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Direct Medical Cost of Pelvic Inflammatory Disease and Its Sequelae:Decreasing,but Still SubstantialDAVID B.REIN,MPA,WILLIAM J.KASSLER,MD,MPH,KATHLEEN L.IRWIN,MD,MPH,AND LARA RABIEEObjective:To estimate direct medical costs and average lifetime cost per case of pelvic inflammatory disease(PID). Methods:We estimated the direct medical expenditures for PID and its three major sequelae(chronic pelvic pain, ectopic pregnancy,and infertility)and determined the aver-age lifetime cost of a case of PID and its sequelae.We analyzed3years of claims data of privately insured individ-uals to determine costs,and3years of national survey data to determine number of cases of PID,chronic pelvic pain, and ectopic pregnancy.We developed a probability model to determine the average lifetime cost of a case of PID. Results:Direct medical expenditures for PID and its sequelae were estimated at$1.88billion in1998:$1.06billion for PID,$166million for chronic pelvic pain,$295million for ectopic pregnancy,and$360million for infertility associated with PID.The expected lifetime cost of a case of PID was $1167in1998dollars.The majority of those costs($843per case)represent care for acute PID rather than diagnosis and treatment of sequelae.Approximately73%of cases will not accrue costs beyond the treatment of acute PID. Conclusion:The direct medical cost of PID is still substan-tial.The majority of PID related costs are incurred in the treatment of acute PID.Because most PID-related costs arise in thefirst year from treatment of acute PID infection, strategies that prevent PID are likely to be cost-effective within a single year.(Obstet Gynecol2000;95:397–402.©2000by The American College of Obstetricians and Gynecologists.)Pelvic inflammatory disease(PID)afflicts as many as1.5 million women in the United States annually.Although most common in young women,its consequences, including chronic pelvic pain,ectopic pregnancy,and infertility,can affect a woman’s health and well-being throughout her lifetime.1The direct medical costs of PID and two of its adverse outcomes,ectopic pregnancy and infertility,were estimated in1990at approximately $2.7billion.2That analysis predicted that direct and indirect costs of PID would grow to as much as$10 billion by the year2000.The Institute of Medicine calculated the1994direct costs of PID as$3.1billion.3 Over the last decade,changes in diagnosis and treat-ment of sexually transmitted diseases(STDs)and in the healthcare system influenced national estimates of the cost of PID.4Several factors might have led to a de-crease in overall PID incidence,such as availability of more sensitive and specific nucleic acid amplification tests that hasten diagnosis,availability of directly ob-served,single-dose therapies that increase adherence to treatment for lower genital tract infections,and imple-mentation of a national,federally funded chlamydia screening program to detect and treat asymptomatically infected women.5,6Significant changes in the organiza-tion,structure,andfinancing of health care have re-sulted in greater use of less expensive outpatient man-agement of PID,and in shorter stays for hospitalized women.7To guide clinicians and decision makers who diagnose and treat PID or allocate healthcare resources, we estimated the direct medical cost of PID and its three major sequelae in1998dollars,using the most recent data.From the United States Centers for Disease Control and Prevention,National Center for HIV,Sexually Transmitted Diseases,and Tubercu-losis Prevention,Division of STD Prevention,Health Services Researchand Evaluation Branch,Atlanta,Georgia;the Joint PhD Program inPublic Policy,Georgia State University/Georgia Institute of Technology,Atlanta,Georgia;and the New Hampshire Department of Health andHuman Services,Concord,New Hampshire.The authors thank Anne Haddix,PhD,and Guoyu Tao,PhD,for theirmethodologic advice.Supported in part by an appointment to the Research ParticipationProgram at the Centers for Disease Control and Prevention(CDC),National Center for HIV,Sexually Transmitted Diseases,and Tubercu-losis Prevention,Division of Sexually Transmitted Diseases Prevention,administered by the Oak Ridge Institute for Science and Educationthrough an interagency agreement between the US Department ofEnergy and the CDC.397 VOL.95,NO.3,MARCH20000029-7844/00/$20.00PII S0029-7844(99)00551-7MethodsWe estimated the number of episodes of PID and its sequelae in the United States and the direct medical cost per episode of illness(unit costs),then multiplied the unit costs by the number of episodes.Once direct cost analysis was completed,we created a probability-based model,based on decision analysis techniques,to esti-mate an average lifetime cost per case of PID.To estimate the number of visits for PID and its three sequelae in the United States,we estimated the number of hospital inpatient visits for1993,1994,and1995from the National Hospital Discharge Survey.8Estimates represented the annual average over the3-year period. Cases for each disease were selected if a disease-related International Classification of Diseases,9th Revision, Clinical Modification(ICD-9-CM)code appeared as one of seven discharge diagnoses.We established case def-initions for PID,chronic pelvic pain,and ectopic preg-nancy on the basis of ICD-9diagnosis codes,9which defined a case of PID as acute,chronic,unspecified salpingitis(614.0–614.2);acute,chronic,or unspecified parametritis(614.3–614.4);acute,unspecified,or other pelvic peritonitis(614.5,614.7);other specified or un-specified inflammatory disease of female pelvic organs and tissues(614.8–614.9);acute,chronic and unspeci-fied disease of the uterus(615.0–615.1,615.9);acute or chronic gonococcal infection of upper genitourinary tract,gonococcal endometritis,or salpingitus,or other upper genitourinary tract gonococcal infection(098.10, 098.16–098.17,098.19,098.30,098.36,098.37,098.39); and gonococcal peritonitis(098.86).Chronic pelvic pain was defined as any unspecified symptom associated with the female genital organs(625.9).(Dr.Robert Rolfs, State of Utah Department of Public Health.Dr.Rolfs observed that a large percentage of cases of chronic pelvic pain from a Seattle cohort study that were coded 625.9represented a past case of acute PID with persis-tent pain.)Ectopic pregnancy was defined as abdominal pregnancy(633.0),tubal pregnancy(633.1),ovarian pregnancy(633.2),and other or unspecified ectopic pregnancy(633.8,633.9).10–12Outpatient cases of PID and its three sequelae diag-nosed among privately insured women were estimated from three surveys of outpatient services:the National Ambulatory Medical Care Survey,the National Hospi-tal Ambulatory Medical Care Survey—Outpatient De-partment File,and the National Hospital Ambulatory Medical Care Survey—Emergency Department File.13–15Case estimates from the threefiles were aggre-gated by disease to calculate one estimate of outpatient cases.Estimates represented the annual average from2 years of data,1994and1995.Variances of outpatient estimates were calculated with special variancefiles from the National Center for Health Statistics.16–18 We assumed that20%of chronic pelvic pain visits and50%of ectopic pregnancies were related to PID.19 The estimated number of outpatient cases of PID, chronic pelvic pain,and ectopic pregnancy from the two surveys used varied widely as a result of few survey observations for those diagnoses.It also was possible that the same case of PID could be counted in more than one outpatient survey.Therefore,we vali-dated our estimate of outpatient visits by calculating the ratio of outpatient to inpatient cases in MarketScan data (The Medstat Group,Ann Arbor,MI)for1993–1995.We applied that ratio to the National Hospital Discharge survey estimate of inpatient PID cases.The estimate of outpatient PID cases from the three surveys was within 10%of the MarketScan–National Hospital Discharge Survey estimate.We estimated the cases of outpatient PID diagnosed at publiclyfinanced sexually transmitted disease(STD) clinics byfirst calculating the proportion of PID cases in the Seattle,Washington,publically funded outpatient STD clinics to the total cases of all STDs in those clinics (Whittington W.Unpublished records from Seattle, Washington,STD clinic system,1998).We applied that proportion to the estimated total number of cases at all STD clinics estimated in a1995survey of STD clinics that was weighted to the national population.20Our case estimates of treated infertility were devised by applying a range of probabilities of infertility related to PID(11–30%)and infertility treatment related to PID (25%)in the literature to the total number of PID cases in this study.19To calculate current PID-related cases of infertility,we assumed that numbers of PID cases in the past(that would result in cases of infertility today)were at least as high as those presented in this study. Costs per episode of PID were based on actual patient and insurance payments(as distinguished from physi-cian charges)using the MarketScan data base,a com-mercial data base that provided payment data for1993, 1994,and1995.21The MarketScan data base represents approximately4million privately insured persons per year over3years,approximately12million individual years of health coverage.To estimate the unit costs of PID,we added all PID-related claims for a given episode of disease,de-fined as all continuous claims for a case.New PID claimsfiled more than60days after a previous claim were defined as new episodes.Inpatient drug costs were available in inpatient claims records.Outpatient pharmacy costs were derived from a subset of women for whom information about prescription drug cover-age was available.Average outpatient drug cost was applied to all cases of outpatient PID.22MarketScan did398Rein et al Pelvic Inflammatory Disease Obstetrics&Gynecologynot provide estimates of the cost of treating a case of PID at a publicly funded STD clinic,so we assumed that cost was the same as treating PID in a private outpatient setting.To estimate the unit costs of chronic pelvic pain,we summed patients’outpatient claims for the year and calculated the average yearly cost per patient.For inpatient cases of chronic pelvic pain,we summed patients’claims by inpatient admission and found the average cost per hospital admission.We included inpa-tient pharmacy costs and costs of drugs supplied intra-venously or by direct observation,but not outpatient prescription and nonprescription pharmacy costs. Unit costs for ectopic pregnancy were calculated in the same manner.Outpatient costs were estimated on a yearly basis,and inpatient costs were estimated per hospital admission.Inpatient pharmacy costs,the cost of intravenous and directly observed medications,were included in cost estimates,but not outpatient prescrip-tion or nonprescription pharmacy costs.We calculated expected lifetime costs by adding costs of adverse sequelae to costs of initial treatments.The expected costs of sequelae were calculated by multiply-ing their probability and cost(present value calcula-tions were performed using a5%discount rate).We added those costs to the cost of treating a case of PID.23 Probabilities of each sequela were drawn from the literature19and multiplied by the cost of each sequela to determine which stage of disease accounted for most PID-related costs.We assumed that half of ectopic pregnancies were PID-related.23,24We further assumed that ectopic pregnancies that resulted from PID did not differ clinically or in cost from those of other etiologies. We assumed that20%of chronic pelvic pain was related to previous cases of PID,that infertility developed in 11–30%of women who suffered from PID,and that of those women,only25%received infertility treatment.19 Treatment was stratified as inpatient or outpatient with the use of percentages of inpatient and outpatient cases in the national hospital and outpatient survey data.The unit costs of chronic pelvic pain,ectopic pregnancy,and infertility were multiplied by their probabilities.We assumed that chronic pelvic pain occurred on average2years after an episode of PID; ectopic pregnancy5years after;and infertility10years after.19The cost of infertility treatment was based on the 1990estimate and adjusted to1998dollars,using the consumer price index.2We conducted a sensitivity analysis by evaluating all unit cost values over a range of$1to twice the unit costs in this study.Probabilities of sequelae and inpatient or outpatient care were evaluated as a range from0–1.We calculated probabilities of the most common outcomes of a case of PID from that model to determine if acute care of PID or care for PID sequelae accounted for the largest proportion of costs.ResultsWe estimated approximately1.2million visits for PID, 1.5million for chronic pelvic pain,and290,000for ectopic pregnancy in1995.A total of300,000visits for chronic pelvic pain,145,000for ectopic pregnancy,and as many as78,000cases of treated infertility were estimated as related to cases of PID.Thus,we estimated 1.76million inpatient,outpatient,and STD clinic visits for acute PID and its three main sequelae annually from 1993–1995(Table1).Total direct medical costs for PID and sequelae,with the use of a high estimation of probability of infertility (30%),was$1.88billion in1998,and with the use of a low estimation of probability of infertility(11%),was $1.62billion.Of those costs,PID accounted for$1.07 billion,chronic pelvic pain for$166million,ectopic pregnancy for$295million,and infertility from$120to $360million(Table1).Cases of PID treated as inpatients were more costly. The average lifetime cost for a case of PID treated initially as an inpatient was$4673,compared with$777 for cases treated entirely as outpatient.The average lifetime dollar cost per case of PID was estimated at $1167with the use of a midrange estimate of infertility equal to20%(the explicit derivation of the average cost per case of PID,including a copy of the probabilistic model and a table displaying the full results from the sensitivity analysis are available from the authors upon request).According to our model,67.2%of PID cases generated costs equal to the mean cost of treating PID with no sequelae on an outpatient basis($451).Of those patients,10.5%will suffer from infertility that they choose not to treat.A total of81.1%of cases of PID generated costs less than the average cost of all cases of PID($1167).Applying our average cost per case esti-mate of$1167to our estimate of1.2million visits,we estimated that visits for PID in1998would generate $1.44billion in current and future direct medical costs. Sensitivity analysis showed that expected cost of a case of PID was influenced most by probability that a case of PID would be treated as an inpatient and the probability of subsequent ectopic pregnancy.Our aver-age cost estimate was not sensitive to wide variation in the unit cost per case of an inpatient or outpatient case of PID.DiscussionWe estimated that the direct medical expenditures for PID and its three major sequelae in the United StatesVOL.95,NO.3,MARCH2000Rein et al Pelvic Inflammatory Disease399were$1.88billion per year in1998dollars.This estimate is less than the$3.12billion of direct costs presented in the most recent review of PID costs for19943and is substantially lower than the$10billion of direct and indirect costs projected for the year2000.2That decrease is due largely to fewer cases of PID and a shift from inpatient to less costly outpatient management of PID. The decline in PID incidence coincides with and might be attributable to an expansion of national and regional programs that screen women for asymptomatic chla-mydial infections,one common cause of PID.6The lower cost estimate also might be explained by new methods and data sources including calculating PID and sequelae case estimates from national survey data that were validated with an independent database; calculating costs on actual payments rather than physi-cians’charges,chart reviews,or expert opinions, sources that tend to inflate cost estimates;and calculat-ing the average cost model based on inpatient-to-outpatient case ratios in the survey and MarketScan data rather than on expert opinion.The latter method-ologic approach was critical because the sensitivity analysis illustrated that the expected cost model was highly dependent on the proportion of PID cases treated on an inpatient basis.This study was limited by at leastfive factors that tend to underestimate the costs of PID and its sequelae. Therefore,our estimate was likely to be a minimum estimate of PID-related costs.The direct medical cost estimate relies on the validity and representativeness of the MarketScan data set.The MarketScan data set is not designed as a statistically representative source of per-sons diagnosed with PID(as a probabilistic survey would be),but it is an unusually large and regionally distributed sample.This data set is likely to generate a closer estimate of unit costs than data previously used to estimate PID and sequelae costs.Second,one unpublished study from Seattle that compared insurance claims for60PID patients to their chart records indicated that some PID costs—such as the cost of diagnostic services before a PID diagnosis, PID hospitalizations not recorded as such due to coding error,and laboratory and diagnostic tests not marked with a PID diagnosis code—might be missed when costs are estimated from claims data only(personal communication with Dr.David Magid,Seattle Health Net).If missed costs are generalizable to cases of PID nationwide,they could increase our cost per case esti-mate by as much as30%.Third,we used a conservative estimate of the cost of infertility diagnosis and treatment($4625).Specifically, we matched older estimates of infertility costs with older probabilities of treatment rather than matching new estimates of cost to previous estimates of demand. We chose this method because no new estimates of numbers of persons seeking treatment for infertilityTable1.Number of Yearly Visits and Cost for PID and its Three Major SequelaeCondition and type of treatment Number of clinicalvisits(ϮSE)Unit costper visit(ϮSD)($)*Annual directmedical costs(in million$)*PIDInpatient129,495(4641)4366($5843)565 Outpatient1,107,814(163,397)451($912)500 Total1,237,309860.901065 Chronic pelvic painInpatient16,842(538)2512(2572)42 Outpatient282,883(42,066)439(956)124 Total299,725555.48166 Ectopic pregnancyInpatient21,671(1868)6862(4030)149 Outpatient121,485(29,977)1204(2452)146 Total143,1562061295 Infertility†Low estimate25,964(NA)4625(NA)120 High estimate77,891(NA)4625(NA)360 TotalUsing a low estimate of infertility1,706,1541105‡1646 Using a high estimate of infertility1,758,0811235‡1886SEϭstandard error;SDϭstandard deviation;PIDϭpelvic inflammatory disease;NAϭnot applicable.*In1998United States dollars.†Infertility estimates draw from the literature to assume that between11%(low estimate)and30%(high estimate)of women with PID become infertile.Of these women,only25%seek infertility treatment.‡These numbers reflect average lifetime cost per case of PID including sequelae,calculated by multiplying the probability of each disease event and treatment by the cost of that event and treatment.400Rein et al Pelvic Inflammatory Disease Obstetrics&Gynecologyrelated to PID were available.According to more recent studies,the current(1998)cost of infertility can range from two to20times the estimate we used in this analysis.25However,the increases in the costs of infer-tility treatment might have reduced the probability that women who had PID would seek infertility treatment. Fourth,as in previous studies,our cost analysis did not capture the outpatient prescription or nonprescrip-tion pharmacy costs of treating chronic pelvic pain and ectopic pregnancy because they are difficult to estimate accurately.To the extent that those costs might be significant,our estimates will be conservative.Fifth,as others have done,we assumed that our cost and case estimates for1998did not differ greatly from those that used data from a few years earlier.2,5,10 Actual costs from1998might differ from those esti-mated from1993–1995data.Although the absolute number of cases of PID,direct medical costs,and cost per case of PID including its three major sequelae were lower than previous esti-mates,the direct medical costs of PID are still substan-tial.Direct medical costs underestimate the true burden of a disease because they do not capture intangible costs (decreased quality of life,emotional consequences of chronic pelvic pain,ectopic pregnancy,and infertility) or indirect costs(lost work days,lowered productivity resulting from illness,or lost wages).The indirect costs for other STDs have been estimated as at least three times the direct medical costs.3Our analysis found that the majority of PID-related costs are related to treating acute PID rather than its sequelae,indicating that PID prevention activities are likely to be cost-effective within1year.26Although the total United States burden of PID has fallen consider-ably since1990,additional savings might be achieved. Examples of PID prevention efforts include screening at-risk women for bacterial STDs,promoting condom use and safe sexual practices,periodically assessing patients’behavioral risks for exposure,using sensitive tests to diagnose lower genital tract infection,and using appropriate treatment regimens.1References1.Centers for Disease Control and Prevention.1998Guidelines fortreatment of sexually transmitted diseases.MMWR Morb Mortal Wkly Rep1998;47(RR-1):79–88.2.Washington AE,Katz P.Cost of and payment source for pelvicinflammatory disease.Trends and projections,1983through2000.JAMA1991;266:2565–9.3.Siegel JE.Estimates of the economic burden of STDs:Review of theliterature with updates.In:Eng TR,Butler WT,eds.Institute of Medicine.The hidden epidemic.Washington DC:National Acad-emy Press,1997:330–56.4.American Social Health Association.STD counseling and treat-ment guide.Research Triangle Park,NC:1995:209–19.5.Haddix AC,Hillis SD,Kassler WJ.The cost effectiveness ofazithromycin for chlamydia trachomatis infections in women.Sex Transm Dis1995;22:274–80.6.Hillis S,Black C,Newhall J,Walsh C,Groseclose SL.Newopportunities for chlamydia prevention:Applications of science to public health practice.Sex Transm Dis1995;22:197–202.7.Centers for Disease Control and Prevention.Prevention and man-aged care:Opportunities for managed care organizations,purchas-ers of health care and public health agencies.MMWR Morb Mortal Wkly Rep1995;44(RR-14):1–12.8.National Center for Health Statistics.1993,1994,1995Nationalhospital discharge survey:Public use data tape documentation.Hyattsville,MD:1993–1995.9.American Medical Association.International classification of dis-eases,ninth revision,clinical modification(ICD-9-CM).Salt Lake City,UT:Medicode Publications,1996.10.Washington AE,Arno PS,Brooks MA.The economic cost of pelvicinflammatory disease.JAMA1986;255:1735–8.11.Washington AE,Cates W Jr,Zaidi AA.Hospitalizations for pelvicinflammatory disease:Epidemiology and trends in the United States,1975to1981.JAMA1984;251:2529–33.12.Rolfs RT,Galaid EI,Zaidi AA.Pelvic inflammatory disease:Trendsin hospitalizations and office visits,1979through1988.Am J Obstet Gynecol1992;166:983–90.13.National Center for Health Statistics.1994,1995National ambula-tory medical care survey.Public-use data tape documentation.Hyattsville,MD:1994–1995.14.National Center for Health Statistics.1994,1995National hospitalambulatory medical care survey—outpatient departmentfile.Pub-lic-use data tape documentation.Hyattsville,MD:1994–1995. 15.National Center for Health Statistics.1994,1995National hospitalambulatory medical care survey—Emergency departmentfile.Public-use tape documentation.Hyattsville,MD:1994–1995. 16.National Center for Health Statistics.1994,1995NAMCS andNHAMCS OD/ER Variance Files.Public-use tape.Hyattsville, MD:1994–1995.17.Software for Survey Data Analysis(SUDAAN),Version7.50.Research Triangle Park,NC:Research Triangle Institute,1997. 18.Shah BV.SESUDAAN:Standard errors program for computingstandardized rates from sample survey data.Research Triangle Park,North Carolina:Research Triangle Institute,1981.19.Westro¨m L,Mårdh P.Acute pelvic inflammatory disease(PID).In:Holmes KK,Mårdh P,Sparling PF,Wiesner PJ,Cates W Jr,Lemon SM,et al,eds.Sexually transmitted diseases.New York:McGraw-Hill Information Services Company,1990:593–613.ndry DJ,Forrest JD.Public health departments providing sexu-ally transmitted disease services.Fam Plann Perspect1996;28: 261–6.21.MarketScan®.MarketScan®database user’s guide.Ann Arbor,MI:The MEDSTAT Group Inc.,1997.22.Physicians’desk reference.51st ed.Montvale,NJ:Medical Eco-nomics Company,1997.23.Haddix AC,Teutsch SM,Schaffer PA,Dun˜et DO.Preventioneffectiveness:A guide to decision analysis and economic evalua-tion.New York:Oxford University Press,1996.24.Curran JW.Economic consequences of pelvic inflammatorydisease in the United States.Am J Obstet Gynecol1980;138:848–51.25.Van Voorhis BJ.Cost of therapy,infertility treatment:What is acost-effective approach?Drug Benefit Trends July1998:22–9. 26.Scholes D,Stergachis A,Heidrich FE,Andrilla H,Holmes KK,Stamm WE.Prevention of pelvic inflammatory disease by screen-ing for cervical chlamydial infection.N Engl J Med1996;334: 1362–6.VOL.95,NO.3,MARCH2000Rein et al Pelvic Inflammatory Disease401Address reprint requests to:David B.Rein,MPADivision of STD PreventionCenters for Disease Control and Prevention 1600Clifton Road,Mail Stop E-44 Atlanta,GA30333E-mail:dhr7@Received May21,1999.Received in revised form August17,1999.Accepted August27,1999.Copyright©2000by The American College of Obstetricians and Gynecologists.Published by Elsevier Science Inc.402Rein et al Pelvic Inflammatory Disease Obstetrics&Gynecology。