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The article describes the case of an adolescent who has end stage manifestations of her rare underlying genetic disease and is soon to become a ward of state. Topics include the ethical question surrounding the case, states that addressed the issue of surrogate consent for research as of 2010, and possible solution if the ethical, legal, and practical issues cannot be quickly resolved.

The article focuses on extracting real world data (RWD) from compassionate use and expanded access programs in the wake of the COVID-19 pandemic. Topics discussed include the U.S. Food and Drug Administration's (FDA's) system of expanded access, the expansion of the use of RWD within trial themselves in many jurisdictions, and argument on an optimal pragramatic expanded access program.

The article offers information on the preapproval nontrial access to investigational drugs and biologics, expanded access (EA) and right to try (RTT). It mentions the best way for patients to gain access to investigational drugs and therapeutics is by participating in clinical trials; and also mentions patients must be ineligible for clinical trials for the desired investigational drug in both pathways.

The article informs that physicians' ethical and professional obligations about Right-to-Try amidst a pandemic. Topics include obligations within that relationship can conflict with a broader, more general public health ethic; and knowledge with the evolving clinical evidence about the pathophysiology of COVID-19, and render a decision about its potential benefits for patients.

The article focuses on Pediatric research that provides no direct benefit to participants raises ethical questions regarding fundamental permissibility and acceptable risks. Topic include children with Sickle Cell Disease (SCD) to face morbidity and premature mortality, novel therapies for SCD are needed.

The article offers information on the normative analysis of the human subjects participating in clinical trials has been dominated by issues of consent, coercion, and undue inducement. It mentions that increasing payment would make participation less exploitative; and also mentions the move toward a social justice framework for protecting professional guinea pigs is a welcome addition to the existing efforts.

The article discusses the model of communication between physicians and patients and their families regarding nonstandard treatment in order to access unapproved, investigated drugs.

The article discusses the challenges of resource distribution in the Expanded Access Program (EAP) for treating Spinal muscular atrophy 1. It talks about the need to increase the capacity to take care of more patients, avoid treatment delays and to determine an order in which patients can be treated.

The recent Ebola outbreak in West Africa began in the spring of 2014 and has since caused the deaths of over 6,000 people. Since there are no approved treatments or prevention modalities specifically targeted at Ebola Virus Disease (EVD), debate has focused on whether unproven interventions should be offered to Ebola patients outside of clinical trials. Those engaged in the debate have responded rapidly to a complex and evolving crisis, however, and this debate has not provided much opportunity for in-depth analysis. Additionally, the existing literature on access to unproven therapies has focused on contexts like HIV/AIDS and oncology, which are very different than the Ebola epidemic. In this paper, we examine the ethical issues surrounding access to unproven therapies in the context of the recent Ebola outbreak to yield new insights about this controversial and unsettled issue. We argue first that, in this context, the interests of patients in obtaining access to unproven therapies are not fully aligned with the interests of their providers and drug developers. Second, we focus on the resource constraints facing providers, funders, and patients and conclude that they often counsel against the use of unproven interventions against EVD. [ABSTRACT FROM AUTHOR]

There are competing ethical concerns when it comes to designing any clinical research study. Clinical trials of possible treatments for Ebola virus are no exception. If anything, the competing ethical concerns are exacerbated in trying to find answers to a deadly, rapidly spreading, infectious disease. The primary goal of current research is to identify experimental therapies that can cure Ebola or cure it with reasonable probability in infected individuals. Pursuit of that goal must be methodologically sound, practical and consistent with prevailing norms governing human subjects research. Some maintain that only randomized controlled trials (RCTs) with a placebo or standard-of-care arm can meet these conditions. We maintain that there are alternative trial designs that can do so as well and that sometimes these are preferable to RCTs. [ABSTRACT FROM PUBLISHER]

The author responds to the article "Selecting the right tool for the job," by Arthur Caplan, Carolyn Plunkett, and Bruce Levin that appeared within the issue, in which they presented an argument against randomized controlled trials of investigational interventions for Ebola virus disease (EVD). Topics mentioned include the difference between the goals of research during an epidemic and those under ordinary medical circumstances, and the reasons for favoring randomized selection trials.

In the article, the authors discuss issues involved in the design of clinical trials for establishing safe and effective treatments for Ebola virus disease (EVD) as of April 2015. Also cited are the criticism hurled by A. L. Caplan, C. Plunkett, and B. Levin on the use of the best accessible standard of care as a control group (SOC-RCT), the proposed randomized selection (RS) trial proposed by Caplan's group, and the concerns raised by Doctors Without Borders on the issues.

The authors explain the placement of unproven interventions within a clinical ethical taxonomy of treatments in Ebola virus disease (EVD) and how it will affect whether or not they are ethically permissible, obligatory or impermissible. Topics mentioned include the importance of delivering the interventions with sustained excellent infection control, and the factors that must be considered when providing therapies to patients with potential EVD.

Many health care systems include programs that allow patients in exceptional circumstances to access medical interventions of as yet unproven benefit. In this article we consider the ethical justifications for—and demands on—these special access programs (SAPs). SAPs have a compassionate basis: They give patients with limited options the opportunity to try interventions that are not yet approved by standard regulatory processes. But while they signal that health care systems can and will respond to individual suffering, SAPs have several disadvantages, including the potential to undermine regulatory and knowledge-generation structures that constitute significant public goods. The “balance” between these considerations depends in part on how broadly SAPs are used, but also on whether SAPs can be made to contribute to the generation of knowledge about the effects of health interventions. We argue that patients should usually be required to contribute outcome data while using SAPs. [ABSTRACT FROM PUBLISHER]

The article offers information on Response to Open Peer Commentary "Making It Count: Extracting Real World Data from Compassionate Use and Expanded Access Programs. It mentions Randomizing only a fraction of the patients that participated in the expanded access program would have yielded far more actionable insights—urgently needed in times of a pandemic.

Clinical research under the usual regulatory constraints may be difficult or even impossible in a public health emergency. Regulators must seek to strike a good balance in granting as wide therapeutic access to new drugs as possible at the same time as gathering sound evidence of safety and effectiveness. To inform current policy, I reexamine the philosophical rationale for restricting new medicines to clinical trials, at any stage and for any population of patients (which resides in the precautionary principle), to show that its objective to protect public health, now or in the future, could soon be defeated in a pandemic. Providing wider therapeutic access and coordinating observations and natural experiments, including service delivery by cluster (wedged cluster trials), may provide such a balance. However, there are important questions of fairness to resolve before any such research can proceed. [ABSTRACT FROM AUTHOR]

In the article, the authors present their opinion on the proper design of clinical trials to find treatment of contagious diseases like the Ebola virus disease. They support the position by Caplan, Plunkett, and Levin against the use of randomized controlled trial (RCT) in finding treatments against such diseases. They also discuss the move to develop new improved personal protective equipment (PPE) against such diseases.

In the article, the author discusses issues in the design of clinical trials to find treatments for Ebola virus disease as of April 2015. She claims that the issues are similar to those raised during the early years of AIDS trials. Also cited are the criticisms by A. L. Caplan, C. Plunkett, and B. Levin on randomized control trial (RCT), the use of best available supportive care (BASC) control group, and the proposed non-RCT design.

The author responds to an article within the issue entitled "Selecting the right tool for the job," by A. L. Caplan, C. Plunkett, and B. Levin, about the need for a scientifically and ethically valid approach to fight the Ebola outbreak. Topics mentioned include the authors' misrepresentations of randomized controlled trials for Ebola, and their reasons for preferring estimation instead of testing in trials. Also mentioned are cluster-level randomization and adaptive treatment allocation.

The authors discuss the article "Examining the ethics of clinical use of unproven interventions outside of clinical trials during the Ebola epidemic," by S. K. Shah, D. Wendler and M. Danis which appeared within the issue. Topics include the medical situations in which physicians are permitted and obligated to offer interventions that have not been proven, and the pillars of medical ethics which support the argument that physicians are ethically required to provide unproven treatments.

The authors comment on an article about the use of randomized controlled trials (RCT) for experimental treatments for Ebola virus disease (EVD) in West Africa, by A. Caplan, C. Plunkett and B. Levin which was published within the issue. Topics mentioned include the usefulness of RCT over other trial designs, the hindering factors for the development of effective interventions for EVD, and the different approaches to understanding infectious diseases like Ebola.

The article discusses data donation for the learning health care system, including special access programs (SAPs), particularly in the area of amyotrophic lateral sclerosis (ALS) research. Topics discussed include publication of findings on lithium use by patient-powered research network (PPRN) PatientsLikeMe.com, SAPs becoming conditional on systematic data submission (data-SAP) by patients, and risks and benefits of having data-SAP in place and as an early access condition.

The article discusses the issue of access of people with catastrophic illnesses to unapproved medical interventions and investigational new agents. Topics discussed include voluntary participation in clinical research to guarantee clinical research integrity and not as means to gain access to investigational new agents, sharing of patient information and need to ensure efficient evaluation of available data, and equitable access of clinically eligible patients to investigational new agents.

The article discusses how the implementation by the U.S. Food and Drug Administration (FDA) of expanded access program (EAP) for investigational drugs and biological products addresses concerns on special access programs (SAP). Topics discussed include patients granted expanded access are participants in an FDA-regulated clinical investigation conducted under an investigational new drug (IND), and FDA may require submission of intermediate-size treatment IND to ensure uniform data collection.

The article presents a proposal describing integration of special access programs (SAPs) into the regulatory structure of a clinical research trial. Topics discussed include incorporation of data from SAP into randomized controlled trial (RCT) as real-life data, obtained from participants with serious life-threatening illnesses, can be provided by SAPs, potential of drug or device development improvement with integration, and possible better estimation of side effects and dosages from SAP data.

The author discusses research during public health emergencies in response to the article "Ethics of clinical science in a public health emergency: Drug discovery at the bedside," published elsewhere in the issue by S. J. L. Edwards. Topics include cluster randomized controlled trials (CRCTs), the precautionary principle, and drug trials.

The author discusses a free-market strategy in clinical data collection in response to the article "Ethics of clinical science in a public health emergency: Drug discovery at the bedside," published elsewhere in the issue by Sarah J. L. Edwards. Topics include drug regulation and development, randomized controlled trials (RCTs), and differences between individual- and population-level ethics.

The author reflects on appropriate research practices during pandemics in response to the article "Ethics of clinical science in a public health emergency: Drug discovery at the bedside," published elsewhere in the issue by S. J. L. Edwards. Topics include randomized trials in emergency situations, case fatality rate (CFR), and experimental design.

The article focuses on assistance of pharmaceutical firm Janssen by New York University School of Medicine's Division of Medical Ethics in development of a framework for allocation of drug daratumumab and application of the same for allocation of drug nusinersen. Topics discusssed include creation of Compassionate Use Advisory Committee, requirement of advanced care for patients suffering from respiratory insufficiency, and no supply restrictions on nusinersen from biotechnology firm Biogen.

The article discusses expanded access programs describing the usage of experimental therapy that benefits research participants. Topics discussed information on Food and Drug Administration's approval of nusinersen for the treatment of spinal muscular atrophy (SMA), justification for patient selection criteria on the bases of utilitarian and deontological arguments, and incremental improvement in well-being.

The author comments on the article "Selecting the Right Tool for the Job," by A. L. Chaplan, C. Plunkett and B. Levin published within the issue, which looked into the question regarding experimental interventions for Ebola virus disease (EVD). Topics mentioned include the growing concern on the lack of effective therapeutic agents against EVD, the authors' proposed adaptive trial design that has no concurrent control group, and the options available for policymakers for fighting the disease.

An introduction is presented in which the editor discusses the report on the issue of expanded access programs (EAPs) or compassionate use for access to unapproved drugs by patients, within the issue.

The author reflects on potential clinical science conflicts of interest during public health emergencies in response to the article "Ethics of clinical science in a public health emergency: Drug discovery at the bedside," published elsewhere in the issue by S. J. L. Edwards. Topics include the H1N1 influenza pandemic in 2009, pharmaceutical companies, and drug research and development (R&D).

The authors discuss the use of stepped wedge cluster and other experimental designs in response to the article "Ethics of clinical science in a public health emergency: Drug discovery at the bedside," published elsewhere in the issue by S. J. L. Edwards. Topics include randomized trials in emergency situations, interventions and controls, and sequential design and analysis.

A response by Arthur L. Caplan, Carolyn Plunkett and Bruce Levin to the letters to the editor about their article "Selecting the Right Tool for the Job" about the treatments for Ebola virus disease (EVD) in a 2015 issue is presented.

A response by Philip M. Rosoff to a letter to the editor about his article "Caring for the Suffering: Meeting the Ebola Crisis Responsibly" in a 2015 issue is presented.

A response from Mary Jean Walker et al, to a letter to the editor, in response to their article "Ethical Justifications for Access to Unapproved Medical Interventions: An Argument for (Limited) Patient Obligations," is presented.

The article focuses on a case in research ethics that explores the ethical obligations concerning open-label extension trials in groups of patients in whom the drug did not demonstrate sufficient efficacy to obtain regulatory approval. It discusses the results of a case study in which subjects were enrolled in a randomized clinical trial of an investigational drug for pulmonary hypertension that was followed by an open-label extension.