This essay outlines the moral dilemma of funding orphan drug research and development. To date, ethical aspects of priority setting for research funding have not been an issue of discussion in the bioethics debate. Conflicting moral obligations of beneficence and distributive justice appear to demand very different levels of funding for orphan drug research. The two types of orphan disease, rare diseases and tropical diseases, however, present very different ethical challenges to questions about allocation of research funds. (...) The dilemma is analysed considering utilitarian and rights based theories of justice and moral obligations of non-abandonment and a professional obligation to advance medical science. The limitations of standard economic evaluation tools and other priority setting tools used to inform health policy decision makers on research funding decisions are outlined. (shrink)

The PRIME Institute of the College of Pharmacy, University of Minnesota, recently released preliminary research findings indicating a trend of extraordinary pharmaceutical industry pricing of drug products in the United States (U.S.). According to researchers at the PRIME Institute, such extraordinary price increases are defined as any price increase that is equal to, or greater than, 100% at a single point in time. In some instances, PRIME Institute researchers found that drugs exhibiting extraordinary price increases are categorized as " (...) class='Hi'>orphan drugs" (or blood-related biologic treatments) and often life-saving or life-sustaining for treating the cause or symptoms of diseases affecting fewer than 200,000 people in the U.S., or where there is prevalence of less than 5 per 10,000 people afflicted with a disease or symptoms in the community. Because of extraordinary price increases for orphan drugs — some exceeding 1000% at a single point in time -this article addresses two interrelated questions: Are extraordinary orphan drug price increases socially responsible behavior? If so, are the pharmaceutical industry's policies providing orphan drug access to American consumers in dire need of available life-sustaining and life-enhancing pharmaceuticals considered "socially responsible" behavior? The author concludes, after an interdisciplinary analysis of the legal, economic, sociopolitical, and ethical dimensions of orphan drug pricing, that they are not socially responsible – unless justified by cost and availability of health care marketplace/patient options. Furthermore, the author recommends a socially responsible industry strategic approach to insure that patients ultimately receive -regardless of cost -timely access to life-saving and life-sustaining orphan drugs. (shrink)

In recent years, the issue of accepting a higher cost per health improvement for orphan drugs has been the subject of discussion in health care policy agencies and the academic literature. This article aims to provide an analysis of broadly egalitarian arguments for and against accepting higher costs per health improvement. More specifically, we aim to investigate which arguments one should agree upon putting aside and where further explorations are needed. We identify three kinds of arguments in the (...) literature: considerations of substantial equality, formal equality, and opportunity cost. We argue that considerations of substantial equality do not support higher costs per health improvement orphan drugs, even if such considerations are considered valid. On the contrary, arguments of formal equality may support accepting a higher cost per health improvement for orphan drugs. However, in order to do so, a number of both normative and empirical issues must be resolved; these issues are identified in the article. For instance, it must be settled to what extent the opportunity cost in terms of foregone health for other patients is acceptable in order to uphold formal equality. We conclude that certain arguments can be set aside, and future focus should be put on the unresolved normative and empirical issues related to formal equality and opportunity cost. (shrink)

With the human genome mapped, and with the mapping of more than one hundred animal genomes in progress, the amount of genetic data available is increasing exponentially. This exponential increase in data is having an immediate impact on the process of drug development. By using techniques of information technology to manipulate data regarding the genes, proteins, and biochemical pathways associated with various diseases, scientists are beginning to be able to design drugs in a systematic fashion. In the context of (...) any given disease, scientists look to see whether a gene, a protein for which the gene codes, or another protein in the relevant biochemical pathway could be the “target” biological molecule, the “knocking out” of which would halt or slow the disease's progression. Once a target molecule has been identified and characterized structurally, drug therapies that would be likely to knock out this target can be identified and tested systematically. The merger of information technology and genetic technology has changed the process of pharmaceutical development so much that a new term—bioinformatics—has been coined to describe this new approach to such development. (shrink)

For a significant number of patients, there exists no, or only little, interest in developing a treatment for their disease or condition. Especially with regard to rare diseases, the lack of commercial interest in drug development is a burning issue. Several interventions have been made in the regulatory field in order to address the commercial disinterest in these conditions. However, existing regulations mainly focus on the provision of incentives to the sponsors of clinical trials of orphan drugs, and (...) leave unanswered the overarching question about the rightful place of orphan drugs in resource allocation systems. In this article, we analyse the ethical aspects of funding research and development in the field of rare diseases. We then propose an ethical framework that can help health policy makers move forward in the difficult matter of fairly allocating resources for the prevention, diagnosis and treatment of rare diseases. (shrink)

Mucopolysaccharidosis type I (MPS I) is a rare lysosomal storage disorder treated with bone marrow transplantation or enzyme replacement therapy with laronidase, a high-cost orphan drug. Laronidase was approved by the US Food and Drug Administration and the European Medicines Agency in 2003 and by the Brazilian National Health Surveillance Agency in 2005. Many Brazilian MPS I patients have been receiving laronidase despite the absence of a governmental policy regulating access to the drug. Epidemiological and treatment data concerning MPS (...) I are scarce. This study aims to present a demographic profile of Brazilian patients with MPS I, describe the routes of access to laronidase in Brazil, and discuss associated ethical issues relating to public funding of orphan drugs. (shrink)

In recent years, the biopharmaceutical industry has seen an increase in the development of so-called orphan drugs for the treatment of rare and neglected diseases. This increase has been spurred on by legislation in the United States, Europe, and elsewhere designed to promote orphan drug development. In this article, we examine the drivers of corporate social responsibility (CSR) activities in orphan drug markets and the extent to which biopharmaceutical firms engage in these activities with a strategic (...) orientation. The unique context of orphan drugs constitutes a research opportunity to test the applicability of existing theoretical perspectives on CSR and strategic CSR. Using Schwartz and Carroll’s (Bus Ethics Q, 13(4):503–530, 2003) three-domain approach to CSR and the literature on strategic CSR as a theoretical background, we employ a combination of semi-structured interviews and a quantitative website content analysis to study practices of biopharmaceutical firms in the United States and European Union. Our findings show that both US- and EU-based companies engaged in orphan drugs development perceive their involvement as a responsible business activity beyond the economic dimension of CSR. However, for the majority of these companies their CSR activities do not qualify as strategic according to the criteria established in the literature. We also find significant differences between larger and smaller firms in their use of CSR. Based on these findings, we make several suggestions regarding orphan drug legislation and other measures that might help firms exploit strategic CSR benefits. (shrink)

The rule of rescue describes the moral impulse to save identifiable lives in immediate danger at any expense. Think of the extremes taken to rescue a small child who has fallen down a well, a woman pinned beneath the rubble of an earthquake, or a submarine crew trapped on the ocean floor. No effort is deemed too great. Yet should this same moral instinct to rescue, regardless of cost, be applied in the emergency room, the hospital, or the community clinic? (...) -/- In health care, the desire to save lives at any cost must be reconciled with the reality of resource scarcity. As one example, the estimated cost for prophylactic Factor VIII to treat one patient with hemophilia for one year is $300,000. Costs of this magnitude have been accepted by public and private insurers in the developed world, even though, in principle, these sums could provide greater overall health benefit if allocated to pay for the unmet health care needs of many other patients. Looking forward, however, broad application of the rule of rescue will be increasingly untenable. But the moral instinct will remain: the desire to help those weakest among us, especially when their small numbers allow us to see them as unique individuals. What, then, is the ethical framework that can guide coverage and reimbursement decisions for orphan drugs into the future? (shrink)

Die Entwicklung einer „personalisierten Medizin“ ist zurzeit in aller Munde. Insbesondere die personalisierte Arzneimitteltherapie gewinnt infolge der pharmakologischen und molekulargenetischen Entwicklungen immer mehr an Bedeutung. Dies macht es erforderlich, die Auswirkungen der personalisierten Arzneimitteltherapie auf die gesetzliche Krankenversicherung (GKV) und die Patientenversorgung zu untersuchen. In diesem Zusammenhang stellt sich die Frage nach einer „Orphanisierung“: Könnten Arzneimittel der personalisierten Medizin regelmäßig als Orphan Drugs, also als Arzneimittel für seltene Leiden, ausgewiesen werden, würde für sie nach dem Arzneimittelneuordnungsgesetz (AMNOG) grundsätzlich (...) kein Nachweis des Zusatznutzens im Rahmen der vom Gemeinsamen Bundesausschuss (GBA) vorzunehmenden frühen Nutzenbewertung erforderlich werden. Entscheidend für die Ausweisung des Arzneimittels als Orphan Drug ist unter anderem die Prävalenzrate der Patientengruppe, deren Erkrankung mit dem Arzneimittel behandelt werden soll. In diesem Zusammenhang kommt der Stratifizierung von Patientengruppen im Rahmen der personalisierten Arzneimitteltherapie eine besondere Bedeutung zu. Eine solche „Orphanisierung“ hätte für die GKV wegen der mangelnden Kenntnis von dem Zusatznutzen des Arzneimittels insbesondere preisrechtliche Konsequenzen; für die Patienten sind die Folgen durchaus differenzierter zu betrachten. (shrink)

Children and pregnant women are often excluded from clinical research. This has resulted in a paucity of evidence on how medicines work for fetuses, neonates, infants, and adolescents. It also raises bioethics, scientific, and public health concerns. For over half a century, doctors have prescribed medicines to children largely on the basis of how they work in adults, despite children’s varied physiologies and differences in how their bodies absorb and metabolize drugs. Regulations and legislation have led to an increase (...) in the number of pediatric studies and to better drug labeling. However, children at all stages of their lives often remain “therapeutic orphans” owing to insufficient evidence about how medicines work for them. (shrink)

BackgroundApproximately 7% of the general population is affected by an orphan disease, which, in the United States, is defined as affecting fewer than 1 in 1500 people. Disease awareness is often low and time-to-diagnosis delayed. Different legislations worldwide have created incentives for pharmaceutical companies to develop drugs for orphan diseases. A journalistic article in Bloomberg Businessweek has claimed that pharmaceutical companies have tried marketing orphan drugs by placing a specific disease into the popular television series (...) “House, M.D.” which features diagnostic journeys and was produced between 2004 and 2012. This study aimed to describe the presentation of orphan diseases in the television series “House, M.D.”, to test in an exploratory fashion the hypothesis that treatable orphan conditions are overrepresented in “House, M.D.” and to discuss whether such marketing practices may or may not be ethical.MethodsA list of all medical cases depicted in the television series “House, M.D.” was obtained and classified as orphan or non-orphan according to the Orphanet database. The ratios of orphan diseases among all diseases, such with an orphan drug designation and such with an orphan drug approval by the FDA were then compared with conservative approximations of real world conditions (chi-squared tests for equality of proportions). STROBE criteria were respected.ResultsOut of a total of n = 181 different medical diagnoses, n = 42 (23.2%) were orphan diseases. The difference in percentages in between “House, M.D.” and reality was not statistically significant for orphan diseases overall (p = 0.96), yet was statistically significantly higher for both orphan diseases with one or more orphan drug designations (p = 0.0192) and such with one or more approved orphan drugs (p < 0.0001).ConclusionsOrphan diseases with a designated and/or approved orphan drug were overrepresented in the television series “House, M.D.” with statistical significance while orphan diseases overall were not. This may be explained by (so far) undocumented efforts of pharmaceutical companies to place their orphan drugs in the television series, as described in the article in Bloomberg Businessweek. Further research is needed into marketing practices in popular and emerging media formats. (shrink)

This article is about the justifiability of accepting worse cost effectiveness for orphan drugs, that is, treatments for rare diseases, in a publicly financed health care system. Recently, three arguments have been presented that may be used in favour of exceptionally advantageous economic terms for orphan drugs. These arguments share the common feature of all referring to considerations of justice or fairness: the argument of the irrelevance of group size, the argument from the principle of need, (...) and the argument of identifiability. It is argued that all of these arguments fail to support the conclusion that orphan drugs should be subsidized to a larger extent than treatments for common diseases. The argument of the irrelevance fails to distinguish between directly and indirectly relevant considerations of fairness or justice. The recent attempt to revive the moral relevance of identifiability has provided no novel reasons to think that identifiability is morally relevant in itself or due to considerations of fairness and justice. The argument from the principle of need does not fail due to any inherent flaw in the principle as such. Rather, this principle can be interpreted in different ways, and none of these interpretations support exceptionally advantageous terms economically for treating rare diseases specifically. It is concluded that we are awaiting justice based reasons for the preferential treatment of orphan drugs. (shrink)

Rare diseases are a heterogenic group of disorders with a little in common except of their rarity affecting by less than 5 : 10.000 people. In the world is registered about 6000-8000 rare diseases with 6-8% suffering population only in the European Union. In spite of rarity, they represent an important medical and social problem due to their incidence. For many rare diseases have no treatment, but if it exists and if started on time as being available to patients, there (...) is a good prognosis for them to be able for normal life. The problems of patients affected by rare diseases are related to the lack of diagnosis and timely undergoing as well as their treatment or prevention. Orphan drugs are products intended for treatment, diagnosis or prevention of rare diseases, but for their development and marketing the industry has not been interested in yet because of their marketing reasons. Patients suffering from a rare disease although belonging to the vulnerable group for their specific health needs, is becoming invisible in the health care system due to their additional needs un properly recognized. Ethical problems faced by patients, but also health care professionals are related to the allocation of medical diagnostics, unequal approach to health care, inappropriately specialized social services as well as therapy and rare orphan drugs unavailability. Ethical questions related to clinical trails on orphan drugs, population screening and epidemiology testing on rare diseases will also be discussed in this paper. [Projekat Ministarstva nauke Republike Srbije, br. 41004: Rare diseases: Molecular pathophysiology, the diagnostic and therapeutical modalities, social, ethical and legal aspects] Retke bolesti su veoma heterogena grupa poremecaja i imaju malo toga zajednickog osim retkosti, posto pogadjaju manje od pet osoba na 10.000 ljudi. U svetu je evidentirano izmedju 6.000 i 8.000 retkih bolesti koje pogadjaju sest do osam procenata stanovnistva samo u Evropskoj uniji. Dakle, iako retke, one predstavljaju vazan medicinski i socijalni problem s obzirom na broj obolelih. Za mnoge retke bolesti nema terapije, a ukoliko ona postoji i ako se na vreme zapocne i bude dostupna pacijentima, postoje dobri izgledi da ce oboleli moci da zive normalnim zivotom. Problemi s kojima se susrecu pacijenti sa retkim bolestima vezani su za dijagnostikovanje u smislu nemogucnosti ili nepravovremenog postavljanja dijagnoze, kao i same terapije ili prevencije pojave bolesti. Orphan lekovi su proizvodi koji su namenjeni za lecenje, dijagnozu ili prevenciju retkih bolesti, za ciji razvoj i marketing industrija nije zainteresovana iz trzisnih razloga. Pacijenti s retkim bolestima, iako pripadaju osetljivoj grupi, jer imaju specificne zdravstvene potrebe, ostaju nevidljivi u zdravstvenom sistemu, jer se njihove dodatne specificne potrebe ne prepoznaju. Eticki problemi s kojima se susrecu pacijenti, ali i zdravstveni radnici, ticu se alokacije zdravstvene dijagnostike, nejednakog pristupa zdravstvenoj zastiti i nezi, nedostatka specijalizovanih socijalnih usluga, kao i nepostojanja i nedostupnosti terapije orphan lekovima. Eticka pitanja retkih klinickih ispitivanja orphan lekova i populacionih i skrining ispitivanja u vezi sa retkim bolestima takodje su razmatrani u ovom radu. PR Projekat Ministarstva nauke Republike Srbije, br. 41004: Rare diseases: Molecular pathophysiology, the diagnostic and therapeutical modalities, social, ethical and legal aspects. (shrink)

Orphan drug policy often gives ‘special treatment’ to rare diseases, by giving additional priority or making exceptions to specific drugs, based on the rarity of the conditions they aim to treat. This essay argues that the goal of orphan drug policy should be to make prevalence irrelevant to funding decisions. It aims to demonstrate that it is severity, not prevalence, which drives our judgments that important claims are being overlooked when treatments for severe rare diseases are not (...) funded. It shows that prioritising severity avoids problems caused by prioritising rarity, and that it is compatible with a range of normative frameworks. The implications of a severity-based view for drug development are then derived. The severity-based view also accounts for what is wrong with how the current system of drug development unfairly neglects common diseases that burden the developing world. Lastly, the implications of a severity-based view for current orphan drug policies are discussed. There are no data in this work. (shrink)

Children who experience well-being are engaging more confidently and positively with their caregiver and peers, which helps them to profit more from available learning opportunities and support current and later life outcomes. The goodness-of-fit theory suggests that children’s well-being might be a result of the interplay between their temperament and the environment. However, there is a lack of studies that examined the association between children’s temperament and well-being in early childhood education and care, and whether this association is affected by (...) ECEC process quality. Using a multilevel random coefficient approach, this study examines the association between toddlers’ temperament and well-being in Norwegian ECEC and investigates whether process quality moderates this association. Results reveal an association between temperament and well-being. Staff-child conflict moderates the association between shyness and well-being, and between activity and well-being. Moreover, high emotional behavioral support moderates the association between activity and well-being. Extra attention should be paid by the staff to these children’s needs. (shrink)

How to handle orphan drugs for rare diseases is a pressing problem in current health-care. Due to the group size of patients affecting the cost of treatment, they risk being disadvantaged in relation to existing cost-effectiveness thresholds. In an article by Niklas Juth it has been argued that it is irrelevant to take indirectly operative factors like group size into account since such a compensation would risk discounting the use of cost, a relevant factor, altogether. In this article (...) we analyze Juth’s argument and observe that we already do compensate for indirectly operative factors, both outside and within cost-effectiveness evaluations, for formal equality reasons. Based on this we argue that we have reason to set cost-effectiveness thresholds to integrate equity concerns also including formal equality considerations. We find no reason not to compensate for group size to the extent we already compensate for other factors. Moreover, groups size implying a systematic disadvantage also on a global scale, i.e. taking different aspects of the health condition of patients suffering from rare diseases into account, will provide strong reason for why group size is indeed relevant to compensate for. (shrink)

In The Ethics of Food, Gregory E. Pence brings together a collection of voices who share the view that the ethics of genetically modified food is among the most pressing societal questions of our time. This comprehensive collection addresses a broad range of subjects, including the meaning of food, moral analyses of vegetarianism and starvation, the safety and environmental risks of genetically modified food, issues of global food politics and the food industry, and the relationships among food, evolution, and human (...) history. (shrink)

The National Institute for Health and Care Excellence, the UK’s main healthcare priority-setting body, recently reaffirmed a longstanding claim that in recommending technologies to the National Health Service it cannot apply the ‘rule of rescue’. This paper explores this claim by identifying key characteristics of the rule and establishing to what extent these are also features of NICE’s approach to evaluating ultra-orphan drugs through its highly specialised technologies programme. It argues that although NICE in all likelihood does not (...) act because of the rule in prioritising these drugs, its actions in relation to HSTs are nevertheless in accordance with the rule and are not explained by the full articulation of any alternative set of rationales. That is, though NICE implies that its approach to HSTs is not motivated by the rule of rescue, it is not explicit about what else might justify this approach given NICE’s general concern with overall population need and value for money. As such, given NICE’s reliance on notions of procedural justice and its commitment to making the reasons for its priority-setting decisions public, the paper concludes that NICE’s claim to reject the rule is unhelpful and that NICE does not currently meet its own definition of a fair and transparent decision-maker. (shrink)

It is hard to argue with the proposition that value for money should guide health spending. However, even after decades of development, economic evaluation is still a work in progress. As applied, it deals poorly with issues of social justice, ageing and end of life issues; cases involving small numbers—such as decisions about orphan drugs—are also contested. Unfortunately, differences in incremental cost-effectiveness ratios are presented with a degree of precision which contributes to an ‘illusion of validity’.1 Nobel Laureate (...) Amartya Sen has suggested that ‘when all the requirements of ubiquitous market-centred evaluation have been incorporated into the procedures of cost–benefit analysis, it is not so much a discipline as a daydream’.2 As with any approach to public decision making, the use of economic evaluation rests on an implicit social licence, including that the decision making is fair and reasonable. Many countries have developed special policies for rare, ‘ultrarare’ or ‘orphan’ diseases to moderate the effect of a ubiquitous application of economic evaluation. The threshold for defining ‘small’ or rare is a matter of judgement and ranges between 2 and 80 per 100 000 population.3 Magalhaes challenges the ethical basis of special programmes for low incidence conditions and argues against such provisions. In this commentary, I will argue the contrary: that there are good reasons …. (shrink)

While ethics and evidence‐based medicine are often viewed as separate domains of inquiry and practice, what we know influences what we can ethically justify doing, and what we see as our moral obligations shapes the way we interpret evidence. The boundaries between the moral and epistemic spheres become particularly blurred when the health of people is at stake and even more so when no “officially” recommended medical intervention is available to help a patient in need. The treatment of major hemorrhages (...) using recombinant factor VIIa (rFVIIa), which was originally approved under orphan drug legislation to treat hemophilia, is a case in point.Following reports in the late 1990s that rFVIIa was success­fully used to stop bleeding in gunshot trauma, there was much excitement about its potential to help patients with uncontrolled bleeding in other clinical settings, leading to wide‐spread off‐label use of the drug. In recent years, new evidence has raised questions about the off‐label use of rFVIIa for severe bleeding. Nonetheless, while some clini­cians are now adamantly opposed to prescribing rFVIIa for massive bleed­ing, many remain determined to continue the practice. This raises the question: why do clinicians have such variable responses to the same body of evidence?We analyzed the debate around off‐label use of rFVIIa and character­ized its main conceptual features and tensions. We did not seek to provide a normative analysis as to whether the evidence supports the case for off‐label prescribing, nor did we try to provide a historical analysis of how attitudes and clinical practice have changed. Rather, we sought to make visible the moral and epistemic values underpinning stakeholders’ opinions and practices. On the basis of our analysis, which is described in this ar­ticle, we suggest that debates such as those surrounding rFVIIa will not be resolved simply by conducting more studies and that, therefore, there is also a need for conceptual and pro­cedural frameworks that more sys­tematically incorporate values into clinical policy‐making. (shrink)

Die Arzneimittelzulassung und der Aufnahmeprozess zur Kostenerstattung sollen die Entwicklung und Vermarktung von pharmazeutischen Innovationen mit Patientennutzen nicht behindern, zugleich aber die Wirtschaftlichkeit der Arzneimittelversorgung für die Kostenträger nicht gefährden. Eine Anpassung der Verfahren an die Merkmale personalisierter Arzneimittel erscheint notwendig. Dabei ist allerdings zu fragen, ob eine ungerechtfertigte Privilegierung erfolgt. In den USA und in der EU werden die jeweiligen Zulassungsverfahren für Arzneimittel und Tests schrittweise angepasst und integriert. Zulassung und Erstattungsentscheidungen sollen koordiniert werden. Eine Privilegierung, wie bei Arzneimitteln (...) für seltene Indikationen (Orphan Drugs), findet jedoch für personalisierte Medizin nicht statt. Es bestehen keine unzumutbaren Hürden für die Hersteller. Zurückhaltung bei der Entwicklung innovativer Produkte wäre deshalb nicht gerechtfertigt. (shrink)

BackgroundNusinersen is one of an increasing number of new, expensive orphan drugs to receive authorization. These drugs strain public healthcare budgets and challenge principles for resource allocation. Nusinersen was introduced in the Norwegian public healthcare system in 2018. A national expert group consisting of physicians was formed to oversee the introduction and continuation of treatment in light of specific start and stop criteria.MethodsWe have studied experiences within the expert group with a special emphasis on their application of (...) the start and stop criteria, rationing of treatment, and experienced moral dilemmas. A research interview with six members of the national expert group was performed, then analysed with manifest content analysis. The analysis was supplemented with publically available sources on priority setting and the process leading up to the introduction of nusinersen and the establishment of the expert group.ResultsSixty-six patients have received treatment within the first 25 months since the national expert group’s establishment. Treatment has not been discontinued for any patient. No patients under 18 years of age have been denied treatment, as those who were referred at this age were all deemed to fulfill the start criteria. The expert group has, however, increased geographical treatment equity and facilitated important cooperation at the national level. Furthermore, it has enhanced open and critical discussions of both medical issues and new ethical dilemmas.ConclusionAlthough facilitating equal access to treatment for SMA patients, the national expert group has not discontinued treatment for any patient. It is suggested that in order for clinicians to be able to ration care for individual patients, they require both adequate support and sufficient formal authority. Start and stop criteria need to be re-evaluated as more knowledge and experience are gained regarding the treatment. (shrink)

In June 2021, an 1856 British Guiana 1c magenta stamp sold for US$8.3m. It is the only known specimen of its kind in existence and on a gram-for-gram basis the most valuable item in the world. Clearly, in some spheres of human engagement, rarity carries a premium. Should this logic be applied in healthcare? Magalhaes thinks not.1 They explore the topic of whether pricing and reimbursement systems should give a premium to orphan drugs for rare diseases. They argue (...) that rarity is irrelevant to pharmaceutical policy on ethical grounds, and instead drug incentives should be prioritised by disease severity. At a time when incentives for orphan medicines are being revisited globally, Magalhaes is provoking an important discussion. The author seeks to disentangle the interwoven concepts of rarity, severity and unmet need that factor into decisions on orphan drug policy. They perhaps overstate the emphasis on rarity within existing regulatory and P&R frameworks. Yes, this is one of the criteria for orphan drug designation, but in payer systems rarity is seldom explicitly referenced. For example, of the five largest European countries, only the United Kingdom formally adjusts willingness-to-pay thresholds by prevalence. In contrast, concepts of severity and unmet need feature widely in global regulatory processes (eg, Breakthrough Therapy designation from …. (shrink)

The rise of liberal market economies, propagated by neoliberal free market thought, has created a vacant responsibility for public interests in the market order of society. This development has been critiqued by Catholic social teaching (CST), forcefully arguing that governments and businesses should be directed to the common good. In this debate, no attention has yet been given to the Reformational tradition and its principle of sphere sovereignty, which provides guidelines on the responsibilities of governments and companies for the public (...) interest of society. This article analyzes the differences and similarities between CST and the Reformational philosophy in their critiques of the neoliberal free market perspective of Hayek. We apply the three perspectives to the case of orphan drugs in the pharmaceutical industry and show that CST and the Reformational philosophy offer valuable insights in correction to Hayek’s views on the responsibilities of governments and companies for public health interests. (shrink)

ZusammenfassungDie Entwicklung einer „personalisierten Medizin“ ist zurzeit in aller Munde. Insbesondere die personalisierte Arzneimitteltherapie gewinnt infolge der pharmakologischen und molekulargenetischen Entwicklungen immer mehr an Bedeutung. Dies macht es erforderlich, die Auswirkungen der personalisierten Arzneimitteltherapie auf die gesetzliche Krankenversicherung (GKV) und die Patientenversorgung zu untersuchen. In diesem Zusammenhang stellt sich die Frage nach einer „Orphanisierung“: Könnten Arzneimittel der personalisierten Medizin regelmäßig als Orphan Drugs, also als Arzneimittel für seltene Leiden, ausgewiesen werden, würde für sie nach dem Arzneimittelneuordnungsgesetz (AMNOG) grundsätzlich (...) kein Nachweis des Zusatznutzens im Rahmen der vom Gemeinsamen Bundesausschuss (GBA) vorzunehmenden frühen Nutzenbewertung erforderlich werden. Entscheidend für die Ausweisung des Arzneimittels als Orphan Drug ist unter anderem die Prävalenzrate der Patientengruppe, deren Erkrankung mit dem Arzneimittel behandelt werden soll. In diesem Zusammenhang kommt der Stratifizierung von Patientengruppen im Rahmen der personalisierten Arzneimitteltherapie eine besondere Bedeutung zu. Eine solche „Orphanisierung“ hätte für die GKV wegen der mangelnden Kenntnis von dem Zusatznutzen des Arzneimittels insbesondere preisrechtliche Konsequenzen; für die Patienten sind die Folgen durchaus differenzierter zu betrachten. (shrink)

ZusammenfassungDie Arzneimittelzulassung und der Aufnahmeprozess zur Kostenerstattung sollen die Entwicklung und Vermarktung von pharmazeutischen Innovationen mit Patientennutzen nicht behindern, zugleich aber die Wirtschaftlichkeit der Arzneimittelversorgung für die Kostenträger nicht gefährden. Eine Anpassung der Verfahren an die Merkmale personalisierter Arzneimittel erscheint notwendig. Dabei ist allerdings zu fragen, ob eine ungerechtfertigte Privilegierung erfolgt. In den USA und in der EU werden die jeweiligen Zulassungsverfahren für Arzneimittel und Tests schrittweise angepasst und integriert. Zulassung und Erstattungsentscheidungen sollen koordiniert werden. Eine Privilegierung, wie bei Arzneimitteln (...) für seltene Indikationen (Orphan Drugs), findet jedoch für personalisierte Medizin nicht statt. Es bestehen keine unzumutbaren Hürden für die Hersteller. Zurückhaltung bei der Entwicklung innovativer Produkte wäre deshalb nicht gerechtfertigt. (shrink)

The fair distribution of health resources is critical to health justice. But distributing healthcare equitably requires careful attention to the existing distribution of other resources, and the economic system which produces these inequalities. Health is strongly determined by socioeconomic factors, such as the effects of racism on the health of communities of colour, as well as the broader market-oriented healthcare and pharmaceutical systems that put the pursuit of profit above the alleviation of suffering. Two papers in this issue confront health (...) injustices at different scales, and make far-reaching recommendations for more just healthcare allocation policies. Orphan drugs are those that pharmaceutical companies are unwilling to develop unless they are offered financial incentives to do so. When a target patient group is very small, or very poor, producing drugs is unprofitable. If patients are to benefit from these drugs in a marketised pharmaceutical regime, governments must step in to provide incentives for research and development. Yet government spending ought to prioritise value for money, and is generally guided by a utilitarian framework. In the case of neglected tropical diseases, there is no moral conflict: large numbers of people would benefit greatly from these treatments. However, there are practical limitations: the governments of affected populations are often unable to fund incentives for research and development, and solidarity from elsewhere is limited.1 2 In the case of rare diseases, Global North governments usually can afford to incentivise the development of treatments to serve their populations, but given the small numbers of beneficiaries, doing so seems a questionable use of resources. Many Global North governments make an exception to the general utilitarian heuristic to accommodate the moral intuition that the claims of a person with a rare …. (shrink)

One of the most pressing issues that confronts the Food and Drug Administration (FDA) is learning how to better address and assist in medical product development. FDA needs to prepare today so the agency can efficiently evaluate the technologies of tomorrow. Clearly, this is an area that impacts not only health care consumers but also our economies and financial markets. If the FDA can be a more aggressive part of the solution, they can help not only ease some of the (...) pressures that are driving up health care costs but also help all of us to maximize the value of medical innovations. The high cost of research and development is forcing many companies to make the short-term business decision to focus product development on those molecules that have a much higher potential to recoup expenditures. Unfortunately, this trumps attempts to develop potentially risky but breakthrough products for diseases affecting smaller populations, the orphan drugs. FDA's critical path initiative will enable innovative growth companies to better and more efficiently attack the steep hurdles facing them, allowing them to compete more effectively against the bigger, better-funded players in the market on a more level playing field. That means a real change in the risk/benefit equation for both the emerging growth companies and the public health. (shrink)

As the 20th century began, few effective therapies existed. This soon changed with major therapeutic discoveries turning the century into what has been called the golden age of therapeutics.1 The emphasis of most of these developments was on medicines for common disorders as they presented the greatest need. However, it also allowed pharmaceutical manufacturers to produce blockbuster drugs that provided a large return on investment. Rare disorders were overlooked because most are genetic in origin and scientific knowledge was lacking, (...) making it difficult to find treatments. The first genetic disorder with a therapy was phenylketonuria. The biochemist who proposed the first successful treatment in the 1950s was actively discouraged as phenylketonuria was genetic and ‘incurable’.2 Another reason was an absence of incentives to invest in developing medicines for which the return was limited, given the small numbers of potential patients. This changed from 1983 as several countries began introducing orphan drug policies, with Canada being a notable exception. As the millennium changed, some drugs for rare disorders were available, but the sequencing of the human genome in the early 2000s provided scientific knowledge to develop many more. The new therapies are often costly because they require millions, even billions, of dollars and years to develop, test and satisfy regulatory standards. …. (shrink)

Introduction to the study of African Christian ethics -- Foundations of contemporary African ethics -- Foundations of Western ethics -- Foundations of Christian ethics -- Foundations of African Christian ethics -- Applying African Christian ethics -- Church and state -- War and violence -- Strikes -- Poverty -- Corruption -- Fund-raising -- Procreation and infertility -- Reproductive technologies -- Contraception -- Polygamy -- Domestic violence -- Divorce and remarriage -- Widows and orphans -- Rape -- Incest -- Prostitution and sex (...) trafficking -- Female circumcision -- Homosexuality -- HIV/AIDS -- Abortion -- Euthanasia and infanticide -- Strikes and medical services -- Drug and alcohol abuse -- Witchcraft. (shrink)

The paper discusses the possibility that the benefits of pharmacogenomics will not be distributed equally and will create orphan populations. I argue that since these inequalities are not substantially different from those produced by ‘traditional’ drugs and are not generated with the intention to discriminate, their production needs not be unethical. Still, the final result is going against deep-seated moral feelings and intuitions, as well as broadly accepted principles of just distribution of health outcomes and healthcare. I thus (...) propose two provisos that would prevent the most offensive outcomes and moderate the scope of the produced inequalities. The first proviso rejects pharmacogenomics innovations that worsen existing group inequalities and aggravate the disadvantage of communities with a history of discrimination. The second proviso requires that there is a strategy in place to even out as much as possible the distribution of benefits in the future and that a system of compensations is in place for pharmacogenomic orphans. Given that only one moral problem generated by pharmacogenomics has been tackled, the list of provisos might be expanded when other issues are considered. (shrink)

Of the future technologies arising from the Human Genome Project, pharmacogenomics will probably be the first to have a widespread impact on the everyday practice of medicine. This technology offers great benefits but also presents some difficult ethical challenges. This paper explains what pharmacogenomics is and examines three of the issues that it raises: orphan populations, the use of ethnicity in drug trials, and potential obstacles to informed consent for genetic testing.

Normal 0 false false false EN-MY X-NONE AR-SA Normal 0 false false false EN-MY X-NONE AR-SA /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:24.0pt; mso-para-margin-right:0cm; mso-para-margin-bottom:0cm; mso-para-margin-left:0cm; mso-para-margin-bottom:.0001pt; text-align:justify; line-height:200%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:24.0pt; mso-para-margin-right:0cm; mso-para-margin-bottom:0cm; mso-para-margin-left:0cm; mso-para-margin-bottom:.0001pt; text-align:justify; line-height:200%; mso-pagination:widow-orphan; font-size:11.0pt; (...) font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;}This study explores the significance of the family factors on drug use and its effects on relapse. In this respect, the effects of parental substance use , family conflict , and family structure are discussed in this research. The family, as a fundamental social unit of society, can be expected to exert remarkable influences on the development of social behaviors such as adolescent substance use and also relapse ADDIN EN.CITE Rouholamini 2002 90 90 90 32 Rouholamini,S Formative research on familial characteristics of drug users in Iran Master 2002 New Haven Yale (Rouholamini, 2002) . Since nearly 90% of drug abusers in Iran live with a family member ADDIN EN.CITE Mokri 2002 6 6 6 17 Mokri, A A brief overview of the status of drug abuse in Iran Archives of Iranian Medicine 184-190 5(3) 2002 (Mokri, 2002) , therefore family has an important role to reduce the high rates of relapse after detoxification. Therefore, this study considers three factors: Parental substance use , Family Conflict , and Family Structure. The objective of this study is to examine the effects of family factors on relapse behavior among male adolescent opiate users in Kerman. In this research 226 adolescents between the ages of 13 to 20 were selected based on ten rehabilitation centers to answer the Self-administered questionnaire. Results showed that there were important relationships between these factors with relapse in adolescents. The study proposes some suggestions in order to prevent relapse after treatment in adolescents. (shrink)

In recent years, a debate has emerged on whether bodily sensations are typically accompanied by a sense of body ownership, namely a distinctive experience of one's body or body part as one's own. Realists about the sense of body ownership heavily rely on evidence from experimentally-induced bodily illusions (e.g., the rubber hand illusion) and pathological disownership syndromes (e.g. somatoparaphrenia). In this chapter, I will introduce novel evidence regarding body disownership syndromes induced by psychoactive drugs rather than pathological conditions, and (...) discuss its relevance to the debate on the sense of body ownership. (shrink)

Most people who are regular consumers of psychoactive drugs are not drug addicts, nor will they ever become addicts. In neurobiological theories, non-addictive drug consumption is acknowledged only as a “necessary” prerequisite for addiction, but not as a stable and widespread behavior in its own right. This target article proposes a new neurobiological framework theory for non-addictive psychoactive drug consumption, introducing the concept of “drug instrumentalization.” Psychoactive drugs are consumed for their effects on mental states. Humans are able (...) to learn that mental states can be changed on purpose by drugs, in order to facilitate other, non-drug-related behaviors. We discuss specific “instrumentalization goals” and outline neurobiological mechanisms of how major classes of psychoactive drugs change mental states and serve non-drug-related behaviors. We argue that drug instrumentalization behavior may provide a functional adaptation to modern environments based on a historical selection for learning mechanisms that allow the dynamic modification of consummatory behavior. It is assumed that in order to effectively instrumentalize psychoactive drugs, the establishment of and retrieval from a drug memory is required. Here, we propose a new classification of different drug memory subtypes and discuss how they interact during drug instrumentalization learning and retrieval. Understanding the everyday utility and the learning mechanisms of non-addictive psychotropic drug use may help to prevent abuse and the transition to drug addiction in the future. (shrink)

Philosophical and empirical research on bodily awareness has mostly focused so far on bodily disorders – such as anorexia nervosa, somatoparaphrenia, or xenomelia (body integrity dysphoria) – and bodily illusions induced in an experimental setting – such as the rubber hand illusion, or the thermal grid illusion. Studying these conditions can be illuminating to investigate a broad range of issues about the nature, function, and etiology of bodily experience. However, a number of psychoactive compounds can also induce a remarkably wide (...) variety of bodily effects that have received little attention despite their relevance to these issues. Some of these effects are similar to those associated with bodily disorders or experimental bodily illusions, while others appear to be unique. The purpose of this chapter is to provide an overview of these lesser known bodily effects of psychoactive compounds, and outline some ways in which they can bear on recent debates regarding bodily awareness and bodily ownership. (shrink)

This article examines the attempt by the Kingdom of Morocco—a country of pivotal geopolitical importance in the late 1970s and early 1980s—to secure a research reactor. It finds that by treating that reactor as a diplomatic object, we can observe the different diplomatic frameworks in which that object was conceived of, contextualized, and negotiated. The historical emergence of these frameworks occurred in close relationship with the IAEA, which acted as an intermediary linking various administrations, programs, and countries, including Morocco. In (...) the end, this history reveals that the late Cold War nuclear world involved multilateral actions and forces, some of which encouraged Morocco in its bid to acquire a reactor, but others of which left that same reactor orphaned and unfinished. (shrink)

Use of humanities content in American medical education has been debated for well over 60 years. While many respected scholars and medical educators have purported the value of humanities content in medical training, its inclusion remains unstandardized, and the undergraduate medical curriculum continues to be focused on scientific and technical content. Cited barriers to the integration of humanities include time and space in an already overburdened curriculum, and a lack of consensus on the exact content, pedagogy and instruction. Edmund Pellegrino, (...) physician and scholar of the latter twentieth century, spent much of his professional life promoting the value and importance of the humanities in medical education, seeking the best way to incorporate and teach this content in clinically relevant ways. His efforts included the founding of multiple enterprises starting in the 1960s and 1970s to promote human values in medical education, including the Society for Health and Human Values and its Institute on Human Values in Medicine. Regardless of his efforts and those of many others into the current century, the medical humanities remains a curricular orphan, unable to find a lasting home in medical education and training. (shrink)

Prabhpal Singh has defended a relational account of the difference in moral status between fetuses and newborns. Newborns stand in the parent-child relation while fetuses do not, and standing in the parent-child relationship brings with it higher moral status for newborns. Orphans pose a problem for this account because they do not stand in a parent-child relationship. I argue that Singh has not satisfactorily responded to the problem.