Core outcome set developers’ response to COVID-19 (15th April 2020)

Many clinical trials and systematic reviews are already underway, or will begin shortly, to strengthen the evidence base for the COVID-19 response. Core outcome sets (COS), showing the outcomes that should be measured and reported in these studies, will ensure that this evidence base will contain, as a minimum, the key information needed by decision makers about the effects of interventions. This briefing paper has been prepared by COMET to summarise work to date on COS for COVID-19 and the COMET team will try to respond to any queries you have about it. COMET will also facilitate contact with COS developers to help determine which COS may be most relevant to your particular research study.

Background
In February 2020, three COVID-19 COS projects were registered in the COMET database [1-3]. A fourth was registered in March [4], with the aim of engaging patients in the COS development process, and is therefore complementary to the existing initiatives. Each COS is slightly different in its scope or methods, including the range of stakeholders involved, and they are complementary to one another.
Earlier work by ISARIC sought to standardize outcome data collected by research networks conducting clinical and epidemiological research in preparation for and during epidemics and pandemics [5]. In addition, existing COS projects for specific interventions used in and after critical care may be relevant [6-9]. A summary of all this work is available in the COMET database - http://www.comet-initiative.org/Studies/Details/1538 and will be updated as further evidence becomes available.
Teleconferences have been convened with representatives of the four COVID-19 COS (Junhua Zhang, John Marshall, Ruijin Qiu, Allison Tong) and the COMET Initiative (Paula Williamson, Liz Gargon, Mike Clarke). These discussions will continue, in order to maintain awareness of work on this topic, determine what information to disseminate more widely, and promote the uptake of COS in relevant research.

(1) COS for studies of any intervention in hospitalised patients with confirmed or suspected COVID-19


Table 1

The three completed COS [1-3] overlap, and a ‘meta-COS’ for research in adult hospitalised patients (Table 1) was agreed by the leads of the COS development projects [1-3] during a teleconference on 2nd April 2020. The preliminary results of the fourth COS [4] also agree with the meta-COS, and Table 1 has been updated accordingly. The analysis of the full results of this work is still underway, and Table 2 will be updated in due course.

Adverse events: Adverse events, relevant to the particular research question, should also be measured and reported.

Paediatric studies: During the COVID-19 pandemic, children have generally presented with mild disease. The rates of clinical infection, hospitalisation, need for respiratory support, and mortality, are low. Current and future clinical trials are focussed on adults with COVID-19 who are acutely or critically ill, and hospitalised or on intensive care. From a paediatric perspective it is reasonable to utilise the adult meta-COS for COVID-19 in studies of children, or those in which children are included with adults. As clinical trials are developed to evaluate vaccines and prophylactic medications, the studies may be more focussed on children and relevant efficacy and safety outcomes for this age group may need to be reconsidered.

Each of the COS include other core outcome domains for hospitalised patients, and also core outcome domains for those patients with asymptomatic or mild disease who are not hospitalised. These other outcomes deemed core but not in all COS are described in Table 2.

COS for COVID-19 studies

[1] http://www.comet-initiative.org/Studies/Details/1528
Lead: John Marshall, University of Toronto, Canada on behalf of the WHO Working Group on the Clinical Characteristics of COVID-19 infection
Summary: WHO has published a master protocol for COVID-19 studies, which recommends the outcomes to be measured in each of these. The WHO Working Group undertook a consensus exercise to agree a COS and the report will be published on the WHO website. In the meantime, please contact Liz Gargon, gargon01@liv.ac.uk , to obtain a copy.

[2] http://www.comet-initiative.org/Studies/Details/1523
Lead: Junhua Zhang, Evidence-Based Medicine Center, Tianjin University of Traditional Chinese Medicine, Tianjin, China
Summary: This COS is published - https://www.sciencedirect.com/science/article/pii/S2095809920300424?via%3Dihub
A Case Report Form for this COS has been drafted. Please contact Janneke van’t Hooft, janneke@stanford.edu , to obtain a copy.

[3] http://www.comet-initiative.org/Studies/Details/1507
Lead: Ruijin Qiu, Dongzhimen Hospital, Beijing University of Chinese Medicine, China
Summary: The COS is published on a preprint server and will be edited for English language soon –
https://medrxiv.org/cgi/content/short/2020.03.23.20041533v1

[4] http://www.comet-initiative.org/Studies/Details/1548
Lead: Allison Tong, University of Sydney, Australia
Summary: The protocol for this study has been written. It will have a particular focus on patients, family and community members. The results are expected by 16th April 2020.

[5] http://www.comet-initiative.org/Studies/Details/617
Lead: Calum Semple, University of Liverpool, UK on behalf of ISARIC
Summary: This work was done in 2014 with the aim to change how research is carried out during and between epidemics. Results of the work completed are available via the link. It informed the development of the WHO-ISARIC COVID-19 Clinical Platform (CCP) study case report form, which is available from Calum Semple, M.G.Semple@liverpool.ac.uk , prior to its publication on the WHO website.


Intervention-specific COS that may also be relevant for research in hospitalised patients with confirmed or suspected COVID-19


[6] http://www.comet-initiative.org/Studies/Details/292
Lead: Bronagh Blackwood, Queen's University Belfast, UK
Summary: This is a COS for trials of interventions intended to modify the duration of ventilation for patients being treated in an Intensive Care Unit.

[7] http://www.comet-initiative.org/Studies/Details/288
Lead: Bronwen Connolly, Queen's University Belfast, UK
Summary: This is an ongoing COS for trials of physical rehabilitation in critically ill patients, within intensive care units (ICU) and following their discharge from ICU and hospital. Please contact Bronwen Connolly for more information and preliminary results, bronwen.connolly@nhs.net.

(2) COS for studies of any intervention post-discharge



[8] http://www.comet-initiative.org/Studies/Details/1019
Lead: Dale Needham, Johns Hopkins University, US
Summary: This is a published COS for all clinical research studies evaluating acute respiratory failure survivors after hospital discharge. This COS is appropriate for both observational and intervention studies that want to evaluate post-discharge outcomes.

Intervention-specific COS that may also be relevant for post-discharge studies



[7] http://www.comet-initiative.org/Studies/Details/288
Lead: Bronwen Connolly, Queen's University Belfast, UK
Summary: This is an ongoing COS for trials of physical rehabilitation in critically ill patients, within intensive care units (ICU) and following their discharge from ICU and hospital.

[9] http://www.comet-initiative.org/Studies/Details/786
Lead: M Major, European School of Physiotherapy, Amsterdam University of Applied Sciences, Amsterdam, The Netherlands
Summary: This is a COS for trials of physical therapy in the post-hospital rehabilitation of people who have survived critical illness.


To download this summary as a PDF, click here.

Keyword: Coronavirus

Contributors

Paula Williamson (University of Liverpool)
Liz Gargon (University of Liverpool)
Mike Clarke (Queen's University Belfast)
John Marshall (WHO)
Junhua Zhang (Tianjin University of Traditional Chinese Medicine)
Ruijin Qiu (Beijing University of Chinese Medicine)
Bronagh Blackwood (Queen’s University Belfast)
Ian Sinha (Alder Hey Children’s Hospital)
Calum Semple (Alder Hey Children’s Hospital)
Allison Tong (University of Sydney)

Further Study Information

Current Stage: Ongoing
Date: March 2020 - April 2020
Funding source(s): None


Health Area

Disease Category: Infectious disease

Disease Name: Coronavirus

Target Population

Age Range: Unknown

Sex: Either

Nature of Intervention: Any

Stakeholders Involved

Study Type

- COS for clinical trials or clinical research

Method(s)