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Lee NJ, McDonagh M, Chan B, et al. Drug Class Review: Topical Calcineurin Inhibitors: Final Report [Internet]. Portland (OR): Oregon Health & Science University; 2008 Oct.

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Drug Class Review: Topical Calcineurin Inhibitors: Final Report [Internet].

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Appendix FAssessing the strength of comparative evidence (using the modified GRADE approach)

We assessed the overall strength of evidence for the efficacy/effectiveness of included trials. The overall strength of evidence for a particular key question reflects the de sign, quality, consistency, directness, and precision of the effect estimate. We rate the overall strength of evidence as low, moderate, high, or insufficient using a modified GRAD E approach established by the Evidence-based Practice Centers. High strength of evidence indicates high confidence in the estimate of effect and that the evidence reflects the true effect; further research is unlikely to change our confidence. Moderate strength of evidence indicates moderate confidence that the evidence reflects the true effect; further research may change our confidence in the estimate and may change the estimate. Low strength of evidence indicates low confidence that the evidence reflects the true effect; further research is likely to change our confidence in the estimate and is likely to change the estimate. Insufficient indicates that evidence is unavailable or does not permit estimation of an effect.

For this review we used a “point system” for each domain to help guide our overall assessment. Listed below is a description of our “point system.” Further information regarding the modified GRADE approach can be found in the Effective Health Care Program Methods Manual, http://effectivehealthcare.ahrq.gov.

Risk of bias

(+1): If adequate description of methods for randomization, allocation concealment, blinding, ITT, reasonable withdrawal/drop out rates—would be rated good.

(−1): If limited description of methods for randomization, allocation concealment, and blinding—would be rated fair.

(−2 or −3): Additional points would be taken if there were problems with analysis (for example inadequate ITT population), high withdrawal/drop out rates, and/or significant selective reporting (of outcomes or harms) in addition to inadequate randomization, allocation concealment, and blinding—would be rated poor.

Study design

(+1): If study designs were randomized trials.

(−1): If patients were nonrandomized, open-label, or post-hoc subgroup analyses.

Consistency

(+1): Yes- direction of effect similar across studies.

(−1): No- significant variation in effect across studies.

Directness

(+1): If patient relevant health outcome were measured/evaluated.

(−1): If outcome was an intermediate outcome with some validity demonstrating correlation to main health outcome of interest.

(−2 or −3): Additional points would be taken if outcome was an intermediate outcome with unclear or no validity established and lacking strong correlation to main health outcome of interest or if indirect bodies of evidence were used to make comparisons between interventions.

Precision

(+1): Yes-estimate would allow clinically useful conclusion.

(−1): No-confidence interval is wide enough to include clinically distinct conclusions.

A. Mild to moderate disease

No. of studies (# subjects)Risk of bias: (study design/quality)ConsistencyDirectnessPrecisionCommentsOverall strength of evidence
Outcome: Achieving treatment success
Tacrolimus 0.03% ointment compared with pimecrolimus 1% cream
2 (562)H2H/Fair+1−1+1Pooled RR, 1.19, 0.98–1.45Moderate-high
4 (425)RCT/Fair+1−2+1Pooled RR, 0.97, 0.63–1.48Moderate
Tacrolimus 0.1% ointment compared with pimecrolimus 1% cream
No studiesH2H/Fair--------------------Insufficient
No studiesRCT/Fair--------------------Insufficient
Outcome: Reduction in pruritus
Tacrolimus 0.03% ointment compared with Pimecrolimus 1% cream
2 (562)H2H/Fair+1−1Unable to determineDid not pool results due to heterogenous outcome reporting but qualitative assessment shows minimal differenceModerate
4 (425)RCT/Fair+1−2Unable to determineDid not pool results due to heterogenous outcome reportingUnable to make comparison
Tacrolimus 0.1% ointment compared with pimecrolimus 1% cream
No studiesH2H/Fair--------------------Insufficient
No studiesRCT/Fair--------------------Insufficient
Outcome: Patient assessment of overall disease control
Tacrolimus 0.03% ointment compared with pimecrolimus 1% cream
No studiesH2H/Fair--------------------Insufficient
No studiesRCT/Fair--------------------Insufficient
Tacrolimus 0.1% ointment compared with pimecrolimus 1% cream
No studiesH2H/Fair--------------------Insufficient
No studiesRCT/Fair--------------------Insufficient

Abbreviations: H2H, head-to-head trial; RCT, randomized controlled trial; RR, relative risk; WMD, weighted mean difference

B. Moderate to severe disease

No. of studies (# subjects)Risk of bias: (study design/quality)ConsistencyDirectnessPrecisionCommentsOverall strength of evidence
Outcome: Achieving treatment success
Tacrolimus 0.03% ointment compared with pimecrolimus 1% cream
No studiesH2H/Fair--------------------Insufficient
4 (457)RCT/Fair+1−2−1Pooled RR, 0.89 (95% CI, 0.38–2.07)Low
Tacrolimus 0.1% ointment compared with Pimecrolimus 1% cream
1 (224)H2H/FairUnable to determine (1 study)−1+1RR, 1.83 (95% CI, 1.13–2.96)Moderate
4 (456)RCT/Fair+1−2−1Pooled RR, 1.12 (95% CI, 0.48–2.57)Low
Outcome: Reduction in pruritus
Tacrolimus 0.03% ointment compared with pimecrolimus 1% cream
No studiesH2H/Fair--------------------Insufficient
4 (457)RCT/Fair+1−2−1Pooled WMD, 0.86 (95% CI, −0.69 to 2.41)Low
Tacrolimus 0.1% ointment compared with Pimecrolimus 1% cream
1 (224)H2H/FairUnable to determine−1+1Change in pruritus score from baseline −3.7 cm compared with −2.0 cm, P ≤ 0.01Moderate-low
4 (456)RCT/Fair+1−2−1Pooled WMD, 0.74 (95% CI, −0.83 to 2.31)Low
Outcome: Patient assessment of overall disease control
Tacrolimus 0.03% ointment compared with pimecrolimus 1% cream
No studiesH2H/Fair--------------------Insufficient
4 (457)RCT/Fair+1−2−1Pooled RR, 0.98 (95% CI, 0.56–1.73)Low
Tacrolimus 0.1% ointment compared with pimecrolimus 1% cream
No studiesH2H/Fair--------------------Insufficient
4 (456)RCT/Fair+1−2−1Pooled RR, 1.07 (95% CI, 0.53–2.13)Low

Abbreviations: H2H, head-to-head trial; RCT, randomized controlled trial; RR, relative risk; WMD, weighted mean difference

Copyright © 2008, Oregon Health & Science University, Portland, Oregon.
Bookshelf ID: NBK10456
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