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The Importance of Considering Differences in Study Design in Network Meta-analysis: An Application Using Anti-Tumor
Chris Cameron1, Emmanuel Ewara2, Florence R Wilson1
1Cornerstone Research Group Inc., Burlington, ON, Canada (CC, FRW, AV).
Background And Aims:
Adaptive trial designs present a methodological challenge when performing network meta-analysis (NMA), as data from such adaptive trial designs differ from conventional parallel design randomized controlled trials (RCTs). We aim to illustrate the importance of considering study design when conducting an NMA.
Methods:
Three NMAs comparing anti-tumor necrosis factor drugs for ulcerative colitis were compared and the analyses replicated using Bayesian NMA. The NMA comprised 3 RCTs comparing 4 treatments (adalimumab 40 mg, golimumab 50 mg, golimumab 100 mg, infliximab 5 mg/kg) and placebo. We investigated the impact of incorporating differences in the study design among the 3 RCTs and presented 3 alternative methods on how to convert outcome data derived from one form of adaptive design to more conventional parallel RCTs.
Results:
Combining RCT results without considering variations in study design resulted in effect estimates that were biased against golimumab. In contrast, using the 3 alternative methods to convert outcome data from one form of adaptive design to a format more consistent with conventional parallel RCTs facilitated more transparent consideration of differences in study design. This approach is more likely to yield appropriate estimates of comparative efficacy when conducting an NMA, which includes treatments that use an alternative study design.
Conclusions:
RCTs based on adaptive study designs should not be combined with traditional parallel RCT designs in NMA. We have presented potential approaches to convert data from one form of adaptive design to more conventional parallel RCTs to facilitate transparent and less-biased comparisons.
Insights
Adaptive trial designs in network meta-analysis (NMA) require careful handling. Converting data from adaptive designs to parallel randomized controlled trials (RCTs) ensures less-biased comparative efficacy estimates.
Area of Science:
- Clinical Trial Design
- Biostatistics
- Pharmacoeconomics
Background:
- Adaptive trial designs pose methodological challenges for network meta-analysis (NMA).
- Data from adaptive designs differ significantly from conventional parallel randomized controlled trials (RCTs).
- Considering study design is crucial for accurate NMA.
Purpose of the Study:
- To illustrate the importance of accounting for study design variations in NMA.
- To present methods for converting adaptive trial data for NMA.
- To investigate the impact of study design on NMA results.
Main Methods:
- Replicated Bayesian NMAs of anti-tumor necrosis factor drugs for ulcerative colitis.
- Included 3 RCTs comparing 4 treatments (adalimumab, golimumab, infliximab) and placebo.
- Investigated 3 methods to convert adaptive design data to parallel RCT format.
Main Results:
- Combining RCTs without considering design variations biased effect estimates against golimumab.
- Alternative methods for data conversion facilitated transparent consideration of study design differences.
- Converted data yielded more appropriate estimates of comparative efficacy.
Conclusions:
- Adaptive and parallel RCT designs should not be directly combined in NMA.
- Presented approaches for data conversion enable transparent and less-biased NMA.
- Proper handling of adaptive designs improves the reliability of comparative efficacy estimates.
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