SPIRIT and CONSORT extensions for early phase dose-finding clinical trials:the DEFINE (DosE FIndiNg Extensions) study protocol

Introduction Early phase dose-finding (EPDF) studies are critical for the development of new treatments, directly influencing whether compounds or interventions can be investigated in further trials to confirm their safety and efficacy. There exists guidance for clinical trial protocols and reporting of completed trials in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 and CONsolidated Standards Of Reporting Randomised Trials (CONSORT) 2010 statements. However, neither the original statements nor their extensions adequately cover the specific features of EPDF trials. The DEFINE (DosE-FIndiNg Extensions) study aims to enhance transparency, completeness, reproducibility and interpretation of EPDF trial protocols (SPIRIT-DEFINE) and their reports once completed (CONSORT-DEFINE), across all disease areas, building on the original SPIRIT 2013 and CONSORT 2010 statements. Methods and analysis A methodological review of published EPDF trials will be conducted to identify features and deficiencies in reporting and inform the initial generation of the candidate items. The early draft checklists will be enriched through a review of published and grey literature, real-world examples analysis, citation and reference searches and consultation with international experts, including regulators and journal editors. Development of CONSORT-DEFINE commenced in March 2021, followed by SPIRIT-DEFINE from January 2022. A modified Delphi process, involving worldwide, multidisciplinary and cross-sector key stakeholders, will be run to refine the checklists. An international consensus meeting in autumn 2022 will finalise the list of items to be included in both guidance extensions. Ethics and dissemination This project was approved by ICR’s Committee for Clinical Research. The Health Research Authority confirmed Research Ethics Approval is not required. The dissemination strategy aims to maximise guideline awareness and uptake, including but not limited to dissemination in stakeholder meetings, conferences, peer-reviewed publications and on the EQUATOR Network and DEFINE study websites

Enhancing Quality and Impact of Early Phase Dose-Finding Clinical Trial Protocols:The SPIRIT DoseFinding Extension (SPIRIT-DEFINE) Guidance The SPIRIT-DEFINE Statement

International audienc

Enhancing Reporting Quality and Impact of Early Phase Dose-Finding Clinical Trials:The CONSORT Dose-Finding Extension (CONSORT-DEFINE) Guidance The CONSORT-DEFINE Statement

International audienceThe CONSORT (CONsolidated Standards Of Reporting Trials) 2010 statement is the standard guideline for reporting completed randomised trials. The CONSORT Dose-finding Extension (DEFINE) extends the guidance (with 21 new items and 19 modified items) to early phase dose-finding trials with interim dose escalation or de-escalation strategies. Such trials generally focus on safety, tolerability, activity, and recommending dosing and scheduling regimens for further clinical development. These trials are often inadequately reported, hampering their informativeness and making evidence informed decisions difficult. The CONSORT-DEFINE guidance aims to develop an international, consensus driven guideline for reporting early phase dose-finding trials to promote transparency, completeness, reproducibility, and facilitate the interpretation of the results. The CONSORT-DEFINE guidance provides recommendations for essential items that should be reported in early phase dose-finding trials to promote greater clarity, reproducibility, informativeness, and usefulness of results

Earthworm activity in a simulated landfill cover soil shifts the community composition of active methanotrophs

Landfills represent a major source of methane into the atmosphere. In a previous study, we demonstrated that earthworm activity in landfill cover soil can increase soil methane oxidation capacity (Héry et al., 2008). In this study, a simulated landfill cover soil mesocosm (1 m x 0.15 m) was used to observe the influence of earthworms (Eisenia veneta) on the active methanotroph community composition, by analyzing the expression of the pmoA gene, which is responsible for methane oxidation. mRNA-based pmoA microarray analysis revealed that earthworm activity in landfill cover soil stimulated activity of type I methanotrophs (Methylobacter, Methylomonas, Methylosarcina spp.) compared to type II methanotrophs (particularly Methylocystis spp.). These results, along with previous studies of methanotrophs in landfill cover soil, can now be used to plan in situ field studies to integrate earthworm-induced methanotrophy with other landfill management practises in order to maximize soil methane oxidation and reduce methane emissions from landfills

Reporting quality of early phase dose-finding clinical trials: a rapid methodological review protocol.

DF-CONSORT: protocol for the rapid methodological revie

British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults.

Iron deficiency anaemia (IDA) is a major cause of morbidity and burden of disease worldwide. It can generally be diagnosed by blood testing and remedied by iron replacement therapy (IRT) using the oral or intravenous route. The many causes of iron deficiency include poor dietary intake and malabsorption of dietary iron, as well as a number of significant gastrointestinal (GI) pathologies. Because blood is iron-rich it can result from chronic blood loss, and this is a common mechanism underlying the development of IDA-for example, as a consequence of menstrual or GI blood loss.Approximately a third of men and postmenopausal women presenting with IDA have an underlying pathological abnormality, most commonly in the GI tract. Therefore optimal management of IDA requires IRT in combination with appropriate investigation to establish the underlying cause. Unexplained IDA in all at-risk individuals is an accepted indication for fast-track secondary care referral in the UK because GI malignancies can present in this way, often in the absence of specific symptoms. Bidirectional GI endoscopy is the standard diagnostic approach to examination of the upper and lower GI tract, though radiological scanning is an alternative in some situations for assessing the large bowel. In recurrent or refractory IDA, wireless capsule endoscopy plays an important role in assessment of the small bowel.IDA may present in primary care or across a range of specialties in secondary care, and because of this and the insidious nature of the condition it has not always been optimally managed despite the considerable burden of disease- with investigation sometimes being inappropriate, incorrectly timed or incomplete, and the role of IRT for symptom relief neglected. It is therefore important that contemporary guidelines for the management of IDA are available to all clinicians. This document is a revision of previous British Society of Gastroenterology guidelines, updated in the light of subsequent evidence and developments

SPIRIT and CONSORT extensions for early phase dose-finding clinical trials: the DEFINE (DosE-FIndiNg Extensions) study protocol

Peer reviewed: TrueAcknowledgements: The authors acknowledge the support of E. Garrett-Mayer, D. Ashby and J. Isaacs, members of the Independent Expert Panel, in contributing their expertise and support to this initiative, and Siew Wan Hee for proofreading an earlier protocol version. The authors also thank the late D. Altman for his enthusiasm, inspiration and significant contribution to the initial conception of this work.Introduction: Early phase dose-finding (EPDF) studies are critical for the development of new treatments, directly influencing whether compounds or interventions can be investigated in further trials to confirm their safety and efficacy. There exists guidance for clinical trial protocols and reporting of completed trials in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 and CONsolidated Standards Of Reporting Randomised Trials (CONSORT) 2010 statements. However, neither the original statements nor their extensions adequately cover the specific features of EPDF trials. The DEFINE (DosE-FIndiNg Extensions) study aims to enhance transparency, completeness, reproducibility and interpretation of EPDF trial protocols (SPIRIT-DEFINE) and their reports once completed (CONSORT-DEFINE), across all disease areas, building on the original SPIRIT 2013 and CONSORT 2010 statements. Methods and analysis: A methodological review of published EPDF trials will be conducted to identify features and deficiencies in reporting and inform the initial generation of the candidate items. The early draft checklists will be enriched through a review of published and grey literature, real-world examples analysis, citation and reference searches and consultation with international experts, including regulators and journal editors. Development of CONSORT-DEFINE commenced in March 2021, followed by SPIRIT-DEFINE from January 2022. A modified Delphi process, involving worldwide, multidisciplinary and cross-sector key stakeholders, will be run to refine the checklists. An international consensus meeting in autumn 2022 will finalise the list of items to be included in both guidance extensions. Ethics and dissemination: This project was approved by ICR’s Committee for Clinical Research. The Health Research Authority confirmed Research Ethics Approval is not required. The dissemination strategy aims to maximise guideline awareness and uptake, including but not limited to dissemination in stakeholder meetings, conferences, peer-reviewed publications and on the EQUATOR Network and DEFINE study websites. Registration details: SPIRIT-DEFINE and CONSORT-DEFINE are registered with the EQUATOR Network