Property:Additional Notes
This is a property of type Text.
A
Afonseca et al. (2013): Vitamin E for prevention of oxaliplatin-induced peripheral neuropathy: A pilot randomized clinical trial +
PRO:
* Ethical approval obtained.
* Intention-to-treat analysis conducted.
CONTRA:
* Small sample size.
* Blinding lifted before data analysis.
* Overall 11% dropout with unclear group distribution.
* No information on compliance.
* Poor reporting quality (e.g., very brief methods and results sections, no information on Vitamin E administration and timing of endpoint collection, some data only available from graphics). +
Akiba et al. (2018): Vitamin D Supplementation and Survival of Patients with Non–small Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial +
PRO:
* Ethics vote
* Groups comparable to baseline
* Double blinding
* Power analysis with planned interim analysis
* Intention-to-treat analysis for overall survival
CONTRA:
* Flowchart: placebo arm n=78, where it was noted n=78 received intervention (placebo), but n=8 did not receive it
* Due to lack of efficacy on RSF at interim analysis, recruitment was stopped, so that neither the previously calculated nor recalculated number of subjects was reached
* No indication of the number of subjects per group for low or high 25(OH)D level
* Low number of subjects for subgroup analyses +
Ansari et al. (2016): Efficacy of Ginger in Control of Chemotherapy Induced Nausea and Vomiting in Breast Cancer Patients Receiving Doxorubicin- Based Chemotherapy +
Adherence intervention-arm vs. placebo-arm: 76 % vs. 82 % +
PRO:
* Ethics vote
* Power analysis
* Supplementary period of 2 years was chosen based on the median survival time of metastatic colorectal cancer (almost 24 months)
* Comparability of the groups
CONTRA:
* Small sample size
* Little information on the general conditions of the study, as well as other events (such as side effects) during the study
* Open
* Only graphical representation of the overall survival given, and overall very superficial presentation of the results
* Info: Due to poor compliance, vitamin D levels were not checked at regular intervals during and after treatment, therefore it is unknown whether the vitamin D status of the patients has improved +
Argyriou et al. (2006): A randomized controlled trial evaluating the efficacy and safety of vitamin E supplementation for protection against cisplatin-induced peripheral neuropathy: final results +
PRO:
* Ethical approval obtained.
CONTRA:
* No blinding of investigators/patients.
* Moderate dropout (13% & 16%).
* Small sample size without power analysis.
* Separate intention-to-treat (ITT) and per-protocol (PP) analyses, but most endpoints reported only for PP.
* Poor reporting quality (e.g., partially missing information on the ITT population, no information on cancer stage, no data on the progression of CIPN during the study). +
Argyriou et al. (2006): Preventing Paclitaxel-Induced Peripheral neuropathy: A Phase 2 Trial of Vitamin E Supplementation +
PRO:
* Ethical approval obtained.
CONTRA:
* No blinding of investigators/patients.
* Moderate dropout (11% & 16%).
* Small sample size without power analysis.
* Separate intention-to-treat (ITT) and per-protocol (PP) analyses, but most endpoints reported only for PP.
* Poor reporting quality (e.g., partially missing information on the ITT population, no information on cancer stage, no data on the progression of PIPN during the study). +
Asfour et al. (2006): Effect of high-dose sodium selenite therapy on polymorphonuclear leukocyte apoptosis in non-Hodgkin's lymphoma patients +
PRO:
* Detailed medical examination.
* Comparability of values for measured endpoints given.
CONTRA:
* Very small sample size and no power analysis.
* No blinding or placebo arm.
* No mention of ethics approval.
* Discrepancies between ejection fraction data in the abstract and table.
* No inclusion or balancing based on participants' baseline values (very simple statistical calculation with high risk of bias).
* Infection rate is significant in text but not indicated as significant in the table (p>0.05 but marked as "S" for significant).
* Very superficial presentation of results.
* Imprecise and insufficient description of side effects.
* No statistical proof of arm comparability at baseline regarding demographic variables.
* No information on the randomization process or possible drop-outs.
* No indication of when follow-up on cardiac ejection fraction took place.
* No age specification.
* Although selenium serum measurement is mentioned, no data is provided. +
Azizi et al. (2015): Efficacy of Topical and Systemic Vitamin E in Preventing Chemotherapy-induced Oral Mucositis +
PRO:
* Blinding of investigators.
CONTRA:
* Unclear randomization.
* No blinding of patients.
* Small sample size without power analysis.
* Very high dropout rate (after the fourth CTX cycle: Vitamin E paste: 27%, Vitamin E oral: 33%, Placebo: 46%).
* No information on compliance.
* Multiple testing without time-based models.
* Poor reporting quality (e.g., no information on cancer types or stages, no standard deviations or 95% confidence intervals, no baseline values of the variables studied). +
B
Bairati et al. (2005): A Randomized Trial of Antioxidant Vitamins to Prevent Second Primary Cancers in Head and Neck Cancer Patients +
PRO:
* Ethics vote
* Comparably high compliance in both arms
* Information on the development of beta-carotene/vitamin E levels
* Low dropout (T3: 3%)
* Performance of power analyses
* Double blinding
* Intention-to-treat analysis
* Consideration of possible confounding variables (e.g. clinical or smoking status)
CONTRA:
* Possible group differences from baseline in the subgroups (beta-carotene + vitamin E/ vitamin E only, were not analyzed separately)
* Differently sized groups despite the indication of a 1:1 randomization
* Changes to the study protocol during the course of the study
* Poor report quality, sometimes contradictory information in the individual publications (see Study Note) for results +
Bairati et al. (2005): Randomized Trial of Antioxidant Vitamins to Prevent Acute Adverse Effects of Radiation Therapy in Head and Neck Cancer Patients +
PRO:
* Ethics vote
* Comparably high compliance in both arms
* Information on the development of beta-carotene/vitamin E levels
* Low dropout (T3: 3%)
* Performance of power analyses
* Double blinding
* Intention-to-treat analysis
* Consideration of possible confounding variables (e.g. clinical or smoking status)
CONTRA:
* Possible group differences from baseline in the subgroups (beta-carotene + vitamin E/ vitamin E only, were not analyzed separately)
* Differently sized groups despite the indication of a 1:1 randomization
* Changes to the study protocol during the course of the study
* Poor report quality, sometimes contradictory information in the individual publications (see Study Note) for results +
Bairati et al. (2006): Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients +
PRO:
* Ethics vote
* Comparably high compliance in both arms
* Information on the development of beta-carotene/vitamin E levels
* Low dropout (T3: 3%)
* Performance of power analyses
* Double blinding
* Intention-to-treat analysis
* Consideration of possible confounding variables (e.g. clinical or smoking status)
CONTRA:
* Possible group differences from baseline in the subgroups (beta-carotene + vitamin E/ vitamin E only, were not analyzed separately)
* Differently sized groups despite the indication of a 1:1 randomization
* Changes to the study protocol during the course of the study
* Poor report quality, sometimes contradictory information in the individual publications (see Study Note) for results +
Barton et al. (1998): Prospective evaluation of vitamin E for hot flashes in breast cancer survivors +
PRO:
* Large sample according to power analysis
* Double blinding
CONTRA:
* Dropout: 21/125 (17%): 5 vitamin E/placebo not taken and 16 dropouts (vitamin E: 9, placebo: 7)
* No information on compliance
* Poor report quality (e.g. some results missing) +
Brown et al. (2019): Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Body Composition among Patients with Advanced or Metastatic Colorectal Cancer: A Randomized Trial +
PRO
* Ethics vote
* Study protocol
* Blinding
* Randomization
* Pre/post level control of vitamin D (mean increase 25 (OH) D level over 1. 8 CTX cycles in intervention arm vs.placebo arm: mean difference 20.0 ng/mL; (95% CI: 14.7, 25.2); p<0.001)
* High treatment adherence with regard to vitamin D3: median: 98%
* Intention-to-treat analysis
CONTRA
* No indication of p-values for baseline differences +
Büntzel et al. (2010): Limited effects of selenium in the prevention of radiation-associated toxicities - results of a randomized study in head neck cancer patients +
PRO:
* Ethics approval obtained.
* Clear presentation of results.
* Detailed description of the research question and selenium level testing.
CONTRA:
* Unequal arm sizes despite randomization.
* No power analysis.
* No placebo and thus no blinding possible.
* Unclear randomization process.
* No information on the comparability of arms at baseline in the results section or how this was achieved—especially considering the unequal arm sizes.
* Lack of additional demographic variables such as comorbidities, tumor stage, etc.
* No detailed description of the assessments in the individual clinics and whether they were comparable. +
C
Cavallini et al. (2005): Acetyl-L-carnitine plus propionyl-L-carnitine improve efficacy of sildenafil in treatment of erectile dysfunction after bilateral nerve-sparing radical retropubic prostatectomy +
PRO:
* Ethical approval obtained.
* Double-blind and control confirmed.
* Monitoring of correct medication/placebo intake.
* Detailed presentation of attrition and drop-outs.
* Randomized block analysis (matching).
* Active and passive control groups.
CONTRA:
* Unclear why group sizes were unequal at randomization.
* Inconsistent reporting of the number in the placebo group (with/without attrition – abstract vs. main text).
* No effect sizes reported.
* No significance values reported, especially for IIEF.
* No intention-to-treat analysis.
* No group comparison for ICI.
* No information on who conducted the interviews or how/where variables were collected.
* Unclear recruitment method.
* No reliability data for measurement instruments provided.
* Assessment of ICI success partially subjective.
* High number of drop-outs due to protocol violations, raising feasibility concerns.
* Table lacks description of data (means, SD?).
* No details on how much sildenafil was actually taken (as needed?).
* Analysis assumes groups took it as prescribed. +
Chung et al. (2016): Randomized Trial of Vitamin C/E Complex for Prevention of Radiation- Induced Xerostomia in Patients with Head and Neck Cancer +
PRO:
* Ethics vote
* Double blinding
* Intention-to-treat
CONTRA:
* No proper group comparisons between intervention and placebo arm on xerostomia questionnaire and xerostomia score
* Small sample without power analysis
* Unequal dropout (intervention arm: 4%, placebo arm: 23%)
* No validation information on the measurement instruments used
* Poor reporting quality (e.g. results reported confusingly) +
Crew et al. (2012): Phase IB Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Women with Hormone Receptor–Negative Breast Cancer +
PRO:
* Multicentre study
* Ethics vote
* Wash-out and control of confounding factors: avoidance of tea substances and restricted consumption of caffeine from 30 days before the start of the study until the end of the study
* Use of CRM (continuous reassessment method) and thus also recording of long-term effects
CONTRA:
* Recording of hormonal side effects such as irregular menstruation difficult, as postmenopausal women were also included in the study
* Intent-to-treat analysis of side effects can lead to side effects being underestimated (per protocol would be better here)
* Statistical comparison of side effects not separated by dose and grade (by definition, the study design ensures that the arms do not differ too much with regard to grade II and grade III side effects, as it is predetermined that the dose will be reduced if grade II side effects occur)
* Baseline apparent differences: in Poly E arms 47% of patients were stage I and 30% stage II, in placebo-arm 20% stage I and 60% stage II) +
Cruciani et al. (2009): L-Carnitine Supplementation in Patients with Advanced Cancer and Carnitine Deficiency: A Double-Blind, Placebo-Controlled Study +
PRO:
* Ethical approval obtained.
* Intention-to-treat analysis.
* Block randomization according to RTX or CTX, gender, and hemoglobin level.
* Power analysis conducted.
* Explanation provided for unequal group sizes (block randomization).
* Critical discussion of results.
CONTRA:
* Inclusion of baseline values only in an additional secondary analysis (PPA).
* Effects in PPA only for control of baseline values and age.
* Small sample size.
* Differing reports of required free carnitine for men in the abstract and main text. +
Cruciani et al. (2012): L-Carnitine Supplementation for the Management of Fatigue in Patients With Cancer: An Eastern Cooperative Oncology Group Phase III, Randomized, Double-Blind, Placebo-Controlled Trial +
PRO:
* Ethics approval available.
* Balanced by gender, PS (0-1 vs. 2-3), and CTX.
* Control for current carnitine intake.
* High Cronbach's alpha for BFI at all times.
* Subgroup analysis to exclude or identify moderator effects.
* Detailed collection of adverse events and tabular representation.
CONTRA:
* Placebo arm had higher pain with BPI or analgesic use compared to intervention arm (intervention: 61% vs. placebo: 49.7%; p = 0.04).
* Attrition and reporting of remaining group sizes not accurate.
* Timing of results for secondary endpoints unclear.
* High drop-out/attrition (44% attrition, over 60 refused treatment, unclear why).
* No intention-to-treat analysis.
* No report of individual p-values for comparisons (e.g., baseline values).
* No information on patient age, cancer diagnoses, and data collection period.
* Unclear from appendix which AEs are “definitely therapy-associated.”
* Death possibly therapy-associated; unclear in which arm, cause of death, and what about NOS deaths (2x).
* Representation of side effects not clear.
* Discrepancies between text and table (number); also, description of reasons for deaths inconsistent between text and table. +
Côté et al. (2016): Improving Quality of Life With Nabilone During Radiotherapy Treatments for Head and Neck Cancers: A Randomized Double-Blind Placebo-Controlled Trial +
PRO:
* Ethical approval
* Power analysis
* Intent-to-treat analysis
* Baseline comparability
* Mention of drop-out comparison in the discussion, though no statistical values are provided
CONTRA:
* Lack of blinding control
* No correction for multiple testing
* Superficial and inadequate presentation of results: results are only shown graphically, with no mean/SD values available, lacking transparency
* Very high drop-out rate, with 12 out of 15 participants in placebo arm who dropped out receiving Radiochemotherapy
* Exact dosing from week 3 onward may vary for each participant
* Apart from the primary endpoint, no specific timing provided for final comparisons +