A Two-Stage Sampling Method for Clinical Surveillance of Individuals in Care for HIV Infection in the United States

Transcription

1 Reserch Articles A Two-Stge Smpling Method for Clinicl Surveillnce of Individuls in Cre for HIV Infection in the United Sttes Ptrick S. Sullivn, DVM, PhD John M. Kron, PhD Fye E. Mlitz, MPH b Stephnie Broyles, MPH c Eve D. Mokotoff, MPH d Susn E. Buskin, PhD e Ptrici L. Fleming, PhD SYNOPSIS Objectives. The gols of this study were two-fold: (1) to describe methods for drwing popultion-bsed smple of individuls in cre for HIV infection nd (2) to compre dt from the smple with dt from existing surveillnce systems tht describe cre for HIV. Methods. The uthors implemented two-stge smpling method, using locl HIV/AIDS surveillnce dt s smpling frme of HIV cre providers in three sttes. At selected providers, medicl records of rndom smple of ptients were bstrcted. Results. The medicl records of number of ptients, rnging from 253 to 374 individuls per stte, were bstrcted. The demogrphics of smpled individuls nd of individuls reported to the locl HIV/AIDS surveillnce progrm were similr; however, differences existed in the proportion of individuls receiving HIV cre consistent with tretment guidelines between the smple nd contemporry fcility-bsed supplementl surveillnce project. The medin design effect for outcomes collected in the smple ws 1.8 (rnge ). Conclusions. This survey method is fesible for collecting popultion-bsed dt on ptients in cre for HIV. Smple size nd some design elements should be chnged in future studies to increse precision of estimtes nd usefulness of dt for locl plnning nd evlution. Division of HIV/AIDS Prevention Surveillnce nd Epidemiology, Ntionl Center for HIV, STD, nd TB Prevention, Centers for Disese Control nd Prevention, Atlnt, GA b Office of Science nd Epidemiology, HIV/AIDS Bureu, Helth Resources nd Services Administrtion, Rockville, MD c HIV/AIDS Surveillnce Progrm, Louisin Office of Public Helth, New Orlens, LA d HIV/AIDS Surveillnce, Michign Deprtment of Community Helth, Detroit nd Lnsing, MI e Public Helth Settle & King County; Deprtment of Epidemiology, University of Wshington, Settle, WA Address correspondence to: Ptrick S. Sullivn, DVM, PhD, Centers for Disese Control nd Prevention, 1600 Clifton Rd. NE, MS E46, Atlnt, GA 30333; tel ; fx ; e-mil <pss0@cdc.gov>. 230

2 Two-Stge Smpling Method for Clinicl Surveillnce of HIV-Infected Ptients 231 HIV infection is mjor public helth problem in the United Sttes, nd billions of dollrs of public funds re spent nnully on the cre nd tretment of people infected with HIV. Monitoring the morbidity of individuls living with HIV infection is importnt to (1) understnd the popultion impct of dvnces in the medicl mngement of HIV infection; (2) document needs for nd utiliztion of cre services; (3) inform guidelines for monitoring clinicl sttus, cre, nd tretment; nd (4) document the impct of public funds spent on cre for people living with HIV infection. 1 3 Helth deprtments re primrily responsible for dministering nd evluting federl, stte, nd locl funds for cre. Although AIDS surveillnce dt hve represented nerly complete census of ll individuls with AIDS nd re vilble in ll helth deprtments, these dt re indequte to meet the sttes informtion needs for plnning HIV-relted services. Surveillnce cse reports contin only limited demogrphic, behviorl risk, nd clinicl dt; supplementl studies re required to obtin dt on ccess to, use of, qulity of, nd impct of tretment. Idelly, dt on clinicl outcomes of HIV cre should be representtive nd useful t both the ntionl nd locl levels. In the pst, different methods of dt collection hve hd different strengths nd weknesses. During the mid- 1990s, the HIV Cost nd Services Utiliztion Study (HCSUS) estimted HIV helth cre costs nd utiliztion in ntionlly representtive smple of HIV fcilities nd ptients. 4,5 This wtershed survey produced useful ntionl-level estimtes of HIV cre utiliztion, but it did not llow for clcultion of stte level estimtes for locl plnning purposes. In the lte 1980s, the Centers for Disese Control nd Prevention (CDC) nd 10 stte nd locl helth deprtments developed the Adult nd Adolescent Spectrum of HIV-relted Disese Study (ASD), n ongoing longitudinl review of medicl records of HIV-infected individuls in more thn 100 hospitls nd clinics chosen by the prticipting helth deprtments. 6,7 ASD hs collected observtionl dt on morbidity, tretment, insurnce, nd helth services utiliztion. 8 However, the representtiveness of ASD is limited nd inference to the entire United Sttes is not possible. In n ttempt to develop surveillnce method for clinicl outcomes tht would both provide representtive dt nd be useful t the locl level, the CDC nd the Helth Resources nd Services Administrtion instituted pilot project in 1998: the Survey of HIV Disese nd Cre Project (SHDC). The primry gol of the pilot study ws to develop nd ssess the fesibility of two-stge smpling design to produce representtive smple of ptients in cre for HIV infection in the U.S., using HIV nd AIDS cse subject reporting dt s smpling frme of HIV cre providers. The gol of this report is to describe the method nd its fesibility nd to compre the dt from SHDC with other existing systems tht mesure chrcteristics of individuls in cre for HIV infection. We mke recommendtions for the design of future surveillnce ctivities t the stte nd locl levels tht will provide representtive dt for trgeting nd evluting progrms t modest incrementl cost. Finlly, we describe plns for n pproch with similr methodology tht cn generte ntionlly representtive dt to provide sound bsis for lloction of resources for HIV prevention, tretment, nd cre. METHODS Survey of HIV Disese nd Cre Project Prticipting res. The survey ws conducted in three project res during 1999, to collect informtion bout cre for HIV infection delivered during The project res were King County in Wshington Stte, which includes the Settle metropolitn re; the Louisin Stte Helth Regions 1, 2, 3, 4, nd 9, representing pproximtely the southern onethird of Louisin nd including New Orlens nd Bton Rouge; nd the entire stte of Michign. 9 During the study period, HIV infection without AIDS ws reportble to the helth deprtments in Michign nd Louisin, but not in King County. Ptients were chosen for the survey using two-stge smpling procedure. The first stge ws selection of smple of medicl cre providers; the second stge ws weighted, strtified systemtic smple of ptients within selected providers. Selection of the smple of providers. The smpling frme for the first stge ws bsed on dt from the HIV/AIDS Reporting System (HARS). A medicl provider ws recorded for ll individuls with HIV infection (with or without AIDS) who (1) were reported to the stte HIV/AIDS surveillnce system, (2) resided in the eligible geogrphic re t the time of dignosis, nd (3) were presumed to be live t some time during the study period, The provider ws either the most recent provider reporting the cse of HIV infection or AIDS, or, if vilble, the medicl cre provider who most recently hd ordered CD4 count or virl lod tests for the ptient (which we presumed to indicte provision of clinicl cre). The smpling frme of providers consisted of ll medicl cre providers who cred for or reported t lest one such cse subject (except in Michign, where only providers who cred for or reported t lest three cse subjects were included) to the stte or county helth deprtment HIV/ AIDS surveillnce system. The initil list of providers ws reviewed to remove providers who hd closed or merged, who were sources of HIV infection reports tht did not provide medicl cre (such s HIV testing sites tht did not provide primry HIV cre), nd who were outside the specified geogrphic re. Correctionl fcilities were excluded from the provider smpling frme in ll sites becuse of the difficulty in obtining ptient lists nd medicl records from these fcilities. For ech re, the smpling frme of providers ws strtified s smll, medium, or lrge, bsed on numbers of ptients ttributed to tht provider in the HIV/AIDS surveillnce system. The definitions of smll, medium, nd lrge providers were different in ll three res: King County strtified the smple s smll 30 ptients, medium ptients, nd lrge 100; Louisin strtified the smple s smll 20, medium , nd lrge 100; nd Michign strtified the smple s smll 10, medium 10 99, nd lrge 100. In ll sites, lrge providers were strtified on Ryn

3 232 Reserch Articles White Comprehensive AIDS Resources Emergency (CARE) Act funding to ensure tht dequte numbers of ptients in cre supported by Ryn White CARE Act (RWCA) funds were included. 10 In Michign, providers were further strtified by size of the metropolitn sttisticl re (MSA) in which the providers were locted, so tht we could compre cre by lrge providers with nd without RWCA funds. Within ech strtum, providers were smpled without replcement with probbility proportionl to the number of HIV/AIDS ptients ssigned to the provider. To select provider smple for our study, we generted list ordered by size within ech strtum using the S-Plus smple function, specifying the probbility of smpling s the proportion of ptients from the strtum t the provider. 11 We obtined the smple by choosing the desired number of providers, strting t the top of the list for ech strtum. Ech selected provider ws contcted to verify willingness nd bility to prticipte. Prticiption required tht (1) the provider could supply list of ll HIV-infected ptients in cre for the clendr yer 1998, including the rce nd sex of ech ptient, nd (2) the provider would llow informtion to be bstrcted from medicl records. If selected provider refused or ws unble to prticipte (e.g., becuse of inbility to supply list of individuls with HIV infection in cre during the yer), or if the provider ws found lter not to be eligible (e.g., becuse of providing no medicl cre in the reference yer), the next provider on the ordered smple list ws pproched s n lternte. Selection of the smple of ptients. Within ech geogrphic re, the helth deprtment decided how to strtify the ptient popultion on rce/ethnicity nd sex, bsed on the demogrphic chrcteristics of the HIV-infected popultion. For exmple, Louisin identified strt of blck men, other men, nd women. Within ech provider strtum, we ttempted to llocte the ptient smple eqully cross the rce/sex strt. We defined smpling frction for ech rce/sex strtum bsed on the totl number of ptients to be smpled for tht rce/sex strtum nd the totl number of ptients who hd t lest one visit to the providers in tht provider strtum. For ech rce/sex strtum, the sme smpling frction ws used t ll providers within provider strtum. Ech provider ws instructed to develop list of ptients ordered by dte of birth or medicl record number for ech rce/sex combintion or to provide list of ptients tht included the demogrphics, which would llow helth deprtment personnel to crete the ptient smpling frme. Ptients then were selected using systemtic smpling bsed on smpling intervl determined from the smpling frction nd rndom strt (provided by the CDC). The ptient list ws considered wrp-round, so tht if selected ptient s medicl records could not be found, the next ptient on the list t the smpling intervl ws chosen. Smple size. The totl smple size ws chosen for ech study site bsed on sttisticl considertions (precisions of estimtes of interest) nd vilble resources t the locl level. Ech study site trgeted totl smple size of pproximtely 300 ptients. This smple size would llow clcultion of n estimte of proportion with 95% confidence intervl (CI) 9.8%, ssuming design effect of 3.0. The smple of 300 ptients ws llocted mong the provider size strt, guided by the proportions of ll living ptients from providers of the vrious sizes obtined from surveillnce dt. Approximtely hlf the smple for the lrge providers ws llocted to providers receiving RWCA support nd hlf to providers not receiving RWCA support. Dt collection. For selected ptients, medicl records t the smpled fcilities were reviewed to determine if the ptient ws in cre during 1998, s well s to determine informtion bout prescribed medictions, dignosed illnesses, lbortory test results, nd service utiliztion (inptient, outptient, nd emergency room visits). If informtion ws vilble in the primry medicl record bout cre received t other providers (e.g., copies of records from hospitl dmission or consulttion report), those dt were collected nd treted s cre received during the period. If the sme individul ws selected t multiple providers, informtion bout cre ws bstrcted only from the medicl records of the provider t which the individul ws first selected. This study did not ttempt to collect informtion from ll fcilities t which the individul ccessed cre during 1998, due to the lrge numbers of providers potentilly involved nd resource constrints. Humn subjects. The study ws determined by the CDC to be non-reserch. Of the three prticipting stte nd locl helth deprtments, the protocol ws reviewed nd received Institutionl Review Bord (IRB) pprovl in two, nd in one, it ws determined to be exempt from IRB review. Anlysis Clcultion of smpling weights. The dt nlysis used methods tht ccounted for the strtified two-stge cluster design nd the vrition in the selection probbilities for ptients from different providers. Becuse selection of ptients within provider ws bsed on systemtic smple with rndom strt, ll ptients selected from the sme provider nd sme rce/sex strtum hd equl selection probbilities. To ccount for these selection probbilities, the weight for ech ptient ws the inverse of the probbility tht the individul ws smpled. This probbility ws computed s the probbility of smpling the provider t which the ptient received cre, multiplied by the probbility of smpling the ptient t the provider. Clcultion of weighted point estimtes, stndrd errors, nd confidence intervls. Using SAS PROC SURVEY MEANS, we clculted point estimtes (mens, proportions), their stndrd errors (SEs), nd 95% CIs. 12 For some mesures (such s number of outptient visits in the study intervl), medin vlues were estimted. Estimtes of medins nd their SEs, nd 95% CIs were clculted using PROC DESCRIPT in SUDAAN with DESIGN WR (with replcement). 13 As result of the cluster smple design, the vrince of n estimte ws usully lrger thn the vrince from simple rndom smple of the sme size. The mgnitude of the incresed vrince due to clustering ws mesured s the design effect, defined s the rtio of vrince incorporting the smpling design to the vrince from simple rndom smple of the sme size. 14 We clculted the design effect for severl helth cre outcome mesures of interest.

4 Two-Stge Smpling Method for Clinicl Surveillnce of HIV-Infected Ptients 233 Comprison of SHDC dt with dt from other surveillnce ctivities Adult nd Adolescent Spectrum of HIV Disese Project. The ASD is multicenter medicl record review of pproximtely 100 clinics in 10 U.S. cities; its methods hve been described. 6 A stndrdized instrument ws used to collect informtion from medicl records on the ptients clinicl conditions nd tretments t bseline nd every six months until the ptient s deth or until the lst contct with the ptient t one of the prticipting fcilities. In this nlysis, we included dt bstrcted in the Settle, Detroit, nd New Orlens sites for cre received during Certin clinicl nd demogrphic chrcteristics hve been shown previously to be ssocited with the extent to which ptients re treted ccording to tretment guidelines. 15,16 Since demogrphic chrcteristics of ptients could differ for ASD nd SHDC, estimtes for ASD helth cre mesures were stndrdized to the SHDC popultion of ptients receiving medicl cre in the Detroit, New Orlens, nd Settle metropolitn res. Estimtes were stndrdized ccording to the weighted proportion of ptients in SHDC by rce (blck, Hispnic, other ), HIV risk mode nd sex (men who hve sex with men [MSM], injecting drug user [IDU] mle, IDU femle, other risks mle, other risks femle), nd ge group ( 30 yers, 30 yers). HIV/AIDS Reporting System dt. In order to compre the demogrphic chrcteristics of individuls observed in the SHDC project to the chrcteristics of individuls dignosed with HIV infection (with or without AIDS) in the sme project res, we used locl HIV/AIDS surveillnce dt. HARS is implemented in ll U.S. sttes, with well-chrcterized completeness of reporting. 17 We used locl surveillnce dt reported through Jnury 2003 to clculte numbers of individuls with HIV dignoses known to be living with HIV t ny point in 1998 (dignosed before December 31, 1998, nd not known to be ded s of December 31, 1997). Definitions of stndrds of cre In order to describe the extent to which cre for HIV infection complied with stndrds of prctice, we used United Sttes Public Helth Service/Infectious Disese Society of Americ (USPHS/IDSA) tretment guidelines in effect during Bsed on these guidelines, specific definitions for stndrds of cre to be evluted in our study were estblished nd pper on this pge (see right). RESULTS Of 51 providers pproched to prticipte in the project, four (8%) declined prticiption. The sites were not consistent in their refusl rtes; King County hd 75% prticiption (12 of 16 providers prticipted), nd the other two sites hd 100% prticiption. Medicl records were reviewed for 915 HIV-infected ptients receiving medicl cre t prticipting fcilities in The number of records bstrcted per site rnged from 253 to 374 ptients per site. Demogrphic chrcteristics of the 915 ptients observed in SHDC nd of the 5,266 ptients followed during 1998 by the ASD Project in the sme sttes re shown in Tble 1; these dt should be interpreted with the understnding Definitions of stndrds of cre Bsed on the United Sttes Public Helth Service/Infectious Disese Society of Americ Guidelines for the Prevention of Opportunistic Infections in Individuls Infected with HIV, the following definitions were used during the Survey of HIV Disese nd Cre Project (SHDC) to evlute the extent to which cre complied with stndrds of prctice. Highly ctive ntiretrovirl therpy (HAART) Met stndrd: Prescription of AZT (ddi, ddc, or 3TC) (ny protese inhibitor or ny non-nucleoside reverse trnscriptse inhibitor), D4T (ddi or 3TC) (ny protese inhibitor or ny non-nucleoside reverse trnscriptse inhibitor), combivir (ny protese inhibitor or ny non-nucleoside reverse trnscriptse inhibitor), bcvir AZT ddc, bcvir ddi 3TC, or trizivir (ddc or ddi or ny protese inhibitor or ny nonnucleoside reverse trnscriptse inhibitor). Protese inhibitors included squinvir, ritonvir, indinvir, nelfinvir, mprenvir, tiprnvir, kletr. Non-nucleoside reverse trnscriptse inhibitors included delvirdine, nevirpine, efvirenz, emivirine, cprvirine. Eligibility: History of n AIDS-defining opportunistic illness dignosis, CD4 500, PCR 20000, or bdna 10,000 Pneumocystis crinii pneumoni (PCP) prophylxis Met stndrd: Prescription of dpsone, pentmidine, or trimethoprim-sulfmethoxzole Eligibility: History of PCP dignosis or CD4 200 Mycobcterium vium (MAC) prophylxis Met stndrd: Prescription of clrithromycin, zithromycin, or rifbutin. Eligibility: History of M. vium dignosis or CD4 50 cells/µl Tuberculosis skin test (TST) Met stndrd: Any tuberculin skin test during 1998 Eligibility: No tuberculosis dignosis or sputum culture positive to M. tuberculosis prior to 1998 Influenz vccine Met Stndrd: Received influenz vccintion during 1998 Eligibility: All individuls observed tht in Michign nd Louisin, the ASD projects re conducted in Detroit nd New Orlens, but the SHDC dt represent the entire stte of Michign nd the southern helth districts of Louisin. The modl ge group for subjects in both projects ws yers in ll res except the ASD project in Michign, where the modl ge group ws yers; most subjects in ll res were mle. The proportions of the SHDC smple who did not hve mjor HIV risk fctor documented in their medicl records rnged from 25% to 50%; the proportions of ptients observed in ASD who did not hve this informtion rnged from 9% to 20%. The distribution of demogrphic chrcteristics of individuls reported to HARS in the study res of King County, helth districts 1,2,3,4 nd 9 in Louisin, nd Michign re compred with the weighted SHDC smple in Tble 2. For ll project res, higher proportions of women were observed by SHDC (11% to 31%) thn by HARS (8% to 26%). In ll three project res, the most common ge group of

5 234 Reserch Articles Tble 1. Demogrphic chrcteristics of ptients observed in SHDC nd ptients enrolled in ASD b in southern Louisin, Michign stte, nd King County, Wshington, during 1998 King County Louisin Michign SHDC ASD SHDC ASD SHDC ASD (N 288) (N 1,211) (N 253) (N 2,702) (N 374) (N 1,412) Chrcteristic n (percent) n (percent) n (percent) n (percent) n (percent) n (percent) Sex Mle 178 (62) 991 (82) 158 (62) 1,926 (71) 258 (69) 903 (64) Femle 110 (38) 220 (18) 95 (38) 776 (29) 116 (31) 509 (36) Age (1) 9 (1) 16 (6) 39 (1) 9 (2) 14 (1) (18) 160 (13) 43 (17) 473 (18) 40 (11) 153 (11) (46) 590 (49) 111 (44) 1,194 (44) 151 (40) 486 (34) (26) 357 (29) 58 (23) 764 (28) 123 (33) 565 (40) (10) 95 (8) 25 (10) 232 (9) 51 (14) 194 (14) Rce White, non-hispnic 143 (50) 738 (61) 92 (36) 946 (35) 175 (47) 355 (25) Blck, non-hispnic 84 (29) 248 (20) 152 (60) 1,670 (62) 179 (48) 1,010 (72) Hispnic 30 (10) 144 (12) 7 (3) 78 (3) 9 (2) 37 (3) Asin/Pcific Islnder 17 (6) 31 (3) 1 (0) 8 (0) 0 (0) 5 (0) Americn Indin/Alsk Ntive 11 (4) 50 (4) 0 (0) 0 (0) 2 (1) 0 (0) Other/unknown 3 (1) 0 (0) 1 (0) 0 (0) 9 (2) 5 (0) Risk ctegory MSM 105 (36) 667 (55) 61 (24) 999 (37) 94 (25) 607 (43) MSM/IDU 18 (6) 179 (15) 13 (5) 262 (10) 6 (2) 87 (6) IDU 27 (9) 150 (12) 46 (18) 435 (16) 52 (14) 365 (26) HRH 67 (23) 99 (8) 42 (17) 428 (16) 35 (9) 229 (16) Other/unknown 71 (25) 116 (10) 91 (36) 531 (20) 187 (50) 124 (9) Clinicl/immunologicl CD or AIDS-defining opportunistic illness 108 (38) 424 (35) 87 (34) 1,177 (44) 167 (45) 684 (48) CD (27) 444 (37) 56 (22) 823 (30) 58 (16) 447 (32) CD4 350 or unknown 102 (35) 343 (28) 110 (43) 702 (26) 149 (40) 281 (20) NOTE: The columns for geogrphic res re not directly comprble becuse for Louisin nd Michign, the SHDC nd the ASD collected dt in different (but overlpping) geogrphic res. In Michign, the geogrphic re of the cohort study ws limited to the Detroit metropolitn re, but the geogrphic re of the smpling study ws the entire stte. In Louisin, the geogrphic re of the cohort study ws limited to the New Orlens metropolitn re, but the geogrphic re of the smpling study ws severl helth districts in the southern third of the stte. The Survey of HIV Disese nd Cre Project (SHDC) is probbility smple of individuls in cre for HIV infection. b The Adult nd Adolescent Spectrum of HIV-relted Disese Study (ASD) is fcility-bsed cohort study of individuls with HIV infection. MSM men who hve sex with men IDU injection drug user HRH high risk heterosexul individuls observed in SHDC or reported to HARS ws yers. In Michign, individuls observed in SHDC were older thn individuls reported to HARS (48% vs. 29% older thn 39 yers). The proportions of ptients in King County nd Michign with other or no identified trnsmission risk fctors for HIV in the SHDC dt were much higher thn those reported to HARS in those sme project res (24% vs. 7% for King County; 46% vs. 9% for Michign). An evlution of the provision of cre in ccordnce with guidelines in effect in 1998 is presented in Tble 3. In most cses, the point estimtes for cre prmeters from ASD sites were within the 95% CIs determined in SHDC, with some exceptions. For exmple, in King County, the SHDC estimtes of proportions of individuls with t lest one documented virl lod ssy or CD4 mesurement were higher thn proportions from individuls observed in ASD. The opposite ws true in Michign. Similrly, helth cre services utiliztion dt indicted tht the point estimtes for utiliztion prmeters in ASD were in most cses within the 95% CIs clculted by SHDC methods (see Tble 4). ASD ptients in King County hd more virl lod testing nd less CD4 testing per six months

6 Two-Stge Smpling Method for Clinicl Surveillnce of HIV-Infected Ptients 235 Tble 2. Demogrphic chrcteristics of ptients observed in SHDC nd ptients with HIV infection reported to the locl HIV/AIDS Reporting System (HARS) in southern Louisin, Michign stte, nd King County, Wshington, during 1998 King County Louisin Michign SHDC HARS SHDC HARS SHDC HARS (N 288) (N 4,121) (N 253) (N 8,633) (N 374) (N 9,532) Weighted Weighted Weighted Chrcteristic percent percent percent percent percent percent Sex Mle Femle Age Rce White, non-hispnic Blck, non-hispnic Hispnic Asin/Pcific Islnder Americn Indin/Alsk Ntive Other/unknown Risk ctegory MSM MSM/IDU IDU HRH Other/unknown Clinicl/immunologicl CD or AIDS-defining opportunistic illness 39 NC 30 NC 43 NC CD NC 32 NC 14 NC CD4 350 or unknown 36 NC 38 NC 43 NC NOTE: The columns for geogrphic res re directly comprble. For both the SHDC nd HARS, dt were collected from ptients in the sme geogrphic res. In Michign, the entire stte ws included; in Louisin, helth districts 1,2,3,4, nd 9 were included; nd in Wshington, King County ws included. The Survey of HIV Disese nd Cre Project (SHDC) is probbility smple of individuls in cre for HIV infection. NC not collected for mny HARS cses; therefore dt re incomplete nd not reported MSM men who hve sex with men IDU intrvenous drug user HRH high-risk heterosexul thn ptients observed in SHDC, while ASD ptients in Michign hd more CD4 testing per six months thn SHDC ptients. The medin number of outptient visits s estimted by SHDC rnged from four to six per yer, with no significnt differences between ASD nd SHDC. The design effects for some outcomes of interest re presented in Tble 5. Considerble vrition occurred in design effects cross outcomes nd cross sttes. Most notbly, the design effect for influenz vccintion in Michign ws very high, nd verge cluster sizes in Michign were higher thn in the other project res. Observed design effects of 1.0 indicted tht the smpling pproch resulted in smller vrince thn would be expected with simple rndom smple of the sme size. DISCUSSION The SHDC pilot study demonstrted the fesibility of twostge smpling pproch to obtin popultion-bsed estimtes of indictors of qulity of cre for HIV-infected ptients. The collection of clinicl surveillnce informtion from the medicl records of individuls in cre for HIV

7 236 Reserch Articles Tble 3. Proportion of ptients treted ccording to guidelines mong ptients observed in SHDC nd ptients enrolled in ASD b in southern Louisin, Michign stte, nd King County, Wshington, during 1998 Ptients receiving tretment King County Louisin Michign SHDC ASD SHDC ASD SHDC ASD (N 288) (N 1,211) (N 253) (N 2,702) ((N 374) (N 1,412) Treted/eligible c Treted/eligible c Treted/eligible c (Weighted Treted/eligible c (Weighted Treted/eligible c (Weighted Treted/eligible c percent (Stndrdized percent (Stndrdized percent (Stndrdized Cre provided [95% CI]) percent) [95% CI]) percent) [95% CI]) percent) HAART d 166/ /1, /171 1,508/2, / /1,308 (68 [57, 79]) (64) (64 [58, 70]) (59) (69 [54, 85]) (75) PCP prophylxis e 122/ /544 77/108 1,130/1, / /843 (79 [60, 99]) (83) (73 [54, 92]) (80) (86 [81, 90]) (83) MAC prophylxis f 28/50 132/204 20/47 465/647 37/77 257/457 (64 [46, 82]) (67) (57 [42, 71]) (70) (61 [42, 80]) (61) TB test g 164/ /1, /253 1,144/2, / /829 (55 [37, 74]) (70) (62 [31, 92]) (50) (34 [10, 58]) (52) Influenz vccine h 82/ /1,211 65/ /2,702 50/ /1,412 (27 [17, 37]) (24) (27 [19, 35]) (26) (21 [0, 45]) (28) Virl lod ssy h 264/288 1,013/1, /253 2,019/2, /374 1,156/1,412 (93 [89, 97]) (83) (73 [47, 99]) (74) (47 [27, 67] (84) CD4 mesurement h 271/288 1,024/1, /253 2,223/2, /374 1,197/1,412 (95 [91, 100]) (82) (78 [55, 100]) (82) (68 [50, 86]) (87) NOTE: The columns for geogrphic res re not directly comprble becuse for Louisin nd Michign, the SHDC nd the ASD collected dt in different (but overlpping) geogrphic res. In Michign, the geogrphic re of the cohort study ws limited to the Detroit metropolitn re, but the geogrphic re of the smpling study ws the entire stte. In Louisin, the geogrphic re of the cohort study ws limited to the New Orlens metropolitn re, but the geogrphic re of the smpling study ws severl helth districts in the southern third of the stte. The Survey of HIV Disese nd Cre Project (SHDC) is probbility smple of individuls in cre for HIV infection. b The Adult nd Adolescent Spectrum of HIV-relted Disese Study (ASD) is fcility-bsed cohort study of individuls with HIV infection. c Treted/eligible is the number of individuls receiving cre/number of individuls eligible for cre. d Eligibility for highly ctive ntiretrovirl therpy (HAART) ws defined s CD4 500, PCR 20,000, bdna 10,000, or AIDS-opportunistic illnesses dignosis (ny time before or during 1998). e Eligibility for Pneumocystis crinii pneumoni (PCP) prophylxis ws defined s CD4 200, PCP dignosis (ny time before or during 1998). f Eligibility for Mycobcterium vium complex (MAC) prophylxis ws defined s CD4 50 or Mycobcterium vium dignosis (ny time before or during 1998). g Eligibility for tuberculosis (TB) test ws defined s no TB dignosis or sputum culture positive to M. tuberculosis prior to h All individuls re recommended to receive n nnul influenz vccine nd regulr virl lod ssy nd CD4 T-lymphocyte (CD4) mesurements. CI confidence intervl infection is criticl to the evlution of provision of pproprite cre. Previously, the CDC-supported ASD project ws used to describe trends in HIV-relted morbidity nd nturl history of HIV infection, s well s to inform ntionl surveillnce cse definitions nd tretment guidelines. 7,8,19 24 The SHDC method represents model for collection of dt for similr purposes with incresed representtiveness. Our study differs in two importnt wys from HCSUS, which surveyed lrge ntionl probbility smple of individuls in cre for HIV infection. 4,5,25 First, HCSUS ws generlizble to the entire United Sttes becuse it rndomly smpled providers from throughout the United Sttes, while SHDC ws not becuse it selected three geogrphic res through competitive ppliction. Second, the smpling frme of providers for SHDC benefited by using the HIV/AIDS surveillnce dtbse s smpling frme. The ntionl reporting system for HIV/AIDS is regulrly evluted. Since AIDS is reportble to ll stte nd locl helth deprtments nd AIDS cse subject reporting is known to hve high completeness, investigtors in SHDC hd very complete smpling frme of providers of cre for individuls with HIV infection. 26

8 Two-Stge Smpling Method for Clinicl Surveillnce of HIV-Infected Ptients 237 Tble 4. Chrcteristics of helth cre utiliztion of ptients observed in SHDC nd ptients enrolled in ASD b in southern Louisin, Michign stte, nd King County, Wshington, during 1998 Ptients receiving tretment King County Louisin Michign SHDC ASD SHDC ASD SHDC ASD (N 288) (N 1,217) (N 253) (N 2,711) (N 374) (N 1,356) Weighted Stndrd- Weighted Stndrd- Weighted Stndrd- Utiliztion medin ized medin ized medin ized mesure Medin (95% CI) Medin medin Medin (95% CI) Medin medin Medin (95% CI) Medin medin Outptient visits c (5.2, 7.2) (3.3, 6.2) (1.6, 6.3) Virl lods d (1.4, 1.5) (0.2, 1.4) (0, 1.4) CD4 counts d (1.4, 1.5) (0.5, 1.4) (0, 1.1) NOTE: The columns for geogrphic res re not directly comprble becuse for Louisin nd Michign, the SHDC nd the ASD collected dt in different (but overlpping) geogrphic res. In Michign, the geogrphic re of the cohort study ws limited to the Detroit metropolitn re, but the geogrphic re of the smpling study ws the entire stte. In Louisin, the geogrphic re of the cohort study ws limited to the New Orlens metropolitn re, but the geogrphic re of the smpling study ws severl helth districts in the southern third of the stte. The Survey of HIV Disese nd Cre Project (SHDC) is probbility smple of individuls in cre for HIV infection. b The Adult nd Adolescent Spectrum of HIV-relted Disese Study (ASD) is fcility-bsed cohort study of individuls with HIV infection. c Number of visits in the study yer d Number of tests per six months The dvntge of our design is tht, in theory, the results should provide popultion-bsed estimtes tht represent ll individuls in cre for HIV infection in the prticipting geogrphic res. However, some providers selected from the smpling frme did not llow review of their ptients medicl records. This problem ws encountered in King County, where 75% of selected providers prticipted. In the HCSUS study, 70% to 100% of selected providers prticipted. The extent to which such refusls bis the results of the study depends on whether the providers who refused to prticipte (1) serve substntil proportion of HIV-infected ptients in cre, (2) serve substntively different ptient popultions, or (3) provide substntively different qulity of cre. In our study, most refusls were providers who hd few HIV-infected ptients. The SHDC study design hs dditionl limittions. The design only llows observtion of nd inference to individuls in cre for HIV infection; however, individuls dignosed with HIV infection but not in cre re criticl popultion. 27 With respect to nlysis of eligibility for stndrd cre mesures, some criteri could not be determined with confidence becuse we did not ccess the full medicl history to determine previous dignoses or procedures. Finlly, becuse we did not bstrct records from ll cre providers for ech ptient, our dt represent minimum estimtes of cre received during the yer. Becuse we smpled providers with probbility proportion to size nd without replcement, the vrince estimtes could hve been obtined by tking into ccount joint selection probbilities nd selection without replcement (e.g., using SUDAAN with design UNEQWOR). 13 However, we chose to nlyze dt s though the smpling hd been done with replcement by using SAS PROC SURVEY MEANS nd SUDAAN with design WR (with replcement), s previously done in other studies. 12,13,28,29 This nlytic pproch results in somewht lrger vrince estimtes; however, previous comprisons using pilot dt (dt not shown) demonstrted the resulting increses in vrince to be smll nd cceptble trde-off for the use of simplified nlytic methods nd the bility to use SAS softwre, which is widely vilble to stte helth deprtments. 12 Design effects mesure the extent to which the smpling design incresed the vrince of the estimtes compred with using simple rndom smpling; lrger design effects result in wider CIs. The vrition in design effects tht we observed in our study ws considerble, nd we will conduct dditionl investigtion into the resons for these vritions s we prepre for subsequent studies. It is possible tht there were vritions mong the prticipting study sites in the extent to which smpled providers represented single prctitioners (which would tend to result in higher intr-clss correltion nd higher design effects) vs. groups of physicins (which would tend to result in more heterogeneity of prctice ptterns nd lower intr-clss correltion). Future study designs will increse the number of smpled providers nd reduce the number of smpled ptients per provider in order to reduce design effects. Future cycles lso my include n interview component, which would provide the opportunity to evlute psychosocil fctors not included in the medicl records. Offering

9 238 Reserch Articles Tble 5. Intr-clss correltion coefficients, design effects, nd relted design chrcteristics from SHDC in southern Louisin, Michign stte, nd King County, Wshington, during 1998 Coefficient of Intr-clss Design effect Region Number of Men cluster Number vrition for correltion for proportion Vrible observtions size of clusters weights coefficient (r) b or men c King County (n 288; m 140; ddf 134) HAART d (%) PCP prophylxis e (%) Influenz vccine f (%) Virl lods per six months g (men) Louisin (n 253; m 68; ddf 63) HAART d (%) PCP prophylxis e (%) Influenz vccine f (%) Virl lods per six months g (men) Michign (n 374; m 21; ddf 13) HAART d (%) PCP prophylxis e (%) Influenz vccine f (%) Virl lods per six months g (men) The Survey of HIV Disese nd Cre Project (SHDC) is probbility smple of individuls in cre for HIV infection. b r estimtes were obtined using SUDAAN Proc Regress with R Exchngeble nd model vrible sex. c Design effects were obtined using SUDAAN with option DEFT1 nd DESIGN WR. d Eligibility for highly ctive ntiretrovirl therpy (HAART) ws defined s CD4 500, PCR 20,000, bdna 10,000, or AIDS-opportunistic illnesses dignosis (ny time before or during 1998). e Eligibility for Pneumocystis crinii pneumoni (PCP) prophylxis ws defined s CD4 200, PCP dignosis (ny time before or during 1998). f All individuls re recommended to receive n nnul influenz vccine nd regulr virl lod ssy nd CD4 T-lymphocyte (CD4) mesurements. g SUDAAN cnnot clculte design effect for medins. n totl number of chrts bstrcted m number of primry smpling units ddf denomintor degrees of freedom interviews to individuls with no known cre provider might help identify brriers to entry into cre nd determine needs for helth services mong individuls not in cre for HIV infection. We conclude tht conducting two-stge probbility smpling in the setting of helth deprtment HIV surveillnce progrms is possible. Our estimtes of some indictors of HIV cre were comprble with those of the currently conducted fcility-bsed clinicl surveillnce project, but for importnt outcomes such s intensity of lbortory monitoring of CD4 counts, differences were observed. Helth deprtments re uniquely positioned to conduct such surveillnce projects becuse only they hve well-vlidted smpling frmes of providers of HIV cre nd becuse only they hve sttutory uthority to conduct medicl record reviews for individuls with HIV infection. Beginning in 2006, CDC expects to support rndom smple of sttes to collect clinicl outcomes surveillnce dt by method similr to SHDC. This will represent three-stge cluster smpling design tht cn extend infer- ence to ll ptients in cre for HIV infection in the United Sttes. Further evlution of these methods in more helth deprtments should help to clrify the fesibility of using this study design in diverse public helth settings. Lrger numbers of ptients must be included to provide loclly useful dt. To the extent tht this methodology is fesible, dptble, nd cost effective, it my provide n importnt clinicl surveillnce tool for descriptive epidemiology nd progrm evlution, both ntionlly nd by sttes nd mjor metropolitn res. Acknowledgements re due to the following uthors who comprise the SHDC Pilot Study Group whose input contributed to this study: Hien L. Guyer, MPH, nd Lind L. Wotring, PhD, of HIV/AIDS Surveillnce, Michign Deprtment of Community Helth, Detroit nd Lnsing, MI; A.D. McNghten, PhD, Pul Jones, MS, Debr L. Hnson, MS, John T. Brooks, MD, Dvid Swerdlow, MD, Mitchell I. Wolfe, MD, MPH, nd Mxine Denniston, MS, of the Division of HIV/AIDS Prevention- Surveillnce nd Epidemiology, Ntionl Center for HIV, STD, nd TB Prevention, Centers for Disese Control nd Prevention,

10 Two-Stge Smpling Method for Clinicl Surveillnce of HIV-Infected Ptients 239 Atlnt, GA. The uthors thnk Erik Schwb for developmentl editing nd copyediting of the mnuscript nd Amy Drke for ssistnce with project mngement. REFERENCES 1. Lee LM, Kron JM, Selik R, Nel JJ, Fleming PL. Survivl fter AIDS dignosis in dolescents nd dults during the tretment er, United Sttes, JAMA 2001;285: Report of the NIH pnel to define principles of therpy of HIV infection. MMWR Recomm Rep 1998;47(RR-13): Summers T, Algiri P, Ktes J. Federl HIV/AIDS spending: budget chrtbook, fiscl yer Menlo Prk (CA): The Henry J. Kiser Fmily Foundtion; Also vilble from: URL: /commonspot/security /getfile.cfm&pgeid [cited 2005 Jn 20]. 4. Shpiro MF, Berk ML, Berry SH, Emmons CA, Athey LA, Hsi DC, et l. Ntionl probbility smples in studies of low-prevlence diseses. Prt I: Perspectives nd lessons from the HIV cost nd services utiliztion study. Helth Serv Res 1999;34(5 Prt 1): Frnkel MR, Shpiro MF, Dun N, Morton SC, Berry SH, Brown JA, et l. Ntionl probbility smples in studies of low-prevlence diseses. Prt II: designing nd implementing the HIV cost nd services utiliztion study smple. Helth Serv Res 1999;34(5 Prt 1): Frizo KM, Buehler JW, Chmberlnd ME, Whyte BM, Froelicher ES, Hopkins SG, et l. Spectrum of disese in individuls with humn immunodeficiency virus infection in the United Sttes. JAMA 1992;267: Jones JL, Hnson DL, Dworkin MS, Alderton DL, Fleming PL, Kpln JE, et l. Surveillnce for AIDS-defining opportunistic illnesses, MMWR CDC Surveill Summ 1999;48(2): McNghten AD, Hnson DL, Jones DL, Dworkin MS, Wrd JW. Effects of ntiretrovirl therpy nd opportunistic illness primry chemoprophylxis on survivl fter AIDS dignosis. Adult/Adolescent Spectrum of Disese Group. AIDS 1999;13: Louisin Deprtment of Helth nd Hospitls. Administrtive regions [cited 2005 Jn 15]. Avilble from: URL: Deprtment of Helth nd Humn Services (US), HIV/AIDS Bureu. Ryn White CARE Act [cited 2005 Jn 15]. Avilble from: URL: Insightful Corportion. S-PLUS: Version 6. Wshington: Insightful Corportion; SAS Institute. SAS: Version 8.2. Cry (NC): SAS Institute; Reserch Tringle Institute. SUDAAN user mnul, relese 8.0. Reserch Tringle Prk (NC): Reserch Tringle Institute; Cochrn WG. Smpling techniques. New York: John Wiley & Sons; Moore RD, Stnton D, Gopln R, Chisson RE. Rcil differences in the use of drug therpy for HIV disese in n urbn community. N Engl J Med 1994;330: Hsu LC, Vittinghoff E, Ktz MH, Schwrcz SK. Predictors of use of highly ctive ntiretrovirl therpy (HAART) mong individuls with AIDS in Sn Frncisco, J Acquir Immune Defic Syndr 2001;28: Klevens RM, Fleming PL, Li J, Gines CG, Gllgher K, Schwrcz K, et l. The completeness, vlidity, nd timeliness of AIDS surveillnce dt. Ann Epidemiol 2001;11: United Sttes Public Helth Service nd Infectious Disese Society of Americ. USPHS/IDSA guidelines for the prevention of opportunistic infections in individuls infected with humn immunodeficiency virus [cited 2005 Jn 15]. Avilble from: URL: idsinfo.nih.gov/guidelines/defult_db2.sp?id revised clssifiction system for HIV infection nd expnded surveillnce cse definition for AIDS mong dolescents nd dults. MMWR Recomm Rep 1992;41 (RR-17): Kpln JE, Hnson DL, Jones JL. Erly initition of combintion ntiretrovirl therpy: does it ffect clinicl outcome? Proceeding of the 13th Interntionl AIDS Conference; 2000 July; Durbn, South Afric. Abstrct No.: LbPeB Dworkin MS, Hnson DL, Kpln JE, Jones JL, Wrd JW. Risk for preventble opportunistic infections in individuls with AIDS fter ntiretrovirl therpy increses CD4 T lymphocyte counts bove prophylxis thresholds. J Infect Dis 2000;182: Kpln JE, Hnson JL, Nvin TR, Jones JL. Risk fctors for primry Pneumocystis crinii pneumoni in humn immunodeficiency virusinfected dolescents nd dults in the United Sttes: ressessment of indictions for chemoprophylxis. J Infect Dis 1998;178: Brooks JT. Risk of Mycobcterium vium complex (MAC) infection mong HIV-infected individuls who stop primry prophylxis fter HAART-ssocited immune reconstitution. Proceedings of the Infectious Diseses Society of Americ 40th Annul Meeting; 2000; Sn Diego (CA). Abstrct No.: Blir J, Hnson DL, Jones JL. Do gender differences in virl lod predict differences in HIV disese progression? Proceedings of the 7th Conference on Retroviruses nd Opportunistic Infections; 2000 Feb; Sn Frncisco. Abstrct No.: Bozzette SA, Berry SH, Dun N, Frnkel MR, Leibowitz AA, Lefkowitz D, et l. The cre of HIV-infected dults in the United Sttes. HIV Cost nd Services Utiliztion Study Consortium. N Engl J Med 1998;339: Nkshim AK, Fleming PL. HIV/AIDS surveillnce in the United Sttes, J Acquir Immune Defic Syndr 2003;32 Suppl 1:S68-S Centers for Disese Control nd Prevention. HIV prevention strtegic pln through 2005 [cited 2005 Jn 15]. Avilble from: URL: Hnsen MH, Hurwitz WN, Mdow WG. Smple survey methods nd theory. New York: John Wiley & Sons; Kish L. Survey smpling. New York: John Wiley; 1965.