Literature search
The flowchart of the selection and screening process is shown in Fig. 1. Briefly, the electronic search yielded 8,760 records, after removing duplicates and screening titles and abstracts, a total of 1,648 reports were identified for the full-text assessment. Finally, we included 1,335 eligible RCTs for analysis, of which 1,262 articles with abstract and 37 without abstracts.
Characteristics Of Included Trials
A total of 1,335 RCTs of ICWM for UC were included between Jan 1998 to Feb 2022. The number of these studies increased gradually during the first 10 years, and then presented a rapid increase starting from 2009 (Fig. 2). The most common design of included studies was a single center (97.9%), two parallel arms (93.7%), sample size of 51–100 (70.1%), Chinese herbal formula (94.2%) as CM treatment, and intervention period within 30 days (48.9%). There were 470 (35.2%) studies applied CM diagnosis when recruited UC participants, while only 263 (19.7%) adopted CM-related outcomes to assess the efficacy of treatments. Around 98.5% (1,315) trials concluded a confirmed efficacy of ICWM for UC. However, the missing reporting is common for several critical aspects, such as 97.9% trials did not whether adopt blinding or not, and 75.5% trials did not specify the studied phase(s) of UC (e.g., active, remission, or both). Details are shown in Table 2.
Table 2
Characteristics of included articles (n = 1,335)
Characteristics | N (%) |
Study center | |
Single center | 1,307 (97.9) |
Multicenter | 20 (1.5) |
Not reported | 8 (0.6) |
Journal type | |
English journal, with impact factor 5–10 | 1 (0.07) |
English journal, with impact factor 3–5 | 2 (0.15) |
English journal, with impact factor < 3 | 2 (0.15) |
Chinese core journal | 57 (4.27) |
Chinese non-core journal | 1,273 (95.36) |
Sample size | |
>300 | 6 (0.45) |
101–300 | 266 (19.93) |
51–100 | 936 (70.11) |
≤ 50 | 127 (9.51) |
UC stages of trial participants | |
Active | 293 (21.95) |
Remission | 11 (0.82) |
Both | 21 (1.57) |
Not specified | 1,010 (75.66) |
Number of groups | |
2 | 1,251 (93.71) |
3 | 78 (5.84) |
4 or above | 6 (0.45) |
Blinding | |
Single-blinded | 9 (0.67) |
Double-blinded | 15 (1.12) |
Open label | 4 (0.3) |
Not reported | 1,307 (97.9) |
Intervention type of CM a | |
Chinese herbal formulas | 1,257 (94.16) |
Single herbs | 30 (2.25) |
Moxibustion | 21 (1.57) |
Acupuncture | 11 (0.82) |
Catgut-embedding therapy | 11 (0.82) |
Massage | 2 (0.15) |
Complex intervention b | 3 (0.22) |
Intervention period | |
≤ 30 days | 653 (48.91) |
31–60 days | 444 (33.26) |
61–90 days | 147 (11.01) |
>90 days | 24 (1.8) |
Not reported | 67 (5.02) |
Follow-up period | |
≤ 90 days | 54 (4.04) |
91–180 days | 87 (6.52) |
181–360 days | 58 (4.34) |
>360 days | 13 (0.97) |
Not reported | 1,123 (84.12) |
Type of controls | |
Integrated CM and WM | 1,260 (94.38) |
Including placebo and/or blank as controls | 15 (1.12) |
Solely WM as control | 55 (4.12) |
Solely CM as control | 4 (0.3) |
Solely WM and solely CM | 1 (0.07) |
Diagnostic criteria of UC | |
Both CM and WM | 464 (34.76) |
CM | 6 (0.45) |
WM | 753 (56.4) |
Not reported | 112 (8.39) |
CM-related outcomes | |
CM pattern score | 214 (16.03) |
CM symptoms c | 49 (3.67) |
Not reported | 1,072 (80.3) |
Conclusions on efficacy of ICWM | |
Confirmed efficacy | 1,315 (98.5) |
Beneficial | 20 (1.5) |
a Details were showed in Appendix 3. |
b Complex intervention was used in 2 studies: one used acupuncture combined with moxibustion, the other adopted single herb combined with moxibustion. |
c CM symptoms included the tongue and pulse manifestations. |
Reporting Completeness And Features
The results of adherence to the CONSORT, the CONSORT for Abstract, and ICWM-specific checklist items are presented in Table 3, 4, and 5. For the completeness of the CONSORT checklist, the median (IQR) reporting score was 29 (26–33). Specifically, the reporting quality was excellent (> 90%) in 8 items (2a, 6b, 11b, 12b, 14b, 15, 18, and 22); good (65–90%) in 4 items (4b, 5, 13a and 16); and poor (< 65%) in 25 items (1a, 2b, 3a, 3b, 4a, 6a, 7a, 7b, 8a, 8b, 9, 10, 11a, 12a, 13b, 14a, 17a, 17b, 19, 20, 21, 23, 24 and 25). For the CONSORT for Abstract, the reporting score was 18 (14–21). The quality of reporting was excellent (> 90%) in 3 items (3, 6 and 15); good (65–90%) in 1 item (10); and poor (< 65%) in 13 items (1, 2, 4, 5, 7, 8, 9, 11, 12, 13, 14, 16 and 17).
Table 3
Reporting assessment of included studies based on the CONSORT and ICWM-specific items (n = 1,335)
Section/topic | Item number and description | Fully reported | Partially reported | Not reported |
Title and abstract | 1a. Identification as a randomized trial in the title | 13 (0.97) | - | 1,322 (99.03) |
| 1b. Structured summary of trial design, methods, results, and conclusions | See Table 4 |
Introduction | | | | |
Background | 2a. Scientific background and explanation of rationale | 1,235 (92.51) | - | 100 (7.49) |
Objectives | 2b. Specific objectives or hypotheses | 449 (33.63) | - | 886 (66.37) |
Methods | | | | |
Trial design | 3a. Description of trial design (such as parallel, factorial) including allocation ratio | 3 (0.22) | 59 (4.42) | 1,273 (95.36) |
| 3b. Important changes to methods after trial commencement (such as eligibility criteria), with reasons | 13 (0.97) | - | 1,322 (99.03) |
Participants | 4a. Eligibility criteria for participants | 740 (55.43) | 452 (33.86) | 143 (10.71) |
| 4b. Settings and locations where the data were collected | 931 (69.74) | 85 (6.37) | 319 (23.90) |
Interventions | 5. The interventions for each group with sufficient details to allow replication, including how and when they were actually administered | 958 (71.76) | 371 (27.79) | 6 (0.45) |
Outcomes | 6a. Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed | 2 (0.15) | 542 (40.60) | 791 (59.25) |
| 6b. Any changes to trial outcomes after the trial commenced, with reasons | 1,335 (100) | - | - |
Sample size | 7a. How sample size was determined | 2 (0.15) | 3 (0.30) | 1,330 (99.63) |
| 7b. When applicable, explanation of any interim analyses and stopping guidelines | 31 (2.32) | - | 1,304 (97.68) |
Sequence generation | 8a. Method used to generate the random allocation sequence | 435 (32.58) | 801 (60.00) | 99 (7.42) |
| 8b. Type of randomisation; details of any restriction (such as blocking and block size) | 11 (0.82) | 424 (31.76) | 900 (67.42) |
Allocation concealment mechanism | 9. Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned | 16 (1.20) | 419 (31.39) | 900 (67.42) |
Implementation | 10. Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions | 5 (0.37) | - | 1,330 (99.63) |
Blinding | 11a. If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how | 2 (0.15) | 9 (0.67) | 1,324 (99.18) |
| 11b. If relevant, description of the similarity of interventions | 1,332 (99.78) | 3 (0.22) | - |
Statistical methods | 12a. Statistical methods used to compare groups for primary and secondary outcomes | 13 (0.97) | 1,065 (79.78) | 257 (19.25) |
| 12b. Methods for additional analyses, such as subgroup analyses and adjusted analyses | 0 (0) | - | 1,335 (100) |
Results | | | | |
Participant flow | 13a. For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome | 1,157 (86.67) | 171 (12.81) | 7 (0.52) |
| 13b. For each group, losses and exclusions after randomisation, together with reasons | 41 (3.07) | 31 (2.32) | 1,263 (94.61) |
Recruitment | 14a. Dates defining the periods of recruitment and follow-up | 161 (12.06) | 971 (72.73) | 203 (15.21) |
| 14b. Why the trial ended or was stopped | 1,335 (100) | - | - |
Baseline data | 15. A table showing baseline demographic and clinical characteristics for each group | 1,333 (99.40) | - | 2 (0.60) |
Numbers analyzed | 16. For each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups | 1,157 (86.67) | - | 148 (11.09) |
Outcomes and estimation | 17a. For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) | 0 (0) | 1,327 (99.40) | 8(0.6) |
| 17b. For binary outcomes, presentation of both absolute and relative effect sizes is recommended | 0 (0) | - | 1,335 (100) |
Ancillary analyses | 18. Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory | 1,335 (100) | - | - |
Harms | 19. All-important harms or unintended effects in each group | 480 (35.96) | 22 (1.65) | 833 (62.40) |
Discussion | | | | |
Limitations | 20. Trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses | 161 (12.06) | - | 1,174 (87.94) |
Generalizability | 21. Generalizability (external validity, applicability) of the trial findings | 9 (0.67) | - | 1,326 (99.33) |
Interpretation | 22. Interpretation consistent with results, balancing benefits and harms, and considering other relevant evidence | 1,335 (100) | - | - |
Other information | | | | |
Registration | 23. Registration number and name of trial registry | 3 (0.22) | - | 1,332 (99.78) |
Protocol | 24. Where the full trial protocol can be accessed, if available | 1 (0.07) | 1 (0.07) | 1,333 (99.85) |
Funding | 25. Sources of funding and other support (such as supply of drugs), role of funders | 3 (0.22) | 221 (16.55) | 1,111 (83.22) |
Table 4
Reporting assessment of included studies based on the CONSORT for Abstract checklist (n = 1,262)
Section/topic | Item number and description | Fully reported | Partially reported | Not reported |
Title | 1. Identification of the study as randomized | 13 (1.03) | - | 1,249 (98.97) |
Authors | 2. Contact details for the corresponding author | 174 (13.79) | - | 1,088 (86.21) |
Trial design | 3. Description of the trial design (e.g. parallel, cluster, non-inferiority) | 1,178 (93.34) | - | 84 (6.66) |
Participants | 4. Eligibility criteria for participants and the settings where the data were collected | 247(19.57) | 1,012 (80.19) | 3 (0.24) |
Interventions | 5.Interventions intended for each group | 790 (62.60) | 375 (29.71) | 97 (7.69) |
Objective | 6.Specific objective or hypothesis | 1,251 (99.13) | - | 11 (0.87) |
Outcome | 7.Clearly defined primary outcome for this report | 0 (0) | 656 (51.98) | 606 (48.02) |
Randomization | 8.How participants were allocated to interventions | 254 (20.13) | 892 (70.68) | 116 (9.19) |
Blinding | 9.Whether or not participants, care givers, and those assessing the outcomes were blinded to group assignment | 1 (0.08) | 12(0.95) | 1,249 (98.97) |
Numbers randomized | 10.Number of participants randomized to each group | 980 (77.65) | 11(0.87) | 271 (21.47) |
Recruiting objects | 11.Clinical Trial Status | 0 (0) | 641 (50.79) | 621 (49.21) |
Numbers analyzed | 12.Number of participants analyzed in each group | 29 (2.30) | 6 (0.48) | 1,227 (97.23) |
Outcome | 13.For the primary outcome, a result for each group and the estimated effect size and its precision | 0 (0) | 49 (3.88) | 1,213 (96.12) |
Harms | 14.Important adverse events or side effects | 136 (10.78) | 162 (12.84) | 964 (76.39) |
Results | 15.Generalized interpretation of outcome | 1,252 (99.21) | - | 10 (0.79) |
Trial registration | 16.Registration number and name of trial register | 0 (0) | 1 (0.08) | 1,261 (99.92) |
Funding | 17.Source of funding | 0 (0) | 224 (17.75) | 1,038 (82.25) |
Table 5
Reporting assessment of included studies based on ICWM-specific items (n = 1, 335)
Item number and description | Fully reported | Partially reported | Not reported |
Q1. Whether the feature of ICWM was presented in the section of "Title" (e.g., generalized term of ICWM, or specific CM and WM interventions provided in the title)? | 948 (71.01) | - | 387 (28.99) |
Q2. Whether the eligibility criteria of participants included both Chinese and western medical diagnostic criteria in the section of "Methods of Abstract"? | 199(15.77) | 1063(84.23) | - |
Q3. Whether the study objectives or hypotheses were focused on the "ICWM" interventions in Abstract? | 770 (61.01) | - | 492 (38.99) |
Q4. Whether the assessed outcomes included both CM and WM? | 170(25.91) | 486(74.09) | - |
Q5. Whether interpretation of studied ICWM interventions was reported in the section of “Conclusion of Abstract”? | 847(67.12) | - | 415 (32.88) |
Q6. Whether the "Keywords" reflected the feature or design of ICWM study? | 959 (71.84) | 332 (24.87) | 44 (3.30) |
Q7. Whether reason/rational about ICWM intervention for the studied condition was reported in the “Background”? | 221 (16.55) | 403 (30.19) | 711 (53.26) |
Q8. Whether any necessity/advantage about ICWM intervention for the studied condition was reported in the “Background”? | 107 (8.01) | - | 1,228 (91.99) |
Q9. Whether the study objectives or hypotheses were focused on the "ICWM" interventions (e.g., improve the efficacy/safety, or reduce the side-effects)? | 257 (19.25) | | 1,078 (80.75) |
Q10. Whether the eligibility criteria of participants included both Chinese and western medical diagnostic criteria in the section of "Methods"? | 225 (16.85) | 253 (18.95) | 857 (64.19) |
Q11. Whether the specific situation (e.g., treatment points, stages of diseases, types of conditions) of the ICWM usage was reported? | 321 (24.04) | - | 1,014 (75.96) |
Q12. Settings and locations where the trials were conducted (such as hospitals, clinics, research institutes) | 25 (1.87) | - | 1,311 (98.13) |
Q13. Whether the specific type/way (such as overlying, one-after-another, or add-on) of the combination of CM and WM was reported? | 1,213 (90.86) | - | 122 (9.14) |
Q14. In the ICWM group, whether CM intervention (s) was reported with sufficient details to allow replication, including how and when they were actually administered? | 1,017 (76.18) | - | 318 (23.82) |
Q15. In the ICWM group, whether WM interventions was reported with sufficient details to allow replication, including how and when they were actually administered? | 1,206 (90.34) | - | 129 (9.66) |
Q16. Whether the rationale for the choice of the control group(s) was provided? | 1,335 (100) | - | - |
Q17. In the control group, whether sufficient details were reported to allow replication, especially for the placebo? | 1,192 (89.29) | - | 143 (10.71) |
Q18. Whether any description of treatment providers’ background (e.g., qualification and/or experiences in ICWM, or whether the providers conducted CM and WM separately)? | 12 (0.90) | - | 1,323 (99.10) |
Q19. Whether any measures were adopted to evaluate or improve the compliance of participants? | 4 (0.30) | - | 1,331 (99.70) |
Q20. Whether the assessed outcomes included both CM and WM related indicators? | 270 (20.22) | - | 1,065 (79.78) |
Q21. For the studies with open-label, whether any reasons or explanations for such design was reported? | 0 (0) | - | - |
Q22. In the control group(s), did the placebo of WM invention(s) was included? If so, whether sufficient details were provided? | 5 (38.46) | - | 8 (61.54) |
Q23. In the control group(s), did the placebo of CM invention(s) was included? If so, whether sufficient details were provided? | 12 (92.31) | - | 1 (7.69) |
Q24. In the section of “Results”, whether any information about the participants exposed to ICWM treatment prior to recruitment was mentioned in the baseline data? | 0 (0) | - | - |
Q25. Whether any discussion about external validity of ICWM results was reported, particular in different environments? | 0 (0) | - | - |
Q26. Whether interpretation of studied ICWM interventions was reported in the section of “Discussion”? | 285 (21.35) | 520 (38.95) | 530 (39.70) |
Q27. Whether any potential conflicts of interests (involving different stakeholders, such as drug manufacturers, funding sources and trial sponsors) was clearly reported? | 7 (0.52) | 26 (1.95) | 1,302 (97.53) |
The reporting score of the ICWM-specific items was 13 (11–15). Four items were “excellent” (Q13, Q15, Q16, Q23), and “good” reporting in 5 items (Q1, Q5, Q6, Q14, Q17). The remaining 18 items were reported poorly (Q2, Q3, Q4, Q7, Q8, Q9, Q10, Q11, Q12, Q18, Q19, Q20, Q21, Q22, Q24, Q25, Q26, Q27), of which 16 items showed extremely low (< 33%), particular in the rationale for ICWM design with definite objectives or hypotheses, specific timepoint/ stage of integrative therapy for UC, CM-related diagnosis criteria and outcome(s), discussion about the internal and external validity of ICWM results and value of ICWM design were insufficient or not articulated in most studies. The total scores of the CONSORT, the CONSORT for Abstract, and ICWM-specific checklist items were significantly improved after 2010 (all P < 0.01; Table 6).
Table 6
Overall reporting quality scores for included studies, by subgroup
Year of publication(n) | For CONSORT items 1 | For CONSORT for Abstract items 2 | For ICWM-specific items 3 |
1998–2010 (n = 301) | 25 (23–28) | 16 (13–19) | 11 (9–12) |
2011–2022 (n = 1034) | 30 (27–33) * | 18 (15–22) * | 13 (12–15) * |
Total reports (n = 1,335) | 29 (26–33) | 18 (14–21) | 13 (11–15) |
1 A perfect score is 72 for the CONSORT checklist. |
2 A perfect score is 34 for the CONSORT for Abstract checklist. |
3 A perfect score is 54 for the ICWM-specific checklist. |
* Compared with 1998–2010, P <0.01. |