Health technology assessment of biosimilars worldwide: a scoping review.
ABSTRACT: BACKGROUND:Health technology assessment (HTA) should provide an assessment of a technology's effects on health and of the related social, economic, organisational and ethical issues. HTA reports on biosimilars can specifically assess their immunogenicity, their extrapolation to one or more conditions, and the risks of interchangeability and substitution. We aimed to complete a scoping review within the context of HTA organisations to synthesise HTA reports on biosimilars and to map the extension, scope and methodological practices. MAIN BODY:A scoping review methodology was applied. The sources for biosimilars HTA reports were database searches and grey literature from HTA organisation websites up to June 2019. HTA reports of biosimilars were classified as full HTA, mini-HTA or rapid reviews. Data were extracted and recorded on a calibrated predefined data form. We identified 70 HTA reports of biosimilars of 16 biologic products (65.71% in 2015-2018) produced by 13 HTA organisations from 10 countries; 2 full HTAs, 4 mini-HTAs and 64 rapid reviews met the inclusion criteria. Almost all the rapid reviews gave no information regarding any evidence synthesis method and approximately half of the rapid reviews did not appraise the risk of bias of primary studies or the overall quality of evidence. All full-HTAs and mini-HTAs addressed organisational, ethical, social and legal considerations, while these factors were assessed in less than half of the rapid reviews. The immunogenicity and extrapolation of one or more conditions were often considered. The majority of full-HTAs and mini-HTAs contained an assessment of switching and a discussion of an educational approach about biosimilars. No HTA report rejected the adoption/reimbursement of the biosimilar assessed. CONCLUSION:HTA of biosimilars are emerging in the context of HTA organisations and those that exist often duplicate reports of the same biosimilar. Most HTA reports of biosimilars do not conduct a systematic literature review or consider economic issues. No report has rejected the adoption/reimbursement of biosimilars. There is a need to standardise the minimum criteria for the development of HTA on biosimilars to ensure a better understanding and better decision-making.
Project description:<h4>Objectives</h4>The aim of this study was to conduct a review of health technology assessments (HTAs) in cervical cancer screening to highlight the most common metrics HTA agencies use to evaluate and recommend cervical cancer screening technologies.<h4>Methods</h4>The Center for Reviews and Dissemination (CRD), MedLine, and national HTA agency databases were searched using keywords ("cervical cancer screening" OR "cervical cancer" OR "cervical screening") and "HTA" from January 2000 to October 2014. Non-English language reports without English summaries, non-HTA reports, HTAs unrelated to a screening intervention and HTAs without sufficient summaries available online were excluded. We used various National Institute for Health and Care Excellence (NICE) methods to extract key assessment criteria and to determine whether a change in screening practice was recommended.<h4>Results</h4>One hundred and ten unique HTA reports were identified; forty-four HTAs from seventeen countries met inclusion criteria. All reports evaluated technologies for use among women. Ten cervical screening technologies were identified either as an intervention or a comparator. The most common outcome metric evaluated was diagnostic accuracy, followed by economic effectiveness. Additional outcome metrics such as the use of adjunct testing, screening intervals, and age-specific testing were commonly evaluated. Nearly one-third (fifteen of forty-four) of HTAs recommended a change in practice.<h4>Conclusions</h4>This review highlights popular metrics used in HTAs for cervical cancer screening. Clinical and economic effectiveness metrics have been consistently assessed in HTAs, while the use of adjunct testing, screening intervals, and age-specific screening became increasingly prevalent from after 2007. Moreover, we observed an increase in optimized recommendations after 2007.
Project description:BACKGROUND:Conducting a health technology assessment (HTA) of public health interventions (PHIs) poses some challenges. PHIs are often complex interventions, which affect the number and degree of interactions of the aspects to be assessed. Randomized controlled trials on PHIs are rare as they are difficult to conduct because of ethical or feasibility issues. The aim of this study is to provide an overview of the methodological characteristics and to compare the applied assessment methods in HTAs on PHIs. METHODS:We will systematically search HTA agencies for HTAs on PHIs published between 2012 and 2016. We will identify the HTAs by screening the webpages of members of international HTA organizations. One reviewer will screen the list of HTAs on the webpages of members of international HTA organization, and a second review will double-check the excluded records. For this methodological review, we define a PHI as a population-based intervention on health promotion or for primary prevention of chronic or non-chronic diseases. Only full HTA reports will be included. At maximum, we will include a sample of 100 HTAs. In the case that we identify more than 100 relevant HTAs, we will perform a random selection. We will extract data on effectiveness, safety and economic as well as on social, cultural, ethical and legal aspects in a priori piloted standardized tables. We will not assess the risk of bias as we focus on exploring methodological features. Data extraction will be performed by one reviewer and verified by a second. We will synthesize data using tables and in a structured narrative way. DISCUSSION:Our analysis will provide a comprehensive and current overview of methods applied in HTAs on PHIs. We will discuss approaches that may be promising to overcome the challenges of evaluating PHIs.
Project description:<h4>Background</h4>Following approximately 10 years from the beginning of Iran's national Health Technology Assessment (HTA) programme, the present study aims to evaluate its success by examining the impact of HTA and identifying the determinant factors leading to the implementation of HTA report results.<h4>Methods</h4>The triangulation method was employed herein. HTA reports were initially identified and their impact and determinant factors were then examined from the perspectives of both researchers (by preparing a questionnaire according to the Payback model and sending it to HTA principle investigators) and stakeholders (semi-structured interviews held with each HTA stakeholder). Simultaneously, the quality of the HTA reports was examined with relevant critical appraisal checklists.<h4>Results</h4>The impact of 19 equipment technologies and four pharmaceutical technologies were assessed in this study. Twenty researchers replied (response rate, 86.96%) to the questionnaire on the impact of HTA reports from the researcher's perspective. To assess the impact of HTA reports from the stakeholder's perspective, seven policy-makers were chosen and interviewed as the main target audience. The most common step taken to disseminate the results of the HTA projects was publication. Conducting the HTA had taught researchers and their colleagues' new skills and had facilitated the securing of research grants from other organisations. Most reports had used the systematic review method but the relevant details had been scarcely presented regarding outcomes, costs and analysis. The greatest impact of HTA reports on decision-making had been on policy-makers providing and allocating finances. Barriers in stewardship, identification and prioritisation of topics, performance and dissemination of HTA results were the main barriers of implementing HTAs.<h4>Conclusions</h4>In most aspects, the status of HTA impact reports need improvement. Thus far, the barriers and facilitators of the HTA programme in Iran have been investigated in other studies. These findings should be pooled to reach a solution that can be actively applied to the health system to improve the status quo of HTA in Iran.
Project description:Diagnostic tests play an important role in the clinical decision-making process by providing information that enables patients to be identified and stratified to the most appropriate treatment and management strategies. Decision analytic modelling facilitates the synthesis of evidence from multiple sources to evaluate the cost effectiveness of diagnostic tests. This study critically reviews the methods used to model the cost effectiveness of diagnostic tests in UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) reports. UK NIHR HTA reports published between 2009 and 2018 were screened to identify those reporting an economic evaluation of a diagnostic test using decision analytic modelling. Existing decision modelling checklists were identified in the literature and a modified checklist tailored to diagnostic economic evaluations was developed, piloted and used to assess the diagnostic models in HTA reports. Of 728 HTA reports published during the study period, 55 met the inclusion criteria. The majority of models performed well with a clearly defined decision problem and analytical perspective (89% of HTAs met the criterion). The model structure usually reflected the care pathway and progression of the health condition. However, there are areas requiring improvement. These are predominantly systematic identification of treatment effects (20% met), poor selection of comparators (50% met) and assumed independence of tests used in sequence (32% took correlation between sequential tests into consideration). The complexity and constraints of performing decision analysis of diagnostic tests on costs and health outcomes makes it particularly challenging and, as a result, quality issues remain. This review provides a comprehensive assessment of modelling in HTA reports, highlights problems and gives recommendations for future diagnostic modelling practice.
Project description:Since the first biosimilar medicine, Omnitrope<sup>®</sup> (active substance somatropin) was approved in 2006, 53 biosimilars have been authorized in Spain. We estimate the budget impact of biosimilars in Spain from the perspective of the National Health System (NHS) over the period between 2009 and 2019. Drug acquisition costs considering commercial discounts at public procurement procedures (hospital tenders) and uptake data for both originator and biosimilar as actual units consumed by the NHS were the two variables considered. Two scenarios were compared: a scenario where no biosimilars are available and the biosimilar scenario where biosimilars are effectively marketed. All molecules exposed to biosimilar competition during this period were included in the analysis. The robustness of the model was tested by conducting multiple sensitivity analyses. From the payer perspective, it is estimated that the savings produced by the adoption of biosimilars would reach EUR 2306 million over 11 years corresponding to the cumulative savings from all biosimilars. Three molecules (infliximab, somatropin and epoetin) account for 60% of the savings. This study provides the first estimation of the financial impact of biosimilars in Spain, considering both the effect of discounts that manufacturers give to hospitals and the growing market share of biosimilars. We estimate that in our last year of data, 2019, the savings derived from the use of biosimilars relative total pharmaceutical spending in Spain is 3.92%. Although more research is needed, our evidence supports the case that biosimilars represent a great opportunity to the sustainability of the NHS through rationalizing pharmaceutical spending and that the full potential of biosimilar-savings has not been achieved yet, as there is a high variability in biosimilar uptake across autonomous regions.
Project description:Biosimilars are protein products that are sufficiently similar to a biopharmaceutical already approved by a regulatory agency. Several biotechnology companies and generic drug manufacturers in Asia and Europe are developing biosimilars of tumor necrosis factor inhibitors and rituximab. A biosimilar etanercept is already being marketed in Colombia and China. In the US, several natural source products and recombinant proteins have been approved as generic drugs under Section 505(b)(2) of the Food, Drug, and Cosmetic Act. However, because the complexity of large biopharmaceuticals makes it difficult to demonstrate that a biosimilar is structurally identical to an already approved biopharmaceutical, this Act does not apply to biosimilars of large biopharmaceuticals. Section 7002 of the Patient Protection and Affordable Care Act of 2010, which is referred to as the Biologics Price Competition and Innovation Act of 2009, amends Section 351 of the Public Health Service Act to create an abbreviated pathway that permits a biosimilar to be evaluated by comparing it with only a single reference biological product. This paper reviews the processes for approval of biosimilars in the US and the European Union and highlights recent changes in federal regulations governing the approval of biosimilars in the US.
Project description:INTRODUCTION:Numerous factors contribute to uncertainty in test measurement procedures, and this uncertainty can have a significant impact on the downstream clinical utility and cost-effectiveness of testing strategies. Currently, however, there is no clear guidance concerning if or how such factors should be considered within Health Technology Assessments (HTAs) of tests. OBJECTIVE:The aim was to provide an introduction to key concepts in measurement uncertainty for the HTA community and to explore, via systematic review, current methods utilised within HTAs. METHODS:HTAs of in vitro tests including a model-based economic evaluation were identified via the Centre for Reviews and Dissemination (CRD) HTA database and key reimbursement authority websites. Data were extracted to explore the specific components of measurement uncertainty assessed and methods utilised. The findings were narratively synthesised. RESULTS:Of 107 identified HTAs, 20 (19%) attempted to assess components of measurement uncertainty: 15 did so via some form of pre-model assessment (such as a literature review or laboratory survey); four also included components within the economic model; and one considered measurement uncertainty within the model only. One study quantified the impact of measurement uncertainty on cost-effectiveness and found that this parameter significantly changed the results, but did not impact the overall decision uncertainty. CONCLUSION:A minority of HTAs identified from this review used various approaches to assess and/or incorporate the impact of measurement uncertainty, indicating that these assessments are feasible. Uncertainty remains around best practice methodology for conducting such analyses; further research is required to ensure that future HTAs are fit for purpose.
Project description:<h4>Objectives</h4>Model for ASsessment of Telemedicine Applications (MAST) is a health technology assessment (HTA) inspired framework for assessing the effectiveness and contribution to quality of telemedicine applications based on rigorous, scientific data. This study reports from a study of how it was used and perceived in twenty-one pilots of the European project RENEWING HEALTH (RH). The objectives of RH were to implement large-scale, real-life test beds for the validation and subsequent evaluation of innovative patient-centered telemedicine services. The study is a contribution to the appraisal of HTA methods.<h4>Methods</h4>A questionnaire was administered for project leaders of the pilots. It included questions about use and usefulness of MAST for (i) preceding considerations, (ii) evaluation of outcomes within seven domains, and (iii) considerations of transferability. Free text spaces allowed for proposals of improvement. The responses covered all pilots. A quantitative summary of use and a qualitative analysis of usefulness were performed.<h4>Results</h4>MAST was used and considered useful for pilot evaluations. Challenges included problems to scientifically determine alternative service options and outcome within the seven domains. Proposals for improvement included process studies and adding domains of technological usability, responsible innovation, health literacy, behavior change, caregiver perspectives and motivational issues of professionals.<h4>Conclusions</h4>MAST was used according to its structure. Its usefulness in patient centered pilots can be improved by adding new stakeholder groups. Interdependencies between scientific rigor, resources and timeliness should be addressed. Operational options for improvements include process studies, literature reviews and sequential mini-HTAs for identification of areas for more elaborate investigations.
Project description:<h4>Background</h4>Biosimilars have been used for 15 years in the European Union (EU), and have been shown to reduce costs and increase access to important biological medicines. In spite of their considerable exposure and excellent safety record, many prescribers still have doubts on the safety and interchangeability of biosimilars, especially monoclonal antibodies (mAbs) and fusion proteins.<h4>Objectives</h4>The aim of this study was to analyse the short- and long-term safety and interchangeability data of biosimilar mAbs and fusion proteins to provide unbiased information to prescribers and policy makers.<h4>Methods</h4>Data on the safety, immunogenicity and interchangeability of EU-licensed mAbs and fusion proteins were examined using European Public Assessment Reports (EPARs) and postmarketing safety surveillance reports from the European Medicines Agency (EMA). As recent biosimilar approvals allow self-administration by patients by the subcutaneous route, the administration devices were also analyzed.<h4>Results</h4>Prelicensing data of EPARs (six different biosimilar adalimumabs, three infliximabs, three etanercepts, three rituximabs, two bevacizumabs, and six trastuzumabs) revealed that the frequency of fatal treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation of treatment, serious adverse events (SAEs), and main immune-mediated adverse events (AEs) were comparable between the biosimilars and their reference products. The availability of new biosimilar presentations and administration devices may add to patient choice and be an emerging factor in the decision to switch patients. Analysis of postmarketing surveillance data covering up to 7 years of follow-up did not reveal any biosimilar-specific adverse effects. No product was withdrawn for safety reasons. This is in spite of considerable exposure to biosimilars in treatment-naïve patients and in patients switched from the reference medicinal product to the biosimilar. Analysis of data from switching studies provided in regulatory submissions showed that single or multiple switches between the originator and its biosimilar versions had no negative impact on efficacy, safety or immunogenicity.<h4>Conclusions</h4>In line with previous reports of prelicensing studies of biosimilar mAbs and etanercepts, this study demonstrated comparable efficacy, safety, and immunogenicity compared with the reference products. This is the first study to comprehensively analyze postmarketing surveillance data of the biosimilar mAbs and etanercept. An analysis of more than 1 million patient-treatment years of safety data raised no safety concerns. Based on these data, we argue that biosimilars approved in the EU are highly similar to and interchangeable with their reference products. Thus, additional systematic switch studies are not required to support the switching of patients.
Project description:<h4>Introduction</h4>The introduction of disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS) over the last two decades has prompted the economic assessments of these treatments by reimbursement authorities. The aim of this systematic literature review was to evaluate the modeling approach and data sources used in economic evaluations of DMTs for RMS, identify differences and similarities, and explore how economic evaluation models have evolved over time.<h4>Methods</h4>MEDLINE®, Embase®, and EBM Reviews databases were searched using Ovid® Platform from database inception on 25 December 2019 and subsequently updated on 17 February 2021. In addition, health technology assessment agency websites, key conference proceedings, and gray literature from relevant websites were screened. The quality of included studies was assessed using the Drummond and Philips checklists.<h4>Results</h4>A total 155 publications and 30 Health Technology Assessment (HTA) reports were included. Most of these were cost-utility analysis (73 studies and 25 HTA reports) and funded by medicines manufacturers (n = 65). The top three countries where studies were conducted were the USA (n = 29), the UK (n = 16), and Spain (n = 10). Studies predominantly used Markov cohort models (94 studies; 25 HTAs) structured based on the Expanded Disability Status Scale (EDSS) with 21 health states (20 studies; 12 HTA reports). The London Ontario and British Columbia data sets were commonly used sources for natural history data (n = 33; n = 13). Twelve studies and ten HTAs from the UK assumed a waning of DMT effect over the long term, while this was uncommon in studies from other countries. Nineteen studies adjusted for multiple sclerosis (MS)-specific mortality estimates, while 18 studies used data from the national life table without adjustment. Studies prominently referred to mortality data that were about two decades old. The data on treatment effect was generally obtained from randomized controlled trials (43 studies; 7 HTAs) or from published evidence synthesis (23 studies; 24 HTAs). Utility estimates were derived from either published studies and/or supplemented with data from RCTs. Most of the models used the lifetime horizon (n = 37) with a 1-year cycle length (n = 63).<h4>Conclusion</h4>As expected, similarities as well as differences were observed across the different economic models. Available evidence suggests models should continue using the Markov cohort model with 21 EDSS-based states, however, allowing the transition to a lower EDSS state and assuming a sustained treatment effect. With reference to the data sources, models should consider using a contemporary MS-specific mortality data, recent natural history data, and country-specific utility data if available. In case of data unavailability, a sensitivity analysis using multiple sources of data should be conducted. In addition, future models should incorporate other clinically relevant outcomes, such as the cognition, vision, and psychological aspects of RMS, to be able to present the comprehensive value of DMTs.