Study Note
Brief summary
Approximately 250 patients with advanced-stage breast cancer were randomly assigned to one of two arms. In one arm, the partners (or family members or friends) of the patients were trained in the technique of reflexology. They then provided reflexology to the patients about once a week for four weeks. In the other arm, the partners gave the patients some form of attention that was not further specified in the study. After four weeks, participants were free to continue the interventions. All patients were surveyed weekly on various aspects of their physical and psychological well-being. Statistical analysis was carried out rigorously. The arms were comparable in almost all aspects at the start of the study, except for age. However, this was taken into account in the statistical analyses. The quality of the patients' relationships with their study partners and the generally perceived social support were also assessed in both groups and showed no differences.
Following the treatments, particularly in the second, third, and fifth weeks of the study, the patients in the reflexology group reported a greater reduction in symptoms in two out of five areas assessed than those in the other arm. This applies to the questions from the Anderson Symptom Inventory regarding symptom severity and impairment of daily life. In particular, the questions about fatigue and pain were answered significantly more positively. At the same time, no differences could be shown in the other questionnaires, which addressed similar areas, such as physical functioning, satisfaction with social participation, and general quality of life.
One limitation of the study is that it was not stated whether the observed differences between the arms (greater improvement in fatigue and pain) were also significant in magnitude. Furthermore, interpreting the results is complicated by the fact that it was not specified what exactly the patients in the control arm received (did they also receive personal attention or even touch?). To explicitly attribute the effects to reflexology, the patients in the control arm should have been treated with a comparable, ordinary foot massage. Additionally, it should be noted that 20% of the patients dropped out within the first five weeks of the study, and 30% within the entire 11-week study period (only 3.5% due to death or severe illness). The dropout rate and reasons for dropout were comparable between the two arms, so an arm comparison was still valid. However, it can be concluded that neither attention (however it was delivered) nor reflexology in the home setting is suitable for all patients with advanced breast cancer and their study partners.
Es wurden ca. 250 Patientinnen mit Brustkrebs im fortgeschrittenen Stadium zufällig in eine von zwei Gruppen aufgeteilt. In der einen Gruppe wurden die Partner (oder Familienangehörige oder Freunde) der Patientinnen in der Technik der Reflextherapie geschult. Diese haben dann die Patientinnen für vier Wochen ungefähr einmal pro Woche mit einer Reflextherapie behandelt. In der anderen Gruppe haben die Partner den Patientinnen stattdessen irgendeine Art von Aufmerksamkeit zukommen lassen, die in der Studie nicht genauer beschrieben wird. Nach vier Wochen stand es den Teilnehmern offen, die Interventionen fortzusetzen. Alle Patientinnen wurden wöchentlich zu verschiedenen Belangen ihres physischen und psychischen Befindens befragt. Die statistische Analyse wurde nach allen Regeln der Kunst durchgeführt. Die Gruppen waren zu Beginn der Studie in fast allen Belangen außer dem Lebensalter vergleichbar. Dies wurde aber in den statistischen Analysen berücksichtigt. Auch die Qualität der Beziehung der Patientinnen zu ihrem Studienpartner und die grundsätzlich wahrgenommene soziale Unterstützung wurden in beiden Gruppen erfragt und zeigten keine Unterschiede. Nach den Behandlungen, v.a. in der zweiten, dritten und fünften Studienwoche gaben die Patientinnen der Reflextherapiegruppe in zwei von fünf erhobenen Belangen eine größere Symptomabnahme als in der anderen Gruppe an: dies betrifft die Fragen aus dem Fragebogen des Anderson Symptom Inventorys zur Symptomschwere und Beeinträchtigung des alltäglichen Lebens. V.a. die Fragen zu Fatigue und Schmerzen wurden deutlich positiver beantwortet. Gleichzeitig konnten keine Unterschiede in den anderen Fragebögen gezeigt werden, die ähnliche Belange abfragten, nämlich physisches Funktionieren, Zufriedenheit bezüglich der sozialen Teilhabe und der allgemeinen Lebensqualität. Ein Nachteil der Studie ist, dass nicht angegeben wurde, ob die gefundenen Unterschiede zwischen den Gruppen (mehr Verbesserung in Fatigue und Schmerzen) in ihrer Größenordnung auch bedeutsam sind. Desweiteren erschwert sich die Interpretation der Ergebnisse dadurch, dass nicht angegeben wurde, was genau die Patientinnen in der Kontrollgruppe bekommen haben (hat hier auch persönliche Zuwendung oder sogar Berührung stattgefunden?). Um die Effekte explizit der Reflexzonen-Massage zuschreiben zu können, hätte man die Patientinnen in der Kontrollgruppe mit einer vergleichbaren nur gewöhnlichen Fußmassage behandeln müssen. Des Weiteren ist anzumerken, dass 20% der Patientinnen die Teilnahme innerhalb der ersten fünf Studienwochen abgebrochen haben und 30% innerhalb des gesamten Studienzeitraums von 11 Wochen (davon nur 3,5 % wegen Tod oder zu starker Erkrankung). Die Abbruchrate und Abbruchgründe waren innerhalb beider Gruppen vergleichbar, so dass ein Gruppenvergleich dennoch legitim war. Allerdings lässt sich schließen, dass weder Aufmerksamkeit (wie auch immer diese stattgefunden hat) noch Reflextherapie im häuslichen Umfeld für alle fortgeschrittene Brustkrebspatientinnen und ihre Studienpartner geeignet ist.
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
|
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
|
?
|
| Exclusion criteria
|
?
|
| N randomized
|
-999
|
| 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.
|
?
|
| Specifications on analyses
|
?
|
| Countries of data collection
|
?
|
| LoE Level of evidence
|
?
|
| Outcome timeline Data collection times
|
?
|
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.
|
?
|
| Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included
|
?
|
| 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
|
?
|
| Comorbidities
|
?
|
| Current cancer therapies
|
?
|
| Specifications on cancer therapies
|
?
|
| Previous cancer therapies
|
?
|
| Gender
|
?
|
| Gender specifications
|
?
|
| Age groups
|
|
| Age groups specification
|
?
|
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
|
128
|
| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
|
N=0
|
| Drop-out reasons
|
NA
|
| Intervention
|
Foot reflexology
|
| Dosage and regime
|
Reflex therapy by study partners who were trained 2x in a 30min. protocol for reflex therapy by reflexologists (duration: 30 min., study weeks 1-4: minimum requirement 1x/week, real average 1.1/week; SW 5-11: no requirements, average 0.6/week)
|
| 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.
|
4
|
| Side effects / Interactions
|
NI
|
| 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
|
128
|
| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
|
N=0
|
| Drop-out reasons
|
NA
|
| Intervention
|
Attention by study partners
|
| Dosage and regime
|
Attention by study partners (duration: NI, 1x week, 4 weeks in total)
|
| 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.
|
4
|
| Side effects / Interactions
|
NI
|
Outcomes
Symptom load
| Outcome type As specificed by the authors
|
Primary
|
| Outcome specification
|
Summarized scale for symptom severity (study weeks 1-4, 5, 11)
|
| Type of measurement
|
MDASI (M. D. Anderson Symptom 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".
|
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".
|
Sig. lower (better) values for intervention arm than control arm (β= -4.34 [1.85]; p= 0.02), especially in week 2,3 and 5 (week 2: intervention arm: M=27.50 [1.53], control arm: M=33.65 [1.55]; p<0.01; week 3: intervention arm: M= 25. 50 [1.55], control arm: M=30.98 [1.55]; p=0.01; week 5: intervention arm: M=24.64 [1.52], control arm: M=30.50 [1.48]; p<0.01), mainly explained by an improvement in the symptoms fatigue and pain.
|
| 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
|
?
|
Functionality
| Outcome type As specificed by the authors
|
Primary
|
| Outcome specification
|
Summarized scale for restrictions of daily life (study week 1-4, 5, 11)
|
| Type of measurement
|
MDASI (M. D. Anderson Symptom 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".
|
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".
|
Sig. lower (better) values for intervention arm than control arm (β= -3.69 [1.39]; p<0.01) especially in weeks 2,3 and 5 (week 1: intervention arm: M= 14.60 [1.15], control arm: M= 18. 32 [1.17]; p=0.02; week 3: intervention arm: M=11.84 [1.17], control arm: M= 17.57 [1.17]; p<0.01; week 5: intervention arm: M=12.30 [1.15]; control arm: M=16.60 [1.12]; p<0.01)
|
| 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
|
?
|
Physical functioning
| Outcome type As specificed by the authors
|
Secondary
|
| Outcome specification
|
Short forms of the PROMIS: Scale for physical functioning (study weeks 3, 5, 11)
|
| Type of measurement
|
PROMIS (Patient-Reported Outcomes Measurement Information System)
|
| 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".
|
No sig. differences between the arms (β= 0.195 [0.67]; p=0.77)
|
| 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
|
?
|
| Outcome specification
|
PROMIS short forms: Satisfaction with regard to social participation (study weeks 3, 5, 11)
|
| Type of measurement
|
PROMIS (Patient-Reported Outcomes Measurement Information System)
|
| 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".
|
No sig. differences between the arms (β= 1.659 [0.88]; p=0.06)
|
| 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
|
Study week 3,5,11
|
| 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".
|
No sig. differences between the arms (β= 0.599 [0.36]; p=0.10)
|
| 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
?
