SummaryEarly phase dose-finding (EPDF) trials are key in the development of novel therapies, with their findings directly informing subsequent clinical development phases and providing valuable insights for reverse translation. Comprehensive and transparent reporting of these studies is critical for their accurate and critical interpretation, which may improve and expedite therapeutic development. However, quality of reporting of design characteristics and results from EPDF trials is often variable and incomplete. The international consensus-based CONSORT-DEFINE (Consolidated Standards for Reporting Trials Dose-finding Extension) statement, an extension of the CONSORT statement for randomised trials, was developed to improve the reporting of EPDF trials. The CONSORT-DEFINE statement introduced 21 new items and modified 19 existing CONSORT items.This CONSORT-DEFINE Explanation and Elaboration (E&E) document provides important information to enhance understanding and facilitate the implementation of the CONSORT-DEFINE checklist. For each new or modified checklist item, we provide a detailed description and its rationale with supporting evidence, and present examples from EPDF trial reports published in peer-reviewed scientific journals. When reporting the results of EPDF trials, authors are encouraged to consult the CONSORT-DEFINE E&E document, together with the CONSORT and CONSORT-DEFINE statement papers, and adhere to their recommendations. Widespread adoption of the CONSORT-DEFINE statement is likely to enhance the reporting quality of EPDF trials, thus facilitating the peer review of such studies and their appraisal by researchers, regulators, ethics committee members, and funders.FundingThis work is a further extension of the CONSORT-DEFINE study, which was funded by the UK Medical Research Council (MRC)-National Institute for Health and Care Research (NIHR) Methodology Research Programme (MR/T044934/1). The Clinical Trials and Statistics Unit at The Institute of Cancer Research (ICR-CTSU) receives programmatic infrastructure funding from Cancer Research UK (C1491/A25351; CTUQQR-Dec 22/100 004), which has contributed to accelerating the advancement and successful completion of this work.
Background: Patient engagement (PE) or involvement in research is when patient partners are integrated onto teams and initiatives (not participants in research). A number of health research funding organizations have PE frameworks or rubrics but we are unaware of them applying and reporting on their own PE efforts. We describe our work at the Canadian Institutes of Health Research’s Institute of Musculoskeletal Health and Arthritis (CIHR IMHA) to implement, evaluate and understand the impact of its PE strategy.Methods: The Institute hired a PE specialist (who identifies as a patient partner) to design the strategy, its tactics, and timelines. A Patient Engagement Research Ambassador (PERA) group was convened of eight patient partners who lived with conditions represented by the Institute that meet monthly, co-created a mandate and terms of reference, and set priorities. Evaluating the PE strategy and understanding its impact was a collaboration between an external group and PERA. Results: In addition to convening PERA, the Institute produced a number of outputs (modules, video, publications, webinars, blog) to help in doing PE in research. One major output was a How-To Guide to Patient Engagement in Research entirely driven and designed by PERA. The How-To Guide is a series of free, virtual modules for different audiences used by 1,048 individuals to date. The evaluation and impacts of the PE strategy revealed positive impacts with some areas for improvement.Conclusions: Implementing a PE strategy within CIHR IMHA resulted in several PE activities and outputs with impacts within and beyond the Institute. We provide templates and outputs related to this work that may inform the efforts of other health research funding organizations. We encourage health research funders to move beyond encouraging or requiring PE in funded projects to fully ‘walk the talk’ of PE by implementing and evaluating their own PE strategies.
SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 provides guidance for clinical trial protocol writing. However, neither the original guidance nor its extensions adequately cover the features of early phase dose-finding trials. The SPIRIT Dose-finding Extension (DEFINE) statement is a new guideline that provides recommendations for essential items that should be provided in the protocols of these trials. It details extensions to the SPIRIT 2013 guidance, incorporating 17 new items and modifying 15 existing items. The purpose of this guideline is to promote transparency, completeness, reproducibility of methods, and interpretation of early phase dose-finding trial protocols. It is envisioned that the resulting improvements in the design and conduct of early phase clinical trials will ultimately reduce research inefficiencies and inconsistencies, driving transformational advances in clinical care.
Abstract Background During the past decade, patient engagement (PE) has attracted significant attention in the field of drug development. Readiness to accept the central importance of patients’ knowledge and contributions has become evident. This study aimed to synthesize evidence on the current state of PE in drug development: what is actually being done and how. Methods A systematic scoping review was conducted based on a PRISMA-informed protocol. Search was performed in PubMed, EMBASE and Web of Science, covering the period between 2011 and 2021. For analysis of extracted data, we developed a framework for analyzing PE in Drug Development. The Framework distinguishes a number of different PE types that take place at different stages of drug development and are characterized by the different degrees of power patients have in the process. It allowed us to assess depth and intensity of PE initiatives included in this review. Results Most included PE initiatives took place at the stage of designing studies (40 in total). At this stage drug development goals are already set, but the mode of reaching them has not yet been fully determined. PE initiatives on the finetuning details stage followed (16 in total). The finetuning details stage covers the last parts of the drug development trajectory, when only relatively minor issues are still open for patients’ contributions. The least numerous were PE initiatives on the stage of setting up R&D program (13 in total). This stage refers to the early steps in drug development where PE has the potential to make the most impact on shaping the subsequent process. In terms of intensity of engagement, most PE initiatives included in this review align with consultation and involvement types, 26 and 30 initiatives, respectively. Partnership was less frequent in the published accounts of PE (13 initiatives). Conclusions This review delineated a contemporary landscape of PE in drug development. Although attention to PE in drug development is relatively recent, a wide range of PE practices has already been initiated. The results indicate the necessity of distinguishing between different types of PE in order to understand consequences of choices regarding depth and intensity of PE.
Preventing pediatric chronic postsurgical pain is a patient, parent/caregiver, health care professional, and policymaker priority. Poorly managed presurgical and acute postsurgical pain are established risk factors for pediatric chronic postsurgical pain. Effective perioperative pain management is essential to prevent the transition from acute to chronic pain after surgery.The aim of this study was to identify current pediatric surgical pain management practices and assess health system readiness for change at health care institutions conducting pediatric surgery in Canada.An online survey was completed by 85 multidisciplinary health care professionals (nurses, surgeons, anesthesiologists, allied health) from 20 health institutions in Canada regarding institutional pre- and postsurgical pediatric pain care, specialty pain services, and Organizational Readiness for Implementing Change (ORIC).Of all specialty pain services, acute and chronic/complex pain services were most common, primarily with physician and nursing involvement. Alignment to recommended practices for pediatric pre- and postsurgical pain care varied (38.1%-79.8% reported "yes, for every child"), with tertiary/quaternary children's hospitals reporting less alignment than other institutions (community/regional or rehabilitation hospitals, community treatment centers). No significant differences were reported between health care institutions serving pediatric populations only versus those also serving adults. Health care professional experience/practice was the most reported strength in pediatric surgical pain care, with inconsistent standard of care the most common gap. Participants "somewhat agreed" that their institutions were committed and capable of change in pediatric surgical pain care.There is a continued need to improve pediatric pain care during the perioperative period at Canadian health care institutions to effectively prevent the development of pediatric postsurgical pain.Contexte: La prévention de la douleur post-chirurgicale chronique pédiatrique est une priorité des patients, des parents/prestataires de soins, des professionnels de la santé et des décideurs. La douleur pré-chirurgicale et post-chirurgicale aiguë mal prises en charge constituent des facteurs de risque connus de la douleur post-chirurgicale chronique pédiatrique. La prise en charge efficace de la douleur périopératoire est essentielle pour prévenir la transition de la douleur aiguë à la douleur chronique aprés une chirurgie.Buts: Le but de cette étude était de recenser les pratiques actuelles en matiére de prise en charge de la douleur chirurgicale pédiatrique et d’évaluer l'état de préparation au changement du systéme de santé dans les établissements de soins de santé menant des chirurgies pédiatriques au Canada.Méthodes: 85 professionnels de la santé multidisciplinaires (infirmiéres, chirurgiens, anesthésistes, auxiliaires médicaux) ont répondu à un sondage en ligne de 20 établissements de santé au Canada concernant les soins pédiatriques pré et post-chirurgicaux en établissement, les services spécialisés de traitement de la douleur, les services de la douleur spécialisés et la préparation organisationnelle à la mise en œuvre du changement.Résultats: De tous les services de la douleur spécialisés, les services de la douleur aiguë et chronique/complexe étaient les plus fréquents, principalement avec la participation d'un médecin et d'une infirmiére. L’adéquation avec les pratiques recommandées pour les soins pédiatriques pré et post-chirurgicaux était variable (38,1 %-79,8 % ont déclaré « oui, pour chaque enfant »), alors que les hôpitaux pour enfants tertiaires/quaternaires ont déclaré moins d'adéquation que les autres institutions (hôpitaux communautaires/régionaux ou de réadaptation, centres de traitement communautaires). Aucune différence significative n’a été rapportée entre les établissements de soins de santé desservant uniquement les populations pédiatriques et ceux desservant aussi les adultes. L'expérience professionnelle/la pratique en matière de soins de santé a été la force la plus rapportée dans les soins de la douleur chirurgicale pédiatrique, tandis que les normes de soins incoh'rentes constituaient la lacune la plus courante. Les participants ont « quelque peu convenu » que leurs institutions étaient engagées et capables de changer les soins chirurgicaux pédiatriques.Conclusions: ll y a un besoin continu déaméliorer les soins de la douleur pédiatrique pendant la période périopératoire dans les établissements de soins de santé canadiens afin de prévenir efficacement le développement de la douleur postopératoire.
