{"id":3864,"date":"2013-02-27T15:25:08","date_gmt":"2013-02-27T15:25:08","guid":{"rendered":"https:\/\/www.pm360online.com\/?p=3864"},"modified":"2014-01-12T13:09:09","modified_gmt":"2014-01-12T13:09:09","slug":"international-trends-in-health-technology-assessment-hta-implications-for-an-optimal-health-economics-and-outcomes-research-heor-strategy","status":"publish","type":"post","link":"https:\/\/www.pm360online.com\/international-trends-in-health-technology-assessment-hta-implications-for-an-optimal-health-economics-and-outcomes-research-heor-strategy\/","title":{"rendered":"International Trends in Health Technology Assessment (HTA): Implications for an Optimal Health Economics and Outcomes Research (HEOR) Strategy"},"content":{"rendered":"

Understanding the diverse international HTA environment and the nature of individual agency decisions is of growing importance for the development of an optimal health economic and outcomes research strategy.<\/strong><\/p>\n

 <\/p>\n

Today, there are a growing number of health technology assessment (HTA) agencies around the world, some more prominent and systematic in their approach, but all undertaking some form of HTA evaluation. Their approval and reimbursement decisions vary considerably, even when reviewing similar efficacy, safety and economic data, with a consequent variable impact on a drug\u2019s market access profile. And the situation continues to evolve; even countries with more mature processes are still searching for the optimal HTA model.<\/p>\n

 <\/p>\n

For health economics and outcomes researchers, the diversity and heterogeneity of HTA agencies create enormous challenges, including constantly changing evidence requirements, inconsistent availability of appropriate data, variability in methodology and interpretation of that data, and ultimately demonstrating product value across disparate markets. Real-world evidence, for example, is one data element that is used increasingly in decision-making but to different degrees in different countries (Figure 1<\/b>).<\/p>\n

The extent to which HTA outcomes and guidance vary across countries can be seen in the case of sunitinib for renal cell carcinoma (RCC), which received very different ratings from four independent European HTA agencies focused on cost-effectiveness.\u00a0 As shown in <\/span>Figure 2<\/b>, the rulings ranged from full (conditional) reimbursement by the TLV (Tand-och Lakemedelsformansverket) in Sweden to complete denial of access in Scotland following review by the SMC (Scottish Medicines Consortium), reflecting their very different perceptions of the drug\u2019s \u201cvalue\u201d.<\/span><\/p>\n

Growing Need For a New Understanding<\/h3>\n

Understanding the diverse international HTA environment and the nature of individual agency\u00a0decisions is thus of growing importance for the development of an optimal health economic and outcomes research strategy. The challenge is being able to leverage prior learnings and incorporate them as far as possible into the clinical trial program to ensure a positive early reimbursement decision from each of the respective HTA bodies. For manufacturers developing a market access strategy, this requires answers to a number of key questions:<\/p>\n

    \n
  • Did the HTA agency evaluate similar products previously \u2013 either a clinical comparator or pricing comparators? If so:<\/span><\/li>\n
  • Did they interpret the clinical data in the same way?<\/span><\/li>\n
  • What were the key drivers of negative\/positive appraisal decisions?\u00a0<\/span><\/li>\n
  • How likely is it that an appraisal by one HTA will impact appraisals by others?\u00a0<\/span><\/li>\n
  • How can the learnings from previous appraisals be strategically leveraged to maximize the likelihood of a positive reimbursement decision?\u00a0<\/span><\/li>\n
  • If the new product is first-in-class, is there another disease state that could be used as a proxy to assess how HTA agencies are likely to appraise it?<\/span><\/li>\n<\/ul>\n

    To address these issues, there is a clear need within HEOR to monitor the\u00a0influence of the information being provided to HTA agencies and leverage it for the improvement of research over time.\u00a0 This knowledge can serve as the basis for:<\/span><\/p>\n

      \n
    1. Discussions with clinical development <\/b>to determine the design of the Phase II\/III program in relation to: the comparator or comparators that are likely to be faced in reimbursement decisions across multiple jurisdictions, the endpoints (primary and secondary) and effect size.\u00a0<\/span><\/li>\n
    2. Discussions with commercial functions <\/b>to inform decisions around pricing, launch sequencing and the access level that is likely to be achieved, for forecasting and other functional purposes.\u00a0<\/span><\/li>\n
    3. Formulary and reimbursement submissions <\/b>as the basis for designing economic evaluations, modeling assumptions, cross-country communication and pricing negotiations.<\/span><\/li>\n<\/ol>\n

      Systematic Approach to Data Collection<\/h3>\n

      The optimal approach to collecting HTA data will vary by organization size, level of sophistication and the involvement of local affiliates. Responsibility may be assigned to a global HEOR group, local operating companies or an external vendor, depending on availability of manpower, resources and budget. In terms of timing, monitoring ideally should begin prior to the design of pivotal Phase II\/III studies by engaging payers or advisors at HTA agencies early in development to establish key endpoints, continually appraise them, and update as decisions are made.<\/p>\n

      The collection process should give consideration to HTA reviews on competitors but also data on the new compound itself\u2014which can serve as an important internal resource for applying key learnings across the organization\u2019s portfolio of products. Addressing future launches and\/or indications that may be planned for the same compound is also important. The ultimate goal should be a systematic process that includes: regular updates as decisions are made by HTA agencies; details of discussions leading to decisions (where available); and provision for tracking future reviews to anticipate competitor activity.<\/p>\n

      A key issue from a company perspective is to ensure that the collection of data is combined with systematic analysis, i.e., understanding not only the decision that was reached but also the rationale or discussions around it to facilitate forward planning for the type of challenges the compound might face related to reimbursement.<\/p>\n

      The value of systematic collection lies in the immediate access to the data, which is shared across all functional areas within the company and resonates in a way that can influence decisions at key points during research and development (R&D).\u00a0 Done well, such a process can enable:<\/p>\n

        \n
      • Avoidance of potential pitfalls in future submissions and a better understanding of data requirements in each market\u00a0<\/span><\/li>\n
      • Identification of possible data gaps within the clinical trial program and other targeted HEOR projects<\/span><\/li>\n
      • Understanding of the methodologies (accepted\/rejected) around health economic models that should be implemented early on or at the time of submission\u00a0<\/span><\/li>\n
      • Development of more innovative tactics in price negotiations with the HTA\/reimbursement authorities by learning from competitor successes and failures\u00a0<\/span><\/li>\n<\/ul>\n

        Application of HTA Data in Oncology<\/h3>\n

        Oncology is one key therapy area that has attracted increasing attention from payers in recent years following major scientific breakthroughs and strong growth in sales. Based on HTA decisions, product uptake rates vary from one country to another.\u00a0 Analysis of submissions in six countries (France, Spain, England, Scotland, Australia and Canada) between 2004 and 2010 shows that approval rates across four different tumor types (lung, breast, RCC and hematological malignancies) averaged close to 60% (Figure 3<\/b>).<\/p>\n

        For RCC only, the approval rate was 32%\u2014the lowest among the four cancers. From a country perspective, France had the highest percent of HTA approvals for RCC while Australia and Canada had the highest number of rejections. This variation among countries remains true for other tumor types.<\/p>\n

        \u00a0<\/span>Also evident is the growing number of submissions for lung cancer in recent years. In general, positive reviews have also been on the rise, reflecting advancements in treatment for this disease. However, in breast cancer, where medical progress has been more pronounced, the market is somewhat crowded compared to other tumor types. Thus, while the number of submissions is also similarly on the rise, there is no clear trend regarding positive and negative approvals by these agencies.\u00a0 However, in the case of hematological malignancies, almost all submissions were approved, reflecting the unmet needs in this area.<\/p>\n

        1. Drivers of negative outcomes<\/b><\/p>\n

        Most HTA rejections in RCC were the result of unacceptable economic analysis, specifically \u201cunacceptable ICERs\u201d\u2014a label that is open to wide interpretation (Figure 4<\/b>). More granular analysis of HTA decisions for RCC in Australia, Canada and the UK shows that most of the ICERs exceeded a $50K willingness-to-pay threshold, resulting in a negative outcome (Figure 5<\/b>). However, in two cases where the ICER was also above this level (Australia, UK) sunitinib was approved for use. Why?<\/p>\n

          \n
        • Australia: <\/b>In 2007, the manufacturer of sunitinib approached the Australian PBAC three times for feedback. On the first occasion, there was no economic model included in the dossier so the submission was rejected outright. The second time, the cost\/utility for adverse events had been omitted and progression-free survival proxied for overall survival.\u00a0 Finally, on the third attempt, the manufacturer was able to address all the previous requests and, through price negotiations, reduce the ICER to an acceptable level and ultimately gain access in the country. \u00a0\u00a0<\/span><\/li>\n
        • UK:<\/b> Also in 2007, several submissions were made for sunitinib in the UK, where potential denial of access to the drug had triggered a public outcry. Through the ensuing negotiation process, NICE began to rethink its framework for determining reimbursement, particularly in relation to the issue of prolonging life for patients with few therapy options. Sunitinib was eventually approved for a subset of patients where the drug had proven survival benefits compared to immunotherapy. NICE has since been giving more consideration to equity issues and the possibility of applying some form of weighted threshold for different diseases.\u00a0<\/span><\/li>\n<\/ul>\n

          2. Impact of survival data<\/b><\/p>\n

          A further interesting and very relevant analysis is the degree to which overall survival (OS) versus progression-free survival (PFS) has impacted HTA decisions.\u00a0 On the basis of the data collected, there is no discernible salient association between OS and PFS and HTA impact in this particular tumor type.\u00a0 However, it is of note that all trials using PFS without OS were rejected (Figure 6<\/b>).<\/p>\n

           <\/p>\n

          3. ICER differentials<\/b><\/p>\n

          Historical HTA data for RCC reveals significant disparities between the ICER estimates submitted by manufacturers and those developed by the agencies themselves, due largely to different assumptions in economic models. This signals potentially protracted negotiations to adjust the numbers during a period when time is of the essence and pricing discussions would also be ongoing. The key message here is that by ensuring robust data and a reasonable price behind the ICER, there is an opportunity for manufacturers to reduce the negotiation period from approval to reimbursement\/access, and by doing so, also minimize the opportunity costs of time lost during that process.<\/p>\n

           <\/p>\n

          Take Home Learnings<\/h3>\n

          Every situation is different; the lessons vary from one tumor type to another and each approach must be tailored. Knowledge of emerging comparators, products in the pipeline and other developments that will shape the future must also be drawn into the mix.\u00a0 However, purely based on the historic data, there are some key lessons to be learned in this area:<\/p>\n