Real-world patient- and caregiver-reported outcomes in advanced breast cancer.

Background: Advanced breast cancer (abc) represents a substantial burden for patients and caregivers. In the present study, we aimed to estimate quality of life (qol), utility, productivity loss, pain, health care resource utilization, and costs for patients with abc, and qol, utility, and productivity loss for their caregivers. Methods: This multicentre prospective non-interventional study was conducted in Canada. Eligible participants were postmenopausal women with estrogen receptor-positive, her2-negative unresectable abc and their caregivers. Validated questionnaires were used to measure qol, utility, productivity loss, and pain. Patients and caregivers were classified into 4 health states typically used in oncology economic modelling: first-line progression-free (1l-pf), first-line progressive disease (1l-pd), second- or subsequent-line progression-free (≥2l-pf), and second- or subsequent-line progressive disease (≥2l-pd). Results: Most patients and caregivers accepted to participate, with total recruitment of 202 patients and 78 caregivers. Compared with patients in pf, patients in pd had lower mean qol scores (52.9 ± 29.9 for 1l-pd vs. 68.2 ± 23.2 for 1l-pf, and 54.0 ± 23.6 for ≥2l-pd vs. 66.0 ± 22.1 for ≥2l-pf), lower mean utility values (0.64 ± 0.22 for 1l-pd vs. 0.73 ± 0.20 for 1l-pf, and 0.65 ± 0.25 for ≥2l-pd vs. 0.74 ± 0.18 for ≥2l-pf), and greater productivity loss (39.4 ± 27.7 for 1l-pd vs. 27.5 ± 30.1 for 1l-pf, and 37.6 ± 29.2 for ≥2l-pd vs. 32.0 ± 29.0 for ≥2l-pf). Compared with caregivers of patients in pf, caregivers of patients in pd had lower qol scores and utility values, and greater productivity loss. Conclusions: Study results indicate that, for patients and caregivers, pd health states are associated with a deterioration of qol and utility and a decrease in productivity in both 1l and ≥2l.

A global economic model to assess the cost-effectiveness of new treatments for advanced breast cancer in Canada.

Objective Considering the increasing number of treatment options for metastatic breast cancer (MBC), it is important to develop high-quality methods to assess the cost-effectiveness of new anti-cancer drugs. This study aims to develop a global economic model that could be used as a benchmark for the economic evaluation of new therapies for MBC. Methods The Global Pharmacoeconomics of Metastatic Breast Cancer (GPMBC) model is a Markov model that was constructed to estimate the incremental cost per quality-adjusted life years (QALY) of new treatments for MBC from a Canadian healthcare system perspective over a lifetime horizon. Specific parameters included in the model are cost of drug treatment, survival outcomes, and incidence of treatment-related adverse events (AEs). Global parameters are patient characteristics, health states utilities, disutilities, and costs associated with treatment-related AEs, as well as costs associated with drug administration, medical follow-up, and end-of-life care. The GPMBC model was tested and validated in a specific context, by assessing the cost-effectiveness of lapatinib plus letrozole compared with other widely used first-line therapies for post-menopausal women with hormone receptor-positive (HR+) and epidermal growth factor receptor 2-positive (HER2+) MBC. Results When tested, the GPMBC model led to incremental cost-utility ratios of CA$131 811 per QALY, CA$56 211 per QALY, and CA$102 477 per QALY for the comparison of lapatinib plus letrozole vs letrozole alone, trastuzumab plus anastrozole, and anastrozole alone, respectively. Results of the model testing were quite similar to those obtained by Delea et al., who also assessed the cost-effectiveness of lapatinib in combination with letrozole in HR+/HER2 + MBC in Canada, thus suggesting that the GPMBC model can replicate results of well-conducted economic evaluations. Conclusions The GPMBC model can be very valuable as it allows a quick and valid assessment of the cost-effectiveness of any new treatments for MBC in a Canadian context.

Relationship between progression-free survival and overall survival in chronic lymphocytic leukemia: a literature-based analysis.

BACKGROUND: The endpoints of progression-free survival (pfs) and time-to-progression (ttp) are frequently used to evaluate the clinical benefit of anticancer drugs. However, the surrogacy of those endpoints for overall survival (os) is not validated in all cancer settings. In the present study, we used a trial-based approach to assess the relationship between median pfs or ttp and median os in chronic lymphocytic leukemia (cll). METHODS: The pico (population, interventions, comparators, outcomes) method was used to conduct a systematic review of the literature. The population consisted of patients with cll; the interventions and comparators were standard therapies for cll; and the outcomes were median pfs, ttp, and os. Two independent reviewers screened titles, abstracts, and full papers for eligibility and then extracted data from selected studies. Correlation coefficients were calculated to assess the relationship between median pfs or ttp and median os. Subgroup correlation analyses were also conducted according to the characteristics of the selected studies (such as line of treatment and type of treatment under investigation). RESULTS: Of the 1263 potentially relevant articles identified during the literature search, twenty-three were included. On average, median pfs or ttp was 16.0 months (standard deviation: 12.4 months) and median os was 43.5 months (standard deviation: 31.2 months). Results of the correlation analysis indicated that median pfs or ttp is highly correlated with median os (Spearman correlation coefficient: 0.813; p ≤ 0.001). A significant correlation between median pfs or ttp and median os was observed in second- and subsequent-line therapies, but not in the first-line setting. CONCLUSIONS: Our study demonstrates a strong correlation between median pfs or ttp and median os in previously treated cll, which reinforce the hypothesis that pfs and ttp could be adequate surrogate endpoints for os in this cancer setting.

Biologic disease-modifying anti-rheumatic drugs and the risk of non-vertebral osteoporotic fractures in patients with rheumatoid arthritis aged 50 years and over.

UNLABELLED: Prevention of bone mineral density loss in rheumatoid arthritis (RA) has been associated with use of biologic disease-modifying anti-rheumatic drugs (DMARDs). However, in this study, we could not demonstrate a reduction in the risk of non-vertebral fractures. Additional research is required to clarify the impact of biologic DMARDs on fracture risk in RA. INTRODUCTION: Small studies have suggested biologic DMARDs preserve bone mineral density at 6-12 months. Our objective was to determine the association between biologic DMARD use and the risk of non-vertebral osteoporotic fractures in RA subjects aged ≥50 years. METHODS: A nested case-control study was conducted using Quebec physician billing and hospital discharge data. RA subjects were identified from International Classification of Disease-9/10 codes in billing and hospitalisation data and followed from cohort entry until the earliest of non-vertebral osteoporotic fracture, death, or end of study period. Controls were matched to cases (4:1 ratio) on age, sex, and date of cohort entry. Biologic DMARD exposure was defined as being on treatment for ≥180 days pre-fracture (index). Conditional logistic regression was used, adjusting for indicators of RA severity, comorbidity, drugs influencing fracture risk, and measures of health care utilisation. RESULTS: Over the study period, 1,515 cases were identified (6,023 controls). The most frequent fracture site was hip/femur (42.3%). In total, 172 subjects (49 cases and 123 controls) were exposed to biologic DMARDs. The median duration of exposure was 735 (interquartile range (IQR), 564) and 645 (IQR, 903) days in cases and controls, respectively. We were unable to demonstrate an association between biologic DMARDs and fracture risk (odds ratio, 1.03; 95% confidence interval, 0.42-2.53). RA duration significantly increased the fracture risk. CONCLUSIONS: Despite the positive impact of biologic DMARDs on bone remodelling observed in small studies, we were unable to demonstrate a reduction in the risk of non-vertebral osteoporotic fractures in older adults with RA.

The efficacy and harm of prostaglandin analogues for IOP reduction in glaucoma patients compared to dorzolamide and brimonidine: a systematic review.

AIM: To systematically review the literature on the efficacy and harm of prostaglandin analogues (PGAs) compared to brimonidine and dorzolamide in treating elevated intraocular pressure (IOP). METHODS: Keywords were searched in major literature databases to identify relevant randomised clinical trials (RCTs) of PGAs for ophthalmic use. The study quality of RCTs was assessed using the Jadad scale. Outcomes assessed included reduction in IOP in individual patients, adverse events (AEs) and withdrawals due to AEs. RESULTS: Eight unique RCTs evaluating a total of 1,722 individuals were included in this systematic review. Analysis did not show a significant reduction in the mean IOP from patients receiving latanoprost compared with those receiving brimonidine (WMD = -1.04; p = 0.30). On the other hand, the latanoprost group showed a significant reduction in mean IOP compared to the dorzolamide group (WMD = -2.64; p<0.00001). The number of ocular AEs (excluding hyperaemia) was significantly higher in the brimonidine group compared with the latanoprost group (RR = 0.66; p = 0.0005). CONCLUSION: Latanoprost was found to be significantly superior to dorzolamide but not brimonidine. However, ocular adverse events were significantly fewer in latanoprost users than in brimonide users. Neither travoprost nor bimatoprost was compared to dorzolamide or brimonidine in the present literature.

Effect of a fermented milk combining Lactobacillus acidophilus Cl1285 and Lactobacillus casei in the prevention of antibiotic-associated diarrhea: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Antibiotic-associated diarrhea is an important problem in hospitalized patients. The use of probiotics is gaining interest in the scientific community as a potential measure to prevent this complication. The main objective of the present study was to assess the efficacy and safety of a fermented milk combining Lactobacillus acidophilus and Lactobacillus casei that is widely available in Canada, in the prevention of antibiotic-associated diarrhea. METHODS: In this double-blind, randomized study, hospitalized patients were randomly assigned to receive either a lactobacilli-fermented milk or a placebo on a daily basis. RESULTS: Among 89 randomized patients, antibiotic-associated diarrhea occurred in seven of 44 patients (15.9%) in the lactobacilli group and in 16 of 45 patients (35.6%) in the placebo group (OR 0.34, 95% CI 0.125 to 0.944; P=0.05). The median hospitalization duration was eight days in the lactobacilli group, compared with 10 days in the placebo group (P=0.09). Overall, the lactobacilli-fermented milk was well tolerated. CONCLUSION: The daily administration of a lactobacilli-fermented milk was safe and effective in the prevention of antibiotic-associated diarrhea in hospitalized patients.

Painful neuropathic disorders: an analysis of the Régie de l'Assurance Maladie du Québec database.

BACKGROUND/OBJECTIVE: Painful neuropathic disorders (PNDs) refer to neurological disorders involving nerves in which pain is a predominant symptom. In most cases, PNDs involve the peripheral nerves. Treatment of PNDs is likely to use large health care resources. However, little is known about the economic burden of PNDs in Canada. METHOD: The present study was performed using data from a random sample of patients covered by the Régie de l'Assurance Maladie du Quebec drug plan. Subjects with a diagnosis of a peripheral PND were identified. Comorbidities, pain-related medication use and resource utilization were compared between PND patients and control patients without PNDs matched for age and sex in a 1:1 ratio. RESULTS: A total of 4912 patients with PNDs were identified. A higher level of comorbidities was found in the PND group (Von Korff chronic disease score 3.91 versus 2.54; P<0.001). The proportion of users of pain-related medications was significantly higher in the PND cohort than in the control group (chi-squared; P<0.001). The average annual number of physician visits was also significantly higher in the PND group than in the control group (14.7 versus 6.4; P<0.001). From a health ministry perspective, costs of health care resources were significantly higher in the PND group (4,163 dollars versus 1,846 dollars; P<0.001). The proportion of potentially inappropriate medications was 34% among those 65 years of age or older. CONCLUSIONS: PNDs are associated with a higher level of comorbidities, higher medical resources utilization and higher health care costs than non-PND conditions.

Economic evaluation of NMP22 in the management of bladder cancer.

The purpose of this study was to evaluate, from the perspective of the Quebec health system, the cost and cost-efficacy of using NMP22 compared with the currently recommended monitoring procedure following a transurethral resection of a bladder tumor (TURBT). This evaluation was based on results from the study by Soloway, et al. It was performed using a decision analysis technique which compared a follow-up modality using NMP22 with the conventional follow-up monitoring procedure for the first 6 months after an initial transurethral resection of a bladder tumor. Each routine cystoscopy and cytology costs a total of $155. For the 6 months following initial TURBT, the cost for standard follow-up monitoring totaled $311, while the cost for the NMP22 monitoring modality was $257. On average, using NMP22 would have saved $55 per patient during the first 6 months of follow-up, resulting in a cost saving of approximately 18%. As well, 64.3% of patients would have undergone only one cystoscopy during the 6 month period, instead of the two done using the conventional modality. The trade-off for using NMP22 is that some patients would have a 3 month delay before diagnosis of a recurrence. This would occur in 8.9% of patients. NMP22 is less expensive than conventional monitoring follow-up of bladder cancer, and it can decrease patient discomfort by reducing the need for cystoscopy. Implementing it as routine follow-up monitoring should be considered, particularly for patients with low-grade tumors.

Economic evaluation of antibacterials in the treatment of acute sinusitis.

OBJECTIVE: The objective of this study was to compare costs, efficacy and cost efficacy of alternate oral antibacterial regimens for the ambulatory treatment of acute sinusitis. A public third-party perspective was adopted. DESIGN: The analysis was based on a decision tree and considered the episode of care from the decision to initiate an antibacterial until the end of the first course of treatment or the end of a subsequent course of treatment when needed. Efficacy data were retrieved from published clinical trials. Direct medical costs included the costs of physician visits, diagnostic tests and medications. SETTING: The study pertained to adults treated in a primary-care setting in the Canadian province of Québec. INTERVENTIONS: The antibacterials studied were amoxicillin, amoxicillin/clavulanate, azithromycin, cefaclor, cefuroxime axetil and clarithromycin. MAIN OUTCOME MEASURES AND RESULTS: The main outcome measured was the proportion of patients showing resolution or improvement of their symptoms. Initiating a treatment with amoxicillin was associated with similar efficacy and lower overall costs when compared with the other antibacterials. Low dosages of clarithromycin and azithromycin followed amoxicillin in terms of cost-efficacy ratio. CONCLUSIONS: This study confirms the place of amoxicillin as a first choice agent for acute sinusitis, with low dose clarithromycin and azithromycin as second choices.

Economic evaluation of zuclopenthixol acetate compared with injectable haloperidol in schizophrenic patients with acute psychosis.

Zuclopenthixol acetate is a rapid-acting, injectable neuroleptic drug with a duration of action that allows for administration once every 2 to 3 days, in contrast to injectable haloperidol, which may require administration more than once daily. To assess the place of zuclopenthixol acetate in the treatment of acute episodes of schizophrenia, a cost-consequence analysis was performed comparing this new medication with short-acting, injectable haloperidol. The perspective of the Quebec health care system was adopted. The study population comprised patients diagnosed with schizophrenia who experienced an acute episode of psychosis and who were treated with intramuscular (i.m.) haloperidol. The study assessed patients for 9 days after the start of treatment. The literature was the principal source of comparative data about the clinical outcomes of the two treatments. The total cost associated with zuclopenthixol acetate i.m. or haloperidol i.m. was modeled using a decision tree built around the number of i.m. injections required to achieve stabilization. To establish costs, expert panels were consulted and patients' files were reviewed for a sample of schizophrenic patients who had been hospitalized in a large psychiatric or general hospital subsequent to a visit to the emergency department and had received a short-acting i.m. neuroleptic drug. Only a direct medical records costs were considered. Because zuclopenthixol acetate was not on the market at the time of the study, the file review did not allow for a direct estimate of its related costs but did provide an account of haloperidol use. The literature shows that zuclopenthixol acetate is similar to haloperidol with respect to the control of psychotic episodes; however, zuclopenthixol acetate is associated with increased sedation and a lower incidence of extrapyramidal symptoms. Using the base-case estimate for the number of injections required for stabilization, the incremental cost of zuclopenthixol acetate 50 mg over haloperidol was $25.00 (1995 Canadian dollars) per patient at the psychiatric hospital and $21.00 per patient at the general hospital. The results were sensitive to the estimate of the number of injections and the number of minutes of nursing care required by agitated patients. Zuclopenthixol acetate resulted in cost savings over haloperidol if it permits a reduction of 25% in minutes of nursing care or if 85% of patients require 2 injections or less (45% requiring 1 injection and 40% requiring 2). However, whichever drug is used, the cost of the injectable neuroleptic represents a small fraction of the cost of care for acutely psychotic patients.