The shell game: how institutional review boards shuffle words.

Concepts like coercion, vulnerability, and dignitary harm have acquired specialized meanings in the research ethics literature. Institutional Review Boards (IRBs), also called Research Ethics Committees (RECs), sometimes use these concepts in two different ways without acknowledging or even realizing what they are doing. IRBs mislabel any language that encourages subject participation in trials as "coercive," then demand its removal as if it were actually coercive in the sense of a threat of force. An example of language that is treated as coercive is the use of the word "hope" in an educational brochure about clinical trials. The concepts of vulnerability and dignitary harm are similarly misused. The regulations instruct IRBs to protect vulnerable groups; but IRBs sometimes use a group's vulnerability to one threat to protect it against an unrelated and harmless threat, as when homeless people, who are vulnerable to street crime and disease, are protected from the risk of an interview. Finally, the term "dignitary harm" is so vague that IRBs can use it to restrict research that is entirely free of risk, while ignoring the possibility that research might provide the dignitary benefit of contributing to society's health and welfare. Dignitary harm--usually nonphysical "harm" of which the subject is entirely unaware--can be deemed more important than obtaining information that subjects want or actual risk of physical injury. These vague or shifting definitions permit the IRB to play a shell game without either the board or the investigator realizing what is happening.

Elderly patients' experiences using adaptive conjoint analysis software as a decision aid for osteoarthritis of the knee.

BACKGROUND: Decision making in knee osteoarthritis, with many treatment options, challenges patients and physicians alike. Unfortunately, physicians cannot describe in detail each treatment's benefits and risks. One promising adjunct to decision making in osteoarthritis is adaptive conjoint analysis (ACA). OBJECTIVE: To obtain insight into the experiences of elderly patients who use adaptive conjoint analysis to explore treatment options for their osteoarthritis. DESIGN: Participants, all 65 and older, completed an ACA decision aid exploring their preferences with regard to the underlying attributes of osteoarthritis interventions. We used focus groups to obtain insight into their experiences using this software. RESULTS: Content analysis distributed our participants' concerns into five areas. The predicted preferred treatment usually agreed with the individual's preference, but our participants experienced difficulty in four other domains: the choices presented by the software were sometimes confusing, the treatments presented were not the treatments of most interest, the researchers' claims about treatment characteristics were unpersuasive and cumulative overload sometimes developed. CONCLUSION: Adaptive conjoint analysis presented special challenges to our elderly participants; we believe that their relatively low level of computer comfort was a significant contributor to these problems. We suggest that other researchers choose the software's treatments and present the treatment attributes with care. The next and equally vital step is to educate participants about what to expect, including the limitations in choice and apparent arbitrariness of the trade-offs presented by the software. Providing participants with a sample ACA task before undertaking the study task may further improve participant understanding and engagement.

"Snake-oil," "quack medicine," and "industrially cultured organisms:" biovalue and the commercialization of human microbiome research.

BACKGROUND: Continued advances in human microbiome research and technologies raise a number of ethical, legal, and social challenges. These challenges are associated not only with the conduct of the research, but also with broader implications, such as the production and distribution of commercial products promising maintenance or restoration of good physical health and disease prevention. In this article, we document several ethical, legal, and social challenges associated with the commercialization of human microbiome research, focusing particularly on how this research is mobilized within economic markets for new public health uses. METHODS: We conducted in-depth, semi-structured interviews (2009-2010) with 63 scientists, researchers, and National Institutes of Health project leaders ("investigators") involved with human microbiome research. Interviews explored a range of ethical, legal, and social dimensions of human microbiome research, including investigators' perspectives on commercialization. Using thematic content analysis, we identified and analyzed emergent themes and patterns. RESULTS: Investigators discussed the commercialization of human microbiome research in terms of (1) commercialization, probiotics, and issues of safety, (2) public awareness of the benefits and risks of dietary supplements, and (3) regulation. CONCLUSION: The prevailing theme of ethical, legal, social concern focused on the need to find a balance between the marketplace, scientific research, and the public's health. The themes we identified are intended to serve as points for discussions about the relationship between scientific research and the manufacture and distribution of over-the-counter dietary supplements in the United States.

Perspectives on human microbiome research ethics.

Study of ethical, legal, and social implications (ELSI) of human microbiome research has been integral to the Human Microbiome Project (HMP). This study explores core ELSI issues that arose during the first phase of the HMP from the perspective of individuals involved in the research. We conducted semi-structured in-depth interviews with investigators and NIH employees ("investigators") involved in the HMP, and with individuals recruited to participate in the HMP Healthy Cohort Study at Baylor College of Medicine ("recruits"). We report findings related to three major ELSI issues: informed consent, data sharing, and return of results. Our findings demonstrate that investigators and recruits were similarly sensitive to these issues yet generally comfortable with study design in light of current knowledge about the microbiome.

Promoting knowledge of statins in patients with low health literacy using an audio booklet.

BACKGROUND: Statins are generally well tolerated and effective at reducing a patient's risk of both primary and secondary cardiovascular events. Many patients who would benefit from statin therapy either do not adhere to or stop taking their statin medication within the first year. We developed an audio booklet targeted to low health literacy patients to teach them about the benefits and risks of statins to help the patients adhere to their statin therapy. METHODS: Through focus groups and an iterative design, an audio booklet was developed for both English-speaking and Spanish-speaking patients. We then compared the booklet with standard of care in 132 patients from our target patient population to measure its impact on knowledge and understanding of statins. RESULTS: The patients enjoyed the audio booklet and showed significant increases in knowledge after listening to it when compared with those who received the standard of care materials. CONCLUSION: The audio booklet shows promise as a tool that can be used effectively in clinical practice to teach patients about statin therapy.

Equipoise lost: ethics, costs, and the regulation of cancer clinical research.

Cancer is the leading cause of death in Americans younger than 85 years of age and kills one American every 56 seconds. Advances in understanding of cancer biology have given us the potential to develop new, effective targeted therapies. However, progress is slowed by suboptimal/outdated clinical trial design paradigms and by regulatory complexity and rigidity. For instance, simulations suggest that restricting randomized trials to patients expressing drug target, instead of using unselected patient populations, could substantially reduce patient numbers required to demonstrate efficacy. High response rates that are achievable when patients and drugs are matched on the basis of molecular profiles may also make some randomized trials unnecessary or unjustifiable. Moreover, increasing the regulatory rigidity of clinical trials (regulatory fundamentalism) augments trial complexity and costs while slowing progress without demonstrating meaningful safety benefits. Time from drug discovery to marketing increased from 8 years in 1960 to 12 to 15 years currently. Toxic death rates on phase I trials have decreased from 0.8% in 1979 to 0.5% by 2002, but the estimated cost per life-year gained by tighter regulations is $2,700,000 (far higher than costs of other health measures), and simulations suggest that regulatory delays in development of effective therapies result in tens to hundreds of thousands of life-years lost, whereas stringent regulations save extremely few. Dysregulation is also a major disincentive to patient and clinician participation in clinical research. In summary, current approaches squander research resources and discourage research participation, and the marked imbalance between potential life-years lost versus saved renders the regulatory burden potentially unethical. We outline suggested solutions.

Beyond shared decision making: an expanded typology of medical decisions.

The most popular current models of medical decision making, identified by names such as shared decision making, informed decision making, and evidence-based patient choice, portray an empowered patient actively involved in his or her medical choices and generally assume that patient and physician reach agreement. These models are limited to a specific type of decision (in which there is more than one choice) and a specific process (in which agreement is reached). The authors extend the model of medical decision making beyond shared decisions in 2 dimensions. First, the authors incorporate a class of medical decisions in which there is only one medically reasonable treatment option, such as the removal of a primary melanoma. Patient preferences are irrelevant to whether or not the melanoma should be removed, so there is no treatment choice in which the patient can share. When there is only one realistic treatment option, the clinician's job is not to offer alternatives but to explain why there is only one viable choice and move the decision-making process forward. The physician does not thereby abridge the patient's autonomy; rather, the disease process itself constrains both patient and physician. Second, the authors include decisions in which patient and physician do not reach agreement. Sometimes the patient insists on a particular treatment and the physician reluctantly yields, sometimes it is the other way around, but disagreement is commonplace in clinical medicine and its presence deserves inclusion in the way we think about medical decisions. Conflict resolution requires acknowledging the potential for conflict.

Beyond breaking bad news: the roles of hope and hopefulness.

BACKGROUND: Hope is important to patients, yet physicians are sometimes unsure how to promote hope in the face of life-threatening illness. ANALYSIS: Hope in medicine is of two kinds: specific (hope for specific outcomes) and generalized (a nonspecific sense of hopefulness). At the time of diagnosis of a life-ending condition, the specific goal of a long life is dashed, and there may be no medically plausible specific outcome that the patient feels is worth wishing for. Yet the physician may nonetheless maintain an open-ended hopefulness that is compatible with the physician's obligation to be truthful; this hopefulness can help sustain patient and family through the turbulent period of adaptation to the unwelcome reality of major illness. As this adaptation evolves, the physician can help patients and families adapt to suffering and loss of control by selecting and achieving specific goals such as improvement of the patient's environment in hospital or hospice, pain control, and relief of sleeplessness. Thus hope for specific (but far more modest) future events can again become a positive part of the patient s emotional landscape. The authors do not propose that physicians remain upbeat no matter the circumstance, for they must respect the constraints of reality and the patients' mortality. However, physicians can provide both cognitive and affective support as patients learn how to adapt. Hope and hopefulness are both important in this process. SUMMARY: Hope is always important to patients. Physicians can and should promote hopefulness without endorsing unrealistic hope.

Principal investigator views of the IRB system.

We undertook a qualitative e-mail survey of federally-funded principal investigators of their views of the US human subjects protection system, intended to identify the range of investigator attitudes. This was an exploratory study with a 14% response rate. Twenty-eight principal investigators responded; their comments were analyzed to show underlying themes, which are here presented along with supporting quotations.There was consensus that it is important to protect human subjects from research abuse, but disagreement over how well the IRB system is functioning. Some researchers felt that the system is effective and serves its purpose well. Of those who support the system, some endorse its methods, purpose, and daily functioning, as they experience it, without reservation. Others, while expressing some frustration, feel that the purpose is important and their local IRB does its best to make a difficult system work well.Those investigators who were more harshly critical commented on multiple flaws in the system, including (1) consent forms that are inappropriate and incomprehensible, (2) an emphasis on minutiae, and (3) concern with protecting the institution more than research subjects. Respondents told us that the IRB system is a particular burden for research in neurology, emergency medical conditions, repositories, and social sciences in general; a more comprehensive study might identify other problematic areas. Significant concern was expressed about the cost, inefficiency, and irrationality of IRB review. The IRB system works well for some researchers, but our results indicate that other investigators feel the costs outweigh the benefits.

Whose decision is it? The microstructure of medical decision making.

Medical decision making is sometimes viewed as a relatively simple process in which a decision may be made by the patient, by the physician, or by both patient and physician working together. This two-dimensional portrayal eclipses the important role that others, such as other professionals, family, and friends, may play in the process; as an example of this phenomenon, we trace the evolution of a decision of a teenager with cancer who is contemplating discontinuing chemotherapy. This example also shows how a decision can usefully be understood as consisting of a number of identifiable substeps--what we call the "microstructure" of the decision. These steps show how the physician can play an important role without usurping the patient's rightful decisional authority.

Association of spirituality and sobriety during a behavioral spirituality intervention for Twelve Step (TS) recovery.

Twelve-Step (TS) recovery utilizes spirituality to promote sobriety, yet there are no proven programs designed to facilitate spiritual involvement. We developed a seven-week behavioral spirituality intervention titled "Knowing Your Higher Power" for implementation along with usual TS care. Twenty-six participants from a recovery center enrolled. We assessed behavior at baseline, 7-week, and 12-week follow-up. The sample showed significant increase in spiritual involvement and beliefs over the 12-week measurement period and a significantly greater spirituality score in those maintaining total sobriety compared to those that relapsed. These findings encourage a controlled trial to determine if this work has efficacy for practitioners in substance abuse treatment.

[Cp*IrCl2]2-catalyzed indirect functionalization of alcohols: novel strategies for the synthesis of substituted indoles.

We report novel iridium(III)-catalyzed reactions that afford substituted indoles via the indirect functionalization of alcohols via C-3 selective alkylation of indoles with alcohols and a one-pot cascade strategy from amino- or nitro-phenyl ethyl alcohols, which incorporates oxidative cyclization and C-3 alkylation.

Physicians' silent decisions: because patient autonomy does not always come first.

Physicians make some medical decisions without disclosure to their patients. Nondisclosure is possible because these are silent decisions to refrain from screening, diagnostic or therapeutic interventions. Nondisclosure is ethically permissible when the usual presumption that the patient should be involved in decisions is defeated by considerations of clinical utility or patient emotional and physical well-being. Some silent decisions--not all--are ethically justified by this standard. Justified silent decisions are typically dependent on the physician's professional judgment, experience and knowledge, and are not likely to be changed by patient preferences. We condemn the inappropriate exclusion of the patient from the decision-making process. However, if a test or treatment is unlikely to yield a net benefit, disclosure and discussion are at times unnecessary. Appropriate silent decisions are ethically justified by such considerations as patient benefit or economy of time.

The physician's role in the assessment and treatment of spiritual distress at the end of life.

OBJECTIVE: Patients at the end of their life typically endure physical, emotional, interpersonal, and spiritual challenges. Although physicians assume a clearly defined role in approaching the physical aspects of terminal illness, the responsibility for helping their patients' spiritual adaptation is also important. METHODS: This article (1) describes the terms and definitions that have clinical utility in assessing the spiritual needs of dying patients, (2) reviews the justifications that support physicians assuming an active role in addressing the spiritual needs of their patients, and (3) reviews clinical tools that provide physicians with a structured approach to the assessment and treatment of spiritual distress. RESULTS: This review suggests that physicians can and should be equipped to play a key role in relieving suffering at the end of life. SIGNIFICANCE OF RESULTS: Physicians can help their patients achieve a sense of completed purpose and peace.

Alcohol recovery and spirituality: strangers, friends, or partners?

Alcoholics Anonymous, with its steady but nonspecific promotion of belief in a higher power and its emphasis on the group process, long held a near-monopoly in the outpatient alcohol recovery field, but its hegemony has now been challenged by two very different perspectives. The first is a nonspiritual approach that emphasizes the individual's capability to find a personal pathway to sobriety, exemplified by Rational Recovery. The second is a faith-based method, built on a religious understanding of alcoholism, of which Celebrate Recovery is a prominent example, based upon Christianity. Most communities offer a variety of approaches, so clinicians who are aware of these differences are in a good position to help patients make intelligent choices among the competing recovery philosophies.