Property:Additional Notes
This is a property of type Text.
D
Dale et al. (2001): Co-medication with hydrolytic enzymes in radiation therapy of uterine cervix: evidence of the reduction of acute side effects +
PRO:
* Ethics vote available
* Bonferroni Holm correction applied
* Attrition indicated
* Review of patient compliance (counting tablets)
CONTRA:
* No blinding or no placebo group, although this would have been easy to implement
* Only one individual performed all analyses
* Number of Bonferroni-Holm corrections not comprehensible (comparisons of haematological parameters not included?)
* Unclear when attrition took place, as according to the tables all were included in the analysis
* Disproportionately positive presentation, even of non-significant results +
Dardano et al. (2012): The effect of Ginkgo biloba extract on genotoxic damage in patients with differentiated thyroid carcinoma receiving thyroid remnant ablation with Iodine-131 +
CONTRA:
* Not registered +
Delanian et al. (2003): Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis +
PRO:
* Ethical approval obtained.
* Double-blinded.
* Low dropout (N = 2).
CONTRA:
* Very small sample size (though sufficient according to power analysis).
* Baseline group differences not ruled out.
* Placebo arm tends to have lower values (e.g., in terms of surface area and volume; not significant, but this could be due to the small sample size).
* No information on compliance.
* No information on whether assumptions for ANOVA are met (with such a small sample size).
* Poor reporting quality (e.g., no information on pairwise group comparisons). +
Dias et al. (2015): The chemopreventive effect of Ginkgo biloba extract 761 against cisplatin ototoxicity: a pilot study +
CONTRA:
* Not registered. +
PRO:
* Ethics vote available
* Triple blinded
* Attrition reported in detail
* Two investigators recorded patient scores once per week and once per week by one investigator
* Intention-to-treat analysis
* Power analysis
CONTRA:
* Relatively small number of study participants and relatively high attrition
* No description of the blinding procedure
* No statistical values given for endpoints (MW, SD etc.; only graphical representation with p-values)=very simple presentation of results and analyses not presented in a comprehensible manner +
E
Ehrenpreis et al. (2005): A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of Retinol Palmitate (Vitamin A) for Symptomatic Chronic Radiation Proctopathy +
''Cross over results:''
Of the six patients who did not respond to placebo, five were enrolled in the open-label retinol palmitate treatment arm.
- 5/5 met criteria for response to therapy
- significant change in RPSAS-value (p<0.05)
PRO:
* Ethics vote
* Double blinding
CONTRA:
* Very small sample (N < 20)
* Self-developed instrument, no validation data
* Group differences at Baseline (e.g. in intervention arm: 22% female, contrl arm: 0% female; mean value in years post-radiotherapy: intervention arm: 5.08 (range 0.67-19), control arm: 3.69 (range: 1-10)
* Poor report quality, e.g. some information in discussion not reported in results section (e.g. side effects) +
Emami et al. (2014): Double-blinded, randomized, placebo-controlled study to evaluate the effectiveness of green tea in preventing acute gastrointestinal complications due to radiotherapy +
PRO:
* Ethics vote
* Comparability of the groups is given
* Power analysis was performed and criteria are fulfilled
* Exclusion for use of other anti-diarrhoeal medication
CONTRA:
* Small sample size
* No test for normal distribution
* No detailed information on randomisation process
* Hardly any demographic variables (type of cancer, stage, first diagnosis, medication, comorbidities, previous experience with etc. missing) availible
* Information in text only ‘p<’, not very meaningful and inconsistent with information from table (cf. age, group comparisons)
* Unclear to which comparison the p-value in the table belongs, or what was compared (occurrence of vomiting or non-occurrence?)
* Insufficient description of the results in the text
* Statement in the text that vomiting and diarrhoea occurred more frequently on average over the 4 weeks in the placebo arm. This is not statistically substantiated and is therefore misleading reporting.
*Discussion states that the intervention reduces diarrhoea, but there is no statistical evidence for this. The text only states that Friedman's analysis could not find any increase. Correct would be: decrease compared to the control arm.
* The results section reports the frequency of vomiting and diarrhoea during the 1st week, but the measurement did not officially start until the 2nd week - misleading timing.
* Very brief reporting, with few details and inconsistencies. Statistical results not comprehensible and interpretation of results by authors incorrect and misleading. +
F
Fallahi et al. (2013): Does vitamin E protect salivary glands from I-131 radiation damage in patients with thyroid cancer? +
PRO:
* Ethical approval
* Double-blinded
CONTRA:
* Small sample size
* No information on dropout
* No information on compliance
* No control for multiple testing +
Fallon et al. (2017) I: Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies +
PRO:
* Ethical approval obtained
* Arms comparable at baseline
* Power analysis conducted
* Multiple testing controlled for endpoints pain and sleep disruption
* Intent-to-Treat analysis performed
CONTRA:
* High dropout rate (due to study discontinuation or death)
* No information on whether centers were comparable in patient treatment; particularly, "optimal" opioid treatment may vary between countries
* Multiple testing only controlled for pain and sleep disruption +
Fallon et al. (2017) II: Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies +
PRO:
* Ethical approval obtained
* Arms comparable at baseline
* Power analysis conducted
* Multiple testing controlled for endpoints pain and sleep disruption
* Intent-to-Treat analysis performed
CONTRA:
* High dropout rate (due to study discontinuation or death)
* No information on whether centers were comparable in patient treatment; particularly, "optimal" opioid treatment may vary between countries
* Multiple testing only controlled for pain and sleep disruption +
Ferreira et al. (2004): Protective effect of alpha-tocopherol in head and neck cancer radiation-induced mucositis: A double-blind randomized trial +
PRO:
* Ethical approval obtained.
* Double-blinded.
* Adequate sample size according to power analysis.
* Intention-to-treat analysis conducted.
* High compliance (Intervention: 91.2%, Placebo: 100%).
CONTRA:
* Placebos also contained 2.5% Vitamin E (13 IU per 500 mg).
* No information on dropout.
* Poor reporting quality (e.g., no detailed information on compliance, no information on Vitamin E levels). +
Frankling et al. (2021): ‘Palliative-D’ - Vitamin D Supplementation to Palliative Cancer Patients: A Double Blind, Randomized Placebo-Controlled Multicenter Trial +
PRO:
* Ethics vote
* Very detailed descriptions in supplements
* Power analysis
* Control for intra-person correlation
* Comparability of the groups both as ITT and PP sample
* Vitamin D level measurements
* Testing of compliance
CONTRA:
* 4 changes to original design
* Only gastrointestinal tract symptoms, an increase in creatinine levels, hypercalcemia and renal failure had to be reported as side effects according to the protocol
* Fatigue and QoL only assessed by 2 questions each
* According to power analysis, 10 patients too few
* Higher drop-out in A compared to B between T1 and T2 (p=0.02) due to no longer wanting to participate, slightly more drop-outs overall by the end of the study in A (45% vs. 33%); people who dropped out had higher opioid levels at baseline +
G
Ghoreishi et al. (2007): Effect of vitamin E on chemotherapy-induced mucositis and neutropenia in leukemic patients undergoing bone marrow transplantation +
PRO:
* Ethical approval obtained.
* Double-blinded.
* Consideration of dietary Vitamin E intake (no differences).
CONTRA:
* No distinction between primary and secondary endpoints.
* Small sample size without power analysis.
* No information on dropout.
* No information on compliance.
* No control for multiple testing (e.g., only t-tests, no multivariate methods).
* Potentially missing endpoints (e.g., incidence of mucositis/neutropenia not reported).
* Poor reporting quality (e.g., no information on cancer stages). +
Goossens et al. (2016): Phase III randomised chemoprevention study with selenium on the recurrence of non-invasive urothelial carcinoma. The SELEnium and BLAdder cancer Trial +
PRO:
* Ethics approval obtained.
* Intention-to-treat analysis and per-protocol analysis conducted.
* Placebo-controlled and double-blind study.
* Blinding tested with a final survey.
* Compliance checked by counting tablets.
* Baseline selenium level measurement.
* Power analysis performed.
* Very detailed description of criteria for endpoints and cancer stage.
* Inclusion of key demographic variables in the analysis.
* Use of an external review committee.
* Testing of selenium concentration difference at the end of the study.
CONTRA:
* Sample size not adequate according to the power analysis.
* Timeline in the study unclear: T0 is study entry and T3 is after 3 months—uncertain if there is a T2.
* Follow-up time averaged 1½ years, which is not explained; it should have been 3 years.
* No information on the current treatment of patients. +
Grimison et al. (2020): Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial +
PRO:
* Ethical approval
* Power analysis
* Daily contact with staff on days of administration
* Structured assessment of side effects using a checklist
* Adherence monitored through diary entries and capsule counts
* McNemar’s test used to control for within-patient correlation
* Control for order effects (p=0.29)
* Comparability at baseline ensured by study design
CONTRA:
* Correction for multiple testing only for primary endpoints
* 90% confidence interval (CI) (p=0.1) used for primary endpoints and 95% CI for secondary endpoints due to pilot study design (primary endpoint was also significant at 95%)
* No differentiation of primary endpoint into acute or delayed responses, despite being listed in the methodology
* Unclear presentation of when and how each endpoint is measured
* Numerous interactions with pharmaceutical companies
* Capsule dosing individualized, with no subgroup analyses for high vs. low doses +
Gujral et al. (2001): Efficacy of hydrolytic enzymes in preventing radiation therapy-induced side effects in patients with head and neck cancers +
PRO:
* Ethics vote available
* Bonferroni Holm correction for multiple testing applied
* Detailed specification of baseline criteria
* Verification of patient compliance (tablet count)
* Follow-up performed (even if high attrition)
CONTRA:
* No blinding
* No placebo group, although it would have been easy to implement
* In the analyses, the number of patients differed, sometimes with an associated explanation and sometimes without
* Only one individual carried out all analyses +
H
Hajimohammadebrahim-Ketabforoush et al. (2019): Effect of Vitamin D Supplementation on Postcraniotomy Pain After Brain Tumor Surgery: A Randomized Clinical Trial +
PRO
* Ethics vote;
* Pre/post level control of vitamin D (25 (OH) D level, mean (SD): Arm A: T0: 15.9 (3.8), T4: 22.5 (4.3), Arm B: T0:14.5 (3.6), T4: 13.7 (3.8); A vs. B: p<0.001)
CONTRA
* No power analysis
* Unclear blinding
* Descriptive differences regarding tumor pathology
* Unclear randomization
* Insufficient description of interventions in arm A and B
* Unclear calculations (e.g. no information on control variables in the model)
* Poor report quality +
Heggie et al. (2002): A phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue +
? +
Hejazi et al. (2013): A pilot clinical trial of radioprotective effects of curcumin supplementation in patients with prostate cancer +
PRO:
* Ethics approval obtained
* Double-blinding
* High compliance
* Acceptable dropout (10% & 15%)
* Intention-to-treat analysis conducted
* No baseline differences in quality of life
CONTRA:
* Small sample size
* No power analysis calculated
* Baseline differences between arms (total antioxidant capacity; p = 0.045)
* Different endpoints calculated than described in the study protocol; primary endpoints were Progression free survival and PSA after one year, but the study only reported Quality of life and PSA value after three months
* Poor reporting quality +
Hejazi et al. (2016): Effect of Curcumin Supplementation During Radiotherapy on Oxidative Status of Patients with Prostate Cancer: A Double Blinded, Randomized, Placebo-Controlled Study +
PRO:
* Ethics approval obtained
* Double-blinding
* High compliance
* Acceptable dropout (10% & 15%)
* Intention-to-treat analysis conducted
* No baseline differences in Quality of Life
CONTRA:
* Small sample size
* No power analysis calculated
* Baseline differences between arms (total antioxidant capacity; p = 0.045)
* Different endpoints calculated than described in the study protocol; primary endpoints were Progression free survival and PSA after one year, but the studies only reported Quality of life and PSA value after three months
* Poor reporting quality +