Article type
Year
Abstract
Background: In systematic reviews of randomized controlled trials (RCTs), intention-to-treat (ITT) is the standard data analysis method which minimizes bias by including all patients regardless of the treatment received. Instrumental variable (IV) methods have been proposed as a technique to adjust ITT estimates for treatment non-compliance and contamination so that treatment effects in compliers may be estimated.
Objective: To illustrate the value of IV methods by applying them to a published meta-analysis on the screening for breast cancer.
Methods: We used ITT and IV meta-analytic pooled estimates of relative risk (RR) together with baseline risk to calculate number needed to treat to benefit (NNTB) one patient and their 95% confidence intervals. In the context of IV meta-analysis, NNTB can be interpreted as a number of assigned patients needed to comply to benefit one patient.
Results: No heterogeneity was detected for ITT and IV pooled estimates for both non-compliance and contamination adjustedmeta-analysis (I-sq=0%, tau-sq = 0). The patient compliance rate ranged from 65 to 100% and contamination from 3.9 to 19%. The overall ITT estimate RR = 0.85 (95% CI: 0.75–0.96) translates to NNTB = 1904 (95%CI: 929–6378). Under non-compliance alone, for IV the overall RR = 0.81 (95% CI: 0.69–0.95), NNTB = 1645 (95%CI: 980–4348), which is 14% reduction from ITT estimate. Under non-compliance and contamination, for IV the overall RR = 0.78 (95% CI: 0.64–0.95), NNTB = 1421 (95%CI: 806–4167), which is 25% reduction from the ITT estimate.
Conclusions: Given that the U.S. Preventive Services Task Force’s recommendation against screening mammography in women aged 40–49 years were partly influenced by NNTB, the differences of 14% and 25% are not trivial. IV estimates appeal to patients who are eager to comply with their treatment assignment and to clinicians who wish to establish the efficacy of treatment received.
Objective: To illustrate the value of IV methods by applying them to a published meta-analysis on the screening for breast cancer.
Methods: We used ITT and IV meta-analytic pooled estimates of relative risk (RR) together with baseline risk to calculate number needed to treat to benefit (NNTB) one patient and their 95% confidence intervals. In the context of IV meta-analysis, NNTB can be interpreted as a number of assigned patients needed to comply to benefit one patient.
Results: No heterogeneity was detected for ITT and IV pooled estimates for both non-compliance and contamination adjustedmeta-analysis (I-sq=0%, tau-sq = 0). The patient compliance rate ranged from 65 to 100% and contamination from 3.9 to 19%. The overall ITT estimate RR = 0.85 (95% CI: 0.75–0.96) translates to NNTB = 1904 (95%CI: 929–6378). Under non-compliance alone, for IV the overall RR = 0.81 (95% CI: 0.69–0.95), NNTB = 1645 (95%CI: 980–4348), which is 14% reduction from ITT estimate. Under non-compliance and contamination, for IV the overall RR = 0.78 (95% CI: 0.64–0.95), NNTB = 1421 (95%CI: 806–4167), which is 25% reduction from the ITT estimate.
Conclusions: Given that the U.S. Preventive Services Task Force’s recommendation against screening mammography in women aged 40–49 years were partly influenced by NNTB, the differences of 14% and 25% are not trivial. IV estimates appeal to patients who are eager to comply with their treatment assignment and to clinicians who wish to establish the efficacy of treatment received.