Ethical Costs Research Articles

In vitro dynamic model simulating the digestive tract of 6-month-old infants.

BackgroundIn vivo assays cannot always be conducted because of ethical reasons, technical constraints or costs, but a better understanding of the digestive process, especially in infants, could be of great help in preventing food-related pathologies and in developing new formulas with health benefits. In this context, in vitro dynamic systems to simulate human digestion and, in particular, infant digestion could become increasingly valuable.ObjectiveTo simulate the digestive process through the use of a dynamic model of the infant gastroenteric apparatus to study the digestibility of starch-based infant foods.DesignUsing M.I.D.A (Model of an Infant Digestive Apparatus), the oral, gastric and intestinal digestibility of two starch-based products were measured: 1) rice starch mixed with distilled water and treated using two different sterilization methods (the classical method with a holding temperature of 121°C for 37 min and the HTST method with a holding temperature of 137°C for 70 sec) and 2) a rice cream with (premium product) or without (basic product) an aliquot of rice flour fermented by Lactobacillus paracasei CBA L74. After the digestion the foods were analyzed for the starch concentration, the amount of D-glucose released and the percentage of hydrolyzed starch.ResultsAn in vitro dynamic system, which was referred to as M.I.D.A., was obtained. Using this system, the starch digestion occurred only during the oral and intestinal phase, as expected. The D-glucose released during the intestinal phase was different between the classical and HTST methods (0.795 grams for the HTST versus 0.512 for the classical product). The same analysis was performed for the basic and premium products. In this case, the premium product had a significant difference in terms of the starch hydrolysis percentage during the entire process.ConclusionsThe M.I.D.A. system was able to digest simple starches and a more complex food in the correct compartments. In this study, better digestibility of the premium product was revealed.

Ethics Versus Outcomes: Managerial Responses to Incentive-Driven and Goal-Induced Employee Behavior

Management plays an important role in reinforcing ethics in organizations. To support this aim, managers must use incentive and goal programs in ethical ways. This study examines experimentally the potential ethical costs associated with incentive-driven and goal-induced employee behavior from a managerial perspective. In a quasi-experimental setting, 243 MBA students with significant professional work experience evaluated a hypothetical employee’s ethical behavior under incentive pay systems modeled on a business case. In the role of the employee’s manager, participants evaluated the ethicality of the employee’s incentive-driven and goal-induced ethical/unethical behavior and the outcomes of behavior, with consequences that were either favorable or unfavorable to the organization. The results indicated that participants discounted the ethical considerations of incentive-driven and goal-induced behavior when consequences were favorable to the organization. Participants’ morals and outcome orientations were also significantly related to their ethical judgments and intentions to intervene. The implications of these findings for research and practice are discussed.

Covariate-adjusted response-adaptive randomization for multi-arm clinical trials using a modified forward looking Gittins index rule.

SummaryWe introduce a non-myopic, covariate-adjusted response adaptive (CARA) allocation design for multi-armed clinical trials. The allocation scheme is a computationally tractable procedure based on the Gittins index solution to the classic multi-armed bandit problem and extends the procedure recently proposed in Villar et al. (2015). Our proposed CARA randomization procedure is defined by reformulating the bandit problem with covariates into a classic bandit problem in which there are multiple combination arms, considering every arm per each covariate category as a distinct treatment arm. We then apply a heuristically modified Gittins index rule to solve the problem and define allocation probabilities from the resulting solution. We report the efficiency, balance, and ethical performance of our approach compared to existing CARA methods using a recently published clinical trial as motivation. The net savings in terms of expected number of treatment failures is considerably larger and probably enough to make this design attractive for certain studies where known covariates are expected to be important, stratification is not desired, treatment failures have a high ethical cost, and the disease under study is rare. In a two-armed context, this patient benefit advantage comes at the expense of increased variability in the allocation proportions and a reduction in statistical power. However, in a multi-armed context, simple modifications of the proposed CARA rule can be incorporated so that an ethical advantage can be offered without sacrificing power in comparison with balanced designs.

From evidence-based to hope-based medicine? Ethical aspects on conditional market authorization of and early access to new cancer drugs.

There is a strong patient demand for early access to potentially beneficial cancer drugs. In line with this authorization agencies like the European Medicines Agency are providing drugs with conditional market authorisation based on positive interim analyses. This implies that drugs are used with insecure evidence of efficacy and adverse side-effects. Several authors have pointed to ethical problems with such a system but up to date no indepth ethical analysis of this system is found which is the aim of this article. Drawing of the four generally accepted principles of medical ethics: beneficence, nonmaleficence, respect for autonomy and justice the ethical pros and cons of conditional market authorisation are analysed. From the perspective of beneficence and non-maleficence it is found that the main problem is not risk of adverse side-effects to patients, but rather risk of less beneficial outcomes than what can be expected which could change incentives for patients' choice of treatment. This is also related to the extent to which patients might make an autonomous choice, especially taking into account problematic psychological attitudes and biases in medical decision-making. However, the main problem is related to justice and an equitable distribution of scarce health-care resources given the opportunity cost of drugs treatment. When using resources on cancer treatments which later might be found to be less efficacious than was first expected, other patients (in and outside the cancer field) are deprived of potentially more beneficial treatments even though their needs might be equally or more severe. At the same time, demanding more evidence has an ethical cost to patients in terms of depriving them of potential benefits in terms of reduced mortality and morbidity. In order to handle these ethical conflicts further research and analyses are required and it is suggested that pricing strategies and information requirements are alternatives to be further explored.

Integrated testing strategies can be optimal for chemical risk classification

There is an urgent need to refine strategies for testing the safety of chemical compounds. This need arises both from the financial and ethical costs of animal tests, but also from the opportunities presented by new in-vitro and in-silico alternatives. Here we explore the mathematical theory underpinning the formulation of optimal testing strategies in toxicology. We show how the costs and imprecisions of the various tests, and the variability in exposures and responses of individuals, can be assembled rationally to form a Markov Decision Problem. We compute the corresponding optimal policies using well developed theory based on Dynamic Programming, thereby identifying and overcoming some methodological and logical inconsistencies which may exist in the current toxicological testing. By illustrating our methods for two simple but readily generalisable examples we show how so-called integrated testing strategies, where information of different precisions from different sources is combined and where different initial test outcomes lead to different sets of future tests, can arise naturally as optimal policies.

U.S. Entrepreneurial Risk in International Markets: Focus on Bribery and Corruption

Research from the Kauffman Foundation shows that without startups, there would be no net job growth in the U.S. economy. Since the mid-1990s, businesses with fewer than 500 employees have created 60 to 80 percent of U.S. net new employment. The phenomenal growth of the Internet during recent years results in a rational perception by entrepreneurs that rapid access is available to international markets and sales. However, lurking in the allure of international expansion is the very real threat of exposure to widespread bribery and corruption. Every entrepreneur needs to consider their response before being confronted with this problem. Substantial fines, penalties, legal and other expenses and even jail time may result from running afoul of the FCPA, U.K. Bribery Act or other local anti-bribery or corruption laws. While the cost of anti-bribery compliance for entrepreneurs is heavy, the ethical, economic, and social impact of bribery is equally onerous. A review of bribery and corruption among the United States’ top three trading partners (Canada, China, and Mexico) illustrate these risks. I discuss the Foreign Corrupt Practices Act; OECD Convention on Combating Bribery of Foreign Public Officials in International Business Transactions; the U.K. Bribery Act 2010; and offer a few thoughts about the cost of anti-bribery compliance, as well as the ethical and societal cost of corruption. I believe that this article contributes to the existing small-business literature by better equipping entrepreneurs to recognize and understand risk as they plan to enter international markets.

Exploring the Pregnant Guinea Pig as a Model for Group B Streptococcus Intrauterine Infection.

Infection of the amniotic cavity remains a major cause of preterm birth, stillbirth, fetal injury and early onset, fulminant infections in newborns. Currently, there are no effective therapies to prevent in utero infection and consequent co-morbidities. This is in part due to the lack of feasible and appropriate animal models to understand mechanisms that lead to in utero infections. Use of mouse and rat models do not fully recapitulate human pregnancy, while pregnant nonhuman primate models are limited by ethical considerations, technical constraints, and cost. Given these limitations, the guinea pig is an attractive animal model for studying pregnancy infections, particularly as the placental structure is quite similar to the human placenta. Here, we describe our studies that explored the pregnant guinea pig as a model to study in utero Group B Streptococci (GBS) infections. We observed that intrauterine inoculation of wild type GBS in pregnant guinea pigs resulted in bacterial invasion and dissemination to the placenta, amniotic fluid and fetal organs. Also, hyperhemolytic GBS such as those lacking the hemolysin repressor CovR/S showed increased dissemination into the amniotic fluid and fetal organs such as the fetal lung and brain. These results are similar to those observed in mouse and non-human primate models of in utero infection, and support use of the guinea pig as a model for studying GBS infections in pregnancy.

Rethinking super-confidentiality in the age of disclosure: The ethical and social implications of privacy protections in mental health data

Summary Two opposing impulses have marked efforts in medicine and global health to combat stigma and discrimination. Traditionally, threat of stigma leads to efforts to protect patients by enforcing privacy and confidentiality, while more recently, anti-stigma efforts have been dominated by arguments that the best way to fight stigma is through greater disclosure of the facts of illness. By this line of argument, the act of sharing patient experiences with stigmatized conditions will help dismantle stigma. The question of whether and/or when the threat of stigma warrants more privacy or more disclosure in medicine and public health is the topic of this paper. Tracing two historical cases – HIV and mental health – illustrates the shifting pendulum between privacy and disclosure as opposing, yet both well-intentioned responses to the fact of stigma in both medicine and public health. Public health responses to both HIV and mental health can be divided into periods marked by exceptionalism that eventually yielded to calls for greater integration. That the opposite policies of both eras were each justified the same argument that combat stigma makes these historical cases ethically important. Tracing the rise and fall of exceptionalism in these two cases – HIV and mental health – raises both empirical and normative questions about the impulse toward greater privacy as a strategy for stigma protection. These questions include: When is greater privacy an appropriate or effective response to combat stigmatized conditions? Might greater privacy sometimes actually lead to perverse consequences such as exacerbating or perpetuating, rather than mitigating stigma? And if that is indeed a risk, how should public health officials determine in what circumstances disclosure or privacy offers a better strategy toward stigma reduction? This paper concludes by considering the normative aspects of the policy implications raised by such cases of privacy and anti-stigma efforts. These two cases enumerate the social and medical costs of privacy and stigma so that better policy prescriptions can be developed to advance fairness and justice. They should serve to remind or teach us that there may be social and ethical costs associated with the cure (the privacy) as well as the illness (the stigma). Policy responses must evolve with changing social circumstances. The original impulse towards extreme privacy, confidentiality or exceptionalism, noble though it was, and even appropriate for that time, does not today result in its intended goal: reduction of stigma by demonstrating through practice and policy the moral equivalence of different medical conditions. Another lesson from these cases is that in many cases extreme privacy and vertical programs may even detract from that goal of stigma reduction by signaling that the stigmatized condition is so “other” its sufferers require special treatment or to be kept apart (in the isolated clinics of HIV/AIDS for example). More protection will not always be benign, even if well intentioned. The ironic lesson for global health is that privacy practices run the risk of perpetuating the very stigma they were designed to combat.

Assigning ethical weights to clinical signs observed during toxicity testing.

Reducing the number of laboratory animals used and refining experimental procedures to enhance animal welfare are fundamental questions to be considered in connection with animal experimentation. Here, we explored the use of cardinal ethical weights for clinical signs and symptoms in rodents by conducting trade-off interviews with members of Swedish Animal Ethics Committees in order to derive such weights for nine typical clinical signs of toxicity. The participants interviewed represent researchers, politically nominated political nominees and representatives of animal welfare organizations. We observed no statistically significant differences between these groups with respect to the magnitude of the ethical weights assigned, though the political nominees tended to assign lower weights. Overall, hunched posture was considered the most severe clinical sign and body weight loss the least severe. The ethical weights assigned varied considerably between individuals, from zero to infinite value, indicating discrepancies in prioritization of reduction and refinement. Cardinal ethical weights may be utilized to include both animal welfare refinement and reduction of animal use in designing as well as in retrospective assessment of animal experiments. Such weights may also be used to estimate ethical costs of animal experiments.

Editor’s note

ABSTRACTThe United Nations projects that global population, about 7.4 billion today, will reach 11.2 billion in 2100 (with Africa accounting for the lion’s share of growth). For anyone concerned about climate change, this is a sobering prospect. The world already struggles to limit carbon dioxide emissions, so what are the prospects for climate mitigation in a world with 50% more people? But proposals to slow population growth can encounter stiff resistance. The real problem, some argue, is that energy consumption will grow much faster than population as the world gets richer – and in any event, past initiatives to slow population growth have sometimes taken sinister forms. Here, Alex Ezeh (2016) of Nigeria, Alisha Graves (2016) of the United States, and Wang Haibin (2016) of China consider whether population initiatives are a legitimate element of climate mitigation – and whether they can be pursued without exacting unacceptable ethical costs.

The Paradox of Narrative Empathy and the Form of the Novel, or What George Eliot Knew

There is a paradox at the heart of literature that has not been sufficiently explored in theories of the novel, a paradox that could be expressed like this: if readers feel themselves into the fictive Other’s inner life they may simultaneously participate in the generation of the Other—or the Other’s Other. This paradox suggests that empathy in literature is not without its ethical costs. In asking us to empathize with certain characters, empathy is blocked for others. The ethical potential of literature is often assumed to originate in its appeal to our empathy; but if empathy in literature is intimately bound up with processes that create the Other, any straightforward connection between literature and ethics is disrupted. This article uses Silas Marner (1861) as a case study to explore what I call the paradox of narrative empathy, while also revealing an unforeseen ethical insight at the heart of George Eliot’s novel that has not previously been attributed to that “charming minor masterpiece.”

Cold War Anthropology: The CIA, The Pentagon, and the Growth of Dual Use Anthropology by David H. Price

Reviewed by: Cold War Anthropology: The CIA, The Pentagon, and the Growth of Dual Use Anthropology by David H. Price Audra J. Wolfe David H. Price, Cold War Anthropology: The CIA, The Pentagon, and the Growth of Dual Use Anthropology. Durham: Duke University Press, 2016. 488 pp. The publication of Cold War Anthropology extends a remarkable series of works by David H. Price on academic anthropology’s relationship with the US security state. In three prior books, Price has traced US anthropologists’ role in intelligence during World War II (2008), their harassment and repression under anti-Communism (2004), and their more recent role as military advisors in the Global War on Terror (2011). In Cold War Anthropology, Price fills in the missing story by examining anthropologists’ role in supporting and extending US power during the Cold War period, which he implicitly defines as lasting from the end of World War II through the early 1970s. These works are the product of unparalleled research, including a tireless application of the FOIA (Freedom of Information Act) process. Price’s reputation as the leading authority on Cold War anthropology is entirely deserved. Cold War Anthropology presents a massive amount of information on a vast ensemble of researchers, funding agencies, and acronym-laden projects that were either openly or covertly associated with US military or intelligence agencies. Having myself spent several years filing FOIA applications and researching CIA front organizations—albeit mostly concerning scientific fields other than anthropology—I have no doubt of Price’s command of historical fact. The more pressing question is what readers are to do with this information. While Price consistently damns those scholars who knowingly and wittingly consorted with the CIA, his discussion of other sorts of funding arrangements is inconsistent, sometimes maddeningly so. At points, Price seems to offer grudging admiration to researchers who [End Page 595] openly acknowledged their ties to such military agencies as the US Army; elsewhere, he castigates those who contributed to USAID’s development projects as accomplices in US counterinsurgency efforts. What is consistent is Price’s charge that US anthropologists did not fully consider the ethical and political costs that greased the wheels of scientific funding during the Cold War. Price especially draws readers’ attention to the problems inherent in “dual use research,” by which he means investigations designed to answer disciplinary problems that might equally well contribute to national security. As Price puts it, “scientists’ claims of neutrality often meant they had unexamined alignments with the predominating political forces, which went unnoted because they occurred without friction” (xx). These ties only drew attention in the late 1960s and early 1970s, as the extent of the profession’s ties to the security state gradually became clear. Now that this generation of anthropologists is retiring, Price worries that anthropologists have lost their sense of moral outrage. The concern that contemporary anthropologists lack an understanding of “why these relationships endanger prospects of free inquiry” (363) perhaps explains the exhaustive range and scope of Cold War Anthropology, which must be considered a work of historical accounting as much as a work of historical analysis. If the end result is sometimes encyclopedic, that is intentional. The book is, as Price puts it, “an anthropological consideration of anthropology” (xi). The two parts of Cold War Anthropology approach this work of documentation from different angles. Part I, “Cold War Political–Economic Disciplinary Formations,” addresses the financial and institutional arrangements governing relationships between universities, the American Anthropological Association (AAA), the CIA, military agencies, and USAID. Part II, “Anthropologists’ Articulations with the National Security State,” explores the relationships—whether witting or not—between particular individuals or projects and US agencies. Because the book aims to be the definitive account of such relationships, Price is at pains to recount only incidents where he can provide some sort of concrete evidence linking his historical subjects to military or intelligence agencies. Such care is especially welcome because, as Price notes, “documented CIA atrocities [have become] indistinguishable in the public memory from absurd claims” (29). When Price can prove something, he does. When he can’t, but has overwhelming circumstantial evidence to make a case, he tells readers where the paper trail stops. And...

Projection of participant recruitment to primary care research

Background Recruitment to clinical trials remains challenging, particularly in primary care settings. Initial projections of participant recruitment should be as accurate as possible, in order to avoid the financial, clinical and ethical costs of trial extensions or failures. However, estimation of recruitment rates is challenging and often poorly executed. We used qualitative methods to explore the experiences and views of researchers on the planning of recruitment in this setting.

Projection of participant recruitment to primary care research: a qualitative study.

BackgroundRecruitment to clinical trials remains a challenge, particularly in primary care settings. Initial projections of participant recruitment need to be as accurate as possible in order to avoid the financial, clinical and ethical costs of trial extensions or failures. However, estimation of recruitment rates is challenging and often poorly executed, if attempted at all. We used qualitative methods to explore the experiences and views of researchers on the planning of recruitment in this setting.MethodsParticipants had registered accrual to a UK-based primary care research study between April 2009 and March 2012. We conducted nine interviews with chief investigators or study managers, using a semi-structured topic guide. Analysis was conducted using the framework approach.ResultsThree themes are presented: 1) the factors affecting recruitment rates, 2) the use of planning techniques, and 3) influences on poor estimation. 1) A large number of factors affecting recruitment rates were discussed, including those relating to the study protocol, the clinical setting and the research setting. Use of targeted mail-outs to invite apparently eligible individuals to participate was preferred in order to eliminate some of the uncertainty in the recruitment rate associated with opportunistic clinician referrals. 2) The importance of pilot work was stressed. We identified significant uncertainty as to how best to schedule trial timelines to maximise efficiency. 3) Several potential sources of bias involved in the estimation of recruitment rates were explored and framed as technological, psychological or political factors.ConclusionsWe found a large number of factors that interviewees felt impact recruitment rates to primary care research and highlighted the complexity of realistic estimation. Suitable early planning of the recruitment process is essential, and there may be potential to improve the projection of trial timelines by reducing biases involved in the process. Further research is needed to develop formal approaches that would be suitable for use in this setting.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-1002-9) contains supplementary material, which is available to authorized users.

Preliminary safety assessment of C-8 xylitol monoester and xylitol phosphate esters.

Most of the cosmetic compounds with preservative properties available in the market pose some risks concerning safety, such as the possibility of causing sensitization. Due to the fact that there are few options, the proper development of new molecules with this purpose is needed. Xylitol is a natural sugar, and the antimicrobial properties of xylitol-derived compounds have already been described in the literature. C-8 xylitol monoester and xylitol phosphate esters may be useful for the development of skincare products. As an initial screen for safety of chemicals, the combination of in silico methods and in vitro testing can aid in prioritizing resources in toxicological investigations while reducing the ethical and monetary costs that are related to animal and human testing. This study was designed to evaluate the safety of C-8 xylitol monoester and xylitol phosphate esters regarding carcinogenicity, mutagenicity, skin and eye irritation/corrosion and sensitization through alternative methods. For the initial safety assessment, quantitative structure-activity relationship methodology was used. The prediction of the parameters carcinogenicity/mutagenicity, skin and eye irritation/corrosion and sensitization was generated from the chemical structure. The analysis also comprised physical-chemical properties, Cramer rules, threshold of toxicological concern and Michael reaction. In silico results of candidate molecules were compared to 19 compounds with preservative properties that are available in the market. Additionally, in vitro tests (Ames test for mutagenicity, cytotoxicity and phototoxicity tests and hen's egg test--chorioallantoic membrane for irritation) were performed to complement the evaluation. In silico evaluation of both molecules presented no structural alerts related to eye and skin irritation, corrosion and sensitization, but some alerts for micronucleus and carcinogenicity were detected. However, by comparison, C-8 xylitol monoester, xylitol phosphate esters showed similar or better results than the compounds available in the market. Concerning experimental data, phototoxicity and mutagenicity results were negative. As expected for compounds with preservative activity, xylitol-derived substances presented positive result in cytotoxicity test. In hen's egg test, both molecules were irritants. Our results suggested that xylitol-derived compounds appear to be suitable candidates for preservative systems in cosmetics.

디지털콘텐츠 불법복제의 상대적 편익과 비용이 불법복제태도 및 행동에 미치는 영향

본 연구의 목적은 합법복제와 비교한 불법복제에 대한 상대적인 인식을 중심으로, 온라인 디지털콘텐츠 불법복제의 영향요인을 규명하는 데 있다. 이를 위해 기존 문헌과 행동예측이론 기반의 선행연구들에서 주요하게 제시되었던 요인들을 통합하여 비용-편익관점에서 접근하였다. 주요 결과는 다음과 같이 요약할 수 있다. 첫째, 합법복제에 비해 불법복제를 통해 얻을 수 있는 상대적 이익에 관한 결과로, 금전적 효용과 심리적 효용은 불법복제에 대한 태도 및 행동에 긍정적인 영향을 미치는 것으로 나타났다. 특히 금전적 효용은 불법복제행동의 주요 요인으로 나타나 불법복제를 행하는 이유가 금전적인 이유에 있음을 보여준다. 둘째, 불법복제의 상대적 손실요인 중 도덕적 비용은 불법복제태도에 부정적인 영향을 미치는 결정 요인으로 확인되었으며, 기술적 비용은 불법복제행동에 유의한 영향을 미치는 것으로 나타났다. 셋째, 불법복제에 대한 태도와 복제행동은 밀접한 영향관계임이 확인되었다. 이는 태도가 의도를 매개하지 않고도 행동을 이끄는 선행요인이 될 수 있음을 보여주는 결과라 하겠다. The purpose of this study is to identify factors affecting piracy of online digital contents, focusing on relative awareness of illegal duplications, compared to legal duplication. To do this, the current study integrates factors proposed in existing literature and the previous studies based on the theory of planned behavior and accesses them from cost-benefit point of view. Main findings are summarized as followed;- First, with regard to relative benefits gained by illegal duplication, it is shown that monetary and psychological utility have positive effects on attitudes and behaviors of illegal duplication. Particularly, it is found that monetary incentive is the main cause of illegal duplication as monetary gains are major factors affecting illegal duplication behaviors. Second, it is suggested that ethical cost is a definitive factor that has negative effects on illegal duplication behaviors while technological cost has also significant effects on illegal duplication behaviors. Third, it is confirmed that there is a significant relationship between attitudes and behaviors of illegal duplication. This result shows that an attitude to illegal duplication is antecedent of behaviors as the belief and the value regarding illegal duplication can lead actual behaviors.

The effect of unethical behavior and learning on strategic supplier selection

The unethical behavior of suppliers, such as the use of child labor or the use of unsafe processes, is becoming an increasingly common problem in many industries. Despite lower sourcing costs, such social irresponsibility can have a severe negative effect on firms because of growing awareness and punishment from consumers toward unethical practices. To study how ethical behavior of suppliers and supplier learning affect a firm׳s sourcing strategy, we analyze a buying firm׳s strategic sourcing decision on supplier selection between unethical and ethical suppliers by considering the risk likelihood and the impact to the firm of unethical events, and the supplier learning. We show that supplier learning matters and that the benefit of high learning rates may outweigh the concerns of unethical behavior or high ethical sourcing cost and so, long-term contracts are optimal. We also show that the firm may prefer a selection policy contingent on the realization of unethical events only when risk is low or impact is high. In addition, we show that a changing environment may cause the firm to take a more proactive sourcing strategy by adopting short-term switching policies.

Quantifying the Magnitude and Cost of Collecting Extraneous Protocol Data

Although most research professionals believe that protocol designs contain a growing number of unnecessary and redundant procedures generating unused data, incurring high cost, and jeopardizing study success, there are no published studies systematically examining this issue. Between November 2011 and May 2012, Tufts Center for the Study of Drug Development conducted a study among a working group of 15 pharmaceutical companies in which a total of 25,103 individual protocol procedures were evaluated and classified using clinical study reports and analysis plans. The results show that the typical later-stage protocol had an average of 7 objectives and 13 end points of which 53.8% are supplementary. One (24.7%) of every 4 procedures performed per phase-III protocol and 17.7% of all phase-II procedures per protocol were classified as "Noncore" in that they supported supplemental secondary, tertiary, and exploratory end points. For phase-III protocols, 23.6% of all procedures supported regulatory compliance requirements and 15.9% supported those for phase-II protocols. The study also found that on average, $1.7 million (18.5% of the total) is spent in direct costs to administer Noncore procedures per phase-III protocol and $0.3 million (13.1% of the total) in direct costs are spent on Noncore procedures for each phase-II protocol. Based on the results of this study, the total direct cost to perform Noncore procedures for all active annual phase-II and phase-III protocols is conservatively estimated at $3.7 billion annually, not including the indirect costs associated with collecting and managing Noncore procedure data and the ethical costs of exposing study volunteers to unnecessary risks associated with conducting extraneous procedures.

Compensatory immigration challenges predator control: An experimental evidence-based approach improves management

Attempts to control predator numbers through spatially restricted culling typically faces a compensation process via immigration from surrounding source populations. To extend control effort to avoid this issue is in most instances impractical, both logistically and financially. Evidence-based strategy is therefore required to improve management practices. In close collaboration with local managers and hunters, we manipulated culling effort on red fox (Vulpes vulpes) over 5-6 years in 5 areas measuring 246 +/- 53km(2). We estimated fox density in late February each year by spotlight counts with distance sampling and estimated reproductive performance by post-mortem examination of culled foxes. We then used mixed modeling to assess how culling rate (defined as foxes killed/foxes available) affected fox population growth from year to year, accounting for compensatory feedbacks. We found a strong compensatory density feedback acting through immigration, allowing red fox populations to resist high culling rates. Culling appeared ineffective at reducing late winter densities to below 25-32% of the estimated carrying capacity. On average, an annual culling rate equivalent to about 45% of the pre-breeding population was required to maintain density at 1fox/km(2), given a carrying capacity of 1.5foxes/km(2), although there was considerable variation among sites. The required culling rate dropped to 25% if the culling could be performed during winter, after the fox dispersal period. In contrast, culling during the pre-dispersal breeding period was totally compensated for through immigration by the following February. Concentrating culling during the winter could improve the ability of practitioners to control year-to-year trends in fox numbers, taking into account site-specific carrying capacity. A winter strategy would also reduce the number of animals killed and hence the ethical and logistical costs of fox control, given limited financial and human resources. Our study illustrates how collaboration between local practitioners and scientists can make large-scale replicated management experiments achievable, leading to mutually approved guidelines. (c) 2015 The Wildlife Society.

Ventriloquist Theatre and the Omniscient Narrator: Gatz and El pasado es un animal grotesco

ABSTRACT: By replacing dialogue with narration, ventriloquist theatre raises central questions about its ethical and political costs, while challenging our understanding of the limits between drama and narrative. In very different ways, Elevator Repair Service’s Gatz (first performed 2006) and Mariano Pensotti’s El pasado es un animal grotesco [The Past Is a Grotesque Animal] (2010) redraw the boundaries between literary modes, putting characters onstage but replacing their dialogue with narrated text. Staging narration allows us to reconsider literary mechanisms to which we have largely become inured. Rendering the invisible narrator as a presence on the stage lays bare both the arbitrariness of narrative authority and its costs.