Traditional Chinese medicine (TCM), including Chinese herbal medicine (CHM), acupuncture, cupping, and massage, plays an important role in the Chinese health care system, and almost all hospitals in China provide TCM services. Patients around the world also benefit from TCM extract, such as artemisinin, an antimalarial drug [
The randomized controlled trials (RCTs), providing the evidence of efficacy and safety of interventions, are fundamental to generate evidence-based practice guidelines. However, a reader cannot accurately evaluate the conclusion if a clinical trial is not reported with sufficient details. To standardize and improve the reporting quality of RCTs, the CONSORT (Consolidated Standards of Reporting Trials) statement was published in 1996 and updated in 2010 by the CONSORT group [
To the best of our knowledge, the number of CPMs for eczema and the reporting quality of RCTs for the treatment of eczema with CPM in mainland China have not been investigated yet. The aims of this study are to search the circulating CPMs with the indication for eczema in mainland China and to evaluate the reporting quality of RCTs regarding these products by using the CONSORT-CHM formulas 2017.
This study consisted of three parts. First, circulating CPM with the indication for eczema in mainland China was selected by searching drug databases and confirmed by contacting the manufacturers. Second, RCTs of each eligible CPM were selected by retrieving literature databases. Third, the reporting quality of each included RCT was assessed based on the CONSORT-CHM formulas 2017.
By using the search terms “eczema” and “dermatitis,” CPM was collected from the following three drug databases: Sanjiu Yaopintong (
Four Chinese literature databases and four English literature databases were used to search relevant articles from their inception to August 31, 2019, including Chinese National Knowledge Infrastructure database (CNKI), Wanfang Data knowledge service platform (Wanfang), Chongqing Weipu database (VIP), Chinese Biomedical Literature database (SinoMed), PubMed, Cochrane Library, Embase, and Web of Science. The search strategy used for each database was ((“eczema” [Mesh] OR “eczema” [Title/Abstract]) OR (“dermatitis” [Mesh] OR “dermatitis” [Title/Abstract])) AND (“the name of each CPM” [Title/Abstract]). Inclusion criteria were as follows: RCTs published in Chinese or English; participants diagnosed as eczema, regardless of gender, age, or duration of eczema; the experimental group treated with CPM alone or CPM combined with western medicine same as the control group; and the control group treated with placebo or western medicine. Reviews, animal experiments, case reports, non-RCTs, duplicate studies, unavailable full texts, and studies with inappropriate interventions were excluded.
The following information from included RCTs was extracted: year of publication, language of the study, number of research center, sample size, and the type of the first author’s hospital. The reporting quality was assessed by using the CONSORT-CHM formulas 2017, comprising a checklist of 38 items [
All procedures of CPM search, RCT search, data extraction, and assessment of reporting quality were carried out by two authors (ML and BYZ) independently, and discrepancies were resolved by consultation from the third author (LHZ).
The primary outcomes were the number of circulating CPMs with the indication for eczema in mainland China and the mean OQS of included RCTs in accordance with the CONSORT-CHM formulas 2017. The secondary outcomes were the reporting rate of each item of the CONSORT-CHM formulas 2017 and the associations between the reporting quality and the following factors: year of publication and the type of the first author’s hospital.
Continuous variables were presented as mean ± standard deviation (SD), and the independent sample
After removing the duplicates, 136 CPMs were selected from three drug databases. Of those, 46 CPMs without the indication for eczema, 4 CPMs without drug approval number from China NMPA, and 16 CPMs containing western medicine were excluded. Finally, 70 CPMs, including 37 topical CPMs and 33 oral CPMs, met the eligible criteria. The list of 70 included CPMs is summarized in Supplementary Table
In total, 1733 articles were retrieved from four Chinese literature databases and four English literature databases. 1479 articles were excluded as a result of checking titles and abstracts. After screening full texts, 110 articles were excluded. 144 eligible RCTs which involved 21 CPMs were included in the final analysis. 11 out of 21 CPMs (52.38%) had no more than two eligible RCTs. Figure
The flowchart of RCTs selection.
The list of 21 included CPMs and the number of included RCTs of each CPM.
Category of CPM | No. | Name of CPM | Number of included RCTs |
---|---|---|---|
Topical CPM | 1 | Qingpeng ointment | 45 |
2 | Chushi Zhiyang ointment | 20 | |
3 | Binghuang Fule ointment | 19 | |
4 | Wudai ointment | 8 | |
5 | Paeonol ointment | 7 | |
6 | Pifukang lotion | 7 | |
7 | Sophora alopecuroide oil liniment | 6 | |
8 | Erfukang liniment | 6 | |
9 | Qiangyue cream | 6 | |
10 | Meilu Xiaocuo ointment | 2 | |
11 | Geranium ointment | 1 | |
12 | Mayinglong musk hemorrhoid cream | 1 | |
13 | Chushi Zhiyang lotion | 1 | |
14 | Shuangzishen lotion | 1 | |
15 | Jieeryin lotion | 1 | |
Oral CPM | 1 | Xiaofeng Zhiyang granule | 5 |
2 | Piminxiao capsule | 2 | |
3 | Phellodendron bark capsule | 2 | |
4 | Baixuanxiatare tablet | 2 | |
5 | Fangfeng Tongshen granule | 1 | |
6 | Sophora flavescens capsule | 1 |
CPM, Chinese patent medicine; RCT, randomized controlled trial.
All included RCTs were conducted by authors from mainland China. The 144 studies were published from 1996 to 2019, and 50 (34.72%) of them were published in recent five years. Only one article (0.69%) was printed in English in an international journal, and the remaining 143 articles were printed in Chinese in Chinese journals. Except for four multiple-center RCTs, most (97.22%,
General characteristics of 144 included RCTs.
Characteristics | Number (%) of RCTs |
---|---|
Year of publication | |
2019–2015 | 50 (34.72%) |
2014–2010 | 64 (44.45%) |
2009–2005 | 25 (17.36%) |
2004–1996 | 5 (3.47%) |
Language | |
Chinese | 143 (99.31%) |
English | 1(0.69%) |
Research centers | |
Single center | 140 (97.22%) |
Multiple center | 4 (2.78%) |
Sample size | |
<60 | 10 (6.94%) |
60–100 | 82 (56.95%) |
>100 | 52 (36.11%) |
Type of the first author’s hospital | |
University hospital | 73 (50.69%) |
Nonuniversity hospital | 71 (49.31%) |
RCT, randomized controlled trial.
In the 144 RCTs, the mean OQS was 19.85 ± 2.73, ranging from 13 to 32. Three studies (2.08%) scored 27 or more, the OQS of 106 studies (73.61%) varied between 19 and 26, and 35 studies (24.31%) scored 18 or less. The distribution of OQS of 144 RCTs is shown in Table
The distribution of OQS of 144 included RCTs.
The distribution of OQS (percentage of maximum score of 38) | Number (%) of RCTs |
---|---|
38 (100%) | 0 (0%) |
37–35 (99%–90%) | 0 (0%) |
34–31 (89%–80%) | 1 (0.69%) |
30–27 (79%–70%) | 2 (1.39%) |
26–23 (69%–60%) | 11 (7.64%) |
22–19 (59%–50%) | 95 (65.97%) |
18–16 (49%–40%) | 27 (18.75%) |
15–12 (39%–30%) | 8 (5.56%) |
OQS, overall quality score; RCT, randomized controlled trial.
In the subgroup of 38 items, 12 items (3a, 4b, 5, 6a, 12a, 13a, 13b, 14a, 16, 18, 19, and 22) were reported in over 70% of the RCTs, and 6 items (1b, 2a, 4a, 11b, 12b, and 21) were stated in 50%–70% of the RCTs. Reporting rates were less than 50% for 16 items (1a, 1c, 2b, 7a, 8a, 8b, 9, 10, 11a, 15, 17a, 17b, 20, 23, 24, and 25). Among them, 2 items (17a and 17b) were not mentioned at all. In addition, 4 items (3b, 6b, 7b, and 14b) were not applicable in all studies. In the 144 studies, six studies (4.17%) adopted the blinding methods, including four double-blinded studies, one evaluator-blinded study, and one single-blinded study with an uncertain blinded object. Six studies (4.17%) adopted subgroup analysis to evaluate the effect of CPM for different stages of eczema or participants with different ages. Table
The reporting number and percentage for each item of the CONSORT-CHM formulas 2017.
Section | Topic | Item number | % | |
---|---|---|---|---|
Title, abstract, and keywords | Title | 1a | 4/144 | 2.78 |
Abstract | 1b | 100/144 | 69.44 | |
Keywords | 1c | 5/144 | 3.47 | |
Introduction | Background | 2a | 99/144 | 68.75 |
Objectives | 2b | 35/144 | 24.31 | |
Methods | Trial design | 3a | 142/144 | 98.61 |
3b | 0/0 | 0 | ||
Participants | 4a | 82/144 | 56.94 | |
4b | 123/144 | 85.42 | ||
Interventions | 5 | 114/144 | 79.17 | |
Outcomes | 6a | 106/144 | 73.61 | |
6b | 0/0 | 0 | ||
Sample size | 7a | 1/144 | 0.69 | |
7b | 0/0 | 0 | ||
Sequence generation | 8a | 34/144 | 23.61 | |
8b | 4/144 | 2.78 | ||
Allocation concealment mechanism | 9 | 1/144 | 0.69 | |
Implementation | 10 | 1/144 | 0.69 | |
Blinding | 11a | 5/144 | 3.47 | |
11b | 3/6 | 50 | ||
Statistical methods | 12a | 115/144 | 79.86 | |
12b | 4/6 | 66.67 | ||
Results | Participant flow | 13a | 144/144 | 100 |
13b | 137/144 | 95.14 | ||
Recruitment | 14a | 119/144 | 82.64 | |
14b | 0/0 | 0 | ||
Baseline data | 15 | 8/144 | 5.56 | |
Numbers analyzed | 16 | 144/144 | 100 | |
Outcomes and estimation | 17a | 0/144 | 0 | |
17b | 0/143 | 0 | ||
Ancillary analyses | 18 | 6/6 | 100 | |
Harms | 19 | 120/144 | 83.33 | |
Discussion | Limitations | 20 | 8/144 | 5.56 |
Generalizability | 21 | 74/144 | 51.39 | |
Interpretation | 22 | 118/144 | 81.94 | |
Other information | Registration | 23 | 1/144 | 0.69 |
Protocol | 24 | 2/144 | 1.39 | |
Funding | 25 | 9/144 | 6.25 |
CONSORT-CHM formulas, Consolidated Standards of Reporting Trials for Chinese herbal medicine formulas.
The mean OQS of studies published after 2015 was significantly higher than that of studies published before 2015 (21.28 ± 2.76 vs 19.10 ± 2.41, MD: 2.18, 95% CI: 1.31–3.06,
Univariable analysis of reporting rate of each item of the CONSORT-CHM formulas 2017.
Item number | Year of publication | OR (95% CI) | Type of the first author’s hospital | OR (95% CI) | ||||
---|---|---|---|---|---|---|---|---|
≥2015 | <2015 | University hospital | Nonuniversity hospital | |||||
1a | 2/50 (4%) | 2/94 (2.13%) | 1.92 (0.26–14.03) | 0.906 | 3/73 (4.11%) | 1/71 (1.41%) | 3.00 (0.31–29.55) | 0.632 |
1b | 44/50 (88%) | 56/94 (59.57%) | 4.98 (1.93–12.83) | <0.001 | 45/73 (61.64%) | 55/71 (77.46%) | 0.47 (0.23–0.97) | 0.039 |
1c | 4/50 (8%) | 1/94 (1.06%) | 8.09 (0.88–74.43) | 0.092 | 4/73 (5.48%) | 1/71 (1.41%) | 4.06 (0.44–37.23) | 0.379 |
2a | 46/50 (92%) | 53/94 (56.38%) | 8.90 (2.96–26.73) | <0.001 | 53/73 (72.60%) | 46/71 (64.79%) | 1.44 (0.71–2.92) | 0.312 |
2b | 19/50 (38%) | 16/94 (17.02%) | 2.99 (1.36–6.55) | 0.005 | 24/73 (32.88%) | 11/71(15.49%) | 2.67 (1.19–5.99) | 0.015 |
3a | 50/50 (100%) | 92/94 (97.87%) | NE | 0.544 | 71/73 (97.26%) | 71/71 (100%) | NE | 0.497 |
3b | 0/0 (0%) | 0/0 (0%) | NE | NE | 0/0 (0%) | 0/0 (0%) | NE | NE |
4a | 32/50 (64%) | 50/94 (53.19%) | 1.56 (0.77–3.17) | 0.212 | 44/73 (60.27%) | 38/71 (53.52%) | 1.32 (0.68–2.55) | 0.413 |
4b | 46/50 (92%) | 77/94 (81.91%) | 2.54 (0.81–8.01) | 0.103 | 65/73 (89.04%) | 58/71 (81.69%) | 1.82 (0.71–4.71) | 0.211 |
5 | 39/50 (78%) | 75/94 (79.79%) | 0.90 (0.39–2.08) | 0.801 | 62/73 (84.93%) | 52/71 (73.24%) | 2.06 (0.90–4.72) | 0.084 |
6a | 33/50 (66%) | 73/94(77.66%) | 0.56 (0.26–1.19) | 0.131 | 58/73 (79.45%) | 48/71 (67.61%) | 1.85 (0.87–3.94) | 0.107 |
6b | 0/0 (0%) | 0/0 (0%) | NE | NE | 0/0 (0%) | 0/0 (0%) | NE | NE |
7a | 1/50 (2%) | 0/94 (0%) | NE | 0.347 | 1/73 (1.37%) | 0/71 (0%) | NE | 1.000 |
7b | 0/0 (0%) | 0/0 (0%) | NE | NE | 0/0 (0%) | 0/0 (0%) | NE | NE |
8a | 17/50 (34%) | 17/94 (18.09%) | 2.33 (1.06–5.12) | 0.032 | 21/73 (28.77%) | 13/71 (18.31%) | 1.80 (0.82–3.96) | 0.140 |
8b | 2/50 (4%) | 2/94 (2.13%) | 1.92 (0.26–14.03) | 0.906 | 4/73 (5.48%) | 0/71 (0%) | NE | 0.135 |
9 | 1/50 (2%) | 0/94 (0%) | NE | 0.347 | 1/73 (1.37%) | 0/71 (0%) | NE | 1.000 |
10 | 1/50 (2%) | 0/94(0%) | NE | 0.347 | 1/73 (1.37%) | 0/71(0%) | NE | 1.000 |
11a | 1/50 (2%) | 4/94 (4.26%) | 0.46 (0.05–4.22) | 0.821 | 5/73 (6.85%) | 0/71 (0%) | NE | 0.074 |
11b | 1/1 (100%) | 2/5 (40%) | NE | 1.000 | 3/6 (50%) | 0/0 (0%) | NE | NE |
12a | 46/50 (92%) | 69/94 (73.40%) | 4.17 (1.36–12.76) | 0.008 | 60/73 (82.19%) | 55/71 (77.46%) | 1.34 (0.59–3.04) | 0.479 |
12b | 2/2 (100%) | 2/4 (50%) | NE | 0.467 | 2/3 (66.67%) | 2/3(66.67%) | 1.00 (0.03–29.81) | 1.000 |
13a | 50/50 (100%) | 94/94 (100%) | NE | NE | 73/73 (100%) | 71/71 (100%) | NE | NE |
13b | 48/50 (96%) | 89/94 (94.68%) | 1.35 (0.25–7.21) | 1.000 | 70/73 (95.89%) | 67/71 (94.37%) | 1.39 (0.30–6.46) | 0.970 |
14a | 46/50 (92%) | 73/94 (77.66%) | 3.31 (1.07–10.25) | 0.031 | 67/73 (91.78%) | 52/71 (73.24%) | 4.08 (1.52–10.95) | 0.003 |
14b | 0/0 (0%) | 0/0 (0%) | NE | NE | 0/0 (0%) | 0/0 (0%) | NE | NE |
15 | 3/50 (6%) | 5/94 (5.32%) | 1.14 (0.26–4.96) | 1.000 | 8/73 (10.96%) | 0/71 (0%) | NE | 0.012 |
16 | 50/50 (100%) | 94/94 (100%) | NE | NE | 73/73 (100%) | 71/71 (100%) | NE | NE |
17a | 0/50 (0%) | 0/94 (0%) | NE | NE | 0/73 (0%) | 0/71 (0%) | NE | NE |
17b | 0/50 (0%) | 0/93 (0%) | NE | NE | 0/72 (0%) | 0/71 (0%) | NE | NE |
18 | 2/2 (100%) | 4/4 (100%) | NE | NE | 3/3 (100%) | 3/3 (100%) | NE | NE |
19 | 44/50 (88%) | 76/94 (80.85%) | 1.74 (0.64–4.70) | 0.273 | 60/73 (82.19%) | 60/71 (84.51%) | 0.85 (0.35–2.04) | 0.709 |
20 | 6/50 (12%) | 2/94 (2.13%) | 6.27 (1.22–32.34) | 0.038 | 5/73 (6.85%) | 3/71 (4.23%) | 1.67 (0.38–7.25) | 0.746 |
21 | 29/50 (58%) | 45/94 (47.87%) | 1.50 (0.75–3.01) | 0.247 | 35/73 (47.95%) | 39/71 (54.93%) | 0.76 (0.39–1.46) | 0.402 |
22 | 45/50 (90%) | 73/94 (77.66%) | 2.59 (0.91–7.35) | 0.067 | 58/73 (79.45%) | 60/71 (84.51%) | 0.71 (0.30–1.67) | 0.430 |
23 | 1/50 (2%) | 0/94 (0%) | NE | 0.347 | 1/73 (1.37%) | 0/71 (0%) | NE | 1.000 |
24 | 2/50 (4%) | 0/94 (0%) | NE | 0.119 | 2/73 (2.74%) | 0/71 (0%) | NE | 0.497 |
25 | 6/50 (12%) | 3/94 (3.19%) | 4.14 (0.99–17.32) | 0.086 | 9/73 (12.33%) | 0/71 (0%) | NE | 0.007 |
CONSORT-CHM formulas, Consolidated Standards of Reporting Trials for Chinese herbal medicine formulas; CI, confidence interval; OR, odds ratio; NE, not estimable.
The mean OQS of studies with the first author from a university hospital was significantly higher than that of studies with the first author from a nonuniversity hospital (20.42 ± 3.16 vs 19.27 ± 2.08, MD: 1.16, 95% CI: 0.28–2.04,
In this study, we first summarized the number of circulating CPM with the indication for eczema in mainland China. Because most RCTs in mainland China did not have “TCM” or “CPM” in title, abstract, or keyword, we decided to search eligible CPM before retrieving literatures, rather than searching literature directly by using search terms “TCM” and “CPM.” As the result showed, 70 circulating CPMs had the indication for eczema in mainland China, and more than a third of eligible RCTs were published in recent five years, which demonstrated the wide application of CPM for eczema in mainland China. However, only 30% of included CPMs had the eligible RCTs, and 10 out of 21 CPMs had more than two eligible RCTs. The low proportions indicated that more efforts were needed to enhance the clinical evidence of CPM for eczema.
We also investigated the reporting quality of RCTs for the treatment of eczema with CPM by using the CONSORT-CHM formulas 2017, which added one item of “keywords” on the basis of the CONSORT statement. Our results showed that the mean OQS of 144 included RCTs was 19.85, only 52.24% of the maximum score (19.85/38), and few trials scored more than 70% of the maximum score. Similarly, a study on RCTs of TCM for diabetes mellitus in three top TCM journals showed that the total reporting rate of the CONSORT statement was only 45.0% [
The result showed that there were 16 items with a poor report rate (reported in below 50% of trials). Among them, some items are important and essential. When a trial has “randomized” or “RCT” in the title and keyword, it is easily retrieved and identified as a RCT. However, the proportions of two items were 2.78% and 3.47%, respectively, in this study. Other similar studies showed that 0.80%–5.9% of RCTs of TCM treatments mentioned randomization in the title [
Methodological items are pivotal elements for clinical trials. Sample size estimation can decrease the risk of false-negative results and obtain precise outcomes. The previous study showed that 50–200 subjects would need to be enrolled to reduce the risk of missing a true difference in cutaneous surgery therapeutic trials [
Randomization is the major hallmark of a RCT. Its ultimate objectives are to create balanced treatment groups and to minimize the risk of biased results [
Blinding is considered as an essential component for internal validity of RCTs. It aims to prevent bias associated with expectations from patients, investigators, and assessors. Treatment effects may be overestimated or underestimated without blinding [
Discrepancies between registered and published outcomes in clinical trials are common, which may make results attractive but also fake [
In this study, some items had an optimal reporting rate, such as harms. The safety of a drug is as important as its effectiveness, and only safe treatments could be widely applied in clinical practice. In our study, 83.33% of the trials reported adverse events of CPM during the treatment. All adverse events were mild and tolerable, and no serious adverse events were observed. Analogously, harms were reported in 80 out of 110 RCTs (72.72%) in five top dermatology journals [
Like some previous studies [
There are some limitations in this study. First, only CPMs with the indication for eczema were included. In clinical practice, numerous CPMs without the indication for eczema are used to treat eczema, such as Runzao Zhiyang capsule [
In conclusion, there are a large number of CPMs with the indication for eczema in mainland China; however, both the quantity and the reporting quality of RCTs regarding those CPMs are suboptimal. Therefore, more well-designed clinical trials are needed to enhance the level of evidence of CPM for eczema. Authors and journal editors are encouraged to learn and adhere to the CONSORT-CHM formulas 2017 to improve the reporting quality of the RCTs.
The data used to support the results of this study are included within the article and
The authors declare that there are no conflicts of interest regarding the publication of this paper.
Ming Li and Linfeng Li conceptualized and designed the study. Ming Li, Boyang Zhou, and Lihong Zhou conducted the search of CPM and literatures, extracted the data, and assessed the reporting quality. Ming Li and Boyang Zhou performed statistical analysis. Ming Li wrote the manuscript. Linfeng Li revised the manuscript.
Supplementary Table 1: checklist of items for the CONSORT-CHM formulas 2017. Supplementary Table 2: the list of Chinese patent medicine with the indication for eczema. Supplementary File 1: the list of 144 randomized controlled trials on Chinese patent medicine for eczema. Supplementary Table 3: the characteristics of 144 randomized controlled trials on Chinese patent medicine for eczema. Supplementary Table 4: the score of each item for 144 randomized controlled trials based on the CONSORT-CHM formulas 2017.