This paper addresses the concept of moral luck. Moral luck is discussed in the context of medical error, especially an error of omission that occurs frequently, but only rarely has adverse consequences. As an example, a failure to compare the label on a syringe with the drug chart results in the wrong medication being administered and the patient dies. However, this error may have previously occurred many times with no tragic consequences. Discussions on moral luck can highlight conflicting intuitions. (...) Should perpetrators receive a harsher punishment because of an adverse outcome, or should they be dealt with in the same way as colleagues who have acted similarly, but with no adverse effects? An additional element to the discussion, specifically with medical errors, is that according to the evidence currently available, punishing individual practitioners does not seem to be effective in preventing future errors. The following discussion, using relevant philosophical and empirical evidence, posits a possible solution for the moral luck conundrum in the context of medical error: namely, making a distinction between the duty to make amends and assigning blame. Blame should be assigned on the basis of actual behavior, while the duty to make amends is dependent on the outcome. (shrink)

The issue of death due to medical errors is not new. We have all heard horror stories about patients dying in the hospital because of a drug mix-up or a surgery patient having the wrong limb amputated. Most people believed these stories were the exception to the rule until November 1999, when the Institute of Medicine issued a report entitled To Err Is Human: Building A Safer Health System. This report focused on medical errors and patient safety (...) in U.S. hospitals. The report indicated that as many as 44,000 to 98,000 people die each year in hospitals as a result of medical errors. These numbers suggest that more Americans are killed in U.S.hospitals every 6 months than died in the entire Vietnam War, and some have compared the alleged rate to fully loaded jumbo jets crashing every other day. This report was not without its critics. (shrink)

The issue of death due to medical errors is not new. We have all heard horror stories about patients dying in the hospital because of a drug mix-up or a surgery patient having the wrong limb amputated. Most people believed these stories were the exception to the rule until November 1999, when the Institute of Medicine issued a report entitled To Err Is Human: Building A Safer Health System. This report focused on medical errors and patient safety (...) in U.S. hospitals. The report indicated that as many as 44,000 to 98,000 people die each year in hospitals as a result of medical errors. These numbers suggest that more Americans are killed in U.S.hospitals every 6 months than died in the entire Vietnam War, and some have compared the alleged rate to fully loaded jumbo jets crashing every other day. This report was not without its critics. (shrink)

Kwaku Marfo, Danielle Garcia, Saira Khalique, Karen Berger, Amy LuMontefiore Medical Center, Bronx, NY, USABackground: Medication errors are a prime concern for all in healthcare. As such the use of information technologies in drug prescribing and administration has received considerable attention in recent years, with the hope of improving patient safety. Because of the complexity of drug regimens in renal transplant patients, occurrence of medication errors is inevitable even with a well adopted computerized physician order entering (...) system. Our objective was to quantify medication error type and frequency in an inpatient renal transplant unit.Methods: Systemic evaluation of all medication errors during an initial 10-day audit and a 28-day follow-up audit in an inpatient renal transplant unit. Each error was concurrently evaluated for potential to result in adverse patient consequences, error type and associated medication class.Results: A total of 103 clinically significant medication errors were detected during the 10-day and 28-day audit time periods. The most common errors were wrong medication dose ordered and wrong time of drug administration. Thirty-six out of 66 prescribing/ordering errors reached the patient.Conclusions: Even with utilization of computerized physician order entry system in an inpatient renal transplant unit, post-kidney transplant patients are at risk for adverse outcomes due to medication errors. The risk factors may be multifactorial and will require both organizational and technical approaches to resolve.Keywords: medication errors, CPOE, inpatient, renal transplant patients. (shrink)

Mass drug screening offers a deceptively simple solution to the problem of drug use among workers. Even a very effective test is subject to error. In any given group of tested individuals, some will unavoidably be falsely accused. Even though scientific tests appear to provide efficient solutions to social and legal problems, these tests should not be accepted unless they also meet our standards for fair dealing.

Over the last decade, philosophers of science have extensively criticized the epistemic superiority of randomized controlled trials for testing safety and effectiveness of new drugs, defending instead various forms of evidential pluralism. We argue that scientific methods in regulatory decision-making cannot be assessed in epistemic terms only: there are costs involved. Drawing on the legal distinction between rules and standards, we show that drug regulation based on evidential pluralism has much higher costs than our current RCT-based system. We analyze (...) these costs and advocate for evaluating any scheme for drug regulatory tests in terms of concrete empirical benchmarks, like the error rates of regulatory decisions. (shrink)

TOT states may be viewed as a temporary and reversible microamnesia. We investigated the effects of lorazepam on TOT states in response to general knowledge questions. The lorazepam participants produced more commission errors and more TOTs following commission errors than the placebo participants . The resolution of the TOTs was unimpaired by the drug. Neither feeling-of-knowing accuracy nor recognition were affected by lorazepam. The higher level of incorrect recalls produced by lorazepam participants may be due to the (...) fact that they were more frequently temporarily unable to access a known item. For some of these items, the awareness of the retrieval failure resulted in a commission TOT . The resolution of the TOT conflict is discussed in the light of the anxiolytic and anticonflict effects of lorazepam. The data are discussed in terms of contemporary theories of TOTs and the effects that benzodiazepines have on semantic memory. (shrink)

A novel data-driven model-free adaptive control approach is first proposed by combining the advantages of model-free adaptive control and data-driven optimal iterative learning control, and then its stability and convergence analysis is given to prove algorithm stability and asymptotical convergence of tracking error. Besides, the parameters of presented approach are adaptively adjusted with fuzzy logic to determine the occupied proportions of MFAC and DDOILC according to their different control performances in different control stages. Lastly, the proposed fuzzy DDMFAC approach is (...) applied to the control of particle quality in drug development phase of spray fluidized-bed granulation process, and its control effect is compared with MFAC and DDOILC and their fuzzy forms, in which the parameters of MFAC and DDOILC are adaptively adjusted with fuzzy logic. The effectiveness of the presented FDDMFAC approach is verified by a series of simulations. (shrink)

In The Ethics of Food, Gregory E. Pence brings together a collection of voices who share the view that the ethics of genetically modified food is among the most pressing societal questions of our time. This comprehensive collection addresses a broad range of subjects, including the meaning of food, moral analyses of vegetarianism and starvation, the safety and environmental risks of genetically modified food, issues of global food politics and the food industry, and the relationships among food, evolution, and human (...) history. (shrink)

Children who experience well-being are engaging more confidently and positively with their caregiver and peers, which helps them to profit more from available learning opportunities and support current and later life outcomes. The goodness-of-fit theory suggests that children’s well-being might be a result of the interplay between their temperament and the environment. However, there is a lack of studies that examined the association between children’s temperament and well-being in early childhood education and care, and whether this association is affected by (...) ECEC process quality. Using a multilevel random coefficient approach, this study examines the association between toddlers’ temperament and well-being in Norwegian ECEC and investigates whether process quality moderates this association. Results reveal an association between temperament and well-being. Staff-child conflict moderates the association between shyness and well-being, and between activity and well-being. Moreover, high emotional behavioral support moderates the association between activity and well-being. Extra attention should be paid by the staff to these children’s needs. (shrink)

Pain policy is not drug policy. If society wants to improve the lives of people in pain and compress the terrible inequalities in its diagnosis and treatment, we have to tailor policy to the root causes driving our problems in treating pain humanely and equitably. In the United States, we do not. Instead, we have proceeded to conflate drug policy with pain policy, relying on arguably magical thinking for the conclusion that by addressing the drug overdose crisis, (...) we are simultaneously addressing the pain crisis. This is a category error, decades of commitment to which have resulted mostly in a worsening of both public health problems. Disentangling our problems in treating pain fairly and equitably from our problems with drugs and substance use is the only path to humane and ethical policy for each. (shrink)

Addiction is almost universally held to be characterized by a loss of control over drug-seeking and consuming behavior. But the actions of addicts, even of those who seem to want to abstain from drugs, seem to be guided by reasons. In this paper, I argue that we can explain this fact, consistent with continuing to maintain that addiction involves a loss of control, by understanding addiction as involving an oscillation between conflicting judgments. I argue that the dysfunction of the (...) mesolimbic dopamine system that typifies addictions causes the generation of a mismatch between the top-down model of the world that reflects the judgment that the addict ought to refrain from drugs, and bottom-up input caused by cues predictive of drug availability. This constitutes a powerful pressure toward revising the judgment and thereby attenuating the prediction error. But the new model is not stable, and shifts under the pressure of bottom-up inputs in different contexts; hence the oscillation of all-things-considered judgment. Evidence from social psychology is adduced, to suggest that a similar process may be involved in ordinary cases of weakness of will. (shrink)

There is an ongoing debate about loss of control in addiction: Some theorists say at least some addicts’ drug-directed desires are irresistible, while others insist that pursuing drugs is a choice. The debate is long-standing and has essentially reached a stalemate. This essay suggests a way forward. I propose an alternative model of loss of control in addiction, one based not on irresistibility, but rather fallibility. According to the model, on every occasion of use, self-control processes exhibit a low, (...) but non-zero, rate of failure due to error. When these processes confront highly recurrent drug-directed desires, the cumulative probability of a self-control lapse steadily grows. The model shows why the following statement—which has an air of paradox—can in fact be true: Each drug-directed desire the addict faces is fully resistible, but the addict nonetheless has significantly diminished control over eventually giving in. (shrink)

The question I want to discuss is that of the sense and respects in which morality is strictly a matter for the individual. To hear some people talk you would think that it is wholly so. Not only do I have to make my own moral decisions; I have in a way to make them on my own terms, in so far as the rules I take to govern my actions are rules I have freely accepted, or at the least (...) not positively repudiated. In law I can be bound by statutes which I regard as abhorrent or even of whose content I am ignorant ; that a similar situation should obtain in morals is commonly treated as absurd. If I see nothing wrong with a certain practice, such as premarital sex or drug-taking, I can’t be brought morally to book for indulging in it. Morals is not solely a matter of personal taste, for the nature of moral judgment is such that the moral agent legislates not just for himself but for all who are similarly situated; equally, however, it is not something which can be externally enforced. There are no objective moral principles, plain for all to see, against which to measure moral error, and though there is fairly widespread agreement among the respectable that some forms of conduct are morally admirable and others morally deplorable, we are under no obligation to respect these “conventions.” A man’s only true obligation here is to follow his conscience and thus do what he takes to be right, in the light of the best information about the situation he can get. (shrink)

No one has the right to say what should be done to their body after deathIn my opinion any concept of property in the human body either during life or after death is biologically inaccurate and morally wrong. The body should be regarded as on loan to the individual from the biomass, to which the cadaver will inevitably return. Development of immunosuppressive drugs has resulted in the cadaver becoming a unique and invaluable resource to those who will benefit from organ (...) donation. Faced with the biological reality, the moral error of any concept of property in the body, and the quantitative failure of voluntary organ donation, I believe that the right of control over the cadaver should be vested in the state as representative of those who may benefit from organ donation.How one regards the dead human body, the cadaver, is in part governed by one’s familiarity with it. At the present time, very few people ever see a cadaver which has not in some way been altered after death, and even fewer touch, handle, deal in any way with the dead human body. In developed countries, death itself most frequently occurs away from the home, in an institution, under the supervision of professional caregivers. For most people, ideas concerning the cadaver, its nature, the proper way to deal with it, are formed under these conditions.As a pathologist specialising in forensic pathology, for 50 years I have been at the other end of the spectrum of experience. In my daily work I have been privileged to examine the cadaver in all its stages after death from the immediate postmortem moments through all the stages of decomposition to bare bones. Working in a relatively small community, I have sometimes been charged with examining the body of someone I …. (shrink)

Impairment of self-control is often said to be a defining feature of addiction. Yet many addicts display what appears to be a considerable amount of control over their drug-oriented actions. Not only are their actions clearly intentional and frequently carried out in a conscious and deliberate manner, there is evidence that many addicts are responsive to a wide range of ordinary incentives and counter-incentives. Moreover, addicts have a wide variety of reasons for using drugs, reasons which often seem to (...) go a long way towards explaining their drug-oriented behavior. Many use drugs, for example, to cope with stressful or traumatic experiences. In this article I argue that some standard philosophical explanations of addicts’ impairment of self-control are inadequate, and propose an alternative. (shrink)

Biometrics has done damage with levels of R or p or Student’s t. The damage widened with Ronald A. Fisher’s victory in the 1920s and 1930s in devising mechanical methods of “testing,” against methods of common sense and scientific impact, “oomph.” The scale along which one would measure oomph is particularly clear in biomedical sciences: life or death. Cardiovascular epidemiology, to take one example, combines with gusto the “fallacy of the transposed conditional” and what we call the “sizeless stare” of (...) statistical significance. Some medical editors have battled against the 5% philosophy, as did, for example, Kenneth Rothman, the founder of Epidemiology. And decades ago a sensible few in education, ecology, and sociology initiated a “significance test controversy.” But, grantors, journal referees, and tenure committees in the statistical sciences had faith that probability spaces can substitute for scientific judgment. A finding of p <.05 is deemed to be “better” for variable X than p <.11 for variable Y. It is not. It depends on the oomph of X and Y—the effect size, size judged in the light of how much it matters for scientific or clinical purposes. In 1995 a Cancer Trialists’ Collaborative Group, for example, came to a rare consensus on effect size: 10 different studies had agreed that a certain drug for treating prostate cancer can increase patient survival by 12%. An 11th study published in the New England Journal in 1998 dismissed the drug. The dismissal was based on a t-test, not on what William Gosset had called, against Ronald A. Fisher’s machinery, “real” error. (shrink)

As the_number of clinical trials continues to grow, there is an increasing need for education and training in the field. The clinical research climate is less forgiving of errors and oversights and therefore requires more knowledge of regulations and requirements. This brand new edition details new laws and regulations in protecting children participating in clinical trials and how a new focus on privacy of individual health information in the United States has changed how medical records are handled. Includes a (...) manual for investigators, research nurses and study coordinators with minimal experience or who are new to clinical research An easy-to-read and open text design using ‘sidebars’ of examples and information boxes related to the main text Includes a list of Frequently Asked Questions and Glossary Duke Clinical Research Institute is the world’s largest academic clinical research organisation and is well known and respected within the clinical research community. (shrink)

How does aspirin reduce pain and inflammation? How does it prevent heart attacks? Why does it upset the stomach? How do scientists discover the answers? This article examines research and development in the history from willow bark to aspirin to “super aspirins” Celebrex and Vioxx. Scientists adopt various approaches: trial and error, laboratory experiment, clinical test, elucidation of underlying mechanisms, concept-directed research, and rational drug design. Each approach is limited, but they complement each other in unraveling the mystery of (...) a wonder drug. (shrink)

ABSTRACT Dr. Nancy Olivieri has become an icon of research integrity for her insistence on publishing adverse data about a drug she was investigating. She has been celebrated world‐wide as a hero of biomedical ethics for her bravery in disclosing potential dangers to research subjects, in the face of both drug company threats and coercive pressures from her hospital and university. Like so many other ‘whistle‐blowers’ however, she now faces both personal vilification and disturbing accusations of scientific error. (...) The case against Olivieri is assessed and found to be baseless. (shrink)

Whereas using artificial intelligence (AI) to predict natural hazards is promising, applying a predictive policing algorithm (PPA) to predict human threats to others continues to be debated. Whereas PPAs were reported to be initially successful in Germany and Japan, the killing of Black Americans by police in the US has sparked a call to dismantle AI in law enforcement. However, although PPAs may statistically associate suspects with economically disadvantaged classes and ethnic minorities, the targeted groups they aim to protect are (...) often vulnerable populations as well (e.g., victims of human trafficking, kidnapping, domestic violence, or drug abuse). Thus, determining how to enhance the benefits of PPA while reducing bias through better management is important. In this paper, we propose a policy schema to address this issue. First, after clarifying relevant concepts, we examine major criticisms of PPAs and argue that some of them should be addressed. If banning AI or making it taboo is an unrealistic solution, we must learn from our errors to improve AI. We next identify additional challenges of PPAs and offer recommendations from a policy viewpoint. We conclude that the employment of PPAs should be merged into broader governance of the social safety net and audited publicly by parliament and civic society so that the unjust social structure that breeds bias can be revised. (shrink)

Some patients tolerate a given drug well, without adverse reactions. For others, though, an identical dose of the same medication can have toxic effects. Moreover, while a drug can be effective at relieving symptoms for some patients, it may fail to do the same for others suffering with the same disease. With such variability in treatment responses, tailoring medical interventions to individual patients has long been an aspiration of medicine. Until recently, however, medicine lacked a clear understanding of (...) the biological reasons for human variation in drug response. Attempting to adjust treatment to the individual patient, physicians have relied primarily on direct observation, trial-and-error, and, ultimately... (shrink)

Carruthers' case against animal consciousness employs deeply flawed reasoning and is contradicted by both empirical and introspective evidence. Although in principle we cannot objectively establish for certain that anyone -- human or otherwise -- is phenomenally conscious, results of animal research on consciousness-changing drugs are uninterpretable unless one assumes that non-human animals have discriminable subjective states. Carruthers tries to argue that higher-order thoughts are the basis of subjective experiences, but the former are derived from the latter, not the other way (...) around. The position that only humans are conscious is reminiscent of other anthropocentric errors including outmoded notions of an Earth-centered universe created solely for humans. (shrink)

Medical ethics is a realm where four important subjects of philosophy, medicine, theology and law are covered. Physicians and philosophers cooperation in this area will have great efficiency in the respective ethical rules formation. In addition to respect the autonomy of the patient, physician's obligation is to ensure that the medical intervention has benefit for the patient and the harm is minimal. There is an obvious conflict between duty of confidentiality and duty of mandatory reporting. Professional confidentiality is one of (...) the basic components in building a constant physician-patient relationship which nowadays, beside the novelty, it is the subject of discussion. Legal obligation of confidentiality is not absolute. In physician-patient relationship, keeping patient's secrets and maintaining confidentiality is a legal and ethical duty, and disclosure of such secrets is mainly through specific statutes. Thus, there are a number of situations where breach of confidentiality is permitted in different legal systems. One of the situations where breaching confidentiality is permitted is the medical mandatory reporting to the relevant authority which is in accordance with many countries' legal systems. Some situations are considered in many countries legal systems' such as notification of births and deaths, infectious diseases, child abuse, sport and relevant events, medical errors, drug side effects and dangerous pregnancies. In this paper, we will examine and discuss medical mandatory reporting and its ethical and legal aspects in the judicial and legal system of Iran and few other countries. Finally we will suggest making Medical Mandatory Reporting Law in Iran. (shrink)

Impaired performance in verbal fluency tasks is a frequent observation in Parkinson’s disease. As to the nature of the underlying cognitive deficit, it is commonly attributed to a frontal-type dysexecutive syndrome due to nigrostriatal dopamine depletion. Whereas dopaminergic medication typically improves VF performance in PD, e.g., by ameliorating impaired lexical switching, its effect on semantic network activation is unclear. Data from priming studies suggest that dopamine causes a faster decay of semantic activation spread. The aim of the current study was (...) to examine the impact of dopaminergic medication on the dynamic change of word frequency during VF performance as a measure of semantic spreading activation. To this end, we performed a median split analysis of word frequency during phonemic and semantic VF task performance in a PD group tested while receiving dopaminergic medication as well as after drug withdrawal, and in a sample of age-matched healthy volunteers. Dopaminergic medication in the PD group significantly affected phonemic VF with improved word production as well as increased error-rates. The expected decrease of word frequency during VF task performance was significantly smaller in the PD group ON medication than in healthy volunteers across semantic and phonemic VF. No significant group-difference emerged between controls and the PD group in the OFF condition. The comparison between both treatment conditions within the PD group did not reach statistical significance. The observed pattern of results indicates a faster decay of semantic network activation during lexical access in PD patients on dopaminergic medication. In view of improved word generation, this finding is consistent with a concept of more focused neural activity by an increased signal-to-noise ratio due to dopaminergic neuromodulation. However, the effect of dopaminergic stimulation on VF output suggests a trade-off between these beneficial effects and increased error-rates. (shrink)

Over the past decade, US patients and clinicians have endured medication shortages of nearly every class, including many lifesaving medications. These shortages have persisted despite determined efforts by federal, academic, and professional organizations. Medication shortages have resulted in lost lives, medication errors, and substantial financial cost. Economic drivers are the primary cause for drug shortages, exacerbated by manufacturing and quality problems, and unreliable and uncertain sources for many raw materials required to synthesize these drugs. Drug shortages force (...) clinicians to make untenable choices and decide which of their patients should receive a lifesaving scarce medication. The COVID-19 pandemic has stressed many hospitals’ ability to provide basic care and aggravated existing drug shortages. The influx of patients suffering from COVID-19 has exposed flaws in the fractured manner in which essential medications reach patients. The unique nature of COVID-19, often requiring prompt and decisive clinical decision-making, challenges the accepted approach for ethical analysis adopted by clinical ethicists. The author, a clinician and bioethicist, notes the ethical challenges he and other frontline providers have faced in deciding which patients are “more deserving” of a scarce medication. (shrink)

I. Introductory Comments   The Human Genome Project will be completed within 2 years, and “targeted†sequence data from the most promising sections of the genome will be released even sooner. Based on this wealth of information, at least 400 new genetic tests will become available within the next decade. The blending of microelectronic and genetic technology will make the “genetic report card†an affordable and routine part of medical care. The implicit assumption driving much of this push for (...) genetic testing is that information is inherently good and patients should have the right to any information about themselves they desire. However, the informational content of genetic tests for most conditions is not known and may in fact be very low. Under such circumstances, it seems prudent to treat access to genetic testing the same way we currently treat access to other new medical procedures and drugs – that is, access is afforded only 1) in the context of a clinical trial or  2) after the safety and effectiveness of the treatment has been established. The fact is, genetic “information†of uncertain quality is not innocous. II. The Difficulty with Genetic Testing   Everyone is familiar with one difficulty posed by genetic testing: the possibility that a test may show either a “false positive†or a “false negativeâ€.  This is the problem of the analytic accuracy of testing. However, as our analytic techniques become more sophisticated, the incidence of such errors will steadily decline. If nothing else, administration of multiple tests is often (though not always) a simple and effective way of boosting analytic accuracy.   There is, however, a much more serious accuracy problem which has been largely overlooked in the literature.. (shrink)

The argument from inductive risk claims that judgments about the moral severity of errors are relevant to decisions about what should count as sufficient evidence for accepting claims. While this idea has been explored in connection with evidence required for the approval of pharmaceuticals, the role of inductive risk in the post-approval process has been largely neglected. In this article, we examine the ethics of inductive risk in connection with revisions to the product monograph for OxyContin in Canada, which (...) understates the risks of addiction and abuse associated with this drug. Using the concept of inductive risk, we consider what evidence should have been sufficient for Health Canada to revise the product monograph for OxyContin. Given the stakes involved, we argue that a less strict standard of evidence would have been appropriate, yet HC in fact took the opposite course, insisting upon a higher standard of evidence than it normally requires. In addition to providing a novel perspective on the opioid crisis in Canada, this article contributes to existing philosophical work by demonstrating that inductive risks in the post-approval stage are important and linked to pre-approval inductive risks. (shrink)

This guide accompanies the following article(s): ‘Full Disclosure of the “Raw Data” of Research on Humans: Citizens’ Rights, Product Manufacturer’s Obligations and the Quality of the Scientific Database.’Philosophy Compass 6/2 (2011): 90–99. doi: 10.1111/j.1747‐9991.2010.00376.x Author’s Introduction Securing consent (and informed consent) from patients and research study participants is a key concern in patient care and research on humans. Yet, the legal doctrines of consent and informed consent differ in their applications. In patient care, the judicial doctrines of consent and informed (...) consent are disclosure doctrines based on the obligation of physicians to inform their patients of the following types of information: the nature of the procedure the physician is recommending in the patent’s care (P), the alternatives to the physician‐recommendation (A), and the risks of procedure and its alternatives (R). In addition, the physician must provide truthful answers to the patient’s questions (Q) to the best of the physician’s abilities. In research on humans, the onus of disclosure by study sponsors and principal investigators is much greater than in patient care precisely because the purpose of research is not patient care. The purpose of research is the identification and development of new generalizable knowledge. Thus, participation in a research study or trial may not benefit the study volunteer at all. In addition, the participant may carry a heavy risk burden in relationship to any testing of a newly designed drug or device as part of their experiences in the research study. Presently, despite the risks borne by the research study participant, the raw data collected from volunteers in research trials are treated by courts as if they were the private property of the study sponsor rather than generally owed to the public as would be expected by an effort like research participation aimed at contributing to the development of generalizable knowledge. This paper reviews the obligations that study sponsors owe to their study participants based on the very definition of research as a systematic activity whose purpose is to develop generalizable knowledge to help all humans. Author Recommends Court cases Canterbury v. Spence, United States Court of Appeals, District of Columbia Circuit 464 F.2d 772 (1972). (Federal appellate decision heard in the District of Columbia, USA) Reibl v. Hughes, 2 S.C.R. 880 (1980). (Supreme Court of Canada) Rogers v. Whitaker, 175 C.L. R. 479 (1992). (High Court of Australia) Sidaway v. Board of Governors of the Bethlem Royal Hospital and the Maudsley Hospital and Others. 1 A.C. 871 (1985) (House of Lords) Canterbury v. Spence is the landmark Federal informed consent case in the United States heard in the District of Columbia. In this case, Judge Spottswood Robinson articulated the reasonable person standard of informed consent. This standard was subsequently adopted by the Supreme Court of Canada (Reibl v. Hughes, 2 S.C.R. 880 (1980)) and the High Court of Australia (Rogers v. Whitaker, 175 C.L. R. 479 (1992)). The House of Lords rejected the reasonable person standard in England in Sidaway v. Board of Governors of the Bethlem Royal Hospital and the Maudsley Hospital and Others. 1 A.C. 871 (1985). Book Mazur, Dennis J. The Science and Ethics of Research on Humans. Baltimore, MD: Johns Hopkins University Press, 2007. This book is a detailed guide for the review of scientific and ethical aspects of research on humans contained in the research study protocols and research informed consent forms which need to be submitted by study sponsors and principal investigators to institutional review boards (IRBs) for IRB review before a research study can receive approval to be conducted within a human study population in those institutions over which the IRB has authority. It also presents basic definitions in the area of research on humans and basic approaches to help conduct a deep review of the underlying scientific and ethical issues that are present within a research study protocol and its accompanying research informed consent form. Report National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Guidelines for the Protection of Human Subjects of Research. Washington, DC: DHEW Publications, 1978 (78‐0012). This U.S. National Commission in the Belmont Report argued for the necessity of a reasonable volunteer standard in research on humans in the United States. Arguing that the professional standard and the reasonable person standard of consent and informed consent were insufficient to base a disclosure standard in research on humans, this National Commission developed the reasonable volunteer standard where a study participant is to be approached in research informed consent with that information that a reasonable volunteer would want to know. Online Materials Belmont Report: Syllabus Topics for Lecture and Discussion Week I: Introduction and Overview Readings: Rogers v. Whitaker, 175 C.L.R. 479 (1992). (High Court of Australia) Sidaway v. Board of Governors of the Bethlem Royal Hospital and the Maudsley Hospital and Others. 1 A.C. 871 (1985) (House of Lords) Week II: The Different Standards of Consent and Informed Consent Readings: Canterbury v. Spence, 464 F.2d 772 (1972). (Federal appellate opinion heard in the District of Columbia) Sidaway v. Board of Governors of the Bethlem Royal Hospital and the Maudsley Hospital and Others. 1 A.C. 871 (1985) (House of Lords) Week III: Definition of Research Reading: Mazur, Dennis J. The Science and Ethics of Research on Humans. Baltimore, MD: Johns Hopkins University Press, 2007. (Especially Chapters 2 and 3) Week IV: How to Review a Research Study Protocol and Research Informed Consent Form Reading: Mazur, Dennis J. The Science and Ethics of Research on Humans. Baltimore, MD: Johns Hopkins University Press, 2007. (Especially Chapters 4–6, 10, and 12–14) Week V: Obligations in Research of Humans Versus Patient Care Reading: National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Guidelines for the Protection of Human Subjects of Research. Washington, DC: DHEW Publications, 1978 (78‐0012). Focus Questions • How do the judicial doctrines of consent in England and Australia compare to the judicial doctrines of informed consent in the United States and Canada? • How does a professional standard of disclosure differ from a reasonable person standard of disclosure? • What is the definition of research? • How is a research study (study proposal and research informed consent form) reviewed from scientific and ethical bases for considerations of approval by an IRB? • How do the obligations of a study sponsor, a principal investigator, and a research team conducting a research trial on human study participants differ from the obligations of a physician caring for a patient? • Should all raw data of research derived from humans be made available to the public for use in developing generalizable knowledge to help others, or should raw data be considered the private property of the study sponsors (for example, prescription drug manufacturers), who fund the research trials? Seminar/project Idea Draw a timeline of the development of the basic concepts of consent and informed consent in patient care and in patient research. On this timeline, first place the dates of the key court cases in England, the United States, Canada, and Australia on consent and informed consent. Then place the date of the development of the Belmont Report. Why do differences exist between these four countries in terms of the legal requirements of informedness of a patient (in medical care) and a study participant (in medical research)? What roles if any do the concepts of self‐determination and self‐decision have in consent and informed consent in patient care and in informed consent in research on humans among the four countries of interest? What are the realities of research on human participants that require a new standard of informed consent, the reasonable volunteer standard, to be developed beyond the two standards in patient care, the professional standard, and the reasonable person standard? Counterpoint Arguments The following are counterpoint arguments that need to be appreciated to more fully understand the concepts that impact the thesis that ‘raw data’ should be open to the public to allow the opportunity of checking of the results of its associated scientific paper and for further analysis. De‐Identified (Anonymized) Raw Data A current approach to identifying (anonymizinig) raw data is based on the Health Insurance Portability and Accountability Act (HIPAA) of 1996 (P.L.104‐191). HIPAA was enacted by the U.S. Congress in 1996 to keep a person’s medical information private. In a research study, a person’s private medical information can become research data. HIPAA’s Privacy Rule allows a covered entity to de‐identify data by removing all 18 elements that could be used to identify the individual or the individual’s relatives, employers, or household members; these elements are enumerated in the Privacy Rule. The covered entity must also have no actual knowledge that the remaining information could be used alone or in combination with other information to identify the individual who is the subject of the information. Under this method, the identifiers that must be removed are the following: 1 Names. 2 All geographic subdivisions smaller than a state, including street address, city, county, precinct, ZIP Code, and their equivalent geographical codes, except for the initial three digits of a ZIP Code if, according to the current publicly available data from the Bureau of the Census: 2a. The geographic unit formed by combining all ZIP Codes with the same three initial digits contains more than 20,000 people. 2b. The initial three digits of a ZIP Code for all such geographic units containing 20,000 or fewer people are changed to 000. 3 All elements of dates (except year) for dates directly related to an individual, including birth date, admission date, discharge date, and date of death, and all ages over 89 and all elements of dates (including year) indicative of such age, except that such ages and elements may be aggregated into a single category of age 90 or older. 4 Telephone numbers. 5 Facsimile numbers. 6 Electronic mail addresses. 7 Social security numbers. 8 Medical record numbers. 9 Health plan beneficiary numbers. 10 Account numbers. 11 Certificate/license numbers. 12 Vehicle identifiers and serial numbers, including license plate numbers. 13 Device identifiers and serial numbers. 14 Web universal resource locators (URLs). 15 Internet protocol (IP) address numbers. 16 Biometric identifiers, including fingerprints and voiceprints. 17 Full‐face photographic images and any comparable images. 18 Any other unique identifying number, characteristic, or code, unless otherwise permitted by the Privacy Rule for re‐identification. Even though ‘raw data’ can be de‐identified (anonymized) so that there is no way to trace back the data to the study participant from which it was drawn, there are still questions whether the ‘de‐identified raw data’ can be given to other researchers or made public without the original study participant’s approval. It may be the case that this approval could be done at the start of any research study where the individual considering study participation would be counseled on what the process of de‐identification consists of and would be asked whether the participant would allow use of the data by other researchers or made available to the public in a de‐identified state. However, there may be questions of the study participants as to whether the data are truly de‐identified and untraceable back to the study participant since the participant would not be able to see the process actually being carried out in detail in all relevant circumstances. Using Raw Data in Context Simply being in possession of raw data is never enough to build on that data from a research perspective. Researchers need to understand the context of the scientific research study in which the data were collected. This research context includes (but is not limited to): (i) the scientific hypothesis of the research study, (ii) the inclusion and exclusion criteria selected by the research designers of the study to determine which study participants were included and which were excluded from the study, (iii) the methods used to collect the data and possibilities of errors in the data collection processes, and (iv) answers to questions regarding whether any data were excluded from the study data and why these data were excluded. Ownership Rights Over Data There are ownership rights over data. Ownership rights include court decision making related to the question which parties are to be considered as the owners of the data. Possible owners here include (but are not limited to) (i) the study sponsor whose only role was to fund that study, (ii) the principal investigator(s) who developed the scientific hypothesis, and (iii) individual study participants through special contracts made by individual participants who negotiate such contracts with study sponsors and principal investigators to share in the ownership of data. Examples of such data are participant sources of unique gene lines or unique cell lines to be used in future research. Objections to Data Sharing Finally, individual researchers may simply object to sharing data. A researcher’s arguments here may be simply stating that he or she has a right to fully analyze the data since the collection of the data was the researchers’ idea in the first place. These researchers may argue that they have the right to mine the data as fully as they can before deciding to make the data open to the public for others to analyze. Works Cited 1 Kaiser, J. ‘Making Clinical Data Widely Available.’Science 322.5899 (10 Oct. 2008): 217–8. 2 de Lusignan, S., J.F. Metsemakers, P. Houwink, V. Gunnarsdottir, and J. van der Lei. ‘Routinely Collected General Practice Data: Goldmines for Research? A Report of the European Federation for Medical Informatics Primary Care Informatics Working Group (EFMI PCIWG) from MIE2006, Maastricht, The Netherlands.’Informatics in Primary Care 14.3 (2006): 203–9. 3 Sim, I. ‘Human Studies Database Project’, CTSA Data Repositories Symposium (17 Oct. 2008). 23 Nov. 2010. 4 Sim, I., C.G. Chute, H. Lehmann, R. Nagarajan, M. Nahm, and R.H. Scheuermann. ‘Keeping Raw Data in Context.’Science 323.5915 (6 Feb. 2009): 713. 5 U.S. Department of Health and Human Services, National Institutes of Health, HIPAA Privacy Rule, Information for Researchers. 13 Nov. 2010. 6 Wilczynski, N.L., R.B. Haynes, and Hedges Team. ‘EMBASE Search Strategies for Identifying Methodologically Sound Diagnostic Studies for Use by Clinicians and Researchers.’BMC Medicine 29.3 (March 2005): 7. (shrink)

This guide accompanies the following article(s): ‘Full Disclosure of the “Raw Data” of Research on Humans: Citizens’ Rights, Product Manufacturer’s Obligations and the Quality of the Scientific Database.’Philosophy Compass 6/2 (2011): 90–99. doi: 10.1111/j.1747‐9991.2010.00376.x Author’s Introduction Securing consent (and informed consent) from patients and research study participants is a key concern in patient care and research on humans. Yet, the legal doctrines of consent and informed consent differ in their applications. In patient care, the judicial doctrines of consent and informed (...) consent are disclosure doctrines based on the obligation of physicians to inform their patients of the following types of information: the nature of the procedure the physician is recommending in the patent’s care (P), the alternatives to the physician‐recommendation (A), and the risks of procedure and its alternatives (R). In addition, the physician must provide truthful answers to the patient’s questions (Q) to the best of the physician’s abilities. In research on humans, the onus of disclosure by study sponsors and principal investigators is much greater than in patient care precisely because the purpose of research is not patient care. The purpose of research is the identification and development of new generalizable knowledge. Thus, participation in a research study or trial may not benefit the study volunteer at all. In addition, the participant may carry a heavy risk burden in relationship to any testing of a newly designed drug or device as part of their experiences in the research study. Presently, despite the risks borne by the research study participant, the raw data collected from volunteers in research trials are treated by courts as if they were the private property of the study sponsor rather than generally owed to the public as would be expected by an effort like research participation aimed at contributing to the development of generalizable knowledge. This paper reviews the obligations that study sponsors owe to their study participants based on the very definition of research as a systematic activity whose purpose is to develop generalizable knowledge to help all humans. Author Recommends Court cases Canterbury v. Spence, United States Court of Appeals, District of Columbia Circuit 464 F.2d 772 (1972). (Federal appellate decision heard in the District of Columbia, USA) Reibl v. Hughes, 2 S.C.R. 880 (1980). (Supreme Court of Canada) Rogers v. Whitaker, 175 C.L. R. 479 (1992). (High Court of Australia) Sidaway v. Board of Governors of the Bethlem Royal Hospital and the Maudsley Hospital and Others. 1 A.C. 871 (1985) (House of Lords) Canterbury v. Spence is the landmark Federal informed consent case in the United States heard in the District of Columbia. In this case, Judge Spottswood Robinson articulated the reasonable person standard of informed consent. This standard was subsequently adopted by the Supreme Court of Canada (Reibl v. Hughes, 2 S.C.R. 880 (1980)) and the High Court of Australia (Rogers v. Whitaker, 175 C.L. R. 479 (1992)). The House of Lords rejected the reasonable person standard in England in Sidaway v. Board of Governors of the Bethlem Royal Hospital and the Maudsley Hospital and Others. 1 A.C. 871 (1985). Book Mazur, Dennis J. The Science and Ethics of Research on Humans. Baltimore, MD: Johns Hopkins University Press, 2007. This book is a detailed guide for the review of scientific and ethical aspects of research on humans contained in the research study protocols and research informed consent forms which need to be submitted by study sponsors and principal investigators to institutional review boards (IRBs) for IRB review before a research study can receive approval to be conducted within a human study population in those institutions over which the IRB has authority. It also presents basic definitions in the area of research on humans and basic approaches to help conduct a deep review of the underlying scientific and ethical issues that are present within a research study protocol and its accompanying research informed consent form. Report National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Guidelines for the Protection of Human Subjects of Research. Washington, DC: DHEW Publications, 1978 (78‐0012). This U.S. National Commission in the Belmont Report argued for the necessity of a reasonable volunteer standard in research on humans in the United States. Arguing that the professional standard and the reasonable person standard of consent and informed consent were insufficient to base a disclosure standard in research on humans, this National Commission developed the reasonable volunteer standard where a study participant is to be approached in research informed consent with that information that a reasonable volunteer would want to know. Online Materials Belmont Report: Syllabus Topics for Lecture and Discussion Week I: Introduction and Overview Readings: Rogers v. Whitaker, 175 C.L.R. 479 (1992). (High Court of Australia) Sidaway v. Board of Governors of the Bethlem Royal Hospital and the Maudsley Hospital and Others. 1 A.C. 871 (1985) (House of Lords) Week II: The Different Standards of Consent and Informed Consent Readings: Canterbury v. Spence, 464 F.2d 772 (1972). (Federal appellate opinion heard in the District of Columbia) Sidaway v. Board of Governors of the Bethlem Royal Hospital and the Maudsley Hospital and Others. 1 A.C. 871 (1985) (House of Lords) Week III: Definition of Research Reading: Mazur, Dennis J. The Science and Ethics of Research on Humans. Baltimore, MD: Johns Hopkins University Press, 2007. (Especially Chapters 2 and 3) Week IV: How to Review a Research Study Protocol and Research Informed Consent Form Reading: Mazur, Dennis J. The Science and Ethics of Research on Humans. Baltimore, MD: Johns Hopkins University Press, 2007. (Especially Chapters 4–6, 10, and 12–14) Week V: Obligations in Research of Humans Versus Patient Care Reading: National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Guidelines for the Protection of Human Subjects of Research. Washington, DC: DHEW Publications, 1978 (78‐0012). Focus Questions • How do the judicial doctrines of consent in England and Australia compare to the judicial doctrines of informed consent in the United States and Canada? • How does a professional standard of disclosure differ from a reasonable person standard of disclosure? • What is the definition of research? • How is a research study (study proposal and research informed consent form) reviewed from scientific and ethical bases for considerations of approval by an IRB? • How do the obligations of a study sponsor, a principal investigator, and a research team conducting a research trial on human study participants differ from the obligations of a physician caring for a patient? • Should all raw data of research derived from humans be made available to the public for use in developing generalizable knowledge to help others, or should raw data be considered the private property of the study sponsors (for example, prescription drug manufacturers), who fund the research trials? Seminar/project Idea Draw a timeline of the development of the basic concepts of consent and informed consent in patient care and in patient research. On this timeline, first place the dates of the key court cases in England, the United States, Canada, and Australia on consent and informed consent. Then place the date of the development of the Belmont Report. Why do differences exist between these four countries in terms of the legal requirements of informedness of a patient (in medical care) and a study participant (in medical research)? What roles if any do the concepts of self‐determination and self‐decision have in consent and informed consent in patient care and in informed consent in research on humans among the four countries of interest? What are the realities of research on human participants that require a new standard of informed consent, the reasonable volunteer standard, to be developed beyond the two standards in patient care, the professional standard, and the reasonable person standard? Counterpoint Arguments The following are counterpoint arguments that need to be appreciated to more fully understand the concepts that impact the thesis that ‘raw data’ should be open to the public to allow the opportunity of checking of the results of its associated scientific paper and for further analysis. De‐Identified (Anonymized) Raw Data A current approach to identifying (anonymizinig) raw data is based on the Health Insurance Portability and Accountability Act (HIPAA) of 1996 (P.L.104‐191). HIPAA was enacted by the U.S. Congress in 1996 to keep a person’s medical information private. In a research study, a person’s private medical information can become research data. HIPAA’s Privacy Rule allows a covered entity to de‐identify data by removing all 18 elements that could be used to identify the individual or the individual’s relatives, employers, or household members; these elements are enumerated in the Privacy Rule. The covered entity must also have no actual knowledge that the remaining information could be used alone or in combination with other information to identify the individual who is the subject of the information. Under this method, the identifiers that must be removed are the following: 1 Names. 2 All geographic subdivisions smaller than a state, including street address, city, county, precinct, ZIP Code, and their equivalent geographical codes, except for the initial three digits of a ZIP Code if, according to the current publicly available data from the Bureau of the Census: 2a. The geographic unit formed by combining all ZIP Codes with the same three initial digits contains more than 20,000 people. 2b. The initial three digits of a ZIP Code for all such geographic units containing 20,000 or fewer people are changed to 000. 3 All elements of dates (except year) for dates directly related to an individual, including birth date, admission date, discharge date, and date of death, and all ages over 89 and all elements of dates (including year) indicative of such age, except that such ages and elements may be aggregated into a single category of age 90 or older. 4 Telephone numbers. 5 Facsimile numbers. 6 Electronic mail addresses. 7 Social security numbers. 8 Medical record numbers. 9 Health plan beneficiary numbers. 10 Account numbers. 11 Certificate/license numbers. 12 Vehicle identifiers and serial numbers, including license plate numbers. 13 Device identifiers and serial numbers. 14 Web universal resource locators (URLs). 15 Internet protocol (IP) address numbers. 16 Biometric identifiers, including fingerprints and voiceprints. 17 Full‐face photographic images and any comparable images. 18 Any other unique identifying number, characteristic, or code, unless otherwise permitted by the Privacy Rule for re‐identification. Even though ‘raw data’ can be de‐identified (anonymized) so that there is no way to trace back the data to the study participant from which it was drawn, there are still questions whether the ‘de‐identified raw data’ can be given to other researchers or made public without the original study participant’s approval. It may be the case that this approval could be done at the start of any research study where the individual considering study participation would be counseled on what the process of de‐identification consists of and would be asked whether the participant would allow use of the data by other researchers or made available to the public in a de‐identified state. However, there may be questions of the study participants as to whether the data are truly de‐identified and untraceable back to the study participant since the participant would not be able to see the process actually being carried out in detail in all relevant circumstances. Using Raw Data in Context Simply being in possession of raw data is never enough to build on that data from a research perspective. Researchers need to understand the context of the scientific research study in which the data were collected. This research context includes (but is not limited to): (i) the scientific hypothesis of the research study, (ii) the inclusion and exclusion criteria selected by the research designers of the study to determine which study participants were included and which were excluded from the study, (iii) the methods used to collect the data and possibilities of errors in the data collection processes, and (iv) answers to questions regarding whether any data were excluded from the study data and why these data were excluded. Ownership Rights Over Data There are ownership rights over data. Ownership rights include court decision making related to the question which parties are to be considered as the owners of the data. Possible owners here include (but are not limited to) (i) the study sponsor whose only role was to fund that study, (ii) the principal investigator(s) who developed the scientific hypothesis, and (iii) individual study participants through special contracts made by individual participants who negotiate such contracts with study sponsors and principal investigators to share in the ownership of data. Examples of such data are participant sources of unique gene lines or unique cell lines to be used in future research. Objections to Data Sharing Finally, individual researchers may simply object to sharing data. A researcher’s arguments here may be simply stating that he or she has a right to fully analyze the data since the collection of the data was the researchers’ idea in the first place. These researchers may argue that they have the right to mine the data as fully as they can before deciding to make the data open to the public for others to analyze. Works Cited 1 Kaiser, J. ‘Making Clinical Data Widely Available.’Science 322.5899 (10 Oct. 2008): 217–8. 2 de Lusignan, S., J.F. Metsemakers, P. Houwink, V. Gunnarsdottir, and J. van der Lei. ‘Routinely Collected General Practice Data: Goldmines for Research? A Report of the European Federation for Medical Informatics Primary Care Informatics Working Group (EFMI PCIWG) from MIE2006, Maastricht, The Netherlands.’Informatics in Primary Care 14.3 (2006): 203–9. 3 Sim, I. ‘Human Studies Database Project’, CTSA Data Repositories Symposium (17 Oct. 2008). 23 Nov. 2010. 4 Sim, I., C.G. Chute, H. Lehmann, R. Nagarajan, M. Nahm, and R.H. Scheuermann. ‘Keeping Raw Data in Context.’Science 323.5915 (6 Feb. 2009): 713. 5 U.S. Department of Health and Human Services, National Institutes of Health, HIPAA Privacy Rule, Information for Researchers. 13 Nov. 2010. 6 Wilczynski, N.L., R.B. Haynes, and Hedges Team. ‘EMBASE Search Strategies for Identifying Methodologically Sound Diagnostic Studies for Use by Clinicians and Researchers.’BMC Medicine 29.3 (March 2005): 7. (shrink)

In the March 2010 edition of Mayo Clinic Proceedings, Drs. Rose and Curry declared that resident physicians have an ethical duty to reduce error during periods of fatigue. Problematically, however, they argued this means ingesting a stimulant for performance enhancement and sleep avoidance during a shift when a resident physician is experiencing fatigue as the more ethical choice than forgoing ingesting a stimulant. Rather than accepting enhancement as an unstoppable technological imperative, this article will examine the underlying motivations for enhancement (...) embedded in our culture and the corresponding legal framework relating to stimulant drugs. Although our society seems to be engaged in a pharmacological arms race of efficiency, competition, and self “betterment,” the FDA has not approved stimulant drugs such as modafinil for PESA. As a result, the off-label use of modafinil for PESA means these individuals are part of a large-scale experiment that poses serious immediate and long-term side effects to the individual user as well as society. (shrink)

In order to deal with high-dimensional distributed data, this article develops a novel and communication-efficient approach for sparse and high-dimensional data with the penalized quantile regression. In each round, the proposed method only requires the master machine to deal with a sparse penalized quantile regression which could be realized fastly by proximal alternating direction method of multipliers algorithm and the other worker machines to compute the subgradient on local data. The advantage of the proximal ADMM algorithm is that it could (...) make every parameter of iteration to have closed formula even in high-dimensional case, which greatly improves the speed of calculation. As for the communication efficiency, the proposed method does not sacrifice any statistical accuracy and provably improves the estimation error obtained by centralized method, provided the penalty levels are chosen properly. Moreover, the asymptotic properties of the proposed estimation and the convergence of the algorithm are convincible. Especially, it presents extensive experiments on both the numerical simulations and the HIV drug resistance data analysis, which all confirm the significant efficiency of our proposed method in quantile regression for distributed data by comparative and empirical analysis. (shrink)

Two essential periods may be identified in the early stages of the history of vitamin D-resistant rickets. The first was the period during which a very well known deficiency disease, rickets, acquired a scientific status: this required the development of unifying principles to confer upon the newly developing science of pathology a doctrine without which it would have been condemned to remain a collection of unrelated facts with very little practical application. One first such unifying principle was provided by the (...) notion of hygiene; while the blanket explanations provided by this notion alone were much too general to enable rickets to achieve scientific status, it did point out the need to look for specific external causes for the disease and to examine the life-style and dietary habits of the patients. The second phase of the conceptualization of the disease was the assumption of a specific cause — that is, using concepts developed in the area of infectious diseases. This was made possible by fundamental similarities between deficiency and infectious diseases, in spite of their apparent differences. Both types of illness have some of the characteristics of what Georges Canguilhem calls the ontological representation of disease as opposed to dysharmonic representations, which primarily concern the endocrine diseases. It is precisely this shift from one to the other manner of perceiving ill health that enabled the identification of the vitamin D-resistant rickets. Conceptualization of the notion of vitamin D resistancy required that the conditions causing the disease be looked for within the organism rather than outside it; this was thus the first time that endocrine concepts were applied to studying the physiology of vitamin D.The history of resistant rickets therefore represents an interesting model for understanding the growth of biomedical knowledge. It allows the development of a number of more general ideas on the question of the relationship between biology and medicine and on the thorny problem of specificity in medical thinking. As far as this topic is concerned it can be seen that there was an ongoing exchange between medical and biological thinking during the initial period up until 1937, and that one could deny any such specificity in medical thinking during this same period. Albright, for example, used human diseases as spontaneously produced models for experimental biology. It was also more feasible for an experimental biologist to administer toxic doses than for a clinician to do so.What, then, if any, is the place of the specificity of medical thinking in this history? The fact that medicine is characterized not only by it ccognitive content78 but also by its final aim, which is to restore health, makes it necessary to take factors other than objective knowledge into consideration. This is particularly evident in two aspects of medicine, therapeutics and nosology, and in approaching the notion of pathological individuality.Therapeutic activity has a largely empirical approach. Many drugs, such as cod-liver oil, were discovered empirically. Treatment often in the past, and still now, has proceeded by trial and error, upon no established theoretical basis. At this level the relationship between biology and medicine is roughly comparable to that between science and technology79 \3- that is, it is impossible to reduce either therapeutics or technical activities to the simple application of basic science. In this sense, the application of vitamin D to vitamin-resistant rickets is quite typical. Further-more, in the case studied here, the therapeutic activity heralds a definite breaking away from the medicatrix naturae of conventional medicine dating back to ancient times, and it embodies a new concept of the organism and of disease: no longer can the diseased organism be thought of as merely having a perturbed equilibrium requiring restoration by means of a natural style of medicine. On the contrary, vitamin D resistance is an obstacle that indicates profound biological dysfunction, to be rectified only by means of an extremely aggressive and therefore dangerous therapy. The therapy thus serves to reveal the severity of the dysfunction, thereby leading inevitably to conceptual innovation. This sheds light on the theoretical innovations of which the therapeutic activity is capable.Therapeutic activity is also influenced by notions of health and illness, normal and pathological states, none of which may be determined entirely objectively. For example, the term healing as used by Albright in the case of resistant rickets that he described may be discussed in this light.Nosology, or the classification of diseases, depends largely on the description of clinical syndromes, which are themselves mainly based on subjective elements (discomfort, disability, or the extent of a patient's suffering). The advent of pathological anatomy at the beginning of the nineteenth century disrupted classification by introducing the concept of localized anatomical lesions81-and, hence, an element of material objectivity \3- into nosology. Radiological examination further complicated matters by enabling the equivalent of an autopsy on living matter. Lastly, biological examination complicated nosology by showing that biological anomalies may exist in human beings without necessarily leading to a pathological condition. Medical thinking can choose to combine all these elements to describe a disease, but can also separate them and retain only a few, or a single one, according to requirements - as did Albright.The notion of biological and pathological individuality is fundamental to the development of medical thinking. Whatever its theoretical origin, medical thinking has since ancient times incorporated the idea that each individual reacts differently to the same treatment and his own specific pathological tendencies. I mentioned earlier that in the history of vitamin D-resistant rickets the notion of rachitic tendency reflected this type of thinking. After 1937, this history progressed by successively separating new individual entities, affecting smaller and smaller groups of individuals in each case. In other words, the need to understand and to define individual illness more closely required the development of new concepts and the construction of new individual categories of disease linking these concepts to older clinical, radiological, and biochemical elements. (shrink)

Randomized controlled clinical trials play an important role in the development of new medical therapies. There is, however, an ethical issue surrounding the use of randomized treatment allocation when the patient is suffering from a life threatening condition and requires immediate treatment. Such patients can only benefit from the treatment they actually receive and not from the alternative therapy, even if it ultimately proves to be superior. We discuss a novel new way to analyse data from such clinical trials based (...) on the use of the recently developed theory of imprecise probabilities. This work draws an explicit distinction between the related but nevertheless distinct questions of inference and decision in clinical trials. The traditional question of scientific interest asks 'Which treatment offers the greater chance of success?' and is the primary reason for conducting the clinical trial. The question of decision concerns the welfare of the patients in the clinical trial, asking whether the accumulated evidence favours one treatment over the other to such an extent that the next patient should decline randomization and instead express a preference for one treatment. Consideration of the decision question within the framework of imprecise probabilities leads to a mathematical definition of equipoise and a method for governing the randomization protocol of a clinical trial. This paper describes in detail the protocol for the conduct of clinical trials based on this new method of analysis, which is illustrated in a retrospective analysis of data from a clinical trial comparing the anti-emetic drugs ondansetron and droperidol in the treatment of postoperative nausea and vomiting. The proposed methodology is compared quantitatively using computer simulation studies with conventional clinical trial designs and is shown to maintain high statistical power with reduced sample sizes, at the expense of a high type I error rate that we argue is irrelevant in some specific circumstances. Particular emphasis is placed on describing the type of medical conditions and treatment comparisons where the new methodology is expected to provide the greatest benefit. (shrink)

Access to clear and concise medication information is essential to support safe and effective use of prescription drugs. Patient misunderstanding of medication information is a common reason for non-adherence to medication regimens and a leading cause of outpatient medication errors and adverse drug events in the U.S. Medication errors are the most common source of risk to patient safety, leading to poor health outcomes, hospitalizations, and deaths. Over half a million adverse drug events occur in the (...) outpatient setting each year at a cost of approximately $1 billion annually.Nearly half of adults in the U.S. experience difficulty understanding and acting upon health information. Even individuals with high levels of general literacy may find medication information difficult to understand or use. The risk of misunderstanding medication information is compounded for patients with limited English proficiency who may not have access to this information in their own language. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 11.2 (2001) 165-168 [Access article in PDF] UPMC Presbyterian Policy and Procedure Manual Guidelines for Disclosure and Discussion of Conditions and Events with Patients, Families and Guardians* I. Introduction and Background In the course of hospital care, an extensive amount of clinical information is generated. It includes diagnostic findings, treatment options, responses to interventions, and professional opinions. The information can be positive or negative. (...) Clinical events may or may not be caused by clinicians and consequently may be iatrogenic (caused by medical treatment), nosocomial (occurring in the hospital) or natural events.In accordance with the informed consent policy (#4011), Patients' Bill of Rights (# 0154, Section II H), and the Guidelines on Forgoing Life Sustaining Treatment (#4007), patients have the right to information regarding their condition and care. Physicians and other caregivers are obligated to provide accurate information as expeditiously as possible. While it is usually easy to provide positive information, negative information is more difficult to disclose, especially when the cause is iatrogenic."Therapeutic privilege" has been invoked to explain why certain negative information might be withheld. By invoking therapeutic privilege, the physician refrains from full disclosure to protect the patient from the effects of receiving the information itself. The use of therapeutic privilege is increasingly being called into question because it decreases patient autonomy and reduces trust.The following recommendations are provided to clinicians to help guide delivery of sensitive information, positive and negative. Specific recommendations [End Page 165] are provided for situations where the information is about an unfavorable or adverse event, or where the information might best be characterized as "bad news." II. Definitions Unfavorable event or unfavorable condition. For the purposes of these guidelines, an unfavorable condition is an occurrence or diagnosis that results in or is likely to result in a significant negative outcome, and/or a significant alteration in the care plan.An unfavorable event in this context is not the same as a sentinel event, which in policy #4025 is defined as, "a serious, unexpected, adverse patient event which has resulted in, or if repeated would have a significant probability of resulting in, loss of life or serious physical or psychological injury, that is judged to be a warning of an underlying problem involving hospital facilities, policies, procedures, systems or personnel."Adverse Event. An unfavorable event for the purposes of these guidelines is also distinguished from the FDA definition of the term "adverse event", which is a reportable negative effect of a drug or device potentially resulting in death, hospitalization, or medical or surgical intervention. (See policy #4022 Safe Medical Device Act.)Examples of unfavorable events or conditions for the purpose of these guidelines include a new diagnosis of cancer, a perioperative myocardial infarction, or unintended delivery of an incorrect medication that results in clinical change.Examples of events not covered by these guidelines are intravenous saline infiltration and medication dosing errors that have no clinical impact on care.Iatrogenic. Event caused by the treatment of a healthcare provider. III. Guidelines and Principles It is appropriate that UPMC Presbyterian support basic principles for patient and family notification regarding all clinical events and conditions, including unfavorable ones. Physicians must be honest because that is a cornerstone of the patient-physician relationship, and because it fosters patient autonomy.UPMC Presbyterian supports the following AMA position regarding patient information: [End Page 166] It is a fundamental ethical requirement that a physician should at all times deal honestly and openly with patients. Patients have a right to know their past and present medical status and to be free of any mistaken beliefs concerning their conditions. Situations occasionally occur in which a patient suffers significant medical complications that may have resulted from the physician's mistake or judgement. In these situations, the physician is ethically required to inform the patient of all the facts necessary to ensure understanding of what has occurred. Only through full disclosure is a patient able to make informed decisions regarding future medical care. Ethical responsibility includes informing patients of changes in their diagnoses... (shrink)

Patient counseling is a cornerstone of ethical pharmacy practice and high quality pharmaceutical care. Counseling promotes patient compliance with prescription regimens and prevents dangerous drug interactions and medication errors. Counseling also promotes informed consent and protects pharmacists against legal risks. However, economic, social, and technological changes in pharmacy practice often force community pharmacists to choose between their professional obligations to counsel patients and business objectives. State and federal legislatures have enacted laws that require pharmacists to counsel patients, but (...) these laws have had mixed results. This essay argues that community pharmacy's patient counseling conundrum can be solved through additional moral education and moral persuasion, not through additional legal mandates. (shrink)

Recently, companions in guilt strategies have garnered significant philosophical attention as a response to arguments for moral error theory, the view that there are no moral facts and that our moral beliefs are thus systematically mistaken. According to Cuneo (The normative web: an argument for moral realism, Oxford University Press, Oxford, 2007), Das (Philos Q 66:152–160, 2016; Australas J Philos 95(1):58–69, 2017), Rowland (J Ethics Soc Philos 7(1):1–24, 2012; Philos Q 66:161–171, 2016) and others, epistemic facts would be just as (...) metaphysically problematic (or ‘guilty’) as moral facts. But since epistemic error theory is implausible, arguments for moral error theory prove too much and should be rejected. My aim is to argue that the success of this strategy is limited. In particular, the companions in guilt response fails against error-theoretic arguments motivated by concerns about explanatory dispensability, as recently developed by Joyce (The evolution of morality, MIT press, Bradford, 2005) and Olson (Moral error theory: history, critique, defence, Oxford University Press, Oxford, 2014: Ch. 7). To succeed, the response would require a prima facie plausible argument to the effect that epistemic facts are metaphysically dubious because they, too, are explanatorily dispensable. But, as I show, any such argument proves self-effacing: its premise commits us to believing in epistemic facts, while its conclusion forces us to deny their existence. Consequently, companions in guilt strategies don’t offer a panacea against arguments for moral error theory. (shrink)

Unbelievable Errors defends an error theory about all normative judgements: not just moral judgements, but also judgements about reasons for action, judgements about reasons for belief, and instrumental normative judgements. This theory states that normative judgements are beliefs that ascribe normative properties, but that normative properties do not exist. It therefore entails that all normative judgements are false. -/- Bart Streumer also argues, however, that we cannot believe this error theory. This may seem to be a problem for the (...) theory. But he argues that it makes this error theory more likely to be true, since it undermines objections to the theory and it makes it harder to reject the arguments for the theory. -/- He then sketches how certain other philosophical theories can be defended in a similar way. He concludes that to make philosophical progress, we need to make a sharp distinction between a theory's truth and our ability to believe it. (shrink)