医薬品のための医療技術申請

Abstract

Summary

"it must be acknowledged that few pharmaceutical manufacturers, let along biotech companies are equipped to meet these new health technology assessment guidelines"

This essential report will help you:

• Prepare a global dossier to ensure successful formulary listing
• Understand formulary submission guidelines in Australia, UK and USA
• Respond to emerging evidentiary and analytical standards
• Structure your organisation to make a convincing case to the regulators

The rapid uptake of formulary submission guidelines in the last decade is forcing pharmaceutical manufacturers and biotechnology companies to comply with more rigorous evidentiary and analytical standards in clinical and cost-effectiveness evaluations.

Two developments in 2004 further transformed the situation:

• 1. The introduction of a revised health technology assessment guideline by the National Institute for Clinical Excellence (NICE) in the UK; and
• 2. The introduction of revised technology assessment guidelines for new products and for the re-evaluation of products by WellPoint Pharmacy Management (WPM) in the USA.

Where the NICE and WPM guidelines represent a major change in requirements with the need:

• (i) to accommodate adequately uncertainty in modelled cost-effectiveness claims and the requirement for a reference case (NICE); and
• (ii) the requirement for naturalistic, active comparator trials together with ongoing monitoring and validation of claims for cost-effectiveness and systems impact (WPM).

Put together, the NICE and WPM guidelines present formidable challenges to manufacturers in both the UK market and in the US managed care sector. If other health technology assessment and reimbursement gatekeepers adopt these new evidentiary and analytical standards, then manufacturers will have to rethink seriously not only how they adapt their clinical development programs to accommodate the reference case and active comparator requirements in Phase III trials, but the ways in which they present cost-effectiveness and system impact claims to meet monitoring and validation standards.

Preparing health technology submissions for pharmaceutical products - Meeting Formulary Submission Requirements for New Product Assessments and Disease Area and Therapeutic Class Reviews, considers how manufacturers should respond to emerging evidentiary and analytical standards as exemplified by the NICE and WPM guidelines for formulary submissions.

The report considers, in particular, the implications of the standards required in the NICE and WPM guidelines for manufacturers preparing reimbursement submissions and it goes beyond being simply a review of evidentiary and analytical standards required by reimbursement and pricing authorities that have mandated a formulary submission dossier as part of the technology assessment of new products, to establishing the standards required of a global dossier. Meeting the NICE and WPM requirements ensures that specific or targeted dossiers can be assembled to satisfy the requirements of other jurisdictions. A global dossier, therefore, if structured to meet the standards of NICE and WPM, will also meet the requirements of other jurisdictions - where individual formulary submissions are customized to meet the needs of individual health systems.

"a poorly constructed and self-serving case, where the modelled case has clearly been driven by the need to justify cost-effectiveness, seldom stands up to a critical review."

Reasons you company should invest in this report:

• Understand the published guidelines from the major evaluation agencies
• Benefit from over 40 detailed case studies of technology appraisal guidelines
• Learn to prepare an excellent global dossier to ensure formulary acceptance
• Forecast how technology appraisals will develop over the next few years

Table of Contents

• Background
• Overview
• Chapter 1: Global Formulary Submission Requirements
  • Chapter outline
  • 1.1 Introduction
    • 1.1.1 Key documents
    • 1.1.2 The second level
    • 1.1.3 Health technology assessments (HTAs)
    • 1.1.4 The emergence of formulary submission guidelines
  • 1.2 Current formulary submission standards
    • 1.2.1 PBAC: standards for clinical assessment
      • Case study 1.1: The PBAC guidelines
    • 1.2.2 England and Wales, NICE: standards for modeled cost-effectiveness claims
      • Case study 1.2: The NICE guidelines
    • 1.2.3 WellPoint: standards for monitoring and validating claims
      • Case study 1.3: The WellPoint guidelines
    • 1.2.4 The Scottish Medicines Consortium
      • Case study 1.4: The SMC guidelines
    • 1.2.5 US: AMCP - an interim standard
      • Case study 1.5: The AMCP guidelines
    • 1.2.6 Process and dossier submissions
      • Case study 1.6: Identifying reimburser requirements
    • 1.2.7 Transparency and process
  • 1.3 Hierarchy of clinical evidence
  • 1.4 Formulary recommendations and assignments
  • 1.5 The role of guidelines
    • Case study 1.7: The future of NICE - what could be NICER?
  • 1.6 Linking cost-effectiveness and budget-impact claims
    • Case study 1.8: Viagra versus the PBAC
  • 1.7 Overview: managing patient populations
    • Notes
• Chapter 2: Guidelines from a Global Perspective
  • Chapter outline
  • 2.1 A global guideline overview
    • Case study 2.1: The ISPOR guidelines summary
  • 2.2 Formulary submission guidelines: documentation and process
  • 2.3 Health technology assessments (HTAs) and the life cycle of a drug
  • 2.4 Disease area and therapeutic class reviews
  • 2.5 Bias and compliance
  • 2.6 Technology scoping
  • 2.7 The global dossier: meeting evidentiary and analytical standards
  • 2.2: Proposed outline for a global dossier
    • Notes
• Chapter 3: Uncertainty - Net Benefits, Product Ranking and the Reference Case
  • Chapter outline
  • 3.1 Uncertainty in cost-effectiveness claims
  • 3.2 Ranking therapy interventions
    • 3.3 ICERs and net benefit measures
  • 3.4 Defining net benefits
  • 3.5 Interpreting ICERs
  • 3.6 Net monetary benefit
  • 3.7 Probabilistic sensitivity analysis
  • 3.8 Estimating cost-effectiveness acceptability curves
    • Case study 3.1: Modelling a probabilistic sensitivity analysis
  • 3.9 Interpreting, monitoring and validating claims
  • 3.10 The NICE reference case
    • Case study 3.2: NICE reference case requirements
    • Case study 3.3: The EQ-5D and the SF-6D in liver transplant patients
  • 3.11 Implications of the reference case requirements
  • 3.12 Overview: thresholds and evidentiary standards
    • Notes
• Chapter 4: The Clinical Outcomes Case
  • Chapter overview
  • 4.1 Literature searches
    • 4.1.1 Key databases
    • 4.1.2 Reference inclusion/exclusion criteria
      • Case study 4.1: PBAC requirements for literature searches
  • 4.2 Bias and systematic reviews
    • 4.2.1 Randomisation
    • 4.2.2 Follow-up
    • 4.2.3 Blinding
      • Case study 4.2: Bias assessment in clinical trials
    • 4.2.4 Filtering studies
  • 4.3 Hierarchies of clinical evidence
    • Case study 4.3: The PBAC and WellPoint hierarchies of clinical evidence
  • 4.4 Summarising clinical studies
    • Case study 4.4: Meeting PBAC trial summary requirements
  • 4.5 Quality-scoring clinical studies
    • Case study 4.5: The Jadad quality-scoring algorithm
  • 4.6 Pooled clinical data and meta-analyses
    • Case study 4.6: The PBAC requirements for meta-analysis
    • 4.6.1 Identifying relevant studies
    • 4.6.2 Eligibility criteria
    • 4.6.3 Abstracting data
    • 4.6.4 Statistical models
  • 4.7 Adverse events and side-effect profiles
    • Case study 4.7: Pharmacoepidemiology
  • 4.8 Defining comparator products 4
    • Case study 4.8: Comparator therapies in the PBAC guidelines
  • 4.9 Epidemiology
    • Case study 4.9: WellPoint epidemiology profiling requirements
  • 4.10 Place of product in therapy
    • Case study 4.10: The PBAC and expert opinion
  • 4.11 Product profile
    • Case study 4.11: WellPoint product profile requirements
  • 4.12 Therapy intervention strategies
    • Case study 4.12: NICE recommendations for Relenza in the treatment of influenza
  • 4.13 Linking meta-analyses to modelled claims
    • Case study 4.13: Defining clinical parameters for cost-effectiveness modelling
  • 4.14 Monitoring and validating clinical claims
    • Case study 4.14: The NICE appraisal of beta interferon and glatiramer for multiple sclerosis
  • Notes
• Chapter 5: The Health Economics Case I - Generating Modelled Cost-effectiveness Claims
  • Chapter outline
  • 5.1 Types of modelled claim
    • Case study 5.1: Modeling criteria in the PBAC guidelines
  • 5.2 Decision-model frameworks
  • 5.3 Resource units and direct costs
    • Case study 5.2: Current procedure terminology (CPT) codes
  • 5.4 Valuing resource units
  • 5.5 Indirect costs
    • Case study 5.3: Demonstrating workplace productivity benefits
  • 5.6 Measuring outcomes
    • 5.6.1 Construct
  • 5.7 Modelling, sensitivity and simulation analyses
  • 5.8 Spreadsheet models
  • 5.9 Monitoring and validating cost-outcome claims
    • Case study 5.4: The impact of inhaler type on monthly treatment costs of asthma - a retrospective study
  • 5.10 Meta-models
    • Case Study 5.5: The CORE diabetes meta-model
  • Notes
• Chapter 6: The Health Economics Case II - Estimating System Impacts
  • Chapter outline
  • 6.1 Defining terms
  • 6.2 Forecasting product uptake
    • Case study 6.1: SMC requirements for product uptake projections
  • 6.3 Patient switching and target populations
    • 6.3.1 Defining a target population
    • 6.3.2 Market segmentation
  • 6.4 Budget-impact claims
    • 6.4.1 Resource units and unit pricing
  • 6.5 Estimated pharmacy budget impact
  • 6.6 Estimated medical budget impact
  • 6.7 Estimated total budget impact
    • Case study 6.2: PBAC requirements for financial impact assessment
  • Note
• Chapter 7: Responding to Disease Area and Therapeutic Class Reviews
  • Chapter outline
  • 7.1 Life-cycle product assessment
    • 7.1.1 Clinical assessments
    • 7.1.2 Anticipating requests for monitoring and validation
  • 7.2 Assessing claims
  • 7.3 Contractual requirements
  • 7.4 Experimental approaches: naturalistic trial designs
    • Case study 7.1: The role of naturalistic trials
  • 7.5 Non-experimental designs
    • 7.5.1 Case-control studies
    • 7.5.2 Cohort studies
  • 7.6 Practice pattern variations
    • Case study 7.2: The WellPoint agenda
  • Notes
• Chapter 8: Summary and Conclusions
  • Chapter outline
  • 8.1 The future of technology appraisals
  • 8.2 Technology appraisals in the short term
  • 8.3 Technology appraisals in the longer term
    • Glossary
• List of Figures
  • Figure 3.1 Benefit and willingness to pay
  • Figure 3.2 Cost-effectiveness plane
  • Figure 3.3 Net monetary benefit
  • Figure 3.4 Ranking net monetary benefits
  • Figure 3.5 Cost-effectiveness acceptability curve
  • Figure 3.6 Decision model: Therapy A versus Therapy B
  • Figure 3.7 Simulated distribution of differences in costs
  • Figure 3.8 Simulated distribution of differences in outcomes
  • Figure 3.9 Distribution of cost and outcome difference coordinates in the cost-effectiveness plane
  • Figure 3.10 Simulated cost-effectiveness acceptability curve
• List of Tables
  • Table 2.1 Key formulary submission guidelines: documentation and process
  • Table 3.1 Parameter values: Therapies A, B and C
  • Table 3.2 Simulation pairs of cost and outcome differences
  • Table 3.3 Simulated proportion of coordinate cost and outcome difference by willingness-to-pay threshold
  • Table 4.1 Grading of clinical studies