Clinical Trial Performance of Community- vs University-Based Practicesin the Submacular Surgery Trials (SST): SST Report No. 2

Objective  To compare the performance of community- vs university-based clinicalcenters in 3 multicenter randomized clinical trials of intraocular surgery.

Methods  Each Submacular Surgery Trials clinical center was classified as a university-basedcenter, if the contract to perform as a center was signed by a universityofficial, or as a community-based center. The 2 groups of centers were comparedon performance, assessed cumulatively by the Submacular Surgery Trials QualityAssurance and Monitoring Subcommittee.

Outcome Measures  Patient accrual, completion of scheduled examinations, completion ofmasked vision examinations 2 years after enrollment (the designated primarystudy end point evaluation time), timeliness of submission of retinal photographsrequired by protocol to the Photograph Reading Center, completion of health-and vision-related quality-of-life interviews, and timeliness of submissionof the primary outcome data to the Coordinating Center after completion ofthe examination.

Results  Almost all centers performed at a very high (good) level, although therewas a trend for some community-based centers to be at the lower end of mostdistributions.

Conclusions  Most community- and university-based centers performed well in thesemulticenter clinical trials. Monitoring performance and periodically providingfeedback to clinical center investigators may encourage excellent performancein areas critical to the success of clinical trials, regardless of whetherthe center is community or university based.

Monitoring the performance of centers participating in multicenter clinicaltrials is critical to the success of the trials. This type of supervision,for example, allows the study organization to determine whether (1) accrualof study participants is occurring at an acceptable rate, (2) participantsenrolled meet eligibility criteria, (3) procedures are followed per protocol,and (4) loss to follow-up is minimized. A study¹ fromthe oncology field published in 1981 based on monitoring suggested that animportant indicator of the quality of a clinical center in multicenter clinicaltrials was the number of study participants enrolled at that center. The authorssuggested that an institution should not participate in multicenter trialsunless some predetermined minimal number of study participants can be enrolledby investigators at the institution within a specific time.¹ Thestudy generated letters agreeing^2,3 anddisagreeing^4,5 with this conclusion,including an analysis from the Eastern Cooperative Oncology Group⁴, which found that the quality of participation ofinstitutions with few patients entered was similar to that of institutionswith many patients entered when aspects of performance were considered. Thatsame oncology group⁶ subsequently publishedanother study that compared the performance of university hospitals or majortreatment centers with that of community hospitals. They concluded that includingcommunity hospitals in their clinical trials did not reduce the quality ofthe data or compromise the therapeutic outcomes.⁶ Anotheroncology group⁷ also compared the quality ofparticipation of community affiliates with that of universities and foundthat the performance of the community affiliates equaled or surpassed thatof the university centers in most measures.

These results in the oncology field may or may not apply to performancein multicenter clinical trials in ophthalmology for a variety of reasons.For example, ophthalmic problems usually are not life threatening and oftenmay be managed in an outpatient setting. To determine whether there was arelationship between rate of patient enrollment and quality of clinical centerperformance in ophthalmology, performance in 2 multicenter clinical trials(the Macular Photocoagulation Study and the Early Treatment Diabetic RetinopathyStudy) was analyzed.⁸ This evaluation led tothe conclusion that clinical centers enrolling fewer patients in these trialsperformed in some areas as well as or better than centers enrolling largernumber of patients.⁸ However, the evaluationdid not compare the performance of community-based clinical centers with thatof university-based centers.

The purpose of this current analysis is to compare the performance ofcommunity-based clinical centers with that of university-based clinical centersin 3 multicenter clinical trials of intraocular surgery. In addition, thisstudy comments on issues that should be considered when identifying and selectingcommunity- and university-based practices to participate in multicenter randomizedclinical trials and suggests strategies designed to keep performance levelshigh.

The Submacular Surgery Trials (SST) includes 3 randomized clinical trialsdesigned to evaluate whether surgical removal of choroidal neovascularizationand associated blood increases the chance of achieving stable or improvedvision compared with no surgery in selected patients with subfoveal choroidalneovascularization due to age-related macular degeneration, ocular histoplasmosissyndrome, or idiopathic causes.⁹ These trialsare sponsored by the National Eye Institute of the National Institutes ofHealth, US Department of Health and Human Services, Bethesda, Md. The SSTdesign and methods and the activities of the SST resource centers were approvedby an institutional review board of The Johns Hopkins University School ofMedicine, Baltimore, Md. The SST protocol, detailed in the SST Manual of Procedures,¹⁰ was approvedby the SST Executive Committee (responsible for the scientific direction andleadership of the SST); the Data and Safety Monitoring Committee (an independentcommittee appointed by the director of the National Eye Institute); and theinstitutional review board of each participating clinical center before enrollmentof patients began at that center.

After the proposing principal investigators of 3 SST resource centers(the Chairman's Office, Coordinating Center, and Photograph Reading Center)were notified that funding had been awarded to conduct the first trial ofthe SST, invitations to participate in the SST were sent first to ophthalmologistsat 12 clinical centers that had performed well with respect to enrollment,follow-up, and protocol adherence among 18 centers that had participated inan earlier pilot study.¹¹ Four additional centerswere invited to participate because they had an ophthalmologist qualifiedto be a principal investigator who had expressed interest in participatingand had documented the ability to accrue eligible patients. These 16 centers(11 community based and 5 university based) were chosen without regard towhether the center was community based and without completion of a formalapplication. When funding was awarded to conduct 2 additional trials, it wasrecognized that additional clinical centers would be required to meet accrualgoals. A letter was sent by the SST leadership to approximately 1200 ophthalmologistsin the United States identified by the American Academy of Ophthalmology asspecializing in retinal diseases and to US members of 3 retina subspecialtysocieties (the Macula Society, the Retina Society, and the Vitreous Society)requesting an application package by a specified date to indicate an interestin organizing a participating clinical center in the SST.

Applications received by the specified deadline were reviewed by theSST Executive Committee. Items considered in the review included documentationof the proposing investigator's surgical experience, evidence of successfulparticipation in other clinical trials of similar conditions, availabilityof key personnel (eg, clinical center coordinators and retinal photographers)with experience following clinical trial protocols, and documentation of anadequate number of patients diagnosed each year as having the target eye conditionsand of the number who would have met the eligibility criteria for the trials.Based on this information, 11 centers were selected to participate in theSST. No consideration was given to whether the proposing center was communitybased or university based.

The first patient was enrolled in the first trial initiated in April1997; accrual ended in all 3 trials in September 2001. All patients were examinedat baseline; 3, 6, and 12 months after enrollment; and at annual intervalsthereafter for up to 4 years. Additional data were collected 1 and 9 monthsafter enrollment and at the midpoint between annual examinations by telephonecontact or during an in-person examination at the SST clinical center or byanother eye care provider. Scheduled protocol examinations typically includedexamination by an SST-certified ophthalmologist, vision testing, retinal photography,and a centrally administered telephone interview concerning health- and vision-relatedquality of life.^12-15 Thedetails are provided in the SST Manual of Procedures.¹⁰ All patients were followed through the 4-year examination,or through the 2-, 3-, or 4-year annual examination scheduled between October2002 and September 2003, or, in a few cases, until death, whichever came first.

Data from examinations were recorded on paper forms that were faxedto the Coordinating Center. Clinical center personnel were instructed to submiteach form as soon as possible after data were recorded, ideally on the sameday. Photographs were expected to arrive at the Photograph Reading Centerwithin 28 days of photography to allow time for processing before submission.

Personnel at all clinical centers completed SST training and certificationto perform their study roles before initiating accrual of patients to participatein the SST. The SST Quality Assurance and Monitoring Subcommittee was appointedby the Executive Committee in 1997 to monitor clinical center and resourcecenter performance and the performance of individual study personnel withrespect to adherence to the study protocol and to goals set by the ExecutiveCommittee. Selected performance data were discussed in detail as part of eachannual meeting of the SST Research Group. An initial site visit was made toeach clinical center to review operations and, in the case of centers thatalready had initiated patient enrollment and surgery, to compare selecteddata in each patient's clinical chart with the information reported to theSST Coordinating Center. A follow-up site visit for quality-monitoring purposeswas scheduled near the end of the patient follow-up examinations and datacollection at each site. Priorities for site visits were established by theExecutive Committee on the basis of the overall contribution of the centerto the study database, perceptions of problems that prompted an early sitevisit, changes in key personnel, and resources available for site visits.

At the November 17, 2000, meeting, the Executive Committee recommendedthat each principal investigator be sent a report for his or her center thatsummarized performance as reported during a Quality Assurance and MonitoringSubcommittee meeting the previous day. The specific measures of performanceto be included in the summary report were identified. Subsequently, the resourcecenter principal investigators sent individual clinical center summary reportswith a letter to each principal investigator and clinic coordinator. The summaryshowed for each measure of performance the statistic for all centers combined,the range of values across all centers, the statistic for the center, andthe rank of the individual center on that measure. In addition, an overallrank among SST centers was determined for each center, combining all of theperformance measures reported. A follow-up teleconference was conducted witheach principal investigator and clinic coordinator, typically by 2 membersof the Operations Committee (including the principal investigator of the CoordinatingCenter) or 1 member of the Operations Committee and a coinvestigator of theCoordinating Center. The aim of the teleconference would be to review thesummary report and to discuss possible methods of improving performance. Thisprocess was repeated after the Quality Assurance and Monitoring Subcommitteeand Executive Committee meetings in October 2001 and October 2002.

The performance measures included in the individual summary reportsvaried depending on the issues of particular concern each year. However, certainperformance issues were addressed in each report:

Completion of scheduled examinations, expressed as the percentageof those expected that had been completed overall.

Completionm of masked vision examinations 2 years after enrollment(the examination designated for assessing the primary outcome in each trial).

Completion of health- and vision-related quality-of-life interviews.

Timeliness of submission of the visual acuity data to the CoordinatingCenter after completion of the examination, expressed as a percentage of alloutcome examinations completed.

Timeliness of submission of retinal photographs to the PhotographReading Center.

The first summary report considered cumulative performance to that date;subsequent reports considered performance during the year just completed.For comparison of community- and university-based centers in this analysis,a special cumulative analysis of performance measures through June 30, 2002,the cutoff date for the most recent report, was considered.

Each clinical center was classified as community based or universitybased depending on the organization with which funding for that center wascontracted. A university-based center was defined as a site where the contractto perform as an SST clinical center was signed by a university official.A community-based clinical center was defined as one not university based.Classifications were reviewed and approved by the Executive Committee.

Because of the small number of centers in each category (community basedand university based), only descriptive statistics are reported. No formalstatistical tests were used to compare the 2 groups of centers. Individualcenter data are displayed graphically using a method proposed by Canner andcolleagues.¹⁶

Based on a review of all applications submitted by the deadline, 27centers were selected (17 community-based centers and 10 university-basedcenters). The total number of patients enrolled at each center is shown in Figure 1. By 1 year after initiating enrollment,6 centers (4 community based and 2 university based) had failed to accruestudy participants at a rate judged sufficient to meet accrual goals, resultingin a recommendation to halt further accrual of patients at these centers butto continue scheduled follow-up examinations of patients already enrolled.Performance data for these 6 centers are not included in the remaining datadisplays.

Distributions of the percentage of scheduled examinations completed,the percentage of 2-year masked examinations completed, and the percentageof quality-of-life interviews completed (Figure 2A-C) show that most community- and university-based centersperformed at a high level. However, all the centers in the lower portion ofthese distributions were community-based centers. Nevertheless, all but 2centers had values greater than 70%, and most had values greater than 80%,for all 3 measures of performance. When the percentage of scheduled 2-yearexaminations completed was evaluated, distributions were similar to the percentageof all scheduled examinations completed. With respect to timeliness of submissionof materials, more variability was observed among centers. For the percentageof vision examination data received within 3 days of vision measurements,1 outlier clinic achieved this goal for only 27% of vision examinations; otherwise,the distribution for community-based centers was similar to that of university-basedcenters (Figure 2D). With respectto receipt of retinal photographs within 28 days of photography, 2 outliercenters—1 community based and 1 university based—were apparent,with only 27% and 16% of photographs received at the Photograph Reading Centerby 4 weeks after they were taken, respectively (Figure 2E). However, the distributions otherwise were similar forthe 2 groups of clinics. Medians for these performance measures for 21 clinicalcenters by type of center are given in Table 1 and are similar for most measures when comparing community-vs university-based centers.

Overall, community- and university-based centers participating in theSST performed at a high (good) level, although there was a trend for somecommunity-based centers to perform at a lower level than university-basedcenters. In addition, 6 centers (2 university based and 4 community based)chosen to participate did not meet accrual expectations early in the trials,prompting cessation of accrual at these centers. The overall high qualityof performance may have resulted from judicious selection of centers, centraltraining of study personnel at all centers initially, or ongoing monitoringof performance. However, we observed study-wide improvement over time in mostof the areas of performance measured, suggesting that monitoring and feedbackregarding performance at annual meetings and through individual "report cards"contributed to good performance at both community- and university-based centers.

Although there was a trend for some community-based centers not to performas well in some areas compared with university-based centers, most community-basedcenters performed as well as university-based centers on most measures. Conclusionsare limited by the number of centers and by the small number of performancemeasures evaluated. Nevertheless, these results suggest that organizers ofmulticenter clinical trials in ophthalmology should not assume that community-basedcenters will perform either better or worse than university-based centers.

Multicenter clinical trials typically include 1 or more resource centersin the scientific and administrative organization, each with a different role.Performance monitoring and comparisons of resource centers located in differentsettings are outside the scope of this analysis. Also, the performance measureschosen for this analysis were judged to be the most important objective measuresevaluated by the SST Quality Assurance and Monitoring Subcommittee with respectto the goals of these trials. Other objective measures, such as number ofquery rates and missing value rates, were not judged to be as important asthe metrics displayed in Figure 1 and Figure 2. Subjective performance measures,such as the quality of photographs as judged by Photograph Reading Centerpersonnel, although important to study goals, were not included in this analysis.Such information might have modified the conclusions.

The ability to generalize these findings is unknown; they may applyonly to ophthalmic trials or only to trials in which surgery is evaluated.Evaluation of performance in "large, simple" randomized clinical trials, suchas the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart AttackTrial (ALLHAT),¹⁷ showed no difference in recruitmentperformance among the 623 centers used to enroll at least 40 000 studyparticipants when comparing sites with limited or no previous research experiencewith those with more experienced sites. The ALLHAT¹⁷ includeduniversity-affiliated centers (11.4% of sites), "private solo or group practices"(54.7% of sites), "community health centers" (8.0% of sites), health maintenanceorganizations (2.9% of sites), and others. However, these evaluations didnot compare performance in community- vs university-based centers. Other evaluationsof clinical performance by the AIDS Clinical Trials Group¹⁸ orvisual field testing in the Optic Neuritis Treatment Trial¹⁹ alsodid not compare performance in community-based centers with that in university-basedcenters.

Unlike previously published studies in other multicenter clinical trialsevaluating performance, surgical trials have unique challenges that couldaffect the performance measures evaluated. These challenges include financialincentives not to enroll patients to avoid losing surgical fees for patientsassigned to observation or some nonsurgical control arm; patient care costsextending beyond 1 provider (possibly including surgical fees, anesthesiafees, and hospital charges); and logistical issues, such as scheduling operatingroom time that would be needed promptly for study participants assigned tosurgery but cancelled when participants were assigned to observation or someother nonsurgical intervention.

In an attempt to minimize the impact of such issues on performance,open discussions with the SST Research Group (investigators, clinic coordinators,and central resource personnel) were undertaken before and during accrual.Research Group members agreed that financial incentives should not be allowedto affect decisions regarding patient care or participation in these clinicaltrials. In addition, members agreed that if surgery should prove beneficialover observation, evidence from randomized clinical trials likely would providethird-party payers with justification to cover surgical costs in the futurethat otherwise might not be covered as budgetary constraints limit futurereimbursement. The SST Research Group worked closely with surgical schedulingcoordinators at each clinical center so that these employees, who usuallywere not part of the research team, understood the rationale and logisticsof scheduling potential SST study participants before randomization so thatif patients were assigned to surgery, operations could be undertaken soonafter randomization. Close communication with surgical scheduling coordinatorsalso helped them understand why surgical slots on the operating room schedulemight be cancelled suddenly when patients were assigned to observation.

Other challenges that could have affected performance included the needto identify an appropriate institutional review board for some community-basedcenters. Also, 2 community-based centers and 2 university-based centers hadprincipal investigators leave their respective clinical centers to work inanother practice either in the same city or elsewhere. Although turnover ofpersonnel in community- and university-based centers cannot be prevented,loss of a principal investigator in a small practice, whether community basedor university based, can have a negative impact on continuity of patient careand follow-up. Investigators were encouraged to communicate anticipated movesand other personnel changes promptly to provide adequate time to train replacementpersonnel. With commitment to the success of the SST by all investigators(principal investigators and coinvestigators) at the onset of the trials andongoing communication with investigators to manage such scenarios, these potentialproblems were minimized. Success is reflected in the excellent performanceregarding completion of follow-up examinations that otherwise might be difficultfor the age groups (averaging in the mid-70s to early 80s) participating in2 of these trials.

Experiences in the SST parallel the oncology experience^6,7;both community- and university-based centers performed well. As competitionincreases to identify patients with targeted ophthalmic conditions, such asmacular edema from diabetes mellitus or choroidal neovascularization fromage-related macular degeneration, to participate in clinical trials, it isimportant to recognize that community- and university-based centers can achievegood to excellent performance in multicenter clinical trials.

Corresponding author: Neil M. Bressler, MD, Wilmer Eye Institute,Johns Hopkins University School of Medicine, 550 N Broadway, Suite 115, Baltimore,MD 21205-2005 (e-mail: nmboffice@jhmi.edu).

Reprints:Submacular Surgery Trials Coordinating Center, 550 N Broadway, Ninth Floor,Baltimore, MD 21205-2010.

Submitted for publication May 28, 2003; final revision received September25, 2003; accepted October 29, 2003.

Article

Clinical Centers and Personnel Who Contributed Data

Centers are listed in alphabetical order by city. Asterisk indicatescommunity-based center. The number of patients enrolled is given in parenthesesafter the center location. Personnel listed are principal investigators andother personnel who had performed 5 or more examinations or procedures thathad been reported by December 31, 2002.

Emory University Eye Center, Atlanta, Ga: (n= 62) Principal Investigators: G. Baker Hubbard III,MD; Paul Sternberg, Jr, MD (1999-2002); Antonio Capone, Jr, MD (1998-1999). Ophthalmologist: Thomas M. Aaberg, Jr, MD. SST Coordinator: Jayne M. Brown. Vision Examiners: Lindy G. Dubois, COMT; Judy Johnson, COMT; Natalie I. Schmitz. Photographers: James Gilman, CRA; Robert A. Myles, CRA;Ray Swords, CRA.

The Wilmer Ophthalmological Institute, Baltimore,Md: (n = 90) Principal Investigator: JuliaA. Haller, MD. Ophthalmologists: Peter A. Campochiaro,MD; Mark Humayun, MD; Eugene de Juan, Jr, MD; Dante J. Pieramici, MD; IngridZimmer-Galler, MD. SST Coordinators and Vision Examiners: Michaele Hartnett, COT; Patricia L. Hawse, COMT; Tracey L. Porter,COT; Ann Eager Youngblood. Photographers: JudithE. Belt; Dennis Cain, CRA; David Emmert; Rachel E. Falk; Terry George; MarkHerring; Jacquelyn McDonald.

Massachusetts Eye and Ear Infirmary, Boston, Mass: (n = 2) Principal Investigator: Jorge Arroyo,MD.

Northwestern University Medical School, Chicago, Ill: (n = 6) Principal Investigator: David V.Weinberg, MD. Ophthalmologist: Robert Schroeder,MD. SST Coordinator: Jill Koecher. Vision Examiner: Zuzanna Strugala, OMA. Photographers: Marsha Apushkin; Alexander Habib; Jim Yuhr, CRA.

Cole Eye Institute, Cleveland, Ohio*: (n =45) Principal Investigator: Hilel Lewis, MD. Ophthalmologist: Peter K. Kaiser, MD. SST Coordinators: Laura Holody, COA; Larissa S. Schaaf, RN. Vision Examiners: Ginny Ambrose; Joyce Conway; Anthony Fattori; HeleneSiegel. Photographers: Gloria M. Bartram; StephanieL. Burke; Nicole Drozda; Tami Fecko; Deborah J. Ross, CRA.

Retina Associates of Cleveland*: (n = 42) Principal Investigator: Lawrence J. Singerman, MD. Ophthalmologists: Michael A. Novak, MD; Scott Pendergast,MD. SST Coordinators and Vision Examiners: Lori M.Campana; Kim Tilocco DuBois, COA; Susan C. Rath, PA-C; Vivien Tanner, COT. Photographers: John DuBois, CRA; Greg Greanoff; David Lehnhardt,COA; Sheila Smith-Brewer, COT; Kimberley Spagnoletta.

Ohio State University, Columbus: (n = 26) Principal Investigator: Frederick H. Davidorf, MD. Ophthalmologist: Robert Chambers, DO. SST Coordinator: Cynthia Taylor. Vision Examiners: Jill Milliron, COA; Jerilyn Perry, COT. Photographer: Scott Savage, EMT-A.

Texas Retina Associates, Dallas*: (n = 21) Principal Investigator: David G. Callanan, MD. Ophthalmologist: Gary Edd Fish, MD. SST Coordinators: Jodi R. Creighton, COA; Jeff L. Harris, COA; Nancy Resmini; RubyeRollins. Vision Examiner: Marilyn Andrews. Photographers: Hank Aguado, CRA; Bob Boleman; Penny Ellenich.

Duke University Eye Center, Durham, NC: (n= 42) Principal Investigator: Cynthia Toth, MD. Ophthalmologists: Glenn Jaffe, MD; Brooks McCuen, MD. SST Coordinators and Vision Examiners: Malcolm W. Anderson,PA-C, COT; Jennifer V. Caldwell; Photographers: TeresaJackson Hawks; Gregory Hoffmeyer; Jeff Napoli.

Illinois Retina Associates, Harvey and Chicago*: (n= 33) Principal Investigator: Mathew W. MacCumber,MD, PhD. Ophthalmologists: Joseph M. Civantos, MD;Kirk H. Packo, MD. SST Coordinators: Marguerita DeAlba,ST; Bruce L. Gaynes, OD; Laurie Rago, COA; Carrie Violetto. Vision Examiners: Michelle M. Franzyck, COT; Chris Morrison. Photographers: Douglas A. Bryant, CRA; Donald S. Doherty;Frank Morini.

Retina Associates of Hawaii, Honolulu*: (n= 9) Principal Investigator: Neal H. Atebara, MD. SST Coordinator: Susan Pelke. VisionExaminer and Photographer: Deborah J. Nobler.

Midwest Eye Institute, Indianapolis, Ind*: (n= 3) Principal Investigator: John T. Minturn, MD. SST Coordinator: Donna Agugliaro, RN. Vision Examiner: Shelly Cohen. Photographer: CarolynLamb.

University of Iowa, Iowa City: (n = 9) Principal Investigator: James C. Folk, MD. SST Coordinators and Vision Examiners: Betty Folmer; Connie Fountain,COT; Steven A. Wallace. Photographers: Ed Hefron;Carolyn Vogel.

Mid-America Retina Consultants, Kansas City, Mo*: (n = 15) Principal Investigator: WilliamN. Rosenthal, MD. Ophthalmologist: David S. Dyer,MD. SST Coordinators and Vision Examiners: DeniseMoore, RN; Barbara Petro, COT; Dalton J. Thibodeaux. Photographer: R. Scott Varner.

Southeastern Retina Associates, Knoxville, Tenn*: (n = 68) Principal Investigator: John C.Hoskins, MD. Ophthalmologist: Joseph M. Googe, MD. SST Coordinators: Katie E. Carter, COA; Stephanie M. Evans;Tina Thibodeaux Higdon; Jennifer L. Holton. Vision Examiner: Bruce D. Gilliland, OD. Photographers: PaulAndrew Blais; Philip Michael Jacobus.

Retina and Vitreous Associates of Kentucky, Lexington*: (n = 53) Principal Investigator: WilliamJ. Wood, MD. Ophthalmologist: Rick Isernhagen, MD. SST Coordinators: Michelle L. Buck, COA; J. Lynn Cruz,COT; Joni D. James, RN; Tammy L. Jordan, PA-C; Jenny L. Wolfe, RN. Vision Examiners: Christine Brown, COT; Wanda Heath, COT; CatherineMillett, COA. Photographers: Marty Reid, COA; EdwardSlade, CRA, COA.

Jules Stein Eye Institute, Los Angeles, Calif: (n= 61) Principal Investigator: Steven D. Schwartz,MD. Ophthalmologists: Robert Engstrom, MD; Kent Small,MD. SST Coordinators: Jo Eure; Jessica Hsu; RosaleenOstrick, MPH, MA; Dai Tran; Tina Wong. Vision Examiners: Lisa Barnhart; Janine Chen; Melissa Chun, OD; Larissa Johnson; JennieY. Kageyama, OD. Photographers: Mirella Tetreault;Dennis Thayer; Bret Trump.

California Vitreoretinal Associates, Menlo Park*: (n = 1) Principal Investigator: Mark S. Blumenkranz,MD. SST Coordinator: Patricia Mattio.

Vitreoretinal Surgery PA, Minneapolis, Minn*: (n= 35) Principal Investigator: David F. Williams,MD. Ophthalmologists: Sundeep Dev, MD; Robert A.Mittra, MD. SST Coordinators and Vision Examiners: JulianneEnloe; Scott D. Marella; Neal Oestrich. Photographer: HollyN. Cheshier.

McGee Eye Institute, Oklahoma City, Okla: (n= 32) Principal Investigators: Reagan H. Bradford,MD; Sumit K. Nanda, MD (1998-2002). SST Coordinators andVision Examiners: Angela Monlux; Lisa M. Ogilbee; Photographer: Russ Burris, COT, CRA.

Retinal Consultants of Arizona, Phoenix*: (n= 68) Principal Investigator: Jack O. Sipperley,MD. Ophthalmologist: Scott R. Sneed, MD. SST Coordinators: Jaclin J. Jacobsen, CRA, COA; Eleonora Tysiac. Vision Examiners: Denise Freistroffer; Nickie Perez; PearlRosas; Debra Tomaszewski. Photographers: John J.Bucci; Sharon H. Kosecki; John V. Martin.

Retina Vitreous Consultants, Pittsburgh, Pa*: (n= 48) Principal Investigator: Robert L. Bergren,MD. Ophthalmologist: Bernard Doft, MD. SST Coordinators: Donna J. Metz, RN; Kathryn Sedory, RN; ChristinaTrombetta, CST. Vision Examiners: Grace Rigoni; LynnWellman; Linda Wilcox, COA. Photographers: Alan Campbell,CRA; David Steinberg, CRA; Gary Vagstad, CRA.

Oregon Health Sciences University, Portland: (n= 51) Principal Investigator: David J. Wilson, MD. SST Coordinator and Vision Examiner: Susan Pope. Photographers: Ellen Redenbo; Peter Steinkamp; PatrickWallace.

Associated Retinal Consultants, Royal Oak, Mich*: (n = 41) Principal Investigator: George A.Williams, MD. Ophthalmologists: Antonio Capone, MD;Bruce R. Garretson, MD; Alan Ruby, MD. SST Coordinatorsand Vision Examiners: Kristi L. Cumming, RN, MSN; Bobbie Lewis, RN;Patricia Manatrey; Mary Zajechewski. Photographers: CraigBridges; Patricia Steasick; Lynette Szydlowski.

Barnes Retina Institute, St Louis, Mo*: (n= 71) Principal Investigator: Nancy Melberg Holekamp,MD. Ophthalmologists: Daniel P. Joseph, MD; MatthewA. Thomas, MD. SST Coordinators and Vision Examiners: JulieBinning, COT; Lynda Boyd, COT; Janel Gualdoni, COT; Virginia Nobel, COT. Photographers: Rhonda Allen; Bryan Barts; Pamela K. Bauer;Jon Dahl; Timothy S. Holle; Deborah Kaiser, RN, COA; Ella Ort; Matt Raeber;John Mark Rogers.

West Coast Retina Medical Group Inc, San Francisco,Calif*: (n = 33) Principal Investigator: H.Richard McDonald, MD. Ophthalmologist: Robert N.Johnson, MD. SST Coordinators: Margaret Stolarczuk,OD; Pat Wood, LVN. Vision Examiner: Kevan E. Curren. Photographers: Kelly Ann DeBoer; Sarah M. Huggans; JeremyR. Miller; John Uy.

St Vincent Mercy Medical Center, Retina Vitreous Associates,Toledo, Ohio*: (n = 48) Principal Investigator: SamuelR. Pesin, MD. Ophthalmologists: Charles K. Dabbs,MD; Nicholas J. Leonardy, MD. SST Coordinator and VisionExaminer: James M. Haener, COT. Photographers: LaurenM. Cedoz, CRA; Dawn DeFalco; Richard D. Hill.

Resource Centers: The Wilmer Ophthalmological Institute,Baltimore

Chairman's Office, Retinal Vascular Center:Principal Investigator and SST Chairperson: Neil M. Bressler,MD. Traveling Vision Examiners: Kristi L. Cumming,RN, MSN; James M. Haener, COT; Michael Hartnett, COT; Patricia L. Hawse, COMT;Peggy R. Orr, MPH, COMT. Vision Testing Coordinator; EconomicAnalyst: Eric B. Bass, MD, MPH. Other Personnel: Dawn A. Childs; Connie Lawson; Irene L. Felicetti (1997-2002); PatriciaStaflin (1997-2001).

Coordinating Center, Wilmer Clinical Trials and Biometry:Principal Investigator: Barbara S. Hawkins,PhD. Biostatisticians: Ashley L. Childs, MS; Li MingDong, PhD; Marta J. Marsh, MS. Epidemiologist: PäiviH. Miskala, PhD. Quality of Life Advisor: Carol M.Mangione, MD, MSPH (participation supported by a contract between the DavidGeffen School of Medicine, University of California, Los Angeles, and TheJohns Hopkins University). Data Coordination and TelephoneInterviews: Rob G. Casper, MS; Alice D. Keith; Lee D. McCaffrey, MA;Dawn K. Smith. Systems Management and Programming: KurtDreger; Harris A. Jaffee, PhD; M. Marvin Newhouse; Stephen C. Grubb, MS (1997-1999). Other Personnel: Patricia A. James; Lisa Lassiter; ChristineB. Alden (2000-2002); Takisha R. Kiah (1998-2002); Nancy A. Prusakowski, MS(1998-2000).

Photograph Reading Center, Wilmer Photograph ReadingCenter:Principal Investigator: Susan B. Bressler,MD. Ophthalmologists: Dante J. Pieramici, MD (1998-2000);Srinivas R. Sadda, MD (2000-2001); Oliver D. Schein, MD. Consultant: Sharon D. Solomon, MD. AdministrativeDirectors: Judith Alexander (1997-1998); Kelly S. Manos, MAS (1998-2002). SST Coordinators: LaKaye Mbah; Reva W. Strozykowski; IsabelMills (1999-2002). Photograph Graders: Kelly AnnDavies; Rita L. Denbow, MLA; Michael P. Minotti; Deborah A. Phillips; YanTian.

Pathology Center, Emory University Eye Center, Atlanta:Principal Investigator: Hans E. Grossniklaus,MD. SST Coordinator: Pingbo Liu. Consultant Pathologist: W. Richard Green, MD.

Sponsor: The National Eye Institute, National Institutesof Health:Directors: Paul A. Sieving, MD,PhD; Carl Kupfer, MD (1998-2000). Deputy Director: JackA. McLaughlin, PhD. Program Directors: Maryann Redford,DDS, MPH; Mary Frances Cotch, PhD (1997-2001).

Committees and Members

Executive Committee: (reviewed and approvedthis manuscript) Ex Officio Members: Neil M. Bressler,MD (chairperson); Eric B.Bass, MD, MPH; Susan B. Bressler, MD; Hans E. Grossniklaus, MD; Julia A. Haller,MD; Barbara S. Hawkins, PhD; Carol M. Mangione, MD, MSPH; Peggy R. Orr, MPH,COMT; Maryann Redford, DDS, MPH; Paul Sternberg, Jr, MD; Matthew A. Thomas,MD. Rotating Members: Jayne Brown; Nancy M. Holekamp,MD; Samuel R. Pesin, MD; David J. Wilson, MD.

Quality Assurance and Monitoring Subcommittee: BarbaraS. Hawkins, PhD (chairperson); Susan B. Bressler, MD (vice chairperson); Judith E. Belt; Li Ming Dong, PhD; Julia A. Haller, MD;Mike Hartnett, COT; Harris A. Jaffee, PhD; Carol M. Mangione, MD, MSPH; MartaJ. Marsh, MS; Lee D. McCaffrey, MA; Päivi H. Miskala, PhD; Peggy R. Orr,MPH, COMT; Kelly S. Manos, MAS (1998-2002).

Vision Testing Subcommittee: Peggy R. Orr,MPH, COMT (chairperson); MikeHartnett, COT; Patricia L. Hawse, COMT; Marta J. Marsh, MS; Lee D. McCaffrey,MA.

Surgery Subcommittee: Matthew A. Thomas, MD(chairperson); Julia A.Haller, MD (vice chairperson); Eugene de Juan, Jr,MD; Paul Sternberg, Jr, MD.

Patient-Centered Outcomes Subcommittee: CarolM. Mangione, MD, MSPH (chairperson); Eric B. Bass, MD, MPH (vice chairperson); Neil M. Bressler, MD; Ashley L. Childs, MS; Li Ming Dong,PhD; Barbara S. Hawkins, PhD; Harris A. Jaffee, PhD; Marta J. Marsh, MS; LeeD. McCaffrey, MA; Päivi H. Miskala, PhD.

Operations Committee: Neil M. Bressler, MD(SST chairperson); PaulSternberg, Jr, MD, and Matthew A. Thomas, MD (SST vice chairpersons); Susan B. Bressler, MD; Barbara S. Hawkins, PhD; Maryann Redford,DDS, MPH.

Data and Safety Monitoring Committee:Voting Members (Appointed): Argye I. Hillis, PhD (chairperson); Gary W. Abrams,MD; John E. Connett, PhD; Christine Grady, RN, PhD; Earl G. Harrison, LLD;Lee M. Jampol, MD. Nonvoting Members (Ex Officio): NeilM. Bressler, MD; Li Ming Dong, PhD; Barbara S. Hawkins, PhD; Marta J. Marsh,MS; Maryann Redford, DDS, MPH; Mary Frances Cotch, PhD (1997-2000).

Adverse Event Review Committee:Voting Members: Julia A. Haller, MD, (chairperson); Gary W. Abrams, MD; Lee M. Jampol, MD. Ex Officio Member: Barbara S. Hawkins, PhD.

Writing Committee for Submacular Surgery Trials ReportNo. 2: Neil M. Bressler, MD (chairperson);Barbara S. Hawkins, PhD; Susan B. Bressler, MD; Päivi H. Miskala, PhD;Marta J. Marsh, MS. The Submacular Surgery Trials Report No. 2 Writing Committeemembers assume authorship responsibility and had complete access to the rawdata necessary for this study. Each SST clinical center and resource centerprincipal investigator approved this study for publication.