Key Principles for the Conduct of HTA for Resource Allocation Decisions

Michael DrummondCentre for Health Economics,

University of York

Outline of Presentation

• International growth in the use of HTA and economic evaluation

• Impact of HTA/economic evaluation on drug reimbursement

• Key principles for the conduct of HTA• National Institute for Health and Clinical

Excellence(NICE) in the UK: present and future

Background to the Use of HTA• HTA is ‘a multi-disciplinary field of policy

analysis studying the medical, economic, social and ethical implications of the development, diffusion and use of health technologies’ (INAHTA, 2002)

• Prominent in the US in the early 1980s, through the (Congressional) Office of Technology Assessment

• Early agencies in Europe were the SBU (Sweden) and the TNO (The Netherlands)

Formal Use of HTA in Healthcare Decision-making

• Many HTA agencies merely issue reports

• In the 1990s several jurisdictions began to use HTA methods, incorporating economic evaluation, in their reimbursement decisions

• Australia (1993) was the first example of the use of economic evaluation in pharmaceutical reimbursement

Formal Use of Economic Evaluation

• Europe:Belgium Ireland PortugalDenmark Netherlands SwedenFinland Norway Hungary United Kingdom Germany Slovakia

• The Americas:US health plans MexicoBrazil Canada

• Asia/Oceania:New Zealand KoreaAustralia Taiwan

Impact of Health Technology Assessments

• Can lead to a refusal to reimburse or cover the technology concerned

• More often it leads to restrictions to access to technologies (eg 2nd or 3rd line use, only for some patient groups, etc.)

• Some restrictions are harder to enforce than others, and the implementation of recommendations is not automatic

• Sometimes the mere intention to conduct an HTA can impact on use of the product

NICE's Guidance on New Cancer Drugs: May 2000-March 2008: Methods• Data sources

– NICE published appraisals on cancer drugs– EMEA/MHRA licences/SPCs

• Data extraction– Drug, indication, recommendations– Stated justifications:

uncertainty; methodological issues; trial evidence; ICER• For each drug evaluation

– compare recommendation with licence– classify recommendation as:

licence; restricted; no routine use; not licensed• Restricted/no routine use

– 24/55 drug evaluations– reasons for restrictions explored

Mason A and Drummond M. Eur.J.Cancer 2009; 45: 1188-92.

NICE Cancer Recommendations% cancer drug evaluations (N=55)

As licence (55%)

Restricted (29%)

No routine use (15%)

Not licensed (2%)

Key Principles for HTA

• Structure of HTA

• Methods of HTA

• Processes for Conduct of HTA

• Use of HTA in Decision-making

Structure of HTA

• The goal and scope of the HTA should be explicit and relevant to its use.

• HTA should be an unbiased and transparent exercise.

• HTA should include all relevant technologies.

• A clear system for setting priorities for HTA should exist.

Methods of HTA• HTA should incorporate appropriate methods for

assessing costs and benefits.• A full societal perspective should be considered

when undertaking HTAs.• HTAs should explicitly characterize uncertainty

surrounding estimates.• HTAs should consider and address issues of

generalizability and transferability.• HTAs should consider a wide range of evidence and

outcomes.

Principle 5. HTA should incorporate appropriate methods for assessing

costs and benefits• Does the HTA organization consider costs as well

as benefits and harms?• Does the HTA organization have published

methods guidelines for assessing the benefits, harms and costs of health technologies?

• Is a full systematic review of clinical evidence required as a basis for economic modeling?

• Does the team undertaking HTAs on behalf of the organization include individuals with skills in epidemiology/biostatistics, health services research and economics?

Principle 6. HTAs should consider a wide range of evidence and outcomes.

• Does the relevant clinical evidence include observational and non-randomized studies, as well as randomized controlled trials?

• Does the HTA consider impacts on quality of life and other patient-reported outcomes, as well as clinical events?

• Does the HTA consider relevant sub-groups of the patient population (e.g. by baseline risk)?

Principle 7. A full societal perspective should be considered when

undertaking HTAs• Does the HTA consider only consider the impact on a

specific budget, for example for drugs?• Does the HTA consider all health care costs?• Can other costs be included as extra information?• Are productivity gains and losses (ie indirect costs and

benefits) considered when relevant?• Are costs for informal care included when relevant?• Are costs in added years of life included in the cost-

effectiveness ratio?

Processes for Conduct of HTA

• Those conducting HTAs should actively engage all key stakeholder groups.

• Those undertaking HTAs should actively seek all available data.

• The implementation of HTA findings needs to be monitored.

Quality of the Review Process• Some entities review manufacturers’

submissions, and other evidence, in-house, others (eg NICE) commission independent expert reviews.

• Good quality review, using explicit criteria, is critical to the integrity of the HTA process.

• Transparency is important, as mistakes are made and need to be rectified!

Level of Stakeholder Involvement

• Varies from extensive (eg NICE) to very limited (eg PBAC in Australia).

• Most HTA agencies allow company submissions of evidence.

• Other examples of involvement include:-scoping of the assessments (eg. choice of thecomparators, outcomes to be considered) -commenting on draft reports-appeals against recommendations

Transparency in HTA Processes• Transparency is necessary for

understanding the criteria used, the analyses conducted and the reasons for any recommendation.

• Mechanisms can be developed to protect commercial-in-confidence data.

• Transparency may be more of a challenge in the context of private payers.

National Institute for Health and Clinical Excellence (NICE)

• Created in 1999• A Special Authority within the National Health Service

(NHS)• Remit is to consider ‘clinical and cost-effectiveness’• Programmes of work in:

- health technology appraisal- new interventional procedures*- clinical guidelines- public health interventions- medical devices

* Efficacy and safety only

Technology Appraisals versus Clinical Guidelines

• Technology appraisalsDeal with new technologies; narrow focus; many

concern a single technology (eg a drug in a given indication); mandatory on the NHS.

• Clinical guidelinesDeal with existing care; broader focus; aim is to

improve existing care patterns; adoption is voluntary.

NICE’s Procedures

• Remit received from the Department of Health• Scoping exercise undertaken• Submissions invited from key sponsors or

manufacturers of the technology• Independent review of the evidence• Guidance developed (by an expert group)• Guidance issued to the National Health Service

(NHS): mandatory for technology appraisals• Monitoring of guidance and review (3 years)

NICE’s Output to Date*

• Interventional procedures (370)

• Technology appraisals (263)

• Clinical guidelines (157)

• Public health appraisals (38)

* As of 24 August 2012

NICE’s Cost-Effectiveness Threshold

• An analysis of NICE’s initial decisions suggested that there was a cut-off value, or threshold, beyond which NICE was unwilling to recommend new technologies

• NICE later announced that its cost-effectiveness threshold was £20,000-£30,000 per quality-adjusted life-year gained

• The threshold is supposed to ensure that new technologies do not displace existing technologies of higher value

Key Principles: How Does NICE Shape Up?

Assessment Criteria

‘+’ Means that the organization ‘supported’ the Principle in written guidelines or other forms, regardless of whether it was followed.

‘++’ Means that the organization ‘implemented’ the Principle in published reports and that the decisions based on these reports demonstrate adoption of the Principle.

Support and Use of Key HTA Principles by NICE

Key Principle:NICE (UK)Inception:

1999Structure of HTA program

1. The goal and scope of the HTA should be explicit and relevant to its use ++

2. HTA should be an unbiased and transparent exercise ++

3. HTA should include all relevant technologies ++

4. A clear system for setting priorities for HTA should exist ++

Methods of HTA

5. HTA should incorporate appropriate methods for assessing costs and benefits ++

6. HTAs should consider a wide range of evidence and outcomes ++

7. A full societal perspective should be considered when undertaking HTAs

8. HTAs should explicitly characterize uncertainty surrounding estimates ++

9. HTAs should consider & address issues of generalizability & transferability

Note. “+” signifies that the organization “supported” the principle in question in written guidelines or other form, regardless of whether they actually follow it. “++” means that the organization “implemented” the principle in published reports and decisions based on these reports demonstrate adoption of the specific principle.NICE = National Institute for Health and Clinical Excellence.

Support and Use of Key HTA Principles by NICE (contd)Key Principle:

NICE (UK)Inception: 1999

Processes for conducting HTA

10. Those conducting HTAs should actively engage all key stakeholder groups

++

11. Those undertaking HTAs should actively seek all available data ++

12. The implementation of HTA findings needs to be monitored +

13. HTA should be timely +

Use of HTA in decision making

14. HTA findings need to be communicated appropriately to different decision makers

++

15. Link between HTA findings and decision making processes needs to be transparent and clearly defined

+

Note. “+” signifies that the organization “supported” the principle in question in written guidelines or other form, regardless of whether they actually follow it. “++” means that the organization “implemented” the principle in published reports and decisions based on these reports demonstrate adoption of the specific principle.NICE = National Institute for Health and Clinical Excellence.

Current and Future Directions for NICE

• End of Life Guidance

• Patient Access Schemes

• Value-Based Pricing(for pharmaceuticals)

• NHS Quality Standards

Social Values and End-of-Life Guidance

• NICE has always recognized that factors other than cost-effectiveness play a part in ‘deliberative decision-making’.(See Rawlins and Culyer , 2004: Citizens’ Council, 2006)

• Question has always been one of how to operationalize this.

• The end-of-life guidance offers one potential solution.

NICE’s Supplementary Guidance for ‘End of Life’ Therapies

• If the therapy:-is for a small patient population with life expectancy of less than 24 months;

-where the therapy adds three months or more to life expectancy,

• Then:-the QALYs gained should assume full quality of life in the added months;

-in addition the Committee can consider that the QALYs gained should be weighted sufficiently high for the therapy to be approved given NICE’s current threshold.

Examples of UK Patient Access Schemes

• b-IFN and glatiramer for multiple sclerosis – 2002– Prospective cohort – managed by DH

• Bortezomib for multiple myeloma – 2007 – Money back guarantee based on response (M-protein)

• Ranibizumab for acute macular degeneration – 2008– Dose capping scheme (<14 injections per eye)

• Erlotinib for small cell lung cancer – 2008– Cost capping scheme (same overall cost as docetaxel)

• Sunitinib for advanced renal cell carcinoma -2009 – 1st cycle of treatment free to NHS patients

• Lenalidomide for multiple myeloma – 2009– Dose capping scheme (<26 cycles/2yrs)

Source: Chalkidou (2009)

Value-Based Pricing Proposal (UK)

• Stated objectives are to:- improve outcomes through better access to effective drugs- stimulate innovation- improve the process (eg increased transparency, timeliness)- include a wide assessment, alongside clinical effectiveness- ensure value for money from NHS resources

• A technical assessment of the costs and QALYs gained from the drug in its various indications will be conducted as at present

• Instead of NICE making recommendations, there will then follow a negotiation between the company and the DH to determine a (maximum) value-based price (VBP)

Value-Based Pricing Proposal (2)

• Would apply to new branded medicines launched from January 1, 2014

• Recognition that new arrangements may be required for already-existing medicines

• The negotiation would consider:- the ‘basic’ cost-per QALY threshold- the burden of illness and unmet need that the medicine

focuses on- the extent of therapeutic innovation- the wider societal benefits (eg impact on carers)

Challenges in Value-Based PricingDefining the dimensions of ‘value’

- health gain only?- other considerations?

Determining the local decision rule- explicit cost per QALY threshold?- general rating of added value (eg 1-5) impacting on price?

Dealing with multiple indications- price/volume agreements?- weighted price?

Determining the level of transparency- publication of assessments?- publication of negotiated prices?

NHS Quality Standards• A major new role for NICE• Designed to drive and measure priority

quality improvements within a particular area of care

• Are derived from the best available evidence such as NICE guidance and other evidence sources accredited by NICE

• Evidence relating to effectiveness and cost effectiveness, people's experience of using services, safety issues, equality and cost impact are considered during the development process.

Conclusions

• The use of HTA/economic evaluation is now well-established in drug pricing and reimbursement decisions worldwide

• It is possible to specify key principles of good practice

• Each jurisdiction needs to decide on the optimal set of procedures and processes that will be most suitable locally