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Is Ondansetron Cost Effective? Jacqllcs Bonneterre Centre Oscar Lambret, Lille, France

Johnson NE. Nash DB. CarpcntcrCE,ct OIL Ondansetron : costs and resource utilisation in a US Icaching hospital setting. PharmacoEconomics 1993: 3: 471-81

Summary

5-Hydroxytryptaminc3 (5-HT3) receptor antag­onists are a major breakthrough in the prevention of nausea and vomiting induced by cancer chemo­therapy. The acquisition cost of these drugs is con­siderably higher than for more conventional anti­emetics. In this study, the authors reported on the economic consequences of givi ng ondansclfon in Thomas Jefferson University Hospital, Phi ladel­phia, USA.

The st udy was divided into 3 parts. The first part was retrospecti ve, and had the primary aim of com­paring lengths of hospital stay and overall hospital costs for patients who had received intravenous ondansetron or standard antiemetic therapy. The purpose of the second part, which was prospective, was to determine the cost of emesis. In the thi rd part, quality of li fe was stud ied: however. the re­sults of th is part were difficult to interpret because only 27 of the 52 selected patients completed the questionnaire, and only 4 of these patients received standard antiemetic therapy.

In the retrospective study. costs were evaluated for patients who never received ondan setron , those who always received it, and those who received ondansetron during at least I hospital stay. [n the prospective study, the costs associated with vom it­ing were nursing time, time required to obtain an­tiemetic therapy from the pharmacy, telephone calls to contact physicians, additional use of ancil­lary services, and laundry costs for soi led items.

In the retrospective analysis, it was found that

the average length of hospital stay fo r patients who were always given ondansetron was significant ly shorter than for those who never received it. Sim­ilar results were obtained for the subset of patients with respiratory cancer who always or never re­ceived ondansetron, and after excluding patients admitted by I physician whose patients stayed sig­nificantly longer than those admitted by other phy­sicians. The average total hospital costs were not different between these 2 groups, although ondan­setron contributed an additional cost of $US270 per patient. Simi lar resul ts were obtained when comparing the hospital costs of patients during courses with or without ondansetron.

Patients who always received ondansetron were more li kely to be receiv ing highly emetogenic che­motherapy. Moreover. the percentage of Medicare patients in this group was lower.

Specific costs associated with nausea and vom­iting were evaluated prospectively in 88 patients. Complete control o f nausea and vomiting was ob­served in 37% of patients. A total of 801 minutes of nursing time were needed to deal with 189 epi­sodes of vomiting or severe nausea (4 ± 2.2 minutes per episode), Other activities did not contribute significantly to the cost: thus, the average hospital cost was estimated to be $US2.99 per episode. Un­fortunately, all vomiting episodes occurred in pa­tients receiving ondansetron; no comparison with the cost of vomiting in patients not receiving ondansetron is therefore possible.

The authors concluded that hospital costs fo r chemotherapy patients were not significantly higher when intravenous ondansetron was used to control nausea and vomiti ng. despite a 10-fold difference

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In acqu isition COSt S be tween ondunselron and standard ant iemet ic therapy althe study si te.

Commentary

Compared wi th o the r anticmct ics. 5- HTJ recep­to r a ntagonists arc very efficient in preventing acute nausea and vomiting ca used by cytotoxic drugs. In mllny countries. ondanselron was in clin ­ical usc fo r some time before it was approved b y local autho rities because o f extensive media cov­erage. The high d emand for ondansctron by both patient s lind physic ians probabl y explains. aileasl in pan . ils rapid approval by licensing authorities and ils high a cqui sition cost.

Acqui sition cost i s only I component in volved in calcul ating the true cost of drug therapy. In the case o f ant ic mctics. all hospital costs incurred through n ausea and vomit ing should be taken into account before decid ing w hether a treatment is cost cffec tive. Stud ics li ke that cond uctcd b y Johnson et al. arc start ing to appear in the li tcrature: how­ever, cautio n is necessary in interprcting the results o f such stud ies, which might be biased clinically. For example, it is debatable w hether nausca and vomiting necessi tate a longer l ength o f h o·spital stay. Most c hemotherapy regimens are adminis­tered in a day hospi tal and Ihe occurrence of nausea and vomiling docs nOI, in o ur experience. j usli fy hospital isatioll .

There was prob:lbly a se lection bias i n th is study bec:luse ondansetro n l ended t o be used in patients recei ving modcrate ly to highl y c metogenic chemo­therapy. In such piltients, hospitalisation was prob· ably justified for iI reason other than chcmother­apy- induced cmcsis. Howe ver, thi s is acceptable in thi s study becau se trea tme nt wa s g iven on an in­pati ent basis. A sccond po int fo r di scussio n is ond:lnsetron dose. At the time o f approval. Ihe rec­ommended dose of ondanselron was 24 to 32mg intravenously on the day of chcmolhernpy. followed by 8mg omlly every 8 hours for 3 10 5 d ays (not given in this st udy). Recent ly, il has been reported that 8mg intravenously was sufficient on day 1.111 FUrlhermo re, the manufacturer's recomme nded dose is 8mg orally every 12 hours for 3 to 5 days.

fllcqucs &mllclare

At these dosages. the acq uisition cost o f ondanset­ron is at least 3-fo ld lower in Ihe p revention of acute e mesis, and o ne-third lower in de layed e me­sis. However. i t is not yet clear whether a 1- or 2-day course o f ondansetron would be suffic ient : this would enable f urther cost reduct ions.

Acquisi tion costs vary between countries and between institutions wi lhin a country. In addi tion, the cost effecti ve ness o f ondansetro n i s likely to be different in patients rcceiving modcrately e meto­geni c regime ns compared with those rece ivin g highly e metogenic regimens. Ondansetron i s likel y to be most b eneficial in the latter case.

Quality of life was not adequately studied by Johnson and colleagues because few p:l1ie llis com­pleted the questionnaire, and because most of those who did had received o ndansetron. Thus, it was not possible to COmpare quality o f life betwee n treatments.

An in-depth rev iew of pharmacoccono mic stud­ies of ondansetro n has recently been published .lll In a study by Soukop et al.P! Ihe costs per success­full y treated p atient (i.e. no vom iting. retc hing o r adverse effects related to antiemet ic thempy) was £ 184.37 fo r ondansetron and £160.28 for metoelo­pramide. In another sludy,l4l thc 10lal di reci costs in patients rece iving o ndansetron were 2.S- fold hi gher than in palient s receiving rnetoc lopramide: all patie nts received hi ghly e metogenic che mother­apy. However, the cosls per successfu lly treated pa­tient (SO% with ondanselro n and 22% with l11eto­clopramide) were very similar and the 2 treHtments were thus equally cost effecti ve. In another sludy in patients recei ving hi ghly c me togenic c he mo­therapy, ondansetron was as cost cffecti ve as hi gh dose meloclopramide. despitc a 5-fold higher acqui­sition cost. ISI Usi ng a more ·strategic' model. JonesJ61 found that Ihe incremental cost of ondansetron treat ­ment, expressed a s a percentage. was between 3. 1 and 10.4% for acute e mesis and between 11.6 and 33.6% for delayed emesis when compared wilh a ·re ference' treatme nt. Thus, bec:luse it has no clear cli nical advant:lge in delayed emesis and because of its high acquisi tion cost. ondansctro n shou ld n o t be routinely used in this indication.

Current Comment

Cost-effectiveness studies are difficult to con­duct. All medical aspects must be considered (e.g. type of chemotherapy, type of patients, defi nition of success ful trcatment, dose of antiemetic, treat­ment as inpatient or outpatient. reason for treat­ment) as well as all economic aspects le.g. direct costs (acqui sition costs differ between institu­tions), costs of vomiting episodes, indirect costsl. Overall. studies show that ondansetron is generally as cost effecti ve as other antiemetics, and the im­proved clinical efriciency of ondansetron is asso­ciated with reduced costs due 10 nausea and vom­iting. Reducin g the dose of ondanselron allows a significant decrease in the acqu isit ion cost of treat­ment whi le maintaining efriciency. Thus, ondan­selron therapy becomes increasingly cost effecti ve as more clinical data are published.

References I. Seyna,·c C , Schul k r J. BU$Cr K . el at COIOp3ri5(>n of 1Jx, anti­

emelic effICacy of dirren:nt doses of ond~nsclron. given as

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ei lJx,r a continoous infusion or a single inlrJ"cnous dose. in x utc cisplati n· induce<l emes is. A multicentric, double·blind. r.mdomi~w paralle l grou p study. Br J Cancer 1992: 66: 192·7

2. PloskcrGL, Milne RJ . Ondanse lron: a pharmJclICcoOlomic and quality of life eva luation of its anti(mctic ac li vi ly in patienlS r«~iving car\CCr chemotherapy. PharmacoEconomic, 1992; 2: 285·304

) , Sookop M. McQu~ B. Humer E,eiaI.OndanSClrooCQI1lp3n:d wilh metoclopnmide in 1Jx, control of ~mesis and quality of life during n:pcale<l cJx,n1Clher1lpy for brea.~ cancer. Oncol· ogy 1992; 49: 295·3(»

4. Cunningham D. Gore M. Da"id5Oll N. e t al. The n:~1 OOl!ots of emesis. An eronomic analysis of ondansctron " S metoclopr,a· mide in controlli ng cmesis in patients n:ce;" inll chemother· apy for cancer. Eur J Cancer 199): 29A: 30)·6

5. Buxton MJ. O' Brien RJ . Economic c.-aluation or ond~nse lrQfl prc] imin~ry ana l y~is usi"!; clinical I,ia l data prior to Pfice sening. Sr J Cancer 1992; 66: 564·7

6. Jones AI... Lee GJ. Bosanquct N. The budgetary imJXICI or 511T· 3 receptor antagonists in the m~nagClTlc nl of chemothernpy indu,e<l enlCsis. cur J Can,cr 1993: 29A: 51·6

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