Explore the vast range of titles available.

The first-line phase 3 study with tremelimumab did not show an improvement in its primary endpoint, overall survival, and the drug was never licensed.2,7 At least a third of patients randomly assigned to the control group who were alive at the end of the study or censored at any point had received ipilimumab at some stage, which might well have contributed to the negative outcome of the study.3 This conclusion was supported by the finding that outcomes for patients in US and non-US sites were different, with treatment with tremelimumab resulting in significantly better survival in patients treated in non-US centres, where the expanded access programme for ipilimumab was less readily available, and no difference in US centres, where ipilimumab was readily available via the expanded access programme. [...]patient information and consent forms should explicitly state that involvement in a clinical trial might limit access to future treatments that are made available as part of an expanded access programme.

Background Compassionate use is the use of unapproved drugs outside of clinical trials. So far, compassionate use regulations have been introduced in the US, Canada, many European countries, Australia and Brazil, and treatment on a compassionate use basis may be performed in Japan and China. However, there are important differences between relevant regulations in individual countries, particularly that approval by a research ethics committee (institutional review board) is a requirement for compassionate use in some countries (e.g. the US, Spain, and Italy), but not in others (e.g. Canada, the UK, France, and Germany). Discussion The main objective of this article is to present aspects of compassionate use that are important for the discussion of the role of research ethics committees in the review of compassionate use. These aspects include the nature of compassionate use, potential risks to patients associated with the use of drugs with unproven safety and efficacy, informed consent, physicians’ qualifications, and patient selection criteria. Our analysis indicates that the arguments for mandatory review substantially outweigh the arguments to the contrary. Conclusions Approval by a research ethics committee should be obligatory for compassionate use. The principal argument against mandatory ethical review of compassionate use is that it is primarily a kind of treatment rather than biomedical research. Nonetheless, compassionate use is different from standard clinical care and should be subject to review by research ethics committees. First, in practice, compassionate use often involves significant research aspects. Second, it is based on unapproved drugs with unproven safety and efficacy. Obtaining informed consent from patients seeking access to unapproved drugs on a compassionate use basis may also be difficult. Other important problems include the qualifications of the physician who is to perform treatment, and patient selection criteria.

Monitored Emergency Use of Unregistered and Experimental Interventions (MEURI) is an ethical framework developed by the WHO for using unproven interventions in public health emergencies outside the context of medical research. It is mainly intended for use when medical research would be impracticable, but there is still a need to systematically gather data about unproven interventions. As such, it is designed as something of a middle ground between clinical and research ethical frameworks.However, I argue that MEURI does not truly lie at the intersection of clinical care and research. Due to its intent, structure and oversight requirements, it takes on most of the crucial features of research, to the point that it is best understood as a form of research. As a result, cases where MEURI could practicably be applied should instead make use of existing research frameworks. For those circumstances where research is truly impracticable, a more straightforward oversight system than MEURI is needed. While existing practices of compassionate use have some applicability, proposals to make use of clinical ethics committees to oversee unproven interventions may help achieve the right balance in acting in a patient’s best interests when the relevant evidence base is weak.

The President of the United States has repeatedly touted hydroxychlororquine as a likely cure for COVID-19 and urged Americans to try it, stating at one of his media briefings, \"What do you have to lose? What do you have to lose? Take it\" (1). A few others around the world have chimed in to promote one drug or another, this drug in combination with others, or their own favorite untested nostrums. This has led to drug hoarding, the inability of patients who actually need and benefit from certain drugs to access them, and serious side effects and even deaths from self-medication. As it was unclear at the time whether any benefit would come from these interventions, a mechanism called monitored emergency use of unregistered and investigational interventions (MEURI) was created as a bridge to clinical trials in order to curtail unconstrained use of medications.

The Covid-19 pandemic creates an unprecedented threatening situation worldwide with an urgent need for critical reflection and new knowledge production, but also a need for imminent action despite prevailing knowledge gaps and multilevel uncertainty. With regard to the role of research ethics in these pandemic times some argue in favor of exceptionalism, others, including the authors of this paper, emphasize the urgent need to remain committed to core ethical principles and fundamental human rights obligations all reflected in research regulations and guidelines carefully crafted over time. In this paper we disentangle some of the arguments put forward in the ongoing debate about Covid-19 human challenge studies (CHIs) and the concomitant role of health-related research ethics in pandemic times. We suggest it might be helpful to think through a lens differentiating between risk, strict uncertainty and ignorance. We provide some examples of lessons learned by harm done in the name of research in the past and discuss the relevance of this legacy in the current situation.

The Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 signed on May 30, 2018 under President Trump has been championed by patient advocacy groups as a victory for individuals with life threatening illnesses willing to undergo experimental treatment. The act is not a novel idea, but rather a nuanced result of the previous attempts to challenge the US Food and Drug Administration’s (FDA) authority on drug approval and distribution. Currently, right-to-try programs coexist with an already existing expanded access program run by the FDA. The difference is that right-to-try requests eliminate FDA guidance and authorization. The objectives of this study are to review prior historical challenges to the FDA and how they eventually influenced right-to-try movements, examine the law itself and its arguments written by advocates and critics, discuss how its implications fit into the current climate of regulatory flux, and propose the impacts it has on influencing patient care and the scientific process.

Background. Nowadays one of the most critical aspects of innovative cell-based therapies is the unregulated industry, as it is becoming a competitor of the regulated system. Many private clinics, worldwide, advertise and offer cell-based interventions treatments directly to the consumer and this poses a risk to both vulnerable patients and health systems. Several countries have implemented Compassionate Use Programmes (CUP) that provide patients with medicines that have not yet completed the approval pathway, in the event that no reasonable alternative exists. Recently, in the public discourse, compassionate use has been increasingly associated with a patient’s right to try. Thus, the aim of this study was to assess public knowledge of the clinical trials process with specific reference to innovative stem cell treatments, and trust in the institutions responsible for regulatory activities. We also asked people about their “right” to use unregulated therapies. Methods. We developed an ad hoc questionnaire on three main areas of concern and administered it to 300 people in the patient waiting room at an Italian university hospital. Results. Our findings suggest that people have a good knowledge of the clinical trials process and trust in healthcare institutions. Nonetheless, one person in two believes it is a right to use unregulated therapies. Conclusions.We stress the need, in the age of cellular therapies, for a commitment to support vulnerable patients and to strengthen awareness among the public about the substantial boundary that differentiates experimental therapies from unproven therapies. There should not be a “right to try” something that is unsafe but rather approved treatments and in line with good clinical practice. The trend, which emerged on this issue from our study, is quite different, confirming the urgent need to improve health information so that it is as complete as possible.

A month ago, an investigatory television programme, The Hyena, reported that children with incurable diseases such as spinal muscular atrophy were being denied supposedly important treatment, and Italian show-business personalities joined the call to relax rules on stem-cell treatment. Last May, a delegation including representatives of the Italian Medicines Agency (AIFA) and the ISS, the health ministry's national institute, visited the Brescia lab and reported chaotic conditions: ethics-committee approvals had been based on inadequate information, and there were no detailed protocols or patient follow-up, for example.

Background When a new intervention or drug is developed, this has to pass through various phases of clinical testing before it achieves market approval, which can take many years. This raises an issue for drugs which could benefit terminally ill patients. These patients might set their hopes on the experimental drug but are unable to wait since they are likely to pass away before the drug is available. As a means of nevertheless getting access to experimental drug, many seriously ill and terminally ill patients are therefore very willing to participate in randomised controlled trials. However, only very few terminally ill patients are able to actually participate, and those that do participate are at risk of participating solely as a way of getting experimental drugs. Currently, there are, however, ways of getting access to drugs that have not (yet) gained market approval. One such mean is via expanded access or compassionate use programs where terminally ill patients receive experimental new drugs that are not yet market approved. In this paper, I examine some of the common justifications for such programs. Main body The most frequently voiced justifications for compassionate use or expanded access programs could be put in one of three categories. First, there are justifications of justice, where compassionate use programs could be seen as a just or fair way to distribute experimental new drugs to patients who are denied access to RCT’s through no fault of their own. Second, such programs could be justified by reference to the ethical principle of beneficence where it could be claimed that terminally ill patients stand to benefit greatly at very little risk (as they are already dying). Third, there are considerations of autonomy where, it is claimed, patients should be able to exercise their autonomy and have access to such drugs if that is there free choice and they are fully aware of the risks associated with that choice. Short conclusion In this paper, I argue currently all justifications are potentially problematic. If they truly form the basis for justification, compassionate use programs should be designed to maximize justice, beneficence and autonomy.