The development of cancer therapies is a long and arduous process. Because it can take several years for a cancer agent to pass clinical testing and be approved for use, terminal cancer patients rarely have the time to see these experimental therapies become widely available. For most terminal cancer patients the only opportunity they have to access an experimental drug that could potentially improve their prognosis is by joining a clinical trial. Unfortunately, several aspects of clinical (...) class='Hi'>trial methodology that are set in place in order to optimise drug development for the benefit of future generations of cancer patients, pose significant limitations to current patient participation. Therefore, several terminal cancer patients believe that they should have the right to access experimental agents that have passed initial safety testing without having to participate in clinical trials. However, granting off-trial access to patients could be detrimental to the scientific process of drug development, and thus could pose significant risks to the health of future patients relying on sound research. Examining this matter through two divergent ethical lenses, rights-based ethics and communitarian ethics, may provide new insight into the issues surrounding the balance between the autonomous rights of current terminal cancer patients, and the needs of future patients and the values of society. (shrink)

The article discusses the issue of the justification of experimenting on human subjects from the point of view of the individual participant. The discussion is conducted on three levels, which can be viewed as a hierarchy:I. Rationality: does one have good self-regarding reasons to subject oneself to medical experimentation?II. Justice: does one have a duty or an obligation to take part in medical research?III. Virtue: ought one contribute to the long-term attempt to promote medical knowledge and the overall health of (...) human beings?Rationality is shown to have only a limited force in such a justification, since many experiments cannot be shown to serve the interests of the participant in any way. Justice fares slightly better, since it is based on the idea of a social contract which goes beyond individual prudence. But, since many medical experiments promote the health only of future generations, the condition of mutuality, which is one of the bases of a social contract, is not satisfied. Thus, the ultimate reason to take part in medical research is associated with the supererogatory volunteering of people, who are motivated by the wish to contribute to a highly valuable enterprise with no expectation of return.The three types of reasons are complementary rather than exclusive, and the potential failure of all of them may lead to the undesirable commercialization of the field. Der Beitrag untersucht die Frage, ob und wie medizinische Versuche an Menschen aus der Sicht des einzelnen Teilnehmers gerechtfertigt werden können. Die Diskussion dieser Frage wird auf drei Ebenen geführt, die sich in einem Stufenverhältnis darstellen lassen,I. der Ebene der Zweckrationalität: Gibt es gute Gründe, und zwar durchaus des individuellen Eigennutzes, sich selbst für medizinische Versuche zur Verfügung zu stellen?II. der Ebene der Gerechtigkeit: Besteht eine Pflicht oder eine Verbindlichkeit zur Teilnahme an medizinischer Forschung?III. der Ebene der Tugend: Soll man zu dem auf lange Sicht angelegten Versuch beitragen, das medizinische Wissen und die Gesundheit der Menschen insgesamt zu fördern?Es wird gezeigt, daß das Argument der Zweckrationalität für eine mögliche Rechtfertigung nur von begrenzter Bedeutung ist. Denn viele Experimente dienen den Interessen des unmittelbaren Teilnehmers nachweislich in keiner Weise. Das Argument der Gerechtigkeit hat zwar eine etwas größere Kraft, weil Gerechtigkeit auf der Idee eines Gesellschaftsvertrags beruht, die über den Horizont individueller Klugheit hinausreicht. Da aber viele medizinische Experimente nur die Gesundheit zukünftiger Generationen fördern, ist die Bedingung der Gegenseitigkeit, die eine der Grundlagen des Gesellschaftsvertrags bildet, nicht erfüllt. Der dritte und letzte Grund für eine Teilnahme an medizinischer Forschung steht deshalb in enger Verbindung mit dem freiwilligen supererogatorischen Verhalten von Leuten, die durch den Wunsch motiviert sind, ohne Aussicht auf Gegenleistung zu einer höchst wertvollen Unternehmung etwas beizutragen.Die drei Arten von Gründen ergänzen sich mehr, als daß sie sich ausschließen. Ein mögliches Scheitern aller dieser Gründe könnte zu einer unerwünschten Kommerzialisierung der Teilnahme an medizinischen Experimenten führen. (shrink)

The need for continuing provision of beneficial experimental interventions after research is concluded remains a controversial topic in bioethics for research. Based on the principle of beneficence, justice as reciprocity, concerns about exploitation and fair benefits, participants should be able to have continuing access to benefits beyond the research period. However, there is no consensus about whether or not post-trial provision of beneficial interventions should be mandatory for participants from developing countries. This paper summarises recommendations from international and (...) national guidelines. Ethical principles and practical issues relating to post-trial provision are also discussed. In conclusion, post-trial provision is not necessary in all situations and a set of criteria are proposed to identify the situations that beneficial interventions should be provided beyond the research period. However, mandatory post-trial supply of beneficial experimental interventions should be assured for those who still need and are able to benefit from them but have no alternative access. Mandatory provision is based on universal bioethical principles such as beneficence and justice. Furthermore, difficulties associated with implementation of post-trial provision are not unmanageable. Careful advanced planning and a comprehensive partnership among relevant parties would be very helpful in solving these difficulties in practice, which therefore should not be taken as an excuse to escape post-trial responsibility. (shrink)

To what extent does the design of statistical experiments, in particular sequential trials, affect their interpretation? Should postexperimental decisions depend on the observed data alone, or should they account for the used stopping rule? Bayesians and frequentists are apparently deadlocked in their controversy over these questions. To resolve the deadlock, I suggest a three‐part strategy that combines conceptual, methodological, and decision‐theoretic arguments. This approach maintains the pre‐experimental relevance of experimental design and stopping rules but vindicates their evidential, postexperimental (...) irrelevance. †To contact the author, please write to: Tilburg Center for Logic and Philosophy of Science, Tilburg University, P.O. Box 90153, 5000 LE Tilburg, The Netherlands; e‐mail: [email protected]. (shrink)

Today's clinical AIDS research is in trouble. Principal investigators are confronted with young and frequently highly knowledgeable patients. Many of these people with AIDS are often unwilling to adhere to the trial protocols. These PWAs believe they are ethically justified in breaching trial protocols because they do not consider themselves true volunteers in such trials. PWAs argue that they do not really volunteer because existing legislation prevents them from buying and using experimental drugs or from testing alternative (...) treatment strategies. Their only access to such agents is participation in clinical trials. (shrink)

This new edition of Charles Fried's 'Medical Experimentation' includes a general introduction by Franklin Miller and the late Alan Wertheimer, a reprint of the 1974 text, an in-depth analysis by Harvard Law School scholars I. Glenn Cohen and D. James Greiner, and a new essay by Fried reflecting on the original text and how it applies to the contemporary landscape of medicine and medical experimentation.

I read with great bewilderment the unconvincing arguments of Peter F. Omonzejele in his article “Ethical Challenges Posed by the Ebola Virus Epidemic in West Africa” published in the 11 issue of the Journal of Bioethical Inquiry. While the author glaringly mixed up anthropological issues concerning the hygiene of hand-washing and safe burials in an article with a title clearly focused on ethical challenges, he failed to establish how the current Ebola epidemic ravaging some West Africa countries made these human (...) practices ethical challenges. Anecdotal examples cited in the article fit entirely into the realm of anthropological and sociological issues fuelling the spread of Ebola but are not in any way related to ethical challenges. The title was either misleading or the author deliberately discussed anthropological/sociological issues tangentially in an article supposedly written on ethical issues.The author also contradicted himself, having categorized as a compelling need t .. (shrink)

Patients have received experimental pharmaceuticals outside of clinical trials for decades. There are no industry-wide best practices, and many companies that have granted compassionate use, or ‘preapproval’, access to their investigational products have done so without fanfare and without divulging the process or grounds on which decisions were made. The number of compassionate use requests has increased over time. Driving the demand are new treatments for serious unmet medical needs; patient advocacy groups pressing for access to emerging treatments; internet (...) platforms enabling broad awareness of compelling cases or novel drugs and a lack of trust among some that the pharmaceutical industry and/or the FDA have patients’ best interests in mind. High-profile cases in the media have highlighted the gap between patient expectations for compassionate use and company utilisation of fair processes to adjudicate requests. With many pharmaceutical manufacturers, patient groups, healthcare providers and policy analysts unhappy with the inequities of the status quo, fairer and more ethical management of compassionate use requests was needed. This paper reports on a novel collaboration between a pharmaceutical company and an academic medical ethics department that led to the formation of the Compassionate Use Advisory Committee. Comprising medical experts, bioethicists and patient representatives, CompAC established an ethical framework for the allocation of a scarce investigational oncology agent to single patients requesting non-trial access. This is the first account of how the committee was formed and how it built an ethical framework and put it into practice. (shrink)

The outsourcing of clinical trials to Latin America by the transnational innovative pharmaceutical industry began about twenty years ago. Using archival information and field work in Argentina, Brazil, Costa Rica, Mexico and Peru, the authors discuss the regulatory contexts and the ethical dimensions of human experimentation in the region. More than 80% of all clinical trials in the region take place in these countries, and the European Medicines Agency has defined them as priority countries in Latin America. The authors raise (...) questions about the quality of data obtained from the trials and the violation of human rights during their implementation. Their findings are presented in this volume, the first in-depth analysis of clinical trials in the region.. (shrink)

Aim: Streamlining consent for low-risk comparative effectiveness research (CER) could facilitate research, while safeguarding patients' rights. Materials & methods: 2618 adults were randomized to one of seven consent approaches (six streamlined and one traditional) for a hypothetical, low-risk CER study. A survey measured understanding, voluntariness, and feelings of respect. Results: Participants in all arms had a high understanding of the trial and positive attitudes toward the consent interaction. Highest satisfaction was with a streamlined approach showing a video before the (...) medical appointment. Participants in streamlined were more likely to mistakenly think a signature was required. Conclusion: Streamlined consent was no less acceptable than traditional, signed consent. Streamlined and traditional approaches achieved similar levels of understanding, voluntariness and a feeling that the doctor–patient interaction was respectful. (shrink)

We simulate trial data to test speculative claims about research methods, such as the impact of publication bias.

In this paper, Isuggest that placebo effects, as we know them today, should be understood as experimental phenomena, low-level regularities whose causal structure is grasped through particular experimental designs with little theoretical guidance. Focusing on placebo interventions with needles for pain reduction -one of the few placebo regularities that seems to arise in meta-analytical studies- I discuss the extent to which it is possible to decompose the different factors at play through more fine-grained randomized clinical trials. My sceptical (...) argument is twofold. On the one hand, I argue that experiments alone are not enough to standardize interventions, and that it is necessary to include theories. On the other hand, I argue that the social interactions that seem to be part of placebo effects are difficult, if not impossible, to blind. Therefore, the measurement biases arising from the participants’ reactivity to the experimental setup cannot be controlled for. Further decomposition of placebo effects requires a theoretical account of the existing experimental regularities that may guide further tests. (shrink)

This target article is concerned with the implications of the surprisingly different experimental practices in economics and in areas of psychology relevant to both economists and psychologists, such as behavioral decision making. We consider four features of experimentation in economics, namely, script enactment, repeated trials, performance-based monetary payments, and the proscription against deception, and compare them to experimental practices in psychology, primarily in the area of behavioral decision making. Whereas economists bring a precisely defined “script” to experiments for (...) participants to enact, psychologists often do not provide such a script, leaving participants to infer what choices the situation affords. By often using repeated experimental trials, economists allow participants to learn about the task and the environment; psychologists typically do not. Economists generally pay participants on the basis of clearly defined performance criteria; psychologists usually pay a flat fee or grant a fixed amount of course credit. Economists virtually never deceive participants; psychologists, especially in some areas of inquiry, often do. We argue that experimental standards in economics are regulatory in that they allow for little variation between the experimental practices of individual researchers. The experimental standards in psychology, by contrast, are comparatively laissez-faire. We believe that the wider range of experimental practices in psychology reflects a lack of procedural regularity that may contribute to the variability of empirical findings in the research fields under consideration. We conclude with a call for more research on the consequences of methodological preferences, such as the use on monetary payments, and propose a “do-it-both-ways” rule regarding the enactment of scripts, repetition of trials, and performance-based monetary payments. We also argue, on pragmatic grounds, that the default practice should be not to deceive participants. Key Words: behavioral decision making; cognitive illusions; deception; experimental design; experimental economics; experimental practices; financial incentives; learning; role playing. (shrink)

Experimental balance is usually understood as the control for the value of the conditions, other than the one under study, which are liable to affect the result of a test. We will discuss three different approaches to balance. ‘Millean balance’ requires to identify and equalize ex ante the value of these conditions in order to conduct solid causal inferences. ‘Fisherian balance’ measures ex post the influence of uncontrolled conditions through the analysis of variance. In ‘efficiency balance’ the value of (...) the antecedent conditions is decided ex ante according to the efficiency they yield in the estimation of the treatment outcome. Against some old arguments by John Worrall, we will show that in both Fisherian and efficiency balance there are good reasons to randomize the allocation of treatments, in particular when there is no agreement among experimenters as to the antecedent conditions to be controlled for. (shrink)

Throughout the sixteenth century, learned physicians across Europe performed a diverse array of “trials” of phenomena and published reports about them. This essay traces the phrase “periculum facere” (“to make a trial”) and related terms through natural history investigations, drug testing, chymical analysis, and anatomical discoveries. Physicians used ancient precedents, their learned expertise, and pedagogical authority to anchor the epistemic status of their trials and incorporated the historical narratives of their trial-making within arguments to factual and causal knowledge, (...) even philosophical scientia. Developed from engagement with things, ancient texts, other healers, and students, this lively tradition of contrived, first-person empirical trials flourished in some academic institutions, especially the University of Padua. The frequency and visibility of sixteenth-century medical trials, especially in the education of hundreds of students annually, is essential evidence for understanding how experimentation came to be widespread in early modern Europe. (shrink)

Spectacular treatment disasters in recent years have made it clear that informal "let's-try-it-and-see" methods of testing new proposals are more risky now than ever before, and have led many to call for a halt to experimentation in clinical medicine. In this easy-tp-read, philosophical guide to human experimentation, William Silverman pleads for wider use of randomized clinical trials, citing many examples that show how careful trials can overturn preconceived or ill-conceived notions of a therapy's effectiveness and lead to a clearer understanding (...) of clinical anomalies. Because it gives careful guidance on setting up trials and avoiding conceptual pitfalls, this book will be of great interest to all epidemiologists and clinical statisticians, and to a wide varitey of clinicians, pharmacologists, and nurses. Since it requires no medical or statistical knowledge, it will also appeal to ethicists, lawyers, and the general public. (shrink)

Bioethics, Volume 36, Issue 1, Page 25-41, January 2022.

Successful clinical trials are important for all of us, but they can be extremely complicated to design and run, so work must be done to consider what commonly goes wrong and how these issues can be addressed. Gelinas et al suggest an ethical argument for institutional prioritisation of clinical trials conducted among limited populations. This is to ensure successful recruitment and prevent competing trials rendering each other irrelevant through lack of statistical power. But they overlook the fact that effective prioritisation (...) already occurs, and their suggestion produces yet another hurdle for researchers to overcome. Their argument hinges around the claim that allocation of participants to trials represents an inevitable rationing scenario and, like all rationing scenarios, the best methods should be used for objectively determining how limited resources are distributed to achieve the end goal.1 Although they acknowledge that both individuals and clinicians may have preferences as to which trial a patient participates in, trial interventions are by definition experimental, and therefore choosing between trials is not really analogous to choosing between alternative clinical interventions. Here it seems that although clinical instinct is important when determining treatment options, a clinical trial is a specific attempt to create systematic justified knowledge and thus individual patient/clinician autonomy …. (shrink)

Despite ample evidence that speech production is associated with extensive trial-to-trial variability, it remains unclear whether this variability represents merely unwanted system noise or an actively regulated mechanism that is fundamental for maintaining and adapting accurate speech movements. Recent work on upper limb movements suggest that inter-trial variability may be not only actively regulated based on sensory feedback, but also provide a type of workspace exploration that facilitates sensorimotor learning. We therefore investigated whether experimentally reducing or magnifying (...) inter-trial formant variability in the real-time auditory feedback during speech production leads to adjustments in formant production variability that compensate for the manipulation, changes the temporal structure of formant adjustments across productions, and enhances learning in a subsequent adaptation task in which a predictable formant-shift perturbation is applied to the feedback signal. Results show that subjects gradually increased formant variability in their productions when hearing auditory feedback with reduced variability, but subsequent formant-shift adaptation was not affected by either reducing or magnifying the perceived variability. Thus, findings provide evidence for speakers’ active control of inter-trial formant variability based on auditory feedback from previous trials, but–at least for the current short-term experimental manipulation of feedback variability–not for a role of this variability regulation mechanism in subsequent auditory-motor learning. (shrink)

The maternal‐fetal HIV transmission trials, conducted in developing countries in the 1990s, undoubtedly generated one of the most intense, high profile controversies in international research ethics. They sparked off a prolonged acrimonious and public debate and deeply divided the scientific community. They also provided an impetus for the revision of the Declaration of Helsinki – the most widely known guideline for international research. In this paper, I provide a brief summary of the context, outline the arguments for and against the (...) controversial use of placebo controls, and focus on particular areas that I believe merit further discussion or clarification. On balance, I argue that the researchers failed in their duties to protect the best interests of their research subjects, and to promote distributive justice. I discuss the difficulties of obtaining valid consent in this research context, and argue that it is unethical to inform women of their HIV status without at least offering them prophylactic treatment for their unborn children. A global view of justice, which endorses international equity, cannot be squared with international research guidelines that allow ‘local conditions’ to define the scope of duty to the control group. Finally, I suggest that the heated debate reflects a tension, if not an outright war, between two conflicting meta‐ethical systems, or incommensurable paradigms, that underpin scientific research involving human subjects. (shrink)

Tremendous development in recent medical science and the consequent discoveries resulting in successful prevention and also cure of different diseases are shared by clinical research involving the human volunteers. Preceding the trials in the human subjects, and to ensure safety, the proposed drug and other interventions are either tested in animals (vivo) or in laboratory (vitro) to evaluate initial safe starting dose for the human beings and to key out the benchmarks for the clinical monitoring for the potential unfavorable effects. (...) These pre human trials might not necessarily protect against the untoward effects in the human beings as happened in the case of thalidomide tragedy, which caused disability and killed thousands of babies born to the mothers, those who took this medicine. Use of healthy human volunteers in the preliminary experiments or phase I clinical trials either reduces or excludes risks of subsequent undesirable effects in the future trails (1). Phase-1 trials are conducted in order to test the safety, reactions and immunogenicity of vaccines in volunteers. Novel treatments for the cancer are first tested in phase 1 trials enrolling the patients with advanced disease, who have exhausted the standard treatment options. Phase-1 oncology trials are the pivot point in the translation of new cancer therapies from bench to bedside. Nevertheless, these trials remain ethically controversial. The controversy stems from the fact that, classically, phase-1 oncology clinical trials involve first-in-human testing of experimental treatment candidates in patients with a terminal diagnosis, who typically have exhausted standard treatment options. Commentators on the ethics of phase-1 clinical trials make diametrically opposed claims about the prospect of direct medical benefit from participation in these trials-benefits that can be attributed to receiving the experimental treatment intervention. One camp of benefit skeptics, inhabited mainly by bioethicists, characterizes this form of research as lacking any reasonable prospect of direct medical benefit. They see an ethical cloud hovering over phase-1 trials, because the vast majority of patients volunteer for phase-1 trials out of a motivation to receive medical benefit. In the view of these skeptics, such patients therefore harbor a ‘therapeutic misconception’ about research participation. This misconception calls into question the validity of informed consent and thereby undercuts the ethical basis of these trials (2). In this paper, I will discuss the ethical justification of the participation of human volunteers in phase-1 trials. (shrink)

The subject of this article are the definitional and regulatory aspects of experimental (or innovative) therapies, understood either as new and unproven treatment methods that can be tested – and for this purpose used – also in clinical trials, or as applications of these new and unproven procedures in medical practice. After a short introduction, recalling one of the important sources of the concept of experimental or innovative therapy, which was the Belmont Report, I first discuss the problems (...) related to the definition of experimental therapy (as a new and nonvalidated medical procedure used to improve the patient's health), and then the controversial issues related to its regulation (including in particular the required control to which each such therapeutic intervention should be subject). Finally, I point out the importance of the discussions on experimental therapy reported in this article, conducted in other countries or in international contacts, for the necessary revision or reinterpretation of Polish regulations regarding therapeutic experiments. (shrink)

The recent Ebola virus disease outbreak in Western African countries has raised questions regarding the feasibility of adopting conventional trial designs such as randomized controlled trials for conducting experimental trials in the midst of a fatal epidemic. In the context of Ebola ça Suffit trial conducted in Guinea for testing the efficacy and effectiveness of rVSV–ZEBOV, a candidate vaccine, I argue that the trial design and the methodologies adopted for the trial have been rightly chosen (...) for their ethical appropriateness and social utilities rather than only epistemic advantages. In this paper, I propose and defend the view that in varying scientific research contexts, it is entirely legitimate that non-epistemic values may be prioritized over epistemic considerations. Two vital methodological choices scientists should make while designing a clinical trial are: the choice of appropriate control group and the choice of appropriate randomization. Given this background, I show that the choice of delayed vaccination arm as the control group over placebo control group and the choice of cluster randomization over individually controlled randomization for conducting Ebola ça Suffit trial are perfect instances of such a scenario where addressing social and ethical issues have been justifiably prioritized over epistemic values so that the research in a specific scientific context could be conducted in a socially relevant manner. (shrink)

In this introduction, we address some of the complexities associated with the emergence of medicine’s bodies, not least as a means to ‘working with the body’ rather than simply producing a critique of medicine. We provide a brief review of some of the recent discussions on how to conceive of medicine and its bodies, noting the increasing attention now given to medicine as a technology or series of technologies active in constituting a multiplicity of entities – bodies, diseases, experimental (...) objects, the individualization of responsibility for health and even the precarity of life. We contrast what feminist theorists in the tradition of Judith Butler have referred to as the question of matter, and Science and Technology Studies with its focus on practice and the nature of emergence. As such we address tensions that exist in analyses of the ontological status of ‘the body’ – human and non-human – as it is enacted in the work of the laboratory, the randomized controlled trial, public health policy and, indeed, the market that is so frequently entangled with these spaces. In keeping with the recent turns toward ontology and affect, we suggest that we can regard medicine as concerned with the contraction and reconfiguration of the body’s capacities to affect and be affected, in order to allow for the subsequent proliferation of affects that, according to Bruno Latour, marks corporeal life. Treating both contraction and proliferation circumspectly, we focus on the patterns of affects wrought in particular by the abstractions of medicine that are described in the contributions to this special issue. Drawing on the work of A.N. Whitehead, we note how abstractions such as ‘medical evidence’, the ‘healthy human body’ or the ‘animal model’ are at once realized and undercut, mediated and resisted through the situated practices that eventuate medicine’s bodies. Along the way, we touch on the implications of this sort of perspective for addressing the distribution of agency and formulations of the ethical and the political in the medical eventuations of bodies. (shrink)

Definition of the problem: A `experimental treatment' is defined as the use of a not yet approved medical treatment or product in a single patient outside the scope of regular clinical trials. Especially in oncology the patient is usually in a desperate situation and does not respond to other treatments. Even if he or she is fully informed about the risks he or she may occasionally make an irrational decision.Discussion of the problem: The moral problems in experimental treatments (...) have to do with the medical and scientific quality of the treatment and the patient-physician relationship. It is argued that there are also moral duties for pharmaceutical manufacturers and health insurrance companies.Conclusion: A regulation of experimental treatment trials is necessary both for physicians and for pharmaceutical manufacturers. (shrink)

Multisensory integration can alter information processing, and previous research has shown that such processes are modulated by sensory switch costs and prior experience. Here we report an incidental finding demonstrating, for the first time, the interplay between these processes and experimental factors, specifically the presence of the experimenter in the testing room. Experiment 1 demonstrates that multisensory motor facilitation in response to audiovisual stimuli is higher in those trials in which the sensory modality switches than when it repeats. Those (...) participants who completed the study while alone exhibited increased RT variability. Experiment 2 replicated these findings using the letters “b” and “d” presented as unisensory stimuli or congruent and incongruent multisensory stimuli. Multisensory enhancements were inflated following a sensory switch; that is, congruent and incongruent multisensory stimuli resulted in significant gains following a sensory switch in the monitored condition. However, when the participants were left alone, multisensory enhancements were only observed for repeating incongruent multisensory stimuli. These incidental findings therefore suggest that the effects of letter congruence and sensory switching on multisensory integration are partly modulated by the presence of an experimenter. (shrink)

If definitive evidence concerning treatment effectiveness becomes available from an ongoing randomized clinical trial, then the trial could be stopped early, with the public release of results benefiting current and future patients. However, stopping an ongoing trial based on accruing outcome data requires methodological rigor to preserve validity of the trial conclusions. This has led to the use of formal interim monitoring procedures, which include inefficacy monitoring that will stop a trial early when the (...) class='Hi'>experimental treatment appears not to be working. For participants, inefficacy monitoring is especially important as it ensures that they are not being treated worse than if they had not enrolled on the trial. We discuss the importance of reporting with trial results the formal interim inefficacy monitoring guidelines that were utilized, and, if none were used, the reasons for their absence. A survey of two leading medical journals suggests that this is not current practice. (shrink)

Despite their crucial role in the translation of pre-clinical research into new clinical applications, phase 1 trials involving patients continue to prompt ethical debate. At the heart of the controversy is the question of whether risks of administering experimental drugs are therapeutically justified. We suggest that prior attempts to address this question have been muddled, in part because it cannot be answered adequately without first attending to the way labor is divided in managing risk in clinical trials. In what (...) follows, we approach the question of therapeutic justification for phase 1 trials from the viewpoint of five different stakeholders: the drug regulatory authority, the IRB, the clinical investigator, the referring physician, and the patient. Our analysis shows that the question of therapeutic justification actually raises multiple questions corresponding to the roles and responsibilities of the different stakeholders involved. By attending to these contextual differences, we provide more coherent guidance for the ethical negotiation of risk in phase 1 trials involving patients. We close by discussing the implications of our argument for various perennial controversies in phase 1 trial practice. (shrink)

Using a variety of different results from the literature, I show how causal discovery with experiments is limited unless substantive assumptions about the underlying causal structure are made. These results undermine the view that experiments, such as randomized controlled trials, can independently provide a gold standard for causal discovery. Moreover, I present a concrete example in which causal underdetermination persists despite exhaustive experimentation and argue that such cases undermine the appeal of an interventionist account of causation as its dependence on (...) other assumptions is not spelled out. (shrink)

ABSTRACT“Evidence-based” methods, which most prominently include randomized controlled trials, have gained increasing purchase as the “gold standard” for assessing the effect of public policies. But the enthusiasm for evidence-based research overlooks questions about the reliability and applicability of experimental findings to diverse real-world settings. Perhaps surprisingly, a qualitative study of British educators suggests that they are aware of these limitations and therefore take evidence-based findings with a much larger grain of salt than do policy makers. Their experience suggests that (...) the real world is more heterogeneous than the world imagined by evidence-based policy enthusiasts. (shrink)