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Use of composite endpoints in early and intermediate age-related macular degeneration clinical trials - state-of-the-art and future directions

Terheyden, J. H., Schmitz-Valckenberg, S., Crabb, D. P. ORCID: 0000-0001-8754-3902 , Dunbar, H., Luhmann, U. F. O., Behning, C., Schmid, M., Pires, I., Cunha-Vaz, J., Tufail, A., Weissgerber, G., Leal, S., Holz, F. G. & Finger, R. P. (2020). Use of composite endpoints in early and intermediate age-related macular degeneration clinical trials - state-of-the-art and future directions. Ophthalmologica, 244(5), pp. 387-395. doi: 10.1159/000513591


The slow progression of early AMD stages to advanced AMD requires the use of surrogate endpoints in clinical trials. The use of combined endpoints may allow for shorter and smaller trials due to increased precision. We performed a literature search for the use of composite endpoints as primary outcome measures in clinical studies of early AMD stages. PubMed was searched for composite endpoints used in early/intermediate AMD studies published during the last 10 years. A total of 673 articles of interest were identified. After reviewing abstracts and applicable full-text articles, 33 articles were eligible and thus included in the qualitative synthesis. The main composite endpoint categories were: Combined structural and functional endpoints, combined structural endpoints, combined functional endpoints and combined multi-categorical endpoints. The majority of the studies included binary composite endpoints. There was a lack of sensitivity analyses of different endpoints against accepted outcomes (i.e. progression) in the literature. Various composite outcome measures have been used but there is a lack of standardization. To date no agreement on the optimal approach to implement combined endpoints in clinical studies of early stages of AMD exists and no surrogate endpoints have been accepted for AMD progression.

Publication Type: Article
Additional Information: This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Publisher Keywords: Age-related macular degeneration, Composite end points, Trial outcomes
Subjects: R Medicine > RE Ophthalmology
Departments: School of Health & Psychological Sciences > Optometry & Visual Sciences
SWORD Depositor:
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