Economic evaluation of the "paramedics and palliative care: bringing vital services to Canadians" program compared to the status quo.

OBJECTIVE: Based on programs implemented in 2011-2013 in three Canadian provinces to improve the support paramedics provide to people receiving palliative care, the Canadian Partnership Against Cancer and Healthcare Excellence Canada provided support and funding from 2018 to 2022 to spread this approach in Canada. The study objectives were to conduct an economic evaluation of "the Program" compared to the status quo. METHODS: A probabilistic decision analytic model was used to compare the expected costs, the quality-adjusted life years (QALYs) and the return on investment associated with the Program compared to the status quo from a publicly funded healthcare payer perspective. Effectiveness data and Program costs, expressed in 2022 Canadian dollars, from each jurisdiction were supplemented with literature data. Probabilistic sensitivity analyses varying key model assumptions were conducted. RESULTS: Analyses of 5416 9-1-1 calls from five jurisdictions where paramedics provided support to people with palliative care needs between April 1, 2020 and March 31, 2022 indicated that 60% of the 9-1-1 calls under the Program enabled people to avoid transport to the emergency department and receive palliative care at home. Treating people at home saved paramedics an average of 31 min (range from 15 to 67). The Program was associated with cost savings of $2773 (95% confidence interval [CI] $1539-$4352) and an additional 0.00069 QALYs (95% CI 0.00024-0.00137) per 9-1-1 palliative care call. The Program return on investment was $4.6 for every $1 invested. Threshold analyses indicated that in order to be cost saving, 33% of 9-1-1 calls should be treated at home under the Program, the Program should generate a minimum of 97 calls per year with each call costing no more than $2773. CONCLUSION: The Program was cost-effective in the majority of the scenarios examined. These results support the implementation of paramedic-based palliative care at home programs in Canada.

RéSUMé: OBJECTIFS: En fonction des programmes mis en œuvre en 2011-2013 dans trois provinces canadiennes pour améliorer le soutien que les ambulanciers paramédicaux fournissent aux personnes recevant des soins palliatifs. le Partenariat canadien contre le cancer et Excellence des soins de santé Canada a fourni un soutien et du financement de 2018 à 2022 pour diffuser cette approche au Canada. Les objectifs de l'étude étaient d'effectuer une évaluation économique du « programme ¼ par rapport au statu quo. MéTHODES: Un modèle probabiliste d'analyse décisionnelle a été utilisé pour comparer les coûts prévus, les années de vie ajustées en fonction de la qualité (AVAQ) et le rendement du capital investi associés au Programme par rapport au statu quo du point de vue des payeurs de soins de santé financés par l'État. Les données sur l'efficacité et les coûts du Programme, exprimés en dollars canadiens de 2022, de chaque administration ont été complétées par des données documentaires. Des analyses probabilistes de sensibilité ont été effectuées en fonction de diverses hypothèses clés du modèle. RéSULTATS: Des analyses de 5416 appels 9-1-1 provenant de cinq administrations où des ambulanciers paramédicaux ont fourni du soutien aux personnes ayant des besoins en soins palliatifs entre le 1er avril 2020 et le 31 mars 2022 ont indiqué que 60 % des 9Les appels 1-1 dans le cadre du Programme ont permis aux gens d'éviter le transport vers les urgences et de recevoir des soins palliatifs à domicile. Le traitement à domicile a permis aux ambulanciers paramédicaux d'économiser en moyenne 31 minutes (de 15 à 67 minutes). Le programme a permis de réaliser des économies de 2 773 $ (intervalle de confiance [IC] de 95 %, de 1 539 $ à 4 352 $) et de 0,00069 AVAQ supplémentaires (IC à 95 %, de 0,00024 à 0,00137) par appel de soins palliatifs 9-1-1. Le rendement du capital investi du Programme était de 4,6 $ pour chaque dollar investi. Les analyses des seuils ont indiqué que pour réaliser des économies, 33 % des appels 9-1-1 devraient être traités à domicile dans le cadre du Programme, le Programme devrait générer un minimum de 97 appels par année, chaque appel ne dépassant pas 2773 $. CONCLUSION: Le Programme a été rentable dans la majorité des scénarios examinés. Ces résultats appuient la mise en œuvre de programmes de soins palliatifs paramédicaux à domicile au Canada.

Estimating the costs of intensity-modulated and 3-dimensional conformal radiotherapy in Ontario.

BACKGROUND: Radiotherapy is a common treatment for many cancers, but up-to-date estimates of the costs of radiotherapy are lacking. In the present study, we estimated the unit costs of intensity-modulated radiotherapy (imrt) and 3-dimensional conformal radiotherapy (3D-crt) in Ontario. METHODS: An activity-based costing model was developed to estimate the costs of imrt and 3D-crt in prostate cancer. It included the costs of equipment, staff, and supporting infrastructure. The framework was subsequently adapted to estimate the costs of radiotherapy in breast cancer and head-and-neck cancer. We also tested various scenarios by varying the program maturity and the use of volumetric modulated arc therapy (vmat) alongside imrt. RESULTS: From the perspective of the health care system, treating prostate cancer with imrt and 3D-crt respectively cost $12,834 and $12,453 per patient. The cost of radiotherapy ranged from $5,270 to $14,155 and was sensitive to analytic perspective, radiation technique, and disease site. Cases of head-and-neck cancer were the most costly, being driven by treatment complexity and fractions per treatment. Although imrt was more costly than 3D-crt, its cost will likely decline over time as programs mature and vmat is incorporated. CONCLUSIONS: Our costing model can be modified to estimate the costs of 3D-crt and imrt for various disease sites and settings. The results demonstrate the important role of capital costs in studies of radiotherapy cost from a health system perspective, which our model can accommodate. In addition, our study established the need for future analyses of imrt cost to consider how vmat affects time consumption.

Omission of Breast Radiotherapy in Low-risk Luminal A Breast Cancer: Impact on Health Care Costs.

AIMS: The economic burden of cancer care is substantial, including steep increases in costs for breast cancer management. There is mounting evidence that women age ≥ 60 years with grade I/II T1N0 luminal A (ER/PR+, HER2- and Ki67 ≤ 13%) breast cancer have such low local recurrence rates that adjuvant breast radiotherapy might offer limited value. We aimed to determine the total savings to a publicly funded health care system should omission of radiotherapy become standard of care for these patients. MATERIALS AND METHODS: The number of women aged ≥ 60 years who received adjuvant radiotherapy for T1N0 ER+ HER2- breast cancer in Ontario was obtained from the provincial cancer agency. The cost of adjuvant breast radiotherapy was estimated through activity-based costing from a public payer perspective. The total saving was calculated by multiplying the estimated number of luminal A cases that received radiotherapy by the cost of radiotherapy minus Ki-67 testing. RESULTS: In 2010, 748 women age ≥ 60 years underwent surgery for pT1N0 ER+ HER2- breast cancer; 539 (72%) underwent adjuvant radiotherapy, of whom 329 were estimated to be grade I/II luminal A subtype. The cost of adjuvant breast radiotherapy per case was estimated at $6135.85; the cost of Ki-67 at $114.71. This translated into an annual saving of about $2.0million if radiotherapy was omitted for all low-risk luminal A breast cancer patients in Ontario and $5.1million across Canada. CONCLUSION: There will be significant savings to the health care system should omission of radiotherapy become standard practice for women with low-risk luminal A breast cancer.

Cost-effectiveness of a fracture liaison service--a real-world evaluation after 6 years of service provision.

UNLABELLED: The cost-effectiveness of a less intensive fracture liaison service is unknown. We evaluated a fracture liaison service that had been educating and referring patients for secondary prevention of osteoporotic fractures for 6 years. Our results suggest that a less intensive fracture liaison service, with moderate effectiveness, can still be worthwhile. INTRODUCTION: Fragility fractures are common among older patients; the risk of re-fracture is high but could be reduced with treatments; different versions of fracture liaison service have emerged to reduce recurrent osteoporotic fractures. But the cost-effectiveness of a less intensive model is unknown. The objective of this study was to assess the cost-effectiveness of the Ontario Fracture Clinic Screening program, a fracture liaison service that had been educating and referring fragility fracture patients across Ontario, Canada to receive bone mineral density testing and osteoporosis treatments since 2007. METHODS: We developed a Markov model to assess the cost-effectiveness of the program over the patients' remaining lifetime, using rates of bone mineral density testing and osteoporosis treatment and cost of intervention from the program, and supplemented it with the published literature. The analysis took the perspective of a third-party health-care payer. Costs and benefits were discounted at 5 % per year. Sensitivity analyses assessed the effects of different assumptions on the results. RESULTS: The program improved quality-adjusted life-years (QALYs) by 4.3 years and led to increased costs of CAD $83,000 for every 1000 patients screened, at a cost of $19,132 per QALY gained. The enhanced model, the Bone Mineral Density (BMD) Fast Track program that includes ordering bone mineral density testing, was even more cost-effective ($5720 per QALY gained). CONCLUSIONS: The Ontario Fracture Clinic Screening program appears to be a cost-effective way to reduce recurrent osteoporotic fractures.

Cost-effectiveness of intensity-modulated radiotherapy in prostate cancer.

AIMS: To compare the costs and effectiveness of intensity-modulated radiotherapy (IMRT) with three-dimensional conformal radiotherapy (3DCRT) for the radical treatment of localised prostate cancer at elevated doses (>70 Gy). MATERIALS AND METHODS: A cost-effectiveness analysis model was developed using clinical effectiveness estimates from a systematic review. The base case analysis assumes equal biochemical survival for IMRT and 3DCRT, but lower frequency of gastrointestinal toxicity for IMRT. The costs of IMRT and 3DCRT were estimated through activity-based costing, incorporating input from radiation oncologists, physicists and treatment planners. RESULTS: The delivery of IMRT produced 0.023 more quality-adjusted life-years (QALY) than 3DCRT at an additional cost of $621 (QALY and costs discounted at 5% per year), yielding an incremental cost-effectiveness ratio of $26 768 per QALY gained. The treatment cost of IMRT was $1019 more than 3DCRT, but IMRT resulted in less frequent gastrointestinal toxicity, thus avoiding $402 in the treatment of toxicity. In the scenario that compared a higher dose of IMRT (75.6 Gy) to 3DCRT (68.4 Gy), IMRT improved disease control with equal toxicity incidence, and the IMRT strategy dominated (less costly and more effective). In the base case scenario (no survival difference), the cost-effectiveness of IMRT was most sensitive to the treatment cost difference between IMRT and 3DCRT. CONCLUSION: For radical radiation treatment (>70 Gy) of prostate cancer, IMRT seems to be cost-effective when compared with an equivalent dose of 3DCRT.

Cost-effectiveness of intensity-modulated radiotherapy in oropharyngeal cancer.

AIMS: Intensity-modulated radiotherapy (IMRT) is an advanced radiation technique that is particularly suited to treating head and neck cancers because it can conform a high dose to the target volume while preserving the tissue function of neighbouring structures. The objective of this study was to compare the cost and effectiveness of IMRT with three-dimensional conformal radiotherapy (3DCRT) for the treatment of locally advanced oropharyngeal cancer. MATERIALS AND METHODS: We developed a Markov model to estimate the incremental cost per quality-adjusted life-year (QALY) gained by IMRT from the perspective of the Ministry of Health. The costs of IMRT and 3DCRT were estimated through activity-based costing, incorporating input from radiation oncologists, physicists and radiation therapists. We obtained clinical effectiveness estimates from published studies and calculated the number needed to treat to avoid a case of severe long-term xerostomia using data from a randomised controlled trial. RESULTS: The delivery of IMRT produced 0.48 more QALYs than 3DCRT at an additional cost of $2447 (QALY and costs discounted at 5% a year), yielding an incremental cost-effectiveness ratio of $5084 per QALY gained. The cost-effectiveness of IMRT was sensitive to the costs of radiotherapy and the effect of IMRT on health-related quality of life. The cost of IMRT will probably decrease with the addition of volumetric modulated arc therapy, an increasingly used technology, because volumetric modulated arc therapy reduces treatment time. We need to treat less than two patients with IMRT to avoid a case of severe, long-term xerostomia (dry mouth), and the incremental cost to avoid a case of severe, long-term xerostomia was $4532. CONCLUSIONS: In the treatment of locally advanced oropharyngeal carcinoma, the IMRT strategy appears to be cost-effective when compared with 3DCRT.

Progression-free survival as a clinical trial endpoint in advanced renal cell carcinoma.

Traditionally, overall survival (os) has been considered the "gold standard" for evaluating new systemic oncologic therapies, because death is easy to define, is easily compared across disease sites, and is not subject to investigator bias. However, as the available options for continuing therapy increase, the use of os as a clinical trial endpoint has become problematic because of the increasing crossover and contamination of trials. As a result, the approval of promising new therapies may be delayed.Many clinicians believe that progression-free survival (pfs) is a more viable option for evaluating new therapies in metastatic and advanced renal cell carcinoma. As with all endpoints, pfs has inherent biases, and those biases must be addressed to ensure that trial results are not compromised and that they will be accepted by regulatory authorities. In this paper, we examine the issues surrounding the use of pfs as a clinical trial endpoint, and we suggest solutions to ensure that data integrity is maintained.

Differential expression of cxcl-14 during eruptive movement of rat molar germs.

Tooth eruption at the early postnatal period is strictly controlled by the molecules secreted mainly from follicular tissues, which recruit monocytes for osteoclast formation. In this study, it was hypothesized that different molecules can be expressed according to the stages of tooth eruption. Rat molar germs together with follicles were extracted and DD-PCR was performed from the root formation stage 2nd molars germs (after eruptive movement) and cap stage 3rd molar germs (before movement) at postnatal day 9. Cxcl-14, a potent chemoattractant, was detected as one of the differentially expressed molecules from DD-PCR. Its expression increased significantly at the root formation stage, compared with the cap or crown formation stage at both transcription and translation levels. The expression patterns of cxcl-14 were consistent with those of MCP-1 and CSF-1, and opposite to OPG. Immunofluorescence showed that cxcl-14 was localized in the dental follicular tissues only at the root formation stage overlaying the proximo-occlusal region of the molar germs. Many osteoclasts appeared on the surface of the alveolar bone which overlayed the occlusal region of the root formation stage 2nd molar germs and underwent resorption. Cxcl-14 expression was reduced considerably at both the translation and transcription levels by an alendronate treatment. These results suggest that cxcl-14 may be implicated in the formation of the eruptive pathway of tooth germs via osteoclastogenesis.

Evaluation of in vitro cytotoxicity of carboranyl amino acids, their chemical precursors and nido carboranyl amino acids for boron neutron capture therapy.

The purpose of the present study was to define the in vitro cellular toxicity of three carborane-containing amino acids: p-(o-carboran-yl)-phenylalanine (CBPA), O-(o-carboran-1-ylmethyl)-tyrosine (CBT), and o-carboranylalanine (CBA), which are analogues of phenylalanine, tyrosine, and alanine respectively. In addition, two of their chemical precursors: CBACN (B10H11C2-CH2CHNH2CN) and CBTCN (B10H11C2-CH2OC6H4CH2CHNH2CN) and nido CBA were evaluated for their toxicity on human MRA 27 melanoma cells. Hydroxypropyl-beta-cyclodextrin (beta-CD) initially was used to solubilize all the compounds except nido CBA in the toxicity assays Cells were incubated with the test compounds at varying concentrations for 24 hrs, following which the proliferative activity of surviving cells was determined by pulsing with tritiated thymidine ([3H]-TdR) for an additional 18 hrs. CBT at a concentration of 280 micrograms/ml was non-toxic when solubilized with beta-CD. CBA at a concentration of 350 micrograms/ml was non-toxic when solubilized with beta-CD, but when solubilized with DMSO produced a 50% reduction in uptake of [3H]-TdR at a concentration of 75 micrograms/ml. CBPA, solubilized with beta-CD, was nontoxic at a concentration of 400 micrograms/ml, while CBTCN and CBACN at concentrations of 50 micrograms/ml and 40 micrograms/ml, respectively, were both toxic, even when solubilized with beta-CD. Nido CBA at a concentration of 400 micrograms/ml in medium was non-toxic. Although the toxicity of these boron compounds precludes their use as capture agents for Neutron Capture Therapy, they may have some potential for cytoreductive chemotherapy of cancer, and further evaluation may be warranted.

In vitro and in vivo evaluation of o-carboranylalanine as a potential boron delivery agent for neutron capture therapy.

o-Carboranylalanine (B10H10C2CH2CHNH2COOH) is a carborane-containing amino acid, which has been synthesized as a potential capture agent for boron neutron capture therapy (BNCT) of cancer. The purpose of the present study was to develop a rational approach for the in vitro and in vivo evaluation of boron containing compounds that possibly might be used for BNCT. The in vitro uptake of carboranylalanine (CBA) was evaluated using two cell lines, the human melanoma MRA 27, and the murine Harding-Passey melanoma. Uptake of CBA by MRA 27 cells ranged from 135-551 micrograms B/10(9) cells following 3 hrs incubation with medium containing 100-113 micrograms B/ml and was not reduced by exposing the tumor cells to either rotenone, an inhibitor of electron transport, or by culturing them at ambient temperature (approximately 22 degrees C). Cellular uptake and elution of CBA occurred rapidly under in vitro conditions. Uptake of CBA was slightly greater than that of boronophenylalanine (BPA). Following a 3 hr incubation with CBA at a concentration of 106 micrograms B/ml, cell boron content was 255 micrograms B/10(9) MRA 27 cells, compared to 192 micrograms B/10(9) cells when cells were incubated with BPA at a concentration of 95 micrograms B/ml. In vivo studies initially were carried out using the Harding-Passey melanoma, which had been implanted intramuscularly (i.m.) into the right flank of BALB/c mice. Tumors were allowed to grow for 14 days at which time mice were injected intraperitoneally (i.p.) with either CBA or BPA (1.25 mgB/mouse), and were killed 3, 6 and 8 hrs later. CBA attained a low tumor to blood ratio(1.0-1.4), and the tumor boron levels ranged from 15.7-26.2 micrograms B/g at 3 hrs and 3.3-19.9 micrograms B/g at 6 hrs. Higher blood and lower tumor boron levels were observed at all time points with CBA compared to BPA, suggesting that CBA was not taken up selectively by the melanoma. Similar studies, carried out in rats bearing intra-cerebral gliomas, failed to reveal detectable amounts of boron in the tumor. From the present study, it can be concluded that CBA does not appear to possess the requisite properties to be useful as a boron delivery agent for BNCT.