Impact of Case Definitions on Efficacy Estimation in Clinical Trials—A Proof-of-Principle Based on Historical Examples
Efficacy estimations in clinical trials are based on case definitions. Commonly, they are a more or less complex set of conditions that have to be fulfilled in order to define a clinical case. In the simplest variant, such a case is identical with a single positive diagnostic test result. Frequently...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/9/7/379 |
| _version_ | 1797563320407949312 |
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| author | Andreas Hahn Hagen Frickmann Andreas E. Zautner |
| author_facet | Andreas Hahn Hagen Frickmann Andreas E. Zautner |
| author_sort | Andreas Hahn |
| collection | DOAJ |
| description | Efficacy estimations in clinical trials are based on case definitions. Commonly, they are a more or less complex set of conditions that have to be fulfilled in order to define a clinical case. In the simplest variant, such a case is identical with a single positive diagnostic test result. Frequently, however, case definitions are more complex. Further, their conditions often ignore the inherent logical structure of symptoms and disease: A symptom or a set of symptoms may be necessary but not sufficient for the unambiguous identification of a case. After describing the structure of case definitions and its impact on efficacy estimations, we exemplify this impact using data from two clinical trials dealing with the effectiveness of the vaginal application of tenofovir gel for the prevention of HIV infections and with the therapeutic effects of fecal transplantation on recurrent <i>Clostridium difficile</i> infections. We demonstrate that the diagnostic performance of case definitions affects efficacy estimations for interventions in clinical trials. The potential risk of bias and uncertainty is high, irrespective of the complexity of the case definition. Accordingly, case definitions in clinical trials should focus on specificity in order to avoid the risk of bias. |
| first_indexed | 2024-03-10T18:41:00Z |
| format | Article |
| id | doaj.art-d7bd4f9c286648fc85b12c42cd75ac2c |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T18:41:00Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-d7bd4f9c286648fc85b12c42cd75ac2c2023-11-20T05:52:13ZengMDPI AGAntibiotics2079-63822020-07-019737910.3390/antibiotics9070379Impact of Case Definitions on Efficacy Estimation in Clinical Trials—A Proof-of-Principle Based on Historical ExamplesAndreas Hahn0Hagen Frickmann1Andreas E. Zautner2Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock, 18057 Rostock, GermanyInstitute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock, 18057 Rostock, GermanyInstitut für Medizinische Mikrobiologie, Universitätsmedizin Göttingen, 37075 Göttingen, GermanyEfficacy estimations in clinical trials are based on case definitions. Commonly, they are a more or less complex set of conditions that have to be fulfilled in order to define a clinical case. In the simplest variant, such a case is identical with a single positive diagnostic test result. Frequently, however, case definitions are more complex. Further, their conditions often ignore the inherent logical structure of symptoms and disease: A symptom or a set of symptoms may be necessary but not sufficient for the unambiguous identification of a case. After describing the structure of case definitions and its impact on efficacy estimations, we exemplify this impact using data from two clinical trials dealing with the effectiveness of the vaginal application of tenofovir gel for the prevention of HIV infections and with the therapeutic effects of fecal transplantation on recurrent <i>Clostridium difficile</i> infections. We demonstrate that the diagnostic performance of case definitions affects efficacy estimations for interventions in clinical trials. The potential risk of bias and uncertainty is high, irrespective of the complexity of the case definition. Accordingly, case definitions in clinical trials should focus on specificity in order to avoid the risk of bias.https://www.mdpi.com/2079-6382/9/7/379efficacy estimationcase definitionspecificityclinical trial |
| spellingShingle | Andreas Hahn Hagen Frickmann Andreas E. Zautner Impact of Case Definitions on Efficacy Estimation in Clinical Trials—A Proof-of-Principle Based on Historical Examples Antibiotics efficacy estimation case definition specificity clinical trial |
| title | Impact of Case Definitions on Efficacy Estimation in Clinical Trials—A Proof-of-Principle Based on Historical Examples |
| title_full | Impact of Case Definitions on Efficacy Estimation in Clinical Trials—A Proof-of-Principle Based on Historical Examples |
| title_fullStr | Impact of Case Definitions on Efficacy Estimation in Clinical Trials—A Proof-of-Principle Based on Historical Examples |
| title_full_unstemmed | Impact of Case Definitions on Efficacy Estimation in Clinical Trials—A Proof-of-Principle Based on Historical Examples |
| title_short | Impact of Case Definitions on Efficacy Estimation in Clinical Trials—A Proof-of-Principle Based on Historical Examples |
| title_sort | impact of case definitions on efficacy estimation in clinical trials a proof of principle based on historical examples |
| topic | efficacy estimation case definition specificity clinical trial |
| url | https://www.mdpi.com/2079-6382/9/7/379 |
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