The Effectiveness And Mechanism Of Tonifying Kidney And Spleen Method On Preventing And Treatment Of Myelosuppression Induced By Adjuvant Chemotherapy Of Colorectal Cancer Ⅶ

3.3 Quality evaluation of included literature

Among the included literature, the high risk of bias mainly exists in the implementation of blinding of subjects and experimental personnel, allocation concealment and incomplete data results. (1) Generation of random sequence: 24 studies mentioned the method of random sequence generation and were rated as "low risk"; the rest were "unclear risk of bias". (2) Allocation concealment: 2 studies used central randomization or envelope method for concealment and were rated as "low risk"; 7 studies used alternating allocation, medical record number allocation, etc. and were rated as "high risk"; the rest were "unclear risk of bias". (3) Blinding of subjects and researchers: All studies were blank-controlled and could not be blinded, so they were rated as "high risk". (4) Blinding of outcome assessors: None of the studies mentioned the use of blinding for outcome assessors. However, the outcome indicators of this study were all laboratory measurements, or were determined based on laboratory measurements as raw data. The outcome assessors judged that the outcomes would not be affected by the lack of blinding, so it was rated as "low risk"; (5) Incomplete outcome reporting: 8 studies reported missing data, the number of missing data between groups and the reasons were unbalanced, or inappropriate methods were used to handle missing data, so they were rated as "high risk", 24 studies had no missing data, and were rated as "low risk", and the rest were rated as "unclear risk of bias". (6) Selective reporting: None of the studies mentioned the relevant information of the study protocol registration, and were rated as "unclear risk of bias". (7) Other biases: All studies reported the comparability of baseline data, which was rated as "low risk". (Figure 1-2, Figure 1-3)

Figure 1-2 Evaluation of specific projects included in the study ROB

Figure 1-3 Overview of bias risk of included studies

NEW HERBS FOR KIDNEY AND IMMUNITY ENHANCEMENT

3.4 Meta-analysis results

3.4.1 Main outcome indicators

(1) Incidence of leukopenia

Nine studies125-33 reported the incidence of leukopenia, 16 studies[34-49 reported the incidence of grade I/II/I/IV leukopenia, and another study[501 reported the incidence of grade I-II/III-IV leukopenia. After merging the data, it was found that the heterogeneity between the studies was not large (P=29%). The meta-analysis results showed that oral Chinese medicine can reduce the risk of leukopenia caused by adjuvant chemotherapy for colorectal cancer (RR=0.67,95%

CI[0.61,0.75],P<0.00001). (Figure 1-4)

Figure 1-4 Meta-analysis of the incidence of leukopenia caused by Chinese medicine + chemotherapy vs chemotherapy The inverted funnel plot shows a symmetrical trend, which basically supports the results of the meta-analysis. (Figure 1-5)

Figure 1-5 Meta-analysis of leukopenia caused by Chinese medicine + chemotherapy vs chemotherapy

(2) Incidence of hemoglobin reduction

Four studies125.2728.51 reported the incidence of hemoglobin reduction, and 10 studies134.35.3740.42.47.48I reported the incidence of grade I/II/I/IV hemoglobin reduction. The combined data found that the heterogeneity between the studies was small (I²=0%): The results of the meta-analysis showed that oral Chinese medicine can reduce the risk of hemoglobin reduction caused by adjuvant chemotherapy for colorectal cancer (RR=0.75, 95%CI[0.63,0.89], P=0.0009). (Figure 1-6)

Figure 1-6 Meta-analysis of the incidence of hemoglobin reduction in Chinese medicine + chemotherapy vs chemotherapy The inverted funnel plot showed an asymmetric trend, suggesting the possibility of publication bias. (Figure 1-7)

Figure 1-7 Meta-analysis of hemoglobin reduction in Chinese medicine + chemotherapy vs chemotherapy

(3) Incidence of thrombocytopenia

Seven studies [25.27.30-32.50.52| reported the incidence of thrombocytopenia, and 13 studies l34.35.3744.46-48] reported the incidence of grade I/I/II/IV thrombocytopenia. The combined data results showed that the heterogeneity between the studies was not large (P = 28%); the meta-analysis results showed that oral Chinese medicine can reduce the risk of thrombocytopenia caused by adjuvant chemotherapy for colorectal cancer (RR=0.71, 95%CI[0.60,0.82], P<0.0001). (Figure 1-8)

Figure 1-8 Meta-analysis of the incidence of thrombocytopenia caused by Chinese medicine + chemotherapy vs chemotherapy The inverted funnel plot showed a symmetrical trend, which basically supported the results of the meta-analysis. (Figure 1-9)

Figure 1-9 Meta-analysis of thrombocytopenia caused by Chinese medicine + chemotherapy vs chemotherapy

3.4.2 Secondary outcomes

(1) Incidence of bone marrow suppression

Five studies 133.51.53-51 reported the incidence of bone marrow suppression, and five studies [36.56-591 reported the incidence of grade I/II/I/IV bone marrow suppression. The combined data results showed that the heterogeneity between the studies was small (F²=0%); the meta-analysis results showed that taking Chinese medicine can reduce the risk of bone marrow suppression caused by adjuvant chemotherapy for colorectal cancer (RR=0.61, 95%CI[0.46,0.79], P=0.0003). (Figure 1-10)

Figure 1-10 Meta-analysis of the incidence of myelosuppression between traditional Chinese medicine + chemotherapy VS chemotherapy

(2) Incidence of neutropenia

One study l⁵2l reported the incidence of neutropenia, and two studies [40.43 reported the incidence of grade I/I/II/IV neutropenia. The combined data showed little heterogeneity between studies. (F=36%); Meta-analysis results show that oral Chinese medicine can reduce the risk of neutropenia caused by adjuvant chemotherapy for colorectal cancer (RR=0.60, 95%CI[0.46,0.79], P=0.0003) . (Figure 1-11)

Figure 1-11 Meta-analysis of the incidence of neutropenia between traditional Chinese medicine + chemotherapy VS chemotherapy

(3) Incidence of reduced red blood cells

One study [³2] reported the incidence of red blood cell cytopenias, and one study [4] reported the incidence of grade I/II/II/IV red blood cell cytopenias. The combined data showed that the heterogeneity between studies was small (P=0 %): Meta analysis results show that compared with the blank control, oral Chinese medicine has no significant difference in reducing the risk of red blood cell reduction caused by adjuvant chemotherapy for colorectal cancer (RR=0.91, 95%CI[0.58,1.41 ] ,P=0.66). (Figure 1-12)

Figure 1-12 Meta-analysis of the incidence of erythropenia in Chinese medicine + chemotherapy vs chemotherapy (4) Incidence of grade 3 bone marrow suppression

Five studies [36.56-59 reported the incidence of grade I/I/I/IV bone marrow suppression. The combined data showed that the heterogeneity between the studies was small (P=0%); the meta-analysis results showed that oral Chinese medicine can reduce the risk of grade 3 bone marrow suppression caused by adjuvant chemotherapy for colorectal cancer (RR=0.24, 95%CI[0.06,0.92], P=0.04). (Figure 1-14)

Figure 1-14 Meta-analysis of the incidence of grade ≥3 bone marrow suppression in TCM + chemotherapy VS chemotherapy

(5) Incidence of grade ≥3 leukopenia 17 studies reported the incidence of grade ≥3 leukopenia, of which 7 studies [40.42-45.47.50] had grade ≥3 leukopenia in the experimental group/control group, and the remaining studies had no grade ≥3 leukopenia in the experimental group/control group. The combined data results showed that the heterogeneity between the studies was small (²=0%); the meta-analysis results showed that taking TCM can reduce the risk of grade ≥3 leukopenia caused by adjuvant chemotherapy for colorectal cancer (RR=0.36, 95%CI[0.21,0.64], P=0.04). (Figure 1-15)