The Fragility of Scientific Rigour and Integrity in "Sped up Science": Research Misconduct, Bias, and Hype and in the COVID-19 Pandemic.

During the early years of the COVID-19 pandemic, preclinical and clinical research were sped up and scaled up in both the public and private sectors and in partnerships between them. This resulted in some extraordinary advances, but it also raised a range of issues regarding the ethics, rigour, and integrity of scientific research, academic publication, and public communication. Many of the failures of scientific rigour and integrity that occurred during the pandemic were exacerbated by the rush to generate, disseminate, and implement research findings, which not only created opportunities for unscrupulous actors but also compromised the methodological, peer review, and advisory processes that would usually identify sub-standard research and prevent compromised clinical or policy-level decisions. While it would be tempting to attribute these failures of science and its translation solely to the "unprecedented" circumstances of the COVID-19 pandemic, the reality is that they preceded the pandemic and will continue to arise once it is over. Existing strategies for promoting scientific rigour and integrity need to be made more rigorous, better integrated into research training and institutional cultures, and made more sophisticated. They might also need to be modified or supplemented with other strategies that are fit for purpose not only in public health emergencies but in any research that is sped-up and scaled up to address urgent unmet medical needs.

Provider perspectives on liberty and harm in the treatment of persons with tuberculosis and mental illness.

To examine how frontline health care workers (HCWs) and decision-makers working in tuberculosis (TB) care and mental health care conceptualise liberty, harm and the harm principle-which are often invoked in health care legislation to justify liberty restrictions-in the treatment and care of persons with TB and severe and persistent mental illness (SPMI). Qualitative study of 20 semi-structured interviews with HCWs and decision-makers working in public or mental health from three public health units and two psychiatric hospitals in the Greater Toronto Area in Ontario, Canada. Interviews were evaluated using thematic analysis. Three themes were identified: 1) the contextual nature of liberty restrictions; 2) the concept of liberty as a matter of degree; and 3) the challenges of balancing the treatment and care goals of TB and mental health for persons with both TB and SPMI. Harm is understood by HCWs caring for persons with TB and/or SPMI in a context-dependent manner. This is compounded in the case of persons with both TB and SPMI. Liberty restrictions to advance public health goals entail reciprocal obligations from society, including social protections and additional resources, to ease the effects and range of liberty restrictions. Attention is required to ensure that treatment and care for SPMI does not impede that of TB and vice versa. .

Deprescribing antihyperglycemic agents in older persons: evidence-based clinical practice guideline

OBJECTIVE: To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper, stop, or switch antihyperglycemic agents in older adults. METHODS: We focused on the highest level of evidence available and sought input from primary care professionals in guideline development, review, and endorsement processes. Seven clinicians (2 family physicians, 3 pharmacists, 1 nurse practitioner, and 1 endocrinologist) and a methodologist comprised the overall team; members disclosed conflicts of interest. We used a rigorous process, including the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, for guideline development. We conducted a systematic review to assess evidence for the benefits and harms of deprescribing antihyperglycemic agents. We performed a review of reviews of the harms of continued antihyperglycemic medication use, and narrative syntheses of patient preferences and resource implications. We used these syntheses and GRADE quality-of-evidence ratings to generate recommendations. The team refined guideline content and recommendation wording through consensus and synthesized clinical considerations to address common front-line clinician questions. The draft guideline was distributed to clinicians and stakeholders for review and revisions were made at each stage. A decision-support algorithm was developed to accompany the guideline. RECOMMENDATIONS: We recommend deprescribing antihyperglycemic medications known to contribute to hypoglycemia in older adults at risk or in situations where antihyperglycemic medications might be causing other adverse effects, and individualizing targets and deprescribing accordingly for those who are frail, have dementia, or have a limited life expectancy. CONCLUSION: This guideline provides practical recommendations for making decisions about deprescribing antihyperglycemic agents. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.

Canadian survey on pandemic flu preparations.

BACKGROUND: The management of pandemic influenza creates public health challenges.An ethical framework, 'Stand on Guard for Thee: ethical considerations in pandemic influenza preparedness' that served as a template for the World Health Organization's global consultation on pandemic planning, was transformed into a survey administered to a random sample of 500 Canadians to obtain opinions on key ethical issues in pandemic preparedness planning. METHODS: All framework authors and additional investigators created items that were pilot-tested with volunteers of both sexes and all socioeconomic strata. Surveys were telephone administered with random sampling achieved via random digit dialing (RDD). Eligible participants were adults, 18 years or older, with per province stratification equaling provincial percent of national population. Descriptive results were tabulated and logistic regression analyses were used to assess whether demographic factors were significantly associated with outcomes. RESULTS: 5464 calls identified 559 eligible participants of whom 88.5% completed surveys. Over 90% of subjects agreed the most important goal of pandemic influenza preparations was saving lives, with 41% endorsing saving lives solely in Canada and 50% endorsing saving lives globally as the highest priority. Older age (OR = 8.51, p < 0.05) and current employment (OR = 9.48, p < 0.05) were associated with an endorsement of saving lives globally as highest priority. About 90% of respondents supported the obligation of health care workers to report to work and face influenza pandemic risks excepting those with a serious health condition that increased risks. Over 84% supported the government's provision of disability insurance and death benefits for health care workers facing elevated risk. Strong majorities favored stocking adequate protective antiviral dosages for all Canadians (92%) and, if effective, influenza vaccinations (95%). Over 70% agreed Canada should provide international assistance to poorer countries for pandemic preparation, even if resources for Canadians were reduced. While 92% of this group, believed provision should be 7 to 10% of all resources generated, 43% believed the provision should be greater than 10%. CONCLUSIONS: Results suggest trust in public health officials to make difficult decisions, providing emphasis on reciprocity and respect for individual rights.

The ethics of mandatory vaccination against influenza for health care workers.

Vaccination of health care workers (HCW) in long-term care results in indirect protection of patients who are at high-risk for influenza. The voluntary uptake of influenza vaccination among HCW is generally low. We argue that institutions caring for frail elderly have the responsibility to implement voluntary programmes for vaccination against influenza of HCW. When uptake falls short a mandatory programme may be justified. The main justification stems from the duty of care givers not to harm one's patient when one knows there is a significant risk of harm and the intervention to reduce this chance has a favourable balance of benefit over burdens and risks.

Duration and distance of exposure are important predictors of transmission among community contacts of Ontario SARS cases.

We report attack rates and contact-related predictors among community contacts of severe acute respiratory syndrome (SARS) cases from the 2003 Toronto-area outbreak. Community contact data was extracted from public health records for single, well-defined exposures to a SARS case. In total, 8662 community-acquired exposures resulted in 61 probable cases; a crude attack rate of 0.70% [95% confidence interval (CI) 0.54-0.90]. Persons aged 55-69 years were at higher risk of acquiring SARS (1.14%) than those either younger (0.60%) or older (0.70%). In multivariable analysis exposures for at least 30 min at a distance of

An exploratory spatial analysis of pneumonia and influenza hospitalizations in Ontario by age and gender.

Pneumonia and influenza represent a significant public health burden in Canada and abroad. Knowledge of how this burden varies geographically provides clues to understanding the determinants of these illnesses, and insight into the effective management of health-care resources. We conducted a retrospective, population-based, ecological-level study to assess age- and gender-specific spatial patterns of pneumonia and influenza hospitalizations in the province of Ontario, Canada from 1992 to 2001. Results revealed marked variability in hospitalization rates by age, as well as clear and statistically significant patterns of high rates in northern rural counties and low rates in southern urban counties. A moderate yet significant level of positive spatial autocorrelation (Moran's I=0.21, P<0.05) was found in the global data, with significant, age-specific clusters of high values or 'hot spots' identified in several northern counties. Findings illustrate the need for geographically focused prevention strategies, and resource and service allocation policies informed by regional and population-specific demands.

Interactions of viral pathogens on hospital admissions for pneumonia, croup and chronic obstructive pulmonary diseases: results of a multivariate time-series analysis.

Co-circulation of respiratory syncytial virus (RSV) and influenza has made the partitioning of morbidity and mortality from each virus difficult. Given the interaction between chronic obstructive lung disease (COPD) and pneumonia, often one can be mistaken for the other. Multivariate time-series methodology was applied to examine the impact of RSV and influenza on hospital admissions for bronchiolitis, pneumonia, and COPD. The Granger Causality Test, used to determine the causal relationship among series, showed that COPD and pneumonia are not influenced by RSV (P=0.2999 and 0.7725), but RSV does influence bronchiolitis (P=0.0001). Influenza was found to influence COPD, pneumonia, and bronchiolitis (P<0.0001). The use of multivariate time series and Granger causality applied to epidemiological data clearly illustrates the significant contribution of influenza and RSV to morbidity in the population.

Project examining effectiveness in clinical ethics (PEECE): phase 1-- descriptive analysis of nine clinical ethics services.

OBJECTIVE: The field of clinical ethics is relatively new and expanding. Best practices in clinical ethics against which one can benchmark performance have not been clearly articulated. The first step in developing benchmarks of clinical ethics services is to identify and understand current practices. DESIGN AND SETTING: Using a retrospective case study approach, the structure, activities, and resources of nine clinical ethics services in a large metropolitan centre are described, compared, and contrasted. RESULTS: The data yielded a unique and detailed account of the nature and scope of clinical ethics services across a spectrum of facilities. General themes emerged in four areas-variability, visibility, accountability, and complexity. There was a high degree of variability in the structures, activities, and resources across the clinical ethics services. Increasing visibility was identified as a significant challenge within organisations and externally. Although each service had a formal system for maintaining accountability and measuring performance, differences in the type, frequency, and content of reporting impacted service delivery. One of the most salient findings was the complexity inherent in the provision of clinical ethics services, which requires of clinical ethicists a broad and varied skill set and knowledge base. Benchmarks including the average number of consults/ethicist per year and the hospital beds/ethicist ratio are presented. CONCLUSION: The findings will be of interest to clinical ethicists locally, nationally, and internationally as they provide a preliminary framework from which further benchmarking measures and best practices in clinical ethics can be identified, developed, and evaluated.

Craniomaxillofacial injury in sport: a review of prevention research.

Current decision making in prevention of sport related craniomaxillofacial injury is based on available data derived from surveillance and attitude based studies. The literature on this type of injury prevention lacks the high quality scientific design and evidence on which mandatory interventions can be based. Currently available prevention methodology can provide a better understanding of injury mechanisms and produce valid interventions.

Evidence-based health policy: context and utilisation.

Evidence-based decision-making is centred on the justification of decisions. In the shift from an individual-clinical to a population-policy level, the decision-making context becomes more uncertain, variable and complex. To address this we have developed a conceptual framework for evidence-based decision-making, focusing on how context impacts on what constitutes evidence and how that evidence is utilised. We present two distinct orientations towards what constitutes evidence, representing different relationships between evidence and context. We also categorise the decision-making context based on the ways in which context impacts on evidence-based decision-making. Furthermore, we invoke the concept of axes of evidence-based decision-making to describe the relationship between evidence and context as we move from evidence-based medicine to evidence-based health policy. From this, we suggest that it may be more important how evidence is utilised than how it is defined. Based on the research and knowledge utilisation literature, we present a process model of evidence utilisation, which forms the basis for the conceptual framework for context-based evidence-based decision-making. The conceptual framework attempts to capture the role that context plays in the introduction, interpretation and application of evidence. We illustrate this framework with examples from policy development for colorectal cancer screening.

Argumentation and evidence.

This essay explores the role of informal logic and its application in the context of current debates regarding evidence-based medicine. This aim is achieved through a discussion of the goals and objectives of evidence-based medicine and a review of the criticisms raised against evidence-based medicine. The contributions to informal logic by Stephen Toulmin and Douglas Walton are explicated and their relevance for evidence-based medicine is discussed in relation to a common clinical scenario: hypertension management. This essay concludes with a discussion on the relationship between clinical reasoning, rationality, and evidence. It is argued that informal logic has the virtue of bringing explicitness to the role of evidence in clinical reasoning, and brings sensitivity to understanding the role of dialogical context in the need for evidence in clinical decision making.

Ethical issues in international environmental health research.

Environmental health problems are among the world's most significant health concerns. Although environmental risks are experienced disproportionately by people in developing countries, environmental health research (EHR) is conducted primarily in developed countries. Human subjects participate in five main types of EHR: (1) documentation and quantification of exposure to potentially hazardous substances; (2) elucidation of biological responses to these materials; (3) characterization and measurement of susceptibility to harmful effects of hazardous materials; (4) trials involving environmental interventions to reduce risk; and (5) documentation and measurement of various manifestations of disease putatively linked to environmental exposures. Although existing frameworks for the ethics of international clinical research are generally relevant to EHR, they currently lack the specificity necessary to confront three inherent problems in EHR, namely under-determination in EHR findings, the unavoidable nature of some environmental hazards, and environmental justice implications. We examine these issues as they relate to community partnership, risk assessment, and the assessment and management of economic and political interests in EHR. We believe that there are 3 general features of ethical EHR, it has health promoting value, the populations studied are not restricted in their ability to avoid environmental hazards by economic or political repression, and the justification for conducting EHR on populations with known exposure to environmental hazards gets stronger as the limits on populations to reduce the hazards or remove themselves from them becomes greater, as long as the first and second conditions are also met.

Attitudes toward tuberculosis of final year medical students from Canada, India, and Uganda.

BACKGROUND: Tuberculosis, although both preventable and treatable, continues to be the world's leading cause of death from an infectious agent. PURPOSE: To extend the results of our previous study of knowledge and practices of final year medical students regarding tuberculosis at three medical schools from endemic and nonendemic areas and to describe their attitudes. METHODS: Eight statements assessing attitudes, as part of a larger survey, were administered to final year medical students at McMaster University in Canada, Christian Medical College in India, and Makerere University in Uganda. RESULTS: One hundred sixty surveys were returned with 155 completed attitude responses. The response rate was 68.4% (65 of 95) for McMaster University, 39.7% (23 of 58) for the Christian Medical College, and 78.3% (72 of 92) for Makerere University. Analysis showed that six of eight attitude items were slightly statistically different among the schools with minimal effect of curriculum time and patient exposure. CONCLUSIONS: Despite quite varied exposure to tuberculosis, students from endemic and nonendemic areas responded similarly on statements addressing attitudes toward tuberculosis.

Principles for the justification of public health intervention.

OBJECTIVES: The objective of this paper is to discuss principles relevant to ethical deliberation in public health. METHODS: Conceptual analysis and literature review. RESULTS: Four principles are identified: The Harm Principle, The Principle of Least Restrictive Means, The Reciprocity Principle, and The Transparency Principle. Two examples of how the principles are applied in practice are provided. INTERPRETATION: The paper illustrates how clinical ethics is not an appropriate model for public health ethics and argues that the type of reasoning involved in public health ethics may be at potential variance from that of empirical science. Further research and debate on the appropriate ethics for public health are required.

The virtues of evidence.

Evidence-based medicine has been defined as the conscientious and judicious use of current best evidence in making clinical decisions. This paper will attempt to explicate the terms "conscientious" and "judicious" within the evidence-based medicine definition. It will be argued that "conscientious" and "judicious" represent virtue terms derived from virtue ethics and virtue epistemology. The identification of explicit virtue components in the definition and therefore conception of evidence-based medicine presents an important starting point in the connection between virtue theories and medicine itself. In addition, a unification of virtue theories and evidence-based medicine will illustrate the need for future research in order to combine the fields of virtue-based approaches and clinical practice.