Özdelikara et al. (2017): The Effect of Reflexology on Chemotherapy-induced Nausea, Vomiting, and Fatigue in Breast Cancer Patients

Reference ↗
Title	The Effect of Reflexology on Chemotherapy-induced Nausea, Vomiting, and Fatigue on Breast Cancer Patients.
Topic	Reflexology
Author	Özdelikara, A, Tan, M
Year	2017
Journal	Asia-Pacific Journal of Oncology Nursing
DOI	https://doi.org/10.4103/apjon.apjon_15_17

Brief summary

In this study, 60 breast cancer patients were randomly assigned to an arm with reflex therapy or a control arm. In both arms, nausea, fatigue and quality of life were assessed using corresponding questionnaires. The results were presented separately in two publications. The study has considerable methodological shortcomings: Over 50 statistical tests were applied without using a statistical correction, which should be used for 20 tests or more. The results of this study are therefore not meaningful.

In dieser Studie wurden 60 Brustkrebspatientinnen zufällig einem Arm mit Reflextherapie oder einem Kontrollarm zugeteilt. In beiden Arme wurde Übelkeit, Fatigue und Lebensqualität mit entsprechenden Fragebögen erhoben. Die Ergebnisse wurden in zwei Veröffentlichungen getrennt voneinander präsentiert (s.u.). Die Studie weist erhebliche methodische Mängel auf: Es wurden über 50 statistische Tests angewendet ohne eine statistische Korrektur zu verwenden, die man bereits ab 20 Tests verwenden sollte. Die Ergebnisse dieser Studie sind daher nicht aussagekräftig.

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	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	No
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	Being older than 18, knowing the diagnosis of the disease, receiving no radiotherapy, receiving an epirubicin and cyclophosphamide, having received no reflexology therapy before, literate in Turkish, having no hemorrhage, epilepsy, or fever, having no paraplegia or thrombosis, having no gall-kidney stones, having no leg varicosis and foot disease (open wound or fracture on foot), having no diagnosis of psychiatric disorder or dementia, having accepted to participate in the study.
Exclusion criteria	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.	NI
Specifications on analyses	t-test
Countries of data collection	Turkey
LoE Level of evidence	1b Oxford 2009
Outcome timeline Data collection times	NI

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-III
Comorbidities	NI
Current cancer therapies	Chemotherapy
Specifications on cancer therapies	First chemotherapy cycle between April 2011 and October 2013
Previous cancer therapies	NI
Gender	Female
Gender specifications	100 % female
Age groups	Adults (18+)
Age groups specification	Mean (SD): 51 years (11.12)

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	30
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	NI
Drop-out reasons	NI
Intervention	Reflextherapy
Dosage and regime	From the 2nd-4th chemotherapy cycle, during chemotherapy duration: 30-40min
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.	-999
Side effects / Interactions	NI

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	30
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	NI
Drop-out reasons	NI
Intervention	Chemotherapy and usual Care, Routine nursing care (antiemetic application, follow-up of vital signs and laboratory findings and consultancy for chemotherapy, etc.)
Dosage and regime	NA
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.	-999
Side effects / Interactions	NI

Outcomes

CINV (Chemotherapy-Induced Nausea and Vomiting)

Outcome type As specificed by the authors	Primary
Outcome specification	Baseline within 24h after the 1st chemotherapy cycle and three further posttreamtent measurements, each 24h after the 2nd-4th chemotherapy cycle. Baseline within 24h after the 1st chemotherapy cycle and three further posttreamtent measurements, each 24h after the 2nd-4th chemotherapy cycle. INVR: Subscale of experience
Type of measurement	Rhodes Inventory of Nausea
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".	Significant difference between the two arms compared to baseline (mean [SD]: intervention: 18.00 [7.51], placebo: 11.03 [11.24]; p= <0.05). No significant difference at the last measurement time point (mean [SD]: intervention: 3.90 [6.89], placebo: 6.56 [4.09]; p= >0.05).
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	?

CINV (Chemotherapy-Induced Nausea and Vomiting)

Outcome type As specificed by the authors	Primary
Outcome specification	INVR: Subscale of symptom development
Type of measurement	Rhodes Inventory of Nausea
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".	Significant difference between the two arms at baseline (mean [SD]: intervention: 11.10 [4.74], placebo: 6.76 [6.85]; p= <0.05). Significant difference at the last measurement time point (mean [SD]: intervention: 2.50 [4.34], placebo: 9.00 [5.29]; p= 0.000).
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	?

CINV (Chemotherapy-Induced Nausea and Vomiting)

Outcome type As specificed by the authors	Primary
Outcome specification	INVR: Subscale of distress development
Type of measurement	Rhodes Inventory of Nausea
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".	Significant difference between the two arms at baseline (mean [SD]: intervention: 6.90 [2.90]; placebo: 4.2 [4.47]: p= <0.05). Significant difference at the last measurement time point (mean [SD]: intervention: 1.40 [2.59];, placebo: 5.73 [3.55]; p= 0.000).
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	?

Fatigue

Outcome type As specificed by the authors	Secondary
Outcome specification	Fatigue severity
Type of measurement	?, BFI (Brief Fatigue Inventory)
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".	Significant difference between the two arms at baseline (mean [SD]: arm A: 3.67 [1.94], arm B: 1.97 [1.59]; p= 0.000). Significant difference at the last measurement time point (mean [SD]: intervention: 1.20 [1.44], placebo: 2.33 [1.65]; p< 0.05).
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	?

Fatigue

Outcome type As specificed by the authors	Secondary
Outcome specification	Daily life activity exposure levels
Type of measurement	BFI (Brief Fatigue Inventory)
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".	Significant difference between the two arms at baseline (mean [SD]: intervention: 1.88 [1.26], placebo: 1.01 [1.16]; p= <0.05). Significant difference at the last measurement time point (mean [SD]: intervention: 0.41 [0.65], placebo: 1.47 [1.52]; p= 0.001).
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	?
Conflicts 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	?

Additional Notes

?