Evidence tabellen met GRADE-uitwerking

Question: Should Imiquimod cream vs Photodynamic therapy be used for primairy superficial basal cell carcinoma?¹ Bibliography: Arits AHMM, Mosterd K, Essers BAB, et al. Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: A single blind, non-inferiority, randomised controlled trial. The lancet oncology 2013;14:647-54
Quality assessment							Summary of Findings
Participants (studies) Follow up	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Overall quality of evidence	Study event rates (%)		Risk Difference (95% CI)
Participants (studies) Follow up	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Overall quality of evidence	With Photodynamic therapy	With Imiquimod cream	Risk Difference (95% CI)
Complete response (CRITICAL OUTCOME; assessed with: Clinical and Histological assessment²)
385 (1 study⁵) 3 months	serious³	no serious inconsistency	no serious indirectness	no seriousimprecision	undetected	⊕⊕⊕⊝ MODERATE³ due to risk of bias	165/196 (84.2%)	170/189 (90.0%)	Risk Difference -0.06 (-0.12 to 0.01)
Treatment success at 1 yr (CRITICAL OUTCOME; assessed with: Clincial and Histological assessment²)
385 (1 study⁵) 1 years	serious³	no serious inconsistency	no serious indirectness	no seriousimprecision	undetected	⊕⊕⊕⊝ MODERATE³ due to risk of bias	144/196 (73.5%)¹⁰	158/189 (83.6%)¹⁰	Risk Difference -0.10 (-0.18 to 0.02)
Treatment success at 2 yr - not measured
-	-	-	-	-	-	-	-	-	-
Treatment success at 5 yr - not measured
-	-	-	-	-	-	-	-	-	-
Compliance less than 100% (IMPORTANT OUTCOME; assessed with: Patients diary⁶)
391 (1 study⁵) 1 years	serious^3,7	no serious inconsistency	no serious indirectness	no serious imprecision	undetected	⊕⊕⊕⊝ MODERATE^3,7 due to risk of bias	0/200 (0%)	40/191 (20.9%)	Risk Difference 0.17 (0.12 to 0.22)
Good to excellent aesthetic outcome (IMPORTANT OUTCOME; assessed with: Four-point scale ⁸)
370 (1 study) 1 years	serious^3,9	no serious inconsistency	no serious indirectness	serious⁴	undetected	⊕⊕⊝⊝ LOW ^3,4,9 due to risk of bias and imprecision	116/186 (62.4%)	113/184 (61.4%)	Risk Difference -0.01 (-0.11 to 0.09)

¹ Methylaminolevulinate photodynamic therapy

² In case there was clinical suspicion of basal-cell carcinoma recurrence at the follow-up visits, a 3 mm punch biopsy was taken for histological verification.

³ Possible unrecognized heterogeneity of effect of treatment across centers

⁴downgraded one level for imprecision due to wide confidence intervals that include both difference and no difference.

⁵ There is only one RCT which compares Imiquimod cream with a treating regimen of 5x/week for 6 weeks and MAL-PDT directly

⁶ Compliance was calculated as number of cream applications done by the patient divided by the total prescribed number of cream applications.

⁷ Unvalidated patient-reported outcome measure for imiquimod.

⁸ Excellent, good, fair, poor assessed by one observer blinded to treatment assignment

⁹ Subjective outcome

¹⁰Percentages in GRADE and EBRO were calculated using a different methods and therefore slightly differ

Question: Should 5-fluorouracil cream vs Photodynamic therapy be used for primary superficial basal cell carcinoma?¹ Bibliography: Arits AHMM, Mosterd K, Essers BAB, et al. Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: A single blind, non-inferiority, randomised controlled trial. The lancet oncology 2013;14:647-54
Quality assessment							Summary of Findings
Participants (studies) Follow up	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Overall quality of evidence	Study event rates (%)		Relative effect (95% CI)
Participants (studies) Follow up	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Overall quality of evidence	With Photodynamic therapy	With 5-fluorouracil cream	Relative effect (95% CI)
Complete response (CRITICAL OUTCOME; assessed with: Clinical and Histological assessment²)
394 (1 study⁵) 3 months	serious³	no serious inconsistency	no serious indirectness	serious⁴	undetected	⊕⊕⊝⊝ LOW^3,4 due to risk of bias and imprecision	165/196 (84.2%)	174/198 (87.9%)	Risk Difference 3.7 (-3.1 to 10.5)⁴
Treatment success at 1 yr (CRITICAL OUTCOME; assessed with: Clinical and Histological assessment²)
394 (1 study⁵) 1 years	serious³	no serious inconsistency	no serious indirectness	serious⁴	undetected	⊕⊕⊝⊝ LOW^3,4 due to risk of bias and imprecision	144/196 (73.5%)¹⁰	159/198 (80.3%)¹⁰	Risk Difference 6.8 (-1.5 to 15.1)⁴
Treatment succes at 2 yr - not measured
-	-	-	-	-	-	-	-	-	-
Treatment success at 5 yr - not measured
-	-	-	-	-	-	-	-	-	-
Compliance less than 100% (IMPORTANT OUTCOME; assessed with: Patients diary⁶)
395 (1 study⁵) 1 years	serious^3,7	no serious inconsistency	no serious indirectness	no serious imprecision	undetected	⊕⊕⊕⊝ MODERATE^3,7 due to risk of bias	0/200 (0%)	61/195 (31.3%)	Risk Difference 31.3 (24.77 to 37.79)⁴
Aesthetic outcome (IMPORTANT OUTCOME; assessed with: Four-point scale⁸)
379 (1 study) 1 years	serious^3,9	no serious inconsistency	no serious indirectness	serious⁴	undetected	⊕⊕⊝⊝ LOW^3,4,9 due to risk of bias and imprecision	116/186 (62.4%)	111/193 (57.5%)	Risk Difference -4.9 (-14.8 to 5.0)

¹ Methylaminolevulinate photodynamic therapy

² In case there was clinical suspicion of basal-cell carcinoma recurrence at the follow-up visits, a 3 mm punch biopsy was taken for histological verification

³ Possible unrecognized heterogeneity of effect of treatment across centers

⁴ Downgraded one level for imprecision due to wide confidence interval that includes both difference and no difference.

⁵ There is only one RCT which compares 5-fluorouracil cream and MAL-PDT directly

⁶ Compliance was calculated as number of cream applications done by the patient divided by the total prescribed number of cream applications.

⁷ Unvalidated patient-reported outcome measure for 5-fluorouracil.

⁸ Excellent, good, fair, poor assessed by one observer blinded to treatment assignment

⁹ Subjective outcome

¹⁰Percentages in GRADE and EBRO were calculated using a different methods and therefore slightly differ

Question: Should 5-Fluorouracil cream vs Imiquimod cream be used for primairy superficial basal cell carcinoma? Bibliography: Arits AHMM, Mosterd K, Essers BAB, et al. Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: A single blind, non-inferiority, randomised controlled trial. The lancet oncology 2013;14:647-54
Quality assessment							Summary of Findings
Participants (studies) Follow up	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Overall quality of evidence	Study event rates (%)		Relative effect (95% CI)
Participants (studies) Follow up	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Overall quality of evidence	With Imiquimod cream	With 5-Fluorouracil cream	Relative effect (95% CI)
Complete response (CRITICAL OUTCOME; assessed with: Clinical and Histological assessment¹)
387 (1 study⁴) 3 months	serious²	no serious inconsistency	no serious indirectness	serious ³	undetected	⊕⊕⊝⊝ LOW^2,3 due to risk of bias and imprecision	170/189 (90.0%)	174/198 (87.9%)	Risk Difference -2.1 (-8.3 to 4.2)³
Treatment success at 1 yr (CRITICAL OUTCOME; assessed with: Clinical and Histological assessment¹)
387 (1 study⁴) 1 years	serious²	no serious inconsistency	no serious indirectness	serious ³	undetected	⊕⊕⊝⊝ LOW^2,3 due to risk of bias and imprecision	158/189 (83.6%)⁹	159/198 (80.3%)⁹	Risk Difference -3.3 (-11.0 to 4.4)³
Treatment success at 2 yr - not measured
-	-	-	-	-	-	See comment	-	-	-
Treatment success at 5 yr - not measured
-	-	-	-	-	-	See comment	-	-	-
Compliance less than 100% (IMPORTANT OUTCOME; assessed with: Patient's diary⁵)
386 (1 study⁴) 1 years	serious^2,6	no serious inconsistency	no serious indirectness	serious ³	undetected	⊕⊕⊝⊝ LOW^2,3,6 due to risk of bias and imprecision	40/191 (20.9%)	61/195 (31.3%)	Risk Difference 10.3 (1.6 to 19.0)³
Aesthetic outcome (IMPORTANT OUTCOME; assessed with: Four-point scale⁷)
377 (1 study) 1 years	serious^2,8	no serious inconsistency	no serious indirectness	serious ³	undetected	⊕⊕⊝⊝ LOW^2,3,8 due to risk of bias and imprecision	113/184 (61.4%)	111/193 (57.5%)	Risk Difference -3.9 (-13.8 to 6.0)³

¹ In case there was clinical suspicion of basal-cell carcinoma recurrence at the follow-up visits, a 3 mm punch biopsy was taken for histological verification.

² Possible unrecognized heterogeneity of effect of treatment across centers

³ downgraded one level for imprecision due to wide confidence intervals that include both difference and no difference.

⁴ There is only one RCT which compares Imiquimod cream with a treating regimen of 5x/week for 6 weeks and MAL-PDT directly

⁵ Compliance was calculated as number of cream applications done by the patient divided by the total prescribed number of cream applications.

⁶ Unvalidated patient-reported outcome measure for imiquimod.

⁷ Excellent, good, fair, poor assessed by one observer blinded to treatment assignment

⁸ Subjective outcome

⁹Percentages in GRADE and EBRO were calculated using a different methods and therefore slightly differ