Study Note
Brief summary
In this study, various leukemia patients were divided into two different arms prior to bone marrow transplantation. One arm began taking vitamin E seven days before the operation until 28 days afterwards in addition to chemotherapy, while the other received only a placebo instead. The two arms did not differ in terms of the average duration of mucositis (i.e. inflammation of the mucous membranes, a typical side effect of chemotherapy) and neutropenia (i.e. the most common form of white blood cell depletion). Criticisms of this study are that it was not calculated whether the sample size was sufficient to detect statistical differences and generally the poor quality of reporting. For example, there was no information on the failure rate in the two arms and, for example, there is no information on the incidence of the two variables examined in each case, but only the duration is examined and reported.
In dieser Studie wurden verschiedenen Leukämiepatienten vor der Knochenmarktransplantation in zwei verschiedene Gruppen eingeteilt. Eine Gruppe begann sieben Tage vor der Operation bis 28 Tage danach zusätzlich zur Chemotherapie noch Vitamin E einzunehmen, während die andere stattdessen nur ein Placebo erhielt. Die beiden Gruppen unterschieden sich nicht hinsichtlich der durchschnittlichen Dauer von Mukositis (d.h. Schleimhautentzündung, eine typische Nebenwirkung von Chemotherapie) und Neutropenie (d.h. die häufigste Form der Abnahme weißer Blutkörperchen). Kritikpunkte an dieser Studie sind, dass nicht berechnet wurde, ob die Stichprobengröße ausreichend ist um statistische Unterschiede entdecken zu können und allgemein die schlechte Berichtqualität. So gab es z.B. keine Angaben zur Ausfallrate in den beiden Gruppen und es gibt z.B. jeweils keine Angaben zur Inzidenz der beiden untersuchten Variablen, sondern es wird nur die Dauer untersucht und berichtet.
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
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Prospective
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| Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals
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Monocentric
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| 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
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Double
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| Is randomized
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Yes
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| Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control
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No
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| Number of arms
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2
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Study characteristics
| Inclusion criteria
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NI
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| Exclusion criteria
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NI
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| N randomized
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60
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| 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.
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ITT Analysis, NI
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| Specifications on analyses
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ITT not specified, but no drop-out reported.
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| Countries of data collection
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Iran
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| LoE Level of evidence
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1b Oxford 2009
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| Outcome timeline Data collection times
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"The grade of mucositis was recorded daily from day 7 (the first day of conditioning regimen and the beginning of supplementation with vitamin E) until the 28th day after BMT (a total of 35 days), in a chart designed for each patient."
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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.
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NI
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| Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included
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Hematologic Cancers - Leukemia (Acute Lymphocytic/Acute Myeloid/Chronic Lymphocytic/Chronic Myeloid)
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| 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
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NA
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| Specifications on cancer stages
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NA
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| Comorbidities
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NI
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| Current cancer therapies
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Surgery, Chemotherapy
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| Specifications on cancer therapies
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Allogenic bone marrow transplantation
"All the patients received cyclophosphamide 60 mg/kg for 2 days (on day -2 and -3, total dose 120 mg/kg) and busulfan 4 mg/kg for 4 days (on day -7 until day -4, total dose 16 mg/kg) as the conditioning regimen. In order to prevent GVHD, cyclosporine A 3 mg/kg/day i.v. was administered 3 days before BMT until the 5th day after BMT. Thereafter, oral cyclosporine A at 12.5 mg/kg/day was begun. Moreover, methotrexate 10 mg/m²/day i.v. for one day (+1) and 6 mg/m²/day for 3 days (+3, +6, and +11) was administered. Established GVHD was treated with a combination of intravenous methyl prednisolone and then oral prednisolone. All the patients received granulocyte colony stimulating factor 300 mg/day i.v. until their absolute neutrophil count returned to 1000 cells/mL for 3 consecutive days."
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| Previous cancer therapies
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NI
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| Gender
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Mixed
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| Gender specifications
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53% female
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| Age groups
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Adults (18+)
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| Age groups specification
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Mean (SD) = 27 (9.8)
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Arms
| Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment
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Intervention
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| Number of participants (arm) N randomized
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30
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| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
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0
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| Drop-out reasons
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No drop-out reported
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| Intervention
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Vitamin E
+ all patients chemotherapy and surgery
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| Dosage and regime
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Oral, 400mg, 2x daily
Start: day -7 surgery
Duration: until day 28 after surgery
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| One-time application
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No
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| 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.
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35
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| Side effects / Interactions
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NI
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| Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment
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Placebo
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| Number of participants (arm) N randomized
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30
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| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
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0
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| Drop-out reasons
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No drop-out reported
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| Intervention
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Placebo
+ all patients chemotherapy and surgery
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| Dosage and regime
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Oral, 2x daily
Start: day -7 surgery
Duration: until day 28 after surgery
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| One-time application
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No
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| 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.
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35
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| Side effects / Interactions
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NI
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Outcomes
Mucositis
| Outcome type As specificed by the authors
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Primary
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| Outcome specification
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Length of mucositis, daily assessed
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| Type of measurement
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NCI Grading Scale (National Cancer Institute)
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| 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".
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NA
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| 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".
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No sign. differences according to grade (no values given, only graph and p-values): grade 1: p = 0.31, grade 2: p = 0.25, grade: 3: p = 0.93, grade 4: p = 0.32
Mean length: no significant difference seperated by diagnosis (ALL, CML, AML).
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| Risk of Bias Assessment: Cochrane RoB tool 2.0
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| Bias arising from the randomization process
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?
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| Bias due to deviation from intended intervention (assignment to intervention)
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?
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| Bias due to deviation from intended intervention (adhering to intervention)
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NA
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| Bias due to missing outcome data
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?
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| Bias in measurement of the outcome
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?
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| Bias in selection of the reported result
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?
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| Other sources of bias
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?
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| Overall RoB judgment
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?
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Neutropenia
| Outcome type As specificed by the authors
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Primary
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| Outcome specification
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Length of neutropenia (Neutrophil < 1000/mL)
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| Type of measurement
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Blood Test
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| 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".
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NA
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| 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".
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No significant difference regarding the absolute duration of neutropenia (p = 1); no significant difference seperated by diagnosis
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| Risk of Bias Assessment: Cochrane RoB tool 2.0
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| Bias arising from the randomization process
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?
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| Bias due to deviation from intended intervention (assignment to intervention)
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?
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| Bias due to deviation from intended intervention (adhering to intervention)
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NA
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| Bias due to missing outcome data
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?
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| Bias in measurement of the outcome
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?
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| Bias in selection of the reported result
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?
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| Other sources of bias
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?
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| Overall RoB judgment
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?
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Funding and Conflicts of Interest
| Funding
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NI
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| Conflicts of Interest
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NI
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Further points for assessing the study
Sample
| Power analysis performed
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?
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| - Sample size corresponds to power analysis
|
|
| - Reasons for insufficient sample size based on power analysis
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| If no power analysis performed: at least moderate sample size (n >= 30 per arm)
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?
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| Ethnicity mentioned
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?
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Alternative Explanation
| Other explanations for an effect besides the investigated intervention
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|
| - Possibility of attention effects
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?
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| - Possibility of placebo effects
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?
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| - Other reasons
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?
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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
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?
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| Measurement of compliance
|
?
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| Consistent reporting in numbers (figures, flowchart, abstract, results)
|
?
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| Comprehensive and coherent reporting
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?
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| Cross-over
|
|
| - Sufficient washout period
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?
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| - Tested for carry-over effects
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?
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| - Tested for sequence effects
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?
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Interpretation of results
| Effect sizes reported (clinical vs. statistical significance)
|
?
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| Side effects systematically recorded
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?
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| Side effects considered in result interpretation
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?
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| Ethics votum
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?
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Additional Notes
