Zusammenfassung Compassionate Use beschreibt die Anwendung zulassungsüberschreitender Arzneimittel für Patient*innengruppen, die an einer lebensbedrohlichen oder zu einer schweren Behinderung führenden Erkrankung leiden, ohne dass eine alternative Therapieoption besteht. An Ärzt*innen vorbei werden solche Programme ausschließlich von Pharmaunternehmen initiiert, was viele ethische Konflikte mit sich bringt. Eine neue Dimension erreichte das 2020 gestartete Programm für _Onasemnogenum abeparvovecum_ zur Therapie von Spinaler Muskelatrophie bei Kindern, welches die Krankheit nach nur einmaliger Gabe stoppen sollte. Die globale Allokation von nur 100 zur Verfügung gestellten (...) Dosierungen per Losverfahren stellte ein Novum bei der Allokation in Compassionate Use-Programmen dar und wurde vielfach kritisiert. Diese Arbeit untersucht mögliche alternative Allokationsprinzipien auf das Beispiel von _Onasemnogenum abeparvovecum_. Für jedes in Frage kommende Prinzip der Allokation medizinischer Güter bestehen Aspekte, die im Hinblick auf die drängende Zeit und die globale Verteilung bedacht werden müssen. Dies lässt einige Prinzipien wie First-Come-First-Served vernachlässigbar erscheinen. Verbliebene Prinzipien werden hierarchisch geordnet, um einen Algorithmus abzuleiten, der eine Alternative zum Losverfahren darstellen kann. Eine Kombination von Teilnahmebereitschaft bei Forschung, Dringlichkeit und Erfolgsaussicht (bezogen auf die Existenz supportiver Therapieoptionen) kann in ähnlichen Fällen bei zukünftigen globalen Compassionate Use-Programmen bei Kindern erwogen werden. Da universelle Algorithmen nur schwer definierbar sind, sollten Allokationskriterien in jedem Fall durch ein unabhängiges Expert*innengremium diskutiert werden. Sowohl die Konstitution eines solchen Gremiums sowie deren verpflichtende Konsultierung sind gefordert, um für Entlastung aller Beteiligten zu sorgen und Willkür vorzubeugen. (shrink)

Definition of the problem Compassionate use is the use of unapproved drugs in groups of patients suffering from a disease that, in the absence of an alternative treatment option, is life-threatening or leads to severe disability. Physicians are not in charge because access to the drug is only granted by pharmaceutical companies, which comes along with many ethical issues. Launched in 2020, the program of Onasemnogenum abeparvovecum against spinal muscular atrophy in children reached a new dimension. The intent of this (...) drug is to stop the progression of the disease with just a single dose, but the company limited the doses in the program to only 100. The global allocation was by lottery, which was considered a novelty in compassionate use history and therefore widely criticized. This paper investigates alternative allocation principles. Arguments Each possible principle is accompanied by many aspects that need to be considered with regard to urgency and global distribution. This makes some principles like first-come-first-served seem negligible. Remaining principles are ordered hierarchically to derive an algorithm that can represent an alternative to a lottery. A combination of willingness to participate in research, urgency, and likelihood of success (relative to the availability of supportive treatment options) may be considered in similar cases in future global compassionate use programs with children. Conclusion Since universal algorithms are difficult to define, allocation criteria should always be discussed by an independent panel of experts. Both the constitution of such a panel and its mandatory consultation are necessary in order to decrease the burden for all those involved and to prevent arbitrariness. (shrink)

Clarifying the meaning of ethical concepts is fundamental for medical ethics. Many of the best papers in the Journal of Medical Ethics have advanced our understanding of the limits and implications of ethical concepts. This issue includes a number of papers that give us reason to reflect on the use, implications and grounding of some important ethical concepts. The concepts we use are rarely neutral. For example, those arguing against assisted dying are more likely to use terms such as ‘euthanasia’ (...) or perhaps even ‘killing’, while those arguing in favour of it might opt for ‘aid in dying’ or ‘facilitated aid in dying’. Of course, these are different concepts and do not mean the same thing, but the different associations and implications of concepts can weaken or strengthen a position. Woollard analyses the way in which the terms used in public information and discussions about breastfeeding can be morally loaded and thereby cause guilt or detract from the effectiveness of public information.1 She argues that normative concepts such as ‘harm’ or ‘dangerous’ and slogans such as ‘breast is best’ can imply moral duties or criticism when it is unhelpful and inappropriate to do so. She does this by showing how concepts such as ‘harm’ and ‘risk’, …. (shrink)

BackgroundThe biopharmaceutical industry operates at the intersection of life sciences, clinical research, clinical care, public health, and business, which presents distinct operational and ethical challenges. This setting merits focused bioethics consideration to complement legal compliance and business ethics efforts. However, bioethics as applied to a biopharmaceutical industry setting often is construed either too broadly or too narrowly with little examination of its proper scope.Main textAny institution with a scientific or healthcare mission should engage bioethics norms to navigate ethical issues that (...) arise from the conduct of biomedical research, delivery of clinical care, or implementation of public health programs. It is reasonable to assume that while bioethics norms must remain constant, their application will vary depending on the characteristics of a given setting. Context “specification” substantively refines ethics norms for a particular discipline or setting and is an expected, needed and progressive ethical activity. In order for this activity to be meaningful, the scope for bioethics application and the relevant contextual factors of the setting need to be delineated and appreciated. This paper defines biopharmaceutical bioethics as: the application of bioethics norms (concepts, principles, and rules) to the research, development, supply, commercialization, and clinical use of biopharmaceutical healthcare products. It provides commentary on this definition, and presents five contextual factors that need to be considered when applying bioethics norms to a biopharmaceutical industry setting: (1) dual missions; (2) timely and pragmatic guidance; (3) resource stewardship; (4) multiple stakeholders; and (5) operational complexity.ConclusionUnderstanding the scope of the biopharmaceutical enterprise and contextual factors of a biopharmaceutical industry setting is foundational for the application of bioethics norms. Establishing a common language and approach for biopharmaceutical bioethics will facilitate breadth and depth of discussion and subsequent implementation to benefit patients, the healthcare system and society. (shrink)

BackgroundExpanded access is the use of investigational drugs (IDs) outside of clinical trials. Generally it is performed in patients with serious and life-threatening diseases who cannot be treated satisfactorily with authorized drugs. Legal regulations of expanded access to IDs have been introduced among others in the USA, the European Union (EU), Canada and Australia. In addition, in the USA an alternative to expanded access is treatment under the Right-to-Try law. However, the treatment use of IDs is inherently associated with a (...) number of ethically relevant problems.Main textThe objective of this article is to present a coherent framework made up of eight requirements which have to be met for any treatment use of an ID to be ethical. These include a justified need for the use of an ID, no threat to clinical development of the ID, adequate scientific evidence to support the treatment, patient’s benefit as the primary goal of the use of an ID, informed decision of a patient, fair access of patients to IDs, independent review, as well as the dissemination of treatment results.ConclusionsWhile this framework is essentially consistent with the legal regulations of expanded access of the USA, the EU, Canada and Australia, it is substantially wider in scope because it addresses some important issues that are not covered by the regulations. Overall, the framework that we developed minimizes the risks and threats, and maximizes potential benefits to each of the four key stakeholders involved in the treatment use of IDs including patients, doctors, drug manufacturers, and society at large. (shrink)