Keywords
Core outcome sets; clinical trialists; uptake
This article is included in the All trials matter collection.
Core outcome sets; clinical trialists; uptake
A core outcome set (COS) is an agreed standardized set of outcomes that should be measured and reported, as a minimum, in all clinical trials in specific areas of health or health care.1 The concept of COS was introduced in China in 2013.2 Chinese researchers have registered more than 80 COS for research in the Core Outcome Measures in Effectiveness Trials (COMET) database by 2022, the majority of them are focused on traditional Chinese medicine (TCM).
A search of the COMET database shows that more than 500 completed COS studies have been published by 2022. The number of COS varies by disease category. The top five disease categories are cancer, rheumatology, neurology, heart and circulation, orthopaedics and trauma.3 However, the number of candidates vary by disease category. In addition, there are more than one COS for some conditions, while no COS exists in some other important conditions. Whether there are gaps between COS research and the burden of disease in China remains unclear.
There are some benefits to using COS in clinical trials, which include improving the consistency of outcome reporting, increasing the relevance of outcomes measured to decision-makers, and helping to identify potential selective bias. However, previous research has shown that COS uptake is low in most research areas.4,5 Research shows that clinical trialists’ awareness and understanding of COS may facilitate the use of COS.6 However, Chinese clinical trialists’ awareness, understanding and using of COS are unknown. In China, COS research is mainly focused on traditional Chinese medicine. The differences of COS knowledge, awareness, and understanding between TCM trialists and Western medicine trialists are also unclear.
The aims of this study are to examine: (1) whether the top 25 diseases with the highest burden in China have relevant COS; (2) the use of COS in clinical trials registered in 2021 and 2022 in the Chinese Clinical Trial Registry for these 25 diseases; and (3) views of these clinical trialists on the knowledge, perceptions, and use of COS in relation to choosing outcomes, and whether there are differences between TCM and Western medicine trialists.
The top 25 causes of disability-adjusted life-years (DALY) in China in 2019 have been identified from the tool of Global Burden of Disease (GBD).7 Two researchers (RQ and XF) will also discuss subtypes of disease according to practice guidelines or textbook of internal medicine if necessary. The initial list of diseases for the study is shown in Table 1.
We will manually search the COMET database and identify COS for diseases/subtypes in the diseases list. We will identify if there are ongoing or completed relative COS research since 2012, when COS were introduced in China. The study began on April 7th, 2023 and is ongoing.
(1) The scope appears relevant to a disease in the diseases list;
(2) COS for research that are well developed, meeting existing standards8;
(3) The COS was published after 2012, and the full article can be retrieved.
RQ will identify COS from the COMET database, and XF will check the results. Any discrepancies will be resolved by consensus discussion or by consulting a third reviewer (PW). The COS-STAD recommendation8 will be used to assess the quality of COS by RQ and PW. RQ and PW will discuss all the COS for the 25 causes of DALY and determine which COS are eligible.
We will search the Chinese Clinical Trial Registry (https://www.chictr.org.cn/historyversionpub.aspx) according to the disease name extracted for the published COS.
Inclusion criteria for clinical trials:
(1) Randomised and non-randomised clinical trials;
(2) The objectives of clinical trials are for disease therapy;
(3) The prospective registration time should be in 2021 and 2022.
Exclusion criteria for clinical trials: The clinical trials are to assess the mechanisms of effect of interventions.
If the disease name in the COS is broader, we will further search subtypes of disease. RQ and XF will discuss the list of subtypes of disease, any disagreement will be discussed with a third investigator (HS). XF, WW, ZC, and SL will search for clinical trials from the Chinese Clinical Trial Registry and apply the inclusion and exclusion criteria to identify the eligible clinical trials. RQ will check the results.
Inclusion criteria:
(1) An eligible COS exists.
(2) The number of clinical trials with matching scope to an eligible COS is not less than 40.
After discussion by MK, PW, HS, and RQ, they believe that a COS developed by Chinese researchers may be significant for Chinese clinical trialists. If there is an eligible COS developed by Chinese researchers, it will be included. If it does not meet the inclusion criteria for comparison of COS with clinical trials, then the prospective registration time for clinical trials will be expanded.
We will describe the number of ongoing and published COS for the highest burden of disease in China. Full texts will be retrieved for published COS only.
Data will be retrieved from previous COMET systematic reviews. Extracted data for COS will include: author, title, publication time, condition, population, intervention, outcomes, and outcome measurement instruments (if applicable).
Extracted data for clinical trials will include: applicant, the applicant’s email and telephone number, the primary investigator’s name, the primary investigator’s email and telephone number, title, applicant’s institutions, study type, disease name, population, intervention, outcomes, and outcome measurement instruments.
For comparing trial outcomes and COS, only published COS will be used. If there are more than two COS for a specific disease, the differences in scope between these COS will be discussed by two reviewers.
We will compare the overlap in scope between clinical trials and COS according to the framework used in previous research.9 The framework is shown in Table 2.
Intervention | |||||
---|---|---|---|---|---|
COS is narrow | Exact match | COS is broader | Different intervention | ||
Population | COS is narrow | A | B | C | d |
Exact match | E | F | G | h | |
COS is broader | I | J | K | l | |
Different subgroup of the population | M | N | O | p |
We will calculate the median percentages of outcomes in each clinical trial that were specific matches, general matches, and non-matches with outcomes in each relevant COS. We will analyze the median of the proportion of outcomes that overlap between the COS and clinical trials for each disease. We will also compare the differences between clinical trials of TCM and Western medicine. We will calculate the number of 100% match between clinical trials and COS and look for trends over time.
A survey will be sent to clinical trialists who will conduct a clinical trial that has overlapped scope between the trial and COS. We will identify the primary investigator’s name, email, and telephone number when we extract eligible clinical trials from the Chinese Clinical Trial Registry. We will send a Chinese translation of the COS deemed relevant to the trialists’ trials with questionnaire. When the primary investigators cannot be contacted via emails, the applicants for registration will be approached. We will examine trialists’ knowledge and awareness of COS. An online survey will be sent to clinical trialists, with one of three versions of the survey: 1) clinical trialists who report a full COS in their clinical trials; 2) clinical trialists who report only a few of outcomes in the COS; and 3) clinical trialists who do not report any outcome in the COS.
The survey will include both closed and open-ended questions. General information, such as gender, age, participants’ role, work experience, geographical area, professional qualification, and educational background will be collected. We will refer the facilitators and barriers identified in previous research, including using of COS and clinical practice guidelines,10,11 to develop open and closed questions to ask all participants. MK, PW, and RQ will discuss the questions in the questionnaires. The survey and other tools will be distributed into Chinese. RQ will translate tools into Chinese and the translation will then be sent to several researchers who have experience in COS research from a Chinese authors' team and we will ask them to give comments. RQ, SL, ZC, and WW will discuss and determine the translation before distribution.
The structured questions in the survey are shown in extended data.
At the end of each survey, we will ask the trialists if they would like to attend a semi-structured interview. We will invite at least 30 trialists who agree to be interviewed to attend an in-person or online interview. The COS publication, translated into Chinese, will be sent to them before the interview. The topic guide is as follows:
1. How many years of experience do you have in the design, management, or analysis clinical trials?
2. How many clinical trials did you participate in the design, management, or analysis?
3. When you design a clinical trial, how did you choose outcomes?
4. Do you know what is COS?
5. Are you familiar with COS?
6. Can you define COS?
7. How comfortable you are with English?
8. How did you become familiar with COS?
9. If there is a relevant COS in your research area, do you want to use it? Why?
10. Whether you know the COS that we sent you? Will you use it in your next trial?
11. What kind of facilitators and barriers for you to use a COS in clinical trial?
12. In your opinion, what should be done to improve the use of COS?
Data collected from the review of COS and clinical trials, and the survey of trialists will be analysed using descriptive methods. The numbers and percentage of trialists who know the COS and would like to use a COS will be calculated. The trialist’s awareness of, and decisions to search for and use a COS will be analyzed by content analysis.
Dissemination
The finding of this research will be disseminated through conferences, peer-reviewed publication, and social media.
COS have been introduced in China for about 10 years. Chinese trialists’ knowledge and awareness of using COS are important to COS developers in China. This study will provide information on the proportion of trialists in China who registered clinical trials in the Chinese Clinical Trial Registry in the areas with the highest burden of disease, and how the outcomes they chose compare to existing COS.
COS are very important for reducing heterogeneity of outcome reporting, potential bias, and research waste when they are used in clinical trials. There are hundreds of COS published in the world. Chinese researchers are also developing COS in some health areas, whether there is a gap between COS and the burden of disease in China remains unclear. This research will provide evidence relevant to COS researchers and clinical trialists.
The project has been approved by the Ethics Committee of Dongzhimen Hospital, Beijing University of Chinese Medicine (2023DZMEC-175-01). The ethical approval agreed to not getting written informed consent from the participants, because they are clinical trialists.
Trial registration: This research is registered in Core Outcome Measures in Effectiveness: https://www.comet-initiative.org/Studies/Details/2563.
DANS-EASY; Questionnaire of trialists’ perceptions in COS. https://doi.org/10.17026/dans-ze4-tby3. 12
This project contains the following extended data:
Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).
We thank the China Scholarship Council for supporting this research. We are grateful to Jamlick Karumbi, from the University of Liverpool for his share on the experience of developing questionnaire.
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Is the rationale for, and objectives of, the study clearly described?
Partly
Is the study design appropriate for the research question?
Yes
Are sufficient details of the methods provided to allow replication by others?
Partly
Are the datasets clearly presented in a useable and accessible format?
Not applicable
Competing Interests: KT is a member of the Executive Group for The Harmonizing Outcome Measures for Eczema and sits on the Methods Committee for the C3 initiative.I confirm that this potential conflict of interest did not affect my ability to write an objective and unbiased review of the article.
Reviewer Expertise: Applied health research, core outcome sets, development and validation of outcome instruments
Is the rationale for, and objectives of, the study clearly described?
Yes
Is the study design appropriate for the research question?
Yes
Are sufficient details of the methods provided to allow replication by others?
Yes
Are the datasets clearly presented in a useable and accessible format?
Not applicable
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Evidence-based medicine research in traditional medicine; clinical epidemiology; COS development
Alongside their report, reviewers assign a status to the article:
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