Nancy M. P. King

Clinical Trials and Medical Care: Defining the Therapeutic Misconception

A key component of informed consent to participate in medical research includes understanding that research is not the same as treatment.

Ethical Principles Guiding Research on Child and Adolescent Subjects

Understanding the ethical principles that should guide research with child and adolescent participants is an essential task for researchers. Principles do not always yield final or uncontroversial answers, but they do serve to clarify and justify decisions, and their use makes individual decisions and research policies more public and open to examination. The principles of scientific importance, scientific soundness, respect for autonomy, beneficence, nonmaleficence, utility, and justice are described herein. The embodiment of these principles in the federal guidelines governing research is discussed, with attention to the differences between wronging and harming subjects and the meaning of informed consent.

The OHRP and SUPPORT - Another view

A group of physicians, bioethicists, and scholars in allied fields agrees with the Office for Human Research Protections about the informed-consent documents in SUPPORT.

Challenges in vector and trial design using retroviral vectors for long-term gene correction in hematopoietic stem cell gene therapy.

Over the past two decades, incredible progress has been made using gene therapy for inherited severe immunodeficiency disorders, such as X-linked severe combined immunodeficiency disorder (SCID-X1) and adenosine deaminase deficiency–severe combined immunodeficiency disorder (ADA-SCID).1,2,3 However, for reasons that remain unclear, gene transfer for SCID-X1 has also been associated with some cases of vector-induced leukemia whereas no cases have been seen in the ADA-SCID trials despite the common use of g-retroviral vectors. The first case was reported in a French gene transfer trial for SCID-X1.4 Over the next six years, an additional three cases were reported in that trial and one in a second SCID-X1 trial that enrolled a combined total of 20 subjects.2 Unfortunately, genotoxicity would not remain confined to SCID-X1. Recent reports of insertional mutagenesis leading to myelodysplastic syndrome in a trial for chronic granulomatous disease and a case of leukemia in a trial for Wiskott-Aldrich syndrome (WAS), both of which used g-retroviral vectors, underscored that this type of toxicity can also apply to other disease settings.5,6,7 In all these cases, insertion of the g-retroviral vector near known proto-oncogenes led to enhancer-mediated expression of these proto-oncogenes.

An Open Letter to Institutional Review Boards Considering Northfield Laboratories' PolyHeme® Trial

At the time of this writing, a widely publicized, waived-consent trial is underway. Sponsored by Northfield Laboratories, Inc. (Evanston, IL) the trial is intended to evaluate the emergency use of PolyHeme®, an oxygen-carrying resuscitative fluid that might prevent deaths from uncontrolled bleeding. The protocol allows patients in hemorrhagic shock to be randomized between PolyHeme® and saline in the field and, still without consent, randomized between PolyHeme® and blood after arrival at an emergency department. The Federal regulations that govern the waiver of consent restrict its applicability to circumstances where proven, satisfactory treatments are unavailable. Blood—the standard treatment for hemorrhagic shock—is not available in ambulances but is available in hospitals. The authors argue that the in-hospital stage of the study fails to meet ethical and regulatory standards.

Ethical issues in stem cell research and therapy

Rapid progress in biotechnology has introduced a host of pressing ethical and policy issues pertaining to stem cell research. In this review, we provide an overview of the most significant issues with which the stem cell research community should be familiar. We draw on a sample of the bioethics and scientific literatures to address issues that are specific to stem cell research and therapy, as well as issues that are important for stem cell research and therapy but also for translational research in related fields, and issues that apply to all clinical research and therapy. Although debate about the moral status of the embryo in human embryonic stem cell research continues to have relevance, the discovery of other highly multipotent stem cell types and alternative methods of isolating and creating highly multipotent stem cells has raised new questions and concerns. Induced pluripotent stem cells hold great promise, but care is needed to ensure their safety in translational clinical trials, despite the temptation to move quickly from bench to bedside. A variety of highly multipotent stem cells - such as mesenchymal stem/stromal cells and stem cells derived from amniotic fluid, umbilical cord blood, adipose tissue, or urine - present the opportunity for widespread biobanking and increased access. With these increased opportunities, however, come pressing policy issues of consent, control, and justice. The imperatives to minimize risks of harm, obtain informed consent, reduce the likelihood of the therapeutic misconception, and facilitate sound translation from bench to bedside are not unique to stem cell research; their application to stem cell research and therapy nonetheless merits particular attention. Because stem cell research is both scientifically promising and ethically challenging, both the application of existing ethical frameworks and careful consideration of new ethical implications are necessary as this broad and diverse field moves forward.

RAC Oversight of Gene Transfer Research: A Model Worth Extending?

linical gene transfer research (GTR) has both a unique history and a complex and layered system C of research oversight, featuring a unique review body, the Recombinant DNA Advisory Committee (RAC).I This paper briefly describes the process of decision-making about clinical GTR, considers whether the questions, problems, and issues raised in clinical GTR are unique, and concludes by examining whether the RACs oversight is a useful model that should be reproduced for other similar areas of clinical research.2

Transparency in Neonatal Intensive Care

Medical teams care for severely premature infants under conditions of emergency and uncertainty that make parental involvement very difficult. Parents can be invited into a decisional relationship with the team that enables them to assess more fully the meaning of their childs illness.

Female genital mutilation

The traditional custom of ritual cutting and alteration of the genitalia of female infants, girls, and adolescents, referred to as female genital mutilation (FGM), persists primarily in Africa and among certain communities in the Middle East and Asia. Immigrants in the United States from areas where FGM is endemic may have daughters who have undergone a ritual genital procedure or may request that such a procedure be performed by a physician. The American Academy of Pediatrics (AAP) believes that pediatricians and pediatric surgical specialists should be aware that this practice has serious, life-threatening health risks for children and women. The AAP opposes all forms of FGM, counsels its members not to perform such ritual procedures, and encourages the development of community educational programs for immigrant populations.

En Route to Ethical Recommendations for Gene Transfer Clinical Trials

In Geneva, Switzerland, on 2–3 April 2007, Clinigene-NoE (the European Network for the Advancement of Clinical Gene Transfer and Therapy) and Consert (program on Concerted Safety and Efficiency Evaluation of Retroviral Transgenesis for Gene Therapy of Inherited Diseases)—two European Union (EU) programs that aim to facilitate the development of sound, safe, and effective human gene transfer—held a joint “think tank” on the ethics of human clinical gene transfer (GT).1