To judge from the rash of recent law review articles, it is a miracle that research with human subjects in the U.S. continues to draw breath under the asphyxiating heel of the rent-seeking, creativity-stifling, jack-booted bureaucrethics that is the current system of research ethics oversight and review. Institutional Review Boards (IRBs), sometimes called Research Ethics Committees (RECs), have been accused of perpetrating “probably the most widespread violation of the First Amendment in our nation's history,” resulting in a “disaster, not only for academics, but for the whole nation.” One member of the President's Council on Bioethics went so far as to assert, “There has been no greater damage to academic freedom in the United States in my lifetime. And my lifetime encompasses McCarthy and it encompasses political correctness, both.” Locked in the bureaucratic “iron cage” of IRB oversight, critics charge that researchers have been transformed into a vulnerable, exposed population, subject to domination, that has been likened in one case to a kind of “Tuskegee in reverse.”

Criticisms of the traditional clinical research pathway and its extensive oversight often focus on proposals for deregulation or assert that as in clinical treatment, clinical research should always offer benefit to patient-subjects. Proponents of medical innovation take a different, middle path, arguing that innovation is distinguishable from both research and treatment. This article considers this third pathway by examining stem cell-based innovation.

Stem cell-based medical innovation is one pathway toward clinical translation. In fact, such an approach was taken in developing umbilical cord blood transplantation, which is now widely viewed as a safe and effective means for treating a range of malignant and non-malignant conditions. While the Guidelines for the Clinical Translation of Stem Cells created by the International Society for Clinical Research (ISSCR) provide an approach to clinical translation that involves “responsible innovation” as an alternative to clinical research, there are at least four sets of unanswered questions regarding the use of an innovation pathway in this context that warrant careful attention.

Institutional Review Board (IRB) decisions hinge on the availability and interpretation of information. This is demonstrated by the following well-known historical example. In 2001, 24-year-old Ellen Roche died from respiratory distress and organ failure as a result of her participation in a study at Johns Hopkins Asthma and Allergy Center. The non-therapeutic physiological study, “Mechanisms of Deep Inspiration-Induced Airway Relaxation,” was designed to examine airway hyperresponsiveness in healthy individuals in order to better understand the pathophysiology of asthma. Participants inhaled hexamethonium, a chemical ganglionic blocker that was not FDA-approved for use as specified in the experimental protocol. Risks of inhaling hexamethonium, including lung damage, had been reported in the 1950s and ‘60s. An investigation conducted after Roche's death determined that the study's principal investigator had failed to adequately search the medical literature; the protocol submitted for IRB review cited articles indexed in online literature databases that went back only as far as the 1970s.

The physician-researcher conflict of interest, a long-standing and widely recognized ethical challenge of clinical research, has thus far eluded satisfactory solution. The conflict is fairly straightforward. Medical research and medical therapy are distinct pursuits; the former is aimed at producing generalizable knowledge for the benefit of future patients, whereas the latter is aimed at addressing the individualized medical needs of a particular patient. When the physician-researcher combines these pursuits, he or she serves two masters and cannot — no matter how well-intentioned — avoid the risk of compromising the duties owed in one of the professional roles assumed. Because of the necessary rigidity of a research protocol, the more demanding of the two masters is frequently the research.

The problem of the physician-researcher conflict has been evident since the first attempts to regulate human research in the United States. Otto E. Guttentag, a physician at the University of California School of Medicine in San Francisco, addressed the conflict in a 1953 Science magazine article.

Deception, cheating, and loopholes within the IRB approval process have received significant attention in the past several years. Surveys of clinical researchers indicate common deception ranging from omitting information to outright lying, and controversy surrounding the FDA's decision not to ban “IRB shopping” (the practice of submitting protocols to multiple IRBs until one is found that will approve the protocol) has raised legitimate concerns about the integrity of the IRB process. One author has described a multicenter trial as being withdrawn from consideration at one institution when rejection was imminent, in order to avoid informing other IRBs reviewing the protocol of the study's rejection (a requirement under the federal regulations for emergency research with an exception from informed consent). This practice and IRB shopping seem at odds with the spirit, if not the “letter,” of the regulations. While at first blush these practices seem to cast aspersions on the integrity of clinical researchers, the moral issues raised go deeper than the ethics of cheating.

A number of unique problems plague human research protection efforts at United States (US) State and Territorial Departments of Health (DOHs). The first problem is related to the number of Institutional Review Boards (IRBs) operated by and Federalwide Assurances (FWAs) held by DOHs. The lack of these two essential regulatory human research protection program mechanisms points to a possible inadequacy of infrastructure at DOHs for protecting human subjects. The second and third problems are related to the use and interpretation of research protection laws and regulations at DOHs. Parsing public health activities into research or practice (1) can be vexing and (2) likely produces variability in (a) how individual DOHs make the determination between research and practice and (b) the outcomes of such decisions for the same or similar projects. A related problem is that DOH or Institutional Review Board (IRB) officials might misclassify public health practice activities as research (and vice versa), which can have costly, adverse consequences.

In much the same way that genomic technologies are changing the complexion of biomedical research, the issues they generate are changing the agenda of IRBs and research ethics. Many of the biggest challenges facing traditional research ethics today — privacy and confidentiality of research subjects; ownership, control, and sharing of research data; return of results and incidental findings; the relevance of group interests and harms; the scope of informed consent; and the relative importance of the therapeutic misconception — have become important policy issues over the last 20 years because of the ways they have been magnified by genomic research efforts. Research that examines the ethical, legal, and social implications (ELSI) of human genomics research has become a burgeoning international field of scholarship over the last 20 years, thanks in part to its support first by the genome research funding bodies in the U.S. and then by national science agencies in other countries.

Access to clear and concise medication information is essential to support safe and effective use of prescription drugs. Patient misunderstanding of medication information is a common reason for non-adherence to medication regimens and a leading cause of outpatient medication errors and adverse drug events in the U.S. Medication errors are the most common source of risk to patient safety, leading to poor health outcomes, hospitalizations, and deaths. Over half a million adverse drug events occur in the outpatient setting each year at a cost of approximately $1 billion annually.

Nearly half of adults in the U.S. experience difficulty understanding and acting upon health information. Even individuals with high levels of general literacy may find medication information difficult to understand or use. The risk of misunderstanding medication information is compounded for patients with limited English proficiency (LEP) who may not have access to this information in their own language.

Major advances, ground-breaking scholarship, and new programs in public health law over the past several decades have helped define and reform the field. The extent to which public health law is established as a distinct topic for graduate academic study, however, is uncertain. In the early 1990s, the numbers of academics whose work focused largely on public health law were few. Only a handful of schools of law, public health, and medicine regularly offered core courses in public health law (although many graduate courses in health law, bio-ethics, or public health policy featured select public health law topics). Collectively, these courses laid a strong foundation of instruction in public health law. Still, questions remain as to whether public health law has progressed as a topic of academic pursuit in American graduate institutions. Who is teaching core courses in public health law? Where are these courses taught? How are they designed and what specific topics are covered?

Increasingly, genomic analysis is being utilized to diagnose children with developmental delay or dysmorphic facial features suggestive of a congenital disorder. Genetic testing has rapidly evolved, and the genome-wide tests that we use today are significantly different from the more targeted single-gene tests of the last decade. Chromosomal microarray analysis (CMA) is now a first line test for children with multiple birth defects, children with intellectual impairment (including autism), and children with an unusual constellation of symptoms that do not fit with a known disease. There are three types of CMA that are currently clinically available. CMA by oligonucleotide array-based comparative genomic hybridization (aCGH) compares the hybridization signal from the patient's DNA to that of a reference DNA sample for each oligonucleotide on the array. Depending on the specific array, this can range from tens of thousands to hundreds of thousands of oligonucleotides.