Can trial quality be reliably assessed from published reports of cancer trials: evaluation of risk of bias assessments in systematic reviews

To evaluate the reliability of risk of bias assessments based on published trial reports, for determining trial inclusion in meta-analyses

Uptake of systematic reviews and meta-analyses based on individual participant data in clinical practice guidelines: descriptive study.

To establish the extent to which systematic reviews and meta-analyses of individual participant data (IPD) are being used to inform the recommendations included in published clinical guidelines

Timely and reliable evaluation of the effects of interventions: a framework for adaptive meta-analysis (FAME)

Most systematic reviews are retrospective and use aggregate data AD) from publications, meaning they can be unreliable, lag behind therapeutic developments and fail to influence ongoing or new trials. Commonly, the potential influence of unpublished or ongoing trials is overlooked when interpreting results, or determining the value of updating the meta-analysis or need to collect individual participant data (IPD). Therefore, we developed a Framework for Adaptive Metaanalysis (FAME) to determine prospectively the earliest opportunity for reliable AD meta-analysis. We illustrate FAME using two systematic reviews in men with metastatic (M1) and non-metastatic (M0)hormone-sensitive prostate cancer (HSPC)

Use of strategies to improve retention in primary care randomised trials: a qualitative study with in-depth interviews.

Objective: To explore the strategies used to improve retention in primary care randomised trials. Design: Qualitative in-depth interviews and thematic analysis. Participants: 29 UK primary care chief and principal investigators, trial managers and research nurses. Methods: In-depth face-to-face interviews. Results: Primary care researchers use incentive and communication strategies to improve retention in trials, but were unsure of their effect. Small monetary incentives were used to increase response to postal questionnaires. Non-monetary incentives were used although there was scepticism about the impact of these on retention. Nurses routinely used telephone communication to encourage participants to return for trial follow-up. Trial managers used first class post, shorter questionnaires and improved questionnaire designs with the aim of improving questionnaire response. Interviewees thought an open trial design could lead to biased results and were negative about using behavioural strategies to improve retention. There was consensus among the interviewees that effective communication and rapport with participants, participant altruism, respect for participant’s time, flexibility of trial personnel and appointment schedules and trial information improve retention. Interviewees noted particular challenges with retention in mental health trials and those involving teenagers. Conclusions: The findings of this qualitative study have allowed us to reflect on research practice around retention and highlight a gap between such practice and current evidence. Interviewees describe acting from experience without evidence from the literature, which supports the use of small monetary incentives to improve the questionnaire response. No such evidence exists for non-monetary incentives or first class post, use of which may need reconsideration. An exploration of barriers and facilitators to retention in other research contexts may be justified

Adaptive platform trials using multi-arm, multi-stage protocols: getting fast answers in pandemic settings [version 2; peer review: 2 approved]

Global health pandemics, such as coronavirus disease 2019 (COVID19), require efficient and well-conducted trials to determine effective interventions, such as treatments and vaccinations. Early work focused on rapid sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), subsequent in-vitro and in-silico work, along with greater understanding of the different clinical phases of the infection, have helped identify a catalogue of potential therapeutic agents requiring assessment. In a pandemic, there is a need to quickly identify efficacious treatments, and reject those that are non-beneficial or even harmful, using randomised clinical trials. Whilst each potential treatment could be investigated across multiple, separate, competing two-arm trials, this is a very inefficient process. Despite the very large numbers of interventional trials for COVID-19, the vast majority have not used efficient trial designs. Well conducted, adaptive platform trials utilising a multi-arm multistage (MAMS) approach provide a solution to overcome limitations of traditional designs. The multi-arm element allows multiple different treatments to be investigated simultaneously against a shared, standard-of-care control arm. The multi-stage element uses interim analyses to assess accumulating data from the trial and ensure that only treatments showing promise continue to recruitment during the next stage of the trial. The ability to test many treatments at once and drop insufficiently active interventions significantly speeds up the rate at which answers can be achieved. This article provides an overview of the benefits of MAMS designs and successes of trials, which have used this approach to COVID-19. We also discuss international collaboration between trial teams, including prospective agreement to synthesise trial results, and identify the most effective interventions. We believe that international collaboration will help provide faster answers for patients, clinicians, and health care systems around the world, including for each further wave of COVID-19, and enable preparedness for future global health pandemics

Adaptive platform trials using multi-arm, multi-stage protocols: getting fast answers in pandemic settings [version 1; peer review: 2 approved]

Global health pandemics, such as coronavirus disease 2019 (COVID-19), require efficient and well-conducted trials to determine effective interventions, such as treatments and vaccinations. Early work focused on rapid sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), subsequent in-vitro and in-silico work, along with greater understanding of the different clinical phases of the infection, have helped identify a catalogue of potential therapeutic agents requiring assessment. In a pandemic, there is a need to quickly identify efficacious treatments, and reject those that are non-beneficial or even harmful, using randomised clinical trials. Whilst each potential treatment could be investigated across multiple, separate, competing two-arm trials, this is a very inefficient process. Despite the very large numbers of interventional trials for COVID-19, the vast majority have not used efficient trial designs. Well conducted, adaptive platform trials utilising a multi-arm multi-stage (MAMS) approach provide a solution to overcome limitations of traditional designs. The multi-arm element allows multiple different treatments to be investigated simultaneously against a shared, standard-of-care control arm. The multi-stage element uses interim analyses to assess accumulating data from the trial and ensure that only treatments showing promise continue to recruitment during the next stage of the trial. The ability to test many treatments at once and drop insufficiently active interventions significantly speeds up the rate at which answers can be achieved. This article provides an overview of the benefits of MAMS designs and successes of trials, which have used this approach to COVID-19. We also discuss international collaboration between trial teams, including prospective agreement to synthesise trial results, and identify the most effective interventions. We believe that international collaboration will help provide faster answers for patients, clinicians, and health care systems around the world, including for future waves of COVID-19, and enable preparedness for future global health pandemics

Effectiveness and acceptability of methods of communicating the results of clinical research to lay and professional audiences: protocol for a systematic review

BACKGROUND: Phase III randomised controlled trials aim not just to increase the sum of human knowledge, but also to improve treatment, care or prevention for future patients through changing policy and practice. To achieve this, the results need to be communicated effectively to several audiences. It is unclear how best to do this while not wasting scarce resources or causing avoidable distress or confusion. The aim of this systematic review is to examine the effectiveness, acceptability and resource implications of different methods of communication of clinical research results to lay or professional audiences, to inform practice. // METHODS: We will systematically review the published literature from 2000 to 2018 for reports of approaches for communicating clinical study results to lay audiences (patients, participants, carers and the wider public) or professional audiences (clinicians, policymakers, guideline developers, other medical professionals). We will search Embase, MEDLINE, PsycINFO, ASSIA, the Cochrane Database of Systematic Reviews and grey literature sources. One reviewer will screen titles and abstracts for potential eligibility, discarding only those that are clearly irrelevant. Potentially relevant full texts will then be assessed for inclusion by two reviewers. Data extraction will be carried out by one reviewer using EPPI-Reviewer. Risk of bias will be assessed using the relevant Cochrane Risk of Bias 2.0 tool, ROBINS-1, AXIS Appraisal Tool or Critical Appraisals Skills Programme Qualitative Checklist, depending on study design. We will decide whether to meta-analyse data based on whether the included trials are similar enough in terms of participants, settings, intervention, comparison and outcome measures to allow meaningful conclusions from a statistically pooled result. We will present the data in tables and narratively summarise the results. We will use thematic synthesis for qualitative studies. // DISCUSSION: Developing the search strategy for this review has been challenging as many of the concepts (patients, clinicians, clinical studies, and communication) are widely used in literature that is not relevant for inclusion in our review. We expect there will be limited comparative evidence, spread over a wide range of approaches, comparators and populations and, therefore, do not anticipate being able to carry out meta-analysis

Methods used to assess outcome consistency in clinical studies: A literature-based evaluation.

Evaluation studies of outcomes used in clinical research and their consistency are appearing more frequently in the literature, as a key part of the core outcome set (COS) development. Current guidance suggests such evaluation studies should use systematic review methodology as their default. We aimed to examine the methods used. We searched the Core Outcome Measures in Effectiveness Trials (COMET) database (up to May 2019) supplementing it with additional resources. We included evaluation studies of outcome consistency in clinical studies across health subjects and used a subset of A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 (items 1-9) to assess their methods. Of 93 included evaluation studies of outcome consistency (90 full reports, three summaries), 91% (85/93) reported performing literature searches in at least one bibliographic database, and 79% (73/93) was labelled as a "systematic review". The evaluations varied in terms of satisfying AMSTAR 2 criteria, such that 81/93 (87%) had implemented PICO in the research question, whereas only 5/93 (6%) had included the exclusions list. None of the evaluation studies explained how inconsistency of outcomes was detected, however, 80/90 (88%) concluded inconsistency in individual outcomes (66%, 55/90) or outcome domains (20%, 18/90). Methods used in evaluation studies of outcome consistency in clinical studies differed considerably. Despite frequent being labelled as a "systematic review", adoption of systematic review methodology is selective. While the impact on COS development is unknown, authors of these studies should refrain from labelling them as "systematic review" and focus on ensuring that the methods used to generate the different outcomes and outcome domains are reported transparently

Diagnostic test accuracy and cost‐effectiveness of tests for codeletion of chromosomal arms 1p and 19q in people with glioma

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To estimate the sensitivity and specificity of each technique for determining 1p/19q codeletion status in glioma, with a view to determining the most sensitive and specific technique(s)