Ethics framework for treatment use of investigational drugs

Abstract

Background Expanded 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 text The 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. Conclusions While 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.

Should the governance of individual treatment attempts (″Individuelle Heilversuche ″) include praxis evaluation? Results from qualitative stakeholder interviews.

“…Relatively strong normative arguments, for example, can be listed for prospectively reviewing ITAs that employ highly experimental, first-in-human therapies. In these cases, it is particularly difficult for physicians to correctly assess the risks and benefits, and conflicts of interest could be more severe [7]. In the USA, an established review practice for the use of experimental drugs outside of clinical research already exists.…”

“…As nonstandard therapies often lack evidence from clinical trials, ITAs are associated with increased uncertainty regarding their risk-benefit ratio [2]. This uncertainty addresses several ethical challenges [6] that have also been discussed in the context of experimental or unapproved therapies [7-9], off-label uses [10, 11], or first-in human therapies [12]. For example, the higher the uncertainty is, the more intuition-based the assessment of risks and benefits.…”

Characteristics of the Compassionate Use Program in Japan: An Analysis of Expanded Access Clinical Trials from 2016 to 2021

“…[2][3][4][5][6] Compassionate use (CU) is a system that allows unapproved investigational drugs to be used on a case-by-case basis to treat serious life-threatening diseases for which existing drugs are ineffective from an ethical or humane perspective. 7 CU generally requires several unique conditions to be met. Implementation in public systems, such as laws, and the exceptional use of unapproved investigational drugs under specific conditions are among the prerequisites.…”

“…Compassionate use (CU) is a system that allows unapproved investigational drugs to be used on a case‐by‐case basis to treat serious life‐threatening diseases for which existing drugs are ineffective from an ethical or humane perspective 7 . CU generally requires several unique conditions to be met.…”

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. Special article: compassionate use and clinical trial on CAR-T cells

“…In Europe, the EMA agency additionally has the attribution of evaluating the requisitions for the compassionate use of an experimental product, however, each member-state has its own system for dealing with this issue, more or less liberally. 11 , 12 …”