P rescribin g pattern s of biologic im m u n om odu latin g m edicin e in
P rescribin g pattern s of biologic im m u n om odu latin g m edicin e in
P rescribin g pattern s of biologic im m u n om odu latin g m edicin e in
P rescribin g pattern s of biologic im m u n om odu latin g m edicin e in th e
th e
th e
th e
S ou th A
S ou th A
S ou th A
S ou th A frican
frican
frican
frican private
private
private health care sector
private
health care sector
health care sector
health care sector
Ilanca R oux
B .P harm
D issertation su bm itted in p artial fulfilm ent of the requ irem en ts for th e d egree M agister P h arm aciae in P harm acy P ractice at the P o tchefstroom cam pus of the N orth -W est U niversity.
S uperv isor: P rofessor M .S . L u bbe
C o-su pervisors: M rs. J.R . B urger
D r. J.C . L am prech t
P otchefstroom
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•
I th an k m y L ord an d h eaven ly F a th er: T h an k you first of all for th e g ifts Y ou bestow ed on m e
th at en abled m e to do th is. T h an k yo u for giv in g m e stren gth an d p eace w h en I felt
d iscou raged and con fu sed, an d for giv in g m e th e w ord s to w rite w h en m in e seem ed to be
in ad equ ate. T h an k y ou for all of Y our b lessings, g ra ce an d lov in g-k in d n ess, b u t m ost of all,
th a nk yo u for surrou nd in g m e w ith am a z ing p eop le an d m ak ing th em p art of m y jo u rn ey and
p art o f m y life. A ll of th e g lory co m es to Y ou an d I p ray th at Y ou are th orou gh ly p leased .
I w ish to express m y sin cere gratitud e to th e m a ny peo p le w ho h elp ed an d su pp orted m e to realise
th is d issertatio n . T h e follow in g p eo p le d eserv e sp ecial ack n o w led gem en t:
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M y su p erv isor, P ro fesso r M .S . L u bbe: “T h a n k you ” d o es n ot begin to exp lain h o w m u ch all th e
h ard w ork , tim e an d effo rt yo u p ut in to th is stu dy are ap precia ted . T h an k you for go ing the
extra m ile an d ensu rin g tha t ev eryth in g w as alw ays accurate and u p to sta nd ard . T h an k you
for sh arin g you r w isdom an d ex p erien ce w ith m e. T o m e it w as a v ery reassu rin g exp erience to
b e ab le to rely on you r expert assistan ce thro ugho u t.
•
M y co-su p erv iso r, D r. J.C . L am p rech t: T h a nk you fo r prov id in g th e m u ch n eed ed in sig ht in to
th e clin ical asp ects of th is stu d y an d for p rov id ing a fresh p ersp ectiv e w h en it w as n ecessary.
T h a n k you for you r con stru ctiv e con tribu tio n s a nd a dv ice an d fo r b eing so con sid erate w ith
regard to m y oth er o bligation s d u rin g th is p eriod .
•
M rs. J.R . B u rger in yo u r capa city a s co-sup erv isor: T h an k you for ag reein g to get in volv ed in
th is stu dy a n d for alw ays being w illin g to h elp . Y our attention to d etail as w ell as yo ur
v alua ble adv ice and suggestio n s h av e b een greatly a p preciated a ll a long . Y ou r inp u t m ea n t
m u ch to m e an d I a m sin cerely gratefu l.
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M y fellow stu d ents: T h an k you so m u ch for m a k ing th is a m em orable exp erien ce an d for th e
o cca sion s th at w e co u ld lau gh togeth er w h en tim es w ere good an d co m p la in togeth er w h en th ey
w ere less good . B u t, th at’s research!
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T o S u n è a nd T iaan , th an k y ou fo r m a k ing th is fu n! T h an k yo u for alw ays being th ere, for yo ur
en couragem ent an d h elp , an d for being th e reason I w en t to th e office every d ay . T h is w ou ld
n o t h av e b een su ch a great exp erien ce if it h ad n ot b een for th e tw o of y ou .
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M y p aren ts, F ra n n ie a nd L in d a: I w an t to th an k you first of all for giv in g m e th e opp ortu n ity
to do th is. T h an k you for you r sup po rt an d m otiv atio n and for alw ays believ ing in m e. T h a n k
y ou for alw ay s en courag ing m e to do g rea t th in gs a n d for being at m y sid e throu g h every effort.
I d ed icate th is d issertatio n to yo u both , because w ithou t you it w o u ld not hav e been po ssible. I
lov e yo u .
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M y broth ers, R u an an d Jean d rè: I k n ow that yo u th in k it strang e th at an yon e w ou ld
w illin gly stu dy for long er th an w h at is ex p ected , b ut you n ev er sh o w ed a ny disco nten t that I
ch ose to d o th is and I am th a n kfu l. T h an k you for su p p orting m e an d m a k ing m e laugh
w h en ev er I to ok th in gs too seriou sly.
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W ayn e, you are m y rock . Y ou en cou raged a n d sup p ort ed m e ev ery step o f th e w ay , an d I
certain ly n eed ed th at. T h a n k you for all o f you r h elp ! T ha n k you for prov id in g a sho u lder for
m e to cry on w h en I felt discourag ed an d for being m y biggest fan w h en I su cceed ed . Y ou k ept
m e san e an d m otiva ted th rough out th is en tire pro cess, an d I am eterna lly gratefu l to yo u . I
lov e yo u .
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D r. S . E llis for yo ur exp ertise on th e sta tistical a n alysis.
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T o th e d ep artm en t of P h arm acy P ractice for fin a n cia l a n d tech n ical su p p ort.
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T o th e P h arm acy B en efit M an ag em ent co m p any for m ak ing th e d atabase availa ble.
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T o M s. M . T erblan ch e for ed iting th e lan gu age th is dissertatio n .
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T o M s. H . H offm a n an d M rs. A .M .E . P retorius for ed itin g th e b ibliograp h y.
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Title: Prescribing patterns of biologic immunomodulating medicine in the South African
private health care sector.
Keywords: biologics, biologic immunomodulating medicine, biological medicine,
autoimmune diseases, rheumatoid arthritis, multiple sclerosis, Crohn’s disease, pharmacoeconomics, drug utilisation review.
Advances in molecular immunology and rapid technical evolution during the past two decades have led to a new class of medicines called biologics. Recently, a large number of biologics, or biologic immunomodulators, directed towards an array of immune-mediated diseases, have entered the market. This has lead to a dramatic change in the immunotherapy of autoimmune diseases, as biologics present new potential to improve or substitute conventional immunosuppressive therapies. According to literature, biologics are used by only a small number of a health plan’s members, (approximately one per cent), but a single occurrence can be relatively expensive. Furthermore, there is an indication that the frequency of use and cost of biologics are on the rise, and as more biologics enter the market, health plans and employers face the challenge of controlling costs while ensuring that biologics are affordable.
The general objective of this study was to determine the prevalence and cost of biologic immunomodulating medicine in the treatment of certain autoimmune diseases during the period 2005 to 2008 in a section of the private health care sector of South Africa, by employing a medicine claims database as a source to obtain necessary information.
A quantitative, retrospective drug utilisation review (rDUR) was performed on computerised medication records (medicine claims data) for four consecutive years (i.e. 2005 to 2008) provided by a pharmacy benefit management company (PBM). The study population consisted of all patients on the database who received at least one medicine item with adalimumab, etanercept, infliximab, interferon beta-1a, interferon 1-b or rituximab as active ingredient and who were diagnosed with either rheumatoid arthritis (RA), multiple sclerosis (MS) or Crohn’s disease between 1 January 2005 and 31 December 2008.
Between 2005 and 2008, an average of 1,305,201 patients appeared on the total database, and of these 0.055% (n = 713) received biologic immunomodulating medicine. More than two thirds of biological users were female and most patients who received these medicine items were between the ages of 39 and 64 years, followed by those patients aged between 25 and
39 years. Biologic immunomodulating medicine items (n = 11,914) and biologic prescriptions (n = 9,537) represented 0.016% of the total number of medicine items (N = 76,129,173) and 0.030% of the total number of prescriptions (N = 31,985,153). The percentage contribution of biologic immunomodulators to the total number of medicine items and prescriptions on the total database increased each year, and in four years’ time the percentage of all the medicine items on the total database that included biologic immunomodulators had tripled, from 0.009% to 0.023%.
The total cost of biologic immunomodulating medicine accounted for 1.278% of the total cost (N = R7, 483,759,176.23) of all medication claimed through the PBM between 2005 and 2008. The percentage contribution of biologic immunomodulators to the total medicine expenditure also increased from one year to another for the four-year study period. The average cost of a biologic immunomodulating medicine item increased with 71.10% from 2005 (R5602.71 ± 2166.61) to (R9586.25 ± 5956.56) in 2008. The CPI for biologic immunomodulators, (CPI = 60.00 for 2005; CPI = 74.62.17 for 2006; CPI = 85.26 for 2007; and CPI = 86.96 for 2008) indicated that biologic immunomodulating medicine items were relatively expensive and the d-value between the average cost per biologic immunomodulator and the average cost per non-biological medicine item (d-value = 2.54 in 2005, d-value = 3.32 in 2006, d-value = 2.23 in 2007 and d-value = 1.59 in 2008) furthermore indicated that the impact of biological therapies was large and practically significant.
Rheumatoid arthritis patients represented 19.78% of the total number of patients (n = 713) who claimed the biologic immunomodulators during the four-year period, MS patients (n = 172) represented 24.12% and Crohn’s patients (n = 11) represented 1.5%. Biological drugs prescribed to RA patients represented 0.28% (n = R20, 708,818.82) of the total cost (N = R7, 483,759,176.23) of all medication claimed through the PBM during the four-year period, while those prescribed to MS patients represented 0.41% (R30, 922,520.07) and those prescribed to Crohn’s disease patients represented 0.015% (R1, 108,568.02).
Although biologic immunomodulating medicine items used in the treatment of RA, MS and Crohn’s disease are relatively expensive, it seems that the number of other medication prescribed to patients with these diseases decreased after treatment with biologics, which may influence the medicine treatment cost of these patients.
It can be concluded that even though biologic immunomodulators are used by only a very small percentage of the total patient population in a section of the private health care sector of South Africa, they are relatively expensive and have a considerable impact not only the medical aid scheme, but also on the patient.
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Titel: Voorskryfpatrone van biologiese immunomodulerende medisyne in die
Suid-Afrikaanse privaat gesondheidsorgsektor.
Sleutelwoorde: biologiese produkte, biologiese immunomodulerende medisyne, biologiese
medisyne, outo-immuun siektes, rumatoïde artritis, veelvuldige sklerose, Crohn se siekte, farmako-ekonomie, medisyneverbruiksevaluering.
Vooruitgang in molekulêre immunologie en ʼn vinnige tegnologiese ontwikkeling gedurende die afgelope twee dekades het ʼn nuwe groep geneesmiddels, bekend as biologiese
produkte, opgelewer. ʼn Groot aantal biologiese produkte, of biologiese
immunomoduleerders, wat gemik is op ʼn verskeidenheid van immuunbemiddelde
siektetoestande het onlangs die medisynemark bereik. Dit het aanleiding gegee tot ʼn ingrypende verandering in immunoterapie van outo-immuun siektes, aangesien biologiese produkte nuwe potensiaal bied om konvensionele immuun-onderdrukkende terapieë te verbeter of te vervang. Volgens die literatuur word biologiese produkte gebruik deur slegs ʼn klein gedeelte van ‘n mediese fonds se lede (ongeveer een persent), maar ‘n enkele voorval kan relatief duur wees. Boonop is daar ʼn aanduiding dat die frekwensie van gebruik, sowel as die koste van biologiese produkte, besig is om te styg en soos wat nuwe biologiese produkte die mark bereik, word mediese fondse en werkgewers gekonfronteer met die uitdaging om die koste van hierdie produkte te beheer terwyl hulle moet verseker dat dit bekostigbaar is.
Die algemene doel van hierdie studie was om die voorkoms en koste van biologiese immunomodulerende medisyne in die behandeling van sekere outo-immuun siektes in ‘n gedeelte van die privaat gesondheidsorgsektor van Suid-Afrika te bepaal vir die periode 2005 tot 2008 deur gebruik te maak van ʼn medisyne-eis databasis as ʼn bron om die nodige inligting te bekom.
Die navorsingsmetode wat gebruik is in hierdie studie was ‘n kwantitatiewe, retrospektiewe medisyneverbruiksevaluering. Data was verkry vanaf gerekenariseerde medisyne rekords (medisyne-eis data) vir vier opeenvolgende jare (2005 tot 2008) wat beskikbaar gestel was deur ‘n apteek voordelebestuursmaatskappy. Die studie populasie het bestaan uit al die pasiënte op die databasis wat ten minste een medisyne item ontvang het wat adalimumab, etanercept, infliximab, interferon beta-1a, interferon 1-b of rituximab as aktiewe bestanddeel gehad het en wat gediagnoseer is met rumatoïde artritis (RA), veelvuldige sklerose (VS) of Crohn se siekte tussen 1 Januarie 2005 en 31 Desember 2008.
Tussen 2005 en 2008 het daar ʼn gemiddeld van 1,305,201 pasiënte op die totale databasis verskyn, waarvan 0.055% (n = 713) biologiese immunomodulerende medisyne ontvang het. Meer as twee derdes van die pasiënte wat biologiese produkte gebruik het was vroulik en meeste van die pasiënte was tussen die ouderdomme van 39 en 64 jaar, gevolg deur pasiënte tussen die ouderdomme van 25 en 39 jaar. Biologiese immunomodulerende medisyne items (n = 11,914) en biologiese voorskrifte (n = 9,537) het 0.016% van die totale aantal medisyne items (N = 76,129,173) en 0.030% van die totale aantal voorskrifte (N = 31,985,153) verteenwoordig. Die persentasie van die totale aantal medisyne items en voorskrifte op die totale databasis wat deur biologiese immunomodulerende medisyne verteenwoordig is, het elke jaar verhoog. In vier jaar se tyd het die persentasie van al die medisyne items op die totale databasis, wat verteenwoordig is deur biologiese immunomoduleerders, verdriedubbel vanaf 0.009% tot 0.023%.
Die totale koste van biologiese immunomodulerende medisyne was verantwoordelik vir 1.278% van die totale koste (N = R7, 483,759,176.23) van al die medikasie wat geëis is deur die apteek voordelebestuursmaatskappy tussen 2005 en 2008. Die persentasie bydrae van biologiese immunomoduleerders tot die totale medisyne uitgawes het ook verhoog van een jaar na die volgende gedurende die vier-jaar periode. Die gemiddelde koste van ‘n biologiese immunomodulerende medisyne item het met 71.10% verhoog vanaf (R5602.71 ± 2166.61) in 2005 na (R9586.25 ± 5956.56) in 2008. Die koste-voorkoms indeks (“CPI”: Cost-prevalence index) vir biologiese immunomoduleerders, (CPI = 60.00 vir 2005; CPI = 74.62.17 vir 2006; CPI = 85.26 vir 2007; en CPI = 86.96 vir 2008) het aangetoon dat biologiese immunomodulerende medisyne items relatief duur was. Die d-waarde tussen die gemiddelde koste per biologiese immunomoduleerder en die gemiddelde koste per nie-biologiese medisyne item (d-waarde = 2.54 in 2005, d- waarde = 3.32 in 2006, d- waarde = 2.23 in 2007 en d- waarde = 1.59 in 2008) het boonop aangetoon dat die impak van biologiese terapieë groot en prakties betekenisvol was.
Pasiënte met RA het 19.78% van die totale aantal pasiënte (n = 713) verteenwoordig wat biologiese immunomoduleerders geëis het gedurende die vier-jaar periode. Pasiënte met VS (n = 172) het 24.12% verteenwoordig en pasiënte met Crohn se siekte (n = 11) het 1.5% verteenwoordig. Biologiese medisyne wat voorgeskryf is vir pasiënte met RA het 0.28% (n = R20, 708,818.82) van die totale koste (N = R7, 483,759,176.23) van alle medikasie wat deur die apteek voordelebestuursmaatskappy geëis is tussen 2005 en 2008 verteenwoordig. Biologiese medisyne wat voorgeskryf is vir pasiënte met VS het 0.41% (R30, 922,520.07) verteenwoordig en die wat voorgeskryf is vir pasiënte met Crohn se siekte het 0.015% (R1, 108,568.02) verteenwoordig.
Alhoewel die biologiese immunomodulerende medisyne wat gebruik word in die behandeling van RA, VS en Crohn se siekte relatief duur is, blyk dit of die aantal ander medisyne items wat voorgeskryf word vir pasiënte met hierdie siektetoestande afneem nadat hulle met biologiese produkte behandel is. Die medisyne behandelingskoste van hierdie pasiënte mag hierdeur beïnvloed word.
Die gevolgtrekking kan gemaak word dat, alhoewel biologiese immunomoduleerders deur slegs ʼn klein gedeelte van die totale pasiënt populasie in ʼn gedeelte van die privaat gesondheidsorg sektor van Suid-Afrika gebruik word, is hierdie middels relatief duur en het hulle ʼn aansienlike uitwerking op beide mediese fondse en pasiënte as betalers.
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C ha pter 1
C ha pter 1
C ha pter 1
C ha pter 1: In trodu ction
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: A n O v erv iew of th e Im m u n e system a n d B iologic Im m u n om od u latin g M ed icin e
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2 .3
2 .3
A b n orm al im m u n e respon ses
A b n orm al im m u n e respon ses
A b n orm al im m u n e respon ses
A b n orm al im m u n e respon ses … … … .
… … … .
… … … ...
… … … .
3 2
3 2
3 2
3 2
2 .3 .1
H yp ersen sitiv ity… … … ...
3 2
2 .3 .2
Im m u n od eficien cy … … … ...
3 2
2 .3 .3
A u to im m u n ity… … … ..
3 2
2 .3 .3 .1
D efin ition… … … ....
3 2
2 .3 .3 .2
G en eral classifica tion… … … ....
3 3
2 .3 .3 .3
E tiology o f a u to im m u n e d iseases… … … ...
3 3
2 .4
2 .4
2 .4
2 .4
B iolog
B iolog
B iolog
B iolog ics: A n O v erv iew
ics: A n O v erv iew
ics: A n O v erv iew
ics: A n O v erv iew … … … ...
… … … ...
… … … ...
… … … ...
3 5
3 5
3 5
3 5
2 .4 .1
In trod u ction… … … ....
3 5
2 .4 .2
A brief h isto ry of bio logics… … … .
3 5
2 .4 .3
C om p osition an d d ev elop m en t… … … ...
3 7
2 .4 .4
B iolog ics v ersus trad ition al sm all m o lecu le d ru gs… … … ..
3 8
2 .5
2 .5
2 .5
2 .5
C lassification an d in d icatio n s of biologics
C lassification an d in d icatio n s of biologics
C lassification an d in d icatio n s of biologics
C lassification an d in d icatio n s of biologics… … … ...
… … … ...
… … … ...
… … … ...
4 0
4 0
4 0
4 0
2 .5 .1
In trod u ction… … … ....
4 0
2 .5 .2
C lassification of bio lo gics… … … .
4 2
2 .5 .3
In d ica tions of bio logics… … … .
4 5
2 .5 .4
P rev alence of u se of biologics… … … .
4 6
2 .6
2 .6
2 .6
2 .6
B iolog ics u sed in th e treatm en t o f au to im m u n e
B iolog ics u sed in th e treatm en t o f au to im m u n e
B iolog ics u sed in th e treatm en t o f au to im m u n e
B iolog ics u sed in th e treatm en t o f au to im m u n e d isea ses… … … .
d iseases… … … .
d iseases… … … .
d iseases… … … .
5 0
5 0
5 0
5 0
T able of con tents
_ __ _ _ __ __ _ _ __ __ _ _ _ _ __ __ _ _ __ __ _ _ __ __ __ _ _ __ __ _ _ __ __ _ __ _ __ __ _ _ __ __ _
2 .7
2 .7
2 .7
2 .7
B iolog ic im m u n om od u lato rs u sed in th e treatm en t o f
B iolog ic im m u n om od u lato rs u sed in th e treatm en t o f
B iolog ic im m u n om od u lato rs u sed in th e treatm en t o f
B iolog ic im m u n om od u lato rs u sed in th e treatm en t o f rh eu m ato id arthritis,
rh eu m ato id arthritis,
rh eu m ato id arthritis,
rh eu m ato id arthritis,
C roh n ’s d isease a n d m u ltiple sclerosis
C roh n ’s d isease a n d m u ltiple sclerosis
C roh n ’s d isease a n d m u ltiple sclerosis
C roh n ’s d isease a n d m u ltiple sclerosis … … … …
… … … …
… … … …
… … …
5 5
5 5
5 5
5 5
2 .7 .1
R h eu m a toid arth ritis (R A )… … …
5 5
2 .7 .1 .1
D efin ition… … … ..
5 5
2 .7 .1 .2
D isease p revalen ce b y age an d gend er… … … .
5 5
2 .7 .1 .3
P ath ogenesis… … … ...
5 6
2 .7 .1 .4
C lin ical p resen tation … … …
5 7
2 .7 .1 .5
D ia gn ostic criteria… … … ...
5 8
2 .7 .1 .6
D esired ou tcom e… … … ...
5 8
2 .7 .1 .7
P h arm a co lo gica l trea tm ent… … … ....
5 9
2 .7 .2
C roh n ’s d isease… … … .
7 3
2 .7 .2 .1
D efin ition… … … ...
7 3
2 .7 .2 .2
D isease p revalen ce b y age an d gend er… … … ..
7 3
2 .7 .2 .3
C lin ical p resen tation … … … .
7 3
2 .7 .2 .4
D ia gn ostic criteria… … … ....
7 4
2 .7 .2 .5
D esired ou tcom e… … … ...
7 4
2 .7 .2 .6
P h arm a co lo gica l trea tm ent… … … ...
7 4
2 .7 .3
M u ltip le sclerosis (M S )… … … .
8 1
2 .7 .3 .1
D efin ition… … … ...
8 1
2 .7 .3 .2
D isease p revalen ce b y age an d gend er… … … .
8 1
T able of con tents
_ __ _ _ __ __ _ _ __ __ _ _ _ _ __ __ _ _ __ __ _ _ __ __ __ _ _ __ __ _ _ __ __ _ __ _ __ __ _ _ __ __ _
2 .7 .3 .4
D ia gn ostic criteria… … … ...
8 2
2 .7 .3 .5
D esired ou tcom e… … … ..
8 2
2 .7 .3 .6
P h arm a co lo gica l trea tm ent… … … ...
8 2
2 .8
2 .8
2 .8
2 .8
A d v erse reaction s, co n tra
A d v erse reaction s, co n tra ----indications a nd drug
A d v erse reaction s, co n tra
A d v erse reaction s, co n tra
in d ication s a n d d rug
in d ication s a n d d rug
in d ication s a n d d rug ----drug interactions of bio lo gic
d rug in teraction s of bio lo gic
d rug in teraction s of bio lo gic
d rug in teraction s of bio lo gic
im m u n om o d u lators
im m u n om o d u lators
im m u n om o d u lators
im m u n om o d u lators… … … ..
… … … ..
… … … ..
… … … ..
9 0
9 0
9 0
9 0
2 .8 .1
In trod u ction… … … ...
9 0
2 .8 .2
A d v erse reaction s… … …
9 0
2 .8 .3
C on tra-in d icatio n s a nd in tera ction s… … … ...
9 3
2 .9
2 .9
2 .9
2 .9
C ost im p a ct of biolo gics
C ost im p a ct of biolo gics
C ost im p a ct of biolo gics
C ost im p a ct of biolo gics … … … ...
… … … ...
… … … ...
… … … ...
9 6
9 6
9 6
9 6
2 .9 .1
In trod u ction… … … ...
9 6
2 .9 .2
G lobal an d regio nal cost im p a ct of biolo gics… … …
9 7
2 .1 0
2 .1 0
2 .1 0
2 .1 0
B iosim ilars: T h e fo llow
B iosim ilars: T h e fo llow
B iosim ilars: T h e fo llow
B iosim ilars: T h e fo llow ----on biologics
on biologics
on biologics
on biologics… … … ..
… … … ..
… … … ..
… … … ..
111108
0 8
0 8
0 8
2 .1 1
2 .1 1
2 .1 1
2 .1 1
L eg islation
L eg islation
L eg islation
L eg islation … … … .
… … … .
… … … .
… … … .
111110
1 0
1 0
1 0
2 .1 2
2 .1 2
2 .1 2
2 .1 2
P h arm a co econ om ic asp e
P h arm a co econ om ic asp e
P h arm a co econ om ic asp e
P h arm a co econ om ic asp ects o f biologic im m u n om od u latin g m ed icin e...… … … …
cts o f biologic im m u n om od u latin g m ed icin e...… … … …
cts o f biologic im m u n om od u latin g m ed icin e...… … … …
cts o f biologic im m u n om od u latin g m ed icin e...… … … …
1 1 2
1 1 2
1 1 2
1 1 2
2 .1 2 .1
In trod u ction… … … ...
1 1 2
2 .1 2 .2
P h arm a co eco nom ics… … … .
1 1 2
2 .1 2 .3
P h arm a co eco nom ic asp ects o f biolog ics… … … ...
1 1 3
2 .1 2 .4
P h arm a co eco nom ics app lied to R h eu m atoid arthritis… … …
1 1 4
2 .1 3
2 .1 3
2 .1 3
2 .1 3
C h ap ter su m m ary
C h ap ter su m m ary
C h ap ter su m m ary
C h ap ter su m m ary … … … …
… … … …
… … …
… … … …
1 1 8
1 1 8
1 1 8
1 1 8
T able of con tents
_ __ _ _ __ __ _ _ __ __ _ _ _ _ __ __ _ _ __ __ _ _ __ __ __ _ _ __ __ _ _ __ __ _ __ _ __ __ _ _ __ __ _
C h ap ter 3 :
C h ap ter 3 :
C h ap ter 3 :
C h ap ter 3 : M ethodo logy an d E m p irical in v estigation
3 .1
3 .1
3 .1
3 .1
R esearch objectiv es
R esearch objectiv es
R esearch objectiv es
R esearch objectiv es… … … .
… … … .
… … … . 119
… … … .
1 1 9
1 1 9
1 1 9
3 .1 .1
G en eral research objectiv e… … … …
1 1 9
3 .1 .2
S p ecific research objectiv es… … … ...
1 2 0
3 .2
3 .2
3 .2
3 .2
R esearch d esign
R esearch d esign
R esearch d esign
R esearch d esign … … … ..
… … … ..
… … … .. 121
… … … ..
1 2 1
1 2 1
1 2 1
3 .2 .1
D ru g u tilisation rev iew … … … ...
1 2 1
3 .2 .1 .1
R etro spective d rug u tilisatio n rev iew (rD U R )… … … …
1 2 3
3 .3
3 .3
3 .3
3 .3
R esearch m eth odo logy
R esearch m eth odo logy
R esearch m eth odo logy
R esearch m eth odo logy … … … .
… … … .
… … … .
… … … . 124
1 2 4
1 2 4
1 2 4
3 .3 .1
D ata sou rce… … … ...
1 2 4
3 .3 .2
S tu d y p op u latio n… … … ....
1 2 4
3 .4
3 .4
3 .4
3 .4
D ata an alysis
D ata an alysis
D ata an alysis
D ata an alysis … … … …
… … … …
… … …
… … … …
1 2 7
1 2 7
1 2 7
1 2 7
3 .4 .1
C lassification system s… … … .
1 2 8
3 .4 .1 .1
M ed ication… … … …
1 2 8
3 .4 .1 .2
D em ograp h ic p ara m eters… … … .
1 2 9
3 .4 .1 .3
G en eral p aram eters… … … .
1 3 0
3 .4 .2
D escrip tiv e m easu res… … … ..
1 3 1
3 .4 .2 .1
P rev alence… … … .
1 3 1
3 .4 .2 .2
P rescribing p atterns… … … …
1 3 2
3 .4 .2 .3
C ost… … … ..
1 3 2
T able of con tents
_ __ _ _ __ __ _ _ __ __ _ _ _ _ __ __ _ _ __ __ _ _ __ __ __ _ _ __ __ _ _ __ __ _ __ _ __ __ _ _ __ __ _
C h ap ter 4 :
C h ap ter 4 :
C h ap ter 4 :
C h ap ter 4 : R esu lts an d d iscu ssion
4 .1
4 .1
4 .1
4 .1
I n trod u ctio n
I n trod u ctio n
I n trod u ctio n
I n trod u ctio n … … … .
… … … .
… … … .
… … … .
1 3 9
1 3 9
1 3 9
1 3 9
4 .1 .1
P resen tation of th e d ata an a lysis… … … .
1 3 9
1 3 9
1 3 9
1 3 9
4 .1 .2
D efin itio n s… … … ..
1 4 1
4 .1 .3
A n n ota tion s concern in g an a lysis o f th e d ata… … … .
1 4 2
4 .2
4 .2
4 .2
4 .2
A
A
A
A n alysis of th e d a tabase
n alysis of th e d a tabase
n alysis of th e d a tabase
n alysis of th e d a tabase… … … .
… … … .
… … … .
… … … .
1 4 4
1 4 4
1 4 4
1 4 4
4 .2 .1
G en eral analysis o f total d atabase… … … ....
1 4 4
4 .2 .2
A n alysis of total d atabase accord in g to d em o grap h ic p aram eters… … … ..
1 4 7
4 .2 .2 .1
A n alysis accord in g to gen der… … … ...
1 4 7
4 .2 .2 .1 .1
A n alysis of claim s m ad e for fem ale p atien ts… … … … ...… … … ....
1 4 8
4 .2 .2 .1 .2
A n alysis of claim s m ad e for m ale p atien ts..… … … ...
1 5 0
3 .4 .3 .1
A rith m etic m ean (A v erage v alu e)… … … ..
1 3 4
3 .4 .3 .2
S ta nd ard d ev iation … … … .
1 3 4
3 .4 .3 .3
C ost-p rev alen ce in d ex… … … ..
1 3 5
3 .4 .3 .4
E ffect siz es / “d ”-v a lue… … … ...
1 3 6
3333 .5
.5
.5
.5
E th ical con sid eration s
E th ical con sid eration s
E th ical con sid eration s
E th ical con sid eration s… … … …
… … … …
… … … …
… … …
1 3 7
1 3 7
1 3 7
1 3 7
3 .6
3 .6
3 .6
3 .6
R eliab ility an d v alid ity of
R eliab ility an d v alid ity of
R eliab ility an d v alid ity of
R eliab ility an d v alid ity of d ata… … … ...… … … .
d ata… … … ...… … … .
d ata… … … ...… … … .
d ata… … … ...… … … .
1 3 7
1 3 7
1 3 7
1 3 7
3 .7
3 .7
3 .7
3 .7
R esu lts an d d iscu ssion
R esu lts an d d iscu ssion
R esu lts an d d iscu ssion
R esu lts an d d iscu ssion … … … …
… … … …
… … … …
… … …
1 3 8
1 3 8
1 3 8
1 3 8
3 .8
3 .8
3 .8
3 .8
C on clu sion s an d recom m end atio n s
C on clu sion s an d recom m end atio n s
C on clu sion s an d recom m end atio n s
C on clu sion s an d recom m end atio n s… … … …
… … … …
… … … …
… … …
1 3 8
1 3 8
1 3 8
1 3 8
3 .9
3 .9
3 .9
T able of con tents
_ __ _ _ __ __ _ _ __ __ _ _ _ _ __ __ _ _ __ __ _ _ __ __ __ _ _ __ __ _ _ __ __ _ __ _ __ __ _ _ __ __ _
4 .2 .2 .1 .3
S u m m ary of an alysis of total d ataba se accord ing to gen d er… … … ...
1 5 3
4 .2 .2 .2
A n alysis acco rd in g to a ge… … … .
1 5 4
4 .2 .2 .2 .1
A n alysis of age grou p 1 (< 2 5 years)… … … ...
1 5 4
4 .2 .2 .2 .2
A n alysis of age grou p 2 (2 5 – 3 9 yea rs)… … … ..
1 5 7
4 .2 .2 .2 .3
A n alysis of age grou p 3 (4 0 – 6 4 yea rs)… … … ..
1 5 9
4 .2 .2 .2 .4
A n alysis of age grou p 4 (≥ 65 years)… … … ..
1 6 2
4 .2 .2 .2 .5
S u m m ary of an alysis of total d ataba se accord ing to age… … … ...
1 6 4
4 .3
4 .3
4 .3
4 .3
A n aly sis of th e target p opu lation
A n aly sis of th e target p opu lation … … … .
A n aly sis of th e target p opu lation
A n aly sis of th e target p opu lation
… … … .
… … … .
… … … .
1 6 7
4 .3 .1
G en eral analysis of th e targ et p op u lation … … … ..
1 6 8
4 .3 .1 .1
N u m ber of p atients an d av erage n u m ber of p rescrip tio n s p er p atient p er y ear… .
1 6 8
4 .3 .1 .2
N u m ber of m ed icin e item s an d av erage cost p er m ed icin e item … … … ...
1 7 0
4 .3 .1 .3
N u m ber of p rescriptio ns an d av era ge co st p er p rescrip tion … … … ...
1 7 5
4 .3 .1 .4
T o tal an n u al m ed icin e exp en d itu re and th e c on tribu tion of th e m edical aid
sch em e an d th e p atien t to th e to tal m ed ication cost… … … .
1 7 8
4 .3 .1 .5
S u m m ary of an alysis of targ et p op u lation… … … ..
1 8 0
4 .3 .2
A n alysis of th e target p op u lation acco rd in g to g en d er… … … .
1 8 2
4 .3 .2 .1
N u m ber of p atien ts an d av erage n u m ber o f p rescrip tion s per patien t per year
accord in g to gen d er… … … ...… … ...
1 8 2
4 .3 .2 .2
N u m ber of p rescriptio ns an d av era ge co st p er p rescrip tion a ccord ing to gend er...
1 8 6
4 .3 .2 .3
T o tal an nu a l m ed icin e ex pen d iture a n d th e c ontrib u tion of th e m ed ica l aid
sch em e an d th e p atien t to th e to tal m ed ication cost accord ing to gend er… … … .
1 9 1
T able of con tents
_ __ _ _ __ __ _ _ __ __ _ _ _ _ __ __ _ _ __ __ _ _ __ __ __ _ _ __ __ _ _ __ __ _ __ _ __ __ _ _ __ __ _
4 .3 .3
A n alysis of target p opu latio n accord in g to ag e… … … ...
1 9 4
4 .3 .3 .1
N u m ber of p atients an d av erage n u m ber of p rescrip tio n s p er p atient p er y ear
accord in g to age g roup s… … … ...
1 9 4
4 .3 .3 .2
N u m ber of p rescriptio ns an d av era ge co st p er p rescrip tion a ccord ing to ag e
grou p s… … … ...
1 9 7
4 .3 .3 .3
T o tal an nu a l m ed icin e ex pen d iture a n d th e c ontrib u tion of th e m ed ica l aid
sch em e an d th e p atien t to th e to tal m ed ication cost accord ing to age grou p s… ...
2 0 5
4 .3 .3 .4
S u m m ary of th e an a ly sis of th e target p op u lation a cco rd in g to a ge group s...… ....
2 0 9
4 .3 .4
S u m m ary of th e targ et p o pu lation… … … .
2 1 0
4 .4
4 .4
4 .4
4 .4
G en eral an aly sis of selected au toim m u n e d isea ses
G en eral an aly sis of selected au toim m u n e d isea ses … … … .
G en eral an aly sis of selected au toim m u n e d isea ses
G en eral an aly sis of selected au toim m u n e d isea ses
… … … .
… … … .
… … … ....
...
...
...
2 1 2
2 1 2
2 1 2
2 1 2
4 .4 .1
A n alysis of p atien ts w ith R h eu m ato id A rth ritis (R A )… … … ..
2 1 3
4 .4 .1 .1
N u m ber of R A p a tien ts o n th e d atabase betw een 2 0 05 an d 2 0 0 8 … … … ..
2 1 3
4 .4 .1 .2
T o p ten m ed icin e item s a nd p h arm acolog ical g rou p s claim ed for R A p atien ts
d u ring each p hase… … … ...
2 1 4
4 .4 .1 .3
N u m ber of m ed icin e item s an d p rescrip tion s claim ed fo r R A p atien ts… … … …
2 2 3
4 .4 .1 .4
A v erage n u m ber o f m ed icin e item s p er p rescrip tion per R A p a tien t… … … … ...
2 2 5
4 .4 .1 .5
A v erage cost p er m ed icin e item a n d p rescrip tion for R A p atien ts p er p ha se… …
2 2 7
4 .4 .1 .6
A n alysis of th e total m ed icin e treatm en t co st o f R A p er p h ase… … … ..
2 3 4
4 .4 .1 .7
A v erage cost p er m ed icin e item p er R A p atien t an d th e av era ge cost p er
p rescription p er R A p atient… … … ..
2 3 8
4 .4 .1 .8
S u m m ary of an alysis of p atien ts w ith rh eu m a toid a rth ritis… … … ..
2 4 0
T able of con tents
_ __ _ _ __ __ _ _ __ __ _ _ _ _ __ __ _ _ __ __ _ _ __ __ __ _ _ __ __ _ _ __ __ _ __ _ __ __ _ _ __ __ _
4 .4 .2 .1
N u m ber of M S p atien ts on th e d a tabase betw een 2 0 0 5 a n d 2 0 0 8… … … .
2 4 1
4 .4 .2 .2
T o p ten m ed icin e item s a nd p h arm acolog ical g rou p s claim ed for M S p a tien ts
d u ring each p hase… … … ...
2 4 2
4 .4 .2 .3
N u m ber of m ed icin e item s an d p rescrip tion s claim ed fo r M S p a tients… … … …
2 5 0
4 .4 .2 .4
A v erage n u m ber o f m ed icin e item s p er p rescrip tion per M S p atien t… … … … ...
2 5 3
4 .4 .2 .5
A v erage cost p er m ed icin e item a n d p rescrip tion for M S p a tien ts p er p h ase… …
2 5 4
4 .4 .2 .6
A n alysis of th e total m ed icin e treatm en t co st o f M S p er p h ase… … … .
2 6 0
4 .4 .2 .7
A v erage cost p er m ed icin e item p er M S p atien t an d th e av erage cost p er
p rescription p er M S p atient… … … .
2 6 4
4 .4 .2 .8
S u m m ary of an alysis of p atien ts w ith M S … … … ..
2 6 6
4 .3 .3
A n alysis of p atien ts w ith C roh n ’s d isease… … … ..
2 6 8
4 .4 .3 .1
N u m ber of C ro h n ’s d isease p atien ts on the d atabase betw een 2 0 0 5 a n d 2 0 08 … .
2 6 8
4 .4 .3 .2
T o p ten m ed icin e item s a nd p h arm acolog ical g rou p s claim ed for C roh n ’s d isea se
p atien ts d u rin g each p h ase… … … ...
2 6 9
4 .4 .3 .3
N u m ber of m ed icin e item s an d p rescrip tion s claim ed fo r C roh n ’s d isease p atien ts
2 7 7
4 .4 .3 .4
A v erage n u m ber o f m ed icin e item s p er p rescrip tion per C ro h n ’s d isease
p atien t… … … ..
2 8 0
4 .4 .3 .5
A v erage cost p er m ed icin e item a n d p rescrip tion for C roh n ’s’ d isease p atien ts p er
p h ase… … … .
2 8 2
4 .4 .3 .6
A n alysis of th e total m ed icin e treatm en t co st o f C rohn ’s d isea se p er p h ase… … ..
2 8 7
4 .4 .3 .7
A n alysis of th e av erag e cost p er m ed icin e item p er C roh n ’s d isease p atien t an d
av erag e cost p er p rescrip tion p er C roh n ’s d isease p atien t… … … ...
2 8 9
T able of con tents
_ __ _ _ __ __ _ _ __ __ _ _ _ _ __ __ _ _ __ __ _ _ __ __ __ _ _ __ __ _ _ __ __ _ __ _ __ __ _ _ __ __ _
4 .5
4 .5
4 .5
4 .5
C h a p ter su m m ary… … … …
C h a p ter su m m ary… … …
C h a p ter su m m ary… … … …
C h a p ter su m m ary… … … …
2 9 2
2 9 2
2 9 2
2 9 2
C h ap ter 5 :
C h ap ter 5 :
C h ap ter 5 :
C h ap ter 5 : C on clu sion s a nd recom m en da tion s
5 .1
5 .1
5 .1
5 .1
C o n clu sion s
C o n clu sion s
C o n clu sion s
C o n clu sion s… … … ...
… … … ...
… … … ...
… … … ...
...
...
... 2 93
2 9 3
2 9 3
2 9 3
5 .2
5 .2
5 .2
5 .2
R eco m m en d ation s
R eco m m en d ation s
R eco m m en d ation s… … … …
R eco m m en d ation s
… … … …
… … … ...
… … … …
… … … ...
… … … ...
… … … ...
...
...
... 3 06
3 0 6
3 0 6
3 0 6
5 .3
5 .3
5 .3
5 .3
L im itation s
L im itation s
L im itation s
L im itation s… … … …
… … … …
… … … …
… … … …
…
…
… 3 06
3 0 6
3 0 6
3 0 6
5 .4
5 .4
5 .4
5 .4
C h a p ter su m m ary
C h a p ter su m m ary
C h a p ter su m m ary
C h a p ter su m m ary … … … …
… … … …
… … … …
… … … …
…
… 3 07
…
3 0 7
3 0 7
3 0 7
B ibliograp h y
B ibliograp h y
B ibliograp h y
B ibliograp h y … … … .
… … … .
… … … . 3 08
… … … .
3 0 8
3 0 8
3 0 8
A p p en d ix A :
A p p en d ix A :
A p p en d ix A :
A p p en d ix A : T herap eutic biological p rod u cts… … … ...
3 2 6
3 2 6
3 2 6
3 2 6
A p p en d ix B :
A p p en d ix B :
A p p en d ix B :
A p p en d ix B :
A p p en d ix tables… … … .
3 3 2
3 3 2
3 3 2
3 3 2
A p p en d ix C :
A p p en d ix C :
A p p en d ix C :
A p p en d ix C : A bstract su bm itted to a n d a ccep ted by IS P O R 1 3
thA n n u a l E u rop ean C ongress.
4 0
4 0
4 0 3
4 0
33
3
_ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ ___ _ _ _ _ _ __ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ ___ _ _ _ _ _ __ _ _ _ __ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ ___ _ _ _ _ _ __ _ _ _ __ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ ___ _ _ _ _ _ __ _ _ _ __ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ __ __ _ _ _ _ _ _ _ _ _ _ __ _ _ __ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _