Trial participants' self-reported understanding of randomisation phrases in participation information leaflets can be high, but acceptability of some descriptions is low, especially those linked to gambling and luck.

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.

Diagnostic Accuracy of 18F-Prostate Specific Membrane Antigen (PSMA) PET/CT Radiotracers in Staging and Restaging of Patients With High-Risk Prostate Cancer or Biochemical Recurrence: An Overview of Reviews.

The aim of this overview was to consolidate existing evidence syntheses and provide a comprehensive overview of the evidence for 18F-prostate specific membrane antigen (PSMA) PET/CT in the staging of high-risk prostate cancer and restaging after biochemical recurrence. An overview of reviews was performed and reported in line with the preferred reporting items for overview of reviews (PRIOR) statement and synthesis without meta-analysis (SWiM) reporting guidelines. A comprehensive database and grey literature search were conducted up to July 18, 2023. Systematic reviews were assessed using the risk of bias in systematic reviews (ROBIS) tool. The certainty of the evidence was assessed using grading of recommendations, assessment, development and evaluations (GRADE). 11 systematic reviews were identified; 10 were at high or unclear risk of bias. Evidence reported on a per-patient, per-lymph node, and per-lesion basis for sensitivity, specificity and overall accuracy was identified. There was a lack of data on dose, adverse events and evidence directly comparing 18F-PSMA PET/CT to other imaging modalities. Evidence with moderate to very low certainty indicated high sensitivity, specificity and accuracy of 18F-PSMA PET/CT in patients with high-risk prostate cancer and biochemical recurrence. There was considerably lower certainty evidence and greater variability in effect estimates for outcomes for the combined intermediate/high-risk cohort. While evidence gaps remain for some outcomes, and most systematic reviews were at high or unclear risk of bias, the current evidence base is broadly supportive of 18F-PSMA PET/CT imaging in the staging and restaging of patients with high-risk prostate cancer and biochemical recurrence.

Influence of Beef Hot Carcass Weight on Sensory Characteristics of Strip Loin, Eye of Round, and Denver Cut Steaks.

The objective of this research was to investigate the influence of beef hot carcass weight (HCW) on consumer sensory attributes. Beef carcasses (n = 116) were selected based on the USDA quality grade and HCW. Lightweight (LW; 296-341 kg), middleweight (MW; 386-432 kg), or heavyweight (HW; 466-524 kg) carcasses with USDA Choice (LC) or USDA Select (SEL) quality grades were used in this study. Carcasses were tracked through fabrication and the semitendinosus, chuck roll, and strip loin were collected and fabricated into eye of round, Denver cut, and strip loin steaks, respectively, for consumer sensory evaluation. USDA Select MW Denver cut steaks had increased overall liking and texture liking scores and were more tender and juicier than the SEL LW steaks (p ≤ 0.02). USDA Select MW strip loin steaks had increased overall and flavor liking scores and were more tender than the SEL LW steaks (p ≤ 0.02). USDA Choice MW eye of round steaks had increased overall, flavor, and texture liking scores and were juicier than the LW eye of round steaks (p ≤ 0.04). The steaks evaluated in this study were differentially impacted by HCW and little to no clear pattern of effects could be determined across cut or quality grade. Additional research is needed to determine the most acceptable HCW from a consumer perspective.

Prospective randomised phase II trial evaluating adjuvant pelvic radiotherapy using either IMRT or 3-Dimensional planning for endometrial cancer.

OBJECTIVE: To compare the incidence of grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity for patients undergoing 3DRT versus IMRT in the postoperative setting for endometrial cancer. METHODS: Eligible patients were post-operatively randomly assigned to one of two parallel groups in a 1:1 ratio, to have their RT delivered using either a 3DRT technique or using IMRT. The prescription dose was 45 Gy in 25 fractions over 5 weeks followed by vaginal vault brachytherapy. Toxicity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 3.0. Fisher's exact tests were used to test for associations between toxicity and arm. Differences in dosimetric parameters for patients with or without toxicity were tested using Mann-Whitney U-tests. RESULTS: 84 patients with a median age of 62 were evaluable for primary outcome. The median follow-up was 52 months. 14 (35%) participants from the 3DRT arm and 15 (34%) from the IMRT arm experienced acute grade ≥2 GI toxicity with older patients having a statistically higher risk of grade ≥2 acute GI toxicity. 20 (50%) participants from the 3DRT arm and 25 (57%) from the IMRT arm experienced acute grade ≥2 GI or GU toxicity (p = .662). 12 (30%) patients from the 3DRT arm and 17 (39%) from the IMRT arm experienced acute grade ≥2 GU toxicity (p = .493). CONCLUSION: Although IMRT can reduce dose to normal tissue, in this study no benefit in acute GI or GU toxicity outcome was seen.

Diagnostic accuracy of 18F Prostate Specific Membrane Antigen (PSMA) PET-CT radiotracers in staging and restaging of high-risk prostate cancer patients and patients with biochemical recurrence: protocol for an overview of reviews.

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).

What is the purpose of clinical trial monitoring?

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.

Ethical values and principles to guide the fair allocation of resources in response to a pandemic: a rapid systematic review.

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.

Factors influencing the statistical planning, design, conduct, analysis and reporting of trials in health care: A systematic review.

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.

An enhanced participant information leaflet and multimedia intervention to improve the quality of informed consent to a randomised clinical trial enrolling people living with HIV and obesity: a protocol for a Study Within A Trial (SWAT).

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).

An evaluation of the process of informed consent: views from research participants and staff.

BACKGROUND: The process of informed consent for enrolment to a clinical research study can be complex for both participants and research staff. Challenges include respecting the potential participant's autonomy and information needs while simultaneously providing adequate information to enable an informed decision. Qualitative research with small sample sizes has added to our understanding of these challenges. However, there is value in garnering the perspectives of research participants and staff across larger samples to explore the impact of contextual factors (time spent, the timing of the discussion and the setting), on the informed consent process. METHODS: Research staff and research participants from Ireland and the UK were invited to complete an anonymous survey by post or online (research participants) and online (research staff). The surveys aimed to quantify the perceptions of research participants and staff regarding some contextual factors about the process of informed consent. The survey, which contained 14 and 16 multiple choice questions for research participants and staff respectively, was analysed using descriptive statistics. Both surveys included one optional, open-ended question, which were analysed thematically. RESULTS: Research participants (169) and research staff (115) completed the survey. Research participants were predominantly positive about the informed consent process but highlighted the importance of having sufficient time and the value of providing follow-up once the study concludes, e.g. providing results to participants. Most staff (74.4%) staff reported that they felt very confident or confident facilitating informed consent discussions, but 63% felt information leaflets were too long and/or complicated, 56% were concerned about whether participants had understood complex information and 40% felt that time constraints were a barrier. A dominant theme from the open-ended responses to the staff survey was the importance of adequate time and resources. CONCLUSIONS: Research participants in this study were overwhelmingly positive about their experience of the informed consent process. However, research staff expressed concern about how much participants have understood and studies of patient comprehension of research study information would seem to confirm these fears. This study highlights the importance of allocating adequate time to informed consent discussions, and research staff could consider using Teach Back techniques. TRIAL REGISTRATION: Not applicable.

Adherence with reporting of ethical standards in COVID-19 human studies: a rapid review.

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.

Preparing accessible and understandable clinical research participant information leaflets and consent forms: a set of guidelines from an expert consensus conference.

BACKGROUND: In line with Good Clinical Practice and the Declaration of Helsinki, it is the investigator's responsibility to ensure that research participants are sufficiently informed, to enable the provision of informed consent. The Participant Information Leaflet/Informed Consent Form is key to facilitating this communication process. Although studies have indicated that clinical research Participant Information Leaflets/Informed Consent Forms are not optimal in terms of accessibility, there is little or no specific guidance available. The aim of this research was to propose and agree a set of guidelines for academic researchers and sponsors for preparing accessible and understandable Participant Information Leaflets/Informed Consent Forms. METHODS: A literature review identified guidance for the preparation of patient-facing documents. Following critical appraisal, key recommendations were extracted and a set of recommendations which can be applied to clinical research Participant Information Leaflets/Informed Consent Forms were prepared. These recommendations were evaluated and amended by an Expert Consensus Conference consisting of a group of key stakeholders. The stakeholders included members of a Research Ethics Committee (both lay and expert), a patient advocate, experienced clinical researchers, a plain English editor and a Data Protection Officer. Consensus was reached regarding a final set of recommendations. RESULTS: 44 recommendations were agreed upon and grouped into five categories: Layout, Formatting, Content, Language and Confirming Readability. These recommendations aimed to maximize accessibility for lay participants, including readers with dyslexia, literacy or numeracy challenges, thereby improving the quality of the consent process. CONCLUSIONS: More empirical research is needed to further improve the informed consent process for research participants. However, these recommendations are informed by the current literature and have been ratified by expert stakeholders. It is hoped that these recommendations will help investigators and sponsors to consistently and efficiently produce more accessible clinical research Participant Information Leaflets/Informed Consent Forms.

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.

Harmonising the human biobanking consent process: an Irish experience.

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 documentation in the form of Participant Information Leaflets and Informed Consent Forms (PILs/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 (GDPR) and the related Irish Health Research Regulation (HRR) 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, GDPR/HRR-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.

An investigation into the factors affecting investigator-initiated trial start-up in Ireland.

BACKGROUND: In common with many countries, Ireland has seen an increasing trend in the number of clinical trials conducted over the past few years. Yet, as elsewhere, trialists in Ireland face several problems and barriers in the starting-up of clinical trials. These barriers impede trial activity significantly, with consequent impacts on patient care. It is critical to understand these issues, to develop approaches to facilitate trial start up. This study identifies the challenges in conducting clinical trials in Ireland and specifically the contractual, ethical, logistical, and regulatory barriers that hinder the start-up of investigator-led trials in Ireland. METHODS: Data for this study were collected in two stages. In the first stage, a survey was conducted among trialists in Ireland. A total of 44 trialists responded to the survey, and information was collected about their experience in conducting clinical trials, the scale and nature of their most recently completed trial, and the details of specific barriers they encountered during the starting-up of the trial. In the second stage, nine semi-structured interviews were conducted with the awardees of 2018 Irish Health Research Board's Definitive Intervention Feasibility Award. These interviews facilitated a deeper exploration of issues and problems in conducting clinical trials in Ireland. RESULTS: This study identified several issues and bottlenecks in starting-up clinical trials in Ireland with contracts and ethical approval cited as the major issues. The data shows that site identification and activation was also problematic in some cases. Several respondents reported difficulties in accessing dedicated time for protocol development and believe that support in this area can be greatly beneficial. It was reported that availability of skilled staff members like statisticians and data managers was as an issue, especially for small trials. CONCLUSION: This study found that several factors impact trial initiation and progression in Ireland. Delays associated with obtaining contract and ethics approval are perceived as major barriers. Specialist supports in areas such as ethics and regulatory affairs and availability of specialised staff members in areas such as statistics and data management are key actions to enable enhanced clinical trial activity in Ireland.

Contributory factors to the evolution of the concept and practice of informed consent in clinical research: A narrative review.

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.

A protocol for a systematic review investigating the factors influencing the statistical planning, design, conduct, analysis and reporting of trials.

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.

Readability and understandability of clinical research patient information leaflets and consent forms in Ireland and the UK: a retrospective quantitative analysis.

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 <12 years recommended by the American Medical Association. 7.1% of PILs/ICFs were evaluated as 'Plain English', 40.3%: 'Fairly Difficult', 51.3%: 'Difficult' and 1.3%: 'Very Difficult'. No PILs/ICFs achieved a CCI >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.

Ethical Considerations for safeguarding human participants in pandemic research: a rapid review protocol.

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.

Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression.

BACKGROUND: The optimal EBRT schedule for MSCC is undetermined. Our aim was to determine whether a single fraction (SF) was non-inferior to five daily fractions (5Fx), for functional motor outcome. METHODS: Patients not proceeding with surgical decompression in this multicentre non-inferiority, Phase 3 trial were randomised to 10 Gy/SF or 20 Gy/5Fx. A change in mobility from baseline to 5 weeks for each patient, was evaluated by a Modified Tomita score: 1 = 'Walk unaided', 2 = 'With walking aid' and 3 = 'Bed-bound'. The margin used to establish non-inferiority was a detrimental change of -0.4 in the mean difference between arms. RESULTS: One-hundred and twelve eligible patients were enrolled. Seventy-three patients aged 30-87 were evaluated for the primary analysis. The 95% CI for the difference in the mean change in mobility scores between arms was -0.12 to 0.6. Since -0.4 is not included in the interval, there is evidence that 10 Gy/SF is non-inferior to 20 Gy/5Fx. One grade 3 AE was reported in the 5Fx arm. Twelve (26%) patients in the 5Fx arm had a Grade 2-3 AE compared with six (11%) patients in the SF arm (p = 0.093). CONCLUSION: For mobility preservation, one 10-Gy fraction is non-inferior to 20 Gy in five fractions, in patients with MSCC not proceeding with surgical decompression. CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland ICORG 05-03; NCT00968643; EU-20952.

A novel dynamic arc treatment planning solution to reduce dose to small bowel in preoperative radiotherapy for rectal cancer.

Preoperative radiotherapy or combined chemoradiotherapy for locally advanced rectal cancer (LARC) can cause acute and late gastrointestinal (GI) side-effects. There is thought to be a dose-volume relationship between small bowel irradiation and the development of these effects. A planning study was undertaken to compare small bowel sparing for a range of 3D conformal and dynamic arc planning solutions. A planning study was carried out for 20 LARC patients. Organs at risk (OAR) contoured included bowel loops and peritoneal space (PS). For each of the 20 patients, 5 plans were created: (1) standard 3D conformal plan; (2) standard dual dynamic arc plan; (3) dual dynamic arc plan with 90° avoidance sector through the anterior portion of the patient; (4) dual dynamic arc plan with an anterior avoidance structure in the optimizer; (5) dual dynamic arc plan with both an anterior avoidance structure and an avoidance sector. The prescription was 50.4 Gy in 28 fractions to the planning target volume (PTV). Five Dose Volume Levels (DVLs; V15 Gy, V20 Gy, V25 Gy, V35 Gy, V40 Gy, and V50.4 Gy) for bowel and PS were selected. The DVLs were compared between the plans using Friedman Tests and Wilcoxon Signed Rank Tests. Comparison of the 5 plans revealed that a dual dynamic arc plan containing both an anterior avoidance sector and structure significantly improved the dose to the bowel compared to a standard 3D conformal plan and to a standard dual dynamic arc plan. This improvement was achieved while maintaining PTV coverage. This novel dual dynamic arc planning technique that uses both an avoidance sector and structure reduces the dose to the bowel and PS, which may lead to a reduction in GI toxicity.