May 2017
Volume 58, Issue 6
Open Access
Editorial  |   May 2017
Foreword: Biomarkers and Surrogate Endpoints in Ophthalmic Clinical Research
Author Affiliations
  • Edoardo Villani
    Special Issue Editors
  • Stela Vujosevic
    Special Issue Editors
Investigative Ophthalmology & Visual Science May 2017, Vol.58, BIOi-BIOii. doi:10.1167/iovs.17-22128
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      Edoardo Villani, Stela Vujosevic; Foreword: Biomarkers and Surrogate Endpoints in Ophthalmic Clinical Research. Invest. Ophthalmol. Vis. Sci. 2017;58(6):BIOi-BIOii. doi: 10.1167/iovs.17-22128.

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This special issue collects original research, reviews, scientific, and regulatory perspectives focusing on biomarkers and surrogate endpoints in ophthalmic clinical research. 
Biomarkers and surrogate endpoints provide an essential set of tools needed to translate scientific concepts into diagnostic and therapeutic approaches and technologies. These tools have significant potential for accelerating basic science, drug discovery, medical product development, and for improving clinical care.1 
The first essential effort to improve the use of biomarkers and surrogate endpoints should aim to get effective and unambiguous communication. For this reason, since 2015 the FDA-NIH Joint Leadership Council developed the BEST (Biomarkers, EndpointS, and other Tools) glossary.2 
In order to improve communication and understanding of the conceptual framework, we felt that it would be important to share with the readership of this special issue some contents of the BEST Resource. 
The currently accepted definition of the term biomarker is “a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. […] A biomarker is not an assessment of how an individual feels, functions, or survives.”2 Categories of biomarkers are summarized in the Table
Table
 
Biomarkers' Categories and Definitions Reported in the FDA-NIH BEST Resource2
Table
 
Biomarkers' Categories and Definitions Reported in the FDA-NIH BEST Resource2
Another central concept is the endpoints' surrogacy. A surrogate endpoint is defined as “an endpoint that is used in clinical trials as a substitute for a direct measure of how a patient feels, functions, or survives. A surrogate endpoint does not measure the clinical benefit of primary interest in and of itself, but rather is expected to predict that clinical benefit or harm based on epidemiologic, therapeutic, pathophysiologic, or other scientific evidence.”2 
Correlation with the clinical endpoint is a necessary but not sufficient condition for surrogacy. A validated surrogate endpoint must be “supported by a clear mechanistic rationale and clinical data providing strong evidence that an effect on the surrogate endpoint predicts a clinical benefit.”2 
As elegantly theorized in 1996 by Fleming and DeMets,3 in the ideal setting for surrogacy, “the surrogate is in the only causal pathway of the disease process, and the intervention's entire effect on the true clinical outcome is mediated through its effect on the surrogate” (Fig. 1). 
Figure 1
 
Conceptual model of valid endpoint surrogacy.
Figure 1
 
Conceptual model of valid endpoint surrogacy.
In the last few years, the role of biomarkers and surrogate endpoints, together with the efforts needed for their validation and the concerns related to their misuse, has become a hot topic in ophthalmology (Fig. 2). 
Figure 2
 
Biomarkers and surrogate endpoint publication volume in ophthalmology, from PubMed abstract search performed on April 1, 2017.
Figure 2
 
Biomarkers and surrogate endpoint publication volume in ophthalmology, from PubMed abstract search performed on April 1, 2017.
This special issue is a great opportunity to take stock of this important and complex topic. The invited and unsolicited reviews provide precious information and novel updates on scientific and regulatory issues. The original research report new advances in biomarkers and surrogate endpoints development, validation and usage in different areas of ophthalmic clinical research and care. 
We would like to thank all the reviewers for their fundamental and anonymous work and all the researchers who have contributed to this special issue. 
We would also like to thank Thomas Yorio, Editor-in-Chief of IOVS, for having shared our enthusiasm for this project and for his invaluable guidance, and Marco Stoutamire, Gayle Claman, and Debbie Chin, IOVS staff, for their work and their kind and constant support in managing the submissions. 
We hope that this special issue will help to increase awareness and to focus attention on the implications of this important topic and will be an incentive for addressing the several open challenges. 
References
Robb MA, McInnes PM, Califf RM. Biomarkers and surrogate endpoints: developing common terminology and definitions. JAMA. 2016; 315: 1107–1108.
FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource. Available at: http://www.ncbi.nlm.nih.gov/books/NBK326791/. Accessed April 22, 2017.
Fleming TR, DeMets DL. Surrogate end points in clinical trials: are we being misled? Ann Intern Med. 1996; 125: 605–613.
Figure 1
 
Conceptual model of valid endpoint surrogacy.
Figure 1
 
Conceptual model of valid endpoint surrogacy.
Figure 2
 
Biomarkers and surrogate endpoint publication volume in ophthalmology, from PubMed abstract search performed on April 1, 2017.
Figure 2
 
Biomarkers and surrogate endpoint publication volume in ophthalmology, from PubMed abstract search performed on April 1, 2017.
Table
 
Biomarkers' Categories and Definitions Reported in the FDA-NIH BEST Resource2
Table
 
Biomarkers' Categories and Definitions Reported in the FDA-NIH BEST Resource2
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