PLoS One. 2014 Jun 5;9(6):e97492. doi: 10.1371/journal.pone.0097492. eCollection 2014.

Do Editorial Policies Support Ethical Research? A Thematic Text Analysis of Author Instructions in Psychiatry Journals.

Strech D1, Metz C2, Knüppel H1.

Author information

• 1Hannover Medical School, CELLS - Centre for Ethics and Law in the Life Sciences, Institute for History, Ethics and Philosophy of Medicine, Hannover, Germany.
• 2Hannover Medical School, CELLS - Centre for Ethics and Law in the Life Sciences, Institute for History, Ethics and Philosophy of Medicine, Hannover, Germany; Leibniz University of Hannover, CELLS - Centre for Ethics and Law in the Life Sciences, Department of Philosophy, Hannover, Germany.

Abstract

INTRODUCTION:

According to the Declaration of Helsinki and other guidelines, clinical studies should be approved by a research ethics committee and seek valid informed consent from the participants. Editors of medical journals are encouraged by the ICMJE and COPE to include requirements for these principles in the journal's instructions for authors. This study assessed the editorial policies of psychiatry journals regarding ethics review and informed consent.

METHODS AND FINDINGS:

The information given on ethics review and informed consent and the mentioning of the ICMJE and COPE recommendations were assessed within author's instructions and online submission procedures of all 123 eligible psychiatry journals. While 54% and 58% of editorial policies required ethics review and informed consent, only 14% and 19% demanded the reporting of these issues in the manuscript. The TOP-10 psychiatry journals (ranked by impact factor) performed similarly in this regard.

CONCLUSIONS:

Only every second psychiatry journal adheres to the ICMJE's recommendation to inform authors about requirements for informed consent and ethics review. Furthermore, we argue that even the ICMJE's recommendations in this regard are insufficient, at least for ethically challenging clinical trials. At the same time, ideal scientific design sometimes even needs to be compromised for ethical reasons. We suggest that features of clinical studies that make them morally controversial, but not necessarily unethical, are analogous to methodological limitations and should thus be reported explicitly. Editorial policies as well as reporting guidelines such as CONSORT should be extended to support a meaningful reporting of ethical research.

Int J Drug Policy. 2014 Apr 29. pii: S0955-3959(14)00090-5. doi: 10.1016/j.drugpo.2014.04.014. [Epub ahead of print]

Making drug policy together: Reflections on evidence, engagement and participation.

Roberts M.

Author information

• Chief Executive, DrugScope, United Kingdom. Electronic address: marcusr@drugscope.org.uk.

Abstract

This commentary considers the relationship between evidence, engagement and participation in drug policy governance. It argues that the use of various forms of evidence (for example, statistical data and service user narratives) is critical for meaningful stakeholder engagement and public participation in drug policy, as well as effective policy design and implementation. The respective roles of these different kinds of evidence in consultation processes need to be better understood. It discusses the limits of evidence, which it suggests is rarely conclusive or decisive for drug policy. This is partly because of the incompleteness of most research agendas and the lack of consensus among researchers, but also because issues in drug policy are inherently contestable, involving considerations that lie outside the competency of drug policy specialist as such. In particular, this is because they involve normative and evaluative issues that are properly political (for example, about the relative weight to be accorded to different kinds of harm and benefit). It concludes by supporting calls for a more nuanced understanding of the relationship between evidence, engagement and politics than is implicit in the term 'evidence based policy'. It also argues that we should view the inherent contestability of drug policy not as something that can or should be resolved by 'objective' evidence, but as a source of vitality and creativity in policy development and evaluation.

“Are paper towels the same as napkins?” (Yes. Also plates and kleenexes.)

Bounty Launches Beginner Series For People New To Paper Towels

NEWS WITH VIDEO • Products • News • Business • ISSUE 50•22 • Jun 4, 2014

 "In addition, sources told reporters that the Bounty Beginners website will contain a regularly updated FAQ section featuring questions such as, “Are paper towels the same as napkins?” “Will my paper towels ever expire?” and “Can paper towels accidentally absorb my child, spouse, or pet?” The site will also include detailed safety information on incorrect uses of paper towels, including eating paper towels as food and using paper towels to wipe up fire."

HT: CA

Cancer Discov. 2014 Jun 3. pii: CD-14-0337. [Epub ahead of print]

AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer.

Cross DA1, Ashton SE2, Ghiorghiu S3, Eberlein C4, Nebhan CA5, Spitzler PJ5, Orme JP6, Finlay MR7, Ward RA3, Mellor MJ8, Hughes G3, Rahi A3, Jacobs VN3,Red Brewer M5, Ichihara E9, Sun J10, Jin H9, Ballard P3, Al-Kadhimi K8, Rowlinson R3, Klinowska T11, Richmond GH12, Cantarini M3, Kim DW13, Ranson MR14, Pao W15.

Author information

• 1Oncology Innovative Medicines, AstraZeneca Darren.Cross@astrazeneca.com.
• 2cancer and infection bioscience, Astrazeneca.
• 3Oncology Innovative Medicines, Astrazeneca.
• 4Oncology, AstraZeneca.
• 5Medicine, Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center.
• 6Discovery Sciences, Astrazeneca.
• 7AstraZeneca, UK.
• 8Oncology iMed, Astrazeneca R&D.
• 9Vanderbilt-Ingram Cancer Center, Vanderbilt University.
• 10Vanderbilt University.
• 11Cancer and Infection Discovery, AstraZeneca.
• 12Global Safety Assessment, AstraZeneca.
• 13Department of Internal Medicine, Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine.
• 14Clinical Experimental Pharmacology, University of Manchester.
• 15Medicine (Division of Hematology/Oncology), Cancer Biology, and Pathology, Microbiology, and Immunology, Vanderbilt-Ingram Cancer Center.

Abstract

First generation EGF receptor tyrosine kinase inhibitors (EGFR TKIs) provide significant clinical benefit in patients with advanced EGFR mutant (EGFRm+) non-small cell lung cancer (NSCLC). Patients ultimately develop disease progression, often driven by acquisition of a second T790M EGFR TKI resistance mutation. AZD9291 is a novel oral, potent and selective third generation irreversible inhibitor of both EGFRm+ sensitizing and T790M resistance mutants that spares wild-type EGFR. This mono-anilino-pyrimidine compound is structurally distinct from other third generation EGFR TKIs and offers a pharmacologically differentiated profile from earlier generation EGFR TKIs. Pre-clinically, the drug potently inhibits signaling pathways and cellular growth in both EGFRm+ and EGFRm+/T790M mutant cell lines in vitro, with lower activity against wild-type EGFR lines, translating into profound and sustained tumor regression in EGFR mutant tumor xenograft and transgenic models. The treatment of two patients with advanced EGFRm T790M+ NSCLC is described as proof of principle.

From George Mason U: Creating Neoliberal Citizens in Morocco: Reproductive Health, Development Policy, and Popular Islamic Beliefs

Med Anthropol. 2014 Jun 3. [Epub ahead of print]

Creating Neoliberal Citizens in Morocco: Reproductive Health, Development Policy, and Popular Islamic Beliefs.

Hughes Rinker C.

Author information

• a Direct communication to her at Department of Sociology and Anthropology George Mason University , 4400 University Drive, MSN 3G5, Fairfax , VA 22030 .

Abstract

Self-governance and responsibility are two traits associated with neoliberal citizenship in scholarly and popular discourses, but little of the literature on this topic focuses on North Africa. My goal, in this article, is not only to fill this void, but also to complicate understandings of neoliberalism through an examination of the relationship between reproductive health care, development policy, and popular Islamic beliefs in Morocco. My discussion is based on fieldwork in Rabat, Morocco, which included observations in health clinics, interviews with patients and staff, and visits to patients' homes. By analyzing the childbearing and childrearing practices of Moroccan women who visited the clinics, I pose that neoliberal logic cannot be pre-defined or understood as a monolithic concept. I demonstrate that women were active in their own governance and accountable for their reproductive behaviors, but they did so because of their understandings of what Islam says about fertility and motherhood.

"We find almost no statistical support for higher energy-dense food being cheaper than low energy-dense food."

Public Health Nutr. 2014 Jun 3:1-7. [Epub ahead of print]

The inverse relationship between food price and energy density: is it spurious?

Davis GC1, Carlson A2.

Author information

• 11Department of Human Nutrition,Foods,and Exercise and Agricultural and Applied Economics,Virginia Tech University,214 Hutcheson Hall,Blacksburg,VA 24061,USA.
• 22US Department of Agriculture,Economic Research Service,Washington,DC,USA.

Abstract

OBJECTIVE:

An important debate in the literature is whether or not higher energy-dense foods are cheaper than less energy-dense foods. The present communication develops and applies an easy statistical test to determine if the relationship between food price and energy density is an artifact of how the data units are constructed (i.e. is it 'spurious' or 'real'?).

DESIGN:

After matching data on 4430 different foods from the National Health and Nutrition Examination Survey with corresponding prices from the Center for Nutrition Policy and Promotion's Food Prices Database, we use a simple regression model to test if the relationship between food price and energy density is 'real' or 'spurious'.

SETTING: USA. SUBJECTS:

Total sample size is 4430 observations of consumed foods from 4578 participants from the non-institutionalized US adult population (aged 19 years and over).

RESULTS:

Over all 4430 foods, the null hypothesis of a spurious inverse relationship between food price per energy density and energy density is not rejected. When the analysis is broken down by twenty-five food groups, there are only two cases where the inverse relationship is not spurious. In fact, the majority of non-spurious relationships between food price and energy density are positive, not negative.

CONCLUSIONS:

One of the main arguments put forth regarding the poor diet quality of low-income households is that high energy-dense food is cheaper than lower energy-dense food. We find almost no statistical support for higher energy-dense food being cheaper than low energy-dense food. While economics certainly plays a role in explaining low nutritional quality, more sophisticated economic arguments are required and discussed.

"The only worse sin is to side actively with the enemy and kill your brothers in arms."

JUNE 3, 2014 6:40 PM

Why Team Obama Was Blindsided by the Bergdahl Backlash 

The president and Ms. Rice seem to think that the crime of desertion in wartime is kind of like skipping class. 

By Ralph Peters

"Both President Obama and Ms. Rice seem to think that the crime of desertion in wartime is kind of like skipping class. They have no idea of how great a sin desertion in the face of the enemy is to those in our military. The only worse sin is to side actively with the enemy and kill your brothers in arms."

HT: PP

Clin Transl Sci. 2014 May 29. doi: 10.1111/cts.12161. [Epub ahead of print]

Development and Maintenance of a Biospecimen Repository for Clinical Samples Derived from Pulmonary Patients.

Schwiebert LM1, Estell K, Meadows T, Thannickal VJ, Rowe S, Sorscher EJ, Harris WT, Gaggar A, Dransfield M, de Andrade JA.

Author information

• 1Department of Cell, Developmental and Integrative Biology; Department of Medicine - Division of Pulmonary, Allergy and Critical Care Medicine.

Abstract

The Pulmonary Biospecimen Repository (PBR) at the University of Alabama at Birmingham (UAB) was launched in 2009. The purpose of the UAB PBR is to provide investigators within the pulmonary community at UAB and elsewhere with clinical samples derived from multiple lung diseases, including transplant recipients, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, cystic fibrosis, and asthma. Cell and fluid samples isolated from bronchoalveolar lavage (BAL), plasma, and serum are collected and stored; samples are assessed routinely for viability. Each sample is linked directly with the respective patient information via the Pulmonary Translational Research and Clinical Database, a Health Insurance Portability and Accountability Act compliant database that includes detailed information allowing for the study of specific patient cohorts. To access samples, investigators must complete a request form, which is reviewed by the UAB PBR Steering Committee. To date, more than 800 patients have provided approximately 7,000 BAL, serum and plasma fluid, and cell samples. Over the past 4 years, nearly 800 of these samples have been distributed to investigators at UAB and elsewhere. Future plans for the UAB PBR include expanding sample collection to additional pulmonary diseases, such as mycobacterial infections, increasing the number of sample users and obtaining external funding to ensure its continued sustainability.

Vaccination against smoking. What could possibly go wrong?

Addiction. 2014 Jun 3. doi: 10.1111/add.12572. [Epub ahead of print]

Vaccination against smoking: an annotated agenda for debate. A review of scientific journals, 2001-13.

Wolters A1, de Wert G, van Schayck OC, Horstman K.

Author information

• 1Department of Health, Ethics, and Society, School CAPHRI, Maastricht University, Maastricht, the Netherlands.

Abstract

BACKGROUND AND AIMS:

The ongoing development of novel nicotine vaccines makes it urgent to identify the normative questions around this innovative health technology against smoking.

METHODS:

A qualitative thematic analysis of peer-reviewed papers on nicotine vaccination published between 2001 and 2013.

RESULTS:

In the scientific discourse, nicotine vaccination is presented in a neurobiological frame as a potent concept for (long-term) smoking cessation. Nicotine vaccination is also considered a hypothetical strategy to prevent nicotine addiction in minors. Ethical assessments are conducted for the use of nicotine vaccination in public health and clinical medicine. Whereas vaccination for primary prevention is usually associated with public health, the hypothetical case of nicotine prevention in minors is also assessed for individualized protection. Therapeutic and preventive applications are given uneven attention: the classic goal of vaccination (primary prevention in minors) receives methodical consideration and invokes lively debate. The unprecedented use of vaccination, namely smoking cessation, is left largely unattended in the ethical analyses.

CONCLUSIONS:

While health innovations such as nicotine vaccination need broad reflection to guide decisions on their further development and possible future implementations, only a small part of the ethical and social issues of this innovative technology has been discussed. For a debate to come into existence, a 'neurobio-psycho-socio-cultural' frame of smoking and quitting appears fruitful. Important topics for reflection are the human activities and social processes in a vaccine-supported quit attempt, next to respect for individuals, possible harms and questions of (global) justice and research ethics.

Philos Ethics Humanit Med. 2014 Jun 2;9(1):11. [Epub ahead of print]

The moral code in Islam and organ donation in Western countries: reinterpreting religious scriptures to meet utilitarian medical objectives.

Rady MY, Verheijde JL.

Abstract

End-of-life organ donation is controversial in Islam. The controversy stems from: (1) scientifically flawed medical criteria of death determination; (2) invasive perimortem procedures for preserving transplantable organs; and (3) incomplete disclosure of information to consenting donors and families. Data from a survey of Muslims residing in Western countries have shown that the interpretation of religious scriptures and advice of faith leaders were major barriers to willingness for organ donation. Transplant advocates have proposed corrective interventions: (1) reinterpreting religious scriptures, (2) reeducating faith leaders, and (3) utilizing media campaigns to overcome religious barriers in Muslim communities. This proposal disregards the intensifying scientific, legal, and ethical controversies in Western societies about the medical criteria of death determination in donors. It would also violate the dignity and inviolability of human life which are pertinent values incorporated in the Islamic moral code. Reinterpreting religious scriptures to serve the utilitarian objectives of a controversial end-of-life practice, perceived to be socially desirable, transgresses the Islamic moral code. It may also have deleterious practical consequences, as donors can suffer harm before death. The negative normative consequences of utilitarian secular moral reasoning reset the Islamic moral code upholding the sanctity and dignity of human life.

A blood test comes back with a critical value result. Should it be repeated?

Christopher M. Lehman, Peter J. Howanitz, Rhona Souers, and Donald S. Karcher (2014) Utility of Repeat Testing of Critical Values: A Q-Probes Analysis of 86 Clinical Laboratories. Archives of Pathology & Laboratory Medicine: June 2014, Vol. 138, No. 6, pp. 788-793.

CAP LABORATORY IMPROVEMENT PROGRAMS

Utility of Repeat Testing of Critical Values: A Q-Probes Analysis of 86 Clinical Laboratories

Christopher M. Lehman, MD; Peter J. Howanitz, MD; Rhona Souers, MS; Donald S. Karcher, MD

From the Pathology Department, University of Utah Health Care, Salt Lake City (Dr Lehman); the Pathology Department, State University of New York Downstate Medical Center, Brooklyn (Dr Howanitz); the Biostatistics Division, College of American Pathologists, Northfield, Illinois (Ms Souers); and the Pathology Department, George Washington University Medical Center, Washington, DC (Dr Karcher).

Context.— A common laboratory practice is to repeat critical values before reporting the test results to the clinical care provider. This may be an unnecessary step that delays the reporting of critical test results without adding value to the accuracy of the test result.

Objectives.— To determine the proportions of repeated chemistry and hematology critical values that differ significantly from the original value as defined by the participating laboratory, to determine the threshold differences defined by the laboratory as clinically significant, and to determine the additional time required to analyze the repeat test.

Design.— Participants prospectively reviewed critical test results for 4 laboratory tests: glucose, potassium, white blood cell count, and platelet count. Participants reported the following information: initial and repeated test result; time initial and repeat results were first known to laboratory staff; critical result notification time; if the repeat result was still a critical result; if the repeat result was significantly different from the initial result, as judged by the laboratory professional or policy; significant difference threshold, as defined by the laboratory; the make and model of the instrument used for primary and repeat testing.

Results.— Routine, repeat analysis of critical values is a common practice. Most laboratories did not formally define a significant difference between repeat results. Repeated results were rarely considered significantly different. Median repeated times were at least 17 to 21 minutes for 10% of laboratories. Twenty percent of laboratories reported at least 1 incident in the last calendar year of delayed result reporting that clinicians indicated had adversely affected patient care.

Conclusion.— Routine repeat analysis of automated chemistry and hematology critical values is unlikely to be clinically useful and may adversely affect patient care.

"...blaming behavior in the context of professional health care is built on nothing stronger than prejudice."

Nurs Philos. 2014 May 29. doi: 10.1111/nup.12061. [Epub ahead of print]

Who can blame who for what and how in responsibility for health?

Snelling PC.

Author information

• Institute of Health and Society, University of Worcester, Worcester, UK.

Abstract

This paper starts by introducing a tripartite conception of responsibility for health consisting of a moral agent having moral responsibilities and being held responsible, that is blamed, for failing to meet them and proceeds to a brief discussion of the nature of the blame, noting difficulties in agency and obligation when the concept is applied to health-threatening behaviours. Insights about the obligations that we hold people to and the extent of their moral agency are revealed by interrogating our blaming behavior, and to facilitate this, my own blaming attitudes and actions are analysed in respect of an imagined adult son who seeks thrills by jumping from a pier into the sea, an activity common around coastlines and intended to be analogous in varying degrees to a range of health-threatening behaviours. I consider my responses to this imagined act in relation to some features of moralism, the excess of morality, concluding that blame can be justified when it is proportionate and within interpersonal relationships. There is evidence that some nurses hold negative blaming attitudes towards groups of patients considered to have caused or contributed to their illness, but this is not justified, not only because of impaired agency, but also because if there is responsibility for health, associated obligations are owed to those who share our lives, and it is those people who are entitled to hold individuals responsible. Nurses who hold negative blaming attitudes towards groups of patients are invited to identify the status of moral agency, the precise natures of their (failed) obligations, and of the patient-nurse relationship. It is concluded that reflection on these matters and the difference between justified blame and moralism demonstrates that blaming behaviour in the context of professional health care is built on nothing stronger than prejudice.

From U Pennsylvania: Would the Elimination of the Capacity to Suffer Solve Ethical Dilemmas in Experimental Animal Research?

Curr Top Behav Neurosci. 2014 Jun 3. [Epub ahead of print]

Would the Elimination of the Capacity to Suffer Solve Ethical Dilemmas in Experimental Animal Research?

Shriver A.

Author information

• Department of Medical Ethics and Health Policy, University of Pennsylvania, Philadelphia, PA, USA, ashriver@wustl.edu.

Abstract

The use of genetic engineering to enhance the welfare of laboratory animals can reduce the amount of suffering in current neuroscience research paradigms. In particular, for some forms of basic research, we can use welfare-enhanced animals to reduce harms to animals without sacrificing any of the scientific validity. In another group of experiments, we can use welfare-enhanced animals to dramatically reduce the number of unprotected animals enduring aversive procedures. Many of the objections to using welfare-enhanced animals for food production do not apply to their use in research, since genetic knockout techniques are already used routinely in research for human ends and since there is no risk for human health. Furthermore, examples of recent knockout experiments suggest that we already have, or are very close to having, the capacity to reduce suffering in laboratories via genetic engineering. If we are truly committed to balancing the advancement of science with the welfare of animals, this option should be further explored.

I am running for the College of American Pathologists Board of Governors. My vision is here.

I am running for the College of American Pathologists Board of Governors.  My vision is here.

Human-Animal Chimera: A Neuro Driven Discussion?

Sci Eng Ethics. 2014 Jun 3. [Epub ahead of print]

Human-Animal Chimera: A Neuro Driven Discussion? Comparison of Three Leading European Research Countries.

Cabrera Trujillo LY1, Engel-Glatter S.

Author information

• 1Institute of Biomedical Ethics, University of Basel, Bernoullistrasse 28, 4056, Basel, Switzerland, Laura.cabrera@unibas.ch.

Abstract

Research with human-animal chimera raises a number of ethical concerns, especially when neural stem cells are transplanted into the brains of non-human primates (NHPs). Besides animal welfare concerns and ethical issues associated with the use of embryonic stem cells, the research is also regarded as controversial from the standpoint of NHPs developing cognitive or behavioural capabilities that are regarded as "unique" to humans. However, scientists are urging to test new therapeutic approaches for neurological diseases in primate models as they better mimic human physiology than all current animal models. As a response, various countries have issued reports on the topic. Our paper summarizes the ethical issues raised by research with human-animal brain chimeras and compares the relevant regulatory instruments and different recommendations issued in national reports from three important European research nations: Germany, Switzerland and the United Kingdom. We assess and discuss the focus and priorities set by the different reports, review various reasons for and perspectives on the importance of the brain in chimera research, and identify critical points in the reports that warrant further specification and debate.

Greta Alì, Agnese Proietti, Serena Pelliccioni, Cristina Niccoli, Cristiana Lupi, Elisa Sensi, Riccardo Giannini, Nicla Borrelli, Maura Menghi, Antonio Chella, Alessandro Ribechini, Federico Cappuzzo, Franca Melfi, Marco Lucchi, Alfredo Mussi, Gabriella Fontanini, (2014) ALK Rearrangement in a Large Series of Consecutive Non–Small Cell Lung Cancers: Comparison Between a New Immunohistochemical Approach and Fluorescent In Situ Hybridization for the Screening of Patients Eligible for Crizotinib Treatment. Archives of Pathology & Laboratory Medicine In-Press.

Early Online Release

ALK Rearrangement in a Large Series of Consecutive Non–Small Cell Lung Cancers: Comparison Between a New Immunohistochemical Approach and Fluorescent In Situ Hybridization for the Screening of Patients Eligible for Crizotinib Treatment

Greta Alì, MD; Agnese Proietti, MD; Serena Pelliccioni, MLT; Cristina Niccoli, MLT; Cristiana Lupi, PhD; Elisa Sensi, PhD; RiccardoGiannini, PhD; Nicla Borrelli, PhD; Maura Menghi, PhD; Antonio Chella, MD; Alessandro Ribechini, MD; Federico Cappuzzo, MD;Franca Melfi, MD; Marco Lucchi, MD; Alfredo Mussi, MD; Gabriella Fontanini, MD

From the Units of Pathological Anatomy (Drs Alì, Proietti, Lupi, and Sensi and Ms Pelliccioni), Pneumology (Dr Chella), Endoscopic Section of Pneumology (Dr Ribechini), and Thoracic Surgery (Drs Melfi and Lucchi), Azienda Ospedaliera Universitaria Pisana, Pisa, Italy; the Units of Pathological Anatomy (Ms Niccoli and Drs Giannini, Borrelli, and Fontanini) and Thoracic Surgery (Dr Mussi), Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy; Diatech Pharmacogenetics, Jesi, Italy (Dr Menghi); and the Department of Oncology, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy (Dr Cappuzzo).

Context.— Echinoderm microtubule associated proteinlike 4–anaplastic lymphoma receptor tyrosine kinase (EML4-ALK) translocation has been described in a subset of patients with non–small cell lung cancer (NSCLC) and has been shown to have oncogenic activity. Fluorescence in situ hybridization (FISH) is used to detect ALK-positive NSCLC, but it is expensive, time-consuming, and difficult for routine application.

Objective.— To evaluate the potential role of immunohistochemistry (IHC) as a screening tool to identify candidate cases for FISH analysis and for ALK inhibitor therapy in NSCLC.

Design.— We performed FISH and IHC for ALK and mutational analysis for epidermal growth factor receptor (EGFR) andKRAS in 523 NSCLC specimens. We conducted IHC analysis with the monoclonal antibody D5F3 (Ventana Medical Systems, Tucson, Arizona) and a highly sensitive detection system. We also performed a MassARRAY-based analysis (Sequenom, San Diego, California) in a small subset of 11 samples to detect EML4-ALK rearrangement.

Results.— Of the 523 NSCLC specimens, 20 (3.8%) were positive for ALK rearrangement by FISH analysis. EGFR andKRAS mutations were identified in 70 (13.4%) and 124 (23.7%) of the 523 tumor samples, respectively. ALK rearrangement and EGFR and KRAS mutations were mutually exclusive. Of 523 tumor samples analyzed, 18 (3.4%) were ALK⁺ by IHC, 18 samples (3.4%) had concordant IHC and FISH results, and 2 ALK⁺ cases (0.3%) by FISH failed to show ALK protein expression. In the 2 discrepant cases, we did not detect any mass peaks for the EML4-ALK variants by MassARRAY.

Conclusions.— Our results show that IHC may be a useful technique for selecting NSCLC cases to undergo ALK FISH analysis.

Sci Eng Ethics. 2014 Jun 3. [Epub ahead of print]

Existential Risks: Exploring a Robust Risk Reduction Strategy.

Jebari K.

Author information

• Royal Institute of Technology, KTH, Teknikringen 78B, 114 28, Stockholm, Sweden, jebarikarim@gmail.com.

Abstract

A small but growing number of studies have aimed to understand, assess and reduce existential risks, or risks that threaten the continued existence of mankind. However, most attention has been focused on known and tangible risks. This paper proposes a heuristic for reducing the risk of black swan extinction events. These events are, as the name suggests, stochastic and unforeseen when they happen. Decision theory based on a fixed model of possible outcomes cannot properly deal with this kind of event. Neither can probabilistic risk analysis. This paper will argue that the approach that is referred to as engineering safety could be applied to reducing the risk from black swan extinction events. It will also propose a conceptual sketch of how such a strategy may be implemented: isolated, self-sufficient, and continuously manned underground refuges. Some characteristics of such refuges are also described, in particular the psychosocial aspects. Furthermore, it is argued that this implementation of the engineering safety strategy safety barriers would be effective and plausible and could reduce the risk of an extinction event in a wide range of possible (known and unknown) scenarios. Considering the staggering opportunity cost of an existential catastrophe, such strategies ought to be explored more vigorously.

Trials. 2014 May 13;15(1):167. [Epub ahead of print]

The challenge of recruiting patients into a placebo-controlled surgical trial.

Hare KB, Lohmander LS, Roos EM.

Abstract

BACKGROUND:

Randomized placebo-controlled trials represent the gold standard in evaluating healthcare interventions but are rarely performed within orthopedics. Ethical concerns or well-known challenges in recruiting patients for surgical trials in general have been expressed and adding a placebo component only adds to this complexity. The purpose of this study was to report the challenges of recruiting patients into an orthopedic placebo-controlled surgical trial, to determine the number of patients needed to be screened and allocated in order to include one participant into the trial, and to identify reasons associated with participation in a placebo-controlled randomized surgical trial.

METHODS:

Data were extracted from an ongoing placebo-controlled randomized controlled trial (RCT) on meniscectomy versus placebo surgery. We calculated the number of patients needed to be screened in order to include the required number of participants into the RCT. Participating patients were asked about their rationale for joining the study and which type of information was most useful for deciding upon participation.

RESULTS:

A total of 476 patients entered the screening group, of which 190 patients fulfilled the inclusion and exclusion criteria. 102 patients declined to participate in the study due to various reasons and 46 were later excluded (no meniscus lesion on the magnetic resonance imaging scan or withdrawn consent). A total of 40 patients were finally included in the RCT. To include one patient into the RCT, 11.9 individuals needed to be screened. A total of 69% of participating patients considered the oral information to be the most important and the most common reason for participating was the contribution to research (90%).

CONCLUSIONS:

Patients are willing to participate in an orthopedic placebo-controlled surgical trial. Oral information given by the surgeon to the patient and the contribution to research are important aspects to enhance patient recruitment.

BMC Public Health. 2014 May 16;14(1):458. [Epub ahead of print]

Ethical considerations of worksite health promotion: an exploration of stakeholders' views.

van Berkel J, Meershoek A, Janssens RM, Boot CR, Proper KI, van der Beek AJ.

Abstract

BACKGROUND:

Developing, implementing and evaluating worksite health promotion requires dealing with all stakeholders involved, such as employers, employees, occupational physicians, insurance companies, providers, labour unions and research and knowledge institutes. Although worksite health promotion is becoming more common, empirical research on ethical considerations of worksite health promotion is scarce.

METHODS:

We explored the views of stakeholders involved in worksite health promotion in focus group discussions and we described the ethicalconsiderations that result from differences between these views. The focus group discussions were organised per stakeholder group. Data were analysed according to the constant comparison method.

RESULTS:

Our analyses show that although the definition of occupational health is the same for all stakeholders, namely 'being able to perform your job', there seem to be important differences in the views on what constitutes a risk factor to occupational health. According to the employees, risk factors to occupational health are prevailingly job-related. Labour unions agree with them, but other stakeholders, including the employer, particularly see employee-related issues such as lifestyle behaviour as risk factors to occupational health. The difference in definition of occupational health risk factors translates into the same categorisation of worksite health promotion; employee-related activities and work-related activities. The difference in conceptualisation of occupational health risk factors and worksite health promotion resonates in the way stakeholders understand 'responsibility' for lifestyle behaviour. Even though all stakeholders agree on whose responsibility lifestyle behaviour is, namely that of the employee, the meaning of 'responsibility' differs between employees, and employers. For employees, responsibility means autonomy, while for employers and other stakeholders, responsibility equals duty. This difference may in turn contribute to ambivalent relationships between stakeholders.

CONCLUSION:

All stakeholders, including employees, should be given a voice in developing, implementing and evaluating worksite health promotion. Moreover, since stakeholders agree on lifestyle being the responsibility of the employee, but disagree on what this responsibility means (duty versus autonomy), it is of utmost importance to examine the discourse of stakeholders. This way, ambivalence in relationships between stakeholders could be prevented.

Health Policy. 2014 May 14. pii: S0168-8510(14)00110-9. doi: 10.1016/j.healthpol.2014.04.011. [Epub ahead of print]

How should we regulate risk in biomedical research? An ethical analysis of recent policy proposals and initiatives.

Rid A.

Author information

• Department of Social Science, Health & Medicine, King's College London, United Kingdom. Electronic address: annette.rid@kcl.ac.uk.

Abstract

The existing regulatory framework for research is increasingly attacked for its "one-size-fits-all" approach. Many stakeholders contend that existing regulations formulate the same regulatory requirements for research involving very different levels of risk, and thereby unnecessarily stifle medical progress. To address this criticism, regulators are currently developing more risk-adapted approaches to regulating research. A key feature of these approaches is that they aim to calibrate subject protections, including ethical review and safety monitoring, to the risks that studies pose to participants. Risk-adapted systems of research oversight are ethically appealing because they have the potential to promote research within the constraints of adequate subject protection. However, this potential can only be realized if the complexities surrounding research risk can be addressed. The present paper offers the first systematic overview and ethical analysis of how European and U.S. regulators approach the development of more risk-adapted regulations. The analysis finds that so-called stratified approaches are ethically preferable because they specify risk categories with corresponding subject protections, and thereby reduce unwarranted variation in how research participants are protected in different studies. But the recent proposals for stratifying risk and subject protections raise various ethical concerns, for example regarding the accuracy of risk categories. Building on this analysis, the paper develops recommendations for future policy.