Compelled to Volunteer: American Conscientious Objectors to World War II as Subjects of Medical Research

This dissertation is a history of the use of World War II-era American conscientious objectors as the subjects of medical research. Under the Selective Training and Service Act of 1940, conscientious objectors had two choices: provide noncombatant service within the military or provide work of national importance under civilian direction under the auspices of a program called Civilian Public Service (CPS). Conscientious objectors who chose assignment to CPS were placed in camps in which the men labored on a work project authorized by the U.S. Selective Service System, the government entity that administered the draft. At the outset of the CPS program, the camps were modeled after the work camps of the Civilian Conservation Corps, a New Deal jobs program. Over time, and largely due to protests that such Civilian Conservation Corps-type forestry and soil conservation work assignments were not the promised work of national importance, other types of CPS camps were developed, with work projects dealing with public health, custodial care for the mentally disabled, or scientific research. In the later, which became commonly known as the guinea pig units, over five hundred conscientious objectors voluntarily participated as research subjects for a diverse assortment of scientific studies, including projects that dealt with infectious diseases, diet, frostbite, psycho-acoustics, and the impacts of temperature extremes and of altitude. In addition to describing the creation and operation of the guinea pig units, this dissertation examines the use of American World War II conscientious objectors as research subjects in light of two specific questions: first, why did these men volunteer to be guinea pigs? And second, was the use of World War II-era conscientious objectors as research subjects in keeping with the ethical standards of the time? This dissertation draws upon a diverse array of sources to answer the question of motivation from the volunteers' perspectives. Likewise, this dissertation relies upon a wide array of sources to piece together what researchers of the day, both military and civilian, would have considered acceptable and unacceptable uses of people in the name of research

Paying for Unapproved Medical Products

This symposium article examines the use of investigational (un-approved) medical products in the United States, with particular focus on who pays for this use. In the United States, the question of who pays for the use of approved medical products for their intended indications is complicated enough, with some expenses borne by private payers, some by public payers, some covered as charity care, and some paid out of pocket by patients. A separate question is off-label use, in which an approved medical product is used for an unapproved indication. In this article, we focus on a narrower issue: what entities in the United States pay for access to unapproved medical products, e.g., investigational drugs, devices, or diagnostics that have not (yet) received Food and Drug Administration (“FDA”) approval. We examine the various forms of preapproval access (“PAA”) to experimental medical products available in the United States—clinical trials and non-trial preapproval access via the Expanded Access (“EA”) and Right to Try (“RTT”) pathways. For each, this paper analyzes which entity—individual, insurer, sponsor, or other—bears the cost and what limitations or caps, if any, exist on these costs. This paper considers various proposed novel payment mechanisms that may permit more equitable use of investigational medical products. Part I outlines payment-related disparities in access in- grained in the current United States healthcare system. Part II focuses on access in the context of clinical trials, which most payers have begun to cover, but where remaining uncovered expenses can disincentivize participation in clinical trials, even among those highly motivated to enroll. Part III discusses non-trial preapproval access pathways, specifically Expanded Access and Right to Try, where coverage is scant. Part IV briefly deals with investigational products (such as stem cell treatments) that are available via unregulated or underregulated direct-to-consumer sales. Part V then re- views the ethical considerations inherent in paying for investigational medical products

Addressing the dichotomy between individual and societal approaches to personalised medicine in oncology

Academic, industry, regulatory leaders and patient advocates in cancer clinical research met in November 2018 at the Innovation and Biomarkers in Cancer Drug Development meeting in Brussels to address the existing dichotomy between increasing calls for personalised oncology approaches based on individual molecular profiles and the need to make resource and regulatory decisions at the societal level in differing health-care delivery systems around the globe. Novel clinical trial designs, the utility and limitations of real-world evidence (RWE) and emerging technologies for profiling patient tumours and tumour-derived DNA in plasma were discussed. While randomised clinical trials remain the gold standard approach to defining clinical utility of local and systemic therapeutic interventions, the broader adoption of comprehensive tumour profiling and novel trial designs coupled with RWE may allow patient and physician autonomy to be appropriately balanced with broader assessments of safety and overall societal benefit. (C) 2019 Published by Elsevier Ltd

Paying for Unapproved Medical Products

This symposium article examines the use of investigational (un-approved) medical products in the United States, with particular focus on who pays for this use. In the United States, the question of who pays for the use of approved medical products for their intended indications is complicated enough, with some expenses borne by private payers, some by public payers, some covered as charity care, and some paid out of pocket by patients. A separate question is off-label use, in which an approved medical product is used for an unapproved indication. In this article, we focus on a narrower issue: what entities in the United States pay for access to unapproved medical products, e.g., investigational drugs, devices, or diagnostics that have not (yet) received Food and Drug Administration (“FDA”) approval. We examine the various forms of preapproval access (“PAA”) to experimental medical products available in the United States—clinical trials and non-trial preapproval access via the Expanded Access (“EA”) and Right to Try (“RTT”) pathways. For each, this paper analyzes which entity—individual, insurer, sponsor, or other—bears the cost and what limitations or caps, if any, exist on these costs. This paper considers various proposed novel payment mechanisms that may permit more equitable use of investigational medical products. Part I outlines payment-related disparities in access in- grained in the current United States healthcare system. Part II focuses on access in the context of clinical trials, which most payers have begun to cover, but where remaining uncovered expenses can disincentivize participation in clinical trials, even among those highly motivated to enroll. Part III discusses non-trial preapproval access pathways, specifically Expanded Access and Right to Try, where coverage is scant. Part IV briefly deals with investigational products (such as stem cell treatments) that are available via unregulated or underregulated direct-to-consumer sales. Part V then re- views the ethical considerations inherent in paying for investigational medical products

Safety Issues in Cell-Based Intervention Trials

We report on the deliberations of an interdisciplinary group of experts in science, law, and philosophy who convened to discuss novel ethical and policy challenges in stem cell research. In this report we discuss the ethical and policy implications of safety concerns in the transition from basic laboratory research to clinical applications of cell-based therapies derived from stem cells. Although many features of this transition from lab to clinic are common to other therapies, three aspects of stem cell biology pose unique challenges. First, tension regarding the use of human embryos may complicate the scientific development of safe and effective cell lines. Second, because human stem cells were not developed in the laboratory until 1998, few safety questions relating to human applications have been addressed in animal research. Third, preclinical and clinical testing of biologic agents, particularly those as inherently complex as mammalian cells, present formidable challenges, such as the need to develop suitable standardized assays and the difficulty of selecting appropriate patient populations for early phase trials. We recommend that scientists, policy makers, and the public discuss these issues responsibly, and further, that a national advisory committee to oversee human trials of cell therapies be established