Pharmacoeconomic Analysis of Pegylated Liposomal Doxorubicin vs. Topotecan

Cost estimation for a pathology treated with any drug is made by identification of the resources used in the process, measuring and quantifying these resources and assigning a standard price to each of these resources (in monetary units).
Usually, in this type of pharmacoeconomic analysis, only direct medical costs are included, without taking into account indirect and intangibles costs.
Three main categories of costs, derived from routine clinical practice in the Spanish hospitals, were considered in the cost-minimisation analysis:

costs of the study drug;

costs of drug administration (e.g. cost of outpatient visits, infusions);

costs of managing adverse events (e.g. cost of additional medication, any associated hospitalisation).

To estimate the costs derived from each arm of the trial, the total amount of study drug per patient, used during the clinical trial, was calculated by multiplying each dose (mg m⁻²) administered by the patient's surface area and summing overall doses administered. The result was then multiplied by the cost of the study drug. The cost for outpatient consultations (at the beginning of each treatment cycle) and outpatient visits (for administration of each dose) were also added. In each administration of T, the use of antiemetic drugs (granisetron and tropisetron, in 66.7 and 33.3% of patients, respectively, according to expert opinion) was also required. Table 1Table 1

	Total mg drug used	Mg per patient	Total cycles	Cycles per patient	Total doses
PLD
(n=239)	94 447	395.18	1164	4.87	1164
Topotecan
(n=235)	15 653	66.60	1349	5.74	6673

PLD=pegylated liposomal doxorubicin hydrochloride.

shows the amounts of study drug and cycles (total and per patient) used to make these estimations (Gordon et al, 2001 (link); Smith et al, 2002 (link)).
The resources used to manage every adverse event were measured for each drug, PLD and T. First, frequency of adverse events by type and severity level for both drugs was analysed, as shown in Table 2Table 2

Adverse event type	Grade	PLD n (%)	Topotecan n (%)
Anemia	Total	319 (100)	985 (100)
	Grade I	199 (62)	363 (37)
	Grade II	101 (32)	476 (48)
	Grade III	18 (6)	134 (14)
	Grade IV	1 (0)	12 (1)
Thrombocytopenia	Total	71 (100)	944 (100)
	Grade I	54 (76)	434 (46)
	Grade II	14 (20)	272 (29)
	Grade III	3 (4)	175 (19)
	Grade IV	0 (0)	63 (7)
Neutropenia	Total	311 (100)	1438 (100)
	Grade I	153 (48)	296 (20)
	Grade II	105 (35)	378 (26)
	Grade III	42 (14)	427 (30)
	Grade IV	11 (3)	337 (24)
Sepsis	Total	4 (100)	17 (100)
	Grade I	0 (0)	0 (0)
	Grade II	1 (25)	5 (35)
	Grade III	3 (75)	3 (15)
	Grade IV	0 (0)	9 (50)
Fever	Total	69 (100)	65 (100)
	Grade I	36 (55)	31 (48)
	Grade II	26 (42)	20 (31)
	Grade III	2 (3)	8 (12)
	Grade IV	0 (0)	5 (9)
Stomatitis/Pharyngitis	Total	378 (100)	130 (100)
	Grade I	202 (53)	91 (70)
	Grade II	144 (38)	37 (28)
	Grade III	31 (8)	2 (2)
	Grade IV	1 (0)	0 (0)
Nausea/Vomiting	Total	386 (100)	567 (100)
	Grade I	236 (61)	333 (59)
	Grade II	110 (28)	175 (31)
	Grade III	37 (10)	51 (9)
	Grade IV	3 (1)	8 (1)
Diarrhoea	Total	74 (100)	126 (100)
	Grade I	42 (57)	68 (54)
	Grade II	26 (35)	47 (37)
	Grade III	5 (7)	10 (8)
	Grade IV	1 (1)	1 (1)
PPE	Total	379 (100)	2 (100)
	Grade I	195 (51)	2 (100)
	Grade II	120 (32)	0 (0)
	Grade III	62 (16)	0 (0)
	Grade IV	2 (1)	0 (0)

PLD=pegylated liposomal doxorubicin hydrochloride; PPE=palmar-plantar erythrodysesthesia.

(Gordon et al, 2001 (link); Smith et al, 2002 (link)). Then, the costs derived from the treatment of each type of adverse event in each of their severity levels were determined. These results were used to calculate the cost per adverse event and per patient. The estimated cost for each adverse event type was then added to obtain a total adverse event management cost per patient.