GM-005 Orphan drugs’ pharmacoeconomic data and the impact on a county hospital’s budget

L’articolo ha l’obiettivo di mettere in luce potenzialità e criticità dell’inclusione della prospettiva dei pazienti nella ricerca sulle malattie rare e sui farmaci orfani. A tal fine, nella prima parte, si propone un’analisi epistemologica dell’utilizzo dei racconti dell’esperienza individuale della malattia nella ricerca scientifica e nei trial clinici, facendo emergere, anche attraverso gli strumenti della medicina narrativa, le sfide teoriche e operative poste dall’inclusione della soggettività del paziente e del vissuto di malattia nonché l’importanza della valorizzazione della prospettiva del paziente, sia in generale sia nella ricerca sulle malattie rare e sui farmaci orfani. Nella seconda parte, il testo analizza in particolare il ruolo degli esiti riportati dai pazienti o Patient Reported Outcomes (PROs), misure per la valutazione complessiva della salute basate sulla prospettiva dei pazienti stessi, incentrandosi sulla sperimentazione clinica nel campo delle malattie rare. In questo contesto, infatti, i racconti di malattia, raccolti e valorizzati da fonti istituzionali e associazioni di pazienti, hanno contribuito a far emergere importanti questioni critiche e difficoltà nell’impiego di outcome centrati sul paziente nello sviluppo di nuovi farmaci e trattamenti, generando una serie di documenti e raccomandazioni relative al loro utilizzo per il benessere della comunità dei malati rari. ---------- This paper aims to highlight the potentiality and criticality of including patients’ perspective in rare diseases and orphan drugs research. In the first part, we propose an epistemological analysis of individual narrations of disease experience as they are used in scientific research and clinical trials. With the help of narrative medicine approach, this analysis points out theoretical and operational challenges of a perspective that includes patient’s subjectivity and illness experience. Furthermore, it reveals the significance of patients’ standpoints in general and in rare diseases as well as in the orphan drugs research. The second part of our article focuses on the role of the Patient reported Outcomes (PROs) – which are measures for the health’s overall assessment based on patient’s perspective – by investigating the impact on clinical trials for rare diseases. In this context, illness stories, which are collected and promoted by institutional sources and patients’ associations, contribute to underline important critical issues at stake in the employment of patient-centered outcomes both in new drugs and in the treatments development. Moreover, these stories are crucial to elaborate documents and recommendations concerning the use of PROs for the rare patients’ community welfare.

Download Full-text

SCIENTIFIC AND SOCIAL VALUE JUDGMENTS FOR ORPHAN DRUGS IN HEALTH TECHNOLOGY ASSESSMENT

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462316000416 ◽

2016 ◽

Vol 32 (4) ◽

pp. 218-232 ◽

Cited By ~ 14

Author(s):

Elena Nicod ◽

Panos Kanavos

Keyword(s):

Health Technology Assessment ◽

Technology Assessment ◽

Health Technology ◽

Orphan Drugs ◽

Social Value ◽

European Medicines Agency ◽

Final Decision ◽

Value Judgments ◽

Accountability For Reasonableness ◽

The Impact

Objectives: We explore how broader aspects of a treatment's value and the impact of the condition on patients not captured by routine health technology assessment (HTA) methods using clinical and economic evidence, defined as “other considerations,” may influence HTA processes in different settings.Methods: Countries included were England, Scotland, Sweden, and France. Data sources were the publicly available reports on HTA recommendations. Ten drugs with European Medicines Agency orphan designation and appraised in England were selected. Qualitative thematic analysis was used to systematically identify and code all “other considerations” based on a previously developed methodological framework, which also coded whether it was provided by stakeholders, and how it influenced the decision.Results: A classification framework of scientific and social value judgments was developed and used throughout the study. A total of 125 “other considerations” were identified and grouped into ten subcategories based on the information provided. Eighteen to 100 percent of these, depending on the agency, were put forward as one of the main reasons for the final decision potentially contributing to accepting a higher incremental cost-effectiveness ratio or uncertain evidence. Some of these were nonquantified or nonelicited and pertained to the assessor's judgment. A taxonomy of these value judgments was created to be used in future cases. Results also contributed to better defining the determinants of social value and improving accountability for reasonableness.Conclusions: The systematic identification of the scientific and social value judgments enables to better understanding the dimensions of value, which can be used to improve their transparency and consistent use across decisions and settings.

Download Full-text

Excluding Orphan Drugs from the 340B Drug Discount Program: the Impact on 18 Critical Access Hospitals

INNOVATIONS in pharmacy ◽

10.24926/iip.v3i1.253 ◽

2012 ◽

Vol 3 (1) ◽

Author(s):

Madeline Carpinelli Wallack ◽

Todd Sorensen

Keyword(s):

Federal Government ◽

Orphan Drug ◽

Orphan Drugs ◽

Safety Net ◽

Original Research ◽

Critical Access Hospitals ◽

Patient Protection ◽

High Prevalence ◽

Safety Net Providers ◽

The Impact

Purpose: The 340B Drug Pricing Program is a federal program designed to reduce the amount that safety net providers spend on outpatient drugs. The Patient Protection and Affordable Health Care Act of 2010 extended eligibility for 340B to critical access hospitals (CAHs) for all drugs except those designated as "orphan." Because this policy is unprecedented, this study quantifies the gross financial impact that this exemption has on a group of CAHs. Methods: Drug spending for 2010 from 18 CAHs in Minnesota and Wisconsin are reviewed to identify the prevalence of orphan drug purchases and to calculate the price differentials between the 340B price and the hospitals' current cost. Results: The 18 CAHs' purchases of orphan drugs comprise an average of 44% of the total annual drug budgets, but only 5% of units purchased, thus representing a very high proportion of their expenditures. In the aggregate, the 18 hospitals would have saved $3.1 million ($171,000 average per hospital) had purchases of drugs with orphan designations been made at the 340B price. Because CAH claims for Medicare are reimbursed on a cost-basis, the Federal government is losing an opportunity for savings. Conclusion: The high prevalence of orphan drug use and considerable potential for cost reduction through the 340B program demonstrate the loss of benefit to the hospitals, Federal government and the states. Type: Original Research

Download Full-text

Access to medicines in Turkey: Evaluation of the process of medicines brought from abroad

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462320000872 ◽

2020 ◽

Vol 36 (6) ◽

pp. 585-591

Author(s):

Enver Kağan Atikeler ◽

H.G.M. (Bert) Leufkens ◽

Wim Goettsch

Keyword(s):

Access To Health Care ◽

Pharmaceutical Expenditure ◽

Healthcare Services ◽

Access To Medicines ◽

Orphan Drugs ◽

Security Institution ◽

Pharmaceutical Expenditures ◽

Supply Mechanism ◽

Reimbursement List ◽

The Impact

AbstractObjectiveTurkey's health reforms started in 2003 with providing changes in regulatory, financing, and healthcare services. Access to health care and pharmaceuticals increased rapidly, and this resulted with an increase in public pharmaceutical expenditures. Our study aims to quantify and to evaluate the impact of a specific process within the Turkish system called “Medicines Brought From Abroad" (MBFA).MethodsWe reviewed the general reimbursement legislations of Social Security Institution (SSI), the guideline on MBFA, the SSI reimbursement list, the list of MBFA published by the Ministry of Health to describe the current supply mechanism of medicines and, in particular, the role of MBFA.ResultsTotal costs of the of MBFA medicines over the period 2011–17 went up to more than $520 million, which takes 7.5 percent of total public pharmaceutical expenditure for 2017. Our results showed that MBFA provides access to many orphan drugs and in total, forty-two orphan drugs listed in MBFA accounted for 83 percent of all MBFA budget in the year 2017. Nine of the top ten MBFA medicines were orphan drugs and total costs were $408 million. The highest budget impact was for eculizumab for “paroxysmal nocturnal hemoglobinuria” (PNH), covering 31 percent of total MBFA costs and 2.3 percent of overall drug costs in 2017.ConclusionsTurkey faced significant challenges for creating an access pathway for innovative medicines while continuing the sustainability of the public pharmaceutical budget like many other countries. Therefore, it may be argued that Turkey needs to create an independent health technology assessment organization to provide sustainable access to medicines in the future.

Download Full-text

The impact of early phase price agreements on prices of orphan drugs

BMC Health Services Research ◽

10.1186/s12913-021-06208-7 ◽

2021 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Mark Nuijten ◽

Philippe Van Wilder

Keyword(s):

Drug Price ◽

Early Phase ◽

Cost Of Capital ◽

Orphan Drugs ◽

Phase Iii ◽

Critical Parameters ◽

Valuation Theory ◽

Minimum Price ◽

The Impact ◽

Maximum Threshold

Abstract Background Innovative orphan drugs often have an incremental cost-effectiveness ratio (ICER) which is higher than the maximum threshold for reimbursement. Payers have limited budgets and often cannot pay the full price of a new product, but pharmaceutical and biotechnology companies require a minimum price to satisfy their investors. The objective of this study was to present a possible solution to bridge this pricing gap by having early phase price agreements, which reduce the risk for investors. Methods We used a Pricing Model, which determines the minimum (break-even) price of an innovative drug from an investor’s perspective. This model is based on economic valuation theory, which uses the expected free cash flows and the required cost of capital. We selected two orphan drugs with a positive clinical assessment and an ICER higsher than the Dutch maximum threshold of €80,000 per QALY gained to use as examples in the model: Spinraza for spinal muscular atrophy and Orkambi for cystic fibrosis. RESULTS: The results show that early pricing agreements before phase III trials can substantially lower the drug price resulting from a lower cost of capital. The minimum price for orphan drugs can be reduced by 27.4%, when cost of capital decreases from 12 to 9%. An additional adjustment of other critical parameters due to early pricing agreements (lower probabilities of phase III failure and lower research and development (R&D) costs) can further reduce the minimal price by 62.8%. Conclusion This study shows that earlier timing of price negotiations resulting in an agreement on drug price can substantially lower the minimal price of orphan drugs for the investor.

Download Full-text

Treating Rare Diseases in Africa: The Drugs Exist but the Need Is Unmet

Frontiers in Pharmacology ◽

10.3389/fphar.2021.770640 ◽

2022 ◽

Vol 12 ◽

Author(s):

Lucio Luzzatto ◽

Julie Makani

Keyword(s):

Rare Diseases ◽

Medical Profession ◽

Orphan Drugs ◽

High Income ◽

African Countries ◽

The Us ◽

History Of ◽

African Patients ◽

The Impact ◽

Human Family

Rare diseases (RD) pose serious challenges in terms of both diagnosis and treatment. Legislation was passed in the US (1983) and in EU (2000) aimed to reverse the previous neglect of RD, by providing incentives for development of “orphan drugs” (OD) for their management. Here we analyse the current situation in Africa with respect to (1) sickle cell disease (SCD), that qualifies as rare in the US and in EU, but is not at all rare in African countries (frequencies up to 1–2%); (2) paroxysmal nocturnal haemoglobinuria (PNH), that is ultra-rare in Africa as everywhere else (estimated <10 per million). SCD can be cured by bone marrow transplantation and recently by gene therapy, but very few African patients have access to these expensive procedures; on the other hand, the disease-ameliorating agent hydroxyurea is not expensive, but still the majority of patients in Africa are not receiving it. For PNH, currently most patients In high income countries are treated with a highly effective OD that costs about $400,000 per year per patient: this is not available in Africa. Thus, the impact of OD legislation has been practically nil in this continent. As members of the medical profession and of the human family, we must aim to remove barriers that are essentially financial: especially since countries with rich economies share a history of having exploited African countries. We call on the Global Fund to supply hydroxyurea for all SCD patients; and we call on companies who produce ODs to donate, for every patient who receives an expensive OD in a high income country, enough of the same drug, at a symbolic price, to treat one patient in Africa.

Download Full-text

Health technology assessment and reimbursement policy for oncology orphan drugs in Central and Eastern Europe

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-020-01556-9 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Krzysztof Piotr Malinowski ◽

Paweł Kawalec ◽

Wojciech Trąbka ◽

Christoph Sowada ◽

Guenka Petrova ◽

...

Keyword(s):

Health Technology Assessment ◽

Eastern Europe ◽

Technology Assessment ◽

Central And Eastern Europe ◽

Health Technology ◽

Orphan Drugs ◽

Gdp Per Capita ◽

Public Budget ◽

Per Capita ◽

The Impact

Abstract Background The reimbursement of orphan drugs (OD) is an increasingly important for country policymakers, and still insufficiently understood, especially in Central and Eastern Europe. The aim of this research was to provide a comprehensive description of country-specific health technology assessment (HTA) policies as well as evaluate the percentage of HTA recommendations and reimbursement decisions for oncology OD. In addition, the study was designed to elucidate the impact of reimbursement of these drugs on the public budget and the agreement between HTA recommendations and reimbursement decisions in the analysed countries. A questionnaire survey was used to collect data on the reimbursement status, HTA recommendation, marketing authorisation, and public expenses on reimbursement in 2014, 2015, and 2016 for all oncology drugs with an orphan designation by the European Medicine Agency in 2017 in Bulgaria, Croatia, Czechia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, and Slovakia. The agreement between the HTA recommendation and reimbursement status was assessed using the kappa coefficient. The Pearson’s correlation was used to analyse the relationship between gross domestic product (GDP) and GDP per capita and reimbursement expenses. Results A total of 36 drugs were analysed (25% conditionally approved; 5.56% approved under exceptional circumstances). The share of reimbursed drugs ranged from 11.11% in Latvia to 41.67% in Poland. The highest share of positive recommendations was observed for Bulgaria and Estonia (36.11%), and the lowest, for Latvia (11.11%). The agreement varied from 0.4 for Poland to 1 for Latvia, Hungary, and Slovakia. Expenses were correlated with GDP (0.95 [0.81–0.99]), and not with GDP per capita (0.54 [− 0.136 to 0.873]). Expenses per capita were not correlated with GDP per capita (0.52 [− 0.15 to 0.87]). Conclusions In Hungary, Latvia, and Slovakia, a positive recommendation was associated with a reimbursement, and a negative one, with the lack of reimbursement. The reimbursement of oncology OD is associated with a growing burden for public budget, and the expenses are correlated with the total GDP. The highest share of drugs with any recommendation was observed in Poland, and the lowest, in Latvia and Romania. The share of reimbursed drugs was the lowest in Latvia and the highest in Poland.

Download Full-text

How to Value Orphan Drugs? A Review of European Value Assessment Frameworks

Frontiers in Pharmacology ◽

10.3389/fphar.2021.631527 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alessandra Blonda ◽

Yvonne Denier ◽

Isabelle Huys ◽

Steven Simoens

Keyword(s):

Cost Effectiveness ◽

Health Benefit ◽

Orphan Drugs ◽

Decision Makers ◽

Data Uncertainty ◽

Accurate Estimation ◽

Successful Implementation ◽

Value Assessment ◽

Life Years ◽

The Impact

Background: Decision-makers have implemented a variety of value assessment frameworks (VAFs) for orphan drugs in European jurisdictions, which has contributed to variations in access for rare disease patients. This review provides an overview of the strengths and limitations of VAFs for the reimbursement of orphan drugs in Europe, and may serve as a guide for decision-makers.Methods: A narrative literature review was conducted using the databases Pubmed, Scopus and Web of Science. Only publications in English were included. Publications known to the authors were added, as well as conference or research papers, or information published on the website of reimbursement and health technology assessment (HTA) agencies. Additionally, publications were included through snowballing or focused searches.Results: Although a VAF that applies a standard economic evaluation treats both orphan drugs and non-orphan drugs equally, its focus on cost-effectiveness discards the impact of disease rarity on data uncertainty, which influences an accurate estimation of an orphan drug’s health benefit in terms of quality-adjusted life-years (QALYs). A VAF that weighs QALYs or applies a variable incremental cost-effectiveness (ICER) threshold, allows the inclusion of value factors beyond the QALY, although their methodologies are flawed. Multi-criteria decision analysis (MCDA) incorporates a flexible set of value factors and involves multiple stakeholders’ perspectives. Nevertheless, its successful implementation relies on decision-makers’ openness toward transparency and a pragmatic approach, while allowing the flexibility for continuous improvement.Conclusion: The frameworks listed above each have multiple strengths and weaknesses. We advocate that decision-makers apply the concept of accountability for reasonableness (A4R) to justify their choice for a specific VAF for orphan drugs and to strive for maximum transparency concerning the decision-making process. Also, in order to manage uncertainty and feasibility of funding, decision-makers may consider using managed-entry agreements rather than implementing a separate VAF for orphan drugs.

Download Full-text

Formation of Lunar Craters and Bright Rays as a Result of Meteorite Impacts

Symposium - International Astronomical Union ◽

10.1017/s0074180900178404 ◽

1962 ◽

Vol 14 ◽

pp. 415-418

Author(s):

K. P. Stanyukovich ◽

V. A. Bronshten

Keyword(s):

Explosive Charge ◽

The Moon ◽

Meteorite Impacts ◽

The Earth ◽

Lunar Craters ◽

The Impact

The phenomena accompanying the impact of large meteorites on the surface of the Moon or of the Earth can be examined on the basis of the theory of explosive phenomena if we assume that, instead of an exploding meteorite moving inside the rock, we have an explosive charge (equivalent in energy), situated at a certain distance under the surface.

Download Full-text

The Geosciences Applied to Lunar Exploration

Symposium - International Astronomical Union ◽

10.1017/s0074180900178222 ◽

1962 ◽

Vol 14 ◽

pp. 169-257 ◽

Cited By ~ 9

Author(s):

J. Green

Keyword(s):

Lunar Surface ◽

Probable Mechanism ◽

Point Of View ◽

Lunar Exploration ◽

Geological Model ◽

Apply Geophysics ◽

Surface Features ◽

The Impact

The term geo-sciences has been used here to include the disciplines geology, geophysics and geochemistry. However, in order to apply geophysics and geochemistry effectively one must begin with a geological model. Therefore, the science of geology should be used as the basis for lunar exploration. From an astronomical point of view, a lunar terrain heavily impacted with meteors appears the more reasonable; although from a geological standpoint, volcanism seems the more probable mechanism. A surface liberally marked with volcanic features has been advocated by such geologists as Bülow, Dana, Suess, von Wolff, Shaler, Spurr, and Kuno. In this paper, both the impact and volcanic hypotheses are considered in the application of the geo-sciences to manned lunar exploration. However, more emphasis is placed on the volcanic, or more correctly the defluidization, hypothesis to account for lunar surface features.

Download Full-text