The impact of quality-of-life data in relative effectiveness assessments of new anti-cancer drugs in European countries.

PURPOSE: The aim of this study is to investigate the role of health-related quality-of-life (QoL) data in relative effectiveness assessments (REAs) of new anti-cancer drugs across European jurisdictions, during health technology assessment procedures. METHODS: Comparative analysis of guidelines and publicly available REAs in six European jurisdictions of anti-cancer drugs approved by EMA between 2011 and 2013. RESULTS: Fourteen anti-cancer drugs were included, adding up to 79 REAs. Whilst all guidelines state that QoL is a relevant endpoint to determine the relative effectiveness of new cancer drugs, QoL data were included in only 54% of the 79 reports and their impact on the recommendations was limited. CONCLUSIONS: Whilst national guidelines recognize the relevance of QoL to determine the relative effectiveness of new anti-cancer drugs, this is not well-reflected in current assessments. Developing and implementing into REAs specific evidence requirements for QoL data would improve the use of this patient-centred outcome in future reimbursement and pricing decisions.

[HTA goes Europe: European collaboration on joint assessment and methodological issues becomes reality]. / HTA goes Europe: Europäische Zusammenarbeit in gemeinsamen Nutzenbewertungen und methodischen Fragen wird real.

INTRODUCTION: The standardisation of European HTA and thus the reduction of redundancies require clearly defined processes and methods. The HTA Core Model®, a tool developed by the European Network EUnetHTA, is intended to ensure the transparent production of standardised and high-quality assessments in international collaboration. METHODS: The present paper describes the experience with already published EUnetHTA assessments as well as possibilities for national/local adaptations of these assessments. The integration of jointly developed methods in routine processes of individual HTA agencies will be explained on the basis of a selected example. Further methodological initiatives in Europe will be presented. RESULTS: So far, EUnetHTA has published four rapid assessments conducted through European cooperation between 6-9 HTA institutes during Joint Action 2 (2012-2015). Two assessments dealt with pharmaceuticals and two with non-pharmaceutical interventions. The overall duration of these assessments ranged from 7 to 9 months. There is initial information about the frequency and manner in which these assessments have been used for national/local HTA reports. According to a survey, a total of 28 HTA institutes have indicated that they want to make use of these assessments in their own context. In Austria, the Ludwig Boltzmann Institute for Health Technology Assessment (LBI-HTA) has produced two reports based on EUnetHTA assessments. A further step towards cross-border collaboration and harmonisation is the implementation of these tools in a national and regional context. Beginning in 2015 the LBI-HTA will adjust two programme lines to the format of the HTA Core Model® in order to increase the transferability of HTAs and to reduce redundancies. DISCUSSION: Barriers to European collaboration include the relevance of topics for individual HTA institutes and the timing of joint assessments. Implementing commonly developed methods as standard practice in local/national HTA institutes is mainly impeded by legislative requirements. CONCLUSION: Despite the initial positive experiences with international collaboration on specific topics and methods, the coming years will have to prove whether existing barriers can be overcome effectively.

Can a Joint Assessment Provide Relevant Information for National/Local Relative Effectiveness Assessments? An In-Depth Comparison of Pazopanib Assessments.

BACKGROUND: In many European jurisdictions, relative effectiveness assessments (REAs) of pharmaceuticals are performed during the reimbursement decision-making process. International collaboration in the production of these assessments may prevent the duplication of information in various jurisdictions. A first pilot of a joint REA (pazopanib for the treatment of renal cell carcinoma) was published in 2011. OBJECTIVE: The objective was to investigate how well the methods used in the joint REA match the methods used in the national/local assessments on the same topic. METHODS: National/local assessments from European jurisdictions, available in English language, were identified through a literature search and an e-mail request to health technology assessment organizations. Data were abstracted from joint and national/local assessments using a structured data abstraction form. Results were compared for differences and similarities. RESULTS: In total, five national/local reports were included (Belgium, England/Wales, France, The Netherlands, and Scotland). The general methods (indication, main comparator, main end points, main trial) were similar. The details of the assessment (e.g., exact wording of indication, additional comparators, additional trials included, and method of indirect comparison), however, varied. Despite these differences, the joint REA included nearly all comparators, end points, trials, and methods of analysis that were used in national/local REA reports. CONCLUSIONS: This study has shown overlap in the methods national/local REA bodies in Europe have chosen for a pazopanib REA for renal cell carcinoma, except for the use and methods of indirect comparisons. Although some additional comparators and outcomes differed between national/local REAs, they can be captured in a comprehensive joint REA.

Which factors may determine the necessary and feasible type of effectiveness evidence? A mixed methods approach to develop an instrument to help coverage decision-makers.

OBJECTIVES: Reimbursement decisions require evidence of effectiveness and, in general, a blinded randomised controlled trial (RCT) is the preferred study design to provide it. However, there are situations where a cohort study, or even patient series, can be deemed acceptable. The aim of this study was to develop an instrument that first examines which study characteristics of a blinded RCT are necessary, and then, if particular characteristics are considered necessary, examines whether these characteristics are feasible. DESIGN: We retrospectively studied 22 interventions from 20 reimbursement reports concerning medical specialist care made by the Dutch National Health Care Institute (ZIN) to identify any factors that influenced the necessity and feasibility of blinded RCTs, and their constituent study characteristics, that is, blinding, randomisation and a control group. A literature review was performed to identify additional factors. Additional expertise was included by interviewing eight experts in epidemiology, medicine and ethics. The resulting instrument was called the FIT instrument (Feasible Information Trajectory), and was prospectively validated using three consecutive reimbursement reports. RESULTS: (Blinded) RCT evidence was lacking in 5 of 11 positive reimbursement decisions and 3 of 11 negative decisions. In the reimbursement reports, we found no empirical evidence supporting situations where a blinded RCT is unnecessary. The literature also revealed few arguments against the necessity of a blinded RCT. In contrast, many factors influencing the feasibility of randomisation, a control group and blinding, were found in the reimbursement reports and the literature; for example, when a patient population is too small or when an intervention is common practice, randomisation will be hindered. CONCLUSIONS: Policy regarding the necessity and feasibility of different types of evidence of effectiveness would benefit from systematic guidance. The FIT instrument has the potential to support transparent, reproducible and well-founded decisions on appropriate evidence of effectiveness in medical specialist care.

European collaboration on relative effectiveness assessments: What is needed to be successful?

OBJECTIVE: The objective of this study is to identify the possible barriers and critical success factors for the implementation of European collaboration in the field of relative effectiveness assessment (REA) of drugs. METHODS: Data were gathered through semi-structured interviews with representatives from eight European health technology assessment (HTA) organisations involved in assessment of drugs for coverage decision-making (AAZ, AIFA, AHTAPol, HAS, HVB, IQWIG, NICE and ZiN). RESULTS: Potential barriers identified mainly relate to methodology, resources and challenges with implementation in the respective national processes (e.g. legal restrictions). The most critical success factors for production of cross-border assessments were the continuous cooperation of competent partners, and the quality and timely availability of the assessment. CONCLUSION: Further adaptation of the process and methods is required for optimal collaboration. In the near future it can be expected that cross-border assessments will meet in particular the needs of smaller/middle-sized European countries and also European countries with less developed HTA systems as the potential efficiency/quality gains are the highest for these countries. Therefore, national implementation of cross-border assessments is especially likely in these countries in the coming years. Once more experience is gained with cross-border assessments, and successes become more evident, efficiency/quality gains may also be likely for some larger countries with well established processes.

Developing the HTA core model for the online environment.

BACKGROUND: A framework for collaborative production and sharing of HTA information, the HTA Core Model, was originally developed within EUnetHTA in 2006-08. In this paper, we describe the further development of the Model to allow implementation and utilization of the Model online. The aim was to capture a generic HTA process that would allow effective use of the HTA Core Model and resulting HTA information while at the same time not interfering with HTA agencies' internal processes. METHODS: The work was coordinated by a development team in Finland, supported by an international expert group. Two pilot testing rounds were organized among EUnetHTA agencies and two extensive core HTA projects tested the tool in a real setting. The final work was also formally validated by a group of HTA agencies. RESULTS: The HTA Core Model Online--available at http://www.corehta.info--is a web site hosting a) a tool to allow electronic utilization of the HTA Core Model and b) a database of produced HTA information. While access to the HTA information is free to all, the production features are currently available to EUnetHTA member agencies only. A policy was crafted to steer the use of the Model and produced information. CONCLUSIONS: We have successfully enabled electronic use of the HTA Core Model and agreed on a policy for its utilization. The system is already being used in subsequent HTA projects within EUnetHTA Joint Action 2. Identified shortcomings and further needs will be addressed in subsequent development.

Standardized reporting for rapid relative effectiveness assessments of pharmaceuticals.

OBJECTIVES: Many European countries perform rapid assessments of the relative effectiveness (RE) of pharmaceuticals as part of the reimbursement decision making process. Increased sharing of information on RE across countries may save costs and reduce duplication of work. The objective of this article is to describe the development of a tool for rapid assessment of RE of new pharmaceuticals that enter the market, the HTA Core Model® for Rapid Relative Effectiveness Assessment (REA) of Pharmaceuticals. METHODS: Eighteen member organisations of the European Network of Health Technology Assessment (EUnetHTA) participated in the development of the model. Different versions of the model were developed and piloted in this collaboration and adjusted accordingly based on feedback on the content and feasibility of the model. RESULTS: The final model deviates from the traditional HTA Core Model® used for assessing other types of technologies. This is due to the limited scope (strong focus on RE), the timing of the assessment (just after market authorisation), and strict timelines (e.g. 90 days) required for performing the assessment. The number of domains and assessment elements was limited and it was decided that the primary information sources should preferably be a submission file provided by the marketing authorisation holder and the European Public Assessment Report. CONCLUSIONS: The HTA Core Model® for Rapid REA (version 3.0) was developed to produce standardised transparent RE information of pharmaceuticals. Further piloting can provide input for possible improvements, such as further refining the assessment elements and new methodological guidance on relevant areas.

Piloting international production of rapid relative effectiveness assessments of pharmaceuticals.

BACKGROUND: This article describes the lessons learned from an international pilot assessment using the first version of the HTA Core Model® and Guidelines for rapid Relative Effectiveness Assessment (REA) of pharmaceuticals based on input from three different perspectives: the assessors, the users (health technology assessment organisations) and the marketing authorisation holder. METHODS: A pilot assessment was performed of pazopanib for the treatment of advanced or metastatic renal cell carcinoma for which 54 individuals from 22 EUnetHTA member organisations from 16 European countries gave their contribution. The work was divided in eight domain teams. Subsequently, results of these domain teams were synthesised in one pilot report. Feedback on the outcomes of the pilot was gathered throughout the project and through structured surveys. RESULTS: The first version of the assessment was produced in six months and consisted of 55 question and answer pairs, 8 domain reports and a synthesis section that combined the results from the different domains. The organisation of the pilot required intense coordination. Main points of criticism on the assessment were the lengthiness of the document and overlap of information throughout the assessment. CONCLUSIONS: A reduction in the number of authoring organisations and individuals participating is necessary to avoid information overlap and increase efficiency in undertaking the assessment. Involving several organisations (e.g. five) in an in-depth review could still ensure the benefit of broad participation from various countries. The focus of a rapid REA should be on the first four domains of the Model.

Comparing the hta core model with a national health technology assessment report.

OBJECTIVES: The HTA Core Model is a framework for producing health technology assessments (HTAs) in a structured format. The Model splits the content of a HTA into assessment elements. The objective is to explore the adaptability of these assessment elements in national report production in a pilot case study comparing a national HTA report and the HTA Core Model. METHODS: An on-going Dutch HTA report on endovascular repair of abdominal aortic aneurysm (EVAR) was chosen as a typical representative of a national report on medical interventions. The author of the EVAR report assessed the relevance and comprehensiveness of the assessment elements of the HTA Core Model for her work. Another researcher annotated the Core Model specific content in the EVAR report. Matching and missing content, as well as the distribution of information in the EVAR report were tabulated and analysed in joint deliberations. RESULTS: Forty percent of the assessment elements of the Core Model were considered relevant for the EVAR report. Some issues relevant for EVAR but missing from the Core Model were identified: they were about re-interventions, secondary prevention, subpopulations that benefit most, and the length of the hospital stay. The distribution of information differed substantially between the Code Model and the national report. CONCLUSIONS: The assessment elements of the HTA Core Model covered most relevant questions of the national report. In order to facilitate easy adaptation of information, the distribution of information should be more consistent in the national report and the Core model.

['Fitting' evidence preferable when evaluating effectiveness of interventions]. / Passend bewijs bij het bepalen van effectiviteit van interventies.

The Dutch Health Care Insurance Board (CVZ) and the Institute for Medical Technology Assessment have developed a questionnaire to help assessors to formulate an answer to the question of which evidence fits best when evaluating the effectiveness of interventions by medical specialists. The Feasible Information Trajectory (FIT) questionnaire is based on the idea that the clinical setting defines the attainable study characteristics and thus possibly available evidence. The FIT questionnaire focuses on study characteristics (randomization, blinding and control groups) and not on study type (e.g. RCT, cohort) as is common within evidence-hierarchy grading systems. Together these attainable characteristics define the most -fitting evidence. The questionnaire should be filled in prior to the literature assessment. Subsequently the most-fitting evidence profile can be modified on the basis of a literature assessment and possibly arguments put forward by healthcare professionals. Filling out the FIT questionnaire is therefore not a static exercise but is part of the search for all relevant arguments in the assessment of effectiveness.

Relative effectiveness assessment of pharmaceuticals: similarities and differences in 29 jurisdictions.

OBJECTIVE: Assessment of the effectiveness compared with alternative treatment(s) plays an important role in many jurisdictions in determining the reimbursement status of pharmaceuticals. This type of assessment is often referred to as a relative effectiveness assessment (REA) and is carried out by many jurisdictions. Increased sharing of information across jurisdictions may save costs and reduce duplication. The objective of this study was to explore the main similarities and differences in the major methodological aspects of REA in multiple jurisdictions. METHODS: Data were gathered with a standardized data extraction form by searching publicly available information and by eliciting information from representatives at relevant organizations. RESULTS: Of the initially included 35 jurisdictions, data were gathered for 29 jurisdictions. There seem to be substantial similarities on the choice of the comparator, the role of indirect comparisons, and preferred end points in REAs (except for the use of health state utilities). Jurisdictions, however, differ in whether effectiveness (usual circumstances of health care practice) is estimated in case no (comparative) effectiveness data are available and how this is done. CONCLUSION: Some important methodological aspects for REA are approached in a similar way in many jurisdictions, indicating that collaboration on assessments may be feasible. Enhanced collaboration in the development of methods and best practices for REA between jurisdictions will be a necessary first step. Important topics for developing best practice are indirect comparisons and how to handle the gap between efficacy and effectiveness data in case good quality comparative effectiveness data are not yet available at the time of reimbursement decisions.