OBJECTIVE: Pilot study to characterize treatment differences between patients treated in clinical trials and those treated in a clinical setting. Previous studies have shown higher survival rates for participants in trials of cancer therapy. This difference is observed even after rates are adjusted for important covariates such as age and stage of disease. DESIGN: Retrospective chart review. SETTING: Oncology outpatient department in a tertiary care hospital. PATIENTS: Ninety women 18 to 70 years of age with early-stage breast cancer who were (...) diagnosed in 1990. Fifty-one of the women were treated through clinical trials and 39 were treated outside of clinical trials. OUTCOME MEASURES: Number of blood tests, telephone calls, clinic visits and imaging procedures as well as intensity of chemotherapy and use of radiation therapy. The age of the patient and the stage of disease were important covariates. RESULTS: After the analysis was controlled for patient age and stage of disease, patients treated through a clinical trial were more likely to receive standard-dose chemotherapy (p = 0.020, 95% confidence interval 1.20 to 200.73) and more frequent blood tests (p < 0.001, 95% confidence interval 1.02 to 1.13) than other patients treated in the clinic. CONCLUSIONS: Our results provide a plausible mechanism for the observed survival advantage for participants in clinical trials in oncology. Further study is called for. If these results are confirmed, they have important implications for informed consent to participate in clinical trials and for clinical practice. (shrink)

To what risks may children participating in research be subjected? Institutional review boards can stand surrogate for parents by filtering out studies whose risk is unacceptably high.

OBJECTIVE: To investigate whether eligibility criteria that exclude the elderly, persons with psychiatric disease, and persons with substance abuse problems from participation in randomized controlled trials (RCTs) are subjective and hence a source of variability in enrolment decisions and investigator uncertainty. DESIGN: Survey questionnaire. PARTICIPANTS: Cancer investigators from the United States and Canada. INTERVENTIONS: Investigators were presented with clinical vignettes from 3 patient categories--eligible, ineligible and uncertain--for each of 5 eligibility criteria--3 subjective and 2 objective--and were asked whether they would (...) enrol the patient in a trial and how sure they were of this decision. Demographic characteristics of the investigators were also collected. OUTCOME MEASURES: The difference in enrolment decisions between subjective and objective criteria, and the difference in the certainty associated with these decisions. RESULTS: Of 365 questionnaires sent out, 224 usable ones were returned. Compared with the objective criteria, the subjective criteria were associated with more variable enrolment decisions (p = 0.07 for the "eligible" scenario and p = 0.0001 for the "ineligible" and "uncertain" scenarios), and investigators were less sure about the decisions they made (p = 0.0001 for all scenarios). Demographic characteristics of the investigators failed to explain the observed differences. CONCLUSIONS: Subjective eligibility criteria may interfere with the conduct and interpretation of RCTs and, therefore, their use ought to be justified explicitly in the study protocol. RCT designers, funding agencies and research ethics boards have an important role in reviewing eligibility criteria for their necessity. (shrink)

Placebo-controlled trials are held by many, including regulators at agencies like the United States Food and Drug Administration, to be the gold standard in the assessment of new medical interventions. Yet the use of placebo controls in clinical trials has been the focus of considerable controversy. In this two-part article, we challenge a number of common beliefs concerning the value of placebo controls. Part I critiques statistical and other scientific justifications for the use of placebo controls in clinical research. The (...) continued use of placebo controls in clinical trials on diseases for which accepted treatment exists raises equally important ethical, legal, and regulatory issues for which various justifications have been given. Defense of this practice relies on normative as well as empirical myths.In their attack on the prevailing use of placebo controls, Kenneth Rothman and Karin Michels emphasize that this practice stands in violation of the World Medical Association's guidelines on the ethics of human experimentation, most commonly known as the Helsinki Declaration. (shrink)

The use of statistics in medical research has been compared to a religion: it has its high priests, supplicants, and orthodoxy. Although the comparison may be more unfair to religion than to research, a useful lesson can nonetheless be drawn: the practice of clinical research may benefit—as does the spirit—from critical self-examination. Arguably, no aspect of the conduct of clinical trials is currently more controversial—and thus in as dire need of critical examination—than the use of placebo controls. The ethical and (...) scientific controversies associated with placebo-controlled trials, never far below the surface, have once again seized public attention. Clearly, concern about these issues within the professional community runs deep and wide, as evidenced by the volume of response generated by Kenneth Rothman and Karin Michels's recent Critique. Criticisms of the use of placebo controls in clinical research are scattered through the literatureo; our objective is to present the case against placebos in a compendious form that takes account of scientific and statistical as well as normative issues. (shrink)

In summary, the usual elements of a typical health care ethics consultation note might reasonably accommodate the needs and expectations of relevant parties, and would therefore include: 1. identification of the relevant ethical issues, questions, or dilemmas; 2. reference to any relevant facts--medical, nursing, social, psychological, spiritual, legal, political, etc.; 3. a prioritized list of recommendations to improve coordinated care; 4. a clear and concise articulation of relevant arguments, wtih specific reference to the list of recommendations as well as to (...) the institution's overall ethos; 5. a contextual statement, identifying the perceived degree of consensus or support for the recommendations and conclusions, as well as any inherent agendas. (shrink)

We studied changes in eligibility criteria--the largest impediment to patient accrual--in two samples of clinical trials. Trials from the NSABP (National Surgical Adjuvant Breast and Bowel Program) and POG (Pediatric Oncology Group) were analyzed. After eliminating duplications, the criteria in each protocol were enumerated and classified according to a novel schema. NSABP trials contained significantly more criteria than POG trials, and added precision criteria (making study populations homogeneous) at a faster rate than POG studies. The difference between NSABP studies (explanatory (...) trials) and POG studies (pragmatic trials) suggest that large numbers of eligibility criteria are not necessary for quality studies. We recommend that: (1) the inclusion/exclusion criteria distinction be abandoned; (2) eligibility criteria be explicitly justified; (3) the need for each criterion be assessed when new trials are planned; (4) criteria in phase III trials restricting patient accrual be minimized; and (5) further research be done to assess the impact of criteria on generalizability. (shrink)

In contrast to attempts that have been made to measure the clarity of reporting of the methods of clinical trials in journal articles, we report here an attempt to measure the accuracy of methods reporting. We focus in this article on eligibility criteria as a test case for the reporting of clinical trial methods. We examined the reporting of eligibility criteria in the protocol, methods paper (if applicable), journal article, and Clinical Alert for articles appearing in print between January 1988 (...) and September 1994 for which a Clinical Alert had been issued. Eligibility criteria were further classified into five categories in order to examine the content of information loss, if any. On average, 82% of protocol eligibility criteria were reported in methods papers. Journal articles and Clinical Alerts fared somewhat worse: 63% of criteria were reported in journal articles, 19% in Clinical Alerts. In all three categories of medical communication, the reporting of criteria that defined the study disease tended to be complete; reporting of criteria relating to trial precision, patient safety, legal and ethical concerns, and administrative considerations, was not complete. We found that criteria for clinical trial eligibility are frequently under-reported in medical communications. Moreover, some of the criteria omitted are of considerable clinical importance. We suggest that in the design phase of clinical trials, proposed eligibility criteria be scrutinized closely. Those criteria that survive this scrutiny and that have clinical import must be reported upon fully and accurately when communicating trial results. (shrink)

The American Academy of Pediatrics Task Force on Circumcision published its policy statement and technical report on newborn circumcision in September 2012.1 ,2 Since that time, some individuals and groups have voiced objections to the work of the Task Force, while others have conveyed their support. The AAP task force is pleased that the policy statement and technical reports on circumcision have stimulated debate on this topic and welcomes respectful discussion and dialogue about the scientific and ethical issues that surround (...) neonatal circumcision. We believe this is a complex issue that does not lend itself to simplistic solutions. The Task Force encourages those of all viewpoints to contribute to a vibrant, thoughtful and respectful evidence-based dialogue. We appreciate that the free exchange of competing ideas is a necessary component of scientific discovery. We also recognise that all clinical decisions carry ethical dimensions and that a respectful and thoughtful dialogue about these issues is important. However, the Task Force also feels strongly that this debate and the academic literature are demeaned when those with an ideological agenda disseminate inaccurate information, misapply scientific principles, make accusations that are unsupported, communicate in a vitriolic tone, and attempt to discredit and mischaracterise alternative views and those who hold them. Healthy debate and …. (shrink)

Motivated ignorance is an incentivized absence of knowledge that arises in circumstances of unequal power relations, a self-protective non-knowing which frees individuals from having to reflect on the privileges they have in virtue of membership in a dominant social group. In philosophical discussions, the term “motivated ignorance” gets used interchangeably with “willful ignorance.” In the first half of this paper, using Charles Mills’ (2007) white ignorance as the defining case, I argue that this is a mistake. A significant swath (...) of cases of motivated ignorance are non-willful, or deep, following Rik Peels (2010). But in all cases, benefits accrued to some in virtue of their social position are gained and maintained at the expense of harms to others. In the second half of this paper, I argue that these harms are what ground attributions of culpability in cases of motivated ignorance and drive the normative requirement that the subject know better, so long as the facts in question are ordinarily and easily knowable (in a sense to be specified). Willfulness is not a necessary condition for culpability, even if it is a sufficient one. (shrink)

: When may a physician legitimately offer enrollment in a randomized clinical trial (RCT) to her patient? Two answers to this question have had a profound impact on the research ethics literature. Equipoise, as originated by Charles Fried, which we term Fried's equipoise (FE), stipulates that a physician may offer trial enrollment to her patient only when the physician is genuinely uncertain as to the preferred treatment. Clinical equipoise (CE), originated by Benjamin Freedman, requires that there exist a (...) state of honest, professional disagreement in the community of expert practitioners as to the preferred treatment. FE and CE are widely understood as competing concepts. We argue that FE and CE offer separable and, in themselves, incomplete justifications for the conduct of clinical trials. FE articulates conditions under which the fiduciary duties of physician to patient may be upheld in the conduct of research. CE sets out a standard for the social approval of research by institutional review boards. Viewed in this way, FE and CE are not necessarily competing notions, but rather address complementary moral concerns. (shrink)

Books reviewed in this article: The Anchor Bible Dictionary. Edited by David Noel Freedman with Gary A. Herion, David F. Graf, John David Pleins. The Gospel of Matthew. By Daniel J. Harrington. Paul: An Introduction to his Thought. By C. K. Barrett. A Radical Jew: Paul and the Politics of Identiy. By Daniel Boyarin. New Testament Theology. By G. B. Caird, completed and edited by L. D. Hurst. The Fatherhood of God from Origen to Athanasius. By Peter Widdicombe. Dieu (...) et le Christ selon Grégoire de Nysse. By Bernard Pottier. Eucharistic Presence: A Study in the Theology of Disclosure. By Robert Sokolowski. Theological Hermeneutics: Development and Significance. By Werner Jeanrond. Theologie aus Efahrung der Gnade. Annäherungen an Karl Rahner: Edited by Mariano Delgado and Mathias‐Lutz Bachmann. Bernhard Welte's Fundamental Theological Approach to Christology.. By Anthony J. Godzieba. Sacred Identity: Exploring a Theology of the Person. By Jane Kopas. A Salvation Audit. By Colin Grant. Medical Ezhics: Sources Of Catholic Teachings, Second Edition. Edited by Kevin O'Rourke and Philip Boyle. Mission and Conversion: Proselytizing in the Religious History of the Roman Empire. By Martin Goodman. Literacy and Power in the Ancient World. Edited by Alan K. Bowman and Greg Woolf. St Cyril of Alexandria: The Christological Controversy. Its History, Theology and Texts. By John A. McGuckin. Ambrose of Milan: Church and Court in a Christian Capital. By Neil B. McLynn. Basil of Cuesareu. By Philip Rousseau. Augustine. By Mary T. Clark. Irenaeus. By Dennis Minns. Divine Heiress: The Virgin Mary and the Creation of Christian Constantinople. By Vasiliki Limberis. The Irish Tradition in Old English Literature. By Charles D. Wright. Relics, Apocalypse and the Deceils of History: Ademar of Chabannes, 989–1034. By Richard Landes. Huguccio: The Life, Works, and Thought of a Twelfth‐Centuy Jurist. By Wolfgang P. Müller. The Presence of God: A History of Western Christian Mysticism, Volume II: The Growth of Mysticism. By Bernard McGinn. Preaching the Crusades: Mendicant Friars and the Cross in the Thirteenth Century. By Christoph T. Maier. Mary Ward: A World in Contemplation. By Henriette Peters. The Letters of Teilhard de Chardin and Lucile Swan. Edited by Thomas M. King and Mary Wood Gilbert. Pseudo‐Marry: By John Donne. Edited, with an Introduction and Commentary, by Anthony Raspa. Donne and the Politics of Conscience in Early Modern England. By M. L. Brown. The Caroline Captivity of the Church: Charles 1 and the Remoulding of Anglicanism. By Julian Davies. Érudition et religion aux XVIIe et XVIIIe siécles. By Bruno Neveu. Cardinal Lavigerie: Churchman, Prophet and Missionary. By François Renault. Dom Columba Marmion: A Biography By Mark Tierney. Christian Mission in the Twentieth Century. By Timothy Yates. Religion in Africa: Experience and Expression. Edited by Thomas D. Blakely, Walter E. A. van Beek and Dennis Thomson. (shrink)

Jean-Jacques Rousseau and Adam Smith are giants of eighteenth century thought. The heated controversy provoked by their competing visions of human nature and society still resonates today. Smith himself reviewed Rousseau's Discourse on Inequality, and his perceptive remarks raise an intriguing question: what would a conversation between these two great thinkers look like? In this outstanding book Charles Griswold analyses, compares and evaluates some of the key ways in which Rousseau and Smith address what could be termed "the question (...) of the self." Both thinkers discuss what we are by nature, who we have become, whether we can know ourselves or each other, how best to articulate the human condition, what it would mean to be free, and whether there is anything that can be done to remedy our deeply imperfect condition. In the course of examining their rich and contrasting views, Griswold puts Rousseau and Smith in dialogue by imagining what they might say in reply to one another. Griswold's wide-ranging exploration includes discussion of issues such as narcissism, self-falsification, sympathy, the scope of philosophy, and the relation between liberty, religion and civic order. A superb exploration of two major philosophers, Jean-Jacques Rousseau and Adam Smith: A Philosophical Encounter is essential reading for students and scholars of these two figures, eighteenth century philosophy, the Enlightenment, moral philosophy, the history of ideas. It will also be of interest to those in related disciplines such as political theory, economics, and religion. (shrink)

Of laws in general -- Of laws directly derived from the nature of government -- Of the principles of the three kinds of government -- That the laws of education ought to be relative to the principles of government -- That the laws given by the legislator ought to be relative to the nature of government -- Consquences of the principles of different governments, with respect to the simplicity of civil and criminal laws, the form of judgements, and inflicting of (...) punishments -- Consquences of the different principles of the three governments, with respect to sumptuary laws, luxury, and the condition of women -- Of the corruption of the principles of the three governments -- Of the laws in the relation they bear to defensive force -- Of laws, in the relation they bear to offensive force. (shrink)

Charles Travis,Corinne Lajoie,Bruno Ambroise.

In [2] Hempel and Oppenheim give a definition of “explanation” for a certain formal language. In [1] Eberle, Kaplan, and Montague prove five theorems demonstrating that the Hempel and Oppenheim definition is not restrictive enough. In [3] Kim proposes two further conditions to supplement the Hempel and Oppenheim definition in order to avoid the objections posed in [1]. In this paper it is shown that the definition of Hempel and Oppenheim supplemented by Kim's conditions is open to a trivialization very (...) analogous to that given in [1]. (shrink)

John Dewey once said of philosophical problems that they are quite different from old soldiers. Not only do they never die, but they do not even fade away. Something similar might be said about the unfavourable Divine attributes of the 1950s and 60s, timelessness or eternity, necessary existence, foreknowledge of creaturely free choices, and immutability. All have contemporary defenders. Even the puzzling, traditional tenet that God is metaphysically simple now has formidable apologists. Perhaps the least popular of the traditional theistic (...) canon, the most likely to fade away, is the tenet that God is impassible. The recent appearance of Richard Creel's Divine Impassibility has shown that even this least popular of attributes can be powerfully articulated and defended. Roughly, the impassibility thesis is the claim that God does not undergo sensory experience including suffering and pain, nor is God subject to corruption, substantial essential change or to external agency. Creel's defence of Divine impassibilism is certainly the most balanced and sophisticated in the current literature. Any argument for passibilism must take Creel's work seriously. I intend to do just that in the course of defending the thesis that the God of Christian theism is passible in an important respect. There are substantive moral and religious reasons to believe God suffers. (shrink)

The COVID-19 pandemic touched off an unprecedented search for vaccines and treatments. Without question, the development of vaccines to prevent COVID-19 was an enormous scientific accomplishment. Further, the RECOVERY and Solidarity trials identified effective treatments for COVID-19. But all was not success. The urgent need for COVID-19 prevention and treatment fueled an embrace of risks—to research participants and to the reliability of the science itself—as allegedly necessary costs to speed scientific progress. Scientists and (even) ethicists supported overturning longstanding norms protecting (...) healthy volunteers in human challenge trials to speed vaccine development, but these trials led to no vaccines. Physicians, with the approval of research ethics committees, designed hundreds of unblinded, single-center clinical trials at high risk of bias to speed the identification of new treatments. But these clinical trials led to no treatments. The lesson for future pandemics is that the acceptance of greater risks to participants or science does not reliably lead to progress. We are better served by science that upholds the highest ethical and methodological standards. (shrink)

Patient outcome after serious brain injury is highly variable. Following a period of coma, some patients recover while others progress into a vegetative state (unresponsive wakefulness syndrome) or minimally conscious state. In both cases, assessment is difficult and misdiagnosis may be as high as 43%. Recent advances in neuroimaging suggest a solution. Both functional magnetic resonance imaging and electroencephalography have been used to detect residual cognitive function in vegetative and minimally conscious patients. Neuroimaging may improve diagnosis and prognostication. These techniques (...) are beginning to be applied to comatose patients soon after injury. Evidence of preserved cognitive function may predict recovery, and this information would help families and health providers. Complex ethical issues arise due to the vulnerability of patients and families, difficulties interpreting negative results, restriction of communication to “yes” or “no” answers, and cost. We seek to investigate ethical issues in the use of neuroimaging in behaviorally nonresponsive patients who have suffered serious brain injury. The objectives of this research are to: (1) create an approach to capacity assessment using neuroimaging; (2) develop an ethics of welfare framework to guide considerations of quality of life; (3) explore the impact of neuroimaging on families; and, (4) analyze the ethics of the use of neuroimaging in comatose patients. (shrink)

In his influential 1987 essay, “Equipoise and The Ethics of Randomized Clinical Research,” Benjamin Freedman argued that Charles Fried’s theoretical equipoise requirement threatened clinical research because it was overwhelmingly fragile and rendered unethical too many randomized clinical trials. Freedman, therefore, proposed an alternative requirement, the clinical equipoise requirement, which is now considered to be the fundamental or guiding principle concerning the ethics of enrolling patients in randomized clinical trials. In this essay I argue that Freedman’s clinical (...) equipoise requirement is ambiguous and can be interpreted in (at least) two different ways. I furthermore claim that, ironically, the best interpretation of the clinical equipoise requirement opens Freedman to the same objection that he leveled against Fried twenty-five years ago; namely, that it (Freedman’s clinical equipoise requirement) renders unethical too many randomized clinical trials. (shrink)

In this issue ofJME, Watsonet alcall for research evaluation of government health programmes and identify ethical guidance, including the Ottawa Statement on the ethical design and conduct of cluster randomised trials, as a hindrance. While cluster randomised trials of health programmes as a whole should be evaluated by research ethics committees (RECs), Watsonet alargue that the health programme per se is not within the researcher’s control or responsibility and, thus, is out of scope for ethics review. We argue that this (...) view is wrong. The scope of research ethics review is not defined by researcher control or responsibility, but rather by the protection of research participants. And the randomised evaluation of health programmes impacts the liberty and welfare interests of participants insofar as they may be exposed to a harmful programme or denied access to a beneficial one. Further, Watsonet al’s claim that ‘study programmes … would occur whether or not there were any … research activities’ is incorrect in the case of cluster randomised designs. In a cluster randomised trial, the government does not implement a programme as usual. Rather, researchers collaborate with the government to randomise clusters to intervention or control conditions in order to rigorously evaluate the programme. As a result, equipoise issues are triggered that must be addressed by the REC. (shrink)