Background
Methods
Analytical framework outlining the value assessment and appraisal characteristics of HTA systems
Responsibilities and structure of HTA agencies
Evidence and evaluation criteria considered in HTAs
Methods and techniques applied in HTAs
Outcomes and implementation of HTAs
Systematic literature review
Inclusion criteria (country selection and study period)
Identification of evidence
Study selection and data extraction
Expert consultation
Results
Responsibilities and structure of national HTA agencies
France (HAS/CEESP) | Germany (IQWiG) | Sweden (TLV) | England (NICE) | Italy (AIFA) | Netherlands (ZIN) | Poland (AOTMiT) | Spain (RedETS/ISCIII or ICPa) | |
---|---|---|---|---|---|---|---|---|
Function | Autonomous, advisory | Autonomous, advisory | Autonomous, regulatory | Autonomous, advisory | Autonomous, regulatory | Autonomous, advisory | Autonomous, advisory | Autonomous, advisory |
Expert committee | CEESP | Assessment: IQWiG scientific personnelb; Appraisal: G-BA | The Board for Pharmaceutical Benefits | Technology Appraisal Committee | AIFA’s Technical Scientific Committee and CPR | Committee for societal consultation regarding the benefit basket | Transparency Council | ICPc
|
Topic selection | HAS (about 90% submitted by the manufacturers, 10% requested by the MoH)d
| Not applicable (all drugs applying for marketing authorization, excluding inpatient) | TLV (only outpatient and high price drugs) | DH in consultation with NICE based on explicit prioritisation criteriae
| AIFA (all drugs submitted by manufacturers) | Mostly on its own initiative; sometimes at the request of MoH | MoHf (in the case of manufacturer submission—triggered by MAH) | Not subject to any specific known procedureg
|
Guidelines for the conduct of economic analysis | Yes | Yes (however, CBA is not standard practice) | Yes | Yes | In progress | Yes | Yes | Spanish recommendations on economic evaluation of health technologies |
Evidence and evaluation criteria considered in HTAs
France (HAS/CEESP) | Germany (IQWiG) | Sweden (TLV) | England (NICE) | Italy (AIFA) | Netherlands (ZIN) | Poland (AOTMiT) | Spain (RedETS/ISCIII or ICP) | |
---|---|---|---|---|---|---|---|---|
Burden of disease
| ||||||||
Severity | Yes, as part of SMR | Yes, as part of added benefit assessment | Yes (impact on WTP threshold)a
| Yes (mainly as part of EoL treatments) | Yes (implicitly) | Yesb
| Yesc
| Yes |
Availability of treatments (i.e. unmet need) | Yes (binary: Yes/No) | True for other technologies rather than pharmaceuticalsd
| Yes, indirectly (captured by severity) | Yes (clinical need as a formal criterion) | Yese
| Yesf
| Yesg
| Yes |
Prevalence (e.g. rarity) | Yes, informally | As part of G-BA’s decision-making processh
| Yes | Yes | YesI
| Yes | Yesj
| Yes |
Therapeutic and safety impact
| ||||||||
Efficacy | Yes (4 classifications via SMR, 5 via ASMR)k
| Yes (6 classifications)l
| Yes | Yes | Yes | Yes | Yesm
| Yes |
Clinically meaningful outcomes | Yes (preferred) | Yes (preferred) | Yes | Yes (preferred) | Yes | Yes | Yesn
| Yes |
Surrogate/intermediate outcomes | Considered | Considered | Considered | Considered | Considered | Considered | Consideredo
| Considered |
HRQoL outcomes | Generic; disease-specific | Generic; disease-specificp
| Generic (preferred); disease-specific | Generic; disease-specific | Generic; disease-specific | Yes | Yesq
| Yes (including patient well-being) |
Safety | Yes | Yesr
| Yes | Yes | Yes | Yes | Yess
| Yes |
Dealing with uncertainty | Implicitly (preference for RCTs), explicitly (robustness of evidence) | Explicitly (classification of empirical studies and complete evidence) | Implicitly (through preference for RCTs) | Explicitly (quality of evidence), implicitly (preference for RCTs), indirectly (rejection if not scientifically robust) | Yes, registries and MEAs are used to address uncertainty | Implicitly (if included in the assessment studies) | Not
| Can be considered as part of economic evaluation |
Innovation level
| ||||||||
Clinical novelty | Yes (as part of ASMR) if efficacy/safety ratio is positive | Implicitly as part of added therapeutic benefit considerationu
| Yes, but only if it can be captured in the CE analysis | Yes | Yes | Yes | Yesv
| Yesw
|
Ease of use and comfort | Not explicitly, in some casesx
| Only if relevant for morbidity/side effects, not explicitly considered for benefit assessmenty
| Yes (to some extent) | Not explicitly | No | Not standard, case-by-case basis | Noz
| Not explicitly, indirectlyaa
|
Nature of treatment/technology | Yes (3 classifications)ab
| Not explicitly considered for benefit assessment | Not explicitly | Yes (when above £20,000) | No | Implicitly | Yesac
| Yes (through the degree of innovation criterion) |
Socio-economic impact
| ||||||||
Public health benefit/value | Yes, rarely via “intérêt de Santé Publique”ad
| Noae
| Yes, indirectlyaf
| As indicated in guidance to NICE to be considered in the evaluation processag
| Implicitly | Yes (explicit estimates) | Yesah
| Social utility of the drug and rationalisation of public drug expenditures |
Social productivity | Not explicitlyai
| Yesaj
| Indirect costs considered explicitly (to some extent) | Productivity costs excluded but informal “caregiving” might be considered | Direct costs onlyak
| Yes | Noal
| Yes, either explicitly or implicitly |
Efficiency considerations
| ||||||||
Cost-effectiveness | Yesam
| Optional (cost-benefit)an
| Yes (cost-efficiency as a principle) | Yes | Yes | Yes | Yes, mandatory by law | Yes (not mandatory) |
CBA/BIA | Not mandatory but BIA is highly recommendedao
| BIA (mandatory) | Cost only considered for treatments of the same condition; BIA not mandatory | BI to NHS, PSS, hospitals, primary care | Yes | Yes | Yes, payer affordability mandatory by law | Yes (BI to NHS) |
Other evidence and criteria
| ||||||||
Place in therapeutic strategy | Yesap
| Evaluation usually specifies the line of treatment | Evaluation usually specifies the line of treatment | Broad clinical priorities for the NHS (by Secretary of State) | Yes | Not explicitly | No | Yesaq
|
Conditions of use | Yes (e.g. the medicine is assessed in each of its indications, if several) | No, drug is in principle reimbursable for the whole indication spectrum listed on its authorisationar
| Yes, coverage can be restricted based on evidence at sub-population level | Yes, coverage can be restricted based on evidence at sub-population level | Implicitly | Yes, indications | Yes, coverage can be restricted to strictly defined sub-populations | Yes (several medicines are introduced with Visado—Prior Authorization Status) |
Ethical considerations | Not incorporated in assessmentas
| Sometimes (implicitly) | Yes | Yesat
| Implicitly | Yes, explicitly (e.g. solidarity and affordability)au
| Considered on the basis of HTA Guidelines | Not explicitly |
Weights/relative importance of different criteria | Not transparent | Not transparent | “Human dignity” usually being overridingav
| Not transparent | Not transparent | Therapeutic value is the most important criterion | Not transparent | Not transparent and not consistent across regionsaw
|
Accepted data sources (for estimating number of patients, clinical benefits and costs) | Clinical trials, observational studies, national statistics, clinical guidelines, surveys, expert opinions | RCTsax, national or local statistics, clinical guidelines, surveys, price lists, expert opinions (including patient representatives) | Clinical trials, observational studies, national statistics, clinical guidelines, surveys, expert opinions | Clinical trials, observational studies, national or local statistics, clinical guidelines, surveys, expert opinions | Clinical trials, observational studies, national statistics, clinical guidelines, surveys, expert opinions, scientific societies‘ opinion | Clinical trials, clinical guidelines, expert opinions | Clinical trials, observational studies, national or local statistics, clinical guidelines, surveys, expert opinions | Clinical trials, observational studies, national statistics, clinical guidelines, surveys, expert opinions |
Evaluation principles and their relevance to priority setting
Evaluation criteria taken into account in HTAs
Burden of disease
Therapeutic impact and safety
Innovation level
Socioeconomic impact
Efficiency
Other types of evidence
Synthesizing the evidence and taking into account all factors: weights
HTA methods and techniques applied
France (HAS/CEESPa) | Germany (IQWiG) | Sweden (TLV) | England (NICE) | Italy (AIFA) | Netherlands (ZIN) | Poland (AOTMiT) | Spain (RedETS/ISCIII or ICP) | |
---|---|---|---|---|---|---|---|---|
Analysis method
| ||||||||
Methods | Comparative efficacy/effectiveness (also CEA, CUA) | CBA but also CUA and CEA (not standard practice) | CUA (also CEA, CBA) | CUA (also CEA, CMA) | CMA, CEA, CUA, CBAb
| CEA, CUA, no CMA | Cost-consequences analysis, CEA or CUA—obligatory, CMA (if applicable) | Comparative efficacy/effectiveness, CMA, CEA, CUA, CBAc
|
Preferred outcome measure | Final outcome, life years (QALY, if CUA; life years, if CEA) | Patient relevant outcome (can be multidimensional)—efficiency frontier | QALY (WTP, if CBA) | QALY (cost per life year gained, if CEA) | Final outcome, life years (QALY, if CUA or CEA; life years, if CEA) | Effectiveness by intention-to-treat principle, and expressed in natural units—preferably LYG or QALY | QALY or LYG | QALY in CUA |
Utility scores elicitation technique | EQ-5D and HUI3, from general French population | Utility scores from patients, direct (e.g. TTO, SG), indirect | Utility scores from patients, direct (e.g. TTO, SG), indirect (EQ-5D) | Utility scores from general English population, direct (e.g. TTO, SG), indirect (EQ-5D), systematic review | Both direct and indirect (EQ-5D) elicitation techniques | Either direct (TTO, SG, VAS), or indirect (EQ-5D); selection should be justified | Direct or indirect utility scoresd
| Utility scores from general Spanish population, direct (e.g. TTO, SG), indirect (EQ-5D)e
|
Comparator | Usually ‘best standard of care’ but can be more than onef
| Usually ‘best standard of care’ but can be more than oneg
| Usually ‘best standard of care’ but can be more than oneh
| Usually ‘best standard of care’ but can be more than oneI
| Usually ‘best standard of care’ but can be more than onej
| Treatment in clinical guidelines of GPs; if not available, most prevalent treatment | ‘Best standard of care’ which is reimbursed in Polandk
| Best standard of care, usual care and/or more cost-effective alternative |
Perspective | Widest possible to include all health system stakeholdersl
| Usually statutory health insurantm
| Societal | Cost payer (NHS) or societal if justified | Italian National Health Servicen
| Societal (report indirect costs separately) | The public payer’s perspective, public payer and patient (by law) | Cost payer (NHS) and societal (rarely used), and they should be presented separately |
Subgroup analysis | Yes (when justified) | Yes | Yes | Yes | Yes | Yes | Yes (if needed, but decreases validity) | Yes |
Clinical evidence
| ||||||||
Preferred study design | Head-to-head RCTs; other designs accepted if no RCTs available | Head-to-head RCTs; other designs accepted in the absence of RCTs | Head-to-head RCTs; other designs accepted if no RCTs available | Head-to-head RCTs; other designs accepted if no RCTs available | Head-to-head RCTs; other designs accepted if no RCTs available | Head-to-head RCTs | Head-to-head RCTs; other designs accepted if no RCTs available | Head-to-head RCTs; other designs accepted if no RCTs available |
Systematic literature reviews for collecting evidence required/conducted by regulator | Yes, guidelines provided/yes, in French | Yes/no | Not mandatory | Yes/yes | Yes/yes | Yes/yes | Yes | Not alwayso
|
Meta-analysis for pooling evidence | Not specified | Not specified for new drugs | Not specified | Yes | Yes | Yes, encouraged | Yes | Nop
|
Data extrapolation | Qualitative only, in absence of effectiveness data form RCTs | No | Quantitative, both in absence of RCT effectiveness data and in absence of long-term effects | Qualitative and quantitative, both in absence of RCT effectiveness data and in absence of long-term effects | Quantitative Qualitative in absence of RCT effectiveness data | Qualitative, in the absence of RCTs and in absence of long-term effects | Possible if needed but not recommended | Quantitative, in the absence of effectiveness data |
Resources/costs
| ||||||||
Types | Direct medical, direct non-medical, indirect (both for patient and carer) | Depending on perspective: direct medical, informal costs, productivity loss (as costs) | Direct medical, direct non-medical, indirect (both for patient and carer) | Direct medical, social services | Direct costs only; indirect costs can be taken into account in a separate analysis | Both direct and indirect costs inside and outside the healthcare system | Direct medical costs, direct non-medical costs | Direct and indirect costs (on rare occasions), costs of labour production losses or lost time, informal care costs |
Data source/unit costs | Direct: PMSI (Programme de Médicalisation des Systèmes d’Information) Indirect: human capital costing, friction costing | Statutory health insurance, further considerations depending on perspective chosen | Drugs: pharmacy prices Indirect: human capital costing | Official DoH listing | Variety of sourcesq
| Reference prices list should be used | Variety of sourcesr
| Official publications, accounts of health care centres, and the fees applied to NHS service provision contracts |
Discounting
| ||||||||
Costs | 4% (up to 30 years) and 2% after | 3% | 3% | 3.5% | Not available (update in progress) | 4% | 5% | 3% |
Outcomes | 4% (up to 30 years) and 2% after | 3% | 3% | 3.5% | Not available (update in progress) | Under review—will probably be set at same level as costs discounting | 3.5% | 3% |
Sensitivity analysis | 0%, 3% (6% max) | 0–5% | 0–5% | 0–6% | Not available (update in progress) | Not obligatory | 5 and 0% for costs and outcomes 0% for outcomes 5% for costss
| 0–5% |
Time horizon
| ||||||||
Time horizon | Long enough so that all treatment outcomes can be included | At least the average (clinical) study duration; longer for chronic conditions, especially if lifetime gains are expected; same horizon for costs and benefits | Time needed to cover all main outcomes and costs | Long enough to reflect any differences on outcomes and costs between technologies compared | Duration of the trial is consideredt
| Primarily based on duration of RCTsu
| Long enough to allow proper assessment of differences in health outcomes and costs between the assessed health technology and the comparators | Should capture all relevant differences in costs and in the effects of health treatments and resourcesv
|
Thresholds
| ||||||||
Thresholds | No threshold (only eligibility threshold to conduct economic evaluation) | Efficiency frontier (Institute’s own approach) | No official threshold; 50% likelihood of approval for ICER between €79,400 and €111,700 | £20,000–£30,000 per QALY; Empirical: £12,936 per QALY | No threshold in use | No official threshold | 3 × GDP per capita for ICUR(QALY) or ICER(LYG) | Unofficial: €21,000–€24,000/QALY (recently provided by SESCSw to the Spanish MoH) |
Analytical methods
Types of clinical evidence considered
Resources/cost evidence
Discounting and time horizon
Acceptable ‘value for money’ thresholds
HTA outcomes and implementation
France (HAS/CEESP) | Germany (IQWiG) | Sweden (TLV) | England (NICE) | Italy (AIFA) | Netherlands (ZIN) | Poland (AOTMiT) | Spain (RedETS/ISCIII or ICP) | |
---|---|---|---|---|---|---|---|---|
Publicly available report | Yes, both in French and Englisha
| Yes | Yes (summary report with some details on cost-effectiveness) | Yes | Yes, in the Official Journal of the Italian Republic (Gazetta Ufficiale) | Yes | Yes (in Polish on the AOTMiT website), but confidential information is publicly unavailable | No for drugsb
|
Policy implication
| ||||||||
Reimbursement | Yes, through SMRc
| Indirectly | Yes | Yes | Yes | Yes | Yes | Yes |
Pricing | Yes, through ASMRd
| Indirectly | Yes | Only indirectly as it has an impact on product’s ICER | Yes | Yes, except certain expensive medicinese
| Yes, if reimbursement decision is positive | Yes |
Access restrictions | Yes, various restrictions in placef
| Existence of managed entry agreements but details not publicly available | Yes, restrictions for specific subpopulations, temporary decisions and risk sharing agreements | Yes, major and minor restrictions as well as performance based agreements | Yes, various managed entry agreementsg
| Yes, system of CED | Yes, including major and minorh
| Yes |
Dissemination | Publicly available online | Dossier assessment, reports, rapid reports, addendums and patient information websites | Informational material distributed to the major stakeholders, decisions published online | Publicly available online | Monthly AIFA publication of price lists of reimbursed products. Annual publication of data on pharmaceutical expenditure and consumption (Rapporto Osmed) | Online for general public and distributed to stakeholders | Publication online | No for drugsI
|
Implementation | Prescription guidelines, drug formularies and positive list | Prescription advice issued by G-BA based on therapeutic assessment (“Therapiehinweise”) | Drug formularies | Prescription guidelines, drug formularies | A product can be assigned to Class A, H or Cj
| Positive list; in case of therapeutic equivalent, the drug is either not accepted for public reimbursement or subject to a reference pricing system | Different reimbursement lists categoriesk
| Inclusion in the national reimbursement list |
Appeal | Yesl
| Yes, through arbitration boardm
| Yes | Yes | Companies can appeal to Court but there is no specific appeal procedure | Yes | No | Yes |
Revision | Yes, every 5 years or sooner if decision from HAS or request from the MoH | Yes, at least one year after benefit assessmentn
| Yes | Yes | Yeso
| Yes, but not on a regular basisp
| Yes, 2 years after first assessment, 3 year after 2nd, 5 years after 3rd assessment | Yes |