| Reference ↗
|
| Title
|
Oral calcitriol in hematopoietic recovery and survival after autologous stem cell transplantation: a randomized clinical trial
|
| Topic
|
Vitamin D
|
| Author
|
Raoufinejad, K, Shamshiri, AR, Pezeshki, S, Chahardouli, B, Hadjibabaie, M, Jahangard-Rafsanjani, Z, Gholami, K, Rajabi, M, Vaezi, M
|
| Year
|
2019
|
| Journal
|
Journal of Pharmaceutical Sciences
|
| DOI
|
https://doi.org/10.1007/s40199-019-00306-y
|
Study Note
Brief summary
The study included 80 patients with Hodgkin lymphoma, non-Hodgkin lymphoma and multiple myeloma awaiting stem cell transplantation with autologous peripheral blood. Randomly assigned, one half received 0.25 μg calcitriol 3 times a day for 30 days after the procedure and the other half received a placebo. Various immunological values, occurrence and duration of mucositis, as well as relapse-free survival and overall survival were recorded. The study showed no improvement in mucositis with calcitriol, but an improvement in two-year survival without disease progression. Overall survival was not influenced by the intervention.
Die Studie schloss 80 Patienten mit Hodgkin Lymphom, Non Hodgkin Lymphom und multiple Myelom, die auf eine Stammzelltransplantation mit autologem peripherem Blut warten, ein. Zufällig eingeteilt erhielt die eine Hälfte in den 30 Tagen nach dem Eingriff 3x täglich 0,25 μg Calcitriol und die andere Hälfte ein Placebo. Erhoben wurden verschiedene immunologische Werte, Auftreten und Länge von Mukositis, sowie rückfallfreies Überleben und Gesamtüberleben. Die Studie zeigt keine Verbesserung der Mukositis durch Calcitriol, jedoch eine Verbesserung des Zweijahresüberlebens ohne Krankheitsfortschritt. Das Gesamtüberleben wurde nicht durch die Intervention beeinflusst.
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
|
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
|
From 18 to 68 years, in complete remission of the disease and bone marrow (NCCN guidelines), with optimal kidney and liver functions
|
| Exclusion criteria
|
With baseline serum corrected total calcium >10.5 mg/dl, phosphorous >4.5 mg/dl, magnesium >2.5 mg/dl, nephrolithiasis in the past 5 years, calcitriol therapy in the previous 30 days, hypersensitivity or inability to take oral calcitriol
|
| N randomized
|
80
|
| 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.
|
ITT Analysis
|
| Specifications on analyses
|
NA
|
| Countries of data collection
|
Iran
|
| LoE Level of evidence
|
Level 2 Oxford 2011
|
| Outcome timeline Data collection times
|
T0: baseline (day 0: allocation)
T1: after 15 days
T2: after 30 days
T3: after 180 days
T4: after 365 days
Follow-up: 2 years
|
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
|
Hematologic Cancers - Lymphoma (Hodgkin and Non-Hodgkin), Hematologic Cancers - Multiple Myeloma
|
| 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
|
Diabetes, Hepatitis B, Cardiovascular disease, Thyroid disease
|
| Current cancer therapies
|
Stem cell or bone marrow transplant
|
| Specifications on cancer therapies
|
Autologous peripheral blood hematopoietic stem cell transplantation
|
| Previous cancer therapies
|
Chemotherapy
|
| Gender
|
Mixed
|
| Gender specifications
|
Intervention arm: 25 (62.5%) male, 15 (37.5%) female
placebo arm: 29 (72.5%), 15 (37.5%) female
|
| Age groups
|
Adults (18+)
|
| Age groups specification
|
Intervention arm: mean (SD): 47.53 (13.49), range: 21-65
placebo arm: mean (SD): 46.93 (14.39), range: 18-68
|
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
|
40
|
| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
|
NA
|
| Drop-out reasons
|
n=4, death before day 30
|
| Intervention
|
Vitamin D
|
| Dosage and regime
|
Oral capsules of calcitriol 0.25 μg, three times daily from day 0 to 30
|
| 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.
|
30
|
| Side effects / Interactions
|
Hyperphosphatemia (>4.5 mg/dl) in 11/40 (27.5%), no significant differences;
hypercalcemia (>10.5 mg/dl) in 1/40 (2.5%)
All side effects were “non-serious” and “mild-level-1,” except for 1/40 (2.5%) recorded as “mild-level-2” due to temporarily holding the intervention for a few doses to successfully reduce the serum calcium and phosphorous and restart calcitriol
|
| 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
|
40
|
| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
|
NA
|
| Drop-out reasons
|
n=2 non-compliance
|
| Intervention
|
Placebo
|
| Dosage and regime
|
Oral capsules of placebo (identical to the calcitriol for color, shape, size, taste, and smell), three times daily from day 0 to 30
|
| 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.
|
30
|
| Side effects / Interactions
|
Hyperphosphatemia (>4.5 mg/dl) in 12/40 (30.0%), no significant differences;
hypercalcemia (>10.5 mg/dl) in 1/40 (2.5%);
All side effects were “non-serious” and “mild-level-1,” except for 3/40 (7.5%) recorded as “mild-level-2” due to temporarily holding the intervention for a few doses to successfully reduce the serum cal- cium and phosphorous and restart placebo
|
Outcomes
Mucositis
| Outcome type As specificed by the authors
|
Secondary
|
| Outcome specification
|
Incidence, duration, and severity
|
| Type of measurement
|
WHO-Scale (World Health Organisation)
|
| 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 values reported, only tables: no significant differences
|
| 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
|
?
|
Fever
| Outcome type As specificed by the authors
|
Secondary
|
| Outcome specification
|
Incidence and duration
|
| Type of measurement
|
Thermometer
|
| 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 values reported, only tables: no significant differences in incidence and duration
|
| 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
|
?
|
Neutropenia
| Outcome type As specificed by the authors
|
Secondary
|
| Outcome specification
|
Duration of severe neutropenia
|
| Type of measurement
|
Blood Test
|
| 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 values reported, only tables: no significant differences in duration
|
| 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
|
?
|
Length of hospital stay
| Outcome type As specificed by the authors
|
Secondary
|
| Outcome specification
|
Transplantation to discharge
|
| 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 values reported, only tables: no significant differences
|
| 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
|
?
|
Additional medication
| Outcome type As specificed by the authors
|
Secondary
|
| Outcome specification
|
Anti-infective medicines in addition to usual care
|
| 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 values reported, only tables: no significant differences
|
| 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
|
?
|
Nutrition status
| Outcome type As specificed by the authors
|
Secondary
|
| Outcome specification
|
Duration of total parenteral nutrition
|
| Type of measurement
|
NI
|
| 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 values reported, only tables: no significant differences
|
| 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
|
?
|
RFS (Recurrence-Free Survival)
| Outcome type As specificed by the authors
|
Secondary
|
| Outcome specification
|
NI
|
| 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".
|
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".
|
Two-year recurrence-free survival was significantly higher in the intervention than the placebo arm (77.0%, SE=7.0% vs. 59.0%, SE=8.0%; p=0.03)
|
| 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
|
?
|
OS (Overall Survival)
| Outcome type As specificed by the authors
|
Secondary
|
| Outcome specification
|
NA
|
| 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".
|
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".
|
Two-year overall survival not significantly different between the arms (p=0.72)
|
| 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
|
?
|
Vitamin D level
| Outcome type As specificed by the authors
|
Others
|
| Outcome specification
|
NI
|
| Type of measurement
|
Blood Test
|
| 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".
|
Mean baseline levels of 1,25-(OH)2-D in intervention and placebo arm: 38.02 ± 17.83 pg/ml vs. 32.65 ± 14.76 pg/ml;
mean levels elevated significantly (by repeated measure ANOVA, adjusted for baseline values, p=0.005) with calcitriol than the placebo on day 15 (48.39 ± 19.78 pg/ml vs. 31.06 ± 22.92 pg/ ml) and day 30 (59.51 ± 24.83 pg/ml vs. 39.60 ± 23.11 pg/ml)
|
| 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
|
?
|
Funding and Conflicts of Interest
| Funding
|
Funded through an educational grant to the researchers from the Hematology-Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
|
| 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
|
?
|
Additional Notes
PRO:
- Ethics vote
- Power analysis
- Intent-to-treat analysis
CONTRA:
- Heterogeneity concerning types of cancer
- Indication of randomization but then reports “KR enrolled the participants and assigned them to interventions.”
- No control for multiple testing
- No information whether there was comparability testing of the groups at baseline
