Using empirical data to inform the ethical evaluation of placebo controlled trials

There has been considerable debate about the ethical acceptability of using placebo-controls in clinical research. Although this debate has been rich in rhetoric, considering that much of this research is predicated upon the assumption that data from this research is vital to clinical decision-making, it is ironic that researchers have introduced little data into these discussions. Using some published research concerning the use of placebo-controls in clinical research in hypertension and psychiatric drug trials, I suggest some ways that such data might be incorporated into the ethical analysis concerning placebo use in clinical trials. This approach promises to be important for enhancing conceptual and scientific understanding as well as public policy decision-making. An earlier version of this paper was presented at an international conference, “Placebo: Its Action and Place in Health Research Today,” held in Warsaw, Poland on 12–13 April, 2003.     

The Inducement of Meaningful Work: A Response to Anderson and Weijer

James A. Anderson and Charles Weijer take the wage payment model proposed by Neil Dickert and Christine Grady and extend the analogy of research participation to unskilled wage labor to include just working conditions. Although noble in its intentions, this moral extension generates unsavory outcomes. Most notably, Anderson and Weijer distinguish between two types of research subjects: occasional and professional. The latter, in this case, receives benefits beyond the moral minima in the form of “the right to meaningful work.” The problem is that meaningful work can itself be a form of inducement, and consequently, may in fact increase the incidence of inducement contrary to the intentions of the wage payment model.     

Healthy Children As Subjects in Pharmaceutical Research

Recruitment of healthy children for drugresearch has emerged due in part to several newAmerican laws and policies that have led to asurge in pharmaceutical research involvingchildren-subjects. In this paper, I review theethical and scientific issues and the argumentsin favor and against this new practice.     

Clinical and Administrative Insights From Delivering Massed Trauma-Focused Therapy to Service Members and Veterans

Despite strong evidence of their effectiveness in reducing symptoms of posttraumatic stress disorder (PTSD), prolonged exposure therapy (PE) and cognitive processing therapy (CPT) remain challenging for some service members and veterans to access and complete. Delivering PE and CPT in time-condensed or “massed” formats may reduce barriers to receiving care. PE and CPT have now been implemented across a range of tempos (e.g., multiple sessions per day across 1 week, one session per day for 3 weeks) and to multiple target populations, in a variety of contexts from individual therapy alone to full intensive outpatient programs. A massed format of treatment delivery has advantages for both patients and providers, including quicker time to recovery, less opportunity for avoidance, and improved treatment completion rates. The time-limited nature of massed treatment also creates accompanying challenges, such as less time to practice homework and greater impact when factors delay or disrupt progress. This paper discusses lessons learned from providers across diverse settings who are experienced in both delivering massed PE and CPT and managing such programs, primarily with military populations.     

Extraordinary claims in the literature on high-intensity interval training (HIIT): IV. Is HIIT associated with higher long-term exercise adherence?

Nonadherence to and dropout from regular exercise and physical activity are important reasons why the field of exercise science has yet to fulfill its promise of improving public health on a global scale. Researchers have claimed that High-Intensity Interval Training (HIIT) is a feasible and sustainable exercise modality that may result in higher long-term adherence than moderate-intensity continuous exercise. If true, this would be a breakthrough discovery that could unlock the potential of exercise as a health-promoting intervention. We performed a systematic search of the literature and identified eight trials comparing HIIT to moderate-intensity continuous exercise, all of which involved follow-up periods of at least 12 months (i.e., SWIFT, Small Steps for Big Changes, SAINTEX-CAD, SMARTEX-HF, Generation 100, FITR, OptimEx-Clin, HITTS). Findings from these trials demonstrate that, while unsupervised, individuals initially assigned to HIIT tend to exercise at lower-than-prescribed intensities and HIIT groups demonstrate no advantage in long-term adherence.     

Ethical aspects of the safety of medicines and other social chemicals

The historical background of the discovery of adverse health effects of medicines, food additives, pesticides, and other chemicals is reviewed, and the development of national and international regulations and testing procedures to protect the public against the toxic effects of these drugs and chemicals is outlined. Ethical considerations of the safety evaluation of drugs and chemicals by human experimentation and animal toxicity studies, ethical problems associated with clinical trials, with the falsification of clinical and toxicological data, and with inadequate experimental methodology, are reviewed, and the ethics of the marketing of drugs and their post-marketing surveillance, are similarly considered. These ethical problems are illustrated with many specific examples, including the drugs neoarsphenamine, chloramphenicol, thalidomide, diethyl stilboestrol and benoxaprofen.     

Case method and casuistry: The problem of bias

Case methods of reasoning are persuasive, but we need to address problems of bias in order to use them to reach morally justifiable conclusions. A bias is an unwarranted inclination or a special perspective that disposes us to mistaken or one-sided judgments. The potential for bias arises at each stage of a case method of reasoning including in describing, framing, selecting and comparing of cases and paradigms. A problem of bias occurs because to identify the relevant features for such purposes, we must use general views about what is relevant; but some of our general views are biased, both in the sense of being unwarranted inclinations and in the sense that they are one of many viable perspectives. This reliance upon general views to determine relevancy creates additional difficulties for defenders who maintain that case methods of moral reasoning are not only useful, but more basic, reliable or prior to other forms of moral reasoning. If we cannot identify the case's relevant features and issues independently of our general views or biases, we need further explanation about why a case method or casuistry should be viewed as prior to or more basic or reliable than other forms of moral reasoning. Problems of bias also arise for other methods of reasoning. In medical science, case reviews are regarded as an unreliable way to form generalizations, and methods such as clinical trials are used to address bias.     

Clinical specificity and the non-generalities of science

Theoretical Medicine and Bioethics - How to improve clinical practice and, in particular, that of physical therapy? Currently, several strategies are used which all fit the label...     

Discrete-trial choice in pigeons: Effects of reinforcer magnitude

The preference of pigeons for large reinforcers which occasionally followed a response versus small reinforcers which invariably followed a response was studied in a discrete-trial situation. Two differently colored keys were associated with the two reinforcement alternatives, and preference was measured as the proportion of choice trials on which the key associated with uncertain reinforcement was pecked. A combination of choice and guidance trials insured that received distributions of reinforcement equalled the scheduled distributions. For five of six subjects, preference for the uncertain reinforcer appeared to be a linear function of the magnitude of the certain reinforcer. In addition, there was greater preference for the response alternative associated with uncertain reinforcement than would be expected on the basis of net reinforcer value.     

Autoshaped responding: A baseline for studying stimulus preference

In an autoshaping procedure with pigeons, trials consisted of the illumination of two keys, each with a different color, and then a response-independent feeder operation. Over successive conditions, all key-color pairs were arranged from the set of amber, red, green, and blue lamps. During sessions with a given pair, the left-right configuration of the colors varied irregularly, and the two colors alternated in illuminating the feeder. With one red and one green key, for example, red appeared sometimes on the left and sometimes on the right, and the feeder was alternately lit red or green on successive trials. Both total pecks and proportion of trials with at least one peck on a key of a given color were generally greater for red and amber than for green and blue, and relations among preferences were generally transitive across different color pairs. Repeating the procedure with decreased red and amber intensities and increased green and blue intensities reduced red and amber pecking relative to green and blue pecking, implying that differences in responding were determined more strongly by intensive than by chromatic properties of the stimuli.