Decade-Long Profile of Imaging Biomarker Use in Ophthalmic Clinical Trials.

Purpose The purpose of this study was to investigate the use of imaging biomarkers in published clinical trials (CTs) in ophthalmology and its eventual changes during the past 10 years. Methods We sampled from published CTs in the fields of cornea, retina, and glaucoma between 2005-2006 and 2015-2016. Data collected included year of publication, phase, subspecialty, location, compliance with Consolidated Standards for Reporting Trials, impact factor, presence and use of imaging biomarkers (diagnostic, prognostic and predictive; primary and secondary surrogate endpoints), and use of centralized reading centers. Results We included 652 articles for analysis, equally distributed in three timeframes (2005-2006, 2010-2011, and 2015-2016), mainly reporting phase IV CTs and trials on procedures (42.2% and 35.4%, respectively). Imaging biomarkers were included in 46.3% of the analyzed CTs and their use significantly increased over time (P < 0.05). Optical coherence tomography was the most frequently used device (27.7%), whereas diagnostic biomarkers and secondary surrogate endpoints were the most frequent biomarker types (19.5% and 22.5%, respectively). Early-phase CTs showed an increase in the use of biomarkers for patient selection and stratification over time (P < 0.05), but not in the use of imaging surrogate endpoints (P = 0.90). Only 3 of 59 (5.1%) of phase III CTs included primary surrogate imaging endpoints, whereas secondary surrogate imaging endpoints were present in 50.8% of these trials (P < 0.001). Retinal CTs had the highest prevalence for each type of imaging biomarker (P < 0.001). Reading centers were used in 52 of 302 CTs (17.2%), with no significant time-related increase. Conclusions Imaging biomarkers are increasingly used in published CTs in ophthalmology. Additional efforts, including centralized reading centers, are needed to improve their validation and use, allowing a wider use of these tools as primary surrogate endpoints in phase III CTs.

[1]  Philip J. Rosenfeld,et al.  Optical Coherence Tomography and the Development of Antiangiogenic Therapies in Neovascular Age-Related Macular Degeneration , 2016, Investigative ophthalmology & visual science.

[2]  Eric Swanson,et al.  The Development, Commercialization, and Impact of Optical Coherence Tomography , 2016, Investigative ophthalmology & visual science.

[3]  R. Califf,et al.  Biomarkers and Surrogate Endpoints: Developing Common Terminology and Definitions. , 2016, JAMA.

[4]  U. Schmidt-Erfurth,et al.  Randomized Trial to Evaluate Tandospirone in Geographic Atrophy Secondary to Age-Related Macular Degeneration: The GATE Study. , 2015, American journal of ophthalmology.

[5]  S. Pocock,et al.  The perils of surrogate endpoints. , 2015, European heart journal.

[6]  J. Wagner,et al.  Measuring Biomarker Progress , 2015, Clinical pharmacology and therapeutics.

[7]  S. Amur,et al.  Biomarker Qualification: Toward a Multiple Stakeholder Framework for Biomarker Development, Regulatory Acceptance, and Utilization , 2015, Clinical pharmacology and therapeutics.

[8]  David A Mankoff,et al.  How Imaging Biomarkers Can Inform Clinical Trials and Clinical Practice in the Era of Targeted Cancer Therapy. , 2015, JAMA oncology.

[9]  David A Mankoff,et al.  How Imaging Can Impact Clinical Trial Design: Molecular Imaging as a Biomarker for Targeted Cancer Therapy , 2015, Cancer journal.

[10]  F Eckstein,et al.  Imaging of cartilage and bone: promises and pitfalls in clinical trials of osteoarthritis. , 2014, Osteoarthritis and cartilage.

[11]  R. Agha,et al.  The reporting quality of parallel randomised controlled trials in ophthalmic surgery in 2011: a systematic review , 2014, Eye.

[12]  Felipe A Medeiros,et al.  Biomarkers and surrogate endpoints in glaucoma clinical trials , 2014, British Journal of Ophthalmology.

[13]  P. Patel,et al.  Ophthalmic imaging. , 2014, British medical bulletin.

[14]  David Moher,et al.  Consolidated standards of reporting trials (CONSORT) and the completeness of reporting of randomised controlled trials (RCTs) published in medical journals. , 2012, The Cochrane database of systematic reviews.

[15]  A. Alm,et al.  Five-year, Multicenter Safety Study of Fixed-combination Latanoprost/Timolol (Xalacom) for Open-angle Glaucoma and Ocular Hypertension , 2011, Journal of glaucoma.

[16]  D. Moher,et al.  CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials , 2010, BMJ : British Medical Journal.

[17]  H. Ahmadieh,et al.  Intravitreal bevacizumab vs. sham treatment in acute branch retinal vein occlusion with macular edema: results at 3 months (Report 1) , 2011, Graefe's Archive for Clinical and Experimental Ophthalmology.

[18]  D. Moher,et al.  CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials , 2011, BMJ : British Medical Journal.

[19]  R. Danis The clinical site-reading center partnership in clinical trials. , 2009, American journal of ophthalmology.

[20]  Imaging outcomes in cardiovascular clinical trials , 2009, Nature Reviews Cardiology.

[21]  J. Tyson,et al.  Clinical research methodology I: introduction to randomized trials. , 2008, Journal of the American College of Surgeons.

[22]  G. Leung,et al.  Quality of Reporting of Key Methodological Items of Randomized Controlled Trials in Clinical Ophthalmic Journals , 2007, Ophthalmic epidemiology.

[23]  Viswanath Devanarayan,et al.  Fit-for-Purpose Method Development and Validation for Successful Biomarker Measurement , 2006, Pharmaceutical Research.

[24]  J. Ioannidis Why Most Published Research Findings Are False , 2005, PLoS medicine.

[25]  Stacey L Knobler,et al.  The Critical Path to New Medical Products , 2005 .

[26]  D. DeMets,et al.  Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework , 2001, Clinical pharmacology and therapeutics.

[27]  N. Black CONSORT , 1996, The Lancet.