Superiority and non-inferiority: Two sides of the same coin?
<h4>Background</h4> <p>The classification of phase 3 trials as superiority or non-inferiority has become routine, and it is widely accepted that there are important differences between the two types of trial in their design, analysis and interpretation.</p> <h4>Main te...
| Hoofdauteurs: | , , |
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| Formaat: | Journal article |
| Taal: | English |
| Gepubliceerd in: |
BioMed Central
2018
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| _version_ | 1826281119696289792 |
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| author | Dunn, D Copas, A Brocklehurst, P |
| author_facet | Dunn, D Copas, A Brocklehurst, P |
| author_sort | Dunn, D |
| collection | OXFORD |
| description | <h4>Background</h4> <p>The classification of phase 3 trials as superiority or non-inferiority has become routine, and it is widely accepted that there are important differences between the two types of trial in their design, analysis and interpretation.</p> <h4>Main text</h4> <p>There is a clear rationale for the superiority/non-inferiority framework in the context of regulatory trials. The focus of our article is non-regulatory trials with a public health objective. First, using two examples from infectious disease research, we show that the classification of superiority or non-inferiority trials is not always straightforward. Second, we show that several arguments for different approaches to the design, analysis and interpretation of superiority and non-inferiority trials are unconvincing when examined in detail. We consider, in particular, the calculation of sample size (and the choice of delta or the non-inferiority margin), intention-to-treat versus per-protocol analyses, and one-sided versus two-sided confidence intervals. We argue that the superiority/non-inferiority framework is not just unnecessary but can have a detrimental effect, being a barrier to clear scientific thought and communication. In particular, it places undue emphasis on tests for significance or non-inferiority at the expense of estimation. We emphasise that these concerns apply to phase 3 non-regulatory trials in general, not just to those where the classification of the trial as superiority or non-inferiority is ambiguous.</p> <h4>Conclusions</h4> <p>Guidelines and statistical practice should abandon the sharp division between superiority and noninferiority phase 3 non-regulatory trials and be more closely aligned to the clinical and public health questions that motivate the trial.</p> |
| first_indexed | 2024-03-07T00:24:00Z |
| format | Journal article |
| id | oxford-uuid:7d7f6c16-dfdb-4c35-804f-8ee497bf0b90 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:24:00Z |
| publishDate | 2018 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:7d7f6c16-dfdb-4c35-804f-8ee497bf0b902022-03-26T21:04:01ZSuperiority and non-inferiority: Two sides of the same coin?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7d7f6c16-dfdb-4c35-804f-8ee497bf0b90EnglishSymplectic Elements at OxfordBioMed Central2018Dunn, DCopas, ABrocklehurst, P <h4>Background</h4> <p>The classification of phase 3 trials as superiority or non-inferiority has become routine, and it is widely accepted that there are important differences between the two types of trial in their design, analysis and interpretation.</p> <h4>Main text</h4> <p>There is a clear rationale for the superiority/non-inferiority framework in the context of regulatory trials. The focus of our article is non-regulatory trials with a public health objective. First, using two examples from infectious disease research, we show that the classification of superiority or non-inferiority trials is not always straightforward. Second, we show that several arguments for different approaches to the design, analysis and interpretation of superiority and non-inferiority trials are unconvincing when examined in detail. We consider, in particular, the calculation of sample size (and the choice of delta or the non-inferiority margin), intention-to-treat versus per-protocol analyses, and one-sided versus two-sided confidence intervals. We argue that the superiority/non-inferiority framework is not just unnecessary but can have a detrimental effect, being a barrier to clear scientific thought and communication. In particular, it places undue emphasis on tests for significance or non-inferiority at the expense of estimation. We emphasise that these concerns apply to phase 3 non-regulatory trials in general, not just to those where the classification of the trial as superiority or non-inferiority is ambiguous.</p> <h4>Conclusions</h4> <p>Guidelines and statistical practice should abandon the sharp division between superiority and noninferiority phase 3 non-regulatory trials and be more closely aligned to the clinical and public health questions that motivate the trial.</p> |
| spellingShingle | Dunn, D Copas, A Brocklehurst, P Superiority and non-inferiority: Two sides of the same coin? |
| title | Superiority and non-inferiority: Two sides of the same coin? |
| title_full | Superiority and non-inferiority: Two sides of the same coin? |
| title_fullStr | Superiority and non-inferiority: Two sides of the same coin? |
| title_full_unstemmed | Superiority and non-inferiority: Two sides of the same coin? |
| title_short | Superiority and non-inferiority: Two sides of the same coin? |
| title_sort | superiority and non inferiority two sides of the same coin |
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