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Economic analysis of terminal care for patients with malignant osteolytic bone disease and pain treated with pamidronate |
Gessner U, Koeberle D, Thuerlimann B, Bacchus L, Horisberger B |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The use of pamidronate, 60 or 90 mg intravenously (i.v.), for palliation of patients with malignant osteolytic bone disease and pain.
Economic study type Cost-effectiveness study.
Study population The study population comprised male and female patients with advanced malignant bone disease and pain. It was stated that the selection criteria had been reported in the publication of the original trial (see Other Publications of Related Interest.
Setting The setting was primary and secondary care. The study was conducted in Switzerland.
Dates to which data relate The patients were recruited between October 1993 and April 1996. The effectiveness, resource use and charge data were obtained using this patient sample and related to the same dates. The price year was 1995.
Source of effectiveness data The effectiveness data were derived from a single study.
Link between effectiveness and cost data The costing was undertaken retrospectively on the same patient sample as that used in the effectiveness study. The cost data were only available for 55 of the 70 patients.
Study sample The study sample comprised 70 patients with a mean age of 62.7 years, who had advanced malignant bone disease. Forty-two patients (60%) had advanced breast cancer, 15 (21%) had multiple myelomas and 13 (19%) had other types of cancers. Twenty-four of the patients (34%) had stable disease, 28 (40%) progressive diseases and the rest were in remission or unclassified. Fifty-four of the patients (77%) received systemic antineoplastic treatment during the study period. It was stated that the sample size was chosen on the basis of statistical considerations of the effectiveness data (including precision and power of tests) and a reasonable timeframe for the study.
Study design The authors used the results of a published, randomised controlled trial (RCT). However, the design of this study was implicitly observational, since the effectiveness data from the two arms were aggregated. It was, therefore, an implicit assumption that the changes in outcome measures without treatment would be zero. For completeness, a single-centre, prospective double-blind RCT was employed in the analysis. Before randomisation, the patients were stratified according to their diagnosis (breast cancer, myeloma or other tumours). The patients were randomly assigned to receive 60 or 90 mg of disodium pamidrone, administered i.v. in 250 mL of 0.9% saline over 90 minutes. The methods of randomisation and blinding were not discussed. The study treatment comprised six cycles with intervals of 3 weeks (approximately 4.5 months). A follow-up of 6 months (or up to 12 months or until censoring wherever possible) was also analysed. The reasons for withdrawal from the study were death during the treatment phase (18 patients), death during the follow-up (14), refusal (1), and cost data unavailable (15).
Analysis of effectiveness It is unclear whether the censoring issue was properly accounted for in the analysis. The analysis seems to have been based on the availability of data on pain intensity, i.e. treatment completers only. The main outcomes were the intensity of the pain and the pain response. The pain response was defined as a reduction in pain intensity of at least 20% from the respective baseline value on at least two consecutive visits. Pain intensity was measured by the patients themselves using a 100-mm linear analogue scale (LASA). The results for pain intensity were evaluated in a total of 61 patients, decreasing to 57 (after the second pamidronate administration) and 34 (after the sixth pamidronate administration).
Effectiveness results The average pain intensity (+/- standard error) at baseline was 53 (+/- 4.8) mm on the LASA scale.
The change from baseline was -15% after the first administration of pamidronate (week 1) and -28% after the second (at week 2). Both were statistically significant, (p<0.05). The results were similar for the two treatment groups.
The changes in pain intensity for the 60-mg group were -14% after the first administration, -22% after the third administration, and -36% after the sixth administration. The changes in pain intensity for the 90-mg group were -15% after the first administration, -33% after the third administration, and -15% after the sixth administration.
No tests of statistically significant differences between the groups were reported.
About 60% (43 patients) were classified as pain responders.
Clinical conclusions The study showed that pamidronate achieved statistically significantly alleviation of pain in the studied patients. No consistent differences between the effectiveness of the two studied dosages (60 and 90 mg) were observed, although no statistical tests were reported.
Measure of benefits used in the economic analysis No summary measure of benefits was used in the economic analysis. The benefits are therefore associated with the pain relief results reported above. Thus, the analysis is of a cost-consequences design.
Direct costs The direct costs were analysed from the perspective of the third-party payer. The costs included were for the pamidronate treatments, and for the inpatient and outpatient costs incurred by patients in the treatment period, 6-month follow-up period and for up to 12 months of follow-up (or until censoring). The costs were incurred over less than 2 years and no discounting was therefore necessary. The charges made by the hospital, or invoiced by the practising physicians and reimbursed by the health insurance companies, were used as proxies of costs. The costs were calculated in ECUs at the 1995 conversion rate. The quantities of hospitalisations and radiotherapy days were also analysed, using data from the hospital participating in the study. There were no data on what the costs would have been with no treatment.
Statistical analysis of costs The costs were treated in a stochastic way. The means and standard errors of the means were reported.
Indirect Costs No indirect costs were included in the analysis.
Currency European currency units (ECU).
Sensitivity analysis No sensitivity analysis was carried out.
Estimated benefits used in the economic analysis See the 'Effectiveness Results' section.
Cost results Only the total cost for the intervention is presented here since the costs by intervention versus comparator were not given. The cost of pamidronate administration (including the cost of the personnel, materials, etc.) was ECU 180 per month. The total costs during the pamidronate treatment phase plus the 6-month follow-up phase were ECU 12,060 (+/-4,380) per patient.
Approximately half of the patients had hospitalisations for a variety of reasons. These results were derived using data from 56 patients during treatment with pamidronate, and 50 patients during the follow-up phase (31 patients during the 6-month follow-up and 19 during the 6- to 12-month follow-up). The median duration of hospitalisation (+/- standard error) was 3.5 (+/-1.0) days in terms of inpatient days per month. The analysis did not show statistically significant differences between the two treatment groups. On the basis of data from 57 patients, of which 30 were prescribed radiotherapy, the patients treated spent on average 1.45 (+/-0.25) days per month in hospital for radiotherapy.
Synthesis of costs and benefits Authors' conclusions The treatment with pamidronate reduced pain significantly but did not add noticeably to the costs.
CRD COMMENTARY - Selection of comparators The choice of the doses of pamidronate was explicitly justified. However, the explicit comparators for effectiveness were different to those used for the economic analysis. The implicit comparator was no treatment. Therefore, the authors appear to have assumed that effectiveness data that showed a reduction in pain in any treatment arm (either 60 or 90 mg) of the RCT was evidence of an improvement, compared with no treatment. In fact, this is equivalent to transforming the RCT into an observational design. Also, the cost data were lacking for no treatment. Finally, on ethical grounds, no treatment is unlikely to be a reasonable comparator in palliative care.
Validity of estimate of measure of effectiveness Although the study was an RCT and the study sample was representative of the study population, it is unclear how the censoring and missing data issues were accounted for in the analysis. It seems that the analysis used only those patients for whom data were available. Thus, the validity of the results could have been compromised. The pain intensity scores were treated as data with linear and quantitative properties, which the authors highlighted as a possible limitation. Moreover, both groups were pooled for the purpose of most of the analyses and compared with baseline, which therefore nullifies any gains arising from the RCT design, as alluded to earlier.
Validity of estimate of measure of benefit The authors did not derive a summary measure of health benefit.
Validity of estimate of costs All the categories of cost relevant to the perspective adopted seen to have been included in the analysis. Charges were used to evaluate the costs. Only the costs of patients for whom data were available were reported and, although statistical analyses of the costs were performed, the validity of the estimates could have been compromised. The resource use was partially addressed through complementary data sources, but no direct relationship with the estimated costs could be established. Appropriate currency conversions were performed. The main problem is that both groups were pooled for the purpose of the cost analyses, thus leaving no cost data for the comparator of no treatment.
Other issues The authors cited relevant studies and compared their findings with some of them. The issue of generalisability to other settings was not explicitly addressed. It was suggested that the inpatient costs could be considered representative for Switzerland. The authors acknowledged some limitations of the study. These included the underestimation of inpatient charges, and the possibility of treating LASA quantitatively and linearly.
Implications of the study The authors claimed that this study showed how an economic analysis can be "piggy-backed" onto an RCT. However, the design they used was wholly inappropriate to show the correlation between the effectiveness and cost, given the lack of data for the implicit comparator of no treatment. In fact, by their lack of acknowledgement of this, their conclusions regarding the reduced pain and "no noticeable" increase in the costs of pamidronate are extremely misleading.
Bibliographic details Gessner U, Koeberle D, Thuerlimann B, Bacchus L, Horisberger B. Economic analysis of terminal care for patients with malignant osteolytic bone disease and pain treated with pamidronate. Supportive Care in Cancer 2000; 8(2): 115-122 Other publications of related interest Koeberle D, Bacchus L, Senn HJ, Thuerlimann B. Pamidronate treatment in patients with malignant osteolytic bone disease and pain: a prospective randomised double-blind trial. Support Care Cancer 1999;7:21-7.
Indexing Status Subject indexing assigned by NLM MeSH Adult; Aged; Aged, 80 and over; Antineoplastic Agents /economics /therapeutic use; Bone Neoplasms /drug therapy /secondary; Diphosphonates /economics /therapeutic use; Double-Blind Method; Female; Hospitalization /economics; Humans; Male; Middle Aged; Pain, Intractable /drug therapy; Switzerland; Terminal Care /economics; Treatment Outcome AccessionNumber 22000000467 Date bibliographic record published 31/01/2003 Date abstract record published 31/01/2003 |
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