How Important is ICER Preparation and Review for U.S. Market Access?

How Important is ICER Preparation and Review for U.S. Market Access?
December 23, 2019 - 3:13 pm, by

John Schneider, PhD and Alexis Doyle, MA

Avalon Health Economics

December 23, 2019

In recent years in the U.S., there has been an increase in the use of cost-effectiveness analysis (CEA) for drug and medical device coverage decisions. While the Center for Medicare and Medicaid Services (CMS) remains considerably behind European countries in the use of CEA in health technology assessment (HTA),1 private health insurers have begun to place greater emphasis on CEA-type thinking; while the CEA incremental cost-effectiveness ratio (ICER) threshold continues to be viewed with healthy skepticism in the U.S., the outcomes of CEA studies have proven useful for comparative purposes in therapeutic areas for which there is more than one treatment option, or in cases where value-based pricing is sought by manufacturers.2

The Institute for Clinical and Economic Review (ICER) is an independent U.S.-focused non-profit organization that conducts value assessments of health technologies, such as pharmaceuticals and medical devices.3 Value is assessed based on the clinical effectiveness of health technology, as well as its long-term economic value and short-term affordability within the U.S. healthcare system. Comparative clinical effectiveness is established via a systematic review of clinical evidence obtained from peer-reviewed publications. Grey literature, such as manufacturer submissions to regulatory agencies, may be included as part of the review when it contains significant evidence that is not yet available in the form of a peer-review publication. ICER constructs cost-effectiveness and budget impact models to estimate economic value, affordability, and value-based price benchmarks.

ICER Process. ICER’s health technology assessment (HTA) process occurs over a time span of approximately 8 months once a topic has been selected. Topics are typically selected when emerging therapies are close to receiving FDA approval. ICER releases several documents throughout the HTA process. These include a scoping document, research protocol, model analysis plan, and evidence report. There are various opportunities for stakeholder engagement prior to the publication of the final evidence report. Manufacturers engage in calls with ICER, submit data and supplemental information, comment on draft documents, and comment on the evidence report during a final public meeting. We recommend that manufacturers read ICER’s “Manufacturer Engagement Guide” to familiarize themselves with the review process and timing of opportunities for engagement.

ICER’s scoping process begins with calls to manufacturers and an open input period. Manufacturers should be prepared to use the open input period to provide contextual information that can inform the direction and scope of the evidence review. Manufacturers should also identify and be prepared to submit citations for key publications that provide evidence of their product’s clinical benefit. ICER considers the following criteria when establishing the scope of its evidence review: population, intervention, comparators, outcomes, timing, setting, and study designs Manufacturers should use the “PICOTS” framework to determine which perspectives best capture their product’s clinical and economic benefit. This will position them to provide well-considered feedback on the draft scoping document.

Manufacturers must have a thorough knowledge of the published literature that ICER is likely to use to inform its clinical evidence review. ICER gathers evidence via a systematic review of published clinical studies, HTAs, and systematic reviews. Although ICER will consider unpublished “grey literature” evidence as necessary, its general policy is to restrict its review to published data that have undergone peer review. However, manufacturers should be aware of any evidence gaps in the literature and be prepared to submit relevant data. ICER will submit formal requests for manufacturer data around Week 7. They provide a sample request for data on the last page of their “Manufacturer Engagement Guide” (see “Appendix A. Sample Request for Data” on pg. 27). Data that may be requested include the following: progression-free survival (PFS) and overall survival (OS) curves and hazard ratios; health-state utility parameter estimates; and the costs associated with treatment and adverse events.

Economic Models. Manufacturers should be familiar with the economic models that have previously been used to evaluate similar products. Manufacturers should anticipate the model structure, assumptions, and inputs that ICER is likely to employ based on existing economic models and available data. They can then project the value-based pricing estimates that ICER’s model will generate at thresholds between $50,000 and $150,000 per QALY gained. Manufacturers should continue developing a cost-effectiveness analysis of their product internally to inform their evaluation of the model ICER will likely develop.

Model Structure. Manufacturers should identify the model structure that best captures their product’s clinical and economic benefits and determine which data are necessary to support this model structure. Manufacturers should be prepared to give feedback if ICER selects a different model structure that fails to account for factors that influence the results.

Model Comparators. Manufacturers should determine which drugs are appropriate comparators for an economic evaluation of their product. They should understand the competitive landscape and know what evidence is available for emerging competitors. Manufacturers should consider exploring how different comparators affect the model results using an indirect treatment comparison if requisite data are publicly available. They should predict the likely comparators that ICER will select and be prepared to give comments. Manufacturers should be aware of how competitor drugs will be marketing themselves, and how their value messages will be similar or dissimilar from their products. They should assess the extent to which different model structures and assumptions support product differentiation and capture the advantages that their product has as compared to existing and emerging drugs in this therapeutic space.

Model Inputs. Manufacturers should attempt to predict the inputs that ICER will include in their model based on those that have been included in similar models. Manufacturers should use their internal model to identify inputs that have a large impact on model results. This will prepare them for comment if ICER fails to include these key inputs in their economic model. Manufacturers should also identify the optimal sources for model input data and be prepared to submit citations for these sources to ICER during the open input period.

Utilities. ICER is likely to request data for utility parameters as part of its formal data request. If manufacturers will not be collecting new utility data from clinical studies, they should assess the quality, accuracy, and appropriateness of extant utility data, and be prepared to justify their use. If there are limitations associated with the use of existing utility data, manufacturers should devise a strategy for addressing this gap.

Model Outcomes. Manufacturers should use their internal model to identify health outcomes that provide evidence of their product’s clinical and economic benefits. Manufacturers should determine which data are required to support the inclusion of key outcomes. Manufacturers should also consider the extent to which these outcomes are aligned with those that patients and clinicians think are important. This will prepare them to identify and comment on key outcomes that ICER excludes from its economic model.

Budget Impact Model. Manufacturers should be prepared to field formal requests for data needed to construct a budget impact model. These data may include estimates for the size of the population that will be eligible to use their product and rates of market uptake. Additional examples can be seen in the sample request for data on pg. 27 of ICER’s “Manufacturer Engagement Guide.”

Summary. Many of the recommendations listed above align with steps that many manufacturers normally undertake in the course of preparing for market launch and technology assessment. We emphasize that manufacturers should prepare for opportunities to provide feedback to ICER, as such feedback can influence the scope and results of the HTA. This feedback should be based on conclusions drawn from manufacturers’ own research and internal models. In sum, we recommend the following as specific steps that manufacturers can take to prepare for an upcoming ICER review:

  • 1) Learn about ICER’s HTA process using ICER’s “Manufacturer Engagement Guide.” Be aware of all opportunities for manufacturer engagement and public input, and the timing of the formal data request. Determine which evidence should be submitted to ICER for consideration;
  • 2) Review the published clinical literature and anticipate the sources that ICER is likely to use to inform its evidence review. Identify evidence that should be included as part of the review or to provide contextual information; update literature if necessary;
  • 3) Identify data gaps and generate new data that could help support or inform the evidence review;
  • 4) Construct internal “interim” (and mostly conceptual) cost-effectiveness and budget impact models, which can serve the following purposes: (a) anticipate the model structure, assumptions, comparators, and inputs that ICER will use in its model; (b) predict the value-based pricing estimates that ICER’s model will generate at thresholds between $50,000 and $150,000 per QALY gained, and (c) be prepared to provide an informed critique of limitations or biases inherent to ICER’s model

1There is some evidence that CMS is beginning to incorporate economic evaluations in reimbursement decisions, but such efforts have been largely ad hoc thus far; see generally J. D. Chambers et al., “Factors Predicting Medicare National Coverage: An Empirical Analysis,” Med Care 50, no. 3 (2012); J. D. Chambers, P. J. Neumann, and M. J. Buxton, “Does Medicare Have an Implicit Cost-Effectiveness Threshold?,” Med Decis Making 30, no. 4 (2010); A. Mason et al., “Comparison of Anticancer Drug Coverage Decisions in the United States and United Kingdom: Does the Evidence Support the Rhetoric?,” J Clin Oncol 28, no. 20 (2010); P. J. Neumann et al., “Medicare’s National Coverage Decisions, 1999-2003: Quality of Evidence and Review Times,” Health Aff (Millwood) 24, no. 1 (2005); P. J. Neumann, M. S. Kamae, and J. A. Palmer, “Medicare’s National Coverage Decisions for Technologies, 1999-2007,” ibid.27, no. 6 (2008); S. D. Pearson and P. B. Bach, “How Medicare Could Use Comparative Effectiveness Research in Deciding on New Coverage and Reimbursement,” ibid.29, no. 10 (2010).

2See generally R. Burkholder, J. S. Dougherty, and L. A. Neves, “Ispor’s Initiative on Us Value Assessment Frameworks: An Industry Perspective,” Value Health 21, no. 2 (2018); L. P. Garrison, Jr. et al., “A Health Economics Approach to Us Value Assessment Frameworks-Summary and Recommendations of the Ispor Special Task Force Report [7],” ibid.; J. P. Jansen, D. Incerti, and J. R. Curtis, “Toward Relevant and Credible Cost-Effectiveness Analyses for Value Assessment in the Decentralized U.S. Health Care System,” J Manag Care Spec Pharm 25, no. 5 (2019); J. Jorgensen, S. Servos, and P. Kefalas, “The Potential Price and Access Implications of the Cost-Utility and Budget Impact Methodologies Applied by Nice in England and Icer in the Us for a Novel Gene Therapy in Parkinson’s Disease,” J Mark Access Health Policy 6, no. 1 (2018); P. J. Neumann, R. J. Willke, and L. P. Garrison, Jr., “A Health Economics Approach to Us Value Assessment Frameworks-Introduction: An Ispor Special Task Force Report [1],” Value Health 21, no. 2 (2018); R. Norman, K. Chalkidou, and A. J. Culyer, “A Health Economics Approach to Us Value Frameworks: Serving the Needs of Decision Making,” ibid.; G. D. Sanders et al., “Recommendations for Conduct, Methodological Practices, and Reporting of Cost-Effectiveness Analyses: Second Panel on Cost-Effectiveness in Health and Medicine,” Jama 316, no. 10 (2016); B. Solow and E. J. Pezalla, “Ispor’s Initiative on Us Value Assessment Frameworks: The Use of Cost-Effectiveness Research in Decision Making among Us Insurers,” Value Health 21, no. 2 (2018); R. J. Willke et al., “Review of Recent Us Value Frameworks-a Health Economics Approach: An Ispor Special Task Force Report [6],” ibid.

3See generally D. Freund and J. Choi, “Is Icer Nicer?,” Pharmacoeconomics 36, no. 4 (2018); Jorgensen, Servos, and Kefalas; P.J. Neumann and J.T. Cohen to Health Affairs Blog, March 12, 2018, 2018; S. D. Pearson, “The Icer Value Framework: Integrating Cost Effectiveness and Affordability in the Assessment of Health Care Value,” Value Health 21, no. 3 (2018); J. T. Snider et al., “Challenges with Forecasting Budget Impact: A Case Study of Six Icer Reports,” ibid.22 (2019).


REFERENCES
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