Search PubMed⌕ Search

Biomedical subjects

A Messori

Publications and source records attributed to A Messori.

At least 19 recordsLinked to original sources
PubMed1998

Adjunctive lamotrigine therapy in patients with refractory seizures: a lifetime cost-utility analysis.

OBJECTIVE: Lamotrigine as add-on treatment (500 mg per day) is effective in patients with refractory epilepsy, but its high cost requires a pharmacoeconomic analysis. We conducted a retrospective lifetime cost utility study in which clinical data were derived from a recent placebo-controlled clinical trial, cost-of-illness data were drawn from a previous ad-hoc study, and quality-of-life values were obtained by prospectively interviewing a separate group of 81 patients referred to our institution with epilepsy. RESULTS: Our analysis showed that chronic lamotrigine treatment implies an incremental lifetime cost of about $1,600,000 for every 100 patients. Incremental lifetime utility was around 40 quality-adjusted life-years (QALYs) for every 100 patients. On the basis of these data, adjunctive lamotrigine was estimated to cost approximately $41,000 per QALY gained. Sensitivity testing suggested a range of $25,000-$85,000 per QALY gained. CONCLUSION: Adjunctive lamotrigine (500 mg per day) in refractory epilepsy seems to have a worse pharmacoeconomic profile than many pharmacological treatments commonly used in areas other than epilepsy. Further data are needed to determine if lamotrigine can be equally effective at lower (and less costly) daily doses which could markedly improve its pharmacoeconomic characteristics.

Adjuvants, Pharmaceutic↗
PubMed1998

Cost-effectiveness of interferon in chronic myeloid leukaemia: analysis of four clinical studies.

BACKGROUND: Analysis of published survival curves can be used as the basis for incremental cost-effectiveness analyses in which two treatments are compared with one another in terms of cost per life-year saved. In patients with chronic myeloid leukaemia in chronic phase, long-term treatment with alpha-interferon has been reported to improve survival in comparison with standard treatments with cytotoxic drugs. To assess the pharmacoeconomic profile of interferon treatment in terms of cost per life-year gained, we conducted an incremental cost-effectiveness analysis. PATIENTS AND METHODS: The clinical material utilised in our analysis derived from four published randomised trials comparing interferon vs. busulphan or hydroxyurea. The Gompertz model was used to estimate the total lifetime values of patient-years of subjects receiving interferon in comparison with subjects given a standard cytotoxic treatment. RESULTS: Our primary analysis showed that maintenance treatment with interferon improved survival expectancy by 37 to 93 discounted years for every 100 patients. The incremental cost-effectiveness ratio of interferon vs. cytotoxic therapy ranged from $93,000 to $226,000 per life-year gained (discounted costs per discounted years). A secondary analysis showed that the dose of interferon had significant influence on the cost-effectiveness ratio. Because our literature search identified a fifth study that showed an extremely favourable outcome using interferon but that was not included in our primary analysis due to its design, we conducted another secondary analysis based on these five studies that, however, confirmed the results of the primary analysis. CONCLUSIONS: Our study indicates that an unselected long-term treatment with interferon implies an unfavourable cost effectiveness ranking in comparison with data of cost per life-year gained which had previously been obtained from other types of medical intervention.

Area Under Curve↗
PubMed1997

Adjuvant cyclophosphamide, methotrexate and fluorouracil for node-positive breast cancer: a lifetime cost-utility analysis based on a modified Q-TWIST method.

The Q-TWIST (time spent without symptoms and toxicity) method [1-4] and the Gompertz extrapolation method [5-11] are two techniques that have been proposed for evaluating survival in cancer patients. The mathematical basis of the Q-TWIST method relies on estimating the area under the survival curve and partitioning its value into three components with different levels of quality of life (presence of toxicity, presence of symptoms, absence of symptoms and toxicity). The Gompertz approach utilises a curve-fitting procedure to extrapolate the survival curves to infinity. A recent report [12] has described a combined application of the Q-TWIST method and the Gompertz approach ("extrapolated Q-TWIST" method), which allows one to conduct a cost-utility analysis with the calculation of the cost per QALY (quality-adjusted life year) gained. In this paper, we describe a reappraisal of an earlier cost-effectiveness study [7] by application of this extrapolated Q-TWIST method [12]. Our cost-effectiveness study [7] evaluated the pharmacoeconomic profile of adjuvant cyclophosphamide, methotrexate and fluorouracil (CMF) in patients with node-positive breast cancer [13] and utilised a Gompertz analysis to estimate lifetime overall survival (OS), which was 862 and 756 discounted years per 100 patients in the CMF and the control groups, respectively. In applying the extrapolated Q-TWIST method to this data set, a second Gompertz analysis is carried out on the disease-free survival (DFS) curve of the two patient groups. Lifetime DFS of Bonadonna's patients can thus be estimated as 741 years in the CMF group and 572 years in the controls (discounted values normalised to 100 patients). Figure 1 shows the two curves of OS and DFS for the CMF group and the partition of the area under the OS curve into its three components. To introduce an assessment of quality of life into these data, the Q-TWIST method partitions the value of OS into the three components called TWIST (absence of symptoms and toxicity), TOX (time spent with toxicity) and REL (survival after relapse). Hence, OS = TWIST + REL + TOX, where REL = OS - DFS. In the control group, TOX = O and TWIST = DFS because no treatment-related toxicity is present.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Survival curve fitting using the Gompertz function: a methodology for conducting cost-effectiveness analyses on mortality data.

The analysis of published survival curves can be the basis for incremental cost-effectiveness evaluations in which two treatments are compared with each other in terms of cost per life-year saved. The typical case is when a new treatment becomes available which is more effective and more expensive than the corresponding standard treatment. When effectiveness is expressed using the end-point of mortality, cost-effectiveness analysis can compare the (incremental) cost associated with the new treatment with the (incremental) clinical benefit measured in terms of number of life-years gained. The (incremental) cost-effectiveness ratio is therefore quantified as cost per life-year gained. This pharmacoeconomic methodology requires that the total patients years for the treatment and the control groups are estimated from their respective survival curves. We describe herein a survival-curve fitting method which carries our this estimation and a computer program implementing the entire procedure. Our method is based on a non-linear least-squares analysis in which the experimental points of the survival curve are fitted to the Gompertz function. The availability of a commercial program (PCNONLIN) is needed to carry out matrix handling calculations. Our procedure performs the estimation of the best-fit parameters from the survival curve data and then integrates the Gompertz survival function from zero-time to infinity. This integration yields the value of the area under the survival curve (AUC) which is an estimate of the number of patients years totalled in the population examined. If this AUC estimation is performed separately for the two survival curves of two treatments being compared, the difference between the two AUCs permits to determine the incremental number of patient years gained using the more effective of the two treatments as opposed to the other. The cost-effectiveness analysis can consequently be carried out. An example of application of this methodology is presented in detail.

Antineoplastic Agents↗
PubMed1997

A retrospective cost-effectiveness analysis of interferon as adjuvant therapy in high-risk resected cutaneous melanoma.

To assess the cost per life year gained of alpha interferon (IFN) as adjuvant therapy for patients with high-risk resected melanoma, we conducted a retrospective, incremental cost-effectiveness analysis on clinical data from a previously published ECOG trial [9]. The Gompertz model was used to estimate the total lifetime values of patient-years of subjects receiving IFN in comparison with subjects given no adjuvant treatment. The ECOG trial involved 143 patients treated with high-dose IFN and 137 given no adjuvant treatment. Estimated drug expenditures were based on the assumption of a cost of $109.25 per 10 MU of IFN. Our analysis of the ECOG results showed that the adjuvant treatment of 100 subjects with high-dose IFN improved survival expectancy by 133.6 discounted life years or 308 undiscounted life years. The use of IFN (compared with no adjuvant treatment) implied an incremental cost of $16,467 per discounted life year saved (95% CI of $4752-50,000) or $7143 per undiscounted life year saved (95% CI of $3226-33,846). Sensitivity testing, in which variations were introduced in the main factors influencing cost and effectiveness, showed that this value always remained below $50,000. Our pharmacoeconomic analysis indicates that adjuvant treatment with high-dose IFN in patients with high-risk resected melanoma implies a favourable cost-effectiveness ratio. Because two other studies showed no significant survival benefit in patients receiving adjuvant IFN at lower values of total dose per patient, the controversy remains and confirmation data are needed for the ECOG trial's results. If these clinical results are confirmed, our analysis shows that the dosage of IFN given in this trial has a favourable pharmacoeconomic profile.

Antineoplastic Agents↗
PubMed1997

Current controversies in the application of meta-analysis (with special reference to oncological treatments)

Meta-analysis was proposed more than 20 years ago as an innovative technique for pooling the results of a series of clinical studies. This technique has a two-fold purpose: i) to retrieve pertinent clinical information without introducing selection biases; ii) to combine these clinical data obtained from different sources into a single synthetic index that summarises all available information. This review highlights the current perspectives in the application of meta-analysis and places particular emphasis on discussing the limitations of this technique that have been identified in recent years. Specific controversies in this area include: i) comparison between meta-analysis of the literature and meta-analysis of individual patient data; ii) heterogeneity of the clinical material introduced in the meta-analytic pooling; and iii) survival meta-analysis as a method for pooling long-term outcome data. After debating these three controversial points, this review examines the newest uses of meta-analysis that have been proposed for the evaluation of cost-effectiveness data and tries to identify the meta-analytic applications that will probably be expanded in the near future as opposed to those that will instead be developed less and less.

Clinical Trials as Topic↗
PubMed1997

Relationship between cathepsin-D content and disease-free survival in node-negative breast cancer patients: a meta-analysis.

Several reports have evaluated the correlation between cathepsin-D and overall survival or disease-free survival in node-negative breast cancer patients. Because conflicting data have so far been reported, a meta-analysis was conducted to clarify this problem. Eleven studies were included in our meta-analysis (total of 2690 patients). A specific meta-analytical methodology for censored data was used, and disease-free survival was the primary end point. Patients with low cathepsin-D levels had a significantly better disease-free survival than patients with high cathepsin-D values (meta-analytical odds ratio from 0.59 to 0.60 over the interval from 1 to 7 years). A secondary meta-analysis conducted exclusively on the data from eight studies based on cytosol assay gave substantially similar results. One limitation of our study is that the cut-off values to define high and low cathepsin-D concentrations were not identical in the various studies included in our meta-analysis (range from 20 to 78 pmol mg(-1) protein), thus introducing a possible bias in the statistical analysis of the data. However, a simulation based on the well-accepted method of the so-called publication bias showed that more than 100 null studies would be required to lead our results to a statistical level of non-significance. Considering the results of our meta-analysis, we conclude that the data presently available confirm a statistically significant association between high cathepsin-D values and poor disease-free survival in node-negative breast cancer patients.

Breast Neoplasms↗
PubMed1997

Cost-effectiveness of autologous bone marrow transplantation in patients with relapsed non-Hodgkin's lymphoma.

The analysis of published survival curves can be used as the basis for conducting cost-effectiveness analyses in which two treatments are compared in terms of cost per life year saved. In patients with relapsed chemosensitive non-Hodgkin's lymphoma, autologous bone marrow transplantation (ABMT) has been reported to improve survival in comparison with control patients who receive standard chemotherapy. An incremental cost-effectiveness analysis was undertaken in which the Gompertz model was used to determine a lifetime estimate of patient-years gained by subjects given ABMT in comparison with controls. Our study utilised the cost data calculated by Uyl-de Groot et al and the clinical data reported by Philip et al. This latter randomised clinical trial involved 55 patients subjected to ABMT and 54 controls given chemotherapy. Lifetime survival advantage for patients of the ABMT group was estimated as 3606 discounted patient-months every 100 patients. The use of ABMT as opposed to standard chemotherapy was found to imply an incremental cost of $9,229 per discounted life year gained (95% CI of $5,390 to $24,012). The cost-effectiveness ratio of ABMT in patients with relapsed chemosensitive non-Hodgkin's lymphoma is noticeably favourable.

Bone Marrow Transplantation↗
PubMed1997

Advanced HIV infection treated with zidovudine monotherapy: lifetime values of absolute cost-effectiveness as a pharmacoeconomic reference for future studies evaluating antiretroviral combination treatments. The Osservatorio SIFO sui Farmaci.

OBJECTIVE: This study was undertaken to evaluate the cost and the effectiveness of zidovudine monotherapy in patients with advanced HIV infection and to derive preliminary data on the cost-effectiveness of the triple treatment with saquinavir plus zalcitabine plus zidovudine compared with zidovudine alone. DESIGN: We used a combined method of survival analysis utilizing both the quality-adjusted time without symptoms or toxicity (Q-TWIST) method and the Gompertz approach. This combined method was applied to assess the absolute cost-effectiveness and cost-utility ratios of zidovudine monotherapy and to perform a preliminary incremental cost-effectiveness comparison of saquinavir plus zalcitabine plus zidovudine versus zidovudine alone. The clinical material used in our study was derived from two reports on the treatment of advanced HIV infection. Data of lifetime costs of HIV infection were obtained from published information. RESULTS: In patients with advanced HIV infection treated with zidovudine monotherapy, lifetime survival was 252.1 discounted person-years per 100 patients. Using an average lifetime cost of $93,000 (discounted) per individual, the absolute ratio of cost-effectiveness for zidovudine monotherapy was $36,980 per life-year, while the absolute cost-utility ratio was $47,112 per quality-adjusted life-year. In the comparative analysis of saquinavir plus zalcitabine plus zidovudine versus zidovudine alone, our calculations showed that the administration of the triple treatment can have an "average" cost-effectiveness, provided that mean lifetime survival per patient (discounted) is improved to at least 3.68 years (with an average survival gain of at least 14 mo per patient). CONCLUSIONS: The values of absolute cost-effectiveness and cost-utility ratios for zidovudine monotherapy are a useful reference point for further pharmacoeconomic studies in the area of antiretroviral drugs.

Anti-HIV Agents↗
PubMed1997

Combined therapy with 5-aminosalicylic acid tablets and enemas for maintaining remission in ulcerative colitis: a randomized double-blind study.

OBJECTIVES: To assess the efficacy of a combination of oral and topical 5-aminosalicylic acid (5-ASA) for the maintenance treatment of ulcerative colitis, we undertook a double-blind randomized clinical trial. METHODS: Patients aged 18 to 65 yr (with disease extent greater than proctitis only) were eligible for inclusion in the study if they met the following criteria: (a) history of two or more relapses in the last year; (b) achievement of remission in the last 3 months (with maintenance of remission for at least 1 month). Patients enrolled in the study were randomly assigned to one of the two following 1-yr treatments: (1) combined therapy with 5-ASA tablets 1.6 g/day and 5-ASA enemas 4 g/100 ml twice weekly; (2) oral therapy with 5-ASA tablets 1.6 g/day and placebo enemas/twice weekly. The main end point of the study was the maintenance of remission at 12 months. RESULTS: Upon completion of the study, relapse occurred in 13 of 33 patients in the combined treatment group versus 23 of 36 patients in the oral treatment group (39 vs 69%; p = 0.036). No significant side effects related to treatment were observed in either group. A simplified pharmacoeconomic analysis shows that this form of combined treatment can have a favorable cost-effectiveness ratio. CONCLUSIONS: Our results indicate that 5-ASA given daily by oral route and intermittently by topical route can be more effective than oral therapy alone. This form of combination treatment can be appropriate for patients at high risk of relapse.

Administration, Oral↗
PubMed1996

Pharmacoeconomic profile of paclitaxel as a first-line treatment for patients with advanced ovarian carcinoma. A lifetime cost-effectiveness analysis.

BACKGROUND: Analysis of published survival curves has recently been proposed as a method for conducting incremental cost-effectiveness analysis in which two treatments are compared with each other in terms of cost per year of life gained. In patients with advanced ovarian carcinoma, the combination of paclitaxel and cisplatin has been reported to improve survival more significantly than standard therapy with cyclophosphamide and cisplatin. However, the high cost of paclitaxel indicates a need for an evaluation of the pharmacoeconomic profile of these treatments. METHODS: The authors conducted an incremental cost-effectiveness analysis to assess the paclitaxel-based regimen in terms of cost per year of life gained. The analysis utilized data from a published controlled long term trial involving 184 patients treated with paclitaxel and cisplatin and 202 patients treated with cyclophosphamide and cisplatin. Gompertz' law was employed to obtain the lifetime estimate of the years gained by patients given the first treatment in comparison with patients given the second. RESULTS: The paclitaxel-based treatment was found to improve life expectancy by 46 years for every 100 patients. Costs of chemotherapy were higher in the paclitaxel group than in the standard-therapy group (the cost difference was $901,723 for every 100 patients; costs for treating febrile neutropenia induced by chemotherapy were taken into account). On the basis of these data of cost and effectiveness, the administration of paclitaxel and cisplatin was found to imply a cost per year of life gained of $19,603 more than standard chemotherapy. CONCLUSIONS: The pharmacoeconomic profile of paclitaxel compares favorably with economic data previously calculated for other types of pharmacologic treatment.

Antineoplastic Agents↗
PubMed1996

Cost-effectiveness of adjuvant chemotherapy with cyclophosphamide+methotrexate+fluorouracil in patients with node-positive breast cancer.

BACKGROUND: The analysis of published survival curves can be used as the basis for incremental cost-effectiveness analyses in which two treatments are compared with each other in terms of cost per life year saved. In patients with node-positive breast cancer adjuvant chemotherapy with cyclophosphamide+ methotrexate+fluorouracil has been reported to improve survival in comparison with patients who are not given this treatment. METHODS: To assess the pharmacoeconomic profile of this adjuvant chemotherapeutic regimen in terms of cost per life-year gained, we conducted an incremental cost-effectiveness analysis in which the Gompertz model was used to calculate the lifetime estimate of the patient-years gained by treated subjects compared to controls. RESULTS: Using data from a published, controlled long-term trial involving 207 patients treated with cyclophosphamide+methotrexate+fluorouracil and 179 controls, we estimated that this adjuvant chemotherapy improved life expectancy by 357 patient-years per 100 subjects. Direct costs, which were almost exclusively related to the administration of chemotherapy, were estimated to be US $159,516 per 100 patients. On the basis of these data, adjuvant chemotherapy was found to imply an incremental cost of US $447 per life-year saved. CONCLUSIONS: The cost-effectiveness ratio of adjuvant chemotherapy with cyclophosphamide+methotrexate+fluorouracil in patients with node-positive breast cancer seems to be particularly favourable in comparison with estimates of cost per life-year saved previously calculated for other types of pharmacological intervention.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis.

We conducted a two-part meta-analysis to assess the effectiveness of fluoroquinolones for preventing bacterial infections in granulocytopenic patients who are receiving chemotherapy for malignancies. Overall, 19 randomized studies met selection criteria and were included in this meta-analysis of 2,112 patients. Thirteen studies that compared the fluoroquinolones alone with control regimens (co-trimoxazole, oral nonabsorbable antibiotics, or placebo) and six studies that compared the fluoroquinolones plus prophylaxis for bacteremia due to gram-positive bacteria with control regimens (fluoroquinolones or oral nonabsorbable antibiotics) were included in the two meta-analyses. The results of the first meta-analysis indicate that fluoroquinolones alone are effective in preventing gram-negative bacteremia (overall odds ratio [OR], 0.09; 95% confidence interval [CI], 0.05-0.16; P < .001), but not gram-positive bacteremia (OR, 1.05; 95% CI, 0.76-1.45; P = .7), fever-related morbidity (OR, 0.76; 95% CI, 0.56-1.04; P = .09), and infection-related mortality (OR, 0.79; 95% CI, 0.47-1.34; P = .4). The results of the second meta-analysis indicate that a combination of fluoroquinolones plus prophylaxis for gram-positive bacteremia (penicillin, vancomycin, or macrolides) significantly reduces the occurrence of gram-positive bacteremia (OR, 0.46; CI, 0.33-0.63; P < .001) without affecting the incidence of fever-related morbidity (OR, 0.83; 95% CI, 0.62-1.13; P = .2) and infection-related mortality (OR, 0.74; 95% CI, 0.40-1.38; P = .3)

Anti-Bacterial Agents↗
PubMed1996

Cost effectiveness of adjuvant intraportal chemotherapy in patients with colorectal cancer.

Recent studies have shown that the analysis of published survival curves allows cost-effectiveness evaluations in which two treatments are compared with each other in terms of cost per life-year saved. In patients with colorectal cancer, the administration of adjuvant intraportal chemotherapy (with mitomycin and fluorouracil) has been reported to improve long-term survival in comparison with patients who are not given this treatment. To assess the pharmacoceconomic profile of this adjuvant chemotherapy, we carried out an incremental cost-effectiveness analysis in which we used the Gompertz model to estimate lifetime patient years gained by patients given this chemotherapy in comparison with controls. Using the data of a published controlled long-term trial involving 252 patients treated with intraportal chemotherapy and 253 controls who were given no such therapy, we estimated that the adjuvant treatment improved life expectancy by 89 discounted patient years (or 218 undiscounted patient years) every 100 patients. Cost of chemotherapy was calculated as $107,720 for every 100 patients. On the basis of these data, the administration of adjuvant intraportal chemotherapy was found to imply an incremental cost of $1,210 per discounted life-year saved or $494 per undiscounted life-year saved. The cost-effectiveness ratio of adjuvant intraportal chemotherapy in patients with colorectal cancer seems to be particularly favorable in comparison with estimates of cost per life-year saved previously obtained in many other areas of pharmacological intervention. Even though systemic fluorouracil + levamisole is the form of adjuvant chemotherapy most widely used in these patients, intraportal chemotherapy has the best cost-effectiveness profile.

Antineoplastic Combined Chemotherapy Protocols↗