Li et al. (2018): Efficacy of Ginger in Ameliorating Acute and Delayed Chemotherapy-Induced Nausea and Vomiting Among Patients With Lung Cancer Receiving Cisplatin-Based Regimens: A Randomized Controlled Trial

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Title	Efficacy of Ginger in Ameliorating Acute and Delayed Chemotherapy-Induced Nausea and Vomiting Among Patients With Lung Cancer Receiving Cisplatin-Based Regimens: A Randomized Controlled Trial
Topic	Ginger
Author	Li, X, Qin, Y, Liu, W, Zhou, X, Li, Y, Wang, L
Year	2018
Journal	Integrative cancer therapies
DOI	https://doi.org/10.1177/153473541775354

Brief summary

In this study, 146 lung cancer patients undergoing chemotherapy were randomly divided into two groups. One group received a capsule containing 250 mg of ginger powder twice daily for 5 days from the start of chemotherapy, while the other group received a placebo. In addition, both groups received standard anti-nausea/anti-vomiting medication. Ginger did not improve nausea/vomiting or quality of life compared to placebo. There were no side effects associated with ginger use. Many patients were able to guess which group they were assigned to, which may have influenced the results. The study is characterized by a clear and understandable presentation of results.

In dieser Studie wurden 146 Lungenkrebspatienten unter Chemotherapie zufällig in zwei Gruppen aufgeteilt. Die eine Gruppe erhielt ab Beginn der Chemotherapie für 5 Tage zweimal täglich eine Kapsel mit 250mg Ingwerpulver, die andere Gruppe erhielt ein Placebo. Zusätzlich bekamen beide Gruppen Standardmedikamente gegen Übelkeit/Erbrechen. Die Einnahme von Ingwer hat im Vergleich zu Placebo zu keiner Verbesserung von Übelkeit/Erbrechen oder der Lebensqualität geführt. Es wurden keine Nebenwirkungen im Zusammenhang mit der Ingwereinnahme festgestellt. Viele Patienten konnten erraten, welcher Gruppe sie zugeteilt waren, was die Ergebnisse beeinflussen könnte. Die Studie zeichnet sich durch eine übersichtliche und verständliche Darstellung der Ergebnisse aus.

Study Design

Prospective / Retrospective Prospective: forward-looking, examples include clinical trials, cohort studies, and long-term observational studies;</br>Retrospective: backward-looking, relying on existing data, examples include case-control studies and retrospective cohort studies	Retrospective
Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals	Monocentric
Blinding No: Open, all parties are aware of group assignments;</br>Single: one party is unaware of group assignments (generally participants);</br>Double: two parties are unaware of group assignments (generally the participants and the researchers); </br>Triple: concealing group assignment from additional parties	Double
Is randomized	Yes
Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control	No
Number of arms	2

Study characteristics

Inclusion criteria	Age of at least 18 years; a diagnosis of lung cancer; patients receiving cisplatin-based regimens; patients receiving standard antiemetic therapy (5-HT3 RAs); the ability to swallow capsules; nonuse of self-prescribed therapies or complementary products
Exclusion criteria	Allergy to ginger; pregnancy or lactation; current radiotherapy; preexisting nausea or vomiting from any cause; the presence of other diseases as a possible cause of nausea or vomiting (hepatitis, gastrointestinal obstruction, or diseases); use of coumadin or heparin for therapeutic anticoagulation; blood disorders or a platelet count <100 000/µL
N randomized	146
Analysis PP: Per Protocol analysis, i.e. only participants included who adhered to the study protocol.</br>ITT: Intention-to-treat analysis, i.e. all randomized participants included regardless of any drop-outs or changes in assignment.</br>mITT: modified Intention-to-treat analysis can refer to analyses in which participants with missing outcome data are excluded or it can refer to analyses in which only participants who received at least one treatment dose are included. In this case, participants dropped out of the study prematurely for reasons unrelated to the treatment.	PP Analysis
Specifications on analyses	Baseline characteristics, QoL, and severity of acute and delayed nausea and vomiting were compared between the 2 groups using independent samples t/nonparametric tests for continuous variables and Pearson’s χ2/Fisher’s exact tests for categorical variables. Incidence of acute and delayed nausea and vomiting was calculated as a binary variable (“yes” if participants had nausea or vomiting or “no” if participants had no nausea or vomiting) and was compared with a Pearson χ2 test. Two-tailed tests with a significance level of .05 were used for all analyses.
Countries of data collection	China
LoE Level of evidence	Level 2 Oxford 2011
Outcome timeline Data collection times	T0: Baseline T1: Acute symptoms 2 days after chemotherapy T2: 5 days after chemotherapy

Characteristics of participants

Setting Refers to cancer therapy setting.</br>- Curative therapy: aims to completely eradicate a disease and achieve a full recovery; </br>- Neo-adjuvant therapy: form of curative therapy, given before the primary treatment for cancer (usually surgery); </br>- Adjuvant therapy: form of curative therapy, given after the primary treatment for cancer (usually surgery); </br>- Palliative therapy: focuses on providing relief from symptoms and improving the quality of life for patients, without necessarily targeting the underlying disease; </br>- Active surveillance: involves close monitoring of disease progression without any intervention (typically used for prostate cancer);</br>- No therapy setting: Patients who completed therapy/are currently not in cancer treatment, cancer survivors.	NI
Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included	Lung Cancer
Cancer stages Early Stage: generally refers to cancer that is localized to the area where it started, mostly stages I and II;</br>Advanced Stage: cancer that has spread beyond its original site, mostly stages III and IV, with stage IV indicating distant metastasis	?
Specifications on cancer stages	NI
Comorbidities	NI
Current cancer therapies	Chemotherapy
Specifications on cancer therapies	Cisplatin-based chemotherapy (few patients with carboplatin or oxaliplatin)
Previous cancer therapies	NI
Gender	Mixed
Gender specifications	Male n(%) per group: ginger-group: 53 (74.65), placebo-group: 47 (68.12) Female n(%) per group: ginger-group: 18 (25.35), placebo-group: 22 (31.88)
Age groups	Adults (18+)
Age groups specification	Age in years, mean (SD) per group: ginger-group: 57.52 (7.24), placebo-group: 57.46 (7.82)

Arms

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Intervention
Number of participants (arm) N randomized	73
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	2
Drop-out reasons	Lack of compliance (n=2)
Intervention	Powdered ginger capsules with 5% gingerol + all participants received standard antiemetic treatment (5-HT3 Ras, ondansetron and dexamethasone), n=92 (65.7%) received aprepitant additionally
Dosage and regime	2x250mg (5% gingerol) every 12 hours from the first day of chemotherapy
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	5
Side effects / Interactions	According to authors no side effects / interactions due to study intervention

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Placebo
Number of participants (arm) N randomized	73
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	4
Drop-out reasons	Lack of compliance (n=4)
Intervention	Placebo with corn starch + all participants received standard antiemetic treatment (5-HT3 Ras, ondansetron and dexamethasone), n=92 (65.7%) received aprepitant additionally
Dosage and regime	2x250 mg every 12 hours from the first day of chemotherapy
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	5
Side effects / Interactions	According to authors no side effects / interactions due to study intervention

Outcomes

CINV (Chemotherapy-Induced Nausea and Vomiting)

Outcome type As specificed by the authors	Primary
Outcome specification	Incidence and intensity of acute CINV
Type of measurement	MAT (Multinational Association of Supportive Care in Cancer-Antiemesis Tool)
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	No significant group differences for incidence of nausea: ginger vs. placebo: 69.0% vs. 56.5% (p=0.174), incidence of vomiting: ginger vs. placebo: 8.5% vs. 15.9% (p=0.309), in the mean nausea scores (p=0.246) and the frequency of vomiting (p=0.256); no differences even after controlling for the intake of aprepitant 2 days after chemotherapy
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NI

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	?
Bias due to deviation from intended intervention (assignment to intervention)	?
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	?
Bias in measurement of the outcome	?
Bias in selection of the reported result	?
Other sources of bias	?
Overall RoB judgment	?

CINV (Chemotherapy-Induced Nausea and Vomiting)

Outcome type As specificed by the authors	Primary
Outcome specification	Incidence and intensity of delayed CINV
Type of measurement	MAT (Multinational Association of Supportive Care in Cancer-Antiemesis Tool)
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NI
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	No significant group differences for nausea: ginger vs. placebo: 60.6% vs. 72.5% (p=0.214), vomiting: ginger vs. placebo: 22.5% vs. 26.1% (p=0.813), in mean nausea scores (p=0.347) and frequency of vomiting (p=0.71)

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	?
Bias due to deviation from intended intervention (assignment to intervention)	?
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	?
Bias in measurement of the outcome	?
Bias in selection of the reported result	?
Other sources of bias	?
Overall RoB judgment	?

Quality of life

Outcome type As specificed by the authors	Others
Outcome specification	Specified type of measurement: FACT-G (General)
Type of measurement	FACT (Functional Assessment of Cancer Therapy)
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NI
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	Ginger vs. placebo, mean (SD): 72.79 (14.00) vs. 72.45 (13.93), p=0.884, no significant group difference

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	?
Bias due to deviation from intended intervention (assignment to intervention)	?
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	?
Bias in measurement of the outcome	?
Bias in selection of the reported result	?
Other sources of bias	?
Overall RoB judgment	?

Funding and Conflicts of Interest

Funding	The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the Peking Union Medical College Hospital.
Conflicts of Interest	According to authors no conflict of interest

Further points for assessing the study

Sample

Power analysis performed	?
- Sample size corresponds to power analysis
- Reasons for insufficient sample size based on power analysis
If no power analysis performed: at least moderate sample size (n >= 30 per arm)	?
Ethnicity mentioned	?

Alternative Explanation

Other explanations for an effect besides the investigated intervention
- Possibility of attention effects	?
- Possibility of placebo effects	?
- Other reasons	?

Statistics

Correct use of parametric and non-parametric tests Testing for normal distribution only necessary if parametric tests are used, NI: use of parametric tests without report of normal distribution testing
Correction for multiple testing	?
Measurement of compliance	?
Consistent reporting in numbers (figures, flowchart, abstract, results)	?
Comprehensive and coherent reporting	?
Cross-over
- Sufficient washout period	?
- Tested for carry-over effects	?
- Tested for sequence effects	?

Interpretation of results

Effect sizes reported (clinical vs. statistical significance)	?
Side effects systematically recorded	?
Side effects considered in result interpretation	?
Ethics votum	?