Placebo use and outcome quality: A protocol for systematic review and meta-analysis.

BACKGROUND: The Pharmaceutical industry sponsorship, research outcome and quality has been already evaluated for clinical trials in order to analyze if this kind of sponsorship affects the results of clinical trials. In this sense, this study has the aim to investigate whether placebo use allows positive outcomes regarding efficacy and safety compared to synthetic medicines. METHODS: We designed and registered a study protocol for a systematic review for methodology data. We will only randomized clinical trials that use placebo as comparator. The main outcome will be the evaluation of placebo use regarding the tendency for positive results (efficacy and security) when comparing to synthetic medicines. PubMed, Cochrane, LILACS (BVS), Web of Science, Scopus, and Excerpta Medica dataBASE (EMBASE) databases will be searched. Gray literature will be identified through the databases Proquest (Dissertation and Theses), OpenGrey and Google Scholar. Two review authors will independently assess trial quality and will extract data in accordance with standard Cochrane methodology. If necessary, we will also contact authors for additional information. The Cochrane Collaboration's risk of bias tool will be used. If feasible, it means homogenous data, we will conduct random effects meta-analysis. Subgroup analyses will be conducted for different justifications for placebo use and for studies sponsored/not sponsored by the pharmaceutical industry. RESULTS: Our present findings will indicate the effects of placebo use as comparator regarding efficacy and safety of the oral synthetic medicines. DISCUSSION: This systematic review will identify, summarize, and analyze if there is a trend for positive efficacy and safety results for synthetic medicines in clinical trials when compared with placebo and if the justification for placebo use is considered ethically acceptable. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018110829.

Health Outcome Prioritization in Alzheimer's Disease: Understanding the Ethical Landscape.

BACKGROUND: Dementia has been described as the greatest global health challenge in the 21st Century on account of longevity gains increasing its incidence, escalating health and social care pressures. These pressures highlight ethical, social, and political challenges about healthcare resource allocation, what health improvements matter to patients, and how they are measured. This study highlights the complexity of the ethical landscape, relating particularly to the balances that need to be struck when allocating resources; when measuring and prioritizing outcomes; and when individual preferences are sought. OBJECTIVE: Health outcome prioritization is the ranking in order of desirability or importance of a set of disease-related objectives and their associated cost or risk. We analyze the complex ethical landscape in which this takes place in the most common dementia, Alzheimer's disease. METHODS: Narrative review of literature published since 2007, incorporating snowball sampling where necessary. We identified, thematized, and discussed key issues of ethical salience. RESULTS: Eight areas of ethical salience for outcome prioritization emerged: 1) Public health and distributive justice, 2) Scarcity of resources, 3) Heterogeneity and changing circumstances, 4) Knowledge of treatment, 5) Values and circumstances, 6) Conflicting priorities, 7) Communication, autonomy and caregiver issues, and 8) Disclosure of risk. CONCLUSION: These areas highlight the difficult balance to be struck when allocating resources, when measuring and prioritizing outcomes, and when individual preferences are sought. We conclude by reflecting on how tools in social sciences and ethics can help address challenges posed by resource allocation, measuring and prioritizing outcomes, and eliciting stakeholder preferences.

The complexity of childhood gender dysphoria.

OBJECTIVE: To explore a developmental understanding of childhood gender dysphoria and to compare it to the prevailing paradigm, gender-affirming care. CONCLUSION: Viewing gender dysphoria through a contemporary developmental frame generates a different understanding of the nature of the phenomenon and its treatment and raises ethical questions about our current gender-affirming approach.

Problemas éticos en el manejo del dolor. Estudio cualitativo mediante entrevista de reflexión abierta / Ethical problems in the management of pain. Qualitative study through open reflection interview

INTRODUCCIÓN: La práctica médica en el área del dolor plantea problemas éticos en la atención a pacientes con una enfermedad que provoca un deterioro funcional, con un pronóstico incierto para su reinserción laboral, y gran consumo de recursos familiares y sociales. Tras la creación de un grupo de trabajo en bioética dentro de la Sociedad Española del Dolor (SED) se intenta analizar dichos problemas. OBJETIVO: Conocer los problemas éticos relacionados con el manejo del dolor (práctica clínica, entorno e instituciones) que preocupan a los profesionales miembros de la SED, así como fomentar una reflexión ética. METODOLOGÍA: Estudio cualitativo, basado en una entrevista semiestructurada, abierta, enviada a los miembros de la SED (n = 1035), mediante acceso electrónico, sobre 4 aspectos bioéticos: los problemas detectados en la práctica clínica, los problemas del entorno de trabajo, los problemas en las organizaciones de trabajo, y posibles sugerencias. Estos se agrupan según se refieran a las indicaciones (beneficencia y no maleficencia), la justicia (entendida como equidad) o la autonomía (información y preferencias). RESULTADOS: Participaron en la entrevista un 6 % de los profesionales (n = 62/1035). Se elaboró un panel con las 10 cuestiones principales identificadas. Destacan la incertidumbre en la toma de decisiones en la terapéutica, la limitación del esfuerzo terapéutico, los condicionamientos del sistema sanitario, las relaciones con la industria farmacéutica y la búsqueda de la excelencia. CONCLUSIONES: Este estudio cualitativo permite identificar problemas éticos que interesan a los profesionales dedicados al dolor. Es conveniente confirmarlos y dimensionarlos mediante estudios cuantitativos

INTRODUCTION: The medical practice in the area of pain associates ethical problems in the care of patients with a disease that causes a functional deterioration, with an uncertain prognosis for their labor reintegration, and a great consumption of family and social resources. After the creation of a working group on bioethics within the Spanish Pain Society (SPS), an attempt is made to analyze these problems. OBJECTIVE: To know which are the ethical problems that identify professionals (clinical practice, environment and institutions) which concerns SPS members; encouranging an ethical reflection. METHODOLOGY: Qualitative study, based on a semistructured, open interview, send to members of the SPS (n = 1035), through electronic access, on 4 bioethical aspects: the problems detected in clinical practice, the problems of the work environment, the problems in the work organizations, and possible suggestions. These are grouped as they refer to the indications (beneficence and non-maleficence), justice (understood as equity), autonomy (information and preferences). RESULTS: A total of 6 % professionals participated in the interview (n = 62/1035). A panel was prepared with the 10 main issues identified. They emphasize the uncertainty in the taking of decisions in the therapeutic, the limitation of the therapeutic effort, the conditioning of the sanitary system, the relations with the pharmaceutical industry and the search of the excellence. CONCLUSIONS: This qualitative study allows identifying ethical problems that interest professionals dedicated to pain. It is convenient to confirm and size them through quantitative studies

Do Some Patients Count More Than Others? Reporting Outcomes of the Same Patient in More Than One Study Requires Disclosure.

Clinical databases allow researchers to test multiple hypotheses. This could result in including outcomes on the same patient or patients in more than 1 study. When this occurs, it is vital for authors to clarify multiple reporting in their study methods to avoid having patients counted more than once in future systematic reviews or meta-analyses. As a caveat, primary authors should consider whether publication of multiple studies is important or whether they are simply generating "least publishable units" (LPUs, also known as salami slicing).

In Experimental Hand Transplantation, Whose Views About Outcomes Should Matter Most?

Consent to any experimental procedure, even when offered as therapeutic, involves extensive discussion between patient-subjects and clinician-researchers. Decision making should be shared with a focus on potential risks and benefits of enrolling in a protocol. Just as patients who underwent nonexperimental interventions might experience regret or reconsider autonomously made choices, patient-subjects who are undergoing or who have undergone experimental therapies should be afforded latitude to reconsider their decisions. Although clinician-researchers tend to be deeply invested in gathering data about patient-subjects' experiences, they are obligated to express respect for patient-subjects' fundamental right to stop being enrolled in research.

Evidence-based medicine-Not a panacea for the problems of a complex adaptive world.

The recent sacking of Peter Gøtzsche from the Cochrane Collaboration Board raised strong responses and highlights the neglected issue about priorities-maintaining the reputation of the organization or vigorously debating the merits of scientific approaches to find answers to complex problems? The Cochrane approach hales the randomized trial (RCT) as the gold standard research approach and affirms that meta-analysis provides the ultimate proof (or platinum standard) to settle contentious issues confronting the clinician. However, most published medical research is wrong, and critics coined the acronym GIGO (garbage in, garbage out) as a meme to highlight the risks of blind faith in the hyped-up procedures of the EBM movement. This paper firstly explores the differences between the prevailing scientific method arising from the linear cause-and-effect assumption and the complex adaptive systems science methods arising from observations that most phenomena emerge from nonlinearity in networked systems. Most medical conditions are characterized by necessary features that by themselves are not sufficient to explain their nature and behaviour. Such nonlinear phenomena require modelling approaches rather than linear statistical and/or meta-analysis approaches to be understood. These considerations also highlight that research is largely stuck at the data and information levels of understanding which fails clinicians who depend on knowledge-the synthesis of information-to apply in an adaptive way in the clinical encounter. Clinicians are constantly confronted with the linked challenges of doing things right and doing the right thing for their patients. EBM and Cochrane with their restrictive approaches are the antithesis to a practice of medicine that is responsive to constantly changing patient needs. As such, the EBM/Cochrane crisis opens a window of opportunity to re-examine the nature of health, illness and disease, and the nature of health care and its systems for the benefits of its professionals and their patients. We are at the cusp of a paradigmatic shift towards an understanding a praxis of health care that takes account of its complexities.

Moral entrepreneurship, the power-knowledge nexus, and the Cochrane "crisis".

BACKGROUND: In 2018, a so-called crisis developed in the international network of systematic reviewers known as Cochrane. It was widely depicted in terms of two competing narratives-"bad behaviour" by one member of Cochrane's Governing Board and scientific and moral decline within Cochrane. OBJECTIVE: Our goal was to distil insights on the structural issues underpinning the crisis, without taking a definitive position on the accuracy of either narrative. APPROACH AND DATASET: In this paper, we draw on (among other theories) Becker's notion of moral entrepreneurship and Foucault's conceptualisation of power to analyse the claims and counterclaims made by different parties. Our dataset consisted of publicly available materials (blogs, journal articles, newspaper articles) to end 2018, notably those relating to the expulsion of one Governing Board member. MAIN FINDINGS: Both narratives include strong moral claims about the science of systematic review and the governance of scientific organizations. The expelled individual and his supporters defined good systematic reviews in terms of a particular kind of methodological rigour and elimination of bias, and good governance largely in terms of measures to achieve independence from industry influence. Most of Cochrane's Governing Board and their sympathizers evaluated systematic reviews according to a broader range of criteria, incorporating factors such as attention to relationships among reviewers and reflexivity and dialogue around scientific and other judgements. They viewed governance partly in terms of accountability to an external advisory group. Power-knowledge alignments in Cochrane have emerged from, and contributed to, a particular system of meaning which is now undergoing evolution and challenge. CONCLUSION: Polarizing Cochrane's "crisis" into two narratives, only one of which is true, is less fruitful than viewing it in terms of a duality consisting of tensions between the two positions, each of which has some validity. Having framed the conflict as primarily philosophical and political rather than methodological and procedural, we suggest how Cochrane and its supporters and critics might harness their tensions productively.

The Impact of Corporate Payments on Robotic Surgery Research: A Systematic Review.

OBJECTIVE: To quantify the influence of financial conflict of interest (COI) payments on the reporting of clinical results for robotic surgery. DATA SOURCES AND STUDY SELECTION: A systematic search (Ovid MEDLINE databases) was conducted (May 2017) to identify randomized controlled trials (RCTs) and observational studies comparing the efficacy of the da Vinci robot on clinical outcomes. Financial COI data for authors (per study) were determined using open payments database. MAIN OUTCOMES AND MEASURES: Primary outcomes assessed were receipt of financial COI payments and overall conclusion reported between robotic versus comparative approach. Quality/risk of bias was assessed using Newcastle-Ottawa Scale (NOS)/Cochrane risk of bias tool. Disclosure discrepancies were also analyzed. DATA EXTRACTION AND SYNTHESIS: Study characteristics, surgical subspecialty, methodological assessment, reporting of disclosure statements, and study findings dual abstracted. The association of the amount of financial support received as a predictor of reporting positive findings associated robotic surgery was assessed at various cut-offs of dollar amount received by receiver operating curve (ROC). RESULTS: Thirty-three studies were included, 9 RCTs and 24 observational studies. There was a median, 111 patients (range 10 to 6420) across studies. A little more than half (17/33) had a conclusion statement reporting positive results in support of robotic surgery, with 48% (16/33) reporting results not in favor [equivocal: 12/33 (36%), negative: 4/33 (12%)]. Nearly all (91%) studies had authors who received financial COI payments, with a median of $3364.46 per study (range $9 to $1,775,378.03). ROC curve demonstrated that studies receiving greater than $9557.31 (cutpoint) were more likely to report positive robotic surgery results (sensitivity: 0.65, specificity: 0.81, area under the curve: 0.73). Studies with financial COI payment greater than this amount were more likely to report beneficial outcomes with robotic surgery [(78.57% vs 31.58%, P = 0.013) with an odds ratio of 2.07 (confidence interval: 0.47-3.67; P = 0.011)]. Overall, studies were high quality/low risk of bias [median NOS: 8 (range 5 to 9)]; Cochrane risk: "low risk" (9/9, 100%)]. CONCLUSION AND RELEVANCE: Financial COI sponsorship appears to be associated with a higher likelihood of studies reporting a benefit of robotic surgery. Our findings suggest a dollar amount where financial payments influence reported clinical results, a concept that challenges the current guidelines, which do not account for the amount of COI funding received.

Ethical Issues in Intrauterine Myelomeningocele Surgery.

Intrauterine surgery shows that the prognosis of neonates with myelomeningocele (MMC) has improved, both in survival and in quality of life. In order to study the current efficacy of intrauterine surgery for MMC and to make an ethical analysis of its proportionality, we conducted a PubMed search using the keywords "myelomeningocele", "intrauterine surgery", "MOMS", and "trial". Thirty-eight articles were found. The literature investigated the risks and benefits of intrauterine surgery based on the physiological parameters of MMC. Intrauterine surgery produces clear benefits. However, it also has disadvantages, such as premature birth, fetal or neonatal death, and uterine complications. The option of surgery is positive. However, since the intervention is risky, the final decision must be prudential, and thus should involve an ethical analysis of therapeutic proportionality. This requires a specific clinical evaluation of the fetus ensuring fetal survival in all cases and minimizing the risks arising from extremely premature birth.

Ethical challenges of outcome measurement in palliative care clinical practice: a systematic review of systematic reviews.

Several outcome measures have been systematically implemented to be used in palliative care. However, routine use in clinical practice is not without ethical challenges, which are not commonly addressed. The objectives of this study are therefore (I) to identify the ethical challenges/issues of outcome measurement in palliative care and (II) to understand how these ethical challenges/issues are addressed in palliative care clinical practice. The study consisted of a systematic review of systematic reviews, which is a type of review that brings together a summary of reviews in one place. We searched PubMed, Web of Science, EBSCOhost searching CINAHL Complete, MEDLINE Complete, Nursing & Allied Health Collection: Comprehensive, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Cochrane Methodology Register, Library, Information Science & Technology Abstracts, MedicLatina, from inception to January 2018. Out of 159 articles screened, only two [2] articles were included for analysis. The main ethical challenge/issue identified in these two reviews was cognitive impairment, particularly in patients with dementia. This challenge was addressed via proxy (family carers or health professionals) reporting outcome measurement. Ethical challenges/issues are poorly addressed in the existing systematic reviews about outcome measurement in palliative care clinical practice. Only two systematic reviews addressed ethical challenges/issues, namely cognitive impairment, particularly in persons with dementia. Further research is needed on this subject and to foster the use of outcome measurement among this vulnerable group of patients.

Psychiatry's ethical involvement in gender-affirming care.

OBJECTIVE: To reflect on the role of psychiatry in authorising physical treatments for Gender Dysphoria and to examine the quality of evidence for gender-reassignment. METHOD: A Medline search was performed with the subject term "transsexualism" or "gender dysphoria" and "outcome" or "follow-up" in the title. Studies published from 2005 onwards reporting psychosocial outcomes were selected for review. RESULTS: Most available evidence indicating positive outcomes for gender reassignment is of poor quality. The few studies with robust methodology suggest that some patients have poor outcomes and may be at risk of suicide. CONCLUSION: The author raises questions about the implications for ethical treatment of transgender individuals.

La calidad como estrategia para lograr mejores resultados en procesos de la salud / Quality as a strategy to achieve better results in health processes

En el presente número de la Revista Cubana de Genética Comunitaria los lectores encontrarán un artículo de revisión en el que se presentan aspectos relacionados con el aseguramiento de la calidad en los laboratorios de diagnóstico vinculados con la genética médica en nuestro país. En este artículo se abordarán de forma más precisa algunos de los aspectos a los que hemos hecho referencia en este editorial. Los artículos originales abarcan temas relacionados con el diagnóstico prenatal de defectos congénitos a través de la ultrasonografía, la relación de la aparición de defectos congénitos en madres con antecedentes personales de diabetes mellitus, hipertensión arterial y obesidad; y dos artículos en los que se utilizan técnicas de biología molecular para la caracterización molecular de dos enfermedades genéticas en nuestro país: la fibrosis quística y el síndrome de Hurler…(AU)

ISPOR Code of Ethics 2017 (4th Edition).

As the leading health economics and outcomes research (HEOR) professional society, ISPOR has a responsibility to establish a uniform, harmonized international code for ethical conduct. ISPOR has updated its 2008 Code of Ethics to reflect the current research environment. This code addresses what is acceptable and unacceptable in research, from inception to the dissemination of its results. There are nine chapters: 1 - Introduction; 2 - Ethical Principles respect, beneficence and justice with reference to a non-exhaustive compilation of international, regional, and country-specific guidelines and standards; 3 - Scope HEOR definitions and how HEOR and the Code relate to other research fields; 4 - Research Design Considerations primary and secondary data related issues, e.g., participant recruitment, population and research setting, sample size/site selection, incentive/honorarium, administration databases, registration of retrospective observational studies and modeling studies; 5 - Data Considerations privacy and data protection, combining, verification and transparency of research data, scientific misconduct, etc.; 6 - Sponsorship and Relationships with Others (roles of researchers, sponsors, key opinion leaders and advisory board members, research participants and institutional review boards (IRBs) / independent ethics committees (IECs) approval and responsibilities); 7 - Patient Centricity and Patient Engagement new addition, with explanation and guidance; 8 - Publication and Dissemination; and 9 - Conclusion and Limitations.

The use of clinical databases in disease outcomes research: Is the ethics of IRB review keeping up?

There is a perceived tension in research ethics between protecting the interests of participants and promoting good research as a societal good. The challenge of balancing the potential benefits of large clinical databases for disease outcomes research while protecting patients' privacy and confidentiality is an example of this dynamic. What is new about this tension in the context of "data warehousing" is the conflation of many differing interpretations of relevant ethics terminology, the proliferation of different kinds of databases, as well as the growth of research on a global level without the requisite harmonization of regulatory frameworks. The evolution of electronic medical records, the blurring of lines between clinical care and research in some rare orphan diseases, the growing trend to advocate for patient-centered research, and the advent of "open science" to facilitate global research initiatives have also contributed to challenging the existing norms for degrees of consent to this kind of research.