Lua et al. (2015): Effects of inhaled ginger aromatherapy on chemotherapy-induced nausea and vomiting and health-related quality of life in women with breast cancer

Reference ↗
Title	Effects of inhaled ginger aromatherapy on chemotherapy-induced nausea and vomiting and health-related quality of life in women with breast cancer
Topic	Ginger
Author	Lua, P, Salihah, N, Mazlan, N
Year	2015
Journal	Complementary Therapies in Medicine
DOI	http://dx.doi.org/10.1016/j.ctim.2015.03.009

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	Prospective
Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals	Multicentric
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	Single
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	Yes
Number of arms	2

Study characteristics

Inclusion criteria	Women aged 18 years and above, with a normal sense of smell; who were diagnosed with breast cancer; whowere receiving chemotherapy and experienced nausea and/or vomiting of any severity; had at least two remaining chemotherapy courses using similar chemotherapeutic agents; consenting to participate in the study.
Exclusion criteria	Patients with other malignancies, being allergic to ginger, perfumes or cosmetics or patients undergoing concurrent radiotherapy.
N randomized	60
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.	mITT Analysis
Specifications on analyses	Two-factor (arm and time) analyses of variance
Countries of data collection	Malaysia
LoE Level of evidence	Level 2 Oxford 2011
Outcome timeline Data collection times	T0: Baseline (before chemotherapy) T1: Day 1 (day of chemotherapy) T2: Day 2 T3: Day 3 T4: Day 4 T5: Day 5 T6: Day 8

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.	Curative
Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included	Breast 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	Early Stage, Advanced Stage
Specifications on cancer stages	Stage I: n = 3 Stage II: n = 18 Stage III: n = 7 Stage IV: n = 2
Comorbidities	NI
Current cancer therapies	Chemotherapy
Specifications on cancer therapies	NI
Previous cancer therapies	NI
Gender	Female
Gender specifications	100% female
Age groups	Adults (18+)
Age groups specification	Mean±SD: 47.3±9.26 years

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	38
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	8
Drop-out reasons	Reasons: delayed chemotherapy > 2 weeks: n = 3 very mild dizziness: n = 1 decline further study participation: n = 4
Intervention	Ginger essential oils
Dosage and regime	Antiemetics + bottle with 2 drops of ginger oil Glass pendant (in the form of a small flask), to be hung approx. 20 cm from the nose, the bottle was held directly under the nose and inhaled deeply at least 3 times a day for 2 minutes each time Start: Day 1 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	Very mild dizziness or light-headedness on day-5 of aromatherapy treatment n= 1

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	37
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	7
Drop-out reasons	Reasons: delayed chemotherapy > 2 weeks: n = 3 time problem: n = 1 decline further study participation: n = 3
Intervention	Ginger frangance oil (placebo)
Dosage and regime	Worn for 5 days at a time from the day of the chemotherapy, inhaled deeply at least 3 times a day for 3 periods of 2 minutes each Start: Day 1 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	No side effects were reported

Outcomes

Nausea

Outcome type As specificed by the authors	Primary
Outcome specification	Severity of nausea, incidence of vomiting ( day 1 of chemotherapy to day 5 of chemotherapy)
Type of measurement	VAS (Visual Analogue Scale)
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".	Day 1 of chemotherapy: Severity of nausea: intervention-arm significantly less nausea than placebo-arm (treatment effect) VAS-Score in mm (mean(SD)) intervention vs. placebo: 38.98(21,65) vs. 42.95(24,82; p=0.040) Incidence of vomiting: no significant arm difference p=0.736
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".	NA

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	Secondary
Outcome specification	Influence of CINV on health-related quality of life at T0 (Baseline), T6 (Day 8 of chemotherapy) with regard to physical, role, emotional, cognitive and social function, fatigue, nausea/vomiting, pain, dyspnea, insomnia, loss of appetite, constipation, diarrhea, financial difficulties
Type of measurement	EORTC QLQ (European Organisation for Research and Treatment of Cancer Core/ Quality of Life questionnaire)
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".	NA
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".	Quality of life: Total score (day 8 of chemotherapy): Intervention-arm significantly superior MD 4.44, 95%CI 1.13 to 7.76, p<0.001 Subcategories (day 8 of chemotherapy), intervention-arm significantly superior in terms of: Role function: MD 1.94, 95%CI -5.35 to 9.24, p=0.001 Fatigue: MD -3.15, 95%CI -8.06 to 1.77, p=0.002 Nausea / vomiting: MD -3.61, 95%CI -7.51 to 0.29, p<0.001 Pain: MD -2.78, 95%CI -6.59 to 1.03, p=0.017 Loss of appetite: MD -6.67, 95%CI -12.50 to -0.83, p<0.001 Constipation: MD -1.67, 95%CI -6.25 to 2.92, p=0.046 Effect of role function and loss of appetite clinically relevant (10 point 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	?

Unspecified effects

Outcome type As specificed by the authors	Secondary
Outcome specification	Evaluation of aromatherapy (odor, applicability, treatment effects)
Type of measurement	Observation
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 differences between arms.
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".	NA

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	Financial support for this project was pro-vided by the Universiti Sultan Zainal Abidin.
Conflicts of Interest	None declared.

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	?