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Objective: The concept of self-efficacy is a determining factor in many behaviours related to health promotion and health education. Several pilot studies have been conducted in different parts of the world on different populations regarding the impact of training based on the Pender Health Promotion Model on self-efficacy, yielding conflicting results. Therefore, the present systematic review and meta-analysis were conducted with the aim of evaluating and summarizing the results of studies on the impact of training based on the Pender Health Promotion Model on self-efficacy. Data Source: MagIran, SID, PubMed, Embase, Web of Science (WoS), Scopus and Google Scholar. Study Inclusion and Exclusion Criteria: Original scientific research articles; Interventional studies; Studies investigating the effects of education based on the Pender Health Promotion Model on self-efficacy; Studies irrelevant to the objective; Cross-sectional studies; case reports; and papers presented in conferences; letters to the editor; systematic and meta-analysis studies. Data Extraction: Two independent reviewers extracted data and assessed the quality of the 18 included studies using a pre-prepared checklist for the systematic review and meta-analysis process. Data Synthesis: We conducted meta-analyses and reported the characteristics, outcomes, and risk of bias of studies. Methods: The present study was conducted according to PRISMA guidelines until December 2022. The quality assessment of the included articles for meta-analysis was performed using the JBI checklist. Heterogeneity of the studies was calculated using the I 2 statistics, and Egger's regression intercept was used to assess publication bias. Results: In the initial search, 13,943 studies were found, and after excluding studies irrelevant to the research objective, a total of 18 articles were included in the meta-analysis. These articles represented a sample size of 1015 individuals in the intervention group and 999 individuals in the control group. The combined results of the studies showed a significant increase in self-efficacy in the intervention group when compared to the control group (1.788 ±.267; CI: 95%, P <.001). With an increase in the year of study and the quality assessment score of the articles, the effect of the intervention decreased (P <.001). Conclusion: The results of this study indicated that training based on the Pender Health Promotion Model significantly increased self-efficacy. Therefore, it seems that training based on this model can have positive effects on individuals' self-efficacy. [ABSTRACT FROM AUTHOR]

Influence from bias is unavoidable in clinical decision-making, and mental health assessment seems particularly vulnerable. Individuals with intellectual disabilities have increased risk of developing co-occurring mental disorder. Due to the inherent difficulties associated with intellectual disabilities, assessment of mental health in this population often relies on a different set of strategies, and it is unclear how these may affect risk of bias. In this theoretical paper, we apply recent conceptualisations of bias in clinical decision-making to the specific challenges and strategies in mental health assessment in intellectual disabilities. We suggest that clinical decision-making in these assessments is particularly vulnerable to bias, including sources of bias present in mental health assessment in the general population, as well as potential sources of bias which may be specific to assessments in this population. It follows that to manage potential bias, triangulating information from multi-informant, multi-method, interdisciplinary assessment strategies is likely to be necessary. [ABSTRACT FROM AUTHOR]

The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main psychoactive alkaloids (dimethyltryptamine [DMT], harmine, harmaline, and tetrahydroharmine), including discussing clinical considerations (within clinical trials or approved settings). A systematic literature search of preclinical, clinical, epidemiological, and pharmacovigilance data (as well as pertinent reviews and case studies) was conducted for articles using the electronic databases of PubMed and Web of Science (to 6 July 2023) and PsycINFO, ClinicalTrials.gov, and Embase (to 21 September 2022) and included articles in English in peer-reviewed journals. Additionally, reference lists were searched. Due to the breadth of the area covered, we presented the relevant data in a thematic format. Our searches revealed 78 relevant articles. Data showed that ayahuasca or DMT is generally safe; however, some adverse human events have been reported. Animal models using higher doses of ayahuasca have shown abortifacient and teratogenic effects. Isolated harmala alkaloid studies have also revealed evidence of potential toxicity at higher doses, which may increase with co-administration with certain medications. Harmaline revealed the most issues in preclinical models. Nevertheless, animal models involving higher-dose synthetic isolates may not necessarily be able to be extrapolated to human use of therapeutic doses of plant-based extracts. Serious adverse effects are rarely reported within healthy populations, indicating an acceptable safety profile for the traditional use of ayahuasca and DMT in controlled settings. Further randomized, controlled trials with judicious blinding, larger samples, and longer duration are needed. [ABSTRACT FROM AUTHOR]

One of the primary objectives of a dose-finding trial for novel anti-cancer agent combination therapies, such as molecular targeted agents and immune-oncology therapies, is to identify optimal dose combinations that are tolerable and therapeutically beneficial for subjects in subsequent clinical trials. The goal differs from that of a dose-finding trial for traditional cytotoxic agents, in which the goal is to determine the maximum tolerated dose combinations. This paper proposes the new design, named 'BOIN-ETC' design, to identify optimal dose combinations based on both efficacy and toxicity outcomes using the waterfall approach. The BOIN-ETC design is model-assisted, so it is expected to be robust, and straightforward to implement in actual oncology dose-finding trials. These characteristics are quite valuable from a practical perspective. Simulation studies show that the BOIN-ETC design has advantages compared with the other approaches in the percentage of correct optimal dose combination selection and the average number of patients allocated to the optimal dose combinations across various realistic settings. [ABSTRACT FROM AUTHOR]

Recently, pharmaceutical companies have been striving to occupy a greater percentage of the global market with clinical research actively being conducted through mutual collaboration networks. In particular, the international Botulinum toxin (BT) market is characterized by intensifying competition. The majority of BT research has been conducted in the United States and Europe, whilst various countries have started their regional research through international collaboration networks. With this trend, this study aimed to examine the current collaboration trend and network of clinical trial research in the field of BT by employing both bibliometric and collaboration network analyses with one of the global academic and research databases. Based on the collaboration network, which is organized by 8,296 articles and 10,298 institutes, four centrality measures successfully present several international and regional clinical BT research leading institutes. Moreover, there are some hidden active institutes in this area, which are not highlighted in this paper's bibliometric analysis. This study contributes to improving the understanding of clinical trials in BTresearch, a relevant medical topic. Moreover, collaboration network analysis is one of the most valuable approaches of examining the international and regional clinical research. [ABSTRACT FROM AUTHOR]

Program theory reconstruction is an often-overlooked aspect of social intervention research. In this paper, we argue that intervention research benefits if the research design is informed by the specific intervention's program theory (i.e., the idea of how the intervention is supposed to lead to the intended outcomes). The purpose of this paper is to offer a comprehensive and accessible guide to program theory reconstruction in research on social interventions and to provide arguments as to how program theory reconstruction can be used to benefit intervention studies. First, we summarize what program theory is and its role in intervention research. Second, we provide a direct "how-to" for researchers, practitioners, and students who may be unfamiliar with the methods of program theory reconstruction but are interested in undertaking a program theory reconstruction. Finally, we conclude with how program theory reconstruction can benefit intervention research. [ABSTRACT FROM AUTHOR]

Background: Despite the enormous success of anterior cruciate ligament (ACL) reconstruction, acute neuropathic pain can develop postoperatively and is both distressing and difficult to treat once established. Pregabalin, an anticonvulsant agent that selectively affects the nociceptive process, has been used as a pain relief agent. The purpose of this systematic review of randomized controlled trials (RCTs) was to evaluate the pain control effect of pregabalin versus placebo after ACL reconstruction. Method: A search of the literature was performed from inception to June 2022, using PubMed, Scopus, Google Scholar, Web of Science, Cochrane and EBSCO. Studies considered for inclusion were RCTs that reported relevant outcomes (postoperative pain scores, cumulative opioid consumption, adverse events) following administration of pregabalin in patients undergoing ACL reconstruction. Result: Five placebo-controlled RCTs involving 272 participants met the inclusion criteria. 75 mg and 150 mg oral pregabalin was used in included trials. Two studies used a single dose of pregabalin one hour before anesthesia induction. Two studies used pregabalin 1 hour before anesthesia induction and 12 hours after. One study used daily pregabalin 7 days before and 7 days after surgery. Out of five papers, three papers found significantly lower pain intensity and cumulative opioid consumption in pregabalin group compared with placebo group. However, a decrease in pain scores was found in all trials. Pregabalin administration was associated with dizziness and nausea. Conclusion: The use of pregabalin may be a valuable asset in pain management after ACL reconstruction. However, future studies with larger sample size and longer follow-up period are required. [ABSTRACT FROM AUTHOR]

The article discusses the 21st anniversary of the Anaesthesia and Intensive Care Jeanette Thirlwell Best Paper Award. It mentions that inaugural Anaesthesia and Intensive Care Junior Investigator Award for 2017 has been awarded to Leigh White of the School of Medicine, University of Wollongong. It also reveals that editorial board of the journal appoints a selection committee of three of its members to adjudicate on the best paper.

Reducing the prevalence of acute kidney injury (AKI) is an important patient safety objective set forth by the National Quality Forum. Despite international guidelines to prevent AKI, there continues to be an inconsistent uptake of these interventions by cardiac teams across practice settings. The IMPROVE-AKI study was designed to test the effectiveness and implementation of AKI preventive strategies delivered through team-based coaching activities. Qualitative methods were used to identify factors that shaped sites' implementation of AKI prevention strategies. Semi-structured interviews were conducted with staff in a range of roles within the cardiac catheterization laboratories, including nurses, laboratory managers, and interventional cardiologists (N = 50) at multiple time points over the course of the study. Interview transcripts were qualitatively coded, and aggregated code reports were reviewed to construct main themes through memoing. In this paper, we report insights from semi-structured interviews regarding workflow, organizational culture, and leadership factors that impacted implementation of AKI prevention strategies. [ABSTRACT FROM AUTHOR]

The principle of clinical equipoise has been variously characterized by ethicists and clinicians as fundamentally flawed, a myth, and even a moral balm. Yet, the principle continues to be treated as the de facto gold standard for conducting randomized control trials in an ethical manner. Why do we hold on to clinical equipoise, despite its shortcomings being widely known and well-advertised? This paper reviews the most important arguments criticizing clinical equipoise as well as what the most prominent proposed alternatives are. In the process, it evaluates the justification for continuing to use clinical equipoise as the gold standard for randomized control trials. [ABSTRACT FROM AUTHOR]

Problem: As community-engaged research (CER) methods evolve, Institutional Review Boards (IRBs) must adapt policies to facilitate CER research. This paper describes a novel collaboration between hospital-based therapy dog volunteer teams (CERs), academic faculty, and an IRB. Subjects: CER volunteers delivered a canine-assisted intervention to hospitalized adults in a clinical trial. Methods: IRB members and faculty developed a human subjects protections training tailored to the volunteer handlers' role as study interventionists including an interactive video- and discussion-based training with a knowledge assessment. Findings: Fourteen volunteer handlers were trained. The expedited IRB review period was similar to national average rates (18 days.) Volunteer handlers have conducted 107 research visits with little patient attrition. Conclusion: Tailored human subjects trainings facilitate research with interventions delivered by people who are not typically involved in research. Bespoke CER human subjects training requires collaboration between researchers and IRBs and flexibility in IRB policy regarding CER. [ABSTRACT FROM AUTHOR]

For people living with psychosis, cognitive impairment is common and can have significant impacts for functional recovery, impacting engagement with treatment and quality of life more broadly. There is now strong evidence for the effectiveness of cognition-focused treatments, such as cognitive remediation to improve clinical and functional outcomes for people with psychosis. However, engagement with treatment has been a long-standing issue in mental health care, including for people with psychosis, who often experience difficulties with motivation. While research on clinical effectiveness of cognition-focused treatment is growing, to date there has been little research focused on the implementation of such treatments and it is not clear how best to support uptake and engagement across diverse mental health settings. Implementation science is the study of methods and strategies to promote the adoption, application, and maintenance of evidence-based practices in routine care. To integrate cognition-focused treatments into routine practice, and improve engagement with treatment and the quality and effectiveness of care for people with psychosis, researchers need to embrace implementation science and research. This paper provides a succinct overview of the field of implementation science, current evidence for implementation of cognition-focused treatments for psychosis and practical guidance for using implementation science in clinical research. The future of psychosis research includes multidisciplinary teams of clinical researchers and implementation scientists, working together with providers and consumers to build the evidence that can improve the implementation of cognition-focused treatments. [ABSTRACT FROM AUTHOR]

Traditional methods based on the assumption that the treatment distribution is a pure shift of the control distribution may not always hold. The possibility that an individual from the treatment group may not respond to the treatment motivates the use of a mixture distribution for the treatment group. This paper considers two test procedures based on the Wilcoxon rank-sum statistic for a group sequential design to detect the one-sided mixture alternative. Error spending functions are used for the allocation of error rates at each stage. The two tests are evaluated individually in determination of critical values and arm sizes and asymptotic multivariate normality is shown to hold for both. Upon comparison, the tests are presented to be asymptotically equivalent. Both test statistics maintain the Type I error rate even if F is misspecified in the design alternative. A more general definition of the treatment effect is used with the mixture distribution. Method of moments estimators and constrained k -means estimators for the treatment effect are evaluated. [ABSTRACT FROM AUTHOR]

Background: Despite Government investment, disparity in access to clinical trials continue between metropolitan and regional & rural sectors (RRR) in Australia and around the world. To improve trial access closer to home for RRR communities and rare cancer patients even in metro settings, the Australasian Teletrial Model (ATM) was developed by Clinical Oncology Society of Australia and implemented in four states. Aim of this paper is to describe the steps and processes involved in the development and implementation of ATM guided by implementation science frameworks. Method: Two implementation science frameworks namely iPARIHS and Strategic Implementation Framework were chosen to guide the project. Details of steps and processes were extracted from COSA final report. Results: ATM met the criteria for worthy innovation. For the development and implementation of the ATM, stakeholders were at national, statewide and clinical levels. A co-design with end-users and inclusion of key stakeholders in steering committees and advisory groups made the implementation smoother. Clinician levers including advocacy were useful to overcome system barriers. During the project, more patients, and clinicians at RRR participated in trials, more primary sites collaborated with RRR sites and more RRR sites gained trial capabilities. Conclusion: Pilot project achieved its objectives including improved access to patients locally, creation of linkages between metro and RRR sites and enhanced capabilities of and access to RRR sites. Implementation science frameworks were useful for identifying the necessary steps and processes at the outset. Ownership by governments and creation of streamlined regulatory systems would enable broader adoption. [ABSTRACT FROM AUTHOR]

Comparative Poisson trials of an experimental treatment versus a control typically condition on the total number of events that occur across both arms (Design A). Inference is based on the binomial distribution. Recently, an approach termed Design C to compare K experimental treatments to the same control was introduced. Under Design C without curtailment, the trial continues until a prespecified number of events occur in the control arm, leading to inference based on the negative multinomial distribution. The question remains of how advantageous it is to conduct one Design C trial comparing K experimental treatment arms to the same control arm as opposed to conducting K separate Design A trials each comparing one experimental treatment arm to a different control arm. This paper, therefore, compares the expected number of subjects to enroll for the two designs under uncurtailed and curtailed settings. The designs are evaluated when the null hypothesis and various assumptions for the alternative hypothesis hold. We simulate a variety of combinations for the Type 1 error, power, and ratio of the incidence rate of events in the experimental treatment to control arms. Design C frequently offers significant savings in terms of sample size relative to Design A. [ABSTRACT FROM AUTHOR]

Background: Phase 3 clinical trials for disease-modifying therapies in relapsing-remitting multiple sclerosis (RRMS) have utilized a limited number of conventional designs with a high degree of success. However, these designs limit the types of questions that can be addressed, and the time and cost required. Moreover, trials involving people with progressive multiple sclerosis (MS) have been less successful. Objective: The objective of this paper is to discuss complex innovative trial designs, intermediate and composite outcomes and to improve the efficiency of trial design in MS and broaden questions that can be addressed, particularly as applied to progressive MS. Methods: We held an international workshop with experts in clinical trial design. Results: Recommendations include increasing the use of complex innovative designs, developing biomarkers to enrich progressive MS trial populations, prioritize intermediate outcomes for further development that target therapeutic mechanisms of action other than peripherally mediated inflammation, investigate acceptability to people with MS of data linkage for studying long-term outcomes of clinical trials, use Bayesian designs to potentially reduce sample sizes required for pediatric trials, and provide sustained funding for platform trials and registries that can support pragmatic trials. Conclusion: Novel trial designs and further development of intermediate outcomes may improve clinical trial efficiency in MS and address novel therapeutic questions. [ABSTRACT FROM AUTHOR]

Background: The classical psychedelics, psilocybin, peyote, ayahuasca/ N,N -dimethyltryptamine, and lysergic acid diethylamide are considered promising new treatments for psychiatric illnesses, such as depression, anxiety, addiction, and obsessive-compulsive disorders. However, their profound and characteristic subjective effects raise concern for distinctive biases in randomized clinical trials. Methods: We performed a systematic literature search to identify all clinical trials on classical psychedelics with patient populations to examine descriptive data and determine the risk of bias. Two independent reviewers searched three databases (PubMed, Embase, and APA PsycNet) and extracted information on study design, study population, use of active or inactive placebo, dropouts, evaluation of blinding of intervention, and reporting of expectancy and therapeutic alliance. Results: We included 10 papers reporting on 10 unique trials. The trials generally included populations that were predominantly white and highly educated. The trials had small samples and considerable dropout. Blinding was either unsuccessful or not reported regardless of type of placebo. Few trials published protocols, statistical analysis plans (SAPs), and outcomes relating to psychotherapy fidelity. All trials but one were rated as high risk of bias. Conclusion: Successful blinding of intervention is a significant challenge in this field. To better accommodate this, we suggest that future trials use a parallel-group design and utilize an active placebo on a psychedelic-naïve population. Future trials should publish trial protocol and SAPs, use clinician-rated outcomes accessed by a blinded rater, evaluate blinding of intervention, and consider measuring expectancy and therapeutic fidelity. [ABSTRACT FROM AUTHOR]

This study aims to investigate the knowledge and attitudes of participants and potential participants in clinical trials toward electronic informed consent. We conducted a survey-based cross-sectional study in Hunan Province, China in March 2021. A total of 547 respondents were included in this study. All questions in an 8-item survey section assessing participants' knowledge of electronic informed consent received correct answers from at least 70% of participants. In terms of attitude scores, most participants (86.3%) believed that electronic informed consent is more convenient than the paper-based version, and more than half (51.2%) believed that electronic informed consent could completely replace the paper-based version. Responses indicated that common concerns about electronic informed consent were its security and confidentiality, legal benefits, and implications for rights protection. [ABSTRACT FROM AUTHOR]

"Readiness cohorts" are an innovation in clinical trial design to tackle the scarcity of time and people in drug studies. This has emerged in response to the challenges of recruiting the "right" research participants at the "right time" in the context of precision medicine. In this paper, we consider how the achievement of "readiness" aligns temporalities, biologies, and market processes of pharmaceutical innovation: how the promise of "willing bodies" in research emerges in relation to intertwined economic and biological time imperatives. Drawing on long-term engagement with the field of Alzheimer's disease prevention and interviews with researchers from academia and the pharmaceutical industry, we describe the discursive construction and practical arrangement of readiness. This paper contributes to understandings of temporal specificity, or "timing," within prevention research and casts critical light on the way this specificity—the threshold for "trial readiness"—relates to an opaque and highly speculative drug development pipeline. Extending the study of biomedical potential, as that which holds promise but may not yet exist, we consider how absences operate in adaptive trials. By highlighting these absences ("ready for what?"), we outline an opportunity for socio-ethical research to intervene in the speculative gaps of drug development. [ABSTRACT FROM AUTHOR]

Factorial allow for the simultaneous evaluation of more than one treatment, by randomizing patients to their possible combinations, including control. However, the statistical power of one treatment can be influenced by the effectiveness of the other, a matter that has not been widely recognized. In this paper, we evaluate the relationship between the observed effectiveness of one treatment and the implied power for a second treatment in the same trial, under a range of conditions. We provide analytic and numerical solutions for a binary outcome, under the additive, multiplicative, and odds ratio scales for treatment interaction. We demonstrate how the minimum required sample size for a trial depends on the two treatment effects. Relevant factors include the event rate in the control group, sample size, treatment effect sizes, and Type-I error rate thresholds. We show that that power for one treatment decreases as a function of the observed effectiveness of the other treatment if there is no multiplicative interaction. A similar pattern is observed with the odds ratio scale at low control rates, but at high control rates, power may increase if the first treatment is moderately more effective than its planned value. When treatments do not interact additively, power may either increase or decrease, depending on the control event rate. We also determine where the maximum power occurs for the second treatment. We illustrate these ideas with data from two actual factorial trials. These results can benefit investigators in planning the analysis of factorial clinical trials, in particular, to alert them to the potential for losses in power when one observed treatment effect differs from its originally postulated value. Updating the power calculation and modifying the associated required sample size can then ensure sufficient power for both treatments. [ABSTRACT FROM AUTHOR]

There has been an increased interest in borrowing information from historical control data to improve the statistical power for hypothesis testing, therefore reducing the required sample sizes in clinical trials. To account for the heterogeneity between the historical and current trials, power priors are often considered to discount the information borrowed from the historical data. However, it can be challenging to choose a fixed power prior parameter in the application. The modified power prior approach, which defines a random power parameter with initial prior to control the amount of historical information borrowed, may not directly account for heterogeneity between the trials. In this paper, we propose a novel approach to pick a power prior based on some direct measures of distributional differences between historical control data and current control data under normal assumptions. Simulations are conducted to investigate the performance of the proposed approach compared with current approaches (e.g. commensurate prior, meta-analytic-predictive, and modified power prior). The results show that the proposed power prior improves the study power while controlling the type I error within a tolerable limit when the distribution of the historical control data is similar to that of the current control data. The method is developed for both superiority and non-inferiority trials and is illustrated with an example from vaccine clinical trials. [ABSTRACT FROM AUTHOR]

Randomised controlled trials (RCTs) play an important role in multiple sclerosis (MS) research, ensuring that new interventions are safe and efficacious before their introduction into clinical practice. Trials have been evolving to improve the robustness of their designs and the efficiency of their conduct. Advances in digital and mobile technologies in recent years have facilitated this process and the first RCTs with decentralised elements became possible. Decentralised clinical trials (DCTs) are conducted remotely, enabling participation of a more heterogeneous population who can participate in research activities from different locations and at their convenience. DCTs also rely on digital and mobile technologies which allows for more flexible and frequent assessments. While hospitals quickly adapted to e-health and telehealth assessments during the COVID-19 pandemic, the conduct of conventional RCTs was profoundly disrupted. In this paper, we review the existing evidence and gaps in knowledge in the design and conduct of DCTs in MS. [ABSTRACT FROM AUTHOR]

Many fields of medicine have benefitted from the formation of clinical trials networks, whereby researchers come together on a large scale to identify high-priority questions and implement coordinated clinical trials. Clinical trials networks in the field of mental health, however, have been rare and largely absent from the Australian context. Here, we present an overview of the newly formed Growing Minds Australia Clinical Trials Network, which represents the first comprehensive clinical trials network in child and youth mental health in Australia. The 60 principal members of the Growing Minds Australia Clinical Trials Network represent teams across 19 diverse areas related to specific forms of psychopathology (e.g. internalising, externalising, neurodevelopmental disorders, early psychosis, substance use), specific research methods and processes (e.g. health economics, eHealth, implementation science) and specialised areas of practice (e.g. school-based systems, parenting interventions, Indigenous mental health, refugee families). Core functions of the Growing Minds Australia Clinical Trials Network include collaborative trial protocol development; peer review, prioritisation and endorsement of proposed trials; training; development of clinical guidelines; and consumer representation. The research by the clinical trials network will encompass the populations typically accessing youth mental health services, while placing a key emphasis on the early periods of life, and the role of parents and caregivers as critical partners in the co-design of research and the delivery of intervention and prevention strategies. The structures and processes built into the network are designed to coordinate collaboration between diverse stakeholders and ensure that provisions for translation are integrated into research from the outset. In this paper, we examine the potential for a dedicated clinical trials network to initiate fundamental improvement in child and youth mental health systems, and discuss the unique and complex challenges associated with establishing such an initiative. [ABSTRACT FROM AUTHOR]

Finally I would like to move away from the important areas of stroke recovery and post-stroke psychological symptoms to hemodynamics, and highlight two papers addressing important common clinical dilemmas in acute stroke. In this months issue of the International Journal of Stroke (IJS), we have three important papers evaluating different ways to improve recovery after stroke, an area under-represented in the major stroke journals. [Extracted from the article]

The article offers the author's insights on the association between vitamin D supplementation and protection from multiple sclerosis (MS). He cites the study "Cardiovascular disease and vitamin D supplementation: Trial analysis, systematic review, and meta-analysis," by John A. Ford and colleagues which performed a randomized trial of vitamin D supplements. He also mentions other systematic analyses of studies which found no beneficial effect of vitamin D supplements on non-skeletal diseases.

This paper introduces the event-probability function, a measure of occurrence of an event of interest over time, defined as the instantaneous probability of an event at a given time point conditional on having survived until that point. Unlike the hazard function, the event-probability function is a proper probability. This paper describes properties and interpretation of the event-probability function, presents its connection with other popular functions, such as the hazard and survival functions, proposes practical flexible proportional-odds models for estimating conditional event-probabilities given covariates with possibly censored and truncated observations, discusses the theoretical and computational aspects of parameter estimation, and applies the proposed models for assessing mortality in patients with metastatic renal carcinoma from a randomized clinical trial. [ABSTRACT FROM AUTHOR]

Global clinical trials depend on a range of standards in order for research results to be comparable. As standardization is more than a mere technical exercise, tensions can arise when things are not uniform. This paper uses empirical data from interviews with principal investigators as well as Clinical Research Organization and pharmaceutical industry representatives working in India's clinical trial industry to critically examine the ways Indian researchers navigate quests for standardization. It turns the analytical lens to the often obfuscated work of standardization aiming to transcend the biological and cultural specificity of research participants and research sites. Drawing on the concept of local biologies, it illustrates that the universal body presumed by clinical trial methodology is, in fact, a specifically Euro-American one: Indian participants not only need to be made globally comparable but also aligned with the drugs' future consumers. Focusing on the tensions between biomedicine's postulation of bodily universality and trial participants' local biologies, this paper advances recent interventions problematizing the structural violence undergirding global clinical trials. It also contributes to the literature on local biologies in its discussion of how these are negotiated in Indian for-profit clinical trials. [ABSTRACT FROM AUTHOR]

When a clinical trial stops early for benefit, the maximum likelihood estimate (MLE) of the treatment effect may be subject to overestimation bias. Several authors have proposed adjusting for this bias using the conditional MLE, which is obtained by conditioning on early stopping. However, this approach has a fundamental problem in that the adjusted estimate may not be in the direction of benefit, even though the study has stopped early due to benefit. In this paper, we address this problem by embedding both the MLE and the conditional MLE within a broader class of penalised likelihood estimates, and choosing a member of the class that is a favourable compromise between the two. This penalised MLE, and its associated confidence interval, always lie in the direction of benefit when the study stops early for benefit. We study its properties using both simulations and analyses of the ENZAMET trial in metastatic prostate cancer. Conditional on stopping early for benefit, the method is found to have good unbiasedness and coverage properties, along with very favourable efficiency at earlier interim analyses. We recommend the penalised MLE as a supplementary analysis to a conventional primary analysis when a clinical trial stops early for benefit. [ABSTRACT FROM AUTHOR]

In sequential testing with binary data, sample size and time to detect a signal are the key performance measures to optimize. While the former should be optimized in Phase III clinical trials, minimizing the latter is of major importance in post-market drug and vaccine safety surveillance of adverse events. The precision of the relative risk estimator on termination of the analysis is a meaningful design criterion as well. This paper presents a linear programming framework to find the optimal alpha spending that minimizes expected time to signal, or expected sample size as needed. The solution enables (a) to bound the width of the confidence interval following the end of the analysis, (b) designs with outer signaling thresholds and inner non-signaling thresholds, and (c) sequential designs with variable Bernoulli probabilities. To illustrate, we use real data on the monitoring of adverse events following the H1N1 vaccination. The numerical results are obtained using the R Sequential package. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, the race to find an effective vaccine or treatment saw an ‘extraordinary number’ of clinical trials being conducted. While there were some key success stories, not all trials produced results that informed patient care. There was a significant amount of waste in clinical research during the pandemic which is said to have hampered an evidence-based response. Conducting trials which could have been predicted to fail to answer the research question (e.g. because they are not large enough to provide a definitive result) is not only a waste of resources but also a breach of research participants’ trust and a violation of research ethics.The issues seen in COVID-19 clinical trials are symptomatic of a wider trial design crisis where many trials do not provide informative results. This paper examines the roles of key stakeholders in delivering ethical and informative trials and whether guidance published by ‘The Good Clinical Trials Collaborative’ could be used to align key stakeholder groups and enable a joined-up approach to improve clinical trial design. [ABSTRACT FROM AUTHOR]

Rare tumor research presents many challenges. Large, randomized clinical trials are often impractical in this field and access to biospecimens may be problematic. These difficulties can best be addressed through multidisciplinary, national and international collaborative efforts among researchers, clinicians, governmental bodies, and patients. Numerous governmental and private organizations now exist to facilitate cooperation between researchers and institutions. Patient advocacy organizations now play an increasingly important role in partnering with traditional research groups to promote rare tumor research. Rare Tumors is now beginning an editorial series focusing on the problems of rare tumor research. We wish to invite all researchers and clinicians who are involved in rare tumor research and treatment to contribute their observations on the problems of working in this field, either as a letter to the editor, an editorial on a select issue, or as a review paper. [ABSTRACT FROM AUTHOR]

Recurrent event responses are frequently encountered during clinical trials of treatments for certain diseases, such as asthma. The recurrence rates of different treatments are often compared by applying the negative binomial model. In addition, a balanced treatment-allocation procedure that assigns the same number of patients to each treatment is often applied. Recently, a response-adaptive treatment-allocation procedure has been developed for trials with recurrent event data, and has been shown to be superior to balanced treatment allocation. However, this response-adaptive treatment allocation procedure is only applicable for the comparison of two treatments. In this paper, we derive response-adaptive treatment-allocation procedures for trials which comprise several treatments. As pairwise comparisons and multiple comparisons with a control are two common multiple-testing scenarios in trials with more than two treatments, corresponding treatment-allocation procedures for these scenarios are also investigated. The redesign of two clinical studies illustrates the clinical benefits that would be obtained from our proposed response-adaptive treatment-allocation procedures. [ABSTRACT FROM AUTHOR]

The objective of this paper was to examine the school-related experiences of youth during the COVID-19 pandemic. Participants represented both clinical and community youth aged 14 to 28 who were sampled as part of a larger study. Feedback from youth attending school during the pandemic was qualitatively examined and youth who planned to attend school prior to the pandemic and did (n = 246) and youth who planned to attend but did not (n = 28) were compared quantitatively. Youth appreciated the flexibility of online learning and some also reported experiencing a lack of support from their school and the need for instructor training on how to deliver virtual classes effectively. Future studies should examine what factors influence student engagement with virtual learning, what strategies could improve supports for student in their long-term career development, and the longitudinal experiences of youth who may have chosen not to go back to school due to the pandemic. This survey was conducted in Ontario, Canada. A more diverse sample collected outside of Ontario would improve generalizability. Qualitative data were based on survey responses and not interviews. Thus we were unable to discern the reasons youth decided to attend school, or not, during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Aims and Method: This paper aims to review the recent literature regarding factors influencing the frequency and number of sessions during a course of electroconvulsive therapy (ECT) for different psychiatric disorders. We systematically reviewed English-language papers of clinical trials of ECT published since the year 2000 in terms of frequency and number of sessions of ECT. Results: None of the 30 studies meeting our inclusion criteria were specifically designed to study frequency or number of sessions of ECT. A preliminary inference may be drawn regarding the number of sessions from the information available in these papers. For depression, patients receiving brief-pulse ECT needed fewer sessions than those receiving ultra-brief ECT when these were delivered at 8-times the threshold with unilateral electrode placement or at 2.5-times the threshold with bilateral placement. For schizophrenia, those receiving bifrontal ECT and ECT at 4-times the threshold-level stimulus needed fewer sessions than those receiving bitemporal ECT and 2-times the threshold-level stimulus, respectively. There were no clinical trials of the frequency of ECT sessions.Clinical Implications: A s there is a dearth of studies specifically examining frequency and number of ECT sessions, broad recommendations from professional bodies should continue to guide practice. [ABSTRACT FROM AUTHOR]

The present paper deals with the problem of designing randomized multiarm clinical trials for treatment comparisons in order to achieve a suitable trade-off among inferential precision and ethical concerns. Although the large majority of the literature is focused on the estimation of the treatment effects, in particular for the case of two treatments with binary outcomes, the present paper takes into account the inferential goal of maximizing the power of statistical tests to detect correct conclusions about the treatment effects for normally response trials. After discussing the allocation optimizing the power of the classical multivariate test of homogeneity, we suggest a multipurpose design methodology, based on constrained optimization, which maximizes the power of the test under a suitable ethical constraint reflecting the effectiveness of the treatments. The ensuing optimal allocation depends in general on the unknown model parameters but, contrary to the unconstrained optimal solution or to some targets proposed in the literature, it is a non-degenerate continuous function of the treatment contrasts, and therefore it can be approached by standard response-adaptive randomization procedures. The properties of this constrained optimal allocation are described both theoretically and through suitable examples, showing good performances both in terms of ethical gain and statistical efficiency, taking into account estimation precision as well. [ABSTRACT FROM AUTHOR]

Between December 2020 and March 2021, the US Food and Drug Administration and the European Medicines Agency issued Emergency Use Authorizations and Conditional Marketing Authorizations for the distribution of the first COVID-19 vaccines. Although these vaccines were thoroughly assessed before their approval, regulators required companies to continue ongoing placebo-controlled clinical trials in order to gather further reliable scientific information on their safety and efficacy, as well as to start new studies to evaluate additional candidates. The aim of this paper is to present and discuss the ethical issues raised by the tension between the need to continue these types of clinical trials and the obligations related to the protection of the rights and well-being of research participants. Specifically, we question whether—how, and to what extent—fundamental principles governing research involving human beings can be applied to the current pandemic situation. We argue that continuing ongoing placebo-controlled clinical trials can be considered ethically justifiable only if all participants are adequately informed of any developments that may affect their willingness to remain enrolled, including the current situation of resource scarcity and the prioritization criteria established for vaccination. However, we also argue that currently approved vaccines, which are considered safe and effective enough to be administered to millions of people as part of the vaccination campaign, necessarily represent the "best proven intervention" currently available and, therefore, should be used as comparators in future studies instead of placebo. [ABSTRACT FROM AUTHOR]

Introduction: This paper provides a report of social validity and its usefulness in understanding study effects. Social validity data were drawn from a larger single-case study designed to investigate the effectiveness of the Matrix Approach in the practice of early intervention visual impairment professionals. Methods: Qualitative measures were used to assess social validity. According to Wolf (1978), validation of a study should encompass the significance of goals, appropriateness of procedures, and importance of outcomes. Therefore, data sources were created to provide evidence of social validity in these areas including pre- and post-intervention interviews of parents and professionals. Results: Three themes emerged from the social validity data. These are organized under the topics introduced by Wolf (1978) and identified as measures of quality by Horner et al. (2005). The themes are (a) Goals: role of the parent as learner and the professional as expert before using the Matrix Approach, (b) Procedures: helpfulness of coaching and the structure of the Matrix Approach, and (c) Outcomes: personal and professional growth as a result of using the Matrix Approach. Discussion: Evaluation of social validity in single-case research is an important component in a study's design and in interpreting the study's outcomes. Wolf's framework proved valuable in promoting a robust evaluation of study effectiveness, especially when incorporated into the study design. Intentionally planning to measure social validity held the researchers accountable to the practical needs of the participants. In fact, there is value in gathering social validity data at various points in a study. Further, hearing the perspective of stakeholders can provide valuable insights as researchers seek to understand the complexities of change evident in the outcomes of a study. Implications for Practitioners: Collaborative planning is an essential component of early intervention. The Matrix Approach shows promise as a mechanism to foster such collaboration. [ABSTRACT FROM AUTHOR]

The amount of data collected from patients involved in clinical trials is continuously growing. All baseline patient characteristics are potential covariates that could be used to improve clinical trial analysis and power. However, the limited number of patients in phases I and II studies restricts the possible number of covariates included in the analyses. In this paper, we investigate the cost/benefit ratio of including covariates in the analysis of clinical trials with a continuous outcome. Within this context, we address the long-running question "What is the optimum number of covariates to include in a clinical trial?" To further improve the benefit/cost ratio of covariates, historical data can be leveraged to pre-specify the covariate weights, which can be viewed as the definition of a new composite covariate. Here we analyze the use of a composite covariate to improve the estimated treatment effect in small clinical trials. A composite covariate limits the loss of degrees of freedom and the risk of overfitting. [ABSTRACT FROM AUTHOR]

Many clinical trials incorporate stopping rules to terminate early if the clinical question under study can be answered with a high degree of confidence. While common in later-stage trials, these rules are rarely implemented in dose escalation studies, due in part to the relatively smaller sample size of these designs. However, even with a small sample size, this paper shows that easily implementable stopping rules can terminate dose-escalation early with minimal loss to the accuracy of maximum tolerated dose estimation. These stopping rules are developed when the goal is to identify one or two dose levels, as the maximum tolerated dose and co-maximum tolerated dose. In oncology, this latter goal is frequently considered when the study includes dose-expansion cohorts, which are used to further estimate and compare the safety and efficacy of one or two dose levels. As study protocols do not typically halt accrual between escalation and expansion, early termination is of clinical importance as it either allows for additional patients to be treated as part of the dose expansion cohort to obtain more precise estimates of the study endpoints or allows for an overall reduction in the total sample size. [ABSTRACT FROM AUTHOR]

The purpose of the present review was to compile and analyze all interventions aimed at improving the sleep–rest pattern of adult caregivers. A database search was performed in PubMed, Embase, Scopus, CINAHL and PsycINFO. Twenty-four papers published between 1998 and 2020 met the inclusion criteria. Informal caregivers can benefit from various types of sleep interventions, including (a) cognitive-behavioral sleep interventions (CBIs), (b) caregiver health interventions (CHIs), and (c) exercise programs. Other types of interventions such as acupressure, back massage, reflexology, music, and heart rate variability biofeedback sessions may have beneficial effects on the sleep of caregivers. Yet, studies on this topic are heterogeneous and often have considerable methodological shortcomings. Few clinical trials have explored sleep problems as a dyadic caregiver–patient relationship. It is necessary to conduct new clinical trials to determine the viability and level of evidence of the various strategies aimed at improving sleep of informal caregivers. [ABSTRACT FROM AUTHOR]

Background: Progressive forms of multiple sclerosis (MS) affect more than 1 million individuals globally. Recent approvals of ocrelizumab for primary progressive MS and siponimod for active secondary progressive MS have opened the therapeutic door, though results from early trials of neuroprotective agents have been mixed. The recent introduction of the term 'active' secondary progressive MS into the therapeutic lexicon has introduced potential confusion to disease description and thereby clinical management. Objective: This paper reviews recent progress, highlights continued knowledge and proposes, on behalf of the International Progressive MS Alliance, a global research strategy for progressive MS. Methods: Literature searches of PubMed between 2015 and May, 2021 were conducted using the search terms "progressive multiple sclerosis", "primary progressive multiple sclerosis", "secondary progressive MS". Proposed strategies were developed through a series of in-person and virtual meetings of the International Progressive MS Alliance Scientific Steering Committee. Results: Sustaining and accelerating progress will require greater understanding of underlying mechanisms, identification of potential therapeutic targets, biomarker discovery and validation, and conduct of clinical trials with improved trial design. Encouraging developments in symptomatic and rehabilitative interventions are starting to address ongoing challenges experienced by people with progressive MS. Conclusion: We need to manage these challenges and realise the opportunities in the context of a global research strategy, which will improve quality of life for people with progressive MS. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the safety profiles of two biosimilar medicines (rituximab and trastuzumab) in the treatment of cancer patients within a Portuguese oncology hospital. Methods: This hospital-based prospective observational study followed a cohort event monitoring approach focused on signalling suspected adverse drug reactions (ADRs). Patients undergoing treatment with rituximab biosimilar CT-P10 (Truxima®) or trastuzumab biosimilar CT-P6 (Herzuma®) were recruited over an 11-month and a 6-month period, respectively. Clinicians identified eligible patients and used paper-based forms to report all ADRs associated with biosimilar medicines. ADR case reports were assessed for seriousness, expectedness and causality in the Pharmacovigilance Unit of Coimbra. Results: Ninety-four patients received biosimilar medicines (rituximab, n = 35; trastuzumab, n = 59). Of those, 4 patients (11.4%) experienced 16 ADRs with rituximab and 1 patient (1.7%) experienced 5 ADRs with trastuzumab. All case reports contained serious and expected ADRs that were at least probably related with biosimilar medicines under study. Based on the MedDRA PT coding, the most reported ADR for rituximab CT-P10 was chest discomfort (n = 4; 19.1%), followed by odynophagia (n = 2; 9.5%). Trastuzumab CT-P6 was associated with back pain, headache, pain in extremity, tachypnoea and tremor (each, n = 1; 4.8%). Conclusion: The results of this study suggest that using biosimilar rituximab and biosimilar trastuzumab to treat cancer patients in the real-world clinical setting is associated with acceptable safety profiles. No new safety problems were identified. [ABSTRACT FROM AUTHOR]

As cases of coronavirus 2019 (COVID-19) keep rising, reported deaths are increasing. Public health measures have been implemented with mixed efficacy. As vaccines are becoming more widely available and accessible globally, treating critically ill COVID-19 patients remains an issue with only dexamethasone found to be therapeutically effective to date. However, trials studying the efficacy of IL-6 inhibitors, namely tocilizumab have been underway with promising results. This paper is a narrative review that aims to review the current evidence provided by randomized clinical trials (RCT) for the use of tocilizumab in COVID-19. Electronic database searches were carried out in Medline, PubMed, Embase, Google Scholar, and ongoing clinical trial registries with the period set from January 1, 2020 to February 20, 2021. Prepublication manuscripts were found using the pre-print repository medRxiv. Keywords included "COVID-19,""coronavirus,""SARS-CoV-2,""sepsis,""pneumonia,""cytokine storm,""cytokine release syndrome,""IL-6 inhibitors," and "tocilizumab," as exact phrases, and a combination of subject headings according to databases syntax. Only trials with a clear and well-defined methodology, at least 100 patients recruited, and which have had results published either after peer review or in pre-print were included. In hospitalized patients with severe COVID-19, who are hypoxic and have a CRP ≥ 75 mg/L, the current evidence favors the use of a combination of tocilizumab and corticosteroids to reduce mortality, among other clinical benefits. There is also overwhelming evidence of the good safety profile of tocilizumab with only few cases of neutropenia reported with a decrease in infection rates. Tocilizumab is currently thought to work through the inhibition of IL-6 receptors (IL-6R), preventing downstream activation of pro-inflammatory reactions and cytokine release syndrome. [ABSTRACT FROM AUTHOR]

Background: It is acknowledged that publishers now require all primary research papers to demonstrate that they have obtained ethical approval for their research. Objectives: To assess the rate of reporting of ethical approval in clinical trials in core nursing journals in mainland China. Research design: A retrospective observational study. Participants: All clinical trials published in all of the 12 core nursing periodicals from 2016 edition China Science and Technology Journal Citation Report (core version) between 2013 and 2016 were retrieved by hand to explicate rate of reporting ethical approval and informed consent. Ethical considerations: The study did not require approval from the research ethics committee as it did not involve human subjects or records. Results: In total, 40,278 papers were published in 12 nursing periodicals between 2013 and 2016. Out of these, 9488 (23.6%) focused on clinical trials. Informed consent obtained from patients or the legally authorized representative was reported in 51.8% of clinical trials. Notably, only 27.4% of clinical trials reported that they had obtained written consent. Furthermore, 25.9% of clinical trials described ethical approval; however, the rate of reporting informed consent and ethical approval in these 12 nursing journals in China during 4 years from 2013 to 2016 improved markedly, with 38.1%, 44.0%, 59.0% and 66.6%, respectively (p < 0.001), and 17.6%, 21.9%, 28.6% and 35.8%, respectively (p < 0.001). In addition, both reporting informed consent and reporting written informed consent had a positive significant correlation with the reporting ethical approval (p < 0.05 or < 0.01). Conclusion: Chinese scientific nursing journals have improved the rate of reporting informed consent and ethical approval in clinical trials during the last 4 years. However, it should be noted that nearly half of clinical trials still did not report either ethical approval or whether informed consent was obtained. Efforts from editors, researchers, sponsors and authors are needed to ensure the transparency of ethical scrutiny and adherence to ethical guidelines in publishing clinical trials in Chinese nursing journals. [ABSTRACT FROM AUTHOR]

The delayed outcome issue is common in early phase dose-finding clinical trials. This problem becomes more intractable in phase I/II clinical trials because both toxicity and efficacy responses are subject to the delayed outcome issue. The existing methods applying for the phase I trials cannot be used directly for the phase I/II trial due to a lack of capability to model the joint toxicity–efficacy distribution. In this paper, we propose a conditional weighted likelihood (CWL) method to circumvent this issue. The key idea of the CWL method is to decompose the joint probability into the product of marginal and conditional probabilities and then weight each probability based on each patient's actual follow-up time. The CWL method makes no parametric model assumption on either the dose–response curve or the toxicity–efficacy correlation and therefore can be applied to any existing phase I/II trial design. Numerical trial applications show that the proposed CWL method yields desirable operating characteristics. [ABSTRACT FROM AUTHOR]

In reliability theory, diagnostic accuracy, and clinical trials, the quantity P (X > Y) + 1 / 2 P (X = Y) , also known as the Probabilistic Index (PI), is a common treatment effect measure when comparing two groups of observations. The quantity P (X > Y) − P (Y > X) , a linear transformation of PI known as the net benefit, has also been advocated as an intuitively appealing treatment effect measure. Parametric estimation of PI has received a lot of attention in the past 40 years, with the formulation of the Uniformly Minimum-Variance Unbiased Estimator (UMVUE) for many distributions. However, the non-parametric Mann–Whitney estimator of the PI is also known to be UMVUE in some situations. To understand this seeming contradiction, in this paper a systematic comparison is performed between the non-parametric estimator for the PI and parametric UMVUE estimators in various settings. We show that the Mann–Whitney estimator is always an unbiased estimator of the PI with univariate, completely observed data, while the parametric UMVUE is not when the distribution is misspecified. Additionally, the Mann–Whitney estimator is the UMVUE when observations belong to an unrestricted family. When observations come from a more restrictive family of distributions, the loss in efficiency for the non-parametric estimator is limited in realistic clinical scenarios. In conclusion, the Mann–Whitney estimator is simple to use and is a reliable estimator for the PI and net benefit in realistic clinical scenarios. [ABSTRACT FROM AUTHOR]

Multi-arm multi-stage clinical trials in which more than two drugs are simultaneously investigated provide gains over separate single- or two-arm trials. In this paper we propose a generic Bayesian adaptive decision-theoretic design for multi-arm multi-stage clinical trials with K (K ≥ 2) arms. The basic idea is that after each stage a decision about continuation of the trial and accrual of patients for an additional stage is made on the basis of the expected reduction in loss. For this purpose, we define a loss function that incorporates the patient accrual costs as well as costs associated with an incorrect decision at the end of the trial. An attractive feature of our loss function is that its estimation is computationally undemanding, also when K > 2. We evaluate the frequentist operating characteristics for settings with a binary outcome and multiple experimental arms. We consider both the situation with and without a control arm. In a simulation study, we show that our design increases the probability of making a correct decision at the end of the trial as compared to nonadaptive designs and adaptive two-stage designs. [ABSTRACT FROM AUTHOR]

The Program for the Education and Enrichment of Relational Skills (PEERS®) was used to provide weekly social skills training to a group of 10 college students with intellectual and developmental disabilities (IDD) between ages 18 and 26 attending an inclusive residential postsecondary college program. Additionally, Circles curriculum was used to supplement the PEERS curriculum for teaching social relationship boundaries. An average of 12 sessions per semester of PEERS® training sessions were conducted over each academic year. The present study examines the impact of the program on social skills, friendship qualities, and conversational skills. Results showed increased social skill knowledge, friendship quality, and conversational skills from pretest to posttest intervention. In this paper, we discuss the training program, results, implications for practice, limitations, and future research needs. [ABSTRACT FROM AUTHOR]

This paper addresses psychological factors that might interfere with informed consent on the part of stable patients as potential early-phase clinical trial participants. Thirty-six semistructured interviews with patients who had either diabetes or gout were conducted. We investigated stable patients' attitudes towards participating in a fictitious first-in-human trial of a novel intervention. We focused on an in-depth analysis of those statements and explanations that indicated the existence of psychological factors impairing decision-making capacity. Three main themes emerged: insufficient comprehension of the inherent logic of clinical trials (actual comprehension), the recourse to trust over comprehension (prioritization of trust), and visceral factors that override deliberative process (visceral factors). Overall, our results indicate a limited psychological capacity on the part of stable patients to meet the requirements of informed consent as set by Declaration of Helsinki. A redesigned informed consent procedure should take account of these psychological realities. [ABSTRACT FROM AUTHOR]

Only two articles explicitly differentiated SAs from NSSIs, and one mentioned NSSI without going into any further details. All evaluated papers stated facts about suicide and/or SA, with an evident underlying assumption of a consensus on the nature and definition of such. The latter was done by searching for the term "self" in available texts - since mention of NSSI/deliberate self-harm (DSH)/self-harm/self-injury or self-injurious behavior would have this term contained within. [Extracted from the article]