Effectiveness of Chinese herbal medicine for cancer palliative care: overview of systematic reviews with meta-analyses

Chinese herbal medicines (CHM) are often used in managing cancer related symptoms but their effectiveness and safety is controversial. We conducted this overview of meta-analyses to summarize evidence on CHM for cancer palliative care. We included systematic reviews (SRs) with meta-analyses of CHM clinical trials on patients diagnosed with any type of cancer. Methodological quality of included meta-analyses was assessed with the Methodological Quality of Systematic Reviews (AMSTAR) Instrument. Fifty-one SRs with meta-analyses were included. They covered patients with lung (20 SRs), gastric (8 SRs), colorectal (6 SRs), liver (6 SRs), breast (2 SRs), cervical (1 SR), esophageal (1 SR), and nasopharyngeal (1 SR) cancers. Six SRs summarized evidence on various types of cancer. Methodological quality of included meta-analyses was not satisfactory. Overall, favorable therapeutic effects in improving quality of life among cancer patients have been reported. Conflicting evidence exists for the effectiveness of CHM in prolonging survival and in reducing chemotherapy and/or radiotherapy related toxicities. No serious adverse effects were reported in all included studies. Evidence indicated that CHM could be considered as an option for improving quality of life among patients receiving palliative care. It is unclear if CHM may increase survival, or reduce therapy related toxicities.


Appendix 1. Search strategies and results for meta-analysis on Chinese herbal medicine for cancer palliative care i) Cochrane Database of Systematic Reviews (CDSR) from inception to 3/9/2014
Appendix 2. Detailed operational guide for applying the AMSTAR tool* Amstar 1. Was an 'a priori' design provided?
The research question and inclusion criteria should be established before the conduct of the review. Operational Definition (OD): A "Yes" will be given if the review has published a protocol for the systematic review.

 Yes  No
Amstar 2. Was there duplicate study selection and data extraction?
There should be at least two independent data extractors and a consensus procedure for disagreements should be in place. OD: A "Yes" will be given if: (i) Two reviewers performed study selection, AND (ii) Two reviewers performed data extraction AND (iii) Consensus process was implemented for resolving disagreement.
 Yes (i + ii + iii)  No (These 3 criteria were not fulfilled)  Could not answer (i.e. not reported)

Amstar 3. Was a comprehensive literature search performed?
At least two electronic sources should be searched. The report must include years and databases used (e.g., CENTRAL, EMBASE, and MEDLINE). Key words and/or MESH terms must be stated and where feasible the search strategy should be provided. All searches should be supplemented by consulting current contents, reviews, textbooks, specialized registers, or experts in the particular field of study, and by reviewing the references in the studies found. OD: A "Yes" will be given if at least two electronic sources plus one supplementary strategy were used (e.g. Cochrane register/CENTRAL counts as two sources; a grey literature search counts as supplementary

Amstar 4. Was the status of publication (i.e. grey literature) used as an inclusion criterion?
The authors should state that they searched for reports regardless of their publication type. The authors should state whether or not they excluded any reports from the systematic review, based on their publication status, language etc. If review indicates that there was a search for "grey literature" or "unpublished literature," indicate "yes." SIGLE database, dissertations, conference proceedings, and trial registries are all considered grey for this purpose. If searching a source that contains both grey and non-grey, must specify that they were searching for grey/unpublished literature. OD: If eligibility criterion is restricted to "non-grey" literature, a "No" will be given, which indicates a methodological shortcoming in this domain.
 Yes  No  Could not answer (i.e. not reported)

Amstar 5. Was a list of studies (included and excluded) provided?
A list of included and excluded studies should be provided. OD: A "Yes" will be given if the included and excluded studies are referenced.

 Yes  No
Amstar 6. Were the characteristics of the included studies provided?
In an aggregated form such as a table, data from the original studies should be provided on the participants, interventions and outcomes. The ranges of characteristics in all the studies analyzed e.g., age, race, sex, relevant  Yes  No socioeconomic data, disease status, duration, severity, or other diseases should be reported. OD: A "Yes" will be given if the information described above is presented appropriately. Amstar 7. Was the scientific quality of the included studies assessed and documented? 'A priori' methods of assessment should be provided (e.g., the use of Cochrane Risk of Bias tool as a mean to assessment); for other types of studies alternative tools will also be acceptable. OD: To score a "Yes", the authors should report risk of bias level in each of the methodological domain included in the risk of bias assessment tool that the authors have chosen to use. The results of the methodological rigor and scientific quality should be considered in the analysis and the conclusions of the review, and considerations on how risk of bias among included study may impact conclusion should be explicitly stated. OD: To score a "Yes", the reviewers must consider risk of bias explicitly when writing the conclusion section of the MA. For example, a reviewer may state: the results should be interpreted with caution due to high risk of bias among included studies. A "No" will be given if answer to Q7 is "No".

 Yes  No
Amstar 9. Were the methods used to combine the findings of studies appropriate?
For meta-analysis, statistical tests should be done to ensure that the studies were combinable by assessing their homogeneity. This can be done by using the Cochran Q test or reporting the I 2 value. OD: "Yes" will be given when one of the two situation applies: (i) Homogeneity is found, and authors used fixed effect model or random effect model, or (ii) Heterogeneity is found, and authors performed appropriate subgroup analysis or meta-regression.
"No" will be given when one of the two situation applies: (i) Heterogeneity is found, and authors used fixed or random effect model and reported the results directly without highlighting the role of heterogeneity; (ii) Heterogeneity is not assessed or reported.

Amstar 10. Was the likelihood of publication bias assessed?
An assessment of publication bias should include a combination of graphical aids (e.g., funnel plot) and/or statistical tests (e.g., Egger regression test). OD: A "No" will be given if no relevant test values or funnel plot was reported. However, a "Yes" will still be given if authors mentioned that publication bias could not be assessed because there were fewer than 10 included studies 1 .