Implementation of the Anchor-Based Indirect Comparison Method for Equivalence Margin Derivation in Biosimilar Development
<b>Background/Objectives</b>: To derive the equivalence margin (EQM), typically, a “classical” meta-analysis on direct within-trial estimation of the effect size of the reference drug compared to the placebo or standard of care is performed: a certain factor of the 95% confidence interva...
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MDPI AG
2025-02-01
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| author | Claudia Hemmelmann Rachid El Galta Jessie Wang Susanne Schmitt Ramin Arani |
| author_facet | Claudia Hemmelmann Rachid El Galta Jessie Wang Susanne Schmitt Ramin Arani |
| author_sort | Claudia Hemmelmann |
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| description | <b>Background/Objectives</b>: To derive the equivalence margin (EQM), typically, a “classical” meta-analysis on direct within-trial estimation of the effect size of the reference drug compared to the placebo or standard of care is performed: a certain factor of the 95% confidence interval for the pooled treatment effect compared to placebo is used. However, treatment regimens in many indications are becoming more complex (e.g., combination treatments), and for most of these clinical study data, direct comparisons are not available. On the other hand, data for the comparison of the common treatment to the reference treatment in one study and to the placebo in another study are available in some situations. <b>Methods</b>: In such situations, an anchor-based indirect comparison can be applied to estimate the treatment effect of Reference vs. Placebo. This treatment effect (Reference vs. Placebo) can be estimated by calculating the difference of the two treatment effects and the variance as the sum of both variances. The 95% confidence interval of this estimated treatment effect can then be used to derive the EQM. To alleviate any concerns about the underlying assumptions of transitivity and consistency, multiple sensitivity analyses can be performed. <b>Results</b>: We present a case study for deriving the EQM using the anchor-based indirect comparison along with sensitivity analyses (i.e., direct comparison against similar reference drug, the impact of variation of treatment effect on Comparator, and effect size Reference vs. Placebo, including trial data with slightly different population characteristics) for a planned efficacy trial in the biosimilar setting. <b>Conclusions</b>: An anchor-based indirect comparison for EQM derivation is an approach health authorities can agree to if sufficiently supported through other means, e.g., relevant sensitivity analyses. |
| format | Article |
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| publishDate | 2025-02-01 |
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| series | Pharmaceuticals |
| spelling | doaj-art-a2fdda24a8e543b2bffed648c35df3772025-08-20T01:48:45ZengMDPI AGPharmaceuticals1424-82472025-02-0118328510.3390/ph18030285Implementation of the Anchor-Based Indirect Comparison Method for Equivalence Margin Derivation in Biosimilar DevelopmentClaudia Hemmelmann0Rachid El Galta1Jessie Wang2Susanne Schmitt3Ramin Arani4Hexal AG, Industriestr. 25, D-83607 Holzkirchen, GermanyHexal AG, Industriestr. 25, D-83607 Holzkirchen, GermanySandoz Inc., 100 College Road West, Princeton, NJ 08540, USAHexal AG, Industriestr. 25, D-83607 Holzkirchen, GermanySandoz Inc., 100 College Road West, Princeton, NJ 08540, USA<b>Background/Objectives</b>: To derive the equivalence margin (EQM), typically, a “classical” meta-analysis on direct within-trial estimation of the effect size of the reference drug compared to the placebo or standard of care is performed: a certain factor of the 95% confidence interval for the pooled treatment effect compared to placebo is used. However, treatment regimens in many indications are becoming more complex (e.g., combination treatments), and for most of these clinical study data, direct comparisons are not available. On the other hand, data for the comparison of the common treatment to the reference treatment in one study and to the placebo in another study are available in some situations. <b>Methods</b>: In such situations, an anchor-based indirect comparison can be applied to estimate the treatment effect of Reference vs. Placebo. This treatment effect (Reference vs. Placebo) can be estimated by calculating the difference of the two treatment effects and the variance as the sum of both variances. The 95% confidence interval of this estimated treatment effect can then be used to derive the EQM. To alleviate any concerns about the underlying assumptions of transitivity and consistency, multiple sensitivity analyses can be performed. <b>Results</b>: We present a case study for deriving the EQM using the anchor-based indirect comparison along with sensitivity analyses (i.e., direct comparison against similar reference drug, the impact of variation of treatment effect on Comparator, and effect size Reference vs. Placebo, including trial data with slightly different population characteristics) for a planned efficacy trial in the biosimilar setting. <b>Conclusions</b>: An anchor-based indirect comparison for EQM derivation is an approach health authorities can agree to if sufficiently supported through other means, e.g., relevant sensitivity analyses.https://www.mdpi.com/1424-8247/18/3/285biosimilarityequivalence marginindirect approachnetwork meta-analysis |
| spellingShingle | Claudia Hemmelmann Rachid El Galta Jessie Wang Susanne Schmitt Ramin Arani Implementation of the Anchor-Based Indirect Comparison Method for Equivalence Margin Derivation in Biosimilar Development Pharmaceuticals biosimilarity equivalence margin indirect approach network meta-analysis |
| title | Implementation of the Anchor-Based Indirect Comparison Method for Equivalence Margin Derivation in Biosimilar Development |
| title_full | Implementation of the Anchor-Based Indirect Comparison Method for Equivalence Margin Derivation in Biosimilar Development |
| title_fullStr | Implementation of the Anchor-Based Indirect Comparison Method for Equivalence Margin Derivation in Biosimilar Development |
| title_full_unstemmed | Implementation of the Anchor-Based Indirect Comparison Method for Equivalence Margin Derivation in Biosimilar Development |
| title_short | Implementation of the Anchor-Based Indirect Comparison Method for Equivalence Margin Derivation in Biosimilar Development |
| title_sort | implementation of the anchor based indirect comparison method for equivalence margin derivation in biosimilar development |
| topic | biosimilarity equivalence margin indirect approach network meta-analysis |
| url | https://www.mdpi.com/1424-8247/18/3/285 |
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