Example Queries II

What effects of selenium have been investigated?

	Outcome name
Asfour et al. (2006): Effect of high-dose sodium selenite therapy on polymorphonuclear leukocyte apoptosis in non-Hodgkin's lymphoma patients	Toxicity Ejection fraction
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	Toxicity
Büntzel et al. (2010): Selenium Substitution During Radiotherapy of Solid Tumours - Laboratory Data from Two Observation Studies in Gynaecological and Head and Neck Cancer Patients	Selenium level
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	RFS (Recurrence-Free Survival) PFS (Progression-Free Survival) Selenium level
Jahangard-Rafsanjani et al. (2013): The efficacy of selenium in prevention of oral mucositis in patients undergoing hematopoietic SCT: a randomized clinical trial	Haematological indices Length of hospital stay Incidence of acute GVHD (Graft-Versus-Host Disease) Mortality rate Non-haematological indices Selenium level Mucositis Fever
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How does selenium influence survival in cancer?

	Results after intervention	Overall RoB judgment	Outcome name
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	ITT: intervention arm n=43 (28%; 95% CI: 0.21, 0.35) and placebo arm n=45 (32%; 95% CI: 0.24, 0.40); HR: 0.85 (95% CI: 0.56, 1.29); p=0.44, not significant PP: (all participants remaining in the study after 3 months): intervention arm n=42 and placebo arm n=39 (28%; 95% CI: 0.20, 0.35); HR: 0.96 (95% CI: 0.62, 1.48)); p=0.85, not significant No influence of age, gender, nicotine consumption, stage, selenium concentration at baseline and hospital Remark: After 3 months: progression in 24 patients, median progression time 22 months in both arms; Patients in intervention arm had 48% more chance of progression than those in the placebo arm, but not statistically significant (HR = 1.48 (95% CI: 0.65, 3.38); p=0.35); Progression in the intervention arm 15x, placebo arm 14x ITT: HR: 0.97 (95% CI: 0.47, 2.00); p=0.93, not significant Significant difference in selenium concentration after 3 years (n=67 (55%)): 187.6 mg/dl ± 57.7 mg/dl intervention arm vs. 88.9 mg/dl ± 22.2 mg/dl placebo arm; p=0.00	some concerns some concerns some concerns	RFS (Recurrence-Free Survival) PFS (Progression-Free Survival) Selenium level
Karp et al. (2012): Randomized, double-blind, placebo-controlled, phase III chemoprevention trial of selenium supplementation in patients with resected stage I non-small-cell lung cancer: ECOG 5597	Intervention arm: 76.8% (SE, 1.6%) vs. placebo arm: 79.9% (SE, 2.1%); p=0.154 Note: Distribution significantly different for smoking status (p=0.027): active smokers or those who had quit within one year showed a 3-year OS of 85.5% (SE, 1.7%) and 5-year OS of 74.9% (SE, 2.4%), whereas participants who had never smoked showed a 3-year OS of 90% (SE, 2.8%) and a 5-year OS of 83.6% (SE, 3.6%); no difference for DFS; p=0.245 Collected in 865 patients in intervention arm and 477 in placebo arm: Grade 1-2 toxicity in intervention arm: 31% and placebo arm: 26% of subjects Grade ≥ 3 toxicity occurred in less than 2% of subjects in intervention arm and 3% in placebo arm n=1 patient in placebo arm had constitutional lethal toxicity no arm comparison performed Selenium level at baseline (n=1,022), year 2 (n=375), and year 4 (n=194): at baseline selenium level mostly in normal range, after 2 and 4 years significantly increased selenium concentration in the intervention arm Interim analysis October 2009: N=83 secondary lung tumors; Rate intervention arm: 1.91 per 100 persons per year vs. 1.36 in placebo arm; p=ns June 2011: N=252 secondary tumors in 224 patients, of which 98 (out of 97 patients) were lung cancer (38.9%); Lung cancer and other cancers (SPT) in intervention arm: 1.62 and 3.54 per 100 persons per year vs. placebo arm: 1.30 and 3.39 per 100 persons per year; p=0.294 5-year DFS: October 2009: Intervention arm: 72% vs. placebo arm: 78%, no significance values given June 2011: Intervention arm: 74.4% vs. placebo arm: 79.6%; p=0.69 Note: 5-year DFS rates with subdivision into low, average and high selenium concentration intervention vs. placebo: 75.5% (SE, 10.3%) vs. 72.9% (SE, 12.7%), 75.6% (SE, 2.27%) vs. 78.2% (SE, 3.3%), and 72.9% (SE, 4.5%) vs. 80.9% (SE, 5.2%)	low risk low risk low risk low risk	OS (Overall Survival) Toxicity Selenium level DFS (Disease-Free Survival)
Mix et al. (2015): Randomized phase II trial of selenomethionine as a modulator of efficacy and toxicity of chemoradiation in squamous cell carcinoma of the head and neck	Overall: No significant differences between arms (grade 3 intervention arm 2x, placebo arm 3x, no grade 4) Only one patient from the intervention arm did not reach CR and died After 12 months: No significant differences between arms After 12 months: No significant differences between arms No significant difference for week 6-8 post-treatment and Follow-up within a year Overall: Hearing dysfunction n=1 each in the intervention arm and placebo arm; elevated creatinine n=1 in the placebo arm; myelosuppression: anemia in the placebo arm n=1; leukopenia in the intervention arm n=3 and placebo arm n=2; dermatitis in the intervention arm n=2; dry mouth in the placebo arm n=2; dysgeusia in the intervention arm n=2, placebo arm n=1; odyno-/dysphagia in the intervention arm n=1, placebo arm n=2; oral/throat pain in the placebo arm n=2; mucus/sputum intervention arm n=3, placebo arm n=1	some concerns low risk low risk low risk some concerns some concerns	Mucositis Tumor response PFS (Progression-Free Survival) OS (Overall Survival) Quality of life Toxicity
Muecke et al. (2010): Multicenter, phase 3 trial comparing selenium supplementation with observation in gynecologic radiation oncology	After 6 weeks post radiotherapy, levels between arms were comparable Overall incidence of grade 2 diarrhea: intervention arm 20.5% vs. control arm 44.5% (p = 0.04) No difference between arms No difference between arms Median follow-up of 49 months (range, 0-75): 5-year disease free survival in the intervention arm was 80.1% vs. 83.2% in the control arm, no significant difference; p = 0.74 Median follow-up of 51 months (range 6-75): 5-year overall survival in the intervention arm was 91.9% vs. 83.1% in the control arm, no significant difference; p = 0.34	some concerns some concerns some concerns some concerns some concerns some concerns	Selenium level Toxicity Performance Status Quality of life DFS (Disease-Free Survival) OS (Overall Survival)
Muecke et al. (2014): Multicenter, phase 3 trial comparing selenium supplementation with observation in gynecologic radiation oncology: follow-up analysis of the survival data 6 years after cessation of randomization	10-year disease-free survival intervention arm 80.1% vs. control arm 83.2%; not significant; p = 0.65 10-year overall survival intervention arm 55.3% vs. control arm 42.7%; not significant; p = 0.09	high risk high risk	DFS (Disease-Free Survival) OS (Overall Survival)

How does selenium influence survival in cancer? - outcome-based

	Outcome name	Results after intervention	Overall RoB judgment
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	PFS (Progression-Free Survival)	Remark: After 3 months: progression in 24 patients, median progression time 22 months in both arms; Patients in intervention arm had 48% more chance of progression than those in the placebo arm, but not statistically significant (HR = 1.48 (95% CI: 0.65, 3.38); p=0.35); Progression in the intervention arm 15x, placebo arm 14x ITT: HR: 0.97 (95% CI: 0.47, 2.00); p=0.93, not significant	some concerns
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	RFS (Recurrence-Free Survival)	ITT: intervention arm n=43 (28%; 95% CI: 0.21, 0.35) and placebo arm n=45 (32%; 95% CI: 0.24, 0.40); HR: 0.85 (95% CI: 0.56, 1.29); p=0.44, not significant PP: (all participants remaining in the study after 3 months): intervention arm n=42 and placebo arm n=39 (28%; 95% CI: 0.20, 0.35); HR: 0.96 (95% CI: 0.62, 1.48)); p=0.85, not significant No influence of age, gender, nicotine consumption, stage, selenium concentration at baseline and hospital	some concerns
Karp et al. (2012): Randomized, double-blind, placebo-controlled, phase III chemoprevention trial of selenium supplementation in patients with resected stage I non-small-cell lung cancer: ECOG 5597	OS (Overall Survival)	Intervention arm: 76.8% (SE, 1.6%) vs. placebo arm: 79.9% (SE, 2.1%); p=0.154 Note: Distribution significantly different for smoking status (p=0.027): active smokers or those who had quit within one year showed a 3-year OS of 85.5% (SE, 1.7%) and 5-year OS of 74.9% (SE, 2.4%), whereas participants who had never smoked showed a 3-year OS of 90% (SE, 2.8%) and a 5-year OS of 83.6% (SE, 3.6%); no difference for DFS; p=0.245	low risk
Karp et al. (2012): Randomized, double-blind, placebo-controlled, phase III chemoprevention trial of selenium supplementation in patients with resected stage I non-small-cell lung cancer: ECOG 5597	DFS (Disease-Free Survival)	Interim analysis October 2009: N=83 secondary lung tumors; Rate intervention arm: 1.91 per 100 persons per year vs. 1.36 in placebo arm; p=ns June 2011: N=252 secondary tumors in 224 patients, of which 98 (out of 97 patients) were lung cancer (38.9%); Lung cancer and other cancers (SPT) in intervention arm: 1.62 and 3.54 per 100 persons per year vs. placebo arm: 1.30 and 3.39 per 100 persons per year; p=0.294 5-year DFS: October 2009: Intervention arm: 72% vs. placebo arm: 78%, no significance values given June 2011: Intervention arm: 74.4% vs. placebo arm: 79.6%; p=0.69 Note: 5-year DFS rates with subdivision into low, average and high selenium concentration intervention vs. placebo: 75.5% (SE, 10.3%) vs. 72.9% (SE, 12.7%), 75.6% (SE, 2.27%) vs. 78.2% (SE, 3.3%), and 72.9% (SE, 4.5%) vs. 80.9% (SE, 5.2%)	low risk
Mix et al. (2015): Randomized phase II trial of selenomethionine as a modulator of efficacy and toxicity of chemoradiation in squamous cell carcinoma of the head and neck	OS (Overall Survival)	After 12 months: No significant differences between arms	low risk
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Which intervention for depression in cancer was investigated in studies with a placebo arm?

	Topic	Intervention	Outcome name	Results during intervention
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	Carnitine	L-Carnitin Placebo	Fatigue Fatigue Depression Pain Performance Status Toxicity Carnitine level	From Baseline to 8 weeks: improvement in fatigue in intervention arm: Mean difference= -0.96; 95% CI: -1.32,-0.60 and placebo arm: Mean difference= -1.11; 95% CI: -1.44,-0.78; no group difference (z-transformed difference= -0.58; p=0.57) After 4 weeks: no difference between arms (p=0.61) After 4 weeks: no difference between arms (p=0.93) After 4 weeks: no difference between arms for pain intensity: p=0.61, disturbance due to pain: p=0.75 After 4 and 8 weeks: no difference between arms (p=0.13, p=0.63) No difference between arms for grade 5 side effect (Fisher's exact p=0.64) After 4 weeks: significant difference between arms, with higher proportion of carnitine deficit in placebo arm (intervention arm: 11%, placebo arm: 33%; p≤.001)
Da Costa et al. (2009): Effectiveness of Guarana (Paullinia cupana) for Postradiation Fatigue and Depression Results of a Pilot Double-Blind Randomized Study	Guarana	75 mg of guayana extract placebo	Depression Fatigue	NA NA
Wyatt et al. (2012): Health-Related Quality-of-Life Outcomes: A Reflexology Trial With Patients With Advanced-Stage Breast Cancer	Reflexology	Reflexology Foot massage (LFM) Conventional therapy, control arm	Quality of life Unspecified effects Nausea Physical functioning Fatigue Fatigue Pain Depression Anxiety	NA NA NA NA NA NA NA NA NA

Side effects of Cannabis in placebo-controlled studies -- study-based

	Intervention	Side Effects / Interactions	Were side effects systematically recorded
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	Nabilon + all patients: additional administration of antiemetics (metoclopramide) and painkillers (acetaminophen (paracetamol), codeine, hydromorphone or transdermal fentanyl) possible Placebo + all patients: additional administration of antiemetics (metoclopramide) and painkillers (acetaminophen (paracetamol), codeine, hydromorphone or transdermal fentanyl) possible	No differences for sleepiness (p=0.32), anxiety (p=0.92) and xerostomia (p=0.83) No differences for sleepiness (p=0.32), anxiety (p=0.92) and xerostomia (p=0.83)	Yes
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	Sativex Placebo	Overall 68% at least one event; assessed as probably intervention-associated with frequency ≥ 5%: Total n=64 (32.2%), of which somnolence n=18 (9%), dizziness n=15 (7.5%), nausea n=10 (5%) 2 severe side effects associated with intervention: 1x constipation (with 360mg/day morphine equivalents), 1x moderate disorientation and somnolence on day 4 (with 2.5 daily sprays of Sativex) None of the deaths related to intervention Overall 64% at least one event; assessed as probably intervention-associated with frequency ≥ 5%: Total n=41 (20.7%), of which somnolence n=6 (3%), dizziness n=6 (3%), nausea n=8 (4%) 2 severe side effects associated with intervention: 1x constipation (with 360mg/day morphine equivalents), 1x moderate disorientation and somnolence on day 4 (with 2.5 daily sprays of Sativex) None of the deaths related to intervention	Yes
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	Sativex Placebo	Part A Overall 60% at least one event, assessed as probably intervention-associated with frequency ≥ 5%: Total n=128, 31.7%, somnolence (n=42, 10.4%), nausea (n=21, 5.2%) and dizziness (n=21, 5.2%) Part B Overall 72% at least one event; assessed as probably intervention-associated with frequency ≥ 5%: Total n=16, 15.5%; somnolence (n=6, 5.8%) More than twice as many patients in Sativex arm discontinued study due to side effects (n=14, 13.6% vs. n=6, 5.8%); no statistical comparison given) None of the deaths related to intervention Part A Overall 60% at least one event, assessed as probably intervention-associated with frequency ≥ 5%: Total n=128, 31.7%, somnolence (n=42, 10.4%), nausea (n=21, 5.2%) and dizziness (n=21, 5.2%) Part B Overall 62% at least one event; assessed as probably intervention-associated with frequency ≥ 5%: Total n=12, 11.7%; somnolence n=0	Yes
Grimison et al. (2020): Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial	THC:CBD Placebo	Moderate or severe cannabinoid-related side effects in intervention arm and placebo arm (31% vs. 7%, p=0.002): Significant differences for sedation (19% vs. 4%, p=0.002) and dizziness (10% vs. 1%, p=0.03) No differences for disorientation (p=0.5) and anxiety (p=1.00) No cannabinoid-related serious adverse events reported 83% of the participants preferred cannabis over placebo and 15% had a preference for placebo (p<0.001) Moderate or severe cannabinoid-related side effects in intervention arm and placebo arm (31% vs. 7%, p=0.002): Significant differences for sedation (19% vs. 4%, p=0.002) and dizziness (10% vs. 1%, p=0.03) No differences for disorientation (p=0.5) and anxiety (p=1.00) No cannabinoid-related serious adverse events reported 83% of the participants preferred cannabis over placebo and 15% had a preference for placebo (p<0.001)	Yes
Johnson et al. (2010): Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain	THC:CBD THC Placebo	Intervention-associated events in n=106 (60%): drowsiness, dizziness, nausea, confusion, vomiting, hypotension, hypercalcemia, increased gamma GT Most side effects were mild/moderate; no statistical comparisons given; one case of syncope probably related to THC; other events not associated with intervention Intervention-associated events in n=106 (60%): drowsiness, dizziness, nausea, confusion, vomiting, hypotension, hypercalcemia, increased gamma GT; Most side effects were mild/moderate; no statistical comparisons given; one case of syncope probably related to THC; other events not associated with intervention NI	Yes
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