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Schematic representation of the drug development process with timeline, attrition rate, and sample sizes of clinical studies.
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The use of health technology assessment (HTA) to inform policy-making is established in most developed countries. Compared to licensing agencies, HTA agencies have different interests and, therefore, different evidence requirements. Criteria for coverage or reimbursement decisions on pharmaceutical compounds vary; however, it is common to include,...
Citations
... Due to the challenges of managing increasing public health care expenditure, demand for evidence and justification of value are increasingly a requirement across global markets to support government funding and reimbursement decisions or price negotiation about new medicines and health technologies [61,62]. ...
Like most private enterprises, the pharmaceutical industry has deeply rooted environmental, social, and governance (ESG) matters that challenge its long-term sustainability. Overcoming these external challenges requires collaborative and proactive steps as well as procedures guiding the adoption of ESG principles by all internal stakeholders. Environmental challenges such as climate change, and in addition the changes in society, have resulted in the need for governance addressing and coordinating efforts. The core function of medical affairs (MA) is connecting with stakeholders within a company and also between the company and external stakeholders. In this article, we describe the involvement of MA in several aspects of ESG, as a contributor, partner, and implementer. MA has a significant opportunity to emerge as a leading function involved in ESG strategies and their tactical implementation. Although the involvement of MA in the environment pillar of ESG is less, the function can implement changes relating to the conduct of meetings, clinical studies, and the digitalization of medical education via virtual platforms. Due to its patient centricity, MA is tasked to address social determinants of health to improve patients' outcomes. As a linking function within a company and with its external stakeholders, MA can provide proactive input in policy generation and enable effective governance by adherence to standards of accountability, ethics, and compliance, as well as transparency. Championing ESG is a collective responsibility that transcends any single department. It mandates a company-wide commitment. MA represents an essential pivot point in catalyzing the integration of ESG principles within industry, contributing to a healthcare ecosystem that is not merely more sustainable and ethical but also more conducive to patient health and public well-being.
... The fact that in Canada for example, a new intervention whose expected additional cost for the health care system is < 50 000$/QALY is acceptable, i.e., considered cost-effective, expresses the fact that new interventions that lead to an increased cost may be acceptable. In other words, the relevant health policy goal is not simply to head off rising costs, but also to promote healthcare innovations, provided they contribute to an increase in the health of the population [17]. ...
Abstract Screening newborns for genetic and other diseases is one of the most effective ways to improve health and reduce disease in a population. In developed countries, newborn screening has been a cornerstone of public health for decades. In many developing countries, however, newborn screening is still in its infancy. Many countries still lack screening programs. When a program is available, it generally lacks well-defined criteria on which decision-makers can justify the choice of diseases screened for and the methods used. One of the reasons put forward to understand this observation is the fact that little consideration is given by decision-makers to economic evaluations as a pillar of decision-making, as is the case in industrialized countries. This article provides a brief description of the challenges of using economic evaluation of newborn screening in developing countries. This will be illustrated by the example of the national newborn screening program in Vietnam.
... The assessments of medicines at the national level are made by health technology assessment (HTA) bodies, taking into account the costeffectiveness, the therapeutic need, and the added value compared to the local standard of care (van Nooten et al., 2012;Gozzo et al., 2016;Angelis et al., 2018;Gozzo et al., 2021b;Gozzo et al., 2022). This can result in access inequalities among European countries, based on the willingness to pay but also on the recognition of drugs' therapeutic value (Ciani and Jommi, 2014;Akehurst et al., 2017;Allen et al., 2017). ...
In accordance with European regulation, medicines containing a new active substance to treat neurodegenerative diseases as well as autoimmune and other immune dysfunctions must be approved by the European Medicines Agency (EMA) through the centralized procedure before they can be marketed. However, after EMA approval, each country is responsible for national market access, following the assessment performed by health technology assessment (HTA) bodies with regard to the therapeutic value. This study aims to provide a comparative analysis of HTA recommendations issued by three EU countries (France, Germany, and Italy) for new drugs for multiple sclerosis (MS) following EMA approval. In the reference period, we identified 11 medicines authorized in Europe for MS, including relapsing forms of MS (RMS; n = 4), relapsing-remitting MS (RRMS; n = 6), secondary progressive MS (SPMS; n = 1), and the primary progressive form (PPMS; n = 1). We found no agreement on the therapeutic value (in particular, the "added value" compared to the standard of care) of the selected drugs. Most evaluations resulted in the lowest score ("additional benefit not proven/no clinical improvement"), underlining the need for new molecules with better efficacy and safety profiles for MS, especially for some forms and clinical settings.
... HTA bodies take a fundamental role in the risk sharing analysis. Indeed, the majority of nations have established evidence and justifications about the costs of drugs by the use of HTAs as an instrument to inform and lead decisional bodies during and after the price definition [30]. An HTA is a multidisciplinary process able to describe, analyze, and judge health technologies based on clinical, ethical, and economic evaluation in the short and long term. ...
This systematic study aims at analyzing the differences between the approach of the European healthcare systems to the pharmaceutical market and the American one. This paper highlights the opportunities and the limitations given by the application of managed entry agreements (MEAs) in European countries as opposed to the American market, which does not regulate pharmaceutical prices. Data were collected from the Organisation for Economic Co-operation and Development (OECD), the European Medicines Agency, and the national healthcare agencies of US and European countries. A literature review was undertaken in PubMed, Scopus, MEDLINE, and Google for a period ten years (2010–2019). The period 2020–2021 was considered to compare health expenditure before and after the SARS-CoV-2 pandemic. Scarce information from national agencies has been given in terms of MEAs related to the COVID-19 pandemic. The comparison between the United States approach and the European one shows the importance of a market access regulation to reduce the cost of therapies, increasing the efficiency of national healthcare systems and the advantages in terms of quality and accessibility to the final users: patients. Nevertheless, it seems that the golden age of MEAs for Europe was during the examined period. Except for Italy, countries will move to other forms of reimbursements to obtain higher benefits, reducing the costs of an inefficient implementation and outcomes in the medium term.
... It is concerned with the medical, organizational, economic, and societal consequences of implementing technology and interventions in health system. The increasing relevance of HTA has reshaped the way clinical pharmaceuticals are designed and entered market [18]. HTA is being transformed, as part of its development in some countries, beyond the supportive role for macro-level policy making to a management tool for healthcare facilities and providers [19]. ...
Health Technology Assessment (HTA) is an important multidisciplinary process for health policymakers and decision-makers to evaluate a range of health technologies, medical devices, and pharmaceuticals to enable the efficiency with finite healthcare budgets. It aids the effectiveness and fairness in decision making. HTA is a mechanism to introduce a value for money in the healthcare system. HTA methods are evolving, and their applications are diverse. This review introduces fundamental aspects and issues of dynamic concept of HTA.
... It is concerned with the medical, organizational, economic, and societal consequences of implementing technology and interventions in health system. The increasing relevance of HTA has reshaped the way clinical pharmaceuticals are designed and entered market [18]. HTA is being transformed, as part of its development in some countries, beyond the supportive role for macro-level policy making to a management tool for healthcare facilities and providers [19]. ...
... Therefore, even if the benefit risk profile should be positive to obtain the conditional approval, uncertainties associated with these products remain and cannot be solved before launch. Acceleration of drug approval might therefore not always translate into positive and/or equally rapid reimbursement decisions due to residual uncertainties around net clinical benefits and the expected high impact on healthcare system, hindering patient access in some countries (Ciani and Jommi, 2014;Akehurst et al., 2017;Allen et al., 2017;Richardson and Schlander, 2019;Jommi et al., 2020). ...
Health Technology Assessment (HTA) is a multidisciplinary process which supports policy “decision-making”, including those related to drug reimbursement and price negotiation based on comprehensive clinical and non-clinical evaluations. The discrepancies in HTA recommendations among European countries are related to the differences in health care systems and willingness to invest in health care, differences in assessment methodologies and appraisal practices, and variations in economic constraints, and may produce disparities in terms of patient access to medicines. The political discussion about the adoption of the European Regulation on HTA lasted for years due to concerns about its feasibility and its implications for national health care systems In this paper we highlighted the importance to harmonize HTA process in Europe and some critical issues emerged during the discussion among experts in the field carried out at the European Regulatory Conference.
... CEA is a well-established part of health technology assessment (HTA) processes in countries such as the United Kingdom, Australia, and Canada to aid decision-making by national health care systems and is increasing in use worldwide [2][3][4] . While minor variations exist across HTA agencies, CEA is typically conducted using a standard set of methods and assumptions. ...
Objectives
Cost-effectiveness analysis (CEA) is useful to assess the value of health care interventions based on clinical effectiveness and costs. However, standard CEA methods make important assumptions that may significantly increase the incremental cost-effectiveness ratio (ICER) for lifelong treatments for rare, chronic diseases. We used the cost-effectiveness of elexacaftor/tezacaftor/ivacaftor and ivacaftor (ELX/TEZ/IVA) for the treatment of cystic fibrosis as a case study to explore how alternative assumptions for (1) discounting, (2) utility measures, (3) disease management costs, and (4) static drug pricing impact cost-effectiveness outcomes.
Materials and methods
Cost-effectiveness of ELX/TEZ/IVA was evaluated using base-case inputs and assumptions reflecting standard CEA methods and was then compared with cost-effectiveness estimates obtained with alternate assumptions: (1) applying a lower discount rate to health benefits (1.5%) than costs (3%); (2) including a treatment-specific utility increment; (3) excluding disease management costs incurred during the period of extended survival attributable to ELX/TEZ/IVA treatment; and (4) decreasing the price of ELX/TEZ/IVA following loss of exclusivity.
Results
Modifying assumptions for these four factors together reduced the ICER by 75% from the base case, with the largest reduction (45%) occurring when the price trajectory was modified to allow for generic entry. Differential discounting, use of a treatment-specific utility increment, and exclusion of additional disease management costs each individually reduced the ICER by 36%, 14%, and 10%, respectively, from the base case.
Conclusions
This study illustrates the impact that modifications to standard CEA methods may have on measures of cost-effectiveness for rare, chronic diseases.
... Therefore, it may happen that the evidence they plan to generate does not align with the evidence required by payers and HTA bodies. To reduce existing misalignments in what evidence should be generated, early dialogs (EDs) between manufacturers and payers have been increasingly encouraged and used for pharmaceuticals (Ciani & Jommi, 2014;Tafuri et al., 2018). For MDs, their use is still relatively limited, but previous research has shown an interest in this policy tool from all parties involved in evidence generation (Blankart et al., 2021;Schnell-Inderst et al., 2015). ...
Payers and manufacturers can disagree on the appropriate level of evidence that is required for new medical devices, resulting in high societal costs due to decisions taken with sub‐optimal information. A cost‐effectiveness model of a hypothetical total artificial heart was built using data from the literature and the (simulated) results of a pivotal study. The expected value of perfect information (EVPI) was calculated from both the payer and manufacturer perspectives, using net monetary benefit and the company's return on investment respectively. A function was also defined, linking effectiveness to market shares. Additional constraints such as a minimum clinical difference or maximum budget impact were introduced into the company's decisions to simulate additional barriers to adoption. The difference in the EVPI between manufacturers and payers varied greatly depending on the underlying decision rules and constraints. The manufacturer's EVPI depends on the probability of being reimbursed, the uncertainty on the (cost‐)effectiveness of the technology, as well as other parameters relating to initial investments, operating costs and market dynamics. The use of Value of information for both perspectives can outline potential misalignments and can be particularly useful to inform early dialogs between manufacturers and payers, or negotiations on conditional reimbursement schemes.
... Despite the successful unification of the European procedures for drug approval, each country is responsible for national market access and pricing and reimbursement agreements, in line with national health needs and resources. This can result in access inequalities among European countries, due to differences not only in terms of willingness to pay but also in the recognition of drug therapeutic value (Ciani and Jommi, 2014;Gozzo et al., 2016;Akehurst et al., 2017;Allen et al., 2017). Indeed, in recent years, MA requests are submitted at earlier stages of development, especially for high-unmet medical need and/or rare diseases, before conclusive data are available, thus potentially leading to reduced quality of evidence and to uncertainty in terms of therapeutic value (Akehurst et al., 2017;Richardson and Schlander, 2019;Jommi et al., 2020;Brancati et al., 2021a;Brancati et al., 2021b). ...
Even for products centrally approved, each European country is responsible for national market access after European Medicines Agency (EMA) approval. This step can result in inequalities in terms of access, due to different opinions about the therapeutic value assessed by Health Technology Assessment (HTA) bodies. This study aims to provide a comparative analysis of HTA recommendations issued by EU countries (France, Germany, and Italy) for new neurological drugs following EMA approval. In the reference period, we identified 11 innovative medicines authorized in Europe for five neurological diseases (cerebral adrenoleukodystrophy, spinal muscular atrophy, metachromatic leukodystrophy, migraine, and polyneuropathy in patients with hereditary transthyretin amyloidosis), including eight drugs for genetic rare diseases. We found no agreement on the therapeutic value (in particular the “added value” compared to the standard of care) of the selected drugs. Despite the differences in terms of assessment, the access has been usually guaranteed even if with various types of limitations. The heterogeneity of the HTA assessment of clinical data among countries is probably related to the uncertainties about clinical value at the time of EMA approval and the lack of long-term data and of direct comparison with available alternatives. Given the importance of new medicines especially for rare diseases, it is crucial to understand and act on the causes of inconsistency among the HTA assessments, in order to ensure rapid and uniform access to innovation for patients who can benefit.
