A REVIEW OF DIABETES COST OF ILLNESS STUDIES

Transcription

1 A REVIEW OF DIABETES COST OF ILLNESS STUDIES George Szava-Kovats 2, Jeffrey A. Johnson 1,2 Workng Paper Faculty of Pharmacy and Pharmaceutcal Scences, Unversty of Alberta, Edmonton, Canada Insttute of Pharmaco-Economcs, Edmonton, Canada

2 ACKNOWLEDGEMENTS Ths research was funded by the Insttute of Pharmaco-Economcs.

3 TABLE OF CONTENTS LIST OF TABLES... ABSTRACT..1 INTRODUCTION Types of Dabetes.. 3 Epdemology of Dabetes..5 THE MAJOR COMPLICATIONS ASSOCIATED WITH DIABETES Acute Metabolc Complcatons....8 Cardovascular Dsease.. 9 Other Macrovascular Dsease Dabetc Nephropathy Dabetc Retnopathy Neuropathy METHODOLOGICAL ISSUES.. 15 Overvew of Cost-of-Illness Methodology...15 Dabetes COI Study Desgns Specfc Issues for Dabetes COI Studes Alternatve Forms of Cost Study.. 24 Purposes of Cost-of-Illness Studes PREVIOUS DIABETES COST OF ILLNESS STUDIES Canadan Studes U.S. Studes Other Internatonal Studes Dscusson of Studes.. 36 CONCLUSIONS REFERENCES

4 LIST OF TABLES TABLE 1: 44 Rsk of hosptalzaton: Dabetc versus non-dabetc patents (age < 45 years) TABLE 2: 44 Rsk of hosptalzaton: Dabetc versus non-dabetc patents ( all ages) TABLE 3:. 45 Estmated Prevalence of Dagnosed NIDDM n the U.S., TABLE 4:..45 Estmated Prevalence of Dagnosed and Undagnosed Dabetes n the U.S.,

5 ABSTRACT Ths paper revews cost-of-llness studes for dabetes melltus (DM) over the last decade. Whle the cost estmates themselves dffer across studes, the one common result s that dabetes and ts complcatons have a sgnfcant publc health mpact world-wde. Results from the U.S. ndcate that 4-5% of the populaton has been dagnosed wth DM, whle a further 5% have the dsease, but reman undagnosed. There s consderable morbdty as well as mortalty assocated wth the complcatons of DM whch results n a large health care burden beng attrbutable to the dsease. The problems of attrbutng costs to dabetes are dscussed n lght of the multfaceted and chronc nature of the dsease. Notable s the lack of any comprehensve study of the costs of ether nsuln-dependent dabetes melltus (IDDM) or non-nsuln dependent dabetes melltus (NIDDM) for Canada durng ths perod. In order to reduce the publc health mpact of dabetes n Canada, t s argued that a cost-of-llness study of dabetes be undertaken as a necessary frst step n quantfyng the burden of the dsease.

6 INTRODUCTION Dabetes melltus (DM) s a chronc dsease wth major long-term mplcatons, not only for the health and well-beng of affected ndvduals, but also for costs to Canadan socety as a whole. There have been numerous attempts to quantfy the costs of dabetes usng a cost-of-llness (COI) methodologcal framework n other jursdctons, but no comprehensve study has yet been carred out for Canada and provnces. As a chronc metabolc dsorder, dabetes melltus can affect all of the body s major organ systems. These effects lead to complcatons whch consttute a sgnfcant burden of the dsease. Consder the followng statstcs from the Natonal Insttute of Health n the US. For example, cardovascular dsease s 2 to 4 tmes more common n people wth dabetes; cardovascular dsease s also present n 75 percent of dabetes-related deaths. The rsk of stroke s 2.5 tmes hgher n people wth dabetes. Hgh blood pressure affects 60 to 65 percent of people wth dabetes. Dabetes s the leadng cause of new cases of blndness among adults 20 to 74 years of age. From 12,000 to 24,000 new cases of blndness per year are caused by dabetc retnopathy. Dabetes s the leadng cause of end-stage renal dsease (treatable by dalyss or transplantaton), accountng for 36 percent of new cases. There were 19,790 new cases n the US n 1992 n people wth dabetes. There were 56,059 people wth dabetes who were undergong dalyss or transplantaton treatment n Nerve dsease s also assocated wth dabetes as up to 50 percent of people wth dabetes have mld to severe forms of dabetc nerve damage (wth such manfestatons as mpared sensaton n the feet or hands, delayed stomach emptyng, carpal tunnel syndrome, perpheral neuropathy). Severe forms of dabetc nerve dsease are a major contrbutng cause of lower extremty amputatons. More than half of lower lmb amputatons n the Unted States occur among people wth dabetes; from 1989 to 1992, the average number of amputatons performed each year among people wth dabetes was 54,000. These complcatons are not only a source of substantal morbdty related costs and sufferng, but can also lead to premature mortalty: n terms of U.S. premature mortalty based on death certfcate data, dabetes contrbuted to the deaths of more than 169,000 persons n It s well known that death certfcate data underrepresent dabetes deaths. Dabetes was the seventh leadng cause of death lsted on U.S. death

7 certfcates n 1993, accordng to the Natonal Center for Health Statstcs. It s the sxth leadng cause of death by dsease. The excess morbdty and mortalty assocated wth dabetes makes t a costly dsease: t was estmated that people wth dagnosed dabetes made up 4.48% of the U.S. populaton, yet accounted for 14.6% of U.S. health care expendtures n 1984 (Rubn et al., 1992). Another U.S. study whch ncluded both drect health care expendtures and ndrect costs due to dsablty and premature death estmated the dsease to represent $91.8 bllon n drect and ndrect costs n 1992 (Fox-Ray et al., 1993). Smlar expendtures have been noted n the U.K. where t s estmated that the 1-2% of the populaton has dagnosed dabetes whereas treatment of the dsease and ts complcatons takes up 4-5% of total health care expendtures (Leese, 1992). The am of ths paper s to brng together recent studes whch have been carred out on the costs of dabetes n an attempt to show what methodologes have been used and what results have been obtaned. In the next secton, we revew the complcatons of dabetes whch consttute much of the damage done by the dsease. The cost-of-llness methodology used by prevous studes s then revewed. Ths s followed by cost estmates from Canadan, U.S. and other studes from outsde North Amerca. A fnal secton offers conclusons. Types of Dabetes Dabetes melltus comprses a set of heterogeneous dseases whch dffer n ther etologcal, clncal, and epdemologcal characterstcs. It can be classfed nto fve major categores: nsuln-dependent dabetes melltus (IDDM), nonnsuln-dependent dabetes melltus (NIDDM), mpared glucose tolerance, gestatonal dabetes melltus and undagnosed dabetes melltus. IDDM or type I dabetes s characterzed by a lack of endogenous nsuln producton and typcally manfests n the early teen years. The lack of nsuln leads to excessve levels of glucose n the body, whch requres strct detary control and njectons of nsuln to control. Although the wdespread percepton s that the dsease s curable wth nsuln, ths s far from true. Complcatons resultng from dabetes melltus are among the leadng causes of blndness, renal falure, cardovascular dsease and

8 lmb amputatons. About 10% of all people dagnosed wth dabetes have the type I varety. The cause of the dsease s not yet fully understood, but t arses from a varety of genetc and envronmental factors. NIDDM or type II dabetes s characterzed by mpared nsuln secreton and mpared senstvty to nsuln. It usually develops after the age of 35, often n obese patents. Obesty s assocated wth nsuln resstance (decreased bndng of nsuln to cell membranes accompaned by decreased numbers of receptors). There may also be dysfuncton of the ntracytoplasmc effectors of the nsuln-receptor message (e.g. the actvaton of glucose transporters) (Rodger, 1991). The dsease s nsdous, n that the patent may reman asymptotc for years whle the above mentoned complcatons develop. Approxmately 90% of all dagnosed cases of dabetes fall nto the type II classfcaton. Snce the dsease s chronc, much of the damage s attrbuted to these complcatons whch develop over tme. Unlke IDDM whose ncdence peaks n puberty, the ncdence of NIDDM rses wth age after puberty. There are several stages n the dsease whch begns wth a genetc susceptblty to the dsease, followed by hypernsulnema and/or nsuln resstance, and progresses to mpared glucose tolerance and overt NIDDM. Thus, IDDM and NIDDM dffer n a varety of ways. From a clncal perspectve, ketoss s common n IDDM, the patents wth IDDM are rarely obese, and the onset of the dsease s relatvely acute. Patents wth NIDDM rarely present wth ketoss, are generally obese, and the dsease onset s nsdous. The dseases are also dstngushed by ther epdemology: the age of onset for IDDM peaks n puberty, unlke NIDDM. However, t should be noted that age of onset alone s not a sutable crtera for dstngushng the two forms of the dsease: t s possble for IDDM to occur late n lfe, whch s known as Maturty Onset Dabetes of the Young (MODY). Also t s possble for NIDDM to develop as early as the teenage years. Gestatonal dabetes melltus (GDM) occurs n two to four percent of pregnant women n the second or thrd trmester. It s usually a transent condton wth mld symptoms whch usually dsappear after delvery; however, specal montorng of these pregnances s suggested. Women wth a hstory of GDM have a hgher rsk of developng NIDDM later n lfe.

9 People wth mpared glucose tolerance (IGT) have hyperglycema but not as severe as those who are dagnosed wth overt dabetes. IGT has not been assocated wth the mcrovascular complcatons of DM, but IGT s assocated wth other rsk factors such as hypertenson, decreased hgh-densty lpoproten levels and ncreased plasma trglycerdes that wll ncrease the chances of developng both coronary heart dsease and overt (NIDDM) dabetes. The people who can be classfed as havng undagnosed dabetes wll generally have NIDDM rather than IDDM (as the acute symptoms of IDDM make t unlkely that t wll reman undagnosed). The numbers who reman undagnosed are dsturbngly large, as t s estmated that there are about as many undagnosed cases of DM as there are dagnosed cases (Harrs et al., 1987). These people wll not therefore not receve the treatment that may prevent or retard the onset of complcatons. Epdemology of Dabetes It s clear from the above dscusson that the varous types of dabetes wll have dfferent epdemologcal profles. IDDM s characterzed as largely a endocrne-metabolc dsease of chldhood wth an prevalence n the age group 0-15 years of between 0.05 to 0.3% n most European and North Amercan populaton (Rewers and Norrs, 1991). Ths prevalence rate s affected by both the ncdence (rate at whch new cases of the dsease appear n the populaton) and by the duraton and case survval rate of these new patents. There s great geographcal varablty n the ncdence of IDDM. For example, the hghest rate n the world s n Fnland wth an ncdence of 35 per 100,000 chldren under 15 years. Ths rate s about 30%-40% hgher than n other Scandnavan countres, 2- to 4- tmes as hgh as n the rest of Europe and North Amerca, 8 tmes as hgh as Russa and 40 tmes as hgh as n Japan, Korea, and manland Chna (Rewers and Norrs, 1991). There s also some ethnc/racal varablty n the ncdence of IDDM: In Montreal, Canada, chldren of Englsh background were about one and a half tmes as lkely to get IDDM as chldren of French background (Sematyck et al., 1989). The dstrbuton of IDDM onset by age s smlar across geographc and ethnc/racal categores wth the ncdence of the dsease declnng after adolescence. The ncdence of the dsease shows much varablty over tme. Most populaton based regstres show an ncreasng ncdence of IDDM over tme wth observed perodc outbreaks (Rewers et al, 1987; Bngley and Gale, 1989; Nystrom et al., 1990;

10 Tuomlehto et al., 1991, Green et al., 1996). New treatment methods for IDDM may reduce the rsk of complcatons and mortalty, thus ncreasng the prevalence of the dsease (Leese, 1995). The prevalence of dagnosed NIDDM n the U.S. n the years has been estmated usng the Natonal Health Intervew Survey (Harrs et al., 1987). From Table 1, one can see that the rsk of dagnosed NIDDM ncreases wth age wth a rate of 10% of the populaton after the age of 65. Snce these numbers only consder dagnosed cases of NIDDM, they are lkely an under-estmate of the true prevalence; Amercan data from the Natonal Health and Nutrton Examnaton Survey (NHNES) suggest that the ncdence of dagnosed DM, non-dagnosed DM, and IGT all rse wth age (see Table 2). In addton, the numbers of non-dagnosed DM and IGT as verfed by laboratory testng are substantally larger than the proporton estmated usng only dagnosed cases. Other than age (especally after 65), other rsk factors for developng NIDDM nclude a famly hstory of NIDDM, a body weght greater than 130% of the deal body weght, hypertenson and/or dyslpdema, race (Afrcan, Natve-Amercans and Hspancs are at greater rsk), and a hstory of IGT. Unfortunately, comprehensve prevalence estmates such as those provded by NHNES n the US are unavalable n Canada. The studes whch have been based on physcan dagnosed cases of dabetes n Canada have generally been have been lmted to small, regonally dstnct populatons; A prevalence rate of 1.53% was estmated for Prnce Edward Island (Tan et al., 1981), whle a later study estmated a prevalence rate of 3.55% n Newfoundland and Labrador (Worrell et al., 1991). Other studes have used regstres, but these are generally lmted to small numbers of IDDM patents (West et al., 1981). Snce natve Amercans are at hgher rsk of NIDDM than Caucasans, a number of studes have focused on aborgnal groups n Ontaro and Mantoba (Young et al., 1985; Evers et al., 1987). Gven the dstnct populatons nvolved, t s dffcult to generalze the results of these lmted studes to estmate dsease prevalence n the general populaton. Another approach s to use are Canadan health-related surveys such as the General Socal Survey (Statstcs Canada, 1991) and the Natonal Populaton Health Survey (Natonal Health and Welfare Canada, 1994) whch both nclude questons regardng dagnosed dabetes. Table 3 gves some prevalence estmates usng the 1991 publc use fles. The results are relatvely consstent wth US

11 estmates, but the sample szes are small, therefore the estmates are not relable. These surveys are also lmted by respondent recall, self-reportng and a lack of medcal record valdaton. Estmaton of the prevalence of dabetes usng the admnstratve health nsurance database n Mantoba has recently been reported (Blanchard, et al., 1996). Dagnostc data from a populatonbased database are used to dentfy ndvduals wth dagnosed dabetes; the estmated prevalence rates for 1986 and 1991 are shown n table 4 wth the overall prevalence rate n Mantoba n 1991 estmated at 6.6% of adults over the age of 25. These agan are smlar to the US prevalence rates for reported dabetes. Of course, to the extant that they do not nclude unreported dabetes, they wll underestmate the true prevalence. Also, they wll underreport IDDM as both surveys and admnstratve databases do not always track those ndvduals under 25 years of age. It s expected that n the future the prevalence and ncdence of NIDDM wll lkely ncrease. Ths s due n part to the agng populaton structure; n the US, the prevalence of dabetes ncreases to 90.5 per 1,000 for those over 65, compared to 54.1 for those between 45 and 64 (Harrs et al., 1987). As well, the long-term complcatons of the dsease are becomng more common as the average age of the populaton ncreases. THE MAJOR COMPLICATIONS ASSOCIATED WITH DIABETES One of the characterstcs of dabetes melltus s that t s assocated wth a large number of other dseases. Ths s relevant to developng cost of llness estmates snce a frst step n the analyss s to dentfy the tangble consequences attrbutable to dabetes; n ths case t s a wde varety of other dseases. The man complcatons of dabetes, whch account for sgnfcant health care costs are ketoacdoss; cardovascular dsease and other macrovascular dsease; renal dsease; vsual problems; and neuropathy. The effects of the complcatons of dabetes can also be seen n terms of hosptalzaton rates for the major complcatons areas of dabetes gven n Tables 1 and 2 (Harrs et al., 1987). The younger dabetc cohort (< 44 years) s 39.8 tmes more lkely to spend tme n hosptal due to ophthalmc complcatons than ther non-dabetc counterparts. The same apples to the other major areas of

12 complcatons. Nor s the problem restrcted to the younger age categores: the longer one has dabetes, the more lkely complcatons are to occur. As the populaton ages, the rates of hosptalzatons rse for the non-dabetcs, but the relatve rsks reman relatvely hgher. Acute Metabolc Complcatons The acute metabolc complcatons of dabetes consst of dabetc ketoacdoss (DKA), hyperosmolar non-ketotc coma (HNC), lactc acdoss (LA), and hypoglycema. DKA and HNC are related to nsuln defcency and subsequent hyperglycema, whle hypoglycema results from the treatment of dabetes, wth oral agents and/or nsuln. DKA s largely a complcaton of IDDM, although t also rarely occurs n NIDDM patents under acute stress; about 20 percent of IDDM cases ntally present wth DKA (Fach et al., 1983). It s a farly common complcaton wth an estmated ncdence of 4.6 per 1,000 dabetc persons per year (Fach et al., 1983). In establshed dabetcs, t can be brought on by poor glycemc control (as a result of poor self-care, lack of dabetes educaton, or non-complance) or varous nfectons or other llnesses. DKA often usually requres hosptalzaton and contnuous medcal care to deal wth the acd-base and electrolyte dsturbances, hence t results n the use of sgnfcant health care resources. In the US n 1988 there were 84,000 hosptal dscharges and 1905 deaths n the US n whch DKA was the prmary dagnoss (Fox-Ray et al., 1992). The mortalty rate of a DKA epsode s estmated at 9 percent (Fach et al., 1983). Far less common s NHC, n whch suffcent nsuln s present to prevent ketoss; t s generally found n older NIDDM patents and comprses about 0.37 percent of all hosptalzatons drectly related to dabetes (Fach et al., 1983). Hosptalzaton s generally short as the patents usually respond well to hydraton and small doses of nsuln n the absence of other medcal problems. LA conssts of elevated lactc acd and can present together wth DKA. It s rare n dabetc patents n North Amerca snce the wthdrawal of phenformn from the market. Myocardal nfracton wth hypoxa s often a precptatng event for LA, whch although rare n dabetc patents, has a hgh mortalty rate. Hypoglycema, on the other hand, s farly common: Mld hypoglycema n chldren n England has been reported at a medan value of 1 epsode every 2 months (Leese, 1992). These epsodes can be

13 managed at home, but may requre the parent to be absent from work. Although t also occurs n NIDDM patents beng treated wth sulfonylurea therapy, hypoglycema remans the most common acute complcaton of IDDM. Severe hypoglycema occurs n up to 80% of adolescents and adults wth IDDM wth an ncdence rate that has been estmated from 40 to 650 epsodes per 1000 patent-years (Leese, 1992). There s evdence from the Dabetes Control and Complcatons Tral (DCCT) that ntensve management of dabetes can reduce the development and slow the progresson of mcrovascular and neurologcal complcatons over conventonal therapy, but at the same tme ntensve treatment has been shown to yeld a three-fold ncrease n severe hypoglycema, defned as requrng assstance of another person to recover (DCCT Research Group, 1993). Cardovascular Dsease The most mportant complcaton of dabetes n terms of mortalty, s cardovascular dsease (CVD). Dabetes ncreases the rsk of varous forms of cardovascular dsease and the two dseases are ntmately related. In the U.S., n 1992, a patent wth dabetes was 3 tmes more lkely to experence a hosptalzaton for a heart related cardovascular complcaton than one wthout dabetes; of all deaths durng 1992 lstng dabetes as a contrbutng cause of death, more than half were due to cardovascular complcatons (Fox-Ray, 1992). Of these cardovascular deaths, about 75% were due to coronary heart dsease (CHD), whle the remanng 25% were the result of accelerated cerebral vascular dsease or perpheral vascular dsease. The probablty of cardovascular complcatons are even greater for women wth dabetes who have a fve tmes greater rsk of developng coronary artery dsease than women wthout dabetes; women wth dabetes also face a three-fold rsk of myocardal nfarcton (MI) compared to non-dabetc women (Kannel, 1985). The NIDDM varety of the dsease s commonly assocated wth obesty and hypertenson whch consttute other rsk factors for cardovascular dsease. The lnk between obesty and type II dabetes s very strong. Among the populaton of people wth dagnosed type II dabetes (approxmately 7.5 mllon), 80 percent are obese (at least 20 percent above ther deal weght). Some researchers have underlned the prmary role of nsuln resstance lnked to obesty n cardovascular morbdty and mortalty; t has been found that obese NIDDM patents dffer from non-obese patents n hypertenson and the use of hypotensve drugs (Pontor et al., 1995). Not only s obesty assocated wth nsuln resstance, but sedentary behavour by tself leads to reduced

14 nsuln acton on muscle. In addton, NIDDM s assocated wth a varety of lpd abnormaltes: ncreased serum trglycerde, slghtly elevated total cholesterol, decreased hgh-densty lpoproten cholesterol, and an ncrease n VLDL-chol (Galloway, 1990). Although a relatonshp between hyperglycema and atheroscleross has not been establshed on the bass of avalable data, some mechansms have been descrbed whch could provde a postve relatonshp; as well, mprovements n the blood lpd profles of non-dabetc populatons have been assocated wth a decrease n cardovascular mortalty (Galloway, 1990). Hypertenson also often accompanes dabetes and s lnked to obesty, hgh cholesterol levels, elevated trglycerdes, a lack of physcal actvty, a famly hstory of hypertenson and coronary heart dsease (CHD), left ventrcular hypertrophy and smokng. In addton, hypertenson exacerbates such complcatons as retnopathy and nephropathy. Hypertenson assocated wth dabetes ncreases the rsk for cardovascular, cerebrovascular and perpheral vascular dsease. In Type 1 dabetes, hypertenson may also suggest kdney dsease. The factors contrbutng to ths hypertenson are all nteractve. A syndrome of nsuln resstance has been descrbed that conssts of varous degrees of glucose ntolerance, dyslpdema (prmarly ncreased trglycerdes and low HDL), hypertenson and obesty. Insuln resstance s the common pathogenc mechansm n ths cascade, whch greatly ncreases the rsk for CHD.

15 Other Macrovascular Dsease One of the other man macrovascular complcatons s perpheral vascular dsease (PAD) whch can lead to nfecton, gangrene and eventual amputaton. The amputaton rate n patents wth dabetes ncreases wth age (Humphery, et al., 1989) and s between 5 and 15 tmes more common n dabetc patents than n non-dabetc patents (Most and Snnock, 1983; Bld et al., 1989). It can strke ether patents wth IDDM or NIDDM, but s 1.7 tmes more common for IDDM as compared to NIDDM patents (Reber, 1993). The average drect costs for healng wth amputaton n a dabetc patent wth foot ulcers were $US 48,100 (range: $US 3780 to $US 138,700) n a Swedsh study (Apelqvst et al., 1994). From 1989 to 1992, the average number of amputatons performed each year among people wth dabetes n the US was 54,000 (Natonal Insttute of Health, 1994). Not only does PAD often severely affect the qualty of lfe of the patent and contrbute to the morbdty related costs, but t s also strongly assocated wth premature mortalty. The overall mortalty rate n patents wth perpheral and coronary artery dsease s 20-30% after 5 years, 40-72% after 10 years and 74% after 15 years (Spttell and Spttel, 1993). There s also a 15-fold ncrease n mortalty due to cardovascular dsease and coronary heart dsease among subjects wth large vessel PAD; the mortalty of patents wth PAD over a 10-year perod was 62% for men and 33% for women compared wth 17% of men and 11.6% of women wthout PAD (Crqu, et al., 1992). Dabetc Nephropathy Although t takes years of lvng wth dabetes to develop severe kdney problems, a sgnfcant fracton of patents wth dabetes wll have a lfe-threatenng encounter wth renal dsease. Duraton of IDDM s a sgnfcant rsk factor; for IDDM patents who have had the dsease for years, 30%- 40% wll eventually develop end stage renal dsease (ESRD) (Anderson et al., 1983). Another rsk factor for those wth IDDM s poor glycemc control as demonstrated by the Dabetes Control and Complcatons Tral (DCCT Research Group, 1993). The prevalence of ESRD among those wth NIDDM s much lower, at 5-10% (Fabre, et al., 1982), but snce the numbers of those wth NIDDM s so much larger than those wth IDDM, roughly equal numbers of patents wth IDDM and NIDDM are develop ESRD each year. The rsk of developng ESRD for those wth NIDDM appears to vary across

16 racal grounds and s hghest among Afrcan Amercan, Hspancs, and Amercan Indans at about 15-20% (Rostand, et al., 1982; Pugh et al., 1987). It also appears, at least from studes of Pma Indans wth NIDDM, that the course of the renal dsease process for NIDDM patents s smlar to patents wth IDDM (Kamenetzkcy, et al., 1974). In the U.S., roughly one out of every three people enterng kdney dalyss have dabetes (Makell and Fredman, 1992). The mortalty from ths complcaton s great: the rsk of death from renal dsease for IDDM patents s 23 tmes greater than for people wthout dabetes (Gess et al., 1985). There s also evdence that dabetc nephropathy s assocated wth hypertenson, as well as dabetc retnopathy and neuropathy (Parvng et al., 1988). In patents wth IDDM, hypertenson can be seen n most of the 40% who develop nephropathy, but s no more frequent n those wthout nephropathy than n the non-dabetc populaton (Norgaard et al., 1990). The costs of renal dsease are hgh and there s evdence that the costs are hgher for patents wth dabetes than those wthout dabetes: n one study, U. S. haemodalyss patents wth IDDM had 37% more days of hosptalzaton per year on average than patents wthout IDDM (Narns and Narns, 1988). In an Israel study of patents wth IDDM, t was found that half of all the drect costs of complcatons of the dsease were due to dabetc nephropathy (Stern and Levy, 1994). Dabetc Retnopathy Dabetes s an mportant cause of mpared vson. It s estmated to account for 5000 new cases of blndness n the US each year (Moss, et al., 1988). Blndness s 29 tmes more common n dabetc than n non-dabetc patents (Klen et al., 1984). There are several vsual problems whch are much more prevalent n patents wth dabetes: dabetc retnopathy, macular edema, glaucoma, and cataracts. Retnopathy, a dsease of the retna, the lght sensng tssue at the back of the eye, s a common concern among people wth dabetes. Dabetc retnopathy damages the tny vessels that supply the retna wth blood. The blood vessels may swell and leak flud. When retnopathy s more severe, new blood vessels may grow from the back of the eye and bleed nto the clear gel that flls the eye, the vtreous. Ths s called prolferatve dabetc retnopathy (PDR). In some cases, patents may be unaware of retnopathy untl they suffer sudden sgnfcant vson loss. Blurred vson may occur when the macula - the part of the retna that provdes sharp, central vson - swells from the leakng flud. Ths condton s

17 called macular edema. If new vessels have grown on the surface of the retna, they can bleed nto the eye, blockng vson. Cataracts nvolve a osmotc swellng of the eye lens whch clouds vson. Glaucoma s a dsease n whch there s loss of vson from damage to the optc nerve fbers due to elevatons n ntraocular pressure. Almost all people wth dabetes wll experence some form of retnopathy; however, only 40 to 50 percent wll progress to prolferatve dabetc retnopathy (PDR). The prevalence of retnopathy ncreases wth age, and more than 97 percent of all people wth dabetes who suffer from total blndness caused by retnopathy are over the age of 50. Retnopathy s present both n patents wth IDDM and those wth NIDDM. It s strongly assocated wth ncreasng duraton of the dsease; for IDDM patents, 3 to 4 years after dagnoss the prevalence of retnopathy was about 20%, after 20 years, 99% had some degree of retnopathy (Klen et al., 1984). In terms of an older-onset group (mostly NIDDM) of patents, 23% had retnopathy 3 years after dagnoss and after 20 years of dabetes, 60% of the group had retnopathy (Klen et al., 1984). The prevalence rate for glaucoma are also much hgher for patents wth dabetes for every age group compared wth the general populaton (Ederer, 1981). In the case of IDDM, the Dabetes Control and Complcatons Tral showed that ntensve glycemc control was assocated wth a reduced rsk of ncdence and progresson of retnopathy and reduced ncdence of macular edema. Another rsk factor assocated wth retnopathy s hypertenson; treatment of hypertenson could also lead to reduced ncdence of vsual mparment (Klen et al., 1984). Intensve nsuln and blood glucose therapy of patents wth IDDM delays the onset and slows the progresson of clncally mportant retnopathy ncludng vson-threatenng lesons, as well as nephropathy and neuropathy by a range of 35 to more than 70 percent. Optmal glycemc and blood pressure control n patents wth dabetes may also delay the onset and progresson of retnopathy. If retnopathy s dscovered before symptoms occur, vsual loss can be slowed, f not stopped completely, by laser photocoagulaton. Although these treatments consume health care resources, the costs of blndness are hgh; the US federal expendture per blnd patent wth dabetes under the age of 65 was $US 14,296 n 1990 (Javtt et al., 1994).

18 Neuropathy Nerve dsease caused by dabetes s called dabetc neuropathy. There are three types of nerve dsease: perpheral, autonomc, and mononeuropathy. Perpheral neuropathy affects the hands, feet, legs, toes, or fngers. A person's feet, legs, and fngertps may lose feelng, burn, or become panful. People wth dabetes are partcularly prone to foot problems that can result n dsablty, prolonged hosptalzaton and even mortalty. In patents wth neuropathy (whch dmnshes sensaton leadng to unawareness of njury or pan) or macrovascular damage, a mnor bruse or cut, large calluses or mproper toenal cuttng can lead to skn ulcers, nfectons, gangrene or even amputaton. Another type of nerve dsease that may occur after several years of dabetes s called autonomc neuropathy. Autonomc neuropathy affects the nternal organs such as the heart, stomach, sexual organs, and urnary tract. It can cause dgestve problems and lead to ncontnence (a loss of ablty to control urne or bowel movements), and sexual mpotence. Mononeuropathy s a form of nerve dsease that affects specfc nerves, most often n the torso, leg, or head. Mononeuropathy may cause pan n the lower back, chest, abdomen, or n the front of one thgh. Sometmes, ths nerve dsease can cause achng n the eye, an nablty to focus the eye, or double vson. Mononeuropathy may also cause facal paralyss, Bell's palsy, or problems wth hearng. The prevalence of neuropathy among dabetc patents s uncertan. Ths s partly due to the varety of dfferent crtera whch are used to dagnose neuropathy. Despte ths uncertanty, t appears that the prevalence of neuropathy s dependent prmarly on the duraton and severty of hyperglycema n both IDDM and NIDDM. In the case of IDDM, t usually does not appear untl fve years after the onset of the dsease and t ultmately affects up to 50% of all patents wth dabetes. METHODOLOGICAL ISSUES The purpose of ths secton s to dscuss the general approach to, and certan major analytcal ssues n performng dabetes cost-of-llness (COI) studes. These COI studes (also known as burden-ofllness studes) attempt to quantfy the consequences of a partcular dsease n monetary terms. The objectve of the frst subsecton s explan what such studes attempt to communcate and why they are

19 structured n the way they are. Some of the lmtatons of the cost-of-llness approach are then outlned. Specfc techncal ssues related to applyng the cost-of-llness framework to dabetes are then addressed. Overvew of Cost-of-Illness Methodology Superfcally a COI study nvolves combnng an epdemologcal database wth fnancal data to generate a monetary amount whch descrbes the costs of a partcular dsease. The central cost concept n neo-classcal economcs s "opportunty cost," and COI studes generally work wthn ths methodologcal framework. Opportunty cost s the market value of resources that are redrected away from uses to whch they would have otherwse been put. The opportunty cost concept n health studes has been refned over numerous studes performed snce the 1950's. The general approach to ths cost methodology n the US was standardzed by a Task Force of the U.S. Publc Health Servce (Rce, 1966; Hodgson and Meners, 1979;. Hodgson and Meners, 1982; Rce et al., 1985) These gudelnes were ntended to reduce methodologcal dfferences between cost-of-llness studes performed for dfferent llnesses, or for studes of the same llnesses performed by dfferent research teams. Although these gudelnes dd not explctly contemplate the methodologcal challenges posed by constructng COI estmates for dabetes, the prncples are general n nature, and have been found to be applcable to the dabetes COI studes performed snce ths tme. The prmary cost categores n COI studes are drect costs and "ndrect" costs. The drect costs for an llness are represented by the value of tangble goods and servces actually delvered to address consequences of that llness. Indrect costs are represented by the value of productve servces that are not performed due to the consequences of the llness. A further dstncton s usually made n dabetes COI studes between costs prmarly wthn a prmary area of dagnoss ( drectly attrbutable consequences ) and costs outsde of the prmary area of dagnoss, but related to the dsease n queston ( costs of complcatons or comorbdty costs ). The conventonal approach s to estmate drect costs on the bass of market prces (e.g. the charge per day of hosptal care or, on an aggregate bass, hosptal expendtures for the year) and to measure ndrect costs by estmatng the loss of productvty

20 due to morbdty and premature mortalty valued n terms of lost output or earnngs. Average prce/cost data s usually used for health care servces such as a day of hosptal care, or a vst to a physcan. There s general consstency across the nternatonal and US studes n terms of the types of costs of dabetes that have been dentfed, although n practce data and other constrants do not allow all of these consequences to be measured and ncluded. In partcular, ntangbles such as pan and sufferng and other qualty of lfe aspects of the dsease are not usually ncluded. A general set of categores s presented n Table 3. There have been a varety of dabetes COI studes n the last 10 years. Some of these are natonal n scope, whle others are lmted to selected populatons or geographc areas. Data sources and methods vary among these studes, and many lmt ther nvestgaton to only one or several of the drect and ndrect economc costs outlned above. The scope of a cost-of-dabetes study can legtmately vary from that of very comprehensve studes whch attempt to estmate as completely as possble all costs assocated wth varous types of dabetes for a naton to a study of only one type of cost for a specfc type of dabetes n a lmted geographc area or among a subset of the populaton. The data needed and avalable wll, of course, vary wth the scope of the study, and nether the comprehensve nor the lmted study wll always have the advantage. Most of the cost of dabetes studes have been conducted n the US, n large part due to ts extensve system of health-related utlzaton and expendture survey databases. Comprehensve studes generally make use of natonal surveys whch provde relable data on health care utlzaton such as the US Natonal Hosptal Dscharge Survey, Natonal Nursng Home Survey, Natonal Ambulatory Care Survey, Natonal Medcal Expendture Survey, and the Natonal Health Intervew Survey. There are also health surveys that nclude medcal verfcaton such as the NHNES.

21 Dabetes COI Study Desgns Songer (1992) has classfed dabetes COI studes nto the followng three desgn categores dependng on whether ther underlyng data source s aggregate data, prevous studes, or ndvdually based data. Aggregate Estmates from General Populaton Data The majorty of the economc cost data n dabetes have been based on natonal health, health care, dsablty and mortalty statstcs. Natonal statstcs are often broken down by dagnostc categores based on the Internatonal Classfcaton of Dseases (ICD) codes. The dagnostc data desgn has been wdely used to estmate the costs of dabetes because the data have been easly avalable and t s a relatvely nexpensve study to conduct. It s mportant not to restrct the costs to only those categores where dabetes s the prmary dagnoss as ths wll underestmate the true cost; the costs where dabetes s a secondary or tertary factor wll be lost. The crtcal pont s that often ndvduals wth complcatons assocated wth dabetes do not have dabetes lsted as the prmary dagnoss upon hosptalzaton or as the underlyng cause of death; some account should be taken of the costs ncurred by these ndvduals. Furthermore, as chronc dseases such as heart dsease occur frequently n the general populaton, analyses usng control groups of non-dabetc ndvduals are needed to separate the excess morbdty costs related to dabetes from those costs that would be expected to occur normally. Another lmtaton of ths desgn s that costs related to IDDM or NIDDM may not be estmated accurately. The ICD dagnostc category for dabetes consders only the general defnton for dabetes: subgroups of dabetes such as IDDM and NIDDM are not entrely dstngushable n dagnostc category data. In addton, t s not possble to determne the economc mpact of dabetes from the perspectve ndvdual who has dabetes or the famly. An ncreasng use s made of admnstratve databases. These often use data provded by HMOs n the US, but another possblty whch s relevant to the Canadan context s the use of provncal admnstratve health databases. These could potentally be used to augment surveys whch are conducted at the natonal level, but whch do not provde much specfc expendture data. One of the dsadvantages of admnstratve databases s that they usually only nclude people over the age of 25,

22 thus the consequences assocated wth IDDM wll be underestmated. Another dsadvantage s that natve Indans lvng on reserves are generally excluded from these databases. The relatvely hgh ncdence and prevalence of dabetes among ths ethnc group consttutes a large publc health mpact. One way of overcomng these lmtatons s the use of regstres whch unfortunately are rare among the general populaton n Canada. In any case, these regstres are manly useful for costng IDDM, as there are few NIDDM regstres. Cost Projectons from Prevous Estmates Dabetes cost estmates have also been predcted from the results of prevous cost studes. In ths study desgn, cost estmates determned n a prevous study and changes n the health care utlzaton and mortalty rates assocated wth dabetes, as well as the change n prevalence and nflaton rates, were utlzed to forecast the economc costs of dabetes. The advantage of ths desgn s that t s even more easy and nexpensve to conduct. However, major lmtatons concernng the mplementaton of the data are present, because ths approach combnes the lmtatons of the prevous studes and those of ts own. The prmary constrant s that the cost estmates are based on the assumpton that the changes n the costs of dabetes wll be smlar to the changes n nflaton, utlzaton, prevalence and mortalty rates; ths may or may not be true.

23 Indvdual-based Estmates The costs of dabetes have also been estmated from the data of dabetc ndvduals dentfed from the general populaton, dabetes regstres, dabetc clncs, hosptals, practces, etc. Cost estmates derved from ths desgn have been determned from the survey data or reported experence of persons wth dabetes. Ths approach dffers from the frst desgn where costs were based upon dagnostc category data. The advantage of surveyng ndvduals s that more precse estmates of the costs of dabetes can be attaned, because ndvdual costs and utlzaton patterns are drectly observed, rather than estmated from aggregated categores whch mask the nfluence of subgroups and ndvduals. The dsadvantage of surveyng costs among a representatve sample of dabetc ndvduals s that t s an expensve and lengthy process to complete. Typcally, the survey based process begns by dentfyng the medcal costs of a small representatve sample of the general populaton. Indvduals wth dabetes are dentfed by ther medcal hstory, and expendtures for the entre dabetc populaton are estmated by multplyng the average costs for the ndvdual wth dabetes by the prevalence estmate for dabetes. These types of studes normally restrct themselves to health care costs only and usually do not consder ndrect costs.

24 Specfc Issues for Dabetes COI studes Vewpont The majorty of COI studes of dabetes take a socetal vewpont n costng the dsease. Thus, all resources whch are a consequence of dabetes are taken nto account, regardless of whether they are ncurred by the patent or by some other provder. Others take the perspectve of a publc or prvate payer of medcal servces to a dabetc populaton. In practce, however, the types of costs whch the study s able to capture s dependent on the data-sources avalable. An mportant lmtaton to these ponts of vew s that the qualty of lfe of the patent s typcally not taken nto account n most COI studes. Prevalence and Incdence-based Estmates Prevalence-based studes measure the costs n a gven year assocated wth the prevalence of dabetes. Such studes are more common because the methodology s relatvely smple and some of the data s usually avalable Incdence-based estmates, on the other hand, calculate the present day value of the lfetme costs assocated wth the current populaton cohort. To the best of our knowledge, there s no large longtudnal study of dabetcs whch has focused on costs. For a dsease such as dabetes whose costs are not commonly ncurred only over the year n queston, ncdence based studes are preferable as they provde more nformaton to the total future costs and benefts of usng resources to reduce the ncdence of dabetes n the current perod. However, no prospectve studes nor comprehensve longtudnal studes of the total long term costs of dabetes exst. Most studes take a prevalence-based cost-of-llness approach whch provde an estmate of the economc burden ncurred n a perod of tme. Included n these costs for the base year are manfestatons of the dsease that may have had ts onset n the base year or at some tme prevously. The costs of the alternatve ncdence-based are dffcult to estmate as they requre knowledge of the lkely outcome of a dsease and ts duraton, ncludng survval rates snce onset, medcal care utlzaton, and the cost of care for the duraton of the dsease, and the mpact of the dsease on employment, housekeepng, and earnngs.

25 IDDM vs. NIDDM Most studes do not make any attempt to dstngush between IDDM and NIDDM. Although the complcatons of the two dseases as hghlghted n the prevous secton are smlar over the long term, the prevalence and costs may be qute dfferent, as would the types of treatments that would lead to good control of the dsease. The tmng of costs of the two dseases are qute dfferent. Consderng IDDM frst, there are three phases of the dsease n terms of resource utlzaton and two cost peaks (Smmell et al., 1996). The frst s seen n the ntal treatment phase, whle the other s n the last stages of the dsease, when the late complcatons develop. Studes whch combne IDDM and NIDDM make t dffcult to study both of these cost peaks. Another reason for separatng out IDDM from NIDDM ndvduals s that the cost mplcatons of the same complcaton may be dfferent; a dsablty for a IDDM patent may lead to greater ndrect costs than for an NIDDM patent snce IDDM patents tend to have dabetes for a greater duraton and are younger when the complcatons strke (Songer, 1992). The man reason that studes do not dstngush between the two forms of the dsease s the lack of satsfactory data. Often the prmary data source wll classfy dseases accordng to the ICD-9 dsease classfcaton; the frst three dgts only specfy DM wthout elaboratng whch type of the dsease s present, whle the remanng two dgts whch specfy IDDM or NIDDM are not generally coded. There are two dfferent ways n whch to dfferentate between NIDDM and IDDM. In a small sample or a regstry, one can medcally verfy that the type of dsease s dentfed. The second method s to use epdemologcal technques such as those employed by Huse for the US. The prevalence of NIDDM was calculated usng the Natonal Health Intervew Survey. The queston on the survey does not specfy what type of dabetes, so the authors take 98% of these to be NIDDM for persons 45 years and older and 65% among persons younger than 65 years. Complcatons of Dabetes The crtcal methodologcal queston n estmatng the costs of dabetes s the extent to whch dabetes-related complcatons should be ncluded. Many studes are lmted by relyng on prncpal dagnoss to attrbute costs to dabetes, snce some costs legtmately vewed as related to the dsease

26 are excluded. In addton, some prevous studes have not fully accounted for the possblty that dabetcs may have hgher costs than non-dabetcs for treatment of the same dabetes-related dsease. Some of the consequences are n prncple straght-forward to quantfy: f a patent has an dentfed epsode n whch the prmary dagnoss s dabetes (e.g. dabetc ketoacdoss) then 100% of the health care resources whch are assocated wth the epsode should be attrbuted to dabetes. The attrbuton of health care resources to a partcular llness has tradtonally been based on the prmary dagnoss recorded on medcal documents, e.g., npatent hosptalzaton records. However, the use of ths methodology fals to nclude the health care utlzaton assocated wth the chronc complcatons of dabetes or the ncreased health-care resources needed to treat a dabetc patent for other comorbd llnesses. The more challengng stuaton s when dabetes s one of multple causes of partcular consequences, such as a myocardal nfarcton, glaucoma, or a stroke. The objectve s to develop an estmate of the proporton of the mult-cause consequence that can be attrbuted to dabetes. Furthermore, the evdence must be assembled that justfes the estmate(s) of how much of the resource utlzaton s caused by dabetes. The proporton of each of these causes of morbdty and mortalty whch can be attrbuted to dabetes must be estmated, deally for dfferent age and gender groups. Snce large-scale populaton based epdemologcal data are generally not avalable to establsh the relatve rsk of partcular dsorders, the attrbuted fractons of dabetes-related morbdty and mortalty can not be determned wth a large degree of confdence. Therefore, one s forced to estmate the attrbutable fractons from less relable sources, such as studes of the excess morbdty and mortalty among clncal or surveyed populatons. In practce, at one extreme, the costs of complcatons are totally gnored. For example, the cost of dabetes n the US n 1984 was estmated to be $14 bllon, wth drect medcal care costs ncurred as a result of dabetes rangng from $ bllon (Entmacher et al., 1984) but ths study excluded costs assocated wth complcatons of dabetes and costs ncurred when dabetes was the secondary or tertary dagnoss. Another approach s to nclude all costs ncurred by dabetc ndvduals regardless of whether they are related to dabetes or not. Of course, here one s overstatng costs by attrbutng other rsk factors to dabetes n consderng a partcular complcaton.

27 Most of the COI studes descrbed later attempt to take the mddle ground and try to capture all the costs of those complcatons whch are due to dabetes. These types of studes dffer prmarly n the avalablty of varous data sources. Indrect Costs Indrect costs nclude producton losses due to short-term llness, early retrement, and death before retrement. Some studes have not ncluded calculatons of these costs because of the dffcultes n choosng approprate monetary values. The most common approach s to use a human captal approach; typcally the number of lost producton days are multpled by average daly wages usually dsaggregated by age and sex. Much debate surrounds the valuaton of the ndrect costs of llness. There are two general methodologes used to estmate ndrect costs: the human captal approach and the wllngness to pay approach. In the human captal approach, ndvduals are regarded as producng output n ther lfetme that can be valued as equal to each ndvdual s earnngs durng that tme. Indrect expenses, then, are seen as the earnngs, present and future, lost to that ndvdual and hs or her employer as a result of the llness. The man crtcsm of the human captal approach s that t values lfe n terms of the earnngs of the ndvdual. Changes n lfe-style due to dsease are expressed by changes n the earnngs of the ndvdual. Thus, the human captal approach may economcally undervalue some segments of socety relatve to others because people are valued by ther baselne earnngs. Another ssue whch arses n calculatng ndrect costs s the dscount rate to use n dscountng future lost productvty. Dscountng s used when future costs are assgned to the current year. Ths has a sgnfcant effect on standard COI studes because the ndrect costs of premature mortalty (.e. future earnngs) nvolve dscountng. Snce no defntve dscount rate exsts, ths ssue can be dealt wth by usng senstvty analyss. Another ssue whch s related to the complcatons of dabetes s that dabetes s rarely mentoned on death certfcates as a prmary cause of death (cardovascular dsease s the leadng cause of death

28 among those wth dabetes), so the numbers of deaths drectly attrbutable to the dsease s not easy to quantfy. Alternatve Forms of Cost Study It would be ncorrect to suggest that the "cost-of-llness" study s the only type of cost study. Whle COI studes have been useful n polcy debates, they are probably less valuable n ths regard than "cost effectveness analyss" (CEA) and "cost beneft analyss" (CBA) studes. Whle t can be mantaned that the most fundamental of the economc studes of dabetes s the COI study, CBA and CEA are related to and buld upon the concepts of COI studes. COI estmates the total cost (economc mpact) of a dsorder n a three step process: Identfy the tangble consequences attrbutable to an llness, quantfy the frequency of these consequences; and Assgn economc values. The same three steps are used n economc evaluatons of nterventons (e.g., preventon and treatment) to analyze the relatve effectveness of strateges at reducng total costs to socety. In cost beneft analyss (CBA) the frst step s to dentfy the consequences of the dsorder whch the nterventon mght effect. The second step s to quantty the effects of the nterventon (relatve to no nterventon, or alternatve nterventons), and the thrd step s to assgn values to the dfferent nterventon effects or tangble consequences) so that expenses of the nterventon (costs) can be compared to the value of the avoded consequences (benefts). The benefts and costs may therefore be drectly compared because they are expressed n common unts (dollars). Cost beneft analyss (CBA) may be used to answer such questons as: Do the benefts of mplementng school-based preventon exceed the costs of the program? How do the economc benefts to socety compare to the costs of a new treatment regmen (such as new drugs for treatng type II dabetes)?