Assessment of the Incorporation of Patient-Centric Outcomes in Studies of Minimally Invasive Glaucoma Surgical Devices

Importance  Minimally invasive glaucoma surgical (MIGS) devices are one option for lowering intraocular pressure in patients with glaucoma.

Objective  To examine how often existing clinical studies of MIGS devices registered on ClinicalTrials.gov measure patient-centric outcomes that patients value directly.

Design, Setting, and Participants  We searched ClinicalTrials.gov, a registry of publicly and privately supported clinical studies, on February 20, 2015, for records of MIGS device studies involving patients with glaucoma. Two investigators independently abstracted study design and outcome details from eligible records. We classified outcomes as patient-centric or not patient-centric using a prespecified definition.

Main Outcomes and Measures  Proportion of patient-centric and nonpatient-centric outcomes registered on ClinicalTrials.gov.

Results  We identified 51 eligible studies specifying 127 outcomes. Reduction in intraocular pressure was the most frequent outcome specified (78/127; 61%) and a primary outcome in 41 studies. Patient-centric outcomes—such as adverse events (n = 19; 15%), topical medication use (n = 16; 13%), visual acuity (n = 4; 3%), and health-related quality of life (n = 1; 1%)—were less frequently specified (n = 40; 32%) and a primary outcome in only 12 studies.

Conclusion and Relevance  Patient-centric outcomes that provide insight into the relative desirability and acceptability of the benefits and risks of MIGS devices are not well represented in current clinical studies.

Glaucoma is a leading cause of blindness in the United States and worldwide.¹ The goal of glaucoma treatment has been to lower intraocular pressure (IOP) to a level where the threat to the optic nerve is minimized. Minimally invasive glaucoma surgical (MIGS) devices are increasingly being used to lower IOP, with a claimed higher safety profile than other glaucoma devices.² While there is no universal definition of a MIGS device, the US Food and Drug Administration (FDA) and the American Glaucoma Society refer to them as devices that are surgically implanted in the eye with minimal to no conjunctival manipulation or scleral dissection and designed to lower IOP by improving the aqueous humor outflow mechanism.³

The FDA approved the first MIGS device in June 2012, and there are more devices presently in various stages of development.⁴ The FDA cosponsored a meeting with the American Glaucoma Society in February 2014 to explore the design of MIGS clinical trials.^5,6Patient preference information, defined as information obtained through “qualitative or quantitative assessments of the relative desirability or acceptability of attributes that differ among alternative diagnostic or therapeutic strategies,” was not the focus of these discussions.⁷ Our objective was to examine how often MIGS studies registered on ClinicalTrials.gov measure the outcomes that patients value directly.

After consultations with glaucoma specialists, we defined a priori outcomes as patient-centric or not patient-centric. Patient-centric outcomes, also referred to as a patient-centered outcome by the Patient-Centered Outcomes Research Institute,⁸ are outcomes that patients notice or report directly, such as how well one can see (including visual acuity measured by an eye chart), ability to drive, a reduction in topical medication use, or adverse events. We classified an outcome as not patient-centric if it is a surrogate measure that patients do not commonly report directly, such as IOP reduction.⁹ Intraocular pressure is neither a direct measure of structural or functional glaucomatous optic neuropathy, nor an outcome that patients directly report, except in cases of very high or very low IOP.¹⁰

Using a search strategy designed by a trained information scientist, we searched ClinicalTrials.gov, a registry of publicly and privately supported clinical studies around the world, on February 20, 2015, for all registered interventional studies examining a MIGS device with glaucoma (or glaucoma combined with cataract) as a condition of interest. Two researchers (J.T.L. and S.V.) trained in epidemiology and clinical trial methods independently abstracted study design details and the outcomes specified in the current outcomes fields of the included records. We then classified each outcome as either patient-centric or not patient-centric. We resolved all discrepancies through group discussion.

Approval for this study was not obtained as we analyzed existing clinical study records registered on ClinicalTrials.gov and we did not have direct contact with patients.

We identified 51 eligible records, specifying 127 unique outcomes. Reduction in IOP was the most frequent outcome specified (78/127; 61%) and was the primary outcome in 80% (41/51) of the records (Table). More than half of the records (26/51; 51%) included at least 1 patient-centric outcome, but patient-centric outcomes represented a small proportion of the 127 outcomes that we found: adverse events (n = 19; 15%), topical medication use (n = 16; 13%), visual acuity (n = 4; 3%), and health-related quality of life (n = 1; 1%). None of the studies specified any other visual function outcomes, such as ability to drive or read fine print.

These findings raise the question of whether current MIGS studies address outcomes that matter most to patients. A natural next step would require engaging with patients in qualitative (eg, semistructured interviews) and quantitative (eg, stated-preference studies and surveys) approaches of collecting patient preference information. Because glaucoma is a condition that has many treatment options but no cure and because patients with glaucoma are willing to consider trade-offs when making these decisions,¹¹ patient preference information can aid in better defining a set of outcomes that best reflects patient-valued aspects of MIGS devices. This effort will contribute to advancing the FDA’s commitment toward incorporating the patients’ perspective into the device evaluation process.^12-15

Patient-centric outcomes that provide insight into the relative desirability and acceptability of the benefits and risks of MIGS devices are currently not well represented in clinical studies.

Corresponding Author: Tianjing Li, MD, MHS, PhD, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, E6011, Baltimore, MD 21205 (tli19@jhu.edu).

Submitted for Publication: January 29, 2016; final revision received May 12, 2016; accepted May 12, 2016.

Published Online: July 7, 2016. doi:10.1001/jamaophthalmol.2016.2101.

Author Contributions: Mr Le and Dr Li had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Le, Tarver, Eydelman, Li.

Acquisition, analysis, or interpretation of data: Le, Viswanathan, Li.

Drafting of the manuscript: Le, Li.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Le, Viswanathan.

Obtained funding: Tarver, Eydelman, Li.

Administrative, technical, or material support: Viswanathan, Eydelman, Li.

Study supervision: Li.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Funding/Support: This project was funded by grant U01 FD004977-01 from the US Food and Drug Administration (FDA) to the Johns Hopkins’ Center of Excellence in Regulatory Science and Innovation (CERSI). Mr Le is a CERSI scholar, and he received training grant T32AG000247 from the National Institute on Aging.

Role of the Funder/Sponsor: The FDA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation of the manuscript; the FDA had a role in the review and approval of the manuscript, and the decision to submit the manuscript for publication. The National Institute on Aging had no role in any aspect of the study.

Previous Presentation: This study was presented at the Food and Drug Administration Office of Regulatory Science and Innovation Science Symposium 2015; April 27, 2015; Silver Spring, Maryland.

Additional Contributions: We thank Kay Dickersin, MA, PhD, and Barbara Hawkins, PhD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, for their valuable feedback and comments on previous versions of this manuscript. We also thank Lori Rosman, MLS, AHIP, of Welch Medical Library, Baltimore, Maryland, for her help with developing the search strategy. They did not receive compensation.