PERSPECTIVE Communicating the Promise for Ocular Gene Therapies: Challenges and Recommendations

SHELLY BENJAMINY, STEPHANIE P. KOWAL, IAN M. MACDONALD, AND TANIA BUBELA

PURPOSE: To identify challenges and pose solutions ECENT SUCCESSES IN OCULAR CLIN- for communications about ocular gene therapy between ical trials have revitalized hopes for a field that was patients and clinicians as clinical research progresses. previously marked by high-profile disappoint- R1 DESIGN: Literature review with recommendations. ments. Pioneering clinical trials to address mutations of METHODS: Literature review of science communica- the RPE65 gene that cause Leber congenital amaurosis tion best practices to inform recommendations for (LCA) established safety and demonstrated improvements patient-clinician discussions about ocular gene therapy. in visual function.2–4 These studies were celebrated by the 5 RESULTS: Clinicians need to employ communications research community and the media, igniting hopes for about ocular gene therapy that are both attentive to gene therapies for related . Our goal here is patient priorities and concerns and responsive to other to identify challenges and pose solutions for communica- sources of information, including overly positive news tions about ocular gene therapy between patients and clini- media and the Internet. Coverage often conflates cians as clinical research progresses. Although we focus on research with therapy—clinical trials are experimental gene therapy, similar considerations apply to other experi- and are not risk free. If proven safe and efficacious, mental biotherapeutics. gene therapy may present a treatment but not a cure The discussion is timely. One research group at the for patients who have already experienced vision loss. University of Pennsylvania reports that positive safety Clinicians can assist patients by providing realistic esti- and efficacy results from the LCA trials have been sustained mates for lengthy clinical development timelines and over time in adults and children6; readministration in the positioning current research within models of clinical second eye of 3 adult patients was both safe and efficacious translation. This enables patients to weigh future thera- after previous exposure to the vector.6 A fully enrolled peutic options when making current disease manage- phase III pediatric clinical trial is underway and expected ment decisions. to report in late 2015 (NCT00999609). The pediatric trial CONCLUSIONS: Ocular gene therapy clinical trials is crucial because LCA studies suggest a therapeutic win- are raising hopes for treating a myriad of hereditary dow for visual gain, with earlier application leading to retinopathies, but most such therapies are many years more dramatic responses.7 in the future. Clinicians should be prepared to counter Although these results appear promising, studies in overly positive messaging, found in news media and on dogs suggest that degenerative processes may continue the Internet, with optimism tempered by evidence to after the gene therapy intervention, if such degeneration support the ethical translation of gene therapy and has already commenced.8 In humans, a second research other novel biotherapeutics. (Am J Ophthalmol group reported that gene therapy improves vision for at 2015;160(3):408–415. Ó 2015 The Authors. least 3 years, but photoreceptor degeneration also con- Published by Elsevier Inc. This is an open access tinues at the same rate as in the natural course of the dis- article under the CC BY-NC-ND license (http:// ease.9 Long-term follow-up (4.5-6 years) from 3 treated creativecommons.org/licenses/by-nc-nd/4.0/).) patients indicated progressive diminution of the areas of improved vision.10 Similar results were reported by a team from the United Kingdom: retinal sensitivity Accepted for publication May 26, 2015. improved after gene therapy but diminished after 11 From the School of Public Health (S.B., S.P.K., T.B.); and the 12 months. Gene therapy may therefore not offer a Department of Ophthalmology and Visual Sciences, University of permanent treatment, and most benefit is likely if the Alberta (I.M.M.), Edmonton, Alberta, Canada. S. Benjaminy is currently with the National Core for Neuroethics, intervention occurs prior to the onset of retinal degener- 8 Department of Medicine, University of British Columbia, Vancouver, ation. Some patients may require a second round of gene BC, Canada. therapy, and gene therapy may best be used in combina- Inquiries to Tania Bubela, School of Public Health, 3-300 Edmonton Clinic Health Academy, 11405 – 87 Ave, Edmonton, AB, Canada T6G tion with other medications, if and when these are devel- 12 1C9; e-mail: [email protected] oped. Research continues to improve gene therapy

408 Ó 2015 THE AUTHORS.PUBLISHED BY ELSEVIER INC. 0002-9394 http://dx.doi.org/10.1016/j.ajo.2015.05.026 V OL . 160 TABLE. Completed or Active Ocular Gene Therapy Clinical Trials Registered in ClinicalTrials.gov by May 2015 and Associated PUBMED Publications ,N O

. Disease Intervention Phase Enrollment Age Group Start Year - End Year Status Sponsor Clinical Trial Identifier 3 AAV2-hCHM I/II 10 A,S 2015–2021 R Spark Therapeuticsa NCT02341807 rAAV2 REP1b II 30 A,S 2015–2018 NYR University of Oxford NCT02407678 rAAV2.REP1b I/II 12 A,S 2011–2015 R University of Oxford NCT01461213c rAAV2.REP1b I 6 A,S 2015–2018 R University of Alberta NCT02077361 Leber congenital amaurosis AAV2-hRPE65v2 III 24 C,A,S 2012–2029 ONR Spark Therapeuticsa NCT00999609 AAV2-hRPE65v2 I/II 12 C,A,S 2010–2026 ONR Spark Therapeuticsa NCT01208389 a d

C AAV2-hRPE65v2 I 12 C,A,S 2007–2024 ONR Spark Therapeutics NCT00516477 MUIAIGTHE OMMUNICATING rAAV2-CB-hRPE65 I/II 12 C,A,S 2008–2027 ONR Applied Genetic Technologiesa NCT00749957 rAAV 2/2.hRPE65p.hRPE65 I/II 12 C,A 2007–N/A ONR University College, London NCT00643747e rAAV2-CBSB-hRPE65 I 15 C,A,S 2007–2026 ONR University of Pennsylvania NCT00481546f rAAV2/4.hRPE65 I/II 9 C,A 2011–2014 Com Nantes University Hospital NCT01496040 rAAV2-hRPE65 I 10 C,A,S 2010–2017 R Hadassah Medical Organization NCT00821340 Leber hereditary scAAV2-P1ND4v2 I 27 A 2014–2019 R John Guy, University of Miami NCT02161380 rAAV2-ND4 N/A 6 C,A 2011–2013 R Bin Li, Huazhong University of Science NCT01267422 P

OIEFOR ROMISE and Technology Neovascular age-related macular rAAV.sFlt-1 I/II 40 A,S 2011–2015 ONR Lions Eye Institute, NCT01494805 degeneration AAV2-sFLT01 I 34 A,S 2010–2018 ONR Genzyme, a Sanofi Coa NCT01024998 RetinoStat I 21 A,S 2011–2015 ONR Oxford BioMedicaa NCT01301443 a

O RetinoStat I 21 A,S 2012–2027 R Oxford BioMedica NCT01678872

CULAR AdGVPEDF.11D I N/A A,S N/A Com GenVeca NCT00109499 pigmentosa rAAV2-VMD2-hMERTK I 6 C,A,S 2011–2023 R Fowzan Alkuraya, King Khaled Eye NCT01482195

G Specialist Hospital

ENE rAAV2tYF-CB-hRS1 I/II 27 C,A,S 2015–2020 NYR Applied Genetic Technologiesa NCT02416622 AAV-RS1 I/II 100 A,S 2014–2017 R NCT02317887 T

HERAPIES Stargardt StarGen I/II 46 C,A,S 2011–2017 R Sanofia NCT01367444 StarGen I/II 28 A,S 2012–2022 R Sanofia NCT01736592 Usher syndrome UshStat I/II 18 A,S 2012–2017 R Sanofia NCT01505062g UshStat I/II 18 A,S 2013–2022 R Sanofia NCT02065011

A ¼ adult; C ¼ child; Com ¼ completed; N/A ¼ not available; NYR ¼ not yet open for participant recruitment; ONR ¼ ongoing, but not recruiting participants; R ¼ recruiting/enrolling by invitation; S ¼ senior. aIndustry sponsor. bNightstaRx AAV2-REP1 product. cResults published by Seitz et al13 (PubMed ID 25744334) and MacLaren et al14 (PubMed ID: 24439297). dResults published by Melillo et al15 (PubMed ID: 22812667), Maguire et al7 (PubMed ID: 19854499), and Maguire et al4 (PubMed ID: 18441370). eResults published by Bainbridge et al11 (PubMed ID: 25938638) and Bainbridge et al2 (PubMed ID: 18441371). fResults published by Jacobson et al10 (PubMed ID: 25936984), Cideciyan et al16 (PubMed ID: 25537204), and Jacobson et al17 (PubMed ID: 21911650). gResults published by Zallocchi et al18 (PubMed ID: 24705452). 409 vectors and surgical delivery to ensure that patients other Internet sources, as well as family and friends. Forty receive an optimal dose for long-lasting effects.12 percent of the American public follow health news stories The LCA trials have paved the way for other retinopa- closely,19 especially those that are personally relevant20; thies (Table). Public and private investments now support Internet access to health information is widespread and companies created to advance clinical development of growing.21 ocular gene therapy. Spark Therapeutics has licensed tech- Media coverage of genetic research, particularly clinical nologies from the Children’s Hospital of Philadelphia, research, is highly positive, framed as a celebration of prog- including those designed for LCA and choroideremia ress in research.22 News articles focus on benefits, while (http://www.sparktx.com/). NightstaRx was similarly omitting or downplaying risks, and provide limited back- launched in the United Kingdom to develop a gene therapy ground information for readers to assess the validity or cred- product for choroideremia (http://www.nightstarx.com/). ibility of the research (including funding sources and Spin-off companies such as these enable scale-up from clin- potential conflicts of interest). They accelerate timelines ical trials to gene therapies available to patients in the by presenting preclinical or early-stage research as an clinic. However, potential financial conflicts of interest imminent therapy or cure.23 News articles often contextu- for researchers conducting clinical trials and involved in alize research with a human-interest story focused on a sponsoring companies must be managed carefully. Clinical hopeful patient or a heroic researcher.24 Media coverage trial participants must be informed of any conflicts of inter- of ocular gene therapy clearly follows this pattern.25 It de- est during consent processes to ensure the integrity of the scribes a range of visual outcomes from slowing vision loss research. Lessons may be taken from the early days of to a cure, even though the latter is clinically infeasible. gene therapy clinical trials. Financial conflicts of interest, This positive coverage of ocular gene therapy generates along with improper informed consent and protocol viola- high expectations in patient communities. For example, af- tions, damaged the reputation and progress of the field ter the highly publicized successes in early-phase LCA tri- following the death of Jesse Gelsinger in a gene therapy als, clinical reports documented a trend of LCA patients clinical trial at the University of Pennsylvania in 1999. and families wishing to access clinical trials.26 Less publi- Against this backdrop, patients and their families are cized was the caveat that the initial LCA trials addressed increasingly likely to request information from clinicians only 1 of 17 known genetic mutations underlying the dis- about emerging therapies. Patients may ask about potential ease, representing only 5% of LCA cases.26 treatment options or about articles on experimental inter- Patient organizations, such as the Foundation Fighting ventions that they have retrieved from external sources; pa- Blindness (www.ffb.ca) and the Choroideremia Research tients may inquire about clinical trials and about the Foundation (cureCHM.org), also contribute to the com- possibility of enrolling in such trials; and patients may munications landscape. These organizations both fund ask about early or compassionate access programs that are innovative research and communicate with patients and available in some countries. These programs allow health the public about associated risks, benefits, and timelines. care providers to apply for the use of investigational prod- Featured prominently on these sites are current and ucts such as unapproved drugs or devices that are still in planned gene therapy clinical trials. The Foundation clinical trial or market approval stages. To be eligible for Fighting Blindness provides up-to-date information on such access programs, patients must have serious or life- clinical trials and genetic testing resources and maintains threatening conditions, have no alternative therapy op- a patient registry as a tool to connect individuals living tions, and have no other product access option (including with inherited eye diseases to scientists researching those clinical trial participation), and the potential benefits of conditions. The Choroideremia Research Foundation the product must outweigh the risks. This risk-vs-benefit ra- operates similarly, and has recently adopted the Founda- tio is difficult to characterize for products that are in early tion Fighting Blindness MyRetinaTracker (https://www. phases of clinical trials. myretinatracker.org),aregistrythatallowspatientstoup- load their genotypic, phenotypic, lifestyle, and other clinical data to enable de-identified research use. Such registries are facilitated by advancements in genetic A COMMUNICATIONS LANDSCAPE OF testing, including next-generation sequencing, that PROMISE enable molecular diagnostics.27,28 While access to genetic testing may be differentially covered by health 29 COMMUNICATIONS ABOUT CUTTING-EDGE RESEARCH care systems and insurance policies, if available, molec- will not occur in an informational vacuum. When discus- ular diagnostics may improve health-related quality of life sing research with patients, clinicians need to be attentive by providing valuable information for reproductive coun- to patient priorities and concerns but also responsive to seling in cases of de novo mutations, information neces- other sources of information. These sources include sary to enroll patients in clinical trials, and empowering news media, patient advocacy organizations, industry, so- patients with knowledge and the opportunity to actively cial media, health and research organization websites, and drive the research process forward.30,31

410 AMERICAN JOURNAL OF OPHTHALMOLOGY SEPTEMBER 2015 In summary, patients increasingly access health informa- and a follow-up study 3 years after treatment in 5 partici- tion from print and broadcast media sources and on the pants.37 While preliminary results appear promising, these Internet and raise this information during clinical visits. are not without the caveats discussed in the introduction. However, it is challenging for patients to assess the accu- More definitive evidence of efficacy for LCA gene therapy racy and credibility of such information, and reports on will emerge from the phase III trial later this year; peer- research into ocular gene therapy and related bio- reviewed, published accounts demonstrating efficacy of therapeutics paint a highly optimistic view of timelines ocular gene therapy remain, at present, limited. and expected outcomes. Studies consistently emphasize the relational nature of care (between patients and their Recommendation. When discussing access to an investi- families and clinicians) and demonstrate better outcomes gational gene therapy product by way of a clinical trial or if the concerns of patients are met.32 Here we discuss otherwise, clinicians should address sources of information, how clinicians might aid patients and families in navi- the goals of different phases of clinical trials, the credibility gating the complex web of information and supporting of the clinical trial (including the site, sponsor, and hope while keeping expectations grounded in current clin- research team), and that clinical trials represent research, ical and research realities. not therapy. Clinicians may point patients and families to credible sources of information. For example, the Foun- dation Fighting Blindness website, while acknowledging patient hopes for a treatment, explicitly states: ‘‘The word CLINICAL COMMUNICATION TOPICS intervention is used instead of the word treatment to AND RECOMMENDATIONS help people remember that the drug and/or surgery that the participant is receiving is not an established treatment. 38 RESEARCH, NOT TREATMENT: Coverage of novel bio- A clinical trial is not a treatment it is an experiment.’’ therapeutics conflates research with therapy. The very use of the term ‘‘therapy’’ in a clinical research context im- PARTICIPATION IN CLINICAL RESEARCH IS NOT RISK plies demonstrated therapeutic effect,1 but cumulative ev- FREE: Media coverage of ocular gene therapy has been 39 idence suggests that fewer than 1% of participants derive a highly positive; like most coverage of genetics, it empha- 25 direct benefit from phase I gene therapy clinical trials.33 sizes benefits and provides minimal information on risks. Media articles use research and treatment terminology While most published accounts of gene therapy have interchangeably,25 confusing research goals and the state shown positive safety profiles, some risks are apparent. of clinical development.34 This confusion is problematic General risks for gene therapy, which remain hypothetical in the context of clinical trial enrollment, as hope for ther- risks for ocular applications, include oncogenic risks from 40 apeutic benefit from early-stage clinical trials exemplifies a insertional mutagenesis and a severe immune response. ‘‘therapeutic misconception.’’35 Such a misconception may Specific risks include surgical complications, loss of undermine consent processes in clinical trial enrollment, an eye owing to endophthalmitis, loss of remaining 2–4 which require participants to understand the research vision, and a theoretical risk of brain toxicity owing to goals.35 integration of the viral vector in the . 4 In reality, research extends along a developmental con- Reported adverse events include a macular hole, foveal 17 14 tinuum from laboratory research using cell and animal thinning, and . Other risks to partic- models to preclinical or enabling research—the goals of ipants include associated financial burdens and psycholog- which are to demonstrate safety and the proposed mode ical stress. While disclosure of risks is an essential of action of the therapeutic for regulatory clinical trial ap- component of the informed consent process for clinical plications—through the phases of clinical trials. Rates of trial participation, urgency to access a trial may divert pa- 34 attrition between phases of clinical trials are high. Of inter- tient attention from the risks. ventions that enter phase 1, only 15% receive market authorization from a regulatory agency following phase 3 Recommendation. When discussing possible participa- clinical trials; the greatest attrition occurs in phase 236 tion in a clinical trial, clinicians should highlight that po- and is likely worse for more complex biotherapeutics. tential risks exist. Clinicians may direct patients to Phase I clinical trials are designed to test safety and the carefully consider and question descriptions of both magni- maximum tolerable dose. Though some safety outcome tude and likelihood of risks during the process of informed measures blur with those for efficacy, small phase 1 studies consent. are inadequately powered to test the latter. For example, the first clinical study on choroideremia gene transfer POTENTIAL TREATMENT, NOT CURE: If proven safe and published in The Lancet reported on 6 patients.14 Similarly, efficacious, gene therapy may present a treatment but not a published accounts of the LCA trials reported on 3 partic- cure for patients who have already experienced vision loss. ipants in the New England Journal of Medicine (2008), a While gene therapy may restore the function of dormant dose-escalation study in 12 participants in The Lancet,7 yet viable photoreceptors and thereby improve visual

VOL. 160,NO. 3 COMMUNICATING THE PROMISE FOR OCULAR GENE THERAPIES 411 challenging. Even for small-molecule drugs, it takes 10-14 years, with estimated costs in the billions, to move from pre- clinical studies to market authorization by a regulatory agency.42 Gene therapy has been hailed as 5 years away from clinical application since the 1990s,43 and media, clini- cians, and patient advocates contribute to patient confusion by expressing vague timelines for its arrival in the clinic.25,34 The media often depict the promise of research without providing context of when the described benefits may be realized. They widen the gap between patient hopes for an imminent treatment and the clinical reality of limited ther- apeutic options for many conditions.44 For example, choroi- FIGURE 1. Visual outcome perspectives of choroideremia gene deremia patients were left uncertain about whether gene therapy stakeholders and ocular gene therapy media representa- therapies would become available within their own thera- tions. peutic window for visual gain.25 Nevertheless, these patients wished to consider future therapeutic options, such as gene therapy, when making current disease management deci- outcome measures, unlike proposed cell therapies, it is not sions. Contextualizing expected times (and uncertainties) 17 regenerative. The LCA trials demonstrate that there may from mutation identification to potential gene therapy clar- be a therapeutic window for efficacy, with earlier interven- ifies media accounts that make a direct link between discov- tion being better, especially if prior to the onset of retinal ery of ‘‘blindness-causing genes’’ and treatments.45 8 degeneration. Nevertheless, the media commonly repre- The history of LCA gene therapy research is illustrative 25 sent gene therapy as a cure for inherited eye diseases. of timelines (Figure 2). The RPE65 mutation was identified One popular book on LCA gene therapy went so far as to in 199746; phase I/II human trials began in 20072 with cur- 41 be titled The Forever Fix. rent trials in phase III (NCT00999609). The gene therapy Other stakeholder perspectives tend to be more product may become the first approved in the United nuanced. Participants in one choroideremia study antici- States, aided in part by financial and regulatory incentives pated outcomes that ranged from no benefit, through slow- that expedite approval for orphan drugs that treat serious ing or halting vision loss, to a cure for choroideremia conditions and fill unmet medical need.47 NightstaRx, for 34 (Figure 1). All stakeholder groups acknowledged the pos- example, recently announced that it has received orphan sibility of no benefit. However, although clinicians and drug status in both the United States and Europe for its advocacy organizations did not express expectations for a choroideremia gene therapy product (http://www. cure and considered slowing vision loss as a realistic nightstarx.com/). While it is a necessary precursor to clin- outcome, patient perspectives ranged from halting vision ical availability, regulatory approval is not the endpoint. loss to a cure. In other words, patients overestimated the Novel biotherapies must still be adopted into clinical set- potential benefits of gene therapy research, which repre- tings and be paid for by public or private insurers.48 These 35 sents a ‘‘therapeutic misestimation.’’ Such overestimation therapies are often very expensive and must clear value as- of benefit may be ethically tolerable if its probability was sessments by cash-strapped health systems and hospitals.49 difficult to convey or perceive,35 but in the case of ocular gene therapy, a cure is highly unlikely. Its long-term effects Recommendation. Patients wish to weigh future thera- 8 are unknown at present. peutic options when making current disease management decisions. Consequently, clinicians should discuss research Recommendation. It is important for clinicians to clearly timelines in relation to their patients’ vision loss and prog- communicate the spectrum of possible visual benefits of noses. Clinicians can assist patients by providing realistic future gene therapies. Gene therapy is not regenerative, timelines and positioning current research within models and therefore will not revive cells that have already degen- of clinical translation. Valuable information includes the erated. Thus, if approved by United States regulators as the phases of clinical trials and their goals, regulatory ap- first ocular gene therapy product following phase III clinical provals, insurance/health system coverage decisions, and trials, Spark Therapeutics’ gene therapy for LCA will be a eventual clinical adoption. Such context will assist patients treatment, not a cure. Mounting evidence suggests that in assessing the likelihood of a gene therapy within a ther- gene therapy may need to be readministered, or adminis- apeutically meaningful window for their vision loss. tered in combination with medications that may still be 12 in development. CELEBRATING HOPES THAT ARE GROUNDED IN CUR- RENT CLINICAL REALITIES: The last 20 years have seen TRANSLATIONAL TIMELINES ARE LENGTHY: The road tremendous advances in research for retinopathies to the clinic for novel biotherapeutics is long and including the identification of over 280 genes and loci

412 AMERICAN JOURNAL OF OPHTHALMOLOGY SEPTEMBER 2015 FIGURE 2. Translational timeline of gene therapy for Leber congenital amaurosis (LCA).50–52 Colors indicate research groupings. Red [ Maguire/Bennett group: University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP); gene therapy product licensed by Spark Therapeutics. Blue [ Jacobson/Cideciyan group: University of Pennsylvania. Green [ Bainbridge group: University College, London.

underlying inherited retinal disorders.53 and a shift from expectations in current clinical realities. In other words, clini- basic science inquiry to targeted preclinical and clinical tri- cians might employ a ‘‘plan for today, hope for tomorrow’’ mes- als using gene transfer, stem cell, drug, and optogenetic ap- sage. Clinicians may employ a wellness-based approach, proaches.54 These developments provide a landscape of emphasizing enhancement in the emotional, psychological, hope, which is rooted in a ‘‘paradox of uncertainty’’55—pos- and spiritual dimensions of quality of life in addition to itive clinical trials have the potential to transform current hopes for physiological improvements.55 prognoses of vision loss but may equally be a source of anx- iety or vulnerability. The latter arises because treatments may not become available within the limited therapeutic windows of patients. CONCLUSION Reflecting on hope, Ruth McGovern, mother of 2 boys with adrenoleukodystrophy, an X-linked metabolic disorder OCULAR GENE THERAPY CLINICAL TRIALS ARE RAISING targeted by gene therapy research, stated: ‘‘hope is uplifting hopes for treating a myriad of hereditary retinopathies. How- and valuable when all around is uncertain for without hope ever, for most diseases, such therapies are many years in the thealternativeformewouldbedespair.’’56 Hope both sup- future. We call for a clinical communications approach that ports and is supported by disease management. But hope respects and contextualizes patient hopes within current clin- may also challenge pragmatic efforts to prepare for a prognosis ical and research realities. Clinicians should be prepared to of vision loss,34 including vocational and assistive technology, counter overly optimistic messaging, especially that found dietary supplementation, and social supports. in news media and on the Internet, with optimism tempered by evidence. Such communications will become increasingly Recommendation. These findings necessitate a commu- important as novel gene and cell therapies advance through nications approach that acknowledges patient hopes clinical development and will support the ethical translation for possible therapeutic interventions, while grounding of these fields.

VOL. 160,NO. 3 COMMUNICATING THE PROMISE FOR OCULAR GENE THERAPIES 413 ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST and none were reported. This work was supported by an Alberta Innovates - Health Solutions, Canada CRIO Team Grant (Alberta Ocular Gene Therapy Team, Co-leads: I.M.M., T.B.), as well as by a Canadian Institutes of Health Research (CIHR) Emerging Team Grant, Rare Diseases (I.M.M., T.B.), and grants from the Foundation Fighting Blindness Canada and the Choroideremia Research Foundation, Canada. All authors attest that they meet the current ICMJE requirements to qualify as authors. The authors thank Mark Bieber and Zackariah Breckenridge, School of Public Health, University of Alberta, for compiling and annotating current ocular gene therapy clinical trials.

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VOL. 160,NO. 3 COMMUNICATING THE PROMISE FOR OCULAR GENE THERAPIES 415 Biosketch

Shelly Benjaminy is a doctoral student at the National Core for Neuroethics at the University of British Columbia. She holds a Bachelor of Science degree with Specialization in Molecular Genetics, and a Master of Science degree in Health Policy Research from the University of Alberta. Ms. Benjaminy specializes in translational ethics and utilizes pragmatic empirical approaches to explore ethical, social and policy dimensions of developing biotechnologies.

415.e1 AMERICAN JOURNAL OF OPHTHALMOLOGY SEPTEMBER 2015 Biosketch

Dr. Tania Bubela (BSc (Hons), PhD, JD) is Professor and Associate Dean (Research) in the School of Public Health, Canada. Her research program addresses barriers to the effective translation of new technologies arising from collaborative science networks in genomics, gene therapy, and stem cell biology, including ethical issues, effective communication of risks and benefits among stakeholder groups, commercialization and regulation.

VOL. 160,NO. 3 COMMUNICATING THE PROMISE FOR OCULAR GENE THERAPIES 415.e2