An introduction into the role of HTA and why it is relevant for value assessment: A taxonomy of processes and evidence

requirments

Panos Kanavos

London School of Economics

Advance-HTA Capacity Building workshop

Warsaw, 25 September 2014, 14.00 – 15.25

Outline

Key aspects of HTA models in EU countries and beyond – Value assessment models/options

– Governance of HTA in Europe

– Responsibility and Membership of HTA entities

– Scope and topic selection

– Data requirements

– Analysis

– Assessment methods

– Role of stakeholders

– Dissemination and implementation

– Setting affordability thresholds

Similarities and differences in HTA

Concluding remarks

What decision-makers want

Safety and Efficacy are first steps to provide evidence for a new drug; Effectiveness and Efficiency need to be proven

Measure of

effect under

“real life”

conditions

Effectiveness Efficacy

Measure of

effect under

ideal

conditions

Efficiency

Relationships

between

costs and

benefits

Safety

Measure of

adverse

effects

• Efficacy does not imply effectiveness and

effectiveness does not imply efficiency

• Safety and efficacy are the competence of regulators,

effectiveness and efficiency are the competence of payers/insurers

• Use of Health Technology Assessment to assess value: evidence-based

information for decision-making

Different approaches to valuing innovation in Europe

• Cost-Effectiveness Pricing and Value-Based Pricing (UK, Sweden, the Netherlands, Denmark, Finland…)

• SMR/ASMR (France) – SMR: medical benefit rendered

– ASMR: improvement in medical service rendered

• The Innovation Assessment Algorithm (Italy)

• Use of clinical evidence in reimbursement negotiation

Governance of HTA in Europe

In the EU, programmes for HTA have been established via provision of new agencies/institutes or in existing academic or governmental entities.

Many countries have several bodies dedicated to HTA, with somewhat unclear and disparate roles and responsibilities.

Heterogeneity of existing HTA bodies reflects the differentiated environments of European health care systems.

Austria Federation of Austrian Social Insurance Institution/Drug

Evaluation Committee

Belgium National Institute for Sickness and Invalidity

Insurance/Commission for Reimbursement for Medicines

Denmark Reimbursement Committee/Danish Centre for Health

Technology Assessment

Finland Pharmaceuticals Pricing Board (PPB)/FinOHTA

Germany Federal Joint Committee/Institute for Quality and

Efficiency in Health Care (IQWiG)/ German Agency for

Health Technology Assessment (DAHTA)

Netherlands National Health Insurance Board/Committee for

Pharmaceutical Aid/Health Council

Norway Pharmaceuticals Pricing Board/Norwegian Centre for

Health Technology Assessment

Sweden Pharmaceutical Benefits Board (TLV)/Swedish Council on

Technology Assessment in Health Care (SBU)

Switzerland Swiss Federal Office of Public Health/Confederal Drug

Commission/Swiss Network for HTA

United

Kingdom

National Institute of Health and Clinical Excellence

(NICE)/National Coordinating Centre for Health

Technology Assessment (NCCHTA)/Scottish Medicines

Consortium (SMC)

Responsibility and Membership of HTA Entities (1)

Most national HTA bodies can be categorised as serving an advisory, regulatory, or coordination role.

– Advisory = render reimbursement or pricing recommendations to a national or regional gov’t, a ministerial department, or self-governance body (e.g., Netherlands, Demark).

– Regulatory = accountable principally to health ministries; assume primary responsibility for the listing and pricing of drugs, medical devices, and other related services (e.g., Finland, France, Sweden – TLV).

– Coordination = responsible for coordinating HTAs and/or developing clinical guidance, and producing and disseminating reports (e.g., Sweden – SBU).

Mandates and responsibilities of review bodies vary by their general mission and overall policy objectives.

Responsibility and Membership of HTA Entities (2)

Most HTA bodies either conduct the assessment in-house or contract independent reviews to external organisations (e.g., academic research institution)

Use of independent reviews presents both advantages and challenges

– + (lends to greater transparency, helps prevent or resolve potential

appeals, widens available expertise, and brings broader perspectives

to process)

– - (introduces disconnects between methodological approaches,

coordination inefficiencies, and divergent agendas)

Review bodies also differ in their role in the decision-making process once the assessment is complete.

– For example, some bodies promulgate clinical guidance, while others are involved in reimbursement and pricing negotiations.

Range of Technologies Evaluated

In many jurisdictions, the HTA effort focuses on drugs, usually because of the remit the HTA entity has been given (eg in the Netherlands)

Consideration of a broader range of technologies is more likely to lead to overall efficiency and gives a ‘level playing field’ (eg NICE)

Topic Selection (1)

Given resource constraints, priority-setting assessment topics has become an important aspect of the HTA process.

Topic agendas are often set by national authorities (i.e, MoH), Departments of Health, or expert committees affiliated with an HTA body.

– Various stakeholders (e.g., industry, patient representatives, providers) may submit topic suggestions or comment on priorities, although the extent of engagement various by country.

While selection criteria differs across review body, they typically include health benefit, disease burden, resource impact, innovation capacity, clinical and political relevance, and feasibility of assessment.

Topic Selection (2)

For those bodies primarily responsible for reimbursement and/or pricing decisions, topics are determined by manufacturer submissions.

Several agencies have developed “early warning” or “horizon scanning” systems to identify new and emerging technologies that might require early or urgent evaluation.

– Netherlands, Sweden, Finland, the UK have established such programmes

– Internationally connected via EuroScan Network

Many HTA agencies lack explicit and transparent processes for prioritisation, including selection methods and stakeholder involvement.

More emphasis should be placed on identifying topics for potential disinvestment.

Evidence and Data Requirements

Manufacturers typically submit a summary of data on a product’s effectiveness and cost-effectiveness, although HTA bodies differ on how such evidence is used in assessments*.

– Netherlands, Sweden, and the UK consider ‘commercial or academic in confidence’ data

Majority of countries have published guidelines to outline data & methodological requirements.

*Relates specifically to drug review.

Austria, Norway, Netherlands: Review

bodies collect and validate manufacturer

data. Manufacturers are required to submit

evidence, based on a systematic review and

summary of published and unpublished data.

Sweden, UK: Review bodies perform the

systematic review in-house or via an

independent entity; evidence used may or

may not include manufacturer data.

Generally involves broader review of various

information sources.

Switzerland, Finland, France: Systematic

reviews are not required (although preferred),

basing assessment primarily on a definite

number of studies (e.g., clinical trials)

provided by manufacturers.

Types of Evidence Considered

Most jurisdictions issue guidelines for

submissions of evidence

For clinical evidence, some entities (eg IQWiG

in Germany) place a major emphasis on RCTs

Others (eg NICE) recognize the relevance of

observational data and economic modelling

Very few entities pay much attention to items

such as productivity gains, or patient/family

costs (TLV in Sweden is an exception)

Analytical Design (1)

Countries employ several different criteria to guide assessments.

While almost all countries firstly consider therapeutic benefit, other factors frame the analysis:

– Disease burden

– Patient quality of life (QoL)

– Cost-effectiveness

– Costs

– Budget impact

– Availability of alternative treatments

Health-related QoL is deemed the most appropriate criterion for a technology’s added value from the patient perspective.

To a lesser extent, level of innovation, equity, and social and ethical implications are considered.

Analytical Design (2)

Time allocated and required to complete an assessment varies between review bodies – typically, 3 to 12 months.

– France: a few weeks, UK & Sweden: 1 year is not uncommon.

Several agencies have introduced “rapid reviews” to provide more timely information to decision-makers and the public.

– NICE recently introduced Single Technology Appraisals (STA) to address concerns regarding the time required for its standard technology assessment approach.

– Places more emphasis on evidence submitted by manufacturers and less on extensive external review.

Early guidance must balance timely product diffusion and availability of sufficient information from which to base the appraisal.

Assessment Methods (1)

While most agencies share similar methodological approaches, there is no standard framework for conducting assessments.

However, cost-effectiveness (CE) and cost-utility analyses (CUA) are most often considered appropriate approaches for assessing relative benefits and costs.

CUA, measuring health outcomes in terms of Quality-Adjusted Life Years (QALYs), has increasingly been recognised as the preferred (and required) indicator of effectiveness.

– Can be applied in comparisons of different therapies and, thereby, employed for priority-setting.

– Associated with fewer methodological issues compared to other approaches.

– Accounts for a societal perspective to the analysis.

Assessment Methods (2)

All countries deem RCTs the most reliable and objective evidence to classify product benefit.

– Preference is toward RCTs in naturalistic settings, in terms of reflecting daily routines and country-specific care delivery.

Even where definitive primary studies exist, however, there are limitations to reliance on such evidence.

– Trials do not often collect a full range of economic data (e.g., indirect costs, health utility measures).

– Study time horizon may be too short to detect longer term outcomes.

– Can restrict subgroup analyses.

Different types of studies should be combined or synthesised to best inform effective decision-making.

– Overall, a broader definition of value and product value should be adopted, including consideration of patient preferences, quality, equity, efficiency, and product acceptability.

Assessment Methods (3)

Assessments are comparative in nature -- choice of comparator is important in determining the outcomes of economic evaluations.

– Inclusion of relevant options is crucial to adequately inform decision-making.

Typically, includes all licensed indications.

Responsibility for selecting comparator(s) rests on the review body and/or manufacturer.

– NICE considers input from a wider range of stakeholders.

Different Approaches to Selecting

Comparator

Finland, Sweden (new drugs only), UK:

Require that a product be compared with up

to three well-defined comparators. In the

case of the UK, all relevant comparators are

required. Appropriate comparators typically

include the most cost-effective therapy,

common practice, or least-expensive

alternative.

Sweden (existing products), Switzerland:

Products compared to all therapies of the

same therapeutic group, based on the WHO

ATC classification system.

France: Combines both approaches.

Assessment Methods (4)

HTA bodies and gov’ts differ on the types of costs allowed for inclusion in assessments.

– Principal difference lies in the inclusion of direct and indirect costs (e.g., Sweden, allows all costs to be included; Netherlands uses only direct costs to the health system).

With indirect costs, there is a lack of agreement on how to account for productivity loss.

– Countries either employ a human capital or friction cost approach.

– Results can differ significantly depending on the method used.

Most costs are based on national data.

A high degree of transparency in cost calculations is imperative. – Includes adequately detailing all sources of data and any

assumptions employed.

Assessment Methods (5)

Most countries require sensitivity analyses and/or economic modelling to allow for uncertainty in the assessment.

– As requirements differ between countries, the choice of parameters and methods should be justified and well documented.

Models are typically generated by manufacturers, review bodies, or both.

– Review bodies often develop models to substantiate estimates provided by manufacturers, or to compensate for missing or incomplete data.

As multiple entities may be involved, transparency and information exchange is key.

Given increasing complexity and sophistication of modelling, more resources should be dedicated to methodology development.

Role of Stakeholders

Majority of HTA bodies involve a diverse array of stakeholders (e.g., physicians, health economists, industry, and patient group representatives).

However, for the most part, agencies support a limited role for patients and consumers in the HTA process.

– NICE established a Citizens Council to allow patients and consumers to comment on assessment priorities and recommendations.

Increased role for industry in the process has also been promulgated.

Greater stakeholder involvement can facilitate better overall assessment, lend to greater transparency, reduce appeals, and result in improved implementation of recommendations and guidance.

Level of Stakeholder Involvement

Varies from extensive (eg NICE in the UK) to very

limited (eg CDR in Canada)

Most HTA agencies allow company submissions of

evidence

Other examples of involvement include:

-scoping of the assessments (eg. choice of the

comparators, outcomes to be considered)

-commenting on draft reports

-appeals against recommendations

HTA Dissemination and Implementation (1)

Countries use a wide variety channels to disseminate HTAs to decision-makers and other stakeholders (e.g., providers, public).

– Reports

– Agency websites

– Clinical/practice guidance

– Seminars and conferences

– Academic/policy publications

– Newsletters

Many review bodies are members of international networks and societies, such as HTAi and EUnetHTA, which helps facilitate effective dissemination.

– National and international cooperation among assessment groups can also serve to enhance the transferability, accountability, and transparency of the overall process.

HTA Dissemination and Implementation (2)

HTA are used to inform a wide range of decisions: – Shape the benefit catalogue

– Plan resource capacities

– Develop clinical practice guidance

– Inform organisational investment decisions

– Acquisition of new technology

While almost all countries require assessments to determine reimbursement status (positive list), differences exist regarding the importance of economic evidence in the decision process.

– France, for example, rarely considers cost-effectiveness.

HTA also plays a role in pricing decisions; again, countries differ in this regard.

– Reimbursement decisions are sometimes made prior to pricing, while in some countries (e.g., Sweden, Finland), the reimbursement and pricing of a product are made simultaneously.

HTA Dissemination and Implementation (3)

Some countries (e.g., Sweden, UK) have a formal appeals process, whereby stakeholders can be heard if they object to HTA evidence/decisions.

Re-evaluation is a key component to the HTA process. – Allows new data to be considered.

– Accounts for uncertainty during the initial valuation process, which is especially important for new, novel products.

Some countries (e.g., Finland, France, UK) conduct re-appraisals at fixed intervals, while others initiate review if new characteristics (e.g., new or expanded indications) or data emerge.

However, protections must be in place so that re-evaluation doesn’t lead to inefficiency, resource burden, or delayed access to treatment.

Defining Willingness to Pay

Revealed or explicit threshold

Fixed threshold

– Advantages

– Limitations

– What is an appropriate metric?

Flexible threshold

– Why have a flexible threshold?

– What factors contribute to it?

– What is an appropriate metric?

Probability

of

Rejection

Cost utility (cost per QALY)

Inflexion A

Inflexion B

£20,000

£30,000

How do we gauge whether a technology is cost effective? An example from the UK setting

Source: Cookson, 2007

Flexible thresholds

Explicit Value Judgements – II

Equity /”need” adjusted reimbursement decisions compared

with a constant cost-effectiveness threshold

Cost/QALY

Degree of severity/”need”

0.5 1.

0

Threshold

Adjusted threshold

0.

9 0.1 0.2 0.3

UK

Netherlands,

Sweden

Therapeutic Value Health System Value Societal Value

Complexity

and breadth

of data

required to

demonstrat

e value

Pharmaceutical

Budget

Health System

Budget

Other Budgets

(e.g. pensions,

social security)

Representative

Country

France UK Sweden

Spectrum of Value (Payers) – Broad Sources and

Perspective of HTAs

Efficiency in resource allocation: HTA tells different stories depending on setting

4

21

47

79

54

62

70

111

26

78

64

19

52

6

61

0% 20% 40% 60% 80% 100%

CanadaCDR/CED

n=130

EnglandNICEn=110

AustraliaPBACn=210

SwedenTLV

n=111

ScotlandSMC

n=193

List LWC DNL Source: Kanavos, Nicod, van den

Aardweg, 2010 LWC = List with Criteria; DNL – Do Not List

Differential coverage decisions and reasoning in Canada, England and Australia

Drug Agen

cy

Outc

ome

Key non-pricing factors affecting differential outcome

Sufficient

evidence

Evidence

accepted

Suitable

Compar.

Indirect

evidence

Subgroup

analysis

ICER

accept.

Special

consid.

Gemcitabine

mBCA CED DNL No

NICE LWC Yes

Panitumumab

mCRC CED LWC Yes

PBAC DNL No

Topotecan

SCLC CED DNL No

NICE DNL Yes

Trastuzumab

mBCA NICE LWC Yes Yes Yes

PBAC DNL No

Bevacizumab

mCRC

(1st line)

CED DNL* No

NICE DNL No

PBAC LWC Yes

Permetrexed

(MPM) CED DNL No

NICE LWC Yes

PBAC L Yes

Sunitinib

malate RCC CED DNL* No

NICE LWC Yes Yes

PBAC LWC Yes Yes

From Cost-effectiveness to Value-Based Pricing: Analytical Design

Countries employ several different criteria to guide assessments. While almost all countries firstly consider therapeutic benefit,

other factors frame the analysis Back to Social Value Judgements

– Disease burden – Patient quality of life (QoL) – Costs and Cost-effectiveness – Budget impact – Availability of alternative treatments – Level of Innovation – Societal perspective and impact on individual, carer, family

To some extent, level of innovation, equity, and social and ethical implications are considered.

As a result, multiple criteria are used, but not in a systematic way

Using Multiple Criteria Decision Analysis to elicit value (criteria + stakeholders)

Source: Kanavos and Angelis, 2013.

Are HTA or VBP a panacea? Challenges to HTA and VBP

While HTA systems increasingly play a role in supporting decision-making, they are not without controversy.

Questions abound surrounding the following issues:

– Role of HTA in decision-making and priority-setting

– Methods employed during the assessment process

– Impact on innovation and access

– Role of stakeholders

What factors

impact

effective

implementation

of HTA?

What

evidence is

required?

How is HTA

evidence

used in the decision-

making

process?

How do HTAs

get

prioritised?

Who

participates in

the process?

Is HTA merely

a mechanism

to restrict

access?

HTA & VBP