The overall objective of the INCEPT research programme is to develop a framework to test many interventions used in intensive care units (ICU) to the benefit of the sickest patients in the hospital, their relatives, and society.
The programme aims to prepare, initiate, and run an adaptive platform trial assessing commonly used interventions in adult critically ill patients acutely admitted to the ICU.
A platform trial focuses on a disease or a setting; thus, the overarching design does not focus on a single intervention. By building a platform trial, we can continuously enroll many ICU patients in Denmark and other countries and randomly allocate them to multiple interventions nested in different domains.
The work unfolds in five overarching working groups:
To ensure transparency and disseminate what we learn, we seek to publish all our finding and work. See our Publications library for a complete list.
Ethics and stakeholder involvement
INCEPT will comply with the latest version of the Declaration of Helsinki, the World Health Organization (WHO) guidance for best practices for clinical trials, Good Clinical Practice (GCP) guidelines, the General Data Protection Regulation (GDPR), and applicable national laws (including the Danish Data Protection Act).
As critical illness requiring acute ICU admission constitutes a medical emergency requiring urgent treatment (including with the interventions assessed in INCEPT), enrolment will occur without prior informed consent, according to the applicable legislation for clinical trials conducted in emergency situations. As soon as possible hereafter, informed consent for continuation in the platform trial (including all applicable domains) will be obtained from a legally designated representative (in Denmark the closest relative) and a legal guardian (in Denmark, a medical doctor who is independent from the trial). Participants will be asked for informed consent as soon as possible hereafter.
Stakeholder involvement is central in INCEPT and ensured through a central advisory board comprising various key stakeholder and national and international research panels consisting of ICU survivors, family members, clinicians, and researchers. Stakeholders have been involved in the development of the overall platform trial, including the core outcome set that the INCEPT core outcomes are based on, and continued involvement in multiple research stages (including research focus and design, recruitment, dissemination, including outcome and domain considerations and prioritisation) is planned with pre-specified minimum requirements for involvement in INCEPT and all domains.
Methods
The methodological framework for INCEPT is outlined in a core protocol, which covers:
- The overaching design (a Bayesian, domain-based adaptive platform trial)
- Core outcomes
- General analytical principles
- Adaptations (adaptive stopping and arm dropping for superiority/inferiority, practical equivalence, and/or futility, and response-adaptive randomisation)
- The simulation framework used to design and evaluate the performance metrics of all INCEPT domains
Specific methodological choices are outlined in domain-specific appendices. In addition, the methods group focuses on development of tools and guidance aimed at facilitating the planning and conduct of adaptive (platform) trials by other researchers, along with studies assessing the use and implications of various adaptive design features.
Data infrastructure
We are building a tailored data infrastructure that caters for the unique needs of adaptive platform trials and enables integration with electronic patient record systems, such as Sundhedsplatformen (Epic), to minimise the risk of transcription errors from, and reduce the time spent on manual data entry. This system will be deployed in a secure server hosted in the Capital Region of Denmark.
The system will, eventually, automate the frequent adaptive analyses and data quality assurance work involved in ensuring only high-quality data are used to inform adaptations in INCEPT domains.
We will also develop an improved method for electronically collecting patient-reported outcome measures (PROMs), with the option to manually enter these data if patients or relatives are unable to provide them using the electronic system.
Funding
We are working on ensuring continuous and lasting funding of INCEPT as a whole along with funding of specific domains.
Clinical domains
The first planned and upcoming domains on INCEPT will assess:
- Albumin for resuscitation and substitution therapy versus no use of albumin in ICU patients with shock [click here to read more]
- Low, intermediate, and weight-based doses of low-molecular weight heparin for thromboprophylaxis in ICU patients
- Continuous blood glucose monitoring vs. standard-of-care in ICU patients who need insulin