What do systematic reviews say?

Aromatherapy vs placebo or control

• Aromatherapy for dementia 2020 · Cochrane Headline outcomes only
  no estimate extracted
  4 studies · 206 participants
  Very low

Chemotherapy (any regimen; added to, or compared with, locoregional treatment) vs Locoregional treatment and/or an alternative chemotherapy regimen

• Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy 2021 · Cochrane All outcomes
  Harms/toxicity were planned but very little quantitative data suitable for analysis were found; toxicity reported narratively and not quantified or GRADE-rated.
  Studies not reported
  GRADE not reported

Chemotherapy vs chemotherapy alone

• Salvage systemic therapy for advanced gastric and oesophago‐gastric junction adenocarcinoma 2020 · Cochrane Headline outcomes only
  no estimate extracted
  4 studies · 448 participants
  High

GnRH agonist plus chemotherapy vs chemotherapy alone

It is very uncertain whether gnRH agonist plus chemotherapy changes adverse effects: hot flush compared with chemotherapy alone (very low certainty).

• Adjuvant gonadotropin‐releasing hormone analogues for the prevention of chemotherapy‐induced premature ovarian failure… 2019 · Cochrane Headline outcomes only
  RR 1.49 [0.16, 13.6]
  4 studies · 731 participants
  Very low

GnRH agonist plus chemotherapy vs chemotherapy alone

GnRH agonist plus chemotherapy showed no clear difference in adverse effects: vaginal dryness compared with chemotherapy alone (moderate certainty).

• Adjuvant gonadotropin‐releasing hormone analogues for the prevention of chemotherapy‐induced premature ovarian failure… 2019 · Cochrane Headline outcomes only
  RR 1.18 [0.68, 2.04]
  2 studies · 488 participants
  Moderate

Antibiotics vs placebo compared

Antibiotic therapy showed no clear difference in treatment harms (adverse events or side effects associated with… compared with placebo compared to placebo (low certainty).

• Antibiotic therapy versus no antibiotic therapy for children aged 2 to 59 months with WHO‐defined non‐severe pneumonia… 2021 · Cochrane Headline outcomes only
  RR 0.81 [0.6, 1.09]
  3 studies · 3253 participants
  Low

Brachytherapy vs brachytherapy plus radiotherapy

Brachytherapy showed no clear difference in adverse effects compared with brachytherapy plus radiotherapy (moderate certainty).

• Interventions for dysphagia in oesophageal cancer 2014 · Cochrane Headline outcomes only
  OR 1.17 [0.44, 3.15]
  2 studies · 554 participants
  Moderate

Pre‐emptive antifungal therapy vs empirical antifungal therapy

• Pre‐emptive antifungal therapy versus empirical antifungal therapy for febrile neutropenia in people with cancer 2022 · Cochrane Headline outcomes only
  no estimate extracted
  4 studies · 1074 participants
  Very low

Laser therapy vs no laser therapy

• Laser therapy for retinopathy in sickle cell disease 2022 · Cochrane Headline outcomes only
  no estimate extracted
  3 studies · 414 participants
  Low

Combined HBO and perioperative antibiotics prior to dental implant therapy vs antibiotics alone

• Interventions for preventing osteoradionecrosis of the jaws in adults receiving head and neck radiotherapy 2019 · Cochrane All outcomes

  1 year
  This comparison was only made in 1 study which reported no serious adverse events associated with HBO therapy. Quality of life measures (oral status, functioning, satisfaction) showed emotional functioning and pain…
  1 study · 26 participants
  Very low

Hyperbaric oxygen therapy (HBO) following extractions vs penicillin G

• Interventions for preventing osteoradionecrosis of the jaws in adults receiving head and neck radiotherapy 2019 · Cochrane All outcomes

  6 months
  Adverse effects were an outcome of interest in the study conducting this comparison, however no mention was made of the presence or absence of any adverse events
  1 study · 74 participants
  Very low

Bevacizumab plus chemotherapy vs chemotherapy alone

Chemotherapy + bevacizumab showed no clear difference in severe adverse effects compared with chemotherapy (low certainty).

• Second‐line systemic therapy for metastatic colorectal cancer 2017 · Cochrane Headline outcomes only
  RR 1.07 [0.93, 1.25]
  4 studies · 1708 participants
  Low

Combination therapy vs monotherapy

It is very uncertain whether combination therapy changes withdrawals due to adverse effects compared with monotherapy (very low certainty).

• First‐line combination therapy versus first‐line monotherapy for primary hypertension 2020 · Cochrane Headline outcomes only
  RR 0.85 [0.53, 1.35]
  3 studies · 568 participants
  Very low

Non-specific immunotherapy (recombinant interleukin-2 or BCG cell wall preparation) plus standard therapy vs Standard therapy alone (radiotherapy or chemoradiotherapy)

Non-specific immunotherapy (recombinant interleukin-2 or BCG cell… showed no clear difference in adverse effects compared with standard therapy alone; GRADE not reported.

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Moderate to severe chills (BCG-CWP, all grades)
  RR 11.00 [0.67, 179.29]
  1 study · 24 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Nausea/vomiting (rIL-2, grades >=3)
  RR 3.40 [0.15, 77.34]
  1 study · 30 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Stomatitis (rIL-2, all grades)
  RR 1.47 [0.75, 2.90]
  1 study · 30 participants
  GRADE not reported

Brachytherapy vs brachytherapy plus radiotherapy

Brachytherapy showed no clear difference in adverse effects ‐ stricture compared with brachytherapy plus radiotherapy (high certainty).

• Interventions for dysphagia in oesophageal cancer 2014 · Cochrane Headline outcomes only
  OR 1.43 [0.16, 12.85]
  2 studies · 277 participants
  High

Initiation of prophylactic therapy guided by colonoscopy vs initiation of prophylactic therapy immediately after surgery

It is very uncertain whether initiation of prophylactic therapy guided by colonoscopy changes adverse effects ( compared with initiation of prophylactic therapy immediately after surgery (very low certainty).

• Colonoscopy‐guided therapy for the prevention of post‐operative recurrence of Crohn’s disease 2020 · Cochrane Headline outcomes only
  RR 0.58 [0.42, 0.82]
  1 study · 63 participants
  Very low

EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Mucositis (all grades)
  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
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Skin toxicity/acneiform rash (cetuximab, all grades)
  RR 6.56 [5.35, 8.03]
  2 studies · 1311 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Xerostomia (grades >=3)
  RR 1.36 [0.80, 2.31]
  2 studies · 1311 participants
  GRADE not reported

Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus… led to higher adverse effects compared with standard therapy alone (radiotherapy or chemoradiotherapy); GRADE not reported.

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  40 to 60 months · Skin toxicity (lapatinib, all grades)
  RR 2.02 [1.23, 3.32]
  1 study · 67 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  40 to 60 months · Gastrointestinal complaints (gefitinib, all grades)
  RR 1.04 [0.98, 1.11]
  1 study · 226 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  40 to 60 months · Gastrointestinal complaints (lapatinib, all grades)
  RR 15.53 [2.18, 110.55]
  1 study · 67 participants
  GRADE not reported

Chemotherapy vs best supportive care

Chemotherapy probably leads to higher severe adverse effects compared with best supportive care (moderate certainty).

• Second‐line systemic therapy for metastatic colorectal cancer 2017 · Cochrane Headline outcomes only
  RR 1.19 [1.01, 1.4]
  1 study · 279 participants
  Moderate

Positional therapy vs continuous positive airway pressure (CPAP)

• Positional therapy for obstructive sleep apnoea 2019 · Cochrane Headline outcomes only
  no estimate extracted
  1 study · 20 participants
  GRADE not reported