Gap finder
Search review questions
Each row is one question a systematic review asked: who, what, compared with what, and which outcome, with the effect it found and how certain that is. Words match anywhere in the field.
1,325 questions in 34 reviews · Oral medicine and oral cancer
current versionsNo studies 164 · 12.4%Ungraded 841 · 63.5%Very low 209 · 15.8%Low 72 · 5.4%Moderate 38 · 2.9%High 1 · 0.1%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
| Question | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Herbal extracts (tea components; Chinese herbal mixture; freeze-dried black raspberry gel) vs Placebo or no treatment Safety of the intervention (adverse effects) · People with a diagnosis of oral leukoplakia · up to 3 months Interventions for treating oral leukoplakia to prevent oral cancer (2016) · Cochrane | SoF 4, Safety of the intervention up to 3 months: '3 studies measured adverse effects: green tea extract capsules caused high frequency (93%) of adverse effects of varying severity in 1 study; the mixed tea study did… | 3 studies | Ungraded |
Paroxetine (antidepressant, 20 mg/day) vs Placebo Relief of burning/discomfort (symptom relief; pain intensity) · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months) Interventions for treating burning mouth syndrome (2016) · Cochrane | Bogetto 1999 (paroxetine) included but data not presented (79% placebo-arm attrition). | 1 study | Ungraded |
Dietary supplements (hypericum perforatum / St John's Wort) vs Placebo Change in quality of life (QoL) · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months), hypericum perforatum Interventions for treating burning mouth syndrome (2016) · Cochrane | Sardella 2008 (43 participants) evaluated QoL from patient self-reports and narratively indicated that both intervention and placebo participants were better able to cope at trial completion. | 1 study · 43 participants | Ungraded |
Physical barriers (tongue protector) vs Placebo Change in feeling of dryness · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months) Interventions for treating burning mouth syndrome (2016) · Cochrane | SoF7: No included studies reported change in feeling of dryness. | 0 studies | No studies |
Dietary supplements (lycopene) vs Placebo Change in quality of life (QoL) · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months), lycopene Interventions for treating burning mouth syndrome (2016) · Cochrane | MD 0.93 [-3.14, 5.00] | 1 study · 50 participants | Very low |
Benzodiazepines (topical clonazepam) vs Placebo Adverse effects: euphoric behaviour · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months), topical clonazepam Interventions for treating burning mouth syndrome (2016) · Cochrane | RR 3.00 [0.13, 70.16] | 1 study · 48 participants | Very low |
Topical treatments (topical urea 10%) vs Placebo Change in taste · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months), topical urea 10% Interventions for treating burning mouth syndrome (2016) · Cochrane | SoF9. Change in taste short-term (Quantitative Sensory Testing gustative threshold): single study narratively reported no difference in short-term gustation thresholds; 38 participants (1 RCT, topical urea); very low. | 1 study · 38 participants | Very low |
Electromagnetic radiation (low-level laser therapy) vs Placebo Change in feeling of dryness · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months) Interventions for treating burning mouth syndrome (2016) · Cochrane | SoF6: No included study reported change in feeling of dryness. | 0 studies | No studies |
Removal of predisposing habits (e.g. tobacco/alcohol cessation) vs Placebo or no treatment Outcome NR · People with a diagnosis of oral leukoplakia Interventions for treating oral leukoplakia to prevent oral cancer (2016) · Cochrane | '...nor did we identify any RCTs of risk factor cessation.' Removal of predisposing habits (e.g. smoking cessation) was a planned intervention; no eligible RCT found. | NR | No studies |
Physical barriers (tongue protector) vs Placebo Change in quality of life (QoL) · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months) Interventions for treating burning mouth syndrome (2016) · Cochrane | MD -9.20 [-26.90, 8.50] | 1 study · 50 participants | Very low |
Dietary supplements (alpha lipoic acid +/- adjunctive ingredients) vs Placebo Adverse effects: headache · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months) Interventions for treating burning mouth syndrome (2016) · Cochrane | RR 10.87 [1.36, 87.03] | 2 studies · 118 participants | Very low |
Vitamin A or retinoids (systemic or topical; incl. 13-cis-retinoic acid, acitretin) vs Placebo or no treatment Safety of the intervention (adverse effects) · People with a diagnosis of oral leukoplakia · 4 to 12 months Interventions for treating oral leukoplakia to prevent oral cancer (2016) · Cochrane | SoF 1, Safety of the intervention at 4 to 12 months: '3 studies (1 each evaluating topical acitretin, topical 13-cis-retinoic acid, 200,000 IU per week of vitamin A) found no adverse effects. Systemic 13-cis-retinoic… | 4 studies | Ungraded |
Bowman-Birk inhibitor vs Placebo or no treatment Safety of the intervention (adverse effects) · People with a diagnosis of oral leukoplakia · up to 6 months Interventions for treating oral leukoplakia to prevent oral cancer (2016) · Cochrane | SoF 6, Safety of the intervention up to 6 months: 'Trial authors reported that there were no significant adverse effects. 33 participants in the intervention group reported 75 adverse effects. 25 participants in the… | 1 study | Ungraded |
Electromagnetic radiation (low-level laser therapy) vs Placebo Adverse effects · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months) Interventions for treating burning mouth syndrome (2016) · Cochrane | SoF6: No included study reported the occurrence of adverse events. | 0 studies | No studies |
Physical barriers (tongue protector) vs Placebo Change in QoL - depression (surrogate marker) · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months) Interventions for treating burning mouth syndrome (2016) · Cochrane | MD -0.64 [-3.98, 2.70] | 1 study · 50 participants | Very low |
Anticonvulsants (gabapentin) vs Placebo Change in feeling of dryness · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months) Interventions for treating burning mouth syndrome (2016) · Cochrane | SoF2: No included studies reported change in feeling of dryness. | 0 studies | No studies |
Dietary supplements (lycopene) vs Placebo Change in QoL - anxiety (surrogate marker) · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months), lycopene Interventions for treating burning mouth syndrome (2016) · Cochrane | MD -2.85 [-5.28, -0.42] | 1 study · 50 participants | Very low |
Dietary supplements (alpha lipoic acid) vs Placebo Change in taste · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months) Interventions for treating burning mouth syndrome (2016) · Cochrane | SoF5: No included studies reported change in taste. | 0 studies | No studies |
Antidepressants (trazodone) vs Placebo Change in feeling of dryness · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months) Interventions for treating burning mouth syndrome (2016) · Cochrane | SoF1: No included studies reported change in feeling of dryness. | 0 studies | No studies |
Benzodiazepines (systemic clonazepam) vs Placebo Change in taste · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months), systemic clonazepam Interventions for treating burning mouth syndrome (2016) · Cochrane | MD -1.00 [-3.11, 1.11] | 1 study · 20 participants | Very low |
Dietary supplements (alpha lipoic acid +/- vitamins) vs Placebo Relief of burning/discomfort (symptom relief; pain intensity) · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · long-term (>3 to 6 months) Interventions for treating burning mouth syndrome (2016) · Cochrane | MD -0.89 [-2.37, 0.59] | 2 studies · 94 participants | Very low |
Anticonvulsants (gabapentin 300 mg/day + alpha lipoic acid 600 mg/day) vs Placebo Relief of burning/discomfort (symptom relief; pain intensity) · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months), gabapentin with adjunctive ALA Interventions for treating burning mouth syndrome (2016) · Cochrane | SoF2 subgroup. Gabapentin + adjunctive ALA vs placebo forms one of two subgroups of the anticonvulsant symptom-relief estimate (RR 4.00, 2.09 to 7.67); no between-subgroup difference vs gabapentin alone; 100… | 1 study · 40 participants | Very low |
Electromagnetic radiation (low-level laser therapy) vs Placebo Change in taste · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months) Interventions for treating burning mouth syndrome (2016) · Cochrane | SoF6: No included study reported change in taste. | 0 studies | No studies |
Antidepressants (trazodone 200 mg/day) vs Placebo Change in quality of life (QoL) · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months) Interventions for treating burning mouth syndrome (2016) · Cochrane | SoF1. Change in QoL short-term (mean Beck Depression Inventory, 0-63, lower better): this single study narratively reported that both intervention and placebo participants were less depressed at trial completion, but… | 1 study · 37 participants | Very low |
Systemic beta carotene or carotenoids (incl. lycopene) vs Placebo or no treatment Clinical resolution (oral lesion not completely resolved) · People with a diagnosis of oral leukoplakia · 5 to 12 months Interventions for treating oral leukoplakia to prevent oral cancer (2016) · Cochrane | SoF 2, Clinical resolution (not completely resolved) at 5 to 12 months: 'The 3 studies could not be combined in meta-analysis. 2 found benefit for systemic beta carotene, and 1 did not.' No GRADE rating. Effects text… | 3 studies | Ungraded |
Topical treatments (capsaicin oral rinse) vs Placebo Relief of burning/discomfort (symptom relief; pain intensity) · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · long-term (>3 to 6 months), capsaicin oral rinse Interventions for treating burning mouth syndrome (2016) · Cochrane | MD -2.60 [-5.11, -0.09] | 1 study · 18 participants | Very low |
Dietary supplements (alpha lipoic acid +/- adjunctive ingredients) vs Placebo Adverse effects: increase in blood pressure · People with primary burning mouth syndrome (BMS), that is, oral mucosal pain with no dental or medical cause for such… · short-term (up to 3 months) Interventions for treating burning mouth syndrome (2016) · Cochrane | RR 1.00 [0.07, 14.85] | 1 study · 38 participants | Very low |
Non-specific immunotherapy (recombinant interleukin-2 or BCG cell wall preparation) plus standard therapy vs Standard therapy alone Adverse effects · People with squamous cell carcinoma of the oral cavity or oropharynx · 24 to 70 months, Moderate to severe chills (BCG-CWP, all grades) Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy (2015) · Cochrane | RR 11.00 [0.67, 179.29] | 1 study · 24 participants | Ungraded |
Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy) Adverse effects · People with squamous cell carcinoma of the oral cavity or oropharynx · 40 to 60 months, Skin toxicity (lapatinib, all grades) Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy (2015) · Cochrane | RR 2.02 [1.23, 3.32] | 1 study · 67 participants | Ungraded |
Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy) Adverse effects · People with squamous cell carcinoma of the oral cavity or oropharynx · 40 to 60 months, Gastrointestinal complaints (gefitinib, all grades) Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy (2015) · Cochrane | RR 1.04 [0.98, 1.11] | 1 study · 226 participants | Ungraded |
Pilocarpine hydrochloride (parasympathomimetic) vs Placebo Xerostomia (subjective dry mouth; positive response = >25 mm change in VAS score) · Patients with radiation-induced salivary gland dysfunction Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy (2015) · Cochrane | Johnson 1993: positive response (>25 mm change in VAS score) in 25% of participants on placebo, 51% on pilocarpine 5 mg tds, 47% on pilocarpine 10 mg tds. LeVeque 1993: positive response in 7% on placebo vs 42% on… | 2 studies · 278 participants | Ungraded |
EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy) Adverse effects · People with squamous cell carcinoma of the oral cavity or oropharynx · 24 to 70 months, Mucositis (all grades) Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy (2015) · Cochrane | Mucositis all grades: not estimable due to high heterogeneity (P=0.0009; I2=86%) between subgroups (cetuximab; nimotuzumab) and within cetuximab (I2=93%); 1417 participants, 3 studies. Table 3, row 1.6 (Ang 2014;… | 3 studies · 1417 participants | Ungraded |
Oral cryotherapy (ice chips, ice-cold water, ice cubes or crushed ice held in the mouth during cancer treatment) vs Control (no treatment or standard/usual oral care, e.g. saline rinse) Oral mucositis (severe) · All patients with cancer who are receiving treatment · High-dose melphalan-based treatment prior to HSCT (haematological cancers) Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy (2015) · Cochrane | RR 0.38 [0.20, 0.72] | 5 studies · 270 participants | Moderate |
Oral cryotherapy (ice chips, ice-cold water, ice cubes or crushed ice held in the mouth during cancer treatment) vs High-dose leucovorin rinse Oral mucositis (severe) · Patients with osteosarcoma (bone cancer) receiving high-dose methotrexate, vincristine and leucovorin Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy (2015) · Cochrane | Oral mucositis (severe). Not estimable - no participants had developed severe oral mucositis by the fourth day after chemotherapy when the data were reported (Zhang 2011, Analysis 4.3, subgroup 3.2); 81 participants in… | 1 study · 81 participants | Ungraded |
Parasympathomimetic drugs (choline esters, cholinesterase inhibitors) vs No treatment Outcome NR · Patients with radiation-induced salivary gland dysfunction Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy (2015) · Cochrane | no estimate extracted | 0 studies | No studies |
Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy) Adverse effects · People with squamous cell carcinoma of the oral cavity or oropharynx · 40 to 60 months, Gastrointestinal complaints (lapatinib, all grades) Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy (2015) · Cochrane | RR 15.53 [2.18, 110.55] | 1 study · 67 participants | Ungraded |
Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy) Adverse effects · People with squamous cell carcinoma of the oral cavity or oropharynx · 40 to 60 months, Skin toxicity (erlotinib, all grades) Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy (2015) · Cochrane | RR 6.57 [3.60, 12.00] | 1 study · 191 participants | Ungraded |
EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy) Adverse effects · People with squamous cell carcinoma of the oral cavity or oropharynx · 24 to 70 months, Skin toxicity/acneiform rash (cetuximab, all grades) Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy (2015) · Cochrane | RR 6.56 [5.35, 8.03] | 2 studies · 1311 participants | Ungraded |
Oral cryotherapy (ice chips, ice-cold water, ice cubes or crushed ice held in the mouth during cancer treatment) vs Control (no treatment or standard/usual oral care, e.g. saline rinse) Number of days of treatment with opioid analgesics · All patients with cancer who are receiving treatment · Fluorouracil (5FU) treatment for solid cancers Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy (2015) · Cochrane | No studies in the 5FU subgroup assessed the number of days of treatment with opioid analgesics. | 0 studies | No studies |
Non-specific immunotherapy (recombinant interleukin-2 or BCG cell wall preparation) plus standard therapy vs Standard therapy alone Disease-free survival · People with squamous cell carcinoma of the oral cavity or oropharynx · 24 to 70 months, Recombinant interleukin-2 + surgery (De Stefani 2002) Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy (2015) · Cochrane | HR 0.66 [0.43, 1.02] | 1 study · 201 participants | Very low |
EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy) Progression-free survival · People with squamous cell carcinoma of the oral cavity or oropharynx · 24 to 70 months, Monoclonal antibody + chemoradiotherapy vs chemoradiotherapy alone Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy (2015) · Cochrane | HR 1.08 [0.89, 1.32] | 1 study · 891 participants | Ungraded |
Oral cryotherapy (ice chips, ice-cold water, ice cubes or crushed ice held in the mouth during cancer treatment) vs Control (no treatment or standard/usual oral care, e.g. saline rinse) Quality of life · All patients with cancer who are receiving treatment · High-dose melphalan-based treatment prior to HSCT (haematological cancers) Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy (2015) · Cochrane | Summary of findings 2 (melphalan/HSCT): Quality of life - '1 study assessed this outcome but the data are currently unavailable as the study report and analysis have not yet been completed' (Toro 2013; measured with… | 1 study | Ungraded |
Oral cryotherapy (ice chips, ice-cold water, ice cubes or crushed ice held in the mouth during cancer treatment) vs Control (no treatment or standard/usual oral care, e.g. saline rinse) Adverse events · All patients with cancer who are receiving treatment · High-dose melphalan-based treatment prior to HSCT (haematological cancers) Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy (2015) · Cochrane | Adverse events reported narratively: one study did not report adverse events (Askarifar 2015); another reported no serious adverse events (Toro 2013); the remaining two reported low rates of shooting pain from the… | 3 studies | Ungraded |
Oral cryotherapy (ice chips, ice-cold water, ice cubes or crushed ice held in the mouth during cancer treatment) vs Low-dose leucovorin rinse Oral mucositis (severe) · Patients with osteosarcoma (bone cancer) receiving high-dose methotrexate, vincristine and leucovorin Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy (2015) · Cochrane | Oral mucositis (severe). Not estimable - no participants had developed severe oral mucositis by the fourth day after chemotherapy when the data were reported (Zhang 2011, Analysis 4.3, subgroup 3.1); 118 participants… | 1 study · 118 participants | Ungraded |
Oral cryotherapy for 30 minutes vs Oral cryotherapy for 60 minutes Oral mucositis (moderate to severe) · Adults with solid cancers receiving fluorouracil (5FU) and leucovorin Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy (2015) · Cochrane | RR 0.68 [0.36, 1.30] | 1 study · 178 participants | Very low |
Non-specific immunotherapy (recombinant interleukin-2 or BCG cell wall preparation) plus standard therapy vs Standard therapy alone Adverse effects · People with squamous cell carcinoma of the oral cavity or oropharynx · 24 to 70 months, Nausea/vomiting (rIL-2, grades >=3) Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy (2015) · Cochrane | RR 3.40 [0.15, 77.34] | 1 study · 30 participants | Ungraded |
Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy) Progression-free survival · People with squamous cell carcinoma of the oral cavity or oropharynx · 40 to 60 months Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy (2015) · Cochrane | HR 0.80 [0.51, 1.28] | 2 studies · 271 participants | Very low |
EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy) Participant satisfaction · People with squamous cell carcinoma of the oral cavity or oropharynx · 24 to 70 months Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy (2015) · Cochrane | No included studies addressed participant satisfaction (review-wide gap). | 0 studies | No studies |
Pilocarpine hydrochloride (parasympathomimetic) vs Placebo Other oral symptoms (oral discomfort, dysphonia) · Patients with radiation-induced salivary gland dysfunction Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy (2015) · Cochrane | Both studies assessed oral discomfort and dysphonia (Johnson 1993; LeVeque 1993); pilocarpine reported to improve associated symptoms of salivary gland dysfunction (oral discomfort, dysphonia). No pooled data. | 2 studies · 278 participants | Ungraded |
Oral cryotherapy (ice chips, ice-cold water, ice cubes or crushed ice held in the mouth during cancer treatment) vs Control (no treatment or standard/usual oral care, e.g. saline rinse) Oral mucositis (mean severity on WHO 0 to 4 scale) · All patients with cancer who are receiving treatment · Radiotherapy to the head and neck Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy (2015) · Cochrane | MD -0.25 [-0.72, 0.22] | 1 study · 40 participants | Very low |