr><tr><td rowspan="3">Inpatient</td><td>460784</td><td>Lump sum for medical imaging payable on admission</td></tr><tr><td>460703</td><td>Consultancy fee payable on admission in a general hospital (in one or more of following hospital departments: A, C, D, E, G, H, I, K, L, M, NIC, Sp-cardiopulmonary, Sp-neurology or Sp-loco motor rehabilitation)</td></tr><tr><td>460821</td><td>Consultancy fee payable to a specialist in radiology with accreditation certificate on admission in a general hospital (in one or more of following hospital departments: A, C, D, E, G, H, I, K, L, M, NIC, Sp-cardiopulmonary, Sp-neurology or Sp-loco motor rehabilitation)</td></tr></tbody></table>

#### Inpatients and 'one day' admissions

Hospitals receive a lump sum per admission, different for each hospital, and a lump sum per stay day, labelled 'consultancy fee' and meant for remuneration of the 'intellectual' act of the performing radiologist. Lump sums are chargeable whether or not any medical imaging act was performed. Consultancy fees are higher for radiologists with an accreditation certificate. As with laboratory tests, lump sum payments to hospitals have little connection with actual services delivered. To restore the link with actual practice for inpatients, lump sum payments were substituted by fee-for-service amounts extrapolated to such an extent that 'theoretical' 100% values were obtained. Consequently lump sum amounts for medical imaging were discarded (cost class 'EXC').

There is however one group of medical imaging codes that is excluded from this inpatient lump sum ruling: angiocardio- and coronarographies (Table 51). For those billings the full reimbursement amounts are recorded in the IMA data.
<table><caption>Table 51. Medical imaging, inpatient codes excluded from lump sum ruling</caption><thead><tr><td>NIHDI code</td><td>Label code</td></tr></thead><tbody><tr><td>453084</td><td>Angiocardiopneumography, one angle of incidence</td></tr><tr><td>464085</td><td>Angiocardiopneumography, one angle of incidence</td></tr><tr><td>453106</td><td>Angiocardiopneumography, two or more angles of incidence</td></tr><tr><td>464100</td><td>Angiocardiopneumography, two or more angles of incidence</td></tr><tr><td>453121</td><td>Coronarography, one angle of incidence</td></tr><tr><td>464122</td><td>Coronarography, one angle of incidence</td></tr><tr><td>453143</td><td>Coronarography, two or more angles of incidence</td></tr><tr><td>464144</td><td>Coronarography, two or more angles of incidence</td></tr></tbody></table>

## Outpatients

For outpatients a different and more complex lump sum system was developed: there are three different lump sum fees, depending on which (set of) MI investigation(s) is performed (see Table 50 and also addendum 10). No lump sum is chargeable without medical imaging being performed and all three lump sum codes are mutually exclusive (see groups A to C in table 15). Consultancy fees come on top and are higher priced for radiologists with an accreditation certificate, yet they are not always chargeable (group E in Table 52). Moreover, not all NIHDI codes for MI are entitled to a lump sum and/or consultancy fee charging (group n/a in Table 52).

<table><caption>Table 52. Lump sum and/or consultancy fee charging for outpatients</caption><thead><tr><td>Consultancy_fee</td><td>460994</td><td>461016</td><td>460972</td><td># NIHDI_codes</td><td>Extrapolation group</td></tr></thead><tbody><tr><td>1</td><td>1</td><td>0</td><td>0</td><td>23</td><td>A</td></tr><tr><td>1</td><td>0</td><td>1</td><td>0</td><td>31</td><td>B</td></tr><tr><td>1</td><td>0</td><td>0</td><td>1</td><td>5</td><td>C</td></tr><tr><td>1</td><td>0</td><td>0</td><td>0</td><td>32</td><td>D</td></tr><tr><td>0</td><td>0</td><td>0</td><td>1</td><td>48</td><td>E</td></tr><tr><td>0</td><td>0</td><td>0</td><td>0</td><td>107</td><td>n/a</td></tr></tbody></table>

This system maintains to some extent connection with actual services delivered. Normally there would be less need for a (rather complex) extrapolation procedure in this sector: provided all MI reimbursements were to be included, we could as well keep the lump sums. However, since we had to sub group MI investigations in 'HBV' and 'nHBV', we were faced to an impossible task to split the corresponding lump sum amounts in proportional fractions, which would be different for each set of services charged per patient and per billing day. The only way to get to a feasible split was to discard the lump sums and extrapolate the fee-for-service amounts.

## Calculation of extrapolation factors

'As good as possible' extrapolation factors for inpatient and for outpatient services respectively were calculated based on final NIHDI accountancy records (doc N) for the year 2006 (Table 53). For outpatient services we were able to calculate a separate EF for each extrapolation group (A to E - see Table 52) through a weighing procedure.
<table><caption>Table 53. Total NIHDI expenses (in EURO) on inpatient medical imaging in 2006</caption><thead><tr><th rowspan="2">Part / Domain</th><th colspan="5">Outpatient</th><th>Inpatient</th></tr><tr><th>Group A</th><th>Group B</th><th>Group C</th><th>Group D</th><th>Group E</th><th>All codes (**)</th></tr></thead><tbody><tr><td>Fee-for-service (*)</td><td>27.535.485</td><td>142.387.754</td><td>145.665</td><td>270.319.534</td><td>55.202.561</td><td>150.471.341</td></tr><tr><td>Lump sums (***)</td><td>62.105.197</td><td>829.240.836</td><td>602.184</td><td>507.817.242</td><td>124.507.195</td><td>97.268.027</td></tr><tr><td>Year total</td><td>89.640.682</td><td>971.628.590</td><td>747.849</td><td>778.136.776</td><td>179.709.757</td><td>247.739.368</td></tr><tr><td>Extrapolation factor</td><td>3,2555</td><td>6,8238</td><td>5,1340</td><td>2,8786</td><td>3,2555</td><td>1,6464</td></tr></tbody></table>

### 5.3.4.3 In patient pharmaceuticals

Until 1983 hospital drugs were completely reimbursed on a fee-for-service basis. Since then, several efforts have been taken in order to control escalating expenditures for pharmaceuticals. A first step towards prospective pharmaceutical budgeting for hospitalized patients was made in 1997 for the prophylactic use of antibiotics with surgical interventions. Registration of prophylactic antibiotic deliveries was done by means of newly introduced NIHDI billing codes, accompanied with the recording of the code of the corresponding intervention (in a 'relative code' field). However, track of the delivered antibiotic brand was lost. This system was applied until July 1, 2006.

Since July 1, 2006 a prospective budget for pharmaceuticals delivered to acute hospital inpatients was introduced, disbursed by means of hospital specific lump sum allocations, chargeable under a new NIHDI code 756000 for each (inpatient) admission, regardless presence or absence of any pharmaceutical consumption. Most – but not all – pharmaceuticals are integrated in this budget for approximately 75% of their reimbursement tariff. The remaining 25% of their public reimbursement tariff is still paid through a set of accompanying new codes (see Addendum 11) recorded along with the brand code of the drug. Theoretically this should allow tracking the consumption of hospital pharmaceuticals delivered.

Prospective budgets for inpatient pharmaceuticals are based on hospitals' (retrospective) case-mix data and the national average cost per APR-DRG and severity of illness (SOI), excluding outliers outside the $Q3 + 2 \times (Q3-Q1)$ limit. Calculations are made on most recent available linked MCD-HBD data<fnref n="9" /> (called 'reference year'). This case-mix based 'fine tuning' results in a different lump sum per admission being calculated for each hospital.

However, not all pharmaceuticals were entered in this system. For rather comprehensible reasons special ATC sub groups of pharmaceuticals were excluded:

therapeutically important innovative medication;

particular 'high cost' medication, including orphan drugs, cytostatics, immunoglobulins, immunosuppressors, human albumin, anti-thrombotics and haemostatics, antidotes, somatostatins, direct acting antivirals including HIV antivirals as well as radio-isotopes.

Since all hepatitis B specific medication falls under this last category, full NIHDI cost recordings are still available in the IMA data after June, 30th 2006 and no need for recalculation is present.

<footnote>(*) Calculated for related MI codes. (**) Angiocardiopneumographies and coronarographies excluded. (***) For outpatient lump sums proportionally weighed over the 5 groups.</footnote>

<footnote n="9">⁹ Linkage process of MCR (minimal clinical records) with HBD (hospital billing data) takes at least 2 years for completion.</footnote>
On the other hand, for medication that falls under the lump sum per admission ruling, full cost price calculation, by substituting with exact 100% tariffs valid at time of delivery (direct extrapolation), turns out to fall beyond reach. Indeed, profound validation analyses on remitted hospital data after introduction of this system has revealed major lacunas in the recordings of quantities delivered (confirmed in present study on data 2006), rendering any effort to directly recalculate ‘100% costs’ per brand code (CNK) futile.

Consequently reimbursement amounts for inpatient medication that fall under ‘lump sum per admission ruling’ were indirectly extrapolated to an estimated 100% value by multiplying them by an overall extrapolation factor calculated on full NIHDI accountancy records (Doc N) of the related NIHDI codes (see see Addendum 11) in the second semester of year 2006. Result of this calculation is presented in Table 54.

<table><caption>Table 54. Pharmaceutical inpatient expenses in 2006, 2nd semester, and all hospitals</caption><thead><tr><td>Part</td><td>Totals</td></tr></thead><tbody><tr><td>Fee-for-service</td><td>35.802.033,65 €</td></tr><tr><td>Lump sum</td><td>125.395.855,20 €</td></tr><tr><td>Total</td><td>161.197.888,85 €</td></tr><tr><td>Extrapolation factor</td><td>4,5025</td></tr></tbody></table>

After flagging all IMA inpatient pharmaceuticals records for their eventual entry date in the lump sum per admission ruling, we multiplied the corresponding fee-for-service reimbursement amounts of lump sum regulation subjective pharmaceuticals with above mentioned extrapolation factor.

### 5.3.4.4 Stay day remunerations

#### Extrapolation

Since July 2002 refunding of not directly patient imputable hospital costs (capital expenditures for housing and medico-technical facilities, hotel function, nursing care, etc.) chiefly is regulated by the ‘Budget of Financial Means’ (BFM) allocated to Belgian hospitals per budget year which runs from July 1 to June 30 of the next year.

For stays reimbursed by compulsory health insurance, disbursement of this budget consists of a fixed and a variable part. The variable part of the BFM applies exclusively to subparts B1 and B2 of the BFM, which specifically cover medical hospital activities and together encompass (theoretically) 20% of the total budget. Disbursement of these 20% is done by means of lump sums ‘per admission’ and/or ‘per stay day’, both charged with a set of specific NIHDI codes (grouped in N-group N87) that are recorded in the IMA billing data of the hospitals. Calculation of the variable part share for each hospital and its corresponding lump sum tariffs is based (amongst other complex criteria) on the number of ‘justified bed occupation days’ and/or the number of hospital admissions in previous year(s), with half yearly revisions. As a result, lump sum allocations vary considerably between hospitals.

The fixed part (approximately 80%) can be attributed to neither an individual stay nor a patient and therefore is disbursed directly to the hospitals through monthly ‘twelfths’. This is also why this fixed part is not available in the IMA individual patients’ billing records. In cost studies this important lacuna in the data has to be taken into account.

For stays under private insurance covering (including e.g. labour accidents) full stay day prices are charged by the hospitals. For that purpose full stay day prices for each hospital are periodically web published by the NIHDIs. Using those tables direct extrapolation to (official) 100% stay day remunerations is feasible.

<footnote>r Lump sums tariffs differ not only per hospital but also per type of bed occupied: acute beds, (chronic) rehabilitation beds, psychiatric beds, beds for severe burns treatment and beds for palliative care. Per admission lump sums apply only to acute beds (including severe burns).</footnote>

<footnote>s at: http://riziv.fgov.be/care/nl/hospitals/specific-information/prices-day/index.htm</footnote>
### Standardization

Lump sums for (in)patient stay day's price differently for each hospital: stays in a 'higher priced' hospital induce a higher HDI cost than their equivalents in a 'cheaper priced' hospital. Neutralization comes with standardization of 100% stay day remunerations for all included stays to a common average ('standard') stay day remuneration, and this per type of bed (acute in present study) occupied.

However, since liver transplant surgery is restricted to 'high tech' university hospitals (3 participating in present study) with higher stay day tariffs, standardization for acute bed stay days was confined to this subgroup (standard tariff = 458,20 €), as opposed to the remaining, non university hospitals (standard tariff = 358,28 €).

#### 5.3.4.5 Integrated cost sub grouping per patient

After going independently through the three previous decision levels, an exercise of integration remains to be done: inclusion-exclusion decisions taken in one level can sometimes be overruled by another, 'higher' level.

### Global rules applied for separating HBV treatment related health care services (HBV) from others (nHBV and SOC)

1. In first instance, all lump sum remunerations for inpatient and day care hospital laboratory tests and medical imaging were totally discarded and replaced by 100% extrapolated 'à l'acte' remunerations (see section 4).

2. Patients' own 'out-of-pocket' contributions (sub group 'PAT') were discarded since they would only give a partial image of this particular field. Indeed, not all such contributions (only 'official') are registered in the IMA data.

3. All hepatitis B specific laboratory tests and subsidiary hepatobiliary interventions (see Table 8) were included in the 'HBV' group, irrespective of the inclusion-exclusion status of the hospital stays (N = 273), with exception, however of the "10 Not active" stage patients: any such intervention eventually found was to be considered as bearing no relation to HBV infection status.

4. All other health care services and medical supplies delivered were flagged following their primary NIHDI code based sub grouping. However, they were discarded if charged in affirmatively excluded hospital stays.

5. Costs related to social security 'low income compensation' regulations (sub group 'SOC') were separated from the other 2 sub groups, since those costs reflect a global, retro-active mechanism of 'compensatory' patient refunding, depending on his taxable income and the cumulative total of all legally imposed personal contributions in health care costs in the corresponding fiscal year.

### Global rules applied for separating HBV treatment related pharmaceutical costs (HBV) from others (nHBV)

1. All hepatitis B specific medication was included in the 'HBV' group (see Table 10 and Addendum 8), irrespective of the inclusion-exclusion status of the hospital stays (N = 273). There is however one exception: for group '01 Non active', any eventual finding of hepatitis B antivirals was considered as not HBV related and therefore labelled as 'nHBV'.

2. All medication under lump sum ruling, in hospital stays affirmatively identified as hepatitis B related (N = 51 included stays, see section 3.1), was also included in the 'HBV' group. In doing so we tried not to exclude medication or interventions related to complications occurred during HBV diagnosis or treatment procedures or its clinical evolution (e.g. metastasis with HCC). There is however one exception for such stays: all specific (and costly) medication or other health care services positively identified as being related to pre-existent or concurrent non HBV pathology was labelled as 'nHBV' (e.g. one case with factor VIII coagulopathy).
3. All other medication under lump sum ruling, in hospital stays not positively identified as hepatitis B related (N= 108), but not excluded was labelled as 'nHBV'.

4. All medication under lump sum ruling, i.e. not HBV related, in hospital stays, affirmatively excluded (N =114), was not withheld for cost calculation.

### 5.3.5 Results

#### 5.3.5.1 Final patient counts

For various reasons another 23 patients were discarded from the costs calculations: high likelihood for 'missing HBV related data': 7 in the 'Not active' group, 9 in the 'Active group', 3 in the 'Comp Cirrh' group and 2 in the 'HCC group'. Another patient in the Active group was excluded because of the finding of specific HIV anti viral treatment. Finally one liver transplant patient deceased within one month after transplantation and consequently was equally discarded. Final counts are to be found in Table 55.

#### 5.3.5.2 Total HDI costs and Average cost per patient, per clinical stage for one year (2006)

Total HDI costs were calculated per clinical stage and per cost sub group. Dividing those totals by the corresponding overall number of patients in each clinical stage group gives us the average cost per clinical stage and per patient for one year, i.e. 2006.
<table><caption>Table 55. Average cost (in EURO) per clinical stage, per cost sub group and per patient for year 2006</caption><thead><tr><th rowspan="2">Path_group</th><th rowspan="2">N patients</th><th colspan="2">HBV related w.o HBV antivirals</th><th colspan="2">HBV related withHBV antivirals</th><th colspan="2">Not HBV related</th><th colspan="2">Low income compensations</th><th colspan="2">All HDI costs</th><th colspan="2">Patient's co-payments</th></tr><tr><th>Total (€)</th><th>Avg p.p./yr</th><th>Total (€)</th><th>Avg p.p./yr</th><th>Total (€)</th><th>Avg p.p./yr</th><th>Total (€)</th><th>Avg p.p./yr</th><th>Total (€)</th><th>Avg p.p./yr</th><th>Total (€)</th><th>Avg p.p./yr</th></tr></thead><tbody><tr><td>Not active</td><td>71</td><td>7.658</td><td>108</td><td>7.658</td><td>108</td><td>164.731</td><td>2.320</td><td>1.988</td><td>28</td><td>174.378</td><td>2.456</td><td>13.830</td><td>195</td></tr><tr><td>Active</td><td>141</td><td>78.044</td><td>554</td><td>329.411</td><td>2.336</td><td>908.666</td><td>6.444</td><td>11.244</td><td>80</td><td>1.249.321</td><td>8.860</td><td>42.696</td><td>303</td></tr><tr><td>Comp Cirrh</td><td>47</td><td>49.104</td><td>1.045</td><td>112.793</td><td>2.400</td><td>258.124</td><td>5.492</td><td>4.494</td><td>96</td><td>375.411</td><td>7.987</td><td>16.245</td><td>346</td></tr><tr><td>Decomp Cirrh</td><td>5</td><td>31.935</td><td>6.387</td><td>39.393</td><td>7.879</td><td>65.598</td><td>13.120</td><td>986</td><td>197</td><td>105.977</td><td>21.195</td><td>1.903</td><td>381</td></tr><tr><td>HCC</td><td>4</td><td>34.111</td><td>8.528</td><td>37.148</td><td>9.287</td><td>11.451</td><td>2.863</td><td>921</td><td>230</td><td>49.520</td><td>12.380</td><td>3.130</td><td>783</td></tr><tr><td>Liver transplant</td><td>5</td><td>468.642</td><td>93.728</td><td>481.548</td><td>96.310</td><td>41.546</td><td>8.309</td><td>2.728</td><td>546</td><td>525.823</td><td>105.165</td><td>4.206</td><td>841</td></tr><tr><td>Post transpl</td><td>41</td><td>281.864</td><td>7.047</td><td>328.840</td><td>8.020</td><td>323.051</td><td>7.879</td><td>7.379</td><td>180</td><td>659.270</td><td>16.080</td><td>16.976</td><td>414</td></tr></tbody></table>

<footnote>(*) calculated on overall sub group patient counts; Avg p.p. / yr: Average per patient per year</footnote>
### 5.3.5.3 Cost distributions per clinical stage

For each clinical stage and cost sub group descriptive statistic parameters were calculated (Table 56). Specific HBV anti viral medication costs are included.

<table><caption>Table 56. Descriptive statistics per clinical stage and cost sub group (Euro)</caption><thead><tr><th>Not Active</th><th>N</th><th>Min</th><th>Q1</th><th>Q2</th><th>Q3</th><th>Max</th><th>Q3+2*(Q3-Q1)</th><th>Outlier count</th></tr></thead><tbody><tr><td>HBV</td><td>71</td><td>9,23</td><td>50,86</td><td>78,00</td><td>129,16</td><td>476,54</td><td>285,76</td><td>5</td></tr><tr><td>nHBV</td><td>71</td><td>9,85</td><td>246,85</td><td>632,44</td><td>2,493,72</td><td>20.203,40</td><td>6.987,47</td><td>8</td></tr><tr><td>SOC</td><td>10</td><td>5,35</td><td>55,48</td><td>151,76</td><td>314,58</td><td>549,60</td><td>832,77</td><td>0</td></tr><tr><th>Active</th><th>N</th><th>Min</th><th>Q1</th><th>Q2</th><th>Q3</th><th>Max</th><th>Q3+2*(Q3-Q1)</th><th>Outlier count</th></tr><tr><td>HBV</td><td>141</td><td>18,37</td><td>398,40</td><td>1.057,59</td><td>4.297,27</td><td>7.915,28</td><td>12.095,01</td><td>0</td></tr><tr><td>nHBV</td><td>141</td><td>2,80</td><td>311,18</td><td>1.041,90</td><td>2.481,21</td><td>353.279,4*</td><td>6.821,27</td><td>17</td></tr><tr><td>SOC</td><td>26</td><td>11,19</td><td>113,42</td><td>195,61</td><td>442,65</td><td>1.799,64</td><td>1.101,12</td><td>5</td></tr><tr><th>Comp. Cirrhosis</th><th>N</th><th>Min</th><th>Q1</th><th>Q2</th><th>Q3</th><th>Max</th><th>Q3+2*(Q3-Q1)</th><th>Outlier count</th></tr><tr><td>HBV</td><td>47</td><td>52,87</td><td>1.071,58</td><td>1.379,21</td><td>3.164,08</td><td>7.810,27</td><td>7.349,07</td><td>2</td></tr><tr><td>nHBV</td><td>47</td><td>11,15</td><td>467,81</td><td>1.274,01</td><td>3.303,79</td><td>100.397,16</td><td>8.975,75</td><td>3</td></tr><tr><td>SOC</td><td>14</td><td>11,83</td><td>106,32</td><td>238,01</td><td>490,06</td><td>840,00</td><td>1.257,54</td><td>0</td></tr><tr><th>Decomp. Cirrhosis</th><th>N</th><th>Min</th><th>Q1</th><th>Q2</th><th>Q3</th><th>Max</th><th>Q3+2*(Q3-Q1)</th><th>Outlier count</th></tr><tr><td>HBV</td><td>5</td><td>1.341,27</td><td>6.040,13</td><td>6.767,82</td><td>9.846,43</td><td>15.397,00</td><td>17.459,03</td><td>0</td></tr><tr><td>nHBV</td><td>5</td><td>395,85</td><td>1.419,00</td><td>1.799,81</td><td>3.649,41</td><td>58.333,98</td><td>8.110,23</td><td>2</td></tr><tr><td>SOC</td><td>2</td><td>153,35</td><td>-</td><td>-</td><td>-</td><td>832,94</td><td>-</td><td>-</td></tr><tr><th>HCC</th><th>N</th><th>Min</th><th>Q1</th><th>Q2</th><th>Q3</th><th>Max</th><th>Q3+2*(Q3-Q1)</th><th>Outlier count</th></tr><tr><td>HBV</td><td>4</td><td>272,49</td><td>1.959,65</td><td>3.904,19</td><td>10.387,84</td><td>29.066,69</td><td>27.244,23</td><td>1</td></tr><tr><td>nHBV</td><td>4</td><td>388,70</td><td>1.002,70</td><td>2.954,49</td><td>4.814,48</td><td>5.153,09</td><td>12.438,04</td><td>0</td></tr><tr><td>SOC</td><td>1</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td></tr><tr><th>Liver transplant</th><th>N</th><th>Min</th><th>Q1</th><th>Q2</th><th>Q3</th><th>Max</th><th>Q3+2*(Q3-Q1)</th><th>Outlier count</th></tr><tr><td>HBV</td><td>5</td><td>71.565,72</td><td>78.847,33</td><td>108.383,04</td><td>108.787,40</td><td>113.964,82</td><td>168.667,54</td><td>0</td></tr><tr><td>nHBV</td><td>5</td><td>4.490,41</td><td>5.837,61</td><td>7.341,79</td><td>10.417,41</td><td>10.417,41</td><td>19.577,02</td><td>0</td></tr><tr><td>SOC</td><td>5</td><td>69,56</td><td>96,86</td><td>154,62</td><td>639,33</td><td>1.710,14</td><td>1.724,27</td><td>0</td></tr><tr><th>Post transplant</th><th>N</th><th>Min</th><th>Q1</th><th>Q2</th><th>Q3</th><th>Max</th><th>Q3+2*(Q3-Q1)</th><th>Outlier count</th></tr><tr><td>HBV</td><td>40</td><td>148,66</td><td>5.059,51</td><td>6.198,03</td><td>7.582,81</td><td>34.289,09</td><td>12.629,41</td><td>5</td></tr><tr><td>nHBV</td><td>40</td><td>1.871,39</td><td>4.919,03</td><td>7.094,13</td><td>8.716,51</td><td>41.578,23</td><td>16.311,48</td><td>1</td></tr><tr><td>SOC</td><td>15</td><td>27,00</td><td>174,44</td><td>304,26</td><td>822,09</td><td>1.306,56</td><td>2.117,39</td><td>0</td></tr></tbody></table>

The 99% confidence intervals of means for cost sub group HBV are listed in Table 57..

<footnote>* Patient with hemophilia, needing huge amounts of factor VIII</footnote>
<table><caption>Table 57. 99% confidence intervals of the means (cost sub group HBV – EURO)</caption><thead><tr><th rowspan="2">Clin. stage</th><th rowspan="2">N</th><th colspan="4">With HBV antivirals</th><th colspan="4">Without HBV antivirals</th></tr><tr><th>Average</th><th>SD</th><th>Lo 99% CI limit</th><th>Up 99% CI limit</th><th>Average</th><th>SD</th><th>Lo 99% CI limit</th><th>Up 99% CI limit</th></tr></thead><tbody><tr><td>Not Active</td><td>71</td><td>107,9</td><td>92,2</td><td>79,7</td><td>136,0</td><td>107,8</td><td>92,2</td><td>79,7</td><td>136,0</td></tr><tr><td>Active</td><td>141</td><td>2.336,3</td><td>2559,4</td><td>1.781,1</td><td>2.891,5</td><td>553,5</td><td>829,7</td><td>373,5</td><td>733,5</td></tr><tr><td>Comp. Cirrhosis</td><td>47</td><td>2.399,9</td><td>2237,5</td><td>1.559,19</td><td>3.240,5</td><td>1.044,7</td><td>1379,4</td><td>526,5</td><td>1.563,0</td></tr><tr><td>Decomp. Cirrhosis</td><td>5</td><td>7.878,5</td><td>4642,2</td><td>2.530,9</td><td>13.226,1</td><td>6.387,1</td><td>5168,8</td><td>432,8</td><td>12.341,3</td></tr><tr><td>HCC</td><td>4</td><td>9.286,9</td><td>11517,1</td><td>-5.546,2</td><td>24.120,0</td><td>8.527,6</td><td>10620,9</td><td>-5.151,2</td><td>22.206,7</td></tr><tr><td>Liver transplantation</td><td>5</td><td>96.309,6</td><td>17494,9</td><td>76.156,4</td><td>116.462,8</td><td>93.728</td><td>15846,9</td><td>75.473,5</td><td>111.983</td></tr><tr><td>Post transplantation</td><td>40</td><td>7.759,5</td><td>6105,74</td><td>5.272,8</td><td>10.246,21</td><td>7.046,6</td><td>6264,2</td><td>4.495,3</td><td>9.597,8</td></tr></tbody></table>

### 5.3.5.4 Cost profiles per clinical stage in cost sub group HBV

From a clinicians' point of view it seems interesting to have an overview of the costs' profiles per clinical stage in cost sub group HBV: see Table 58. Costs were aggregated by NIHDI N-groups. Cost groups lower ≤ 500 € total HDI cost were omitted.

<table><caption>Table 58. Cost profiles (in EURO) per clinical stage in cost sub group HBV</caption><thead><tr><th>Path_group</th><th>N_group</th><th>Label_N-grp_UK</th><th>#Patient</th><th>HDI_cost (€)</th><th>Avg. p.p. (€)</th></tr></thead><tbody><tr><td rowspan="3">Not active</td><td>N01</td><td>Outpatient consultations, home visits and medical advice</td><td>57</td><td>3.987</td><td>69,94</td></tr><tr><td>N60</td><td>Clinical biology - art. 24§1</td><td>68</td><td>2.835</td><td>41,69</td></tr><tr><td>N08</td><td>Clinical biology - accessible for general practitioners (art. 3)</td><td>63</td><td>679</td><td>10,78</td></tr><tr><td rowspan="12">Active</td><td>N86</td><td>Pharmaceutics</td><td>14</td><td>15.741</td><td>1.124,34</td></tr><tr><td>N87</td><td>Hospital nursing</td><td>6</td><td>4.499</td><td>749,87</td></tr><tr><td>N50</td><td>Röntgendiagnosis</td><td>80</td><td>14.611</td><td>182,63</td></tr><tr><td>N60</td><td>Clinical biology - art. 24§1</td><td>139</td><td>22.966</td><td>165,22</td></tr><tr><td>N63</td><td>Anatomopathology</td><td>3</td><td>436</td><td>145,28</td></tr><tr><td>N42</td><td>Gastro-entereology</td><td>17</td><td>2.231</td><td>131,23</td></tr><tr><td>N00</td><td>Surveillance fees for hospitalized patients</td><td>41</td><td>3.823</td><td>93,24</td></tr><tr><td>N01</td><td>Outpatient consultations, home visits and medical advice</td><td>125</td><td>11.610</td><td>92,88</td></tr><tr><td>N13</td><td>General procedures and functions, accessible for all medical specialists</td><td>27</td><td>1.402</td><td>51,94</td></tr><tr><td>N80</td><td>Biosynthetics and disposables art 35 & 35bis</td><td>23</td><td>1.186</td><td>51,58</td></tr><tr><td>N08</td><td>Clinical biology - accessible for general practitioners (art. 3)</td><td>126</td><td>4.764</td><td>37,81</td></tr><tr><td>N04</td><td>Dental care</td><td>39</td><td>1.239</td><td>31,76</td></tr></tbody></table>
<table><thead><tr><th>Path_group</th><th>N_group</th><th>Label_N-grp_UK</th><th># Patient</th><th>HDI_cost (€)</th><th>Avg. p.p. (€)</th></tr></thead><tbody><tr><td rowspan="10">Comp Cirrh</td><td>N87</td><td>Hospital nursing</td><td>10</td><td>8.416</td><td>841,58</td></tr><tr><td>N86</td><td>Pharmaceutics</td><td>6</td><td>4.861</td><td>810,22</td></tr><tr><td>N50</td><td>Röntgendiagnosis</td><td>41</td><td>14.475</td><td>353,05</td></tr><tr><td>N60</td><td>Clinical biology - art. 24§1</td><td>47</td><td>8.270</td><td>175,95</td></tr><tr><td>N42</td><td>Gastro-entereology</td><td>13</td><td>2.223</td><td>171,03</td></tr><tr><td>N01</td><td>Outpatient consultations, home visits and medical advice</td><td>42</td><td>4.140</td><td>98,56</td></tr><tr><td>N63</td><td>Anatomopathology</td><td>15</td><td>1.366</td><td>91,08</td></tr><tr><td>N00</td><td>Surveillance fees for hospitalized patients</td><td>12</td><td>1.016</td><td>84,63</td></tr><tr><td>N08</td><td>Clinical biology - accessible for general practitioners (art. 3)</td><td>44</td><td>2.743</td><td>62,34</td></tr><tr><td>N80</td><td>Biosynthetics and disposables art 35 & 35bis</td><td>9</td><td>443</td><td>49,20</td></tr><tr><td>N04</td><td>Dental care</td><td>11</td><td>263</td><td>23,90</td></tr><tr><td rowspan="10">Decomp Cirrh</td><td>N87</td><td>Hospital nursing</td><td>3</td><td>16.171</td><td>5.390,39</td></tr><tr><td>N86</td><td>Pharmaceutics</td><td>3</td><td>3.067</td><td>1.022,45</td></tr><tr><td>N60</td><td>Clinical biology - art. 24§1</td><td>5</td><td>4.809</td><td>961,82</td></tr><tr><td>N50</td><td>Röntgendiagnosis</td><td>5</td><td>2.553</td><td>510,67</td></tr><tr><td>N00</td><td>Surveillance fees for hospitalized patients</td><td>3</td><td>1.173</td><td>391,11</td></tr><tr><td>N63</td><td>Anatomopathology</td><td>2</td><td>752</td><td>376,18</td></tr><tr><td>N42</td><td>Gastro-entereology</td><td>4</td><td>1.383</td><td>345,68</td></tr><tr><td>N08</td><td>Clinical biology - accessible for general practitioners (art. 3)</td><td>5</td><td>1.242</td><td>248,34</td></tr><tr><td>N01</td><td>Outpatient consultations, home visits and medical advice</td><td>5</td><td>1.036</td><td>207,13</td></tr><tr><td rowspan="15">HCC</td><td>N87</td><td>Hospital nursing</td><td>1</td><td>12.371</td><td>12.371,35</td></tr><tr><td>N86</td><td>Pharmaceutics</td><td>1</td><td>2.321</td><td>2.321,04</td></tr><tr><td>N50</td><td>Röntgendiagnosis</td><td>4</td><td>8.442</td><td>2.110,57</td></tr><tr><td>N60</td><td>Clinical biology - art. 24§1</td><td>4</td><td>3.127</td><td>781,74</td></tr><tr><td>N80</td><td>Biosynthetics and disposables art 35 & 35bis</td><td>2</td><td>1.456</td><td>727,95</td></tr><tr><td>N23</td><td>Abdominal surgery</td><td>1</td><td>724</td><td>723,93</td></tr><tr><td>N14</td><td>Anesthesiology</td><td>1</td><td>545</td><td>544,57</td></tr><tr><td>N42</td><td>Gastro-entereology</td><td>2</td><td>884</td><td>442,24</td></tr><tr><td>N19</td><td>Surcharges for night / weekend services - Article 26, §1 et 1 ter</td><td>1</td><td>327</td><td>326,74</td></tr><tr><td>N46</td><td>Nuclear medicine in vivo</td><td>2</td><td>494</td><td>246,83</td></tr><tr><td>N00</td><td>Surveillance fees for hospitalized patients</td><td>2</td><td>449</td><td>224,73</td></tr><tr><td>N13</td><td>General procedures and functions, accessible for all medical specialists</td><td>3</td><td>560</td><td>186,74</td></tr><tr><td>N01</td><td>Outpatient consultations, home visits and medical advice</td><td>4</td><td>571</td><td>142,87</td></tr><tr><td>N63</td><td>Anatomopathology</td><td>3</td><td>425</td><td>141,79</td></tr><tr><td>N08</td><td>Clinical biology - accessible for general practitioners (art. 3)</td><td>4</td><td>503</td><td>125,75</td></tr><tr><td rowspan="2">Liver transpl</td><td>N86</td><td>Pharmaceutics</td><td>5</td><td>132.481</td><td>26.496,29</td></tr><tr><td>N87</td><td>Hospital nursing</td><td>5</td><td>117.924</td><td>23.584,78</td></tr></tbody></table>
<table><thead><tr><th>Path_group</th><th>N_group</th><th>Label_N-grp_UK</th><th># Patient</th><th>HDI_cost (€)</th><th>Avg. p.p. (€)</th></tr></thead><tbody><tr><td></td><td>N33</td><td>Transplantations</td><td>5</td><td>99.657</td><td>19.931,36</td></tr><tr><td></td><td>N60</td><td>Clinical biology - art. 24§1</td><td>5</td><td>43.080</td><td>8.615,95</td></tr><tr><td></td><td>N50</td><td>Röntgendiagnosis</td><td>5</td><td>19.694</td><td>3.938,87</td></tr><tr><td></td><td>N14</td><td>Anesthesiology</td><td>5</td><td>8.478</td><td>1.695,60</td></tr><tr><td></td><td>N08</td><td>Clinical biology - accessible for general practitioners (art. 3)</td><td>5</td><td>7.628</td><td>1.525,55</td></tr><tr><td></td><td>N12</td><td>Reanimation</td><td>5</td><td>7.462</td><td>1.492,32</td></tr><tr><td></td><td>N80</td><td>Biosynthetics and disposables art 35 & 35bis</td><td>5</td><td>6.695</td><td>1.339,03</td></tr><tr><td></td><td>N19</td><td>Surcharges for night / weekend services - Article 26, §1 et 1 ter</td><td>5</td><td>4.436</td><td>887,16</td></tr><tr><td></td><td>N57</td><td>Physical therapy</td><td>2</td><td>1.446</td><td>722,95</td></tr><tr><td></td><td>N63</td><td>Anatomopathology</td><td>5</td><td>3.416</td><td>683,13</td></tr><tr><td></td><td>N01</td><td>Outpatient consultations, home visits and medical advice</td><td>5</td><td>3.068</td><td>613,63</td></tr><tr><td></td><td>N51</td><td>Percutanuous interventions</td><td>4</td><td>2.030</td><td>507,57</td></tr><tr><td></td><td>N42</td><td>Gastro-entereology</td><td>3</td><td>1.479</td><td>493,08</td></tr><tr><td></td><td>N00</td><td>Surveillance fees for hospitalized patients</td><td>5</td><td>2.267</td><td>453,49</td></tr><tr><td></td><td>N46</td><td>Nuclear medicine in vivo</td><td>2</td><td>753</td><td>376,32</td></tr><tr><td></td><td>N23</td><td>Abdominal surgery</td><td>2</td><td>676</td><td>337,83</td></tr><tr><td></td><td>N06</td><td>Nursery care</td><td>4</td><td>930</td><td>232,56</td></tr><tr><td></td><td>N55</td><td>Cardiology</td><td>5</td><td>1.126</td><td>225,23</td></tr><tr><td></td><td>N05</td><td>Kinesitherapy</td><td>4</td><td>821</td><td>205,31</td></tr><tr><td></td><td>N04</td><td>Dental care</td><td>2</td><td>409</td><td>204,27</td></tr><tr><td></td><td>N82</td><td>Implants & disposables art 28 §1</td><td>3</td><td>568</td><td>189,35</td></tr><tr><td></td><td>N56</td><td>Neuropsychiatry</td><td>3</td><td>488</td><td>162,59</td></tr><tr><td></td><td>N13</td><td>General procedures and punctions, accessible for all medical specialists</td><td>5</td><td>769</td><td>153,73</td></tr><tr><td rowspan="20">Post transpl</td><td>N86</td><td>Pharmaceutics</td><td>36</td><td>184.407</td><td>5.122,41</td></tr><tr><td>N87</td><td>Hospital nursing</td><td>10</td><td>37.012</td><td>3.701,21</td></tr><tr><td>N25</td><td>Thoracal surgery</td><td>1</td><td>1.584</td><td>1.584,36</td></tr><tr><td>N50</td><td>Röntgendiagnosis</td><td>22</td><td>18.443</td><td>838,34</td></tr><tr><td>N51</td><td>Percutanuous interventions</td><td>2</td><td>1.074</td><td>537,10</td></tr><tr><td>N14</td><td>Anesthesiology</td><td>3</td><td>1.572</td><td>524,03</td></tr><tr><td>N80</td><td>Biosynthetics and disposables art 35 & 35bis</td><td>8</td><td>4.127</td><td>515,93</td></tr><tr><td>N42</td><td>Gastro-entereology</td><td>10</td><td>4.836</td><td>483,58</td></tr><tr><td>N60</td><td>Clinical biology - art. 24§1</td><td>40</td><td>15.241</td><td>381,03</td></tr><tr><td>N00</td><td>Surveillance fees for hospitalized patients</td><td>14</td><td>3.177</td><td>226,93</td></tr><tr><td>N63</td><td>Anatomopathology</td><td>10</td><td>1.595</td><td>159,49</td></tr><tr><td>N41</td><td>Pneumology</td><td>2</td><td>300</td><td>149,82</td></tr><tr><td>N05</td><td>Kinesitherapy</td><td>2</td><td>254</td><td>127,10</td></tr><tr><td>N08</td><td>Clinical biology - accessible for general practitioners (art. 3)</td><td>40</td><td>4.206</td><td>105,14</td></tr><tr><td>N01</td><td>Outpatient consultations, home visits and medical advice</td><td>37</td><td>2.986</td><td>80,71</td></tr><tr><td>N04</td><td>Dental care</td><td>10</td><td>358</td><td>35,83</td></tr></tbody></table>
### 5.3.6 Discussion

In present study we faced a complex task to calculate health insurance costs for a specific pathology from administrative reimbursement databases. Several aspects of this work need some reflection and elucidation on feasibility, usefulness and validity of available data as well as, last but not least, constraints and their inherent caveats. First of all we should keep in mind that by "costs" we mean the amounts paid by national health insurance (public health and NIHDI), not those paid by the patient him-/herself, nor other societal costs related to sickness leave and incapability to work.

**Tracking and segregation of hepatitis B virus related reimbursements**

Next, hepatitis B related disease typically emerges as an epiphenomenon with pre-existent and/or concurrent disease. The tables in addenda 2 and 3 perfectly illustrate this: a lot of health care services identified in the data had no bearings with our research focus and approximately 43% of all hospital stays had to be excluded. Only somewhat less than 19% of the stays were affirmatively included by finding a hepatitis B specific diagnostic or therapeutic intervention. For the other near 40% of the admissions as well as all outpatient services we were coerced into a painstaking task of splitting all billing records into at least two categories: those that were related to HBV and those that were not. Indeed, health care insurance databases are about keeping the accounts of health care services' refundings, and patients tend to seek such care for all their sufferings, not only HBV related. Furthermore, NIHDI billing codes usually cover well-defined interventions, but very often they do so regardless clinical indications.

Table 56 as well as the vast listing (data available upon request) of NIHDI billing codes and their frequencies in our study database sheds a more detailed light on the diversity of concomitant disease with hepatitis B infection status: most strikingly, but not exclusively in the 'HBV active' group (the largest group) we found a variety of surgical interventions as well as dialysis for chronic renal failure. After checking as good as possible their clinical context in the data, especially the HBV clinical phase of the patient, the vast majority could be discarded for our cost calculations. However, the more advanced the HBV clinical stage, the more difficult exclusion decisions became. Since we had to consider disease or treatment related complications, some specific (e.g. fibro-endoscopic stenting for bile duct stricture after liver transplant), but most not (e.g. re-operations for post transplant haemorrhage, ICU haemodialysis for acute post transplant renal failure, nosocomial hospital infection ...), our exclusion criteria had to become more lenient. In other terms, in more advanced disease stages we allowed more procedures to be included as related to CHB. Possible 'operator' bias was countered by expert group reviews. There remains of course a certain degree of "all experts' opinion" in all this, but that is exactly what medicine is all about: sound clinical judgement and praxis expertise.

**Utility of administrative databases for clinical outcomes research and health economic studies**

Second, since administrative databases are not meant nor conceived for research purposes, full knowledge of such databases and their SWOT characteristics for research utilization, as well as profound clinical insight in the focused pathology is extremely important.

The use of administrative health care databases for clinical, health services and health economic studies is not a Belgian exclusivity. Indeed, the utility of such administrative data for evaluating the delivery of health services has been well established. As professors Retchin and Ballard listed in their "Commentary: Establishing Standards for the Utility of Administrative Claims Data"^71, the analysis of billing data over the past 20 to 25 years has revealed unexplained practice variations in neighbouring geographic areas^72 and detected opportunities to improve quality of care.^73, 74

<footnote>^71 Strengths, Weaknesses, Opportunities, Threats</footnote>
Furthermore, administrative claims data have also been used to estimate the incidence of disease⁷⁵,⁷⁶ and the outcomes of surgical procedures.⁷⁷-⁸¹

Administrative claims for inpatient as well as outpatient services are collected as a requirement for reimbursement. Since they are so uniformly generated, such registries can offer a relatively unique, population-based health care data source.⁸² Another advantage is that the data are relatively inexpensive to gather and frequently present fewer restrictions in terms of sample size than do data from alternative sources. Despite these advantages, there are also problems inherent in the use of information that is collected for purposes other than to support health services research.⁸³ The information derived from the data may be inaccurate, misleading or even spurious. Moreover, since documentation of care is often nonessential for administrative/reimbursement purposes, some important elements may be incomplete or indistinct. And since the generation of billing data usually follows the utilization patterns of clinical care, disproportionate details are more readily accessible for inpatient episodes than for outpatient care.⁷¹

All this explains why reimbursement data require scrupulous verification when used to describe and evaluate clinical care and several issues should be considered in substantiating their accuracy.⁷¹

## The case of Belgian reimbursement data

Third, the Belgian reimbursement policy for health care services has gone through drastic reforms in the past 20 years. Historically based on a fee-for-service principle and governed by a national stake holders' consensus model - gathering public health officials with representatives of health insurance companies, hospitals and medical professions - it faced, along with all Western countries, rising expenditures and consequently all kinds of 'bulldozed' budget restraints. Our deeply rooted consensus model not favouring a jump forward into 'all in' pathology or case-mix based refunding, Belgium, rather uniquely, engaged in a step-by-step approach of fractionated and partial lump sum settlements for laboratory tests (started in 1988), medical imaging (in 1992), hospital stay day remuneration (in 2002) and inpatient pharmaceuticals (in 2006). All of them, besides not sustaining their initial budgetary goals (Figure 22), left health care researchers with a major drawback: although individual services still are registered by means of their original fee-for-service codes, lump sum payments have little connection with actual services delivered. The consequences are abundantly elaborated in section 4: complex extrapolation exercises in order to reconnect health insurance costs to actual services delivered.

<figure><img src="image_26.png" /><figcaption>Figure 22. Total NIHDI expenditures for lab tests and medical imaging, 1990-2008.</figcaption></figure>
6 REFERENCES

1. Liaw Y, Chun C. Hepatitis B virus infection. Lancet. 2009;373:582-92 (c).

2. Beutels M, Van Damme P, Aelvoet W, Desmyter J, Dondeyne F, Goilav C, et al. Prevalence of hepatitis A, B and C in the Flemish population. Eur J Epidemiol. 1997;13(3):275-80.

3. Alter M. Epidemiology of hepatitis B in Europe and worldwide. J Hepatol. 2003;39:64-9.

4. Hoofnagle JH, Doo E, Liang TJ, Fleischer R, Lok AS. Management of hepatitis B: summary of a clinical research workshop. Hepatology. 2007;45(4):1056-75.

5. Colle I, Adler M, Brenard R, Henrion J, Langlet P, Michielsen P, et al. Management and treatment of chronic hepatitis B virus: Belgian Association for the Study of the Liver (BASL) 2007 guidelines. Acta Gastroenterol Belg. 2007;70(4):389-420.

6. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45(2):507-39.

7. Lok AS, McMahon BJ. Corrections to AASLD guidelines on chronic hepatitis B. Hepatology. 2007.

8. Wedemeyer H, Cornberg M, Protzer U, Berg T, Dollinger MM. German guidelines on diagnosis and therapy of hepatitis B. Deutsche medizinische Wochenschrift (1946). 2007;132(34-35):1775-82.

9. Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N.Engl.J.Med. 2005;352(26):2682-95.

10. Marcellin P, Lau GK, Bonino F, Farci P, Hadziyannis S, Jin R, et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N.Engl.J.Med. 2004;351(12):1206-17.

11. Fleischer RD, Lok ASF. Myopathy and neuropathy associated with nucleos(t)ide analog therapy for hepatitis B. J Hepatol. 2009;51(4):787-91.

12. Liaw YF, Leung NW, Chang TT, Guan R, Tai DI, Ng KY, et al. Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. Gastroenterology. 2000;119(1):172-80.

13. Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology. 2003;125(6):1714-22.

14. Colonno RJ, Rose R, Baldick CJ, Levine S, Pokornowski K, Yu CF, et al. Entecavir resistance is rare in nucleoside naive patients with hepatitis B. Hepatology. 2006;44(6):1656-65.

15. Colonno R, Rose R, Pokornowski K, Baldick CJ, Eggers B, Yu D, et al. Four year assessment of entecavir resistance in nucleoside-naive and lamivudine refractory patients. J Hepatol. 2007;46(suppl 1):S294.

16. Sherman M, Yurdaydin C, Sollano J, Silva M, Liaw YF, Cianciara J, et al. Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B. Gastroenterology. 2006;130(7):2039-49.

17. Shamliyan TA, MacDonald R, Shaukat A, Taylor BC, Yuan J-M, Johnson JR, et al. Antiviral therapy for adults with chronic hepatitis B: a systematic review for a National Institutes of Health Consensus Development Conference. Ann Intern Med. 2009;150(2):111-24.

18. Spackman DE, Veenstra DL. A cost-effectiveness analysis of currently approved treatments for HBeAg-positive chronic hepatitis B. PharmacoEconomics. 2008;26(11):937-49.

19. Veenstra DL, Spackman DE, Bisceglie A, Kowdley KV, Gish RG. Evaluating anti-viral drug selection and treatment duration in HBeAg-negative chronic hepatitis B: A cost-effectiveness analysis. Alimentary Pharmacology & Therapeutics. 2008;27(12):1240-52.

20. Arnold E, Yuan Y, Iloeje U, Cook G. Cost-effectiveness analysis of entecavir versus lamivudine in the first-line treatment of australian patients with chronic hepatitis B. Applied Health Economics and Health Policy. 2008;6(4):231-46.

21. Orlewska E, Zammit D, Yuan Y, Kutikova L, Berak H, Halota W, et al. The cost-effectiveness analysis of entecavir in the treatment of chronic hepatitis B (CHB) patients in Poland. Experimental and Clinical Hepatology. 2008;4(3-4):20-8.
22. Costa AMN, L'italien G, Nita ME, Araujo ESA. Cost-effectiveness of entecavir versus lamivudine for the suppression of viral replication in chronic hepatitis B patients in Brazil. Braz J Infect Dis. 2008;12(5):368-73.

23. Buti M, Brosa M, Casado MA, Rueda M, Esteban R. Modeling the cost-effectiveness of different oral antiviral therapies in patients with chronic hepatitis B. J Hepatol. 2009;51(4):640-6.

24. Veenstra DL, Sullivan SD, Lai M-Y, Lee C-M, Tsai C-M, Patel KK. HBeAg-negative chronic hepatitis B: cost-effectiveness of peginterferon alfa-2a compared to lamivudine in Taiwan. Value Health. 2008;11(2):131-8.

25. Lacey LF, Gane E. The cost-effectiveness of long-term antiviral therapy in the management of HBeAg-positive and HBeAg-negative chronic hepatitis B in Singapore. J Viral Hepat. 2007;14(11):751-66.

26. Lacey L, Chien R-N, Chuang W-L, Pwu R-F. Economic evaluation of chronic hepatitis B treatments in Taiwan. J Gastroenterol Hepatol. 2008;23(4):571-9.

27. Horsmans Y, Thiry N, le Polain M, Adler M, Colle I, Delwaide J, et al. Cost-effectiveness of antiviral treatment of chronic hepatitis B in Belgium. Part 1: Literature review and results of a national study. Health Technology Assessment (HTA). Brussels: Federal Healthcare Knowledge Centre (KCE). KCE reports 127C. 2010. Available from: www.kce.fgov.be

28. Fattovich G, Olivari N, Pasino M. Long-term outcome of chronic hepatitis B in Caucasian patients: mortality after 25 years. Gut. 2008;57:84-90.

29. Cleemput I, Van Wilder P, Vrijens F, Huybrechts M, Ramaekers D. Guidelines for Pharmacoeconomic Evaluations in Belgium. Brussels: Health Care Knowledge Centre (KCE); 2008. Health Technology Assessment (HTA) KCE Reports 78

30. McMahon BJ. The natural history of chronic hepatitis B virus infection. Hepatology. 2009;49(5 Suppl):S45-55.

31. Liaw Y. Natural history of chronic hepatitis B virus infection and long-term outcome under treatment. Liver Int. 2009;29(suppl 1):100-7 (b).

32. Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008;48(2):335-52.

33. Chen Y-C, Chu C-M, Liaw Y-F. Age-specific prognosis following spontaneous hepatitis B e antigen seroconversion in chronic hepatitis B. Hepatology. 2010;51(2):435-44.

34. Hsu Y, Chien R, Yeh C. Long-term outcome after spontaneous HBeAg serconversion in patients with chronic hepatitis B. Hepatology. 2002;35:1522-27.

35. Tsai S-L, Yang P-M, Lai M-Y, Chen D-S, Hsu H-C, Wang T-H, et al. Natural history of hepatitis B surface antigen-positive cirrhosis in Taiwan: A clinicopathological study. Journal of Gastroenterology and Hepatology. 1988;3:583-92.

36. Fattovich G. Natural history of hepatitis B. J Hepatol. 2003;39 Suppl 1:S50-8.

37. Fattovich G, Pantalena M, Zagni I, al. e. Effect of hepatitis B and C virus infections on the natural history of compensated cirrhosis: a cohort study of 297 patients. Am J Gastroenterol 2002;97:2886-95.

38. de Jongh FE, Janssen HL, de Man RA, Hop WC, Schalm SW, van Blankenstein M. Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver. Gastroenterology. 1992;103(5):1630-5.

39. Realdi G, Fattovich G, Hadziyannis S. Survival and prognostic factors in 366 patients with compensated cirrhosis type B: a multicenter study. J Hepatol. 1994;21:656-66.

40. Kirchner G, Kirovski G, Hebestreit A, Scholmerich J, Schlitt HJ, Stoeltzing O, et al. Epidemiology and survival of patients with hepatocellular carcinoma in Southern Germany. Int J Clin Exp Med. 2010;3(2):169-79.

41. Adler M, De Pauw F, Vereerstraeten P, Fancello A, Lerut J, Starkel P, et al. Outcome of patients with hepatocellular carcinoma listed for liver transplantation within the Eurotransplant allocation system. Liver Transpl. 2008;14(4):526-33.

42. Statistics Belgium: FPS Economy, S.M.E.s, Self-employed and Energy [cited March 2d, 2011]. Health consumer price indices: history since 1994. Available from: http://statbel.fgov.be/fr/statistiques/chiffres/economie/prix_consommation/indice_sante/index.js
P
43. Levy AR, Kowdley KV, Iloeje U, Tafesse E, Mukherjee J, Gish R, et al. The impact of chronic hepatitis B on quality of life: a multinational study of utilities from infected and uninfected persons. Value Health. 2008;11(3):527-38.

44. Hui C-K, Leung N, Shek W-H, Zhang H-Y, Luk JM, Poon RTP, et al. Changes in liver histology as a "surrogate" end point of antiviral therapy for chronic HBV can predict progression to liver complications. J Clin Gastroenterol. 2008;42(5):533-8.

45. Heathcote E, Marcellin P, Buti M, Gane E, de Man R, Krastev Z, et al. Three-Year Efficacy and Safety of Tenofovir Disoproxil Fumarate Treatment for Chronic Hepatitis B. Gastroenterology. 2010.

46. Chang T-T, Liaw Y-F, Wu S-S, Schiff E, Han K-H, Lai C-L, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010;52(3):886-93.

47. Feld JJ, Wong DKH, Heathcote EJ. Endpoints of therapy in chronic hepatitis B. Hepatology. 2009;49(5 Suppl):S96-S102.

48. Colombo M. Does chemotherapy prevent HBV-related hepatocellular carcinoma? Cons. Dig Liver Dis. 2010;42 Suppl 3:S298-301.

49. Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N. Engl. J Med. 2004;351(15):1521-31.

50. Papatheodoridis GV, Lampertico P, Manolakopoulos S, Lok A. Incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving nucleos(t)ide therapy: a systematic review. J Hepatol. 2010;53(2):348-56.

51. Statistics Belgium: FPS Economy, S.M.E.s, Self-employed and Energy [cited October 4, 2010]. Mortality tables: Belgium 1998-2009. Available from: http://statbel.fgov.be/fr/modules/publications/statistiques/population/downloads/table_de_morta lite.jsp

52. Fenwick E, O'Brien BJ, Briggs A. Cost-effectiveness acceptability curves - facts, fallacies and frequently asked questions. Health Economics. 2004;13:405-4015.

53. Dakin H, Bentley A, Dusheiko G. Cost-Utility Analysis of Tenofovir Disoproxil Fumarate in the Treatment of Chronic Hepatitis B. Value in Health. 2010;EPUB.

54. Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130(3):678-86.

55. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295(1):65-73.

56. Post SE, Sodhi NK, Peng C-H, Wan K, Pollack HJ. A simulation shows that early treatment of chronic hepatitis B infection can cut deaths and be cost-effective. Health Aff (Millwood). 2011;30(2):340-8.

57. Idris BI, Brosa M, Richardus JH, Esteban R, Schalm SW, Buti M. Estimating the future health burden of chronic hepatitis B and the impact of therapy in Spain. Eur J Gastroenterol Hepatol. 2008;20(4):320-6.

58. Veldhuijzen I, Toy M, Hahne S, De Wit G, Schalm S, De Man R, et al. Screening and Early Treatment of Migrants for Chronic Hepatitis B Virus Infection Is Cost-Effective. Gastroenterology. 2009.

59. Croagh CMN, Bell SJ, Slavin J, Kong YXG, Chen RY, Locarnini S, et al. Increasing hepatitis B viral load is associated with risk of significant liver fibrosis in HBeAg-negative but not HBeAg-positive chronic hepatitis B. Liver Int. 2010;30(8):1115-22.

60. Kobashi H, Miyake Y, Ikeda F, Yasunaka T, Nishino K, Moriya A, et al. Long-term outcome and hepatocellular carcinoma development in chronic hepatitis B or cirrhosis patients after nucleoside analog treatment with entecavir or lamivudine. Hepatol Res. 2011 (Mar 21.).

61. Cleemput I. A social preference valuations set for EQ-5D health states in Flanders, Belgium. Eur J Health Econ. 2009.

62. Aggarwal R, Ghoshal UC, Naik SR. Treatment of chronic hepatitis B with interferon-alpha: cost-effectiveness in developing countries. [see comment]. Natl Med J India. 2002;15(6):320-7.

63. Bondini S, Kallman J, Dan A, Younoszai Z, Ramsey L, Nader F, et al. Health-related quality of life in patients with chronic hepatitis B. [see comment]. Liver Int. 2007;27(8):1119-25.
64. Crowley SJ, Tognarini D, Desmond PV, Lees M. Cost-effectiveness analysis of lamivudine for the treatment of chronic hepatitis B. PharmacoEconomics. 2000;17(5):409-27.

65. Dusheiko GM, Roberts JA. Treatment of chronic type B and C hepatitis with interferon alfa: an economic appraisal (Structured abstract). Hepatology. 1995;22(6):1863-73.

66. Lam ETP, Lam CLK, Lai CL, Yuen MF, Fong DYT, So TMK. Health-related quality of life of Southern Chinese with chronic hepatitis B infection. Health and Quality of Life Outcomes. 2009;7.

67. Ong SC, Mak B, Myat OA, Li SC, Lim SG. Health-related quality of life in chronic hepatitis B patients. Hepatology. 2008;47(4):1108-17.

68. Owens DK, Cardinalli AB, Nease Jr RF. Physicians' assessments of the utility of health states associated with Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) Infection. Quality of Life Research. 1997;6(1):77-86.

69. Pwu R-F, Chan KA. Cost-effectiveness analysis of interferon-alpha therapy in the treatment of chronic hepatitis B in Taiwan. J Formos Med Assoc. 2002;101(9):632-41.

70. Wong JB, Koff RS, Tine F, Pauker SG. Cost-effectiveness of interferon-alpha-2b treatment for hepatitis B e antigen-positive chronic hepatitis B (Structured abstract). Annals of Internal Medicine. 1995;122(9):664-75.

71. Retchin SM, Ballard DJ. Commentary: establishing standards for the utility of administrative claims data. Health Serv Res. 1998;32(6):861-6.

72. Wennberg JE, Freeman JL, Shelton RM, Bubolz TA. Hospital use and mortality among Medicare beneficiaries in Boston and New Haven. N Engl J Med. 1989;321(17):1168-73.

73. Lohr KN. Use of insurance claims data in measuring quality of care. Int J Technol Assess Health Care. 1990;6(2):263-71.

74. Weiner JP, Powe NR, Steinwachs DM, Dent G. Applying insurance claims data to assess quality of care: a compilation of potential indicators. QRB Qual Rev Bull. 1990;16(12):424-38.

75. Hebert PL, Geiss LS, Tierney EF, Engelgau MM, Yawn BP, McBean AM. Identifying persons with diabetes using Medicare claims data. Am J Med Qual. 1999;14(6):270-7.

76. McBean AM, Warren JL, Babish JD. Measuring the incidence of cancer in elderly Americans using Medicare claims data. Cancer. 1994;73(9):2417-25.

77. Riley G, Lubitz J. Outcomes of surgery among the Medicare aged: surgical volume and mortality. Health Care Financ Rev. 1985;7(1):37-47.

78. Riley G, Lubitz J. Outcomes of surgery in the Medicare aged population: rehospitalization after surgery. Health Care Financ Rev. 1986;8(1):23-34.

79. Riley G, Lubitz J, Gornick M, Mentnech R, Eggers P, McBean M. Medicare beneficiaries: adverse outcomes after hospitalization for eight procedures. Med Care. 1993;31(10):921-49.

80. Topal B, Van de Sande S, Fieuws S, Penninckx F. Effect of centralization of pancreaticoduodenectomy on nationwide hospital mortality and length of stay. Br J Surg. 2007;94(11):1377-81.

81. Van de Sande S, Bossens M, Parmentier Y, Gigot JF. National survey on cholecystectomy related bile duct injury--public health and financial aspects in Belgian hospitals--1997. Acta Chir Belg. 2003;103(2):168-80.

82. White KL. The ecology of medical care: origins and implications for population-based healthcare research. Health Serv Res. 1997;32(1):11-21.

83. Mitchell JB, Bubolz T, Paul JE, Pashos CL, Escarce JJ, Muhlaier LH, et al. Using Medicare claims for outcomes research. Med Care. 1993;32(7 Suppl):JS38-51.
<figure><img src="image_27.png" /></figure>
*This page is left intentionally blank.*
KCE reports

1. Efficacité et rentabilité des thérapies de sevrage tabagique. D/2004/10.273/2.

2. Etude relative aux coûts potentiels liés à une éventuelle modification des règles du droit de la responsabilité médicale (Phase I). D/2004/10.273/4.

3. Utilisation des antibiotiques en milieu hospitalier dans le cas de la pyélonéphrite aiguë. D/2004/10.273/6.

4. Leucoréduction. Une mesure envisageable dans le cadre de la politique nationale de sécurité des transfusions sanguines. D/2004/10.273/8.

5. Evaluation des risques préopératoires. D/2004/10.273/10.

6. Recommandation nationale relative aux soins prénatals: Une base pour un itinéraire clinique de suivi de grossesses. D/2004/10.273/14.

7. Validation du rapport de la Commission d'examen du sous financement des hôpitaux. D/2004/10.273/12.

8. Systèmes de financement des médicaments hospitaliers: étude descriptive de certains pays européens et du Canada. D/2004/10.273/16.

9. Feedback: évaluation de l'impact et des barrières à l'implémentation - Rapport de recherche: partie I. D/2005/10.273/02.

10. Le coût des prothèses dentaires. D/2005/10.273/04.

11. Dépistage du cancer du sein. D/2005/10.273/06.

12. Etude d'une méthode de financement alternative pour le sang et les dérivés sanguins labiles dans les hôpitaux. D/2005/10.273/08.

13. Traitement endovasculaire de la sténose carotidienne. D/2005/10.273/10.

14. Variations des pratiques médicales hospitalières en cas d'infarctus aigu du myocarde en Belgique. D/2005/10.273/12

15. Evolution des dépenses de santé. D/2005/10.273/14.

16. Etude relative aux coûts potentiels liés à une éventuelle modification des règles du droit de la responsabilité médicale. Phase II : développement d'un modèle actuariel et premières estimations. D/2005/10.273/16.

17. Evaluation des montants de référence. D/2005/10.273/18.

18. Utilisation des itinéraires cliniques et guides de bonne pratique afin de déterminer de manière prospective les honoraires des médecins hospitaliers: plus facile à dire qu'à faire.. D/2005/10.273/20

19. Evaluation de l'impact d'une contribution personnelle forfaitaire sur le recours au service d'urgences. D/2005/10.273/22.

20. HTA Diagnostic Moléculaire en Belgique. D/2005/10.273/24, D/2005/10.273/26.

21. HTA Matériel de Stomie en Belgique. D/2005/10.273.28.

22. HTA Tomographie par Emission de Positrons en Belgique. D/2005/10.273/30.

23. HTA Le traitement électif endovasculaire de l'anévrysme de l'aorte abdominale (AAA). D/2005/10.273.33.

24. L'emploi des peptides natriurétiques dans l'approche diagnostique des patients présentant une suspicion de décompensation cardiaque. D/2005/10.273/35

25. Endoscopie par capsule. D2006/10.273.02.

26. Aspects médico-légaux des recommandations de bonne pratique médicale. D2006/10.273/06.

27. Qualité et organisation des soins du diabète de type 2. D2006/10.273/08.

28. Recommandations provisoires pour les évaluations pharmacoéconomiques en Belgique. D2006/10.273/11.

29. Recommandations nationales Collège d'oncologie : A. cadre général pour un manuel d'oncologie B. base scientifique pour itinéraires cliniques de diagnostic et traitement, cancer colorectal et cancer du testicule. D2006/10.273/13.

30. Inventaire des bases de données de soins de santé. D2006/10.273/15.

31. Health Technology Assessment : l'antigène prostatique spécifique (PSA) dans le dépistage du cancer de la prostate. D2006/10.273/18.

32. Feedback: évaluation de l'impact et des barrières à l'implémentation - Rapport de recherche: partie II. D2006/10.273/20.

33. Effets et coûts de la vaccination des enfants Belges au moyen du vaccin conjugué antipneumococcique. D2006/10.273/22.

34. Trastuzumab pour les stades précoces du cancer du sein. D2006/10.273/24.
35. Etude relative aux coûts potentiels liés à une éventuelle modification des règles du droit de la responsabilité médicale - Phase III : affinement des estimations. D/2006/10.273/27.

36. Traitement pharmacologique et chirurgical de l'obésité. Prise en charge résidentielle des enfants sévèrement obèses en Belgique. D/2006/10.273/29.

37. Health Technology Assessment Imagerie par Résonance Magnétique. D/2006/10.273/33.

38. Dépistage du cancer du col de l'utérus et recherche du Papillomavirus humain (HPV). D/2006/10.273/36

39. Evaluation rapide de technologies émergentes s'appliquant à la colonne vertébrale : remplacement de disque intervertébral et vertébro/cyphoplastie par ballonnet. D/2006/10.273/39.

40. Etat fonctionnel du patient: un instrument potentiel pour le remboursement de la kinésithérapie en Belgique? D/2006/10.273/41.

41. Indicateurs de qualité cliniques. D/2006/10.273/44.

42. Etude des disparités de la chirurgie élective en Belgique. D/2006/10.273/46.

43. Mise à jour de recommandations de bonne pratique existantes. D/2006/10.273/49.

44. Procédure d'évaluation des dispositifs médicaux émergeants. D/2006/10.273/51.

45. HTA Dépistage du Cancer Colorectal : état des lieux scientifique et impact budgétaire pour la Belgique. D/2006/10.273/54.

46. Health Technology Assessment. Polysomnographie et monitoring à domicile des nourrissons en prévention de la mort subite. D/2006/10.273/60.

47. L'utilisation des médicaments dans les maisons de repos et les maisons de repos et de soins Belges. D/2006/10.273/62

48. Lombalie chronique. D/2006/10.273/64.

49. Médicaments antiviraux en cas de grippe saisonnière et pandémique. Revue de littérature et recommandations de bonne pratique. D/2006/10.273/66.

50. Contributions personnelles en matière de soins de santé en Belgique. L'impact des suppléments. D/2006/10.273/69.

51. Besoin de soins chroniques des personnes âgées de 18 à 65 ans et atteintes de lésions cérébrales acquises. D/2007/10.273/02.

52. Rapid Assessment: Prévention cardiovasculaire primaire dans la pratique du médecin généraliste en Belgique. D/2007/10.273/04.

53. Financement des soins Infirmiers Hospitaliers. D/2007/10 273/06

54. Vaccination des nourrissons contre le rotavirus en Belgique. Analyse coût-efficacité

55. Valeur en termes de données probantes des informations écrites de l'industrie pharmaceutique destinées aux médecins généralistes. D/2007/10.273/13

56. Matériel orthopédique en Belgique: Health Technology Assessment. D/2007/10.273/15.

57. Organisation et Financement de la Réadaptation Locomotrice et Neurologique en Belgique D/2007/10.273/19

58. Le Défibrillateur Cardiaque Implantable.: un rapport d'évaluation de technologie de santé D/2007/10.273/22

59. Analyse de biologie clinique en médecine général. D/2007/10.273/25

60. Tests de la fonction pulmonaire chez l'adulte. D/2007/10.273/28

61. Traitement de plaies par pression négative: une évaluation rapide. D/2007/10.273/31

62. Radiothérapie Conformationelle avec Modulation d'intensité (IMRT). D/2007/10.273/33.

63. Support scientifique du Collège d'Oncologie: un guideline pour la prise en charge du cancer du sein. D/2007/10.273/36.

64. Vaccination HPV pour la prévention du cancer du col de l'utérus en Belgique: Health Technology Assessment. D/2007/10.273/42.

65. Organisation et financement du diagnostic génétique en Belgique. D/2007/10.273/45.

66. Drug Eluting Stents en Belgique: Health Technology Assessment. D/2007/10.273/48.

67. Hadronthérapie. D/2007/10.273/51.

68. Indemnisation des dommages résultant de soins de santé - Phase IV : Clé de répartition entre le Fonds et les assureurs. D/2007/10.273/53.

69. Assurance de Qualité pour le cancer du rectum - Phase I: Recommandation de bonne pratique pour la prise en charge du cancer rectal D/2007/10.273/55

70. Etude comparative des programmes d'accréditation hospitalière en Europe. D/2008/10.273/02

71. Recommandation de bonne pratique clinique pour cinq tests ophtalmiques. D/2008/10.273/05

72. L'offre de médecins en Belgique. Situation actuelle et défis. D/2008/10.273/08
73. Financement du programme de soins pour le patient gériatrique dans l'hôpital classique : Définition et évaluation du patient gériatrique, fonction de liaison et évaluation d'un instrument pour un financement approprié. D/2008/10.273/12

74. Oxygénothérapie Hyperbare: Rapid Assessment. D/2008/10.273/14.

75. Guideline pour la prise en charge du cancer oesophagien et gastrique: éléments scientifiques à destination du Collège d'Oncologie. D/2008/10.273/17.

76. Promotion de la qualité de la médecine générale en Belgique: status quo ou quo vadis ? D/2008/10.273/19.

77. Orthodontie chez les enfants et adolescents D/2008/10.273/21

78. Recommandations pour les évaluations pharmacoéconomiques en Belgique. D/2008/10.273/24.

79. Remboursement des radioisotopes en Belgique. D/2008/10.273/27.

80. Évaluation des effets du maximum à facturer sur la consommation et l'accessibilité financière des soins de santé. D/2008/10.273/36.

81. Assurance de qualité pour le cancer rectal - phase 2: développement et test d'un ensemble d'indicateurs de qualité. D/2008/10.273/39

82. Angiographie coronaire par tomodensitométrie 64-détecteurs chez les patients suspects de maladie coronarienne. D/2008/10.273/41

83. Comparaison internationale des règles de remboursement et aspects légaux de la chirurgie plastique D/2008/10.273/44

84. Les séjours psychiatriques de longue durée en lits T. D/2008/10.273/47

85. Comparaison de deux systèmes de financement des soins de première ligne en Belgique. D/2008/10.273/50.

86. Différenciation de fonctions dans les soins infirmiers : possibilités et limites D/2008/10.273/53

87. Consommation de kinésithérapie et de médecine physique et de réadaptation en Belgique. D/2008/10.273/55

88. Syndrome de Fatigue Chronique : diagnostic, traitement et organisation des soins. D/2008/10.273/59.

89. Evaluation des certains nouveaux traitements du cancer de la prostate et de l'hypertrophie bénigne de la prostate. D/2008/10.273/62

90. Médecine générale: comment promouvoir l'attraction et la rétention dans la profession ? D/2008/10.273/64.

91. Appareils auditifs en Belgique: health technology assessment. D/2008/10.273/68

92. Les infections nosocomiales en Belgique: Volet I, Etude Nationale de Prévalence. D/2008/10.273/71.

93. Détection des événements indésirables dans les bases de données administratives. D/2008/10.273/74.

94. Soins maternels intensifs (Maternal Intensive Care) en Belgique. D/2008/10.273/78.

95. Implantation percutanée des valvules cardiaques dans le cas de maladies valvulaires congénitales et dégénératives: A rapid Health Technology Assessment. D/2007/10.273/80.

96. Construction d'un index médical pour les contrats privés d'assurance maladie. D/2008/10.273/83.

97. Centres de réadaptation ORL/PSY : groupes cibles, preuves scientifiques et organisation des soins. D/2009/10.273/85.

98. Évaluation de programmes de vaccination généraux et ciblés contre l'hépatite A en Belgique. D/2008/10.273/89.

99. Financement de l'hôpital de jour gériatrique. D/2008/10.273/91.

100. Valeurs seuils pour le rapport coût-efficacité en soins de santé. D/2008/10.273/95.

101. Enregistrement vidéo des interventions chirurgicales par endoscopie : une évaluation rapide. D/2008/10.273/98.

102. Les infections nosocomiales en Belgique: Volet II: Impact sur la mortalité et sur les coûts. D/2009/10.273/100.

103. Réformes dans l'organisation des soins de santé mentale : étude d'évaluation des 'projets thérapeutiques' - 1er rapport intermédiaire. D/2009/10.273/05.

104. Chirurgie assistée par robot: health technology assessment. D/2009/10.273/08

105. Soutien scientifique au Collège d'Oncologie: recommandations pour la pratique clinique dans la prise en charge du cancer du pancréas. D/2009/10.273/11

106. Imagerie par résonance magnétique : analyse de coûts. D/2009/10.273/15

107. Indemnisation des dommages résultant de soins de santé. Phase V: impact budgétaire de la transposition du système français en Belgique. D/2009/10.273/17
108. Le Tiotropium dans le traitement des BronchoPneumopathies Chroniques Obstructives: Health Technology Assessment. D/2009/10.273/19

109. A propos de la valeur de l'EEG et des potentiels évoqués dans la pratique clinique. D/2009/10.273/22

110. La tomographie par émission de positrons en Belgique: une mise à jour. D/2009/10.273/25

111. Interventions pharmaceutiques et non pharmaceutiques dans la maladie d'Alzheimer: une évaluation rapide. D/2009/10.273/28

112. Politiques relatives aux maladies orphelines et aux médicaments orphelins. D/2009/10.273/31

113. Le volume des interventions chirurgicales et son impact sur le résultat: étude de faisabilité basée sur des données belges. D/2009/10.273/34.

114. Valves endobronchiales dans le traitement de l'emphysème pulmonaire avancé: un rapid Health Technology Assessment. D/2009/10.273/38

115. Organisation des soins palliatifs en Belgique. D/2009/10.273/41

116. Evaluation rapide des implants inter-épineux et des vis pédiculaires pour la stabilisation dynamique de la colonne vertébrale lombaire. D/2009/10.273/45

117. Utilisation des coagulomètres portables chez les patients sous anticoagulants oraux: Health technology Assessment. D/2009/10.273/48.

118. Avantages, désavantages et faisabilité de l'introduction de programmes "P4Q" en Belgique. D/2009/10.273/51.

119. Douleur cervicales atypiques: diagnostic et traitement. D/2009/10.273/55.

120. Comment assurer l'autosuffisance de la Belgique en dérivés stables du plasma? D/2009/10.273/58.

121. Étude de faisabilité de l'introduction en Belgique d'un système de financement « all-in » par pathologie. D/2010/10.273/02

122. Le financement des soins infirmiers à domicile en Belgique. D/2010/10.273/06

123. Réformes dans l'organisation des soins de santé mentale: étude d'évaluation des 'projets thérapeutiques' - 2ème rapport intermédiaire. D/2010/10.273/09

124. Organisation et financement de la dialyse chronique en Belgique. D/2010/10.273/12

125. Impact du visiteur médical indépendant sur la pratique des médecins de première ligne. D/2010/10.273/15

126. Le système du prix de référence et les différences socio-économiques dans l'utilisation des médicaments moins onéreux. D/2010/10.273/19.

127. Rapport coût-efficacité du traitement antiviral de l'hépatite B chronique en Belgique. Partie I: Examen de la littérature et résultats d'une étude nationale. D/2010/10.273/23.

128. Un premier pas vers la mesure de la performance du système de soins de santé belge. D/2010/10.273/26

129. Dépistage du cancer du sein entre 40 et 49 ans. D/2010/10.273/29.

130. Critères de qualité pour les lieux de stage des candidats-médecins généralistes et candidats-spécialistes. D/2010/10.273/34.

131. Continuité du traitement médicamenteux entre hôpital et domicile. D/2010/10.273/38.

132. Faut-il un dépistage néonatal de la mucoviscidose en Belgique? D/2010/10.273/42.

133. Optimisation du fonctionnement du Fonds Spécial de Solidarité. D/2010/10.273/45.

134. Indemnisation des victimes transfusionnelles du virus de l'hépatite C ou du VIH. D/2010/10.273/48.

135. L'urgence psychiatrique pour enfants et adolescents. D/2010/10.273/50.

136. Surveillance à distance des patients porteurs de défibrillateurs implantés. Evaluation de la technologie et cadre réglementaire général. D/2010/10.273/54.

137. La stimulation cardiaque chez les patients bradycardes en Belgique. D/2010/10.273/57.

138. Le système de santé belge en 2010. D/2010/10.273/60.

139. Recommandations de bonne pratique pour l'accouchement à bas risque. D/2010/10.273/63

140. Rééducation cardiaque: efficacité clinique et utilisation en Belgique. D/2010/10.273/66.

141. Les statines en Belgique: évolutions de l'utilisation et impact des politiques de remboursement. D/2010/10.273/70.

142. Soutien scientifique au Collège d'Oncologie: mise à jour des recommandations de bonne pratique pour la prise en charge du cancer du testicule. D/2010/10.273/73.

143. Soutien scientifique au Collège d'Oncologie: mise à jour des recommandations de bonne pratique pour la prise en charge du cancer du sein. D/2010/10.273/76.

144. Organisation des soins de santé mentale pour les personnes atteintes d'une maladie mentale grave et persistante. Y a-t-il des données probantes? D/2010/10.273/79.
145. Thérapie de resynchronisation cardiaque. Un rapport d'évaluation de technologie de santé. D/2010/10.273/83

146. Réformes dans l'organisation des soins de santé mentale : étude d'évaluation des 'projets thérapeutiques'. D/2010/10.273/86

147. Les systèmes de remboursement des médicaments: comparaison internationale et recommandations aux décideurs. D/2010/10.273/89

148. Etat des lieux de l'ostéopathie et de la chiropraxie en Belgique. D/2010/10.273/92

149. Indicateurs de qualité en oncologie : cancer du testicule. D/2010/10.273/97

150. Indicateurs de qualité en oncologie: Cancer du sein. D/2010/10.273/100

151. Rapport coût-utilité de la vaccination contre la varicelle chez les enfants, et de la vaccination contre le zona chez les adultes en Belgique. D/2010/10.273/103.

152. Indicateurs de qualité en oncologie: Pré-requis pour l'élaboration d'un système de qualité. D/2011/10.273/02.

153. Etat des lieux de l'acupuncture en Belgique. D/2011/10.273/05.

154. Etat des lieux de l'homéopathie en Belgique. D/2011/10.273/13.

155. Rapport coût-efficacité des vaccins antipneumococciques conjugués 10-valent et 13-valent chez l'enfant. D/2011/10.273/20.

156. L'oxygénothérapie à domicile. D/2011/10.273/24.

157. Evaluation économique du traitement antiviral de l'hépatite B chronique en Belgique – Tome 2. D/2011/10.273/28
<figure><img src="image_28.png" /></figure>