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melanoma (ML), nivolumab based treatment versus placebo, meta-analysis of study results

Outcome Relative effect 95%CI LoD Trt. better when I2 k (RCT/OBS) Bayesian probability Overall ROB Publication bias Degree of certainty Endpoint importance Published MA

efficacy endpoints 00

RFS/DFS 0.56 [0.33, 0.95]< 10%1 study (1/-)98.5 %NAnot evaluable important-

safety endpoints 00

AE leading to death (grade 5) 0.93 [0.02, 47.58]< 10%1 study (1/-)51.5 %NAnot evaluable non important-
AE leading to treatment discontinuation (any grade) 3.57 [0.71, 18.07]< 10%1 study (1/-)6.2 %NAnot evaluable non important-
AE leading to treatment discontinuation (grade 3-4) 4.90 [0.55, 43.46]< 10%1 study (1/-)7.8 %NAnot evaluable non important-
SAE (any grade) 1.27 [0.56, 2.87]< 10%1 study (1/-)28.6 %NAnot evaluable non important-
SAE (grade 3-4) 2.51 [0.94, 6.74]< 10%1 study (1/-)3.4 %NAnot evaluable non important-
STRAE (any grade) 6.13 [1.29, 29.17]< 10%1 study (1/-)1.2 %NAnot evaluable non important-
STRAE (grade 3-4) 19.34 [1.09, 342.95]< 10%1 study (1/-)2.3 %NAnot evaluable non important-
TRAE (any grade) 4.29 [1.74, 10.57]< 10%1 study (1/-)0.1 %NAnot evaluable non important-
TRAE (grade 3-4) 5.85 [1.58, 21.65]< 10%1 study (1/-)0.4 %NAnot evaluable non important-
TRAE leading to death (grade 5) 0.93 [0.02, 47.58]< 10%1 study (1/-)51.5 %NAnot evaluable non important-
TRAE leading to discontinuation (any grade) 7.29 [0.86, 61.51]< 10%1 study (1/-)3.5 %NAnot evaluable non important-
TRAE leading to discontinuation (grade 3-4) 9.90 [0.53, 186.01]< 10%1 study (1/-)6.5 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Abdominal pain TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Acute kidney injury TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Adrenal insufficiency TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Alopecia TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Anaemia TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Arthralgia TRAE (grade 3-4) 3.74 [0.16, 84.94]< 10%1 study (1/-)20.7 %NAnot evaluable non important-
Blood and lymphatic system disorders TRAE (grade 3-4) 5.72 [0.28, 116.99]< 10%1 study (1/-)13.2 %NAnot evaluable non important-
Blood creatinine increased TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Chills TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Colitis TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Cough TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Decreased appetite TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Diabetes TRAE (grade 3-4) 1.84 [0.06, 55.93]< 10%1 study (1/-)36.6 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 1.84 [0.06, 55.93]< 10%1 study (1/-)36.6 %NAnot evaluable non important-
Dizziness TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Dry skin TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Dysgeusia TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Dyspepsia TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Dyspnoea TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Endocrine disorders TRAE (grade 3-4) 1.84 [0.06, 55.93]< 10%1 study (1/-)36.6 %NAnot evaluable non important-
Eye disorders TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Gastritis TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Gastrointestinal disorders TRAE (grade 3-4) 1.84 [0.06, 55.93]< 10%1 study (1/-)36.6 %NAnot evaluable non important-
General disorders and administration site conditions TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Headache TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Hepatitis TRAE (grade 3-4) 3.74 [0.16, 84.94]< 10%1 study (1/-)20.7 %NAnot evaluable non important-
Hepatobiliary disorders TRAE (grade 3-4) 3.74 [0.16, 84.94]< 10%1 study (1/-)20.7 %NAnot evaluable non important-
Hypertension TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Hyperthyroidism TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Hypophysitis TRAE (grade 3-4) 1.84 [0.06, 55.93]< 10%1 study (1/-)36.6 %NAnot evaluable non important-
Hypothyroidism TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Increase AST TRAE (grade 3-4) 5.72 [0.28, 116.99]< 10%1 study (1/-)13.2 %NAnot evaluable non important-
Increased ALT TRAE (grade 3-4) 5.72 [0.28, 116.99]< 10%1 study (1/-)13.2 %NAnot evaluable non important-
Increased lipase level TRAE (grade 3-4) 0.91 [0.17, 4.70]< 10%1 study (1/-)54.7 %NAnot evaluable non important-
Infusion-related reactions TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Leucopenia TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Maculopapular rash TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Metabolism and nutrition disorders TRAE (grade 3-4) 1.84 [0.06, 55.93]< 10%1 study (1/-)36.6 %NAnot evaluable non important-
Musculoskeletal and connective tissue disorders TRAE (grade 3-4) 5.72 [0.28, 116.99]< 10%1 study (1/-)13.2 %NAnot evaluable non important-
Myalgia TRAE (grade 3-4) 1.84 [0.06, 55.93]< 10%1 study (1/-)36.6 %NAnot evaluable non important-
Myositis TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Nausea TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Nervous system disorders TRAE (grade 3-4) 3.74 [0.16, 84.94]< 10%1 study (1/-)20.7 %NAnot evaluable non important-
Neutropenia TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Palmar-plantar erythrodysaesthesia syndrome TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Pancreatitis TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Paraesthesia TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Peripheral neuropathy TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Pneumonitis TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Pruritus TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Pyrexia TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Sarcoidosis TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Skin and subcutaneous tissue disorders TRAE (grade 3-4) 1.84 [0.06, 55.93]< 10%1 study (1/-)36.6 %NAnot evaluable non important-
Stomatitis TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Thrombocytopenia TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Thyroiditis TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Uveitis TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Vitiligo TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Vomiting TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Weight decreased TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-

LoD: level of statistical demonstration: Statistically conclusive: statistically significant with a strict control of overall risk of type 1 error (statistically demonstrated), does not take into account the risk of bias; suggested: nominally statistically significant but without a strict control of overall risk of type 1 error; inconclusive: not nominally statistically significant; safety concerns;
Bayesian probability: Bayesian posterior probability of treatment effect (computed with a noninformative prior); ROB: risk of bias; k: number of studies; published MA: number of published meta-analysis on the same topic; degree of certainty adapted from GRADE. Trt. better when: indicates when the relative treatment effect shows that the studied treatment is better than control.