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Background Correct staging and risk stratification is essential in ensuring prostate cancer patients are offered the most appropriate treatment. Interest has been growing in the use of radiotracers targeting prostate specific membrane antigen (PSMA), including the use of 18F-PSMA PET-CT, as part of the primary staging or restaging of prostate cancer. Preliminary scoping identified a number of relevant systematic reviews and meta-analyses; however, individually, these each appear to look at only part of the picture. An overview of reviews aims to systematically identify, appraise and synthesise multiple systematic reviews, related to a relevant research question or questions. We present a protocol for an overview of reviews, which aims to collate existing evidence syntheses exploring the diagnostic accuracy of 18F-PSMA in staging and restaging of prostate cancer. It also aims to highlight evidence gaps in prostate cancer staging or restaging. Methods This protocol is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for systematic review protocols (PRISMA-P). The search strategy will be designed in consultation with a librarian. Searches will be performed in Medline (EBSCO), Embase (Ovid), Google Scholar and the Cochrane Database for Systematic Reviews, supplemented by a targeted grey literature search, forward citation searching and searching reference lists of included reviews. No language or date restrictions will be applied to the eligibility criteria or the search strategy. Title & abstract and full text screening will be performed independently by two reviewers. Data will be extracted by one reviewer and checked in full by a second reviewer. Quality appraisal will be performed using the Risk of Bias in Systematic Reviews (ROBIS) tool independently by two reviewers, and results will be narratively synthesised. Conclusions This overview of reviews may be of interest to healthcare professionals, academics and health policy decision-makers. Registration OSF (September 7, 2023).

Abstract Background Evidence indicates that trial participants often struggle to understand participant information leaflets (PILs) for clinical trials, including the concept of randomisation. We analysed the language used to describe randomisation in PILs and determine the most understandable and acceptable description through public and participant feedback. Methods We collected 280 PILs/informed consent forms and one video animation from clinical research facilities/clinical trial units in Ireland and the UK. We extracted text on how randomisation was described, plus trial characteristics. We conducted content analysis to group the randomisation phrases inductively. We then excluded phrases that appeared more than once or were very similar to others. The final list of randomisation phrases was then presented to an online panel of participants and the public. Panel members were asked to rate each phrase on a 5-point Likert scale in terms of their understanding of the phrase, confidence in their understanding and acceptability of the phrase. Results Two hundred and eighty PILs and the transcribed text from one video animation represented 229 ongoing or concluded trials. The pragmatic content analysis generated five inductive categories: (1) explanation of why randomisation is required in trials; (2) synonyms for randomisation; (3) comparative randomisation phrases; (4) elaborative phrases for randomisation (5) and phrases that describe the process of randomisation. We had 48 unique phrases, which were shared with 73 participants and members of the public. Phrases that were well understood were not necessarily acceptable. Participants understood, but disliked, comparative phrases that referenced gambling, e.g. toss of a coin, like a lottery, roll of a die. They also disliked phrases that attributed decision-making to computers or automated systems. Participants liked plain language descriptions of what randomisation is and those that did not use comparative phrases. Conclusions Potential trial participants are clear on their likes and dislikes when it comes to describing randomisation in PILs. We make five recommendations for practice.

The objective of this study was to determine the influence of grain- and grass-finishing systems on carcass characteristics of bison bulls and proximate and fatty acid compositions of bison steaks. Bison bulls grazed native pasture until approximately 25 mo of age, then were randomly assigned to grain-finishing (n=98) or grass-finishing (n=98) treatments. Bulls were slaughtered at approximately 30 mo of age. Hot carcass weight (HCW), ribeye area, backfat thickness, kidney fat percentage, marbling score, and instrumental color (L*,a*, and b*) of the ribeye and subcutaneous fat were recorded. Skeletal maturity, lean maturity, and fat color were subjectively scored. Strip loins were collected from a sub-sample of carcasses, fabricated into 2.5-cm steaks, and designated for proximate, cholesterol, or fatty acid analyses. Grain-finished bulls had greater (P

Background: Correct staging and risk stratification is essential in ensuring prostate cancer patients are offered the most appropriate treatment. Interest has been growing in the use of radiotracers targeting prostate specific membrane antigen (PSMA), including the use of 18F-PSMA PET-CT, as part of the primary staging or restaging of prostate cancer. Preliminary scoping identified a number of relevant systematic reviews and meta-analyses; however, individually, these each appear to look at only part of the picture. An overview of reviews aims to systematically identify, appraise and synthesise multiple systematic reviews, related to a relevant research question or questions. We present a protocol for an overview of reviews, which aims to collate existing evidence syntheses exploring the diagnostic accuracy of 18F-PSMA in staging and restaging of prostate cancer. It also aims to highlight evidence gaps in prostate cancer staging or restaging. Methods: This protocol is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for systematic review protocols (PRISMA-P). The search strategy will be designed in consultation with a librarian. Searches will be performed in Medline (EBSCO), Embase (Ovid), Google Scholar and the Cochrane Database for Systematic Reviews, supplemented by a targeted grey literature search, forward citation searching and searching reference lists of included reviews. No language or date restrictions will be applied to the eligibility criteria or the search strategy. Title & abstract and full text screening will be performed independently by two reviewers. Data will be extracted by one reviewer and checked in full by a second reviewer. Quality appraisal will be performed using the Risk of Bias in Systematic Reviews (ROBIS) tool independently by two reviewers, and results will be narratively synthesised. Conclusions: This overview of reviews may be of interest to healthcare professionals, academics and health policy decision-makers. Registration: OSF (September 7, 2023).

Abstract Background The sources of information on clinical trial monitoring do not give information in an accessible language and do not give detailed guidance. In order to enable communication and to build clinical trial monitoring tools on a strong easily communicated foundation, we identified the need to define monitoring in accessible language. Methods In a three-step process, the material from sources that describe clinical trial monitoring were synthesised into principles of monitoring. A poll regarding their applicability was run at a UK national academic clinical trials monitoring meeting. Results The process derived 5 key principles of monitoring: keeping participants safe and respecting their rights, having data we can trust, making sure the trial is being run as it was meant to be, improving the way the trial is run and preventing problems before they happen. Conclusion From the many sources mentioning monitoring of clinical trials, the purpose of monitoring can be summarised simply as 5 principles. These principles, given in accessible language, should form a firm basis for discussion of monitoring of clinical trials.

Abstract Background The coronavirus 2019 pandemic placed unprecedented pressures on healthcare services and magnified ethical dilemmas related to how resources should be allocated. These resources include, among others, personal protective equipment, personnel, life-saving equipment, and vaccines. Decision-makers have therefore sought ethical decision-making tools so that resources are distributed both swiftly and equitably. To support the development of such a decision-making tool, a systematic review of the literature on relevant ethical values and principles was undertaken. The aim of this review was to identify ethical values and principles in the literature which relate to the equitable allocation of resources in response to an acute public health threat, such as a pandemic. Methods A rapid systematic review was conducted using MEDLINE, EMBASE, Google Scholar, LitCOVID and relevant reference lists. The time period of the search was January 2000 to 6th April 2020, and the search was restricted to human studies. January 2000 was selected as a start date as the aim was to capture ethical values and principles within acute public health threat situations. No restrictions were made with regard to language. Ethical values and principles were extracted and examined thematically. Results A total of 1,618 articles were identified. After screening and application of eligibility criteria, 169 papers were included in the thematic synthesis. The most commonly mentioned ethical values and principles were: Equity, reciprocity, transparency, justice, duty to care, liberty, utility, stewardship, trust and proportionality. In some cases, ethical principles were conflicting, for example, Protection of the Public from Harm and Liberty. Conclusions Allocation of resources in response to acute public health threats is challenging and must be simultaneously guided by many ethical principles and values. Ethical decision-making strategies and the prioritisation of different principles and values needs to be discussed with the public in order to prepare for future public health threats. An evidence-based tool to guide decision-makers in making difficult decisions is required. The equitable allocation of resources in response to an acute public health threat is challenging, and many ethical principles may be applied simultaneously. An evidence-based tool to support difficult decisions would be helpful to guide decision-makers.

Abstract Background It is the investigator’s responsibility to communicate the relevant information about a clinical trial to participants before they provide informed consent to take part. Systematic reviews indicate that participants often have a poor understanding of the concepts which are key to ensuring valid informed consent, such as randomisation and risks/discomforts. Paper-based participant information leaflets and informed consent forms (PIL/ICFs) are becoming longer and are often too complex for many participants. Multimedia interventions and enhanced PIL/ICFs have been trialled in an attempt to improve participants’ understanding of various aspects of research studies. However, there is insufficient empirical evidence to determine how effective such interventions are. This protocol describes a study to evaluate whether an enhanced PIL/ICF and website help research participants to understand important information about a human immunodeficiency virus (HIV) randomised clinical trial. Methods This Study Within A Trial (SWAT) is a prospective, multi-centre, randomised, controlled, parallel-group study embedded in a host clinical trial. The host trial (the SWIFT trial; EudraCT: 2019-002314-39) is a prospective, multi-centre, randomised, open-label, controlled trial investigating if semaglutide along with dietary advice assists individuals with HIV and obesity to lose weight, compared to dietary advice alone. For the SWAT, participants will be randomised in a 1:1 ratio to either the control (standard PIL/ICF) or the intervention (an enhanced PIL/ICF and a website which includes animations). The enhanced PIL/ICF and website were developed in line with the guidance from organisations which promote plain English and accessible public-facing materials in conjunction with HIV Ireland, a HIV advocacy organisation, and our previous work on consent documents. The primary outcome of the SWAT is the quality of informed consent, assessed by a validated comprehension test—the modified Deaconess Informed Consent Comprehension Test (DICCT). The DICCT will be administered within 48 h of consent to the host trial. The secondary is recall, measured by the modified DICCT questionnaire scores 2 weeks post-consent to the host trial. Discussion The results of this SWAT will add to the methodological evidence base on the use of multimedia to improve the quality of informed consent to randomised clinical trials. Trial registration ClinicalTrials.gov NCT04174755 . EudraCT 2019-002314-39. SWAT 160, Northern Ireland Hub for Trials Methodology Research SWAT repository (Clarke M, et al., Trials. 16:P209, 2015).

Abstract Background Patients with COVID-19 may feel under pressure to participate in research during the pandemic. Safeguards to protect research participants include ethical guidelines [e.g. Declaration of Helsinki and good clinical practice (GCP)], legislation to protect participants’ privacy, research ethics committees (RECs) and informed consent. The International Committee of Medical Journal Editors (ICMJE) advises researchers to document compliance with these safeguards. Adherence to publication guidelines has been suboptimal in other specialty fields. The aim of this rapid review was to determine whether COVID-19 human research publications report compliance with these ethical safeguards. Methods A rapid systematic literature review was conducted in MEDLINE using the search term ‘COVID-19’. The search was performed in April 2020 with no start date and repeated to include articles published in November 2020. Filters were ‘Full free text available’ and ‘English Language’. Two reviewers assessed article title, abstracts and full texts. Non-COVID-19 articles and non-clinical studies were excluded. Independent reviewers conducted a second assessment of a random 20% of articles. The outcomes included reporting of compliance with the Declaration of Helsinki and GCP, REC approval, informed consent and participant privacy. Results The searches yielded 1275 and 1942 articles of which 247 and 717 were deemed eligible, from the April search and November respectively. The majority of journals had editorial policies which purported to comply with ICMJE ethical standards. Reporting of compliance with ethical guidelines was low across all study types but was higher in the November search for case series and observational studies. Reporting of informed consent for case studies and observational studies was higher in the November search, but similar for case series. Overall, participant confidentiality was maintained but some case studies included a combination of details which would have enabled participant identification. Reporting of REC approval was higher in the November search for observational studies. Conclusions While the majority of journal’s editorial policies purported to support the ethical safeguards, many COVID-19 clinical research publications identified in this rapid review lacked documentation of these important safeguards for research participants. In order to promote public trust, ethical declarations should be included consistently.

Plain English summary Researchers must make sure that research participants are given all of the relevant information about a research study or trial. This information helps research people to decide if they wish to take part. The Participant Information Leaflet/Informed Consent Form is an important source of information for potential research participants and their families and friends. However, Participant Information Leaflets/Informed Consent Forms are often not easy for lay readers to understand. They can be especially difficult for readers with dyslexia or those who have problems with reading, or understanding numbers. There are guidelines available for designing information leaflets for lay readers, for example, leaflets about medicines or different health problems. But it would be helpful for researchers if these guidelines were applied to clinical research Participant Information Leaflets/Informed Consent Forms. We searched for and gathered guidance for designing and writing information leaflets for adult, lay readers and checked to see if the sources of the guidance were reliable. We then put together some recommendations for designing and writing information leaflets for research studies or trials. We formed an expert group, made up of both laypersons and researchers, who reviewed and discussed these recommendations. The expert group agreed on a final set of recommendations. We hope that these recommendations will help researchers to prepare Participant Information Leaflets/ Informed Consent Forms that are consistently easier to for participants to read and understand.

Background: Trials in health care are prospective human research studies designed to test the effectiveness and safety of health care interventions, such as medications, surgeries, medical devices and other treatment or prevention interventions. Statistics is an important and powerful tool in trials. Inappropriately designed trials and/or inappropriate statistical analysis produce unreliable results and a lack of transparency when reported, with limited clinical use. Aim: This systematic literature review aimed to identify, describe and synthesise factors contributing to or influencing the statistical planning, design, conduct, analysis and reporting of trials. Methods: Information sources were retrieved from the following electronic citation databases: PubMed, Web of Science, PsycINFO, and CINAHL and the grey literature repository: OpenGrey. 90 articles and guidelines were included in this review. A narrative, thematic synthesis identified the key factors influencing the statistical planning, design, conduct, analysis and reporting of trials in health care. Findings and conclusion: We identified three analytical themes within which factors are grouped. These are: “what makes a statistician?“, “the need for dynamic statistical involvement and collaboration throughout a trial – it's not just about the numbers”, “and the “accountability of statisticians in ensuring the safety of trial participants and the integrity of trial data”. While important insights emerged about the qualifications, training, roles, and responsibilities of statisticians and their collaboration with other team members in a trial, further empirical research is warranted to elicit the perceptions of trial team members at the centre of statistics in trials.

Biobanks are repositories of human biological samples and data. They are an important component of clinical research in many disease areas and often represent the first step toward innovative treatments. For biobanks to operate, researchers need human participants to give their samples and associated health data. In Ireland, research participants must provide their freely given informed consent for their samples and data to be taken and used for research purposes. Biobank staff are responsible for communicating the relevant information to participants prior to obtaining their consent, and this communication process is supported by the Participant Information Leaflets and Informed Consent Form (PI/ICFs). PILs/ICFs should be concise, intelligible, and contain relevant information. While not a substitute for layperson and research staff discussions, PILs and ICFs ensure that a layperson has enough information to make an informed choice to participate or not. However, PILs/ICFs are often lengthy, contain technical language and can be complicated and onerous for a layperson to read. The introduction of the General Data Protection Regulation and the related Irish Health Research Regulation presented additional challenges to the Irish biobank community. In May 2019, the National Biobanking Working Group (NBWG) was established in Ireland. It consists of members from diverse research backgrounds located in universities, hospitals and research centres across Ireland and a public/patient partner. The NBWG aimed to develop a suite of resources for health research biobanks via robust and meaningful patient engagement, which are accessible, General Data Protection Regulation/Health Research Regulation-compliant and could be used nationally, including a PIL/ICF template. This open letter describes the process whereby this national biobank PIL/ICF template was produced. The development of this template included review by the Patient Voice in Cancer Research, led by Professor Amanda McCann at University College Dublin and the Health Research Data Protection Network.

Objectives The first aim of this study was to quantify the difficulty level of clinical research Patient Information Leaflets/Informed Consent Forms (PILs/ICFs) using validated and widely used readability criteria which provide a broad assessment of written communication. The second aim was to compare these findings with best practice guidelines.Design Retrospective, quantitative analysis of clinical research PILs/ICFs provided by academic institutions, pharmaceutical companies and investigators.Setting PILs/ICFs which had received Research Ethics Committee approval in the last 5 years were collected from Ireland and the UK.Intervention Not applicable.Main outcome measures PILs/ICFs were evaluated against seven validated readability criteria (Flesch Reading Ease, Flesh Kincaid Grade Level, Simplified Measure of Gobbledegook, Gunning Fog, Fry, Raygor and New Dale Chall). The documents were also scored according to two health literacy-based criteria: the Clear Communication Index (CCI) and the Suitability Assessment of Materials tool. Finally, the documents were assessed for compliance with six best practice metrics from literacy agencies.Results A total of 176 PILs were collected, of which 154 were evaluable. None of the PILs/ICFs had the mean reading age of 90. Only two documents complied with all six best practice literacy metrics.Conclusions When assessed against both traditional readability criteria and health literacy-based tools, the PILs/ICFs in this study are inappropriately complex. There is also evidence of poor compliance with guidelines produced by literacy agencies. These data clearly evidence the need for improved documentation to underpin the consent process.

Informed consent can be defined as a freely-given decision or agreement following disclosure of relevant information. This review explores how legislation surrounding informed consent has impacted upon clinical research practices, with a focus on clinical trials involving individuals with the capacity to give consent in the non-emergency setting. We also highlight the challenges which remain with the informed consent process, including those which exist in the era of data protection legislation and genetic research.Modern ethicists agree that informed consent encompasses three principal factors: disclosure of information, capacity for decision making, and voluntariness. In the context of clinical research, informed consent is now required by regulatory and ethical frameworks as well as by law, and various guidelines govern the practice of informed consent, including the Declaration of Helsinki and the Good Clinical Practice Guidelines. Historically, however, researchers acted paternalistically and included participants in research without their knowledge or consent. Following societal and political revolution, an autonomy model of consent became prevalent, and individuals became free to make individual choices about whether to participate. Despite this, it is also recognized that an individual's community has a role in supporting their decision making, and this may be a strong influence, particularly within some societies. Research scandals and controversies and whistle-blowers which exposed unethical practices in the area of informed consent also contributed to changes in societal attitudes and legislation changed as a result. Medical journals also have an established, although indirect, role in strengthening good practices surrounding informed consent.

Trials can be defined as prospective human research studies to test the effectiveness and safety of interventions, such as medications, surgeries, medical devices and other interventions for the management of patient care. Statistics is an important and powerful tool in trials. Inappropriately designed trials and/or inappropriate statistical analysis produce unreliable results, with limited clinical use. The aim of this systematic literature review is to identify, describe and synthesise factors contributing to or influencing the statistical planning, design, conduct, analysis and reporting of trials. This protocol will describe the methodological approach taken for the following: conducting a systematic and comprehensive search for relevant articles, applying eligibility criteria for the inclusion of such articles, extracting data and information, appraising the quality of the articles, and thematically synthesizing the data to illuminate the key factors influencing statistical aspects of trials.

COVID-19 is a respiratory disease caused by a coronavirus, designated SARS-CoV-2, which is responsible for a global pandemic in 2020. Public interest in this disease has led to the publication of thousands of articles in the medical literature in a very short timeframe. It is imperative that medical research into COVID-19 is conducted quickly and safely, and that due reference is given to the ethical considerations enshrined in the ICH GCP guidelines, according to the Declaration of Helsinki. In order to review the reporting of ethical considerations in these papers, we hereby propose a protocol for a systematic review of COVID-19 papers up to April 14 th 2020. The search criteria proposed for the review are based upon what would be a reasonable search conducted by a lay member of the public with access to PubMed.gov. Institutional Research Ethics Committees (RECs) face significant challenges in providing thorough and timely ethical review during the COVID-19 pandemic. It is proposed to publish the findings of this rapid review along with a summary of an institutional REC response to the challenges of reviewing and approving clinical research proposals in the time of a pandemic.

Clinical trials can be defined as prospective human research studies to test the effectiveness and safety of interventions, such as medications, surgeries, medical devices and other interventions for the management of patient care. Statistics is an important and powerful tool in clinical trials. Inappropriately designed trials and/or inappropriate statistical analysis produce unreliable results, with limited clinical use. The aim of this systematic literature review is to identify, describe and synthesise factors contributing to or influencing the statistical planning, design, conduct, analysis and reporting of clinical trials. This protocol will describe the methodological approach taken for the following: conducting a systematic and comprehensive search for relevant articles, applying eligibility criteria for the inclusion of such articles, extracting data and information, appraising the quality of the articles, and thematically synthesizing the data to illuminate the key factors influencing statistical aspects of clinical trials.

Abstract Background Our aim was to assess the heterogeneity of high-risk (HR) prostate cancer managed with high-dose external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT). Methods We identified 547 patients who were treated with modern EBRT from 1997 to 2013, of whom 98% received ADT. We analyzed biochemical relapse-free survival (bRFS) and distant metastases-free survival (DMFS). Results Median EBRT dose was 74 Gy, and median ADT duration was 8 months. At 5 years, the DMFS was 85%. On multivariate analysis, significant predictors of shorter bRFS were biopsy Gleason score (bGS) of 8 to 10, higher prostate-specific antigen (PSA) level, shorter duration of ADT and lower radiation dose while predictors of shorter DMFS were bGS of 8 to 10, higher PSA level, and lower radiation dose. We identified an unfavorable high-risk (UHR) group of with 2–3 HR factors based on 2015 National Comprehensive Cancer Network (NCCN) criteria and a favorable high-risk (FHR) group, with 1 HR feature. Comparing very-HR prostate cancer, UHR & FHR, 5 year bRFS rates were 58.2%, 66.2%, and 69.2%, and 5 year DMFS rates were 78.4%, 81.2%, and 88.0%. Conclusion Patients with multiple HR factors have worse outcome than patients with 1 HR factor. Future studies should account for this heterogeneity in HR prostate cancer.