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).

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.

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.

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.

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.

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.

[Biosimilars in Gastroenterology - how much uncertainly is ethically acceptable?] / Biosimilars in der Gastroenterologie ­ Wie viel Unsicherheit ist ethisch akzeptabel?

Biosimilars use raises uncertainties with regards to efficacy despite potentially significant cost reductions. This requires a classical harm-benefit analysis. Important stakeholders include physicians and patients, companies producing biologica (drugs containing biotechnology-derived proteins as active substance), and companies producing biosimilars, as well as health insurance companies and politicians. They all have their distinct interests. In a rule-setting process, transparency is needed to protect the trust between patients and physicians. In an ideal world, the price of biologica without patent protection would be negotiated in a way that makes biosimilars unnecessary.

The Impact of Financial Conflicts of Interest in Plastic Surgery: Are They All Created Equal?

BACKGROUND: Recently, several studies have demonstrated that articles that disclose conflicts of interests (COI) are associated with publication of positive results. The purpose of this study was to learn more about the different types of COI as they relate to the general topic of COI in plastic surgery. Specifically, we aimed to examine whether different types of COI are more likely than others to be associated with the presentation of positive findings. METHODS: We reviewed all original articles in Annals of Plastic Surgery, Journal of Plastic, Reconstructive, and Aesthetic Surgery, and Plastic & Reconstructive Surgery from January 1, 2012, to December 31, 2013. All scientific articles were analyzed, and several article characteristics were extracted. Disclosed COI were categorized into the following categories: consultant/employee, royalties/stock options, and research support. The findings reported in each article abstract were blindly graded as reporting a positive, negative, neutral, or not applicable result. A multivariable analysis was performed to determine whether an association existed between certain types of COI and publication of positive conclusions. RESULTS: A total of 3124 articles were identified of which 1185 fulfilled the inclusion criteria. Financial COI were reported in 153 studies (12.9%). The most common type of COI was "research support" (7.3%), whereas the least common was "royalties/stock options" (1.2%). Rates of different types of COI varied significantly by plastic surgery subspecialty field (P < 0.001). In the multivariable analysis, authors who disclosed COI related to research support, consultant/employee, and royalties/stock options were 1.31, 6.62, and 8.72 times more likely, respectively, to publish positive findings when compared with authors that disclosed no COI after correcting for potential confounding factors. However, consultancy/employee status was the only COI category statistically associated with publication of positive results (P < 0.001). CONCLUSIONS: Self-reported COI are uncommon in plastic surgery research. Our results provide evidence that certain types of financial COI are more likely than others to be associated with the presentation of positive findings. This analysis suggests that certain investigators may be more biased, consciously or unconsciously, by the type of financial benefit offered by industry.

The Asher-McDade Aesthetic Index in Comparison With Two Scoring Systems in Nonsyndromic Complete Unilateral Cleft Lip and Palate Patients.

OBJECTIVE: To compare the Asher-McDade aesthetic index with 2 systems used to score the appearance of the nasolabial area in patients with a complete cleft lip and palate. DESIGN: Retrospective analysis of the results of complete unilateral cleft lip and palate patients. SETTING: Academic Center for Dentistry of Amsterdam and the VU University Medical Center. PATIENTS: Six-year-olds with complete unilateral cleft lip and palate. MAIN OUTCOME MEASURES: Cleft lip and palate patients assessed using the scoring system proposed by Prahl et al, a 5-point ordinal scale, and the scoring system proposed by Asher-McDade et al by 6 judges, 3 orthodontists, and 3 plastic surgeons. A calculation of intra- and interobserver reliability was made. A comparison was made of all the assessment methods using Kendalls' tau. RESULTS: Photographs of 55 children (38 boys and 17 girls) with complete unilateral cleft lip and palate were assessed. For the scoring system of Prahl et al, interobserver reliability varied from 0.43 to 0.53, for the 5-point scale between 0.45 and 0.57, and for the scoring system by Asher-McDade et al these varied between 0.52 and 0.66. Multiple significant correlations were found between the used scoring systems. CONCLUSION: It can be concluded that the Asher-McDade aesthetic index is still superior to the other scoring systems used in this study. However, all 3 scoring systems can reliably be used when 3 or more observers are used.

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.

Surgical report cards: the myth and the reality.

There seems no good reason for doctors to work in secret. Individual users of healthcare and the community in general, which ultimately bears the cost, are perfectly entitled to know how their health services and health providers are performing. The promulgation of surgical report cards has been hailed by some as a liberating step in the right direction. This paper seeks to analyse, from a clinician's perspective, the evolution and limitations of report cards. Ultimately, the importance of report cards will not be their immediate utility, which is minimal, but as a first step in a much wider and far more important debate about how we meaningfully measure the quality of health services and providers (including managers and bureaucrats), the likely cost of such an enterprise, how much we are willing and able to pay and how we reconcile the competing needs of information versus clinical and preventive care when all are competing for the same and inadequate pool of resources.

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.