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metastatic/advanced - colorectal cancer (mCRC), atezolizumab based treatment , 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

deaths (OS) 1.00 [0.80, 1.25]< 10%2 studies (2/-)50.0 %some concernnot evaluable moderatecrucial-
progression or deaths (PFS) 1.31 [1.05, 1.62]< 10%2 studies (2/-)0.7 %some concernnot evaluable moderateimportant-
objective responses (ORR) 1.13 [0.32, 4.04]> 10%2 studies (2/-)57.6 %some concernnot evaluable moderatenon important-

safety endpoints 00

AE (any grade) 0.96 [0.39, 2.38]< 10%2 studies (2/-)53.1 %some concernnot evaluable moderatenon important-
AE (grade 3-4) 0.63 [0.19, 2.11]< 188%2 studies (2/-)77.4 %some concernnot evaluable moderatenon important-
AE leading to death (grade 5) 0.78 [0.18, 3.38]< 10%2 studies (2/-)63.0 %some concernnot evaluable moderatenon important-
AE leading to treatment discontinuation (any grade) 1.23 [0.23, 6.60]< 179%2 studies (2/-)40.6 %some concernnot evaluable moderatenon important-
SAE (any grade) 1.28 [0.40, 4.10]< 183%2 studies (2/-)34.0 %some concernnot evaluable moderatenon important-
STRAE (any grade) 1.41 [0.35, 5.60]< 178%2 studies (2/-)31.4 %some concernnot evaluable moderatenon important-
TRAE (any grade) 0.18 [0.01, 2.73]< 189%2 studies (2/-)88.9 %some concernnot evaluable moderatenon important-
TRAE (grade 3-4) 0.32 [0.05, 2.26]< 194%2 studies (2/-)87.2 %some concernnot evaluable moderatenon important-
TRAE leading to death (grade 5) 0.71 [0.10, 5.06]< 10%2 studies (2/-)63.5 %some concernnot evaluable moderatenon important-

TRAE (grade 3-4) endpoints 00

Dyspnoea TRAE (grade 3-4) 0.89 [0.08, 9.99]< 10%1 study (1/-)53.6 %NAnot evaluable non important-
Increased lipase level TRAE (grade 3-4) 1.37 [0.24, 7.75]< 10%2 studies (2/-)36.0 %some concernnot evaluable moderatenon important-

AE (grade 3-4) endpoints 00

hepatitis (Autoimmune) AE (grade 3-4) 1.61 [0.14, 18.49]< 10%2 studies (2/-)35.2 %some concernnot evaluable moderatenon important-
Abdominal pain AE (grade 3-4) 0.64 [0.16, 2.54]< 127%2 studies (2/-)73.6 %some concernnot evaluable moderatenon important-
Acute kidney injury AE (grade 3-4) 0.63 [0.04, 10.13]< 10%2 studies (2/-)62.7 %some concernnot evaluable moderatenon important-
Anaemia AE (grade 3-4) 1.06 [0.12, 9.33]< 144%2 studies (2/-)47.9 %some concernnot evaluable moderatenon important-
Arthralgia AE (grade 3-4) 0.31 [0.03, 3.47]< 10%2 studies (2/-)82.6 %some concernnot evaluable moderatenon important-
Asthenia AE (grade 3-4) 2.50 [0.51, 12.27]< 10%2 studies (2/-)13.0 %some concernnot evaluable moderatenon important-
Back pain AE (grade 3-4) 2.17 [0.20, 23.63]< 10%2 studies (2/-)26.4 %some concernnot evaluable moderatenon important-
Colitis AE (grade 3-4) 1.79 [0.18, 17.83]< 10%2 studies (2/-)31.1 %some concernnot evaluable moderatenon important-
Constipation AE (grade 3-4) 0.89 [0.07, 11.69]< 10%2 studies (2/-)53.5 %some concernnot evaluable moderatenon important-
Cough AE (grade 3-4) 0.63 [0.04, 10.13]< 10%2 studies (2/-)62.7 %some concernnot evaluable moderatenon important-
Decreased appetite AE (grade 3-4) 0.36 [0.07, 1.91]< 10%2 studies (2/-)88.4 %some concernnot evaluable moderatenon important-
Dermatitis acneiform AE (grade 3-4) 1.37 [0.12, 15.71]< 10%2 studies (2/-)40.1 %some concernnot evaluable moderatenon important-
Diarrhoea AE (grade 3-4) 0.69 [0.07, 7.10]< 174%2 studies (2/-)62.3 %some concernnot evaluable moderatenon important-
Dysgeusia AE (grade 3-4) 0.89 [0.07, 11.69]< 10%2 studies (2/-)53.5 %some concernnot evaluable moderatenon important-
Dysphonia AE (grade 3-4) 0.63 [0.04, 10.13]< 10%2 studies (2/-)62.7 %some concernnot evaluable moderatenon important-
Dyspnoea AE (grade 3-4) 0.44 [0.01, 13.33]< 10%1 study (1/-)67.8 %NAnot evaluable non important-
Fatigue AE (grade 3-4) 0.54 [0.25, 1.19]< 10%2 studies (2/-)93.8 %some concernnot evaluable moderatenon important-
Guillain-Barré syndrome AE (grade 3-4) 0.89 [0.07, 11.69]< 10%2 studies (2/-)53.5 %some concernnot evaluable moderatenon important-
Headache AE (grade 3-4) 0.89 [0.07, 11.69]< 10%2 studies (2/-)53.5 %some concernnot evaluable moderatenon important-
Hypertension AE (grade 3-4) 0.15 [0.05, 0.44]< 113%2 studies (2/-)100.0 %some concernnot evaluable moderatenon important-
Increased ALT AE (grade 3-4) 0.31 [0.03, 3.47]< 10%2 studies (2/-)82.6 %some concernnot evaluable moderatenon important-
Infusion-related reaction AE (grade 3-4) 1.37 [0.12, 15.71]< 10%2 studies (2/-)40.1 %some concernnot evaluable moderatenon important-
Intestinal perforation AE (grade 3-4) 0.31 [0.03, 3.47]< 10%2 studies (2/-)82.6 %some concernnot evaluable moderatenon important-
Mucosal inflammation AE (grade 3-4) 1.37 [0.12, 15.71]< 10%2 studies (2/-)40.1 %some concernnot evaluable moderatenon important-
Myalgia AE (grade 3-4) 0.31 [0.03, 3.47]< 10%2 studies (2/-)82.6 %some concernnot evaluable moderatenon important-
Nausea AE (grade 3-4) 1.37 [0.12, 15.71]< 10%2 studies (2/-)40.1 %some concernnot evaluable moderatenon important-
Palmar–plantar erythrodysesthesia syndrome AE (grade 3-4) 0.03 [0.00, 0.24]< 10%2 studies (2/-)100.0 %some concernnot evaluable moderatenon important-
Peripheral neuropathy AE (grade 3-4) 0.31 [0.03, 3.47]< 10%2 studies (2/-)82.6 %some concernnot evaluable moderatenon important-
Peripheral oedema AE (grade 3-4) 1.37 [0.12, 15.71]< 10%2 studies (2/-)40.1 %some concernnot evaluable moderatenon important-
Pneumonitis AE (grade 3-4) 1.26 [0.11, 14.04]< 10%2 studies (2/-)42.5 %some concernnot evaluable moderatenon important-
Pruritus AE (grade 3-4) 0.63 [0.04, 10.13]< 10%2 studies (2/-)62.7 %some concernnot evaluable moderatenon important-
Pyrexia AE (grade 3-4) 3.23 [0.32, 33.03]< 10%2 studies (2/-)16.3 %some concernnot evaluable moderatenon important-
Rash AE (grade 3-4) 1.08 [0.28, 4.07]< 10%2 studies (2/-)45.8 %some concernnot evaluable moderatenon important-
Rash maculopapular AE (grade 3-4) 0.44 [0.05, 3.83]< 10%2 studies (2/-)76.9 %some concernnot evaluable moderatenon important-
Sepsis AE (grade 3-4) 0.36 [0.07, 1.91]< 10%2 studies (2/-)88.4 %some concernnot evaluable moderatenon important-
Stomatitis AE (grade 3-4) 0.63 [0.04, 10.13]< 10%2 studies (2/-)62.7 %some concernnot evaluable moderatenon important-
Thrombocytopenia AE (grade 3-4) 0.89 [0.07, 11.69]< 10%2 studies (2/-)53.5 %some concernnot evaluable moderatenon important-
Vomiting AE (grade 3-4) 0.89 [0.07, 11.69]< 10%2 studies (2/-)53.5 %some concernnot evaluable moderatenon important-
Weight decreased AE (grade 3-4) 0.63 [0.04, 10.13]< 10%2 studies (2/-)62.7 %some concernnot evaluable moderatenon 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.