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Show NANOS NEWS The Neuro- Ophthalmology Research Disease Investigator Consortium ( NORDIC) T hrough the efforts of members of the North American Neuro- Ophthalmology Society ( NANOS), the Neuro- Ophthalmology Research Disease Investigator Consortium ( NORDIC) was officially established on February 6, 2009, supported by a National Eye Institute ( NEI) U10 5- year grant. MISSION NORDIC is designed to perform prospective clinical research in neuro- ophthalmology. There is a broad spec-trum of neuro- ophthalmologic disorders that collectively affect millions of people. There are also some disorders that fit the U. S. government definition of ‘‘ rare'' diseases and have not been adequately investigated. As a consequence, there is little consensus among practitioners on their diagnostic evaluation or therapy. The aim of NORDIC is to provide an organizational and operational capability to perform multisite observa-tional and treatment trials of these conditions with the support of the NEI and other funding agencies. Expected to include nearly 200 community and academic practitioners, NORDIC will address risks, diagnosis, treatment, and other management aspects of these diseases that could not be studied without a clinical research organization. The NORDIC strategy will provide strong centralized coor-dination and use protocols that can be incorporated into standard clinical practice to facilitate and conduct multiple trials consecutively and in parallel. A multisite open network and structure will allow practitioners to develop new studies, become certified, and participate in specific studies and protocols as appropriate to their expertise and interests. This approach facilitates the recruitment and investigation of powerful numbers of patients who would otherwise be hard to find and to allow their study with a high degree of control over scientific quality. The first disorder to be studied by the NORDIC Network is idiopathic intracranial hypertension ( IIH) ( see below). ORGANIZATIONAL STRUCTURE The NORDIC Network is composed of an Executive Committee ( EC), Data Coordination and Biostatistics Center ( DCBC), certified NORDIC investigators/ sites, and a Data and Safety Monitoring Board. The EC is chaired by Mark Kupersmith, MD ( Roosevelt Hospital, Beth Israel Medical Center, New York Eye and Ear Infirmary) and co- chaired by Neil Miller, MD ( Wilmer Eye Institute, Johns Hopkins University School of Medicine). In addition to DCBC and ad hoc members ( listed below), other EC members include Laura Balcer, MD, MPH ( University of Pennsylvania) and Lynn Gordon MD, PhD ( University of California- Los Angeles). The DCBC is located at the Department of Neuro-logy, University of Rochester, under the direction of Karl Kieburtz, MD, MPH, supported by co- director Michael McDermott, PhD, who directs the biostatistics group, and Deborah Friedman, MD, MPH ( co- investigator). The NORDIC Visual Field Reading Center is directed by John Keltner, MD ( University of California- Davis) and the Photography Reading Center by Steven Feldon, MD, MBA ( University of Rochester). Additional reading centers will be developed and added to the Network as warranted by future studies. Each major protocol will have a Study Steering Committee ( SSC) and a Study Director. Michael Wall, MD ( University of Iowa) is developing and directing the Idiopathic Intracranial Hypertension Treatment Trial ( IIHTT). Drs. Keltner, Feldon, and Wall also serve as ad hoc members of the EC. The Data and Safety Monitoring Board will be constituted by the NEI. A core group will review all NORDIC projects; additional members will be added as needed for specific expertise in each study. The Credential-ing Committee for Investigators will be directed by Mark Kupersmith and includes Neil Miller and Karl Kieburtz. Under the direction of Laura Balcer, the Health Related Quality of Life Committee will develop questions and methodology to investigate the impact of the disorder in each study on vision activities. The Vision System Toxicity Committee does not currently have a director. The New Project Proposal Review Committee will be directed by Neil Miller. The Publications and Data Sharing Committee will ensure that the data collected from each study is used for publications and presentations that are consistent with NORDIC policies and guidelines, reflecting accurate, com-plete, and unbiased analyses. This committee will imple-ment the NORDIC data- sharing policy. For each NORDIC study, the Study Director and SSC members will appoint J Neuro- Ophthalmol, Vol. 29, No. 3, 2009 259 writing committees that include SSC members, study inves-tigators, and additional DCBC or EC personnel if appro-priate. The Study Director will lead the effort for writing manuscripts. All published abstracts and manuscripts will be approved by the NORDIC EC and the Publications and Data Sharing Committee before submission. PLANS NORDIC envisions the following plans: 1. Randomized controlled clinical trials to test the efficacy and safety of diagnostic procedures and treatments for specific neuro- ophthalmologic disorders. 2. Epidemiologic studies, pilot studies, and other planning activities to develop new research projects on compel-ling clinical questions in neuro- ophthalmology that will benefit from the NORDIC Network strategy. 3. Protocols and structured industry- associated studies to determine visual system toxicity of new therapies. The IIHTT will be underway in November 2009. Additional projects are in development, utilizing the NORDIC organization and resources to further the design and implementation. These and other future studies will be piloted during years 2- 5 of the grant to determine the most promising and feasible multicenter study that can be supported by granting agencies or industry or both. WEBSITE NORDIC is creating a Web site for investigators to begin the certification and membership process, organize meetings, announce new projects, submit new project concepts for formal review and feedback, and guide patients in finding NORDIC sites to enter studies. The Web site will be linked to ophthalmic and neurologic organ-izations, including NANOS, the American Academy of Ophthalmology, the American Academy of Neurology, and the National Institutes of Health. GENERATING RESEARCH IDEAS OR PROJECTS Individuals with ideas for new research and data collections should use the NORDIC project proposal template ( posted on the Web site) to develop a brief study objective, rationale, and synopsis of a study design. The proposal should be no longer than 4 pages and should include preliminary data and citations of most relevant literature. NORDIC will provide guidance for study design, hypothesis development, protocol, and procedure evolu-tion. The New Project Proposal Review Committee will review the proposal and present it to the EC if the study has scientific merit and is feasible. If the EC approves the project, NORDIC will work with the individual to develop a protocol, as well as informed consent and data collection forms. The DCBC will be involved in establishing the database and implementing data quality control measures for these studies, Internet data entry if indicated, database maintenance, and statistical analysis of the results. The individual who creates a project will have the opportunity to serve as study director. INVESTIGATOR REQUIREMENTS NORDIC membership is open to all who meet the following qualifications: Neuro- ophthalmologists who are full members of NANOS or, if not, those who have completed a neuro-ophthalmology fellowship or have comparable clinical experience. General ophthalmologists, neurologists, or optometrists experienced in neuro- ophthalmologic diseases or who conduct an active neuro- ophthalmology practice and who have basic knowledge of the clinical disorder under inves-tigation, the necessary clinical skills, and a willingness to follow standardized study procedures and protocols. For studies that involve other subspecialists, potential site investigators must agree to follow the NORDIC Network guidelines and may then be granted investigator status. Each investigator must have a clinical facility and administrative staff that can support a study protocol, including standardized light boxes, EDTRS charts, trial lenses for refraction, examination lanes ( 4 m long), Humphrey computerized perimeters with SITA software, and fundus cameras approved by the Photography Reading Center ( PRC). For some studies, additional equipment may be required. Clinical scientists, biostatisticians, and epidemiologists can serve on committees and contribute to protocol devel-opment and conduct but will not be study investigators. Because NORDIC studies will include a wide variety of systemic, ophthalmologic, and neurological disorders, investigators who do not specifically have expertise in neuro- ophthalmology may be included after being certified on the study protocol and procedures and all NORDIC policies. International NANOS members will be considered for participation in the NORDIC Network if they are able to follow study protocols and have patients who can follow study procedures, obtain approval from an institutional review board ( human subjects committee), use e- mail and have internet access, and demonstrate the ability to maintain subjects in follow- up. Investigators will have specific requirements for each protocol. The SSC and the Certification Committee are responsible for developing certification requirements and approving investigators for each protocol. A NORDIC member can elect to participate in any or all studies for which he or she meets the certification requirements. As 260 q 2009 Lippincott Williams & Wilkins J Neuro- Ophthalmol, Vol. 29, No. 3, 2009 NANOS News NORDIC evolves, investigators may be required to partici-pate in at least one study to maintain active membership. All investigators must follow NORDIC policies and conflict of interest guidelines ( posted on the Web site). FUNDING SUPPORT Investigators will be compensated on a per- subject recruitment basis and for meeting specific study milestones. Compensation will be designed to cover the costs of investigator effort, ancillary personnel, study coordinator, facilities use, and tests or procedures outside the normal standard of clinical care. A portion of the funding will be provided to support preparation of investigational review board submissions and, when a subject is enrolled, for follow- up visits and study completion. When appropriate, each investigator/ site will receive funds to cover start- up costs such as recruitment seminars, advertising, and study-specific equipment purchases. For some trials, salary support for the investigator and/ or site staff may be available. Each investigator must maintain an individual or institutional agreement with NORDIC. The agreement will indicate the payment schedule for the study and the obligations of the investigator and institution. NORDIC IIHTT The IIHTT is a prospective clinical treatment trial on IIH that includes a genetic association study in search of single polymorphisms ( SNPs) to identify metabolic and hormonal factors that differentiate overweight women who have IIH from those who do not. Clinical Trial of Therapy This randomized, double- masked, placebo- controlled trial tests the hypothesis that acetazolamide ( in a dose maxi-mum of 4 g/ day) and a low- sodium, weight- reduction diet are superior to diet alone in restoring vision or preventing visual loss in patients with IIH- induced mild visual loss. IIH patients with 2 to 5 dB baseline Humphrey visual field pattern deviation will be invited to enter. The change in the perimetric mean deviation ( PMD) from baseline to month 6 is to be the primary outcome variable. Additional outcomes measured yearly up to 4 years are changes in papilledema grade, cerebrospinal fluid ( CSF) pressure measurements, other visual field measures, and quality of life measures. Proteomic and Genetic Study The aim of this component of the study is to identify proteomic and genetic risk factors for IIH by screening a large cohort of patients with IIH and control subjects to determine the serum and CSF levels of potential mediators of IIH suggested by the genetic analysis and to conduct an association study to search for SNPs that confer risk for developing IIH. A cohort of 154 patients with IIH and 154 control subjects matched on body mass index, ethnicity, and gender will be genotyped at SNPs contained within gene- encoding molecules likely to be involved in the etiology of IIH using the SNPlex genotyping system. Genes associated with obesity will be profiled. This part of the trial will also test the hypothesis that IIH is associated with abnormal metabolism of leptin or vitamin A or both. Leptin levels, vitamin A, and related factors will be measured at baseline and 6 months. Mark J. Kupersmith, MD Institute for Neurology and Neurosurgery at Roosevelt Hospital, New York Eye and Ear Infirmary and Albert Einstein School of Medicine New York, New York Neil Miller, MD Wilmer Eye Institute and Johns Hopkins University School of Medicine Baltimore, Maryland Laura Balcer, MD, MPH Departments of Neurology and Epidemiology University of Pennsylvania School of Medicine Philadelphia, Pennsylvania Lynn Gordon, MD, PhD Department of Ophthalmology University of California, Los Angeles Department of Surgery Greater Los Angeles Veterans Affairs Healthcare System Los Angeles, California Michael Wall, MD Department of Neurology University of Iowa Iowa City, Iowa John Keltner, MD Department of Ophthalmology University of California, Davis Davis, California Deborah Friedman, MD, MPH Steven Feldon, MD, MBA Michael McDermott, PhD Karl Kieburtz, MD, MPH Departments of Ophthalmology, Neurology, and Biostatistics University of Rochester Rochester, New York mkuper@ chpnet. org 261 NANOS News J Neuro- Ophthalmol, Vol. 29, No. 3, 2009 [CLiihtt] |
