A framework for multi-indication evidence synthesis in oncology Health Technology Assessment

点击翻译按钮获取中文摘要

An increasing number of drugs are used to treat different types of cancer. These present a common mechanism of action, such as blocking cancer blood vessel growth (anti-angiogenics such as bevacizumab). These drugs are typically first licensed by regulatory authorities for use in a specific indication (for a particular cancer histology in a particular line of treatment), and over time their licences are extended to include additional indications. Bevacizumab, for example, is currently approved by regulators for use in 11 indications.Closely after the regulatory license is awarded for a particular indication, the drug is appraised (for clinical and economic value) by health systems to determine whether it is made available (funded) to patients in that indication. This is called Health Technology Assessment (HTA). The evidence supporting HTA typically comprises of an indication-specific study that can be powered on intermediate (surrogate) outcomes, such as progression-free survival, rather than the final patient-relevant endpoints required by HTA agencies (e.g. overall survival). The focus on single indications means that every appraisal is subject to a high level of evidential uncertainty on final endpoints, even where considerable evidence on the drug exists for other indications. We propose exploring whether better use of evidence can be made by looking across, as well as within, indications. Such analyses would share information across indications, reducing decision uncertainty across the existing indications and providing more realistic predictions of the value of the drug in future indications. The overall aim of this project is, therefore, to develop a framework for multi-indication evidence synthesis to support oncology HTA. The framework will outline the judgements and analyses required to specify, conduct, and interpret the synthesis of multi-indication evidence, and will incorporate a package of tools.Three complementary work packages of methodological work will support the development of the framework:WP1: Presenting and summarising evidence In this work package, we will identify the relative effectiveness evidence for bevacizumab across its 11 indications, the real case study that will be used as an exemplar in this programme of work. To support multi-indication analyses, it is important that the evidence base is summarised appropriately for consideration by clinical and policy decision makers. Therefore, we will extend existing methods for the mapping of evidence to the multi-indication oncology setting (across indications, with multiple outcomes, and displaying the level of immaturity of evidence). WP2: Methods for multi-indication evidence synthesisIn this work package, we will develop methods for multi-indication evidence synthesis in oncology. We will consider models for sharing of information across indications on a single endpoint and, alternatively, for sharing of information across indications on surrogate relationships. We will also develop methods for making explicit the level of sharing across indications imposed by the methods, ensuring that the appropriateness of the underlying assumptions can be explicitly considered by decision makers and clinical experts. WP3: Additional work to support a policy framework We will perform a simulation study to generalise from the bevacizumab case study to a broader set of multi-indication drugs and support the framework's recommendations and guiding principles relating to when multi-indication analyses may, or may not, be worthwhile. We will also develop methods for the formal elicitation of the judgment of clinical experts to support multi-indication analyses. Finally, we will demonstrate how the fuller use of multi-indication evidence can contribute to HTA decisions, by evaluating the impact on cost-effectiveness of integrating multi-indication evidence synthesis using the bevacizumab case study.