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    Adv Ther. ; 5 :7 57 .

    OI:10.1007/s12325-008-0085-z

    725

    EVIEW

    Iron Chelation Terapy: ClinicalEffectiveness, Economic Burden

    and Quality of Life in Patients withIron Overload

    Krista A PayneUnited BioSource Corporation, Montreal, Quebec, Canada

    Diana RoailMapi Values, Bollington, Cheshire, UK

    Jean-Franois BaladiNovartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA

    Muriel VialaMapi Values, Lyon, France

    Linda AbetzMapi Values, Bollington, Cheshire, UK

    Marie-Pierre DesrosiersUnited BioSource Corporation, Montreal, Quebec, Canada

    Noreen LordanUnited BioSource Corporation, Concord, Massachusetts, USA

    Khajak IshakIrina ProskorovskyUnited BioSource Corporation, Montreal, Quebec, Canada

    Address correspondence to: Krista A Payne, United BioSourceCorporation, 185 Dorval Ave, Suite 500, Montreal, Quebec,H9S 5J9 Canada. Email: [email protected]

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    Advances in Terapy IC: Clinical Efectiveness, QOL, Economic Burden

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    ABSRAC

    Intro uction: Tis study o UK patients examines clinical, health-

    related quality o lie (HROL) and economic outcomes associatedwith iron chelation therapy (IC). Deserrioxamine (DFO) (Desera ; Novartis, Switzerland) and Deeriprone (Ferriprox ; Apotex,

    Canada) are ICs used to treat iron overload. DFO requires 8- to12-hour in usions a minimum o ve times per week. De eriprone isadministered in an ora dai y regimen. A though pharmaco ogica yecacious, clinical eectiveness o IC within the real-world settingis yet to e ully elucidated.Met o s: A naturalistic cohort study o 60 patients (beta-

    tha assaemia, =40; sick e ce disease, =14; mye odysp asticsyndromes, =6; 63% emale) receiving IC in our UK treatmentcentres was conducted. Serum erritin level data were abstracted rommedical charts. Compliance, HROL, satisaction and resourceutilisation data were collected rom interviews. Maximum ICcosts were estimated using the resource utilisation data associated

    with DFO.Results: Mean serum erritin levels, generally, remained elevated de-spite IC. Compliance was suboptimal and HROL scores werelower than population norms. Te total estimated mean weight-ed annual per-patient cost o DFO treatment was approximately

    19,000. DFO-related equipment, DFO drug, and home healthcarewere estimated to account or 43%, 19% and 24% o costs, respec-tively. Other more minor components o total annual costs were orin-patient inusions, IC home delivery services and monitoringcosts.Conc usion: Generally, patients are not achieving target serum er

    ritin thresholds despite chronic treatment or iron overload. ICappears to negative y impact HROL; comp iance with IC ispoor; and, in the case o DFO, treatment costs well exceed the cost oDFO a one. Tese resu ts suggest that current IC in the rea -wor dsetting is su optimal with respect to various clinical, HROL andeconom c outcomes.

    Keywor s: clinical eectiveness; economic urden; health-relatedquality o li e; IC; iron overload

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    INRODUCION

    Patients with haemato ogica disorders

    such as tha assaemia, sick e ce diseaseand myelodysplastic syndromes (MDS)attend hospita outpatient appointmentsto receive regular lood trans usions. Aconsequence o requent lood trans usions is excess iron or iron over oad, whichcannot e excreted naturally. Tis leads totissue damage and rosis.1,2 Furthermore,a though in the short-term iron over oad

    does not cause visi le symptoms to thepatient, in the long-term i iron overloadis not treated, many patients experiencecardiac complications a main cause odeath in this population. Deserrioxamine(DFO; Deseral , Novartis, Switzerland),an iron chelation therapy (IC), is thestandard lie-long treatment or patients

    with iron overload due to chronic trans-usions.3 DFO is sel-administered by the

    patient at home by subcutaneous inusionover 8 to 12 hours, 5 to 7 days per week,either overnight or during the day.4 Al-though eective, DFO is associated withbothersome local site reactions including

    umps, rashes, ruises and in ections.5,6

    Other side eects experienced y patients

    administered DFO inc ude neutropenia, haematological toxicity, shortness oreath, headaches and dizziness.

    In addition to these side eects, theDFO treatment regimen can a so negatively impact aspects o patients health-related quality o lie (HROL).4,8 Arecent literature review reveale that ewstudies have ocused on HROL in pa

    tients with iron over oa .9 In those thatid, the results showed that or patients re

    ceiving IC, HROL could e impairedin the ollowing domains: depression,10 atigue, dyspnoea, physical unctioning and

    psycho ogica distress.11

    Although less urdensome, the oralormulation o IC, deeriprone (Ferr prox , Apotex, Canada), has been shownto e less eective at lowering hepatic ironthan su cutaneous DFO.12,13 Si e eectsinc uding arthropathy and neutropenia,

    which require strict monitoring duringtherapy, can also e experienced y pa

    tients receiving de eriprone.14o better understand the potential im-

    pact o novel treatments or iron overload,it is important to understand the clinicaleectiveness, HRQOL and economic im-pact o current IC. Te main objectives othe study described in this paper, which wasconducted in a UK cohort were to assess:r $MJOJDBM FFDUJWFOFTT PG DVSSFOU *$5

    in the usual care environmentr )320- PG QBUJFOUT XJUI UIBMBT-

    saemia, sickle cell disease and MDSprescribed IC, by comparing theMedical Outcomes Study Short FormHealth Survey (SF-36) and ChildHealth Questionnaire (CH-PF50)responses against UK norms

    r 1BUJFOU TBUJT BDUJPO BO DPNQ JBODFwith IC therapyr 5PUB BOOVB DPTUT P *$5 VTJOH %'0

    MAERIALS AND MEHODS

    Stu y Design

    Te design and methods o this i-

    national hy rid chart review and singlepatient interview study are reported e se

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    Advances in Terapy IC: Clinical Efectiveness, QOL, Economic Burden

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    where in greater detai .14 In this UK cohort, 60 patients with thalassaemia ( =40),sickle cell disease (n=14) and MDS (n=6)

    currently receiving IC at our UK studysites (St Tomas Hospital, London; TeRoya Bournemouth Hospita , Dorset;Te Whittington Hospita , London;Kings Co ege Hospita and GK Schooo Medicine, London) were invited to participate in one study visit. A small num er(

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    ea th states. Each hea th state is composed o six statements, one rom each

    imension, starting with Physica Func

    tioning and ending in Vitality. A total o9000 possi le health states are de ned inthis way.19

    Utilities were also estimate or the UKpopulation using pu lished algorithms

    eveloped y Brazier et al.19 to trans ormSF-36 scores into utility- ased scores.Utility scores are a measure o health outcome which assigns to each time period a

    weight ranging rom 0 to 1, corresponing to the HROL during that period.20

    Utility scores can range between 1 (per-ect health) and 0 (worst possible health asmeasured by the SF-6D).

    Te CH-PF50 measures HROLin children as reported by the parent. Te

    parent orm (or parents o children aged517 years) contains 50 items yielding 12domains: Physical Functioning; Role/So-cial Limitations Physical; Bodily Pain;General Health; Role/Social Limitations Emotional/Behavioural; Mental Health;Behaviour; Sel-Esteem; Parent Impact ime; Parent Impact Emotional; Fam-i y Activities; and Fami y Cohesion. TeCH-PF50 a so contains two summary

    scores: the Physica Summary Sca e andthe Psychosocia Summary Sca e.

    reatment Satis action with IC

    All participants 10 years o age andolder completed a 28-item sel -administered Satis action with IC questionnaire comprising our domains: the

    Perceived Eectiveness domain, whichmeasures participants perceptions o the

    clinical ene t; the Burden o IC domain, which assesses the impact o ICon daytime and evening activities, s eep

    and loss o independence; the Acceptanceo IC domain, which evaluates participants perceptions o convenience (or inconvenience) o IC, satisaction with themode o administration, and the extent to

    which ene ts o treatment meet expectations; and the Side Eects o IC domain,

    which assesses pain, side eects, and thepotential negative impact o treatment on

    the ody. Scores range rom 1 to 5 where1 represents very dissatisfed and 5 repre-sents very satisfed.

    Annual Costs o IC

    o identiy prior studies reportingcosts o inused IC, a literature review

    was undertaken (EMB reviews, Scirus andOvid Medline [19962005], PubMed[19952005]), using the ollowing key-

    words (including MeSH terms): thalas-saemia, sickle cell disease, myelodysplasticsyndromes, cost, iron chelation, Deseral,deserrioxamine, deeriprone, L1, resourceuse, and reim ursement. Only our studies

    were i enti e that containe ata relate

    to the costs o in use IC.2124

    On the asis o the literature, a singlecomposite list o cost variables (such asdrug, equipment, monitoring toxic eects,and psychotherapist) was created to serveas the asis or the health economics com

    ponent o the case report orm. Frequencyo use an unit cost ata or each o these

    varia les were i enti e rom the litera

    ture, this study, administrative data ases,and medica supp y cata ogues. o estimate

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    the maximum total cost urden o IC,only the cost o treatment with DFO wasestimated given that de eriprone does not

    require equipment or in usions ecauseit is an oral ormulation. Data sources arepresented in the resu ts section a ongsidecost estimates. A costs are reported in2007 GBP ().

    RESULS

    Demographic Characteristics

    Te demographic characteristics othe sixty participants are summarised inable 1. Participants were mostly emale(emale, n=38; male, =22).

    At the time o the study visit, 29(48%) participants were being treated withDFO, 18 (30%) with deeriprone, and 13(22%) were on a combination o both. Meanduration o therapy was 4.94.0 years.Te mean dose and prescribed regimen orDFO monotherapywas 3 .913.1mg/ kg,4.41.3 times/week. For deeripronemonotherapy, the mean total daily dose

    was 82.313.1 mg/kg with a mean totalnum er o doses o 7.00.0 times/week.For patients on com ination therapy, the

    mean DFO dose was 50.924.6 mg/kg,prescri ed 3.21.6 times/week; and themean total daily dose o de eriprone was71.617.6 mg/kg with a mean o 8.03.9 doses/week.

    Efectiveness o IC

    Despite ongoing IC, serum erritin

    eve s remained very high over the meanuration o IC treatment. In DFO-treat

    ed subjects, or whom serum erritin testresults were availa le, mean serum erritineve s over the initia and most recent years

    o IC were 30131370 ng/ml ( =8) and28131740 ng/ml (n=25), respectively.Tese data were not availa le rom theinitial year o IC or su jects on com

    ination, and were unavaila le or all utone su ject on de eriprone. In the mostrecent year o IC, mean serum erritinevels or com ination and de eriprone

    subjects were 33472491 ng/ml ( =13)

    and 29832167 ng/ml ( =19), respectively (Figure 1).

    Table 1. Demographic characteristics ostudy sample.

    n (%)

    All patients 60 (100)Age

    610 years 2 (3)

    1118 years 9 (15)

    19 years 49 (82)

    Gender

    Female 38 (63)

    Male 22 (37)

    Disease

    Talassaemia 40 (67)

    Sickle cell disease 14 (23)

    Myelodysplastic syndromes 6 (10)

    Employment status

    Unemployed 31 (52)

    Retired 6 (10)

    Part-time 7 (12)

    Full-time 16 (27)

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    In general, mean serum erritin levelso patients receiving IC were much high-er than 1000 ng/ml (Figure 1, green line)and in many patients, eve s were higherthan 2500 ng/ml (Figure 1, red line).

    During the interview, non-comp iance with IC during the previous 7 dayswas assessed and 17 o 58 (30%) subjectsmissed at east two doses during this time

    period. In addition to non-comp iance, anota le num er o adverse events to ICover the previous 30 days were o served inthis study cohort (able 2). Site soreness( =20) was the most common adverse

    event in patients taking DFO; site soreness ( =6) and irritation ( =6) were the

    most common adverse events in patientstaking combination; joint pain (n=3) wasthe most common adverse event in pa-tients taking de eriprone. O the 23 DFO

    patients who reported adverse events, 35%

    o these (n=8) also reported that adverseevents resu ted in missed doses during theprevious 30 days (mean number o misseddoses per patient, 4.12.7). Eight o 19 patients (42%) who reported missing at leastone dose o DFO over this same period,did so ecause o adverse events. rends

    were similar in patients on com inationtherapy at the time o the study visit. wo

    o eight (25%) patients in the combination group reporting adverse events a so re

    Figure 1. Mean serum erritin levels (most recent year o IC).

    0Tal

    (n=10)SCD

    (n=11)

    DFO*

    All =28131740 ng/ml

    MDS(n=4)

    Tal(n=17)

    MDS(n=2)

    Deeriprone

    All =29832167 ng/ml

    Tal(n=13)

    Combo

    All =33472491 ng/ml

    1000

    2000

    3000

    4000

    5000

    8000

    7000

    6000

    SFL(meanSD),ng/ml

    *Does not include three patients or whom the initial year o IC equals the most recent year o IC.One patient started the year on deeriprone and switched to DFO.DFO=deserrioxamine; IC=iron chelation therapy; MDS=myelodysplastic syndromes; SCD=sickle

    cell disease; SD=standard deviation; SFL=serum erritin level; Tal=thalassaemia.

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    ported that these resu ted in missed doses(mean number o missed doses in previous30 days, 2.50.7).

    HRQOL

    SF-36 Domain an Summary Scores

    Forty-nine participants o der than

    18 years o age completed the SF-36 questionnaire. Mean SF-36 domain scores or

    males on IC ranged rom 40.81 or General Health to 67.50 or Mental Health.ompared with age- and gender-matched

    norms,25 study participants scored oweron a SF-36 sca es. Speci ca y, point ierences etween UK male norms an

    the UK men on IC in our study samp e( =16) indicated a decrement rangingrom 7.2 or the Mental Health domain to

    36.25 or the Role Limitations Physicaldomain (Figure 2).

    Table 2. IC-related adverse events.

    Adverse event Desferrioxamine* Deferiprone* Combination(AE) (n=29) (n=18) (n=13)

    1 AE 23 (79) 4 (22) 8 (62)

    Site irritation 17 (74) NA* 6 (75)

    Site soreness 20 (87) NA* 6 (75)

    Nausea 3 (13) 1 (25) 3 (38)

    Breathing problems 0 (0) NA* 0 (0)

    Ringing in the ears 4 (17) NA* 0 (0)

    emporary hearing loss 0 (0) NA* 0 (0)

    Decreased night vision 1 (4) NA* 1 (13)

    Blurred vision 2 (9) NA* 0 (0)

    Diarrhoea 3 (13) 0 (0) 2 (25)

    Fever 2 (9) NA* 0 (0)

    Abdominal pain 7 (30) 1 (25) 2 (25)

    Decrease in appetite NA 1 (25) 4 (50)

    Headache NA 2 (50) 2 (25)

    oint pain NA 3 (75) 5 (63)

    *Monotherapy AE.Only one o the patients experiencing an AE reported associated resource utilisation (2 doctor visits,1 nurse visit, 1 A&E visit, 1 admission to the hospital).Patients who experienced at least one AE in relation to IC in the previous 30 days.AE not queried or the type o therapy.IC=iron chelation therapy; NA=not applicable.

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    Te mean SF-36 domain scores oremales on IC in our study ranged rom

    45.61 or Vitality to 66.29 or Social Func

    tioning. Compared with age- and gender-matched norms,25 study participants(n=33) scored lower on all SF-36 scales.Speci cally, decrements ranged rom 3.68or the Mental Health domain to 41.43

    points or Role Limitations Physical(Figure 3).

    Te mean SF-36 summary scores ormales were 38.23 or the Physical Com

    ponent Summary scale and 44.93 or theMenta Component Summary sca e, we

    below the norm o 50. Compared withage-matched norms ( =768), male study

    participants ( =16) scored lower on both

    SF-36 summary scales (decrements o 6.17or the Mental Component Summaryand 14.47 or the Physical ComponentSummary).

    SF-36 summary scores or emales inthe UK on IC were 38.39 or the Physical Component Summary and 45.45 orthe Menta Component Summary. Com

    pared with age-matched norms ( =1107),

    emale study participants ( =33) scoredlower on both SF-36 summary scales (dec

    Figure 2. UK male study participants (mean age, 31.78 years) scored lower on all SF-36 domainscompared with age-matched norms.

    0

    SF-36 domains

    10

    2030

    40

    50

    100

    80

    90

    70

    60

    S

    F-36domainscores

    BP=Bodily Pain; GH=General Health; MH=Mental Health; PF=Physical Functioning;RE=Role Emotional; RP=Role Physical; SF=Social Functioning; V=Vitality.

    PF(800)

    RP(809)

    BP(811)

    55.50

    GH(803)

    74.00

    40.81

    V(808)

    61.10

    43.13

    SF(807)

    86.50

    64.06

    RE(808)

    89.40

    64.06

    MH(809)

    74.7067.50

    UK norms (n) UK study population (n=16)

    92.90

    58.75

    92.50

    56.25

    86.00

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    rements o 3.55 or the Mental Compo-nent Summary and 11.91 or the PhysicalComponent Summary).

    SF-6D Utilities

    mean utility score o 0.66 ( 49;min=0.37, max=0.95) was generated orUK study participants on IC, which isower than that or patients who are re

    ceiving dialysis or chronic kidney disease,who have a utility score o 0.72 ( =38),26

    and lower than that o age-matched norms(0.81, =361). 7

    CHQ-PF50 Domain and SummaryScores

    CH-PF50 HROL data revea edsimi ar resu ts to the SF-36 scores. TeCH-PF50 was completed y parentso all children aged 18 years or younger( =11). UK mean CH-PF50 domainscores ranged rom 46.59 or the GeneralHealth domain to 85.91 or the FamilyCohesion domain. Compared with USage-matched norms,28 UK study par

    ticipants scored ower on a CH-PF50scales (reduced point dierences ranged

    Figure 3. UK emale study participants (mean age, 33.97 years) scored lower on all SF-36 domainscompared with age-matched norms.

    0

    SF-36 domains

    10

    2030

    40

    50

    100

    80

    90

    70

    60

    SF-36domainscores

    BP=Bodily Pain; GH=General Health; MH=Mental Health; PF=Physical Functioning;RE=Role Emotional; RP=Role Physical; SF=Social Functioning; V=Vitality.

    PF(1611)

    RP(1168)

    BP(1174)

    59.79

    GH(1169)

    73.80

    45.94

    V(1175)

    54.7045.61

    SF(1175)

    80.20

    66.29

    RE(1166)

    83.40

    57.58

    MH(1176)

    69.50 65.82

    UK norms (n) UK study population (n=33)

    91.00

    57.42

    88.40

    46.97

    79.90

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    Table 3. Estimated mean weighted annual per-patient cost associated with inused IC drug, equipmentand monitoring.

    Cost component Data sources* Mean annual weighted cost,

    DFO drug 3671Home delivery 297

    Inusions in healthcare setting 1595

    Home healthcare 24 4411

    Equipment

    Pump (purchased) 29 212

    Elastomeric balloon inusor 30 7336

    Portacath 101

    Disposables# 29, 3133 343

    Equipment total 7992

    Monitoring

    Serum erritin level 79

    Audiology 23, 34 203

    Ophthalmology 23, 34 108

    Skeletal survey 23, 34 18

    Psychotherapy visits 23, 34 138

    Adverse events 34 169

    Monitoring total 715

    Total cost 18,681

    *Data sources or resource utilisation profles and unit costs.

    Cost weighted by percentage o patients using resource and or DFO, by patient age. Costs are reported in

    GBP 2007 () using UK medical ination indices.34

    Source: study data.

    Te mean weighted annual cost reecting actual patient-reported compliance is 3671. Cost increases to

    4421 when 100% compliance is assumed.

    Unit costs provided by equipment supply companies.

    Includes annual weighted cost or a portacath, needles or a portacath, and the surgery or theportacath implant.

    #Includes syringes, needles, inusion sets, tape, alcohol pads, gauze, sharp bins and batteries.

    DFO=deserrioxamine; IC=iron chelation therapy.

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    rom 5.58 or Mental Health to 30.99 orFamily Activities) except or Family Cohesion, Behaviour and Sel -Esteem domains.

    H-PF50 summary scores were37.19 or the Physical Summary Scale and6.05 or the Psychosocial Summary Scale.

    Compared with US age-matched norms,UK study participants scored ower onboth CH-PF50 summary scales (decrements were 4.75 or the PsychosocialSummary Scale and 16.41 or the PhysicalSummary Scale).

    Satisaction with IC Scores

    Te Satisaction with IC question-naire was completed by all patients over10 years o age (n 58). Mean scores orthe Satisaction with IC domains werehighest or Perceived Eectiveness o IC(4.36) ollowed by Burden o IC (3.52),and then Acceptance o IC (3.28). SideEects o IC was the lowest mean score(3.14).

    When mean satisaction scores wereplotted against ratings o an overall satis-action question, patients in the satisfedgroup score t e ig est or Perceive Eectiveness and Acceptance o IC, ut

    also had the lowest mean scores or Burdenand Side Eects o IC.

    Annual Costs o IC (DFO)

    Te tota estimated mean weightedannual per-patient cost o DFO treatment

    was approximately 19,000 (able 3).DFO-re ated equipment, DFO drug, and

    home hea thcare, were estimated to accountor 43%, 19% and 24% o costs, respective

    ly. Te largest component o the total annual cost was equipment, estimated to e

    7992. Te estimated annual cost o DFO

    was 3671. I compliance was assumed toe 100%, mean weighted drug costs wouldincrease to 4421. Home hea thcare wasthe next most signi cant contri utor ocost, tota ing 4411. Other more minorcomponents o total annual costs were orin-patient inusions (1595), IC homedelivery services (297) and monitoringcosts (715).

    DISCUSSION

    Overall, data rom this study suggestthat current IC in the real-world set-ting is suboptimal with respect to varioushealth and economic outcomes. Patientsare not achieving their target serum er-ritin thresholds despite chronic treatmentor iron overload, IC appears to nega-tively impact their HROL, and compli-ance to IC is poor. Also, in the case oDFO, treatment costs well exceed the costo DFO alone.

    Despite an average o approximate-y 5 years o IC, mean serum erritinevels in most su jects remained a ove

    2500 ng/m a eve considered e evatedand associated with cardiovascu ar disease3537 and morta ity.37 Improved outcomes are typica y associated with serumerritin levels elow 1000 ng/ml.38

    Adverse events associated with ICduring the 30 days prior to the study visit

    were airly common, with local reactionssuch as irritation and soreness at the in u

    sion site, the most requently reported (approximately 75% o subjects). wo other

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    studies have reported similar ndings. Inthe rst study,39 o the 89% o su jects re

    porting adverse events, the most common

    were redness, itching and pain. In the oter stu y40 the most common side eects oIC were pain, ten erness, itc ing, erythema, swelling and a urning sensation atthe in usion site.

    Given the urdensome DFO regimeno 8- to 12-hour in usions 5 to 7 times per

    week and the prevalence o othersomeside eects o current IC it is not surpris

    ing that comp iance was genera y poor.41Consistent with these studies, a signifcantnumber o subjects in this UK cohort alsoreported that they had not taken theirIC as prescribed. More than hal o thesubjects reported that at least one dose

    was missed in the previous 7 days, while40%50% o subjects (depending on theirregimen) reported missing at least twodoses over this same period. Te associa-tion between IC-related adverse eventsand non-compliance observed in thisstudy is also consistent with the fndingso other earlier studies.42,43

    Patients with thalassaemia, sickle celldisease, and MDS current y undergoingIC had much ower HROL scores

    compared with popu ation norms, and inparticular or the General Health, RoleLimitations Physica , and Physica Functioning omains o t e SF-36. Te ierence etween the SF-36 domain study

    scores an t e popu ation norms were oten 3 to 5 units. Tere ore, these results areclinically meaning ul and signi cant,44,45

    and in er that changes need to e made

    to IC treatment or patients with ironover oad.

    Te CH-PF50 data revea ed simi arresu ts, with participants scoring ower ona CH-PF50 domains compared with

    US population norms, except or Family Cohesion, Behaviour and Sel -Esteemdomains.

    Te ndings that HROL is compromised in patients with IC are in ine with

    previous studies.39 Furthermore, given thatpatients on dialysis have a utility score o0.72, it can e in erred that a utility scoreo 0.66 or patients receiving IC is very

    ow, indicating a re ative y poor hea thstate. 6

    Overall mean satisaction scoresshowed that patients were satisfed withthe perceived eectiveness o their ICbut less with the burden o IC, and sideeects o IC. As a score o 5 representsvery satisfed or all items in a domain, amean o 3.5 or more suggests that most pa-tients were rather satisfed with most or allo the items in the domain. Specifc ques-tions regarding satisaction with IC elic-ited more critical responses, as is generallythe case.46 Consistent with this fnding, acloser examination o mean satisactionscores plotted against ratings o an overallsatis action question rom the Satis action

    with IC questionnaire, demonstratedthat patients identi ed as satis ed wereperhaps not as satis ed with IC as overall scores rst in icate .

    Based on a more comprehensive costing assessment than has een reported

    previously, the total annual cost o in usedIC estimated in this study is signi cantand much higher than the cost o DFO

    alone. Among the our pu lished studieswe identi ed, 124 on y one22 reported the

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    mean annua IC per-patient cost, whichwas estimated to range rom $12,719 to$24,845 (USD 1998), but only the costs

    associate with DFO an home hea tcare services were inclu e . In another othese studies,24 the li etime cost o DFO

    was estimated to be about $63,000 (USD1996). Tree o the studies 1,23,24presente li etime treatment costs o eta-thalassaemia, ut in two o these21,23 it was not

    possi le to disaggregate the cost o DFOtreatment rom that o the treatment or

    under ying disease. In the US imp ementation o this study, which was conductedconcurrently using a standard protocoland case report orm,28 total annual ICtreatment costs were estimated to beabout US$30,000. However, it is dicultto relate current cost estimates to thosereported in the literature, given the smallnumber o previously published studiesand variability in study designs. Further-more, to simpliy the methodology, onlythe per-patient cost o annual treatment

    with DFO was estimated. Given the needor inusion-related equipment and sup-

    plies, it is possible that the DFO costcou d represent an upper imit to ICcost estimates.

    Some a itional limitations o thisstudy deserve comment. Tese resu ts donot distinguish the impact o IC romthat o the underlying condition and theadverse events reported may e a consequence o IC and the patients con

    ition. Further research cou eva uateoutcomes re ated to the patients conditions. In particular, since the HROL o

    iron-over oaded patients is a ready poor,studies cou d exp ore HROL scores

    etween patients de ned as well versusthose who are ill with requent hospitalor doctor visits. A ternative y, HROL

    scores o iron-overloaded patients coulde compared with those o other patientswith chronic con itions rather than UKpopu ation norms.

    Further studies cou d a so investigatethe num er o re loo cell trans usionsthe patients received during therapy, andthe extent to which HROL is re ated tocomp iance.

    Fina y, some caution is necessary inthe interpretation o these results giventhat sample sizes were small. A high de-

    ree o variability was observed across allstudy outcomes, thus studies with largersample sizes may provide greater certaintyo results.

    CONCLUSION

    Tis study provides some evidencethat IC in the real-world setting is sub-optimal with respect to various clinical,HROL and economic outcomes. Over-all, study subjects had not achieved targetserum erritin thresholds despite chronictreatment or iron overloa with IC.

    O served compliance to IC was genera y poor, and treatment appeared to negatively impact the HROL o su jects.ota estimated annua DFO cost per patient was substantial (19,000). Te largest estimated components o total annualcost were those re ated to equipment andthe medication itsel , ollowed y homehealthcare costs. Novel treatments or IC

    which are more tolera le, less urdensomeand ess cost y are warranted.

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    ACKNOWLEDGEMENS

    Tis manuscript was supported y a

    grant rom Novartis Pharmaceuticals Corporation, USA. Te authors give thanksto the c inicians who have assiste in theconduct o this study. In particular, wethank the Principa Investigators and theirresearch sta: Dr Iheanyi Okpala, Dr Ba aInusa, St Tomas Hospita ; Dr Sa y Kiick, Te Roya Bournemouth Hospita ;

    Dr James Ma one-Lee, Te Whittington

    Hospita ; and Dr Swee Lay Tein, KingsCollege Hospital and GK School oMedicine.

    Competing Interests

    uthors Krista Payne, Marie-PierreDesrosiers, Noreen Lordan, Khajak Ishakand Irina Proskorovsky are employees oUnited BioSource Corporation, a con-sultancy that has also received grants orother, unrelated research rom NovartisPharmaceuticals Corporation.

    Diana Roail works as a Senior ProjectManager in the Questionnaire Develop-ment and Validation unit o Mapi Values.She has acted as an advisor or various phar

    maceutica companies regarding their c inica tria s and patient-reported outcomes.Jean-Franois Baladi is employed y

    Novartis Pharmaceutica s Corporationand owns stocks and/or stock options.

    Murie Via a works as a Statisticianin the Questionnaire and Va idation unito Mapi Values. She has acted as an advisor or various pharmaceutical companies

    regarding their c inica tria s and patient-reported outcomes.

    Lin a A etz works as a Director othe Questionnaire and Va idation unito Mapi Values. She has acted as an advi

    sor or various pharmaceutical companiesregarding their c inica tria s and patient-reported outcomes.

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