The 2018 decision to establish an Advisory Council on adding pharmaceuticals to universal health coverage in Canada.

Canada is the only Universal Health Insurance country in the OECD without universal insurance for outpatient prescription drugs, a situation generally perceived as unfair and inefficient. In June 2018, the federal government launched an Advisory Council on the Implementation of National Pharmacare, to report in 2019 on the best strategy to implement a national Pharmacare program that would provide all Canadians access to affordable outpatient prescription drugs. The Council was asked to consider three options: a universal public plan for all Canadians; a public catastrophic insurance plan that would kick off once spending on prescription drugs reaches a given threshold; and a more modest patching of existing gaps, providing coverage to those who are not eligible to any form of insurance. Beyond the relative consensus around the ideas that gaps in coverage should be filled to make drugs affordable to all, and that the costs of drugs are too high in Canada, the Council faces the challenge of addressing three underlying issues: 1) what amount of income redistribution will result from each of the three options; 2) how much savings would the implementation of a single payer generate? 3) what role restricting a national formulary would play in achieving those savings, and what would be the political consequences of narrowing the formulary?

The smart approach: feasibility of lentigo maligna superficial margin assessment with hand-held reflectance confocal microscopy technology.

BACKGROUND: Lentigo maligna may be challenging to clear surgically. OBJECTIVE: To evaluate feasibility of using superficial skin cuts as RCM imaging anchors for attaining negative surgical margins in lentigo maligna. METHODS: Included patients presented with lentigo maligna near cosmetically sensitive facial structures. We evaluated, with hand-held-RCM, microscopic clearance of melanoma beyond its dermoscopically detected edges. Evaluated margins were annotated using shallow skin cuts. If a margin was positive at 'first-step' RCM evaluation, we sequentially advanced the margin radially outward at that segment by 2-mm intervals until an RCM-negative margin was identified. Prior to final surgical excision, we placed sutures at the outmost skin cuts to allow comparison of RCM and histopathological margin assessments. Primary outcome measure was histopathological verification that RCM-negative margins were clear of melanoma. RESULTS: The study included 126 first-step margin evaluations in 23 patients, median age 70 years (range: 43-91). Seventeen patients (74%) had primary in-situ melanoma and six (26%) invasive melanoma, mean thickness 0.3 mm (range 0.2-0.4 mm). Six cases (26%) showed complete negative RCM margins on 'first-step', 11 (48%) were negative at 'second-step', and four (17%) at 'third-step'. In two additional cases (9%), margins clearance could not be determined via RCM due to widespread dendritic cells proliferation. The RCM-negative margins in all 21 cases proved clear of melanoma on histopathology. Of the 15 cases that returned at 1-year follow-up, none showed any residual melanoma on dermoscopic and RCM examinations. Interobserver reproducibility showed fair agreement between bedside RCM reader and blinded remote-site reader, with Spearman's rho of 0.48 and Cohen's kappa of 0.43; using bedside reader as reference, the remote reader's sensitivity was 92% and specificity 57% in positive margin detection. CONCLUSIONS: Margin mapping of lentigo maligna with hand-held-RCM, using superficial skin cuts, appears feasible. This approach needs validation by larger studies.

Feasibility of assessing patient health benefits and incurred costs resulting from early dysphagia intervention during and immediately after chemoradiotherapy for head-and-neck cancer.

BACKGROUND: Resource limitations affect the intensity of speech-language pathology (slp) dysphagia interventions for patients with head-and-neck cancer (hnc). The objective of the present study was to assess the feasibility of a prospective clinical trial that would evaluate the effects on health and patient costs of early slp dysphagia intervention for hnc patients planned for curative concurrent chemoradiotherapy (ccrt). METHODS: Patients with hnc planned for curative ccrt were consecutively recruited and received dysphagia-specific intervention before, during, and for 3 months after treatment. Swallowing function, body mass index, health-related quality of life (qol), and out-of-pocket costs were measured before ccrt, at weeks 2 and 5 during ccrt, and at 1 and 3 months after ccrt. Actuarial percutaneous endoscopic gastrostomy (peg) removal rates and body mass index in the study patients and in a time-, age-, and disease-matched cohort were compared. RESULTS: The study enrolled 21 patients (mean age: 54 years; 19 men). The study was feasible, having a 95% accrual rate, 10% attrition, and near completion of all outcomes. Compared with the control cohort, patients receiving dysphagia intervention trended toward a higher rate of peg removal at 3 months after ccrt [61% (32%-78%) vs. 53% (23%-71%), p = 0.23]. During ccrt, monthly pharmaceutical costs ranged between $239 and $348, with work loss in the range of 18-30 days for patients and 8-12 days for caregivers. CONCLUSIONS: We demonstrated the feasibility of comparing health and economic outcomes in patients receiving and not receiving early slp dysphagia intervention. These preliminary findings suggest that early slp dysphagia intervention for hnc patients might reduce peg dependency despite worsening health. Findings also highlight effects on financial security for these patients and their caregivers.

Cost-benefit of reflectance confocal microscopy in the diagnostic performance of melanoma.

BACKGROUND: The sub-optimal diagnostic accuracy for melanoma leads to excise a high number of benign lesions, with consequent costs. Reflectance confocal microscopy (RCM) improves diagnostic specificity, thus possibly inducing a reduction in unnecessary excisions and related costs. OBJECTIVE: To estimate the influence of RCM on number of benign lesions needed to excise (NNE) a melanoma, in term of clinical outcomes and costs per patient. PATIENTS AND METHODS: Skin neoplasms excised by the dermatology public service in the Province of Modena were retrieved form centralized pathology database. Differences in NNE between the territorial service (using dermoscopy only) and the University Hospital (adding also RCM to the patients' workflow) were calculated and cost analysis was performed through a micro-costing approach. RESULTS: A large reduction in benign lesions excised at University Hospital was evident, leading to NNE of 6.25 for University Hospital, compared to 19.41 for Territorial Dermatology. Since 4320 unnecessary excisions can be saved every million inhabitants, an overall yearly saving of over 280,000 Eur can be expected from the use of RCM. CONCLUSIONS: The systematic use of RCM was dramatically affecting the number of benign lesions excised, and this can be translated in a significant cost-benefit advantage.

Assessment of SIAscopy in the triage of suspicious skin tumours.

BACKGROUND/PURPOSE: Spectrophotometric Intracutaneous Analysis (SIAscopy) is a non-invasive, computerized technique for the diagnosis of pigmented skin tumours. The analysis is based on the evaluation of skin chromophores, i.e. melanin, haemoglobin and collagen within the epidermis and papillary dermis. Our aim was to assess the diagnostic validity of SIAscopy in the detection of melanoma and non-melanoma skin cancers compared to the clinical-dermoscopic diagnosis and the histopathologic results of the excised lesions. METHODS: In total, 188 lesions of 180 patients were examined by dermoscopy and SIAscopy. A SIAscopy scoring system was first compared with the clinical-dermoscopic diagnosis and then with the histopathologic diagnosis of the excised lesions. RESULTS: With respect to the clinical-dermoscopic evaluation, SIAscopy had sensitivity and specificity values of 85.7% and 65.4% respectively. Of the 188 evaluated lesions, 44 were excised with histopathologic examination revealing 31 malignant tumours, including 18 melanomas. With respect to histopathology SIAscopy had a sensitivity of 83.9%. Seven of the 13 benign excised lesions were scored as malignant by SIAscopy resulting in a specificity of 46.1%. CONCLUSION: SIAscopy cannot replace the standard of care in skin cancer diagnosis, which includes clinical and dermoscopic examination. However, considering that the technique does not require specific training and expertise, it might represent an additional, relatively cost-effective tool to select lesions for referral.

In vivo assessment of chronological ageing and photoageing in forearm skin using reflectance confocal microscopy.

BACKGROUND: Skin ageing is a complex process due to intrinsic chronological factors (chronoageing) and extrinsic environmental factors. The primary extrinsic factor is cumulative ultraviolet (UV) exposure, and is therefore termed photoageing. The current standards for measuring cumulative sun damage are biopsy histology and skin microtopography. However, skin biopsies are too invasive for population studies and skin replicas render only superficial skin architecture data. Reflectance confocal microscopy (RCM) is a noninvasive imaging tool that allows for in vivo imaging of the skin at quasihistological resolution. OBJECTIVES: To define and identify RCM features associated with chronological ageing and photoageing on the forearm in two age groups with different skin phototypes and to assess whether these results agree with previous findings. METHODS: We obtained RCM images of dorsal and volar nonlesional skin of the lower forearm of 75 individuals with skin Fitzpatrick phototypes I-III in two age groups (20-30 years and 50-60 years). From each participant and body site, 21 RCM features were assessed and statistically significant differences between the two age groups and different forearm sites determined. RESULTS: RCM enabled identification of changes in architecture, cell morphology and extracellular matrix (collagen) at the level of the epidermis, dermoepidermal junction and papillary dermis. Changes that were correlated with chronological ageing and which were aggravated on the UV-exposed dorsal forearm were: loss of small skin furrows resulting in wider and less intersecting furrows; irregularity of the epidermal honeycomb pattern; irregularly distributed (mottled) pigmented keratinocytes/melanocytes; irregularity of the papillary rings and/or effacement of the rete ridges; and loss of thin collagen fibres and presence of collagen clods. CONCLUSION: We have tested previously reported and new parameters for skin ageing evaluation by RCM, and identified 15 statistically significant RCM features that can be used to quantify ageing and photoageing in forearm skin noninvasively.

Prolonged hospitalisation for immigrants and high risk patients with positive smear pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Tuberculosis (TB) occurring in immigrants and resistance to drugs are major problems for TB control in Western countries. Directly observed therapy (DOT) reduces disease transmission, but this approach may have poor results among illegal immigrants. Our aim was to evaluate a prolonged hospitalisation programme to improve early outcome of TB treatment in high risk patients. METHODS: All the consecutive adult patients with sputum smear-positive pulmonary TB admitted to 2 Italian referral TB Centres were evaluated. Hospital-based DOT was provided to high risk patients up-to smear conversion. Demographic, microbiological and clinical conditions, as potential factors associated with confirmed smear conversion at 60 and 90 days of anti-tuberculous therapy were evaluated. RESULTS: 122 patients were studied, 45.9% of them were immigrants (20% illegal) from high-prevalence TB countries. HIV testing was negative in all cases. Twelve patients had M. tuberculosis resistant to > or = 1 first-line anti-tuberculous agents. The rate of defaulting from TB treatment was 73%. Sputum smear became negative in 84.4% cases after 60 days and 933% cases after 90 days. At such time, smear conversion rates were similar among different high risk subgroups such as illegal immigrants (95.9%), legal foreign-born (92.5%) and Italian persons (94.8%). Persistent sputum smear positivity was independently correlated with the extent of pulmonary lesions at 60 (p < 0.0001) and 90 days (p = 0.038) of hospital-based DOT. CONCLUSIONS: These findings suggest that prolonged hospitalisation for illegal immigrants and high risk TB patients, may positively influence the early outcome of TB treatment despite of drug resistance and legal status.

A comparative analysis of monthly out-of-pocket costs for patients with breast cancer as compared with other common cancers in Ontario, Canada.

BACKGROUND: Monthly out-of-pocket costs (oopc) for Ontario patients with cancer have previously been reported, but little detail has been provided on differences based on tumour type. METHODS: A questionnaire administered in cancer clinics in the province of Ontario, with a mix of urban and rural patients, was analyzed using descriptive statistics and a regression analysis of cross-sectional data. The dependent variable was oopc (Canadian dollars), analyzed separately for total oopc (excluding imputed travel costs), and for each of the individual cost categories. RESULTS: Compared with colorectal, lung, and prostate cancer patients combined, breast cancer patients had statistically significantly higher total oopc ($393 vs. $149, p = 0.02), device costs ($142 vs. $12, p = 0.018), and family care costs ($38 vs. $3, p = 0.01). By contrast, they trended toward lower costs for travel ($225 vs. $426, p = 0.055) and had lower costs for parking ($32 vs. $53, p = 0.0198). Compared with non-breast cancer patients, patients with breast cancer reported a greater perceived financial burden (31% vs. 17% p = 0.0133). INTERPRETATION: These findings highlight that financial burden for cancer patients can vary by tumour type, and that patients with breast cancer may require a different mix of supportive services than do patients with other common tumour types. Supportive care programs related to financial burden should consider the likelihood and nature of financial burden when counselling breast cancer patients.

An examination of cancer patients' monthly 'out-of-pocket' costs in Ontario, Canada.

Ontario cancer patients' monthly out-of-pocket costs (OOPC) were assessed to determine whether these costs were problematic. A self-administered questionnaire was administered to breast (n = 74), colorectal (n = 70), lung (n = 68) and prostate (n = 70) cancer patients between October 2001 and April 2003. It measured categorical OOPC, which were analysed using linear regression modelling, to determine whether any of a variety of independent variables influenced OOPC. Monthly OOPC (mean, range) were: parking/fares ($47, $0-450), devices ($46, $0-2350), prescription drugs ($45, $0-1400), accommodation ($43, $0-1500), complementary and alternative medicine ($29, $0-5000), vitamins ($25, $0-400), homemaking ($14, $0-1000), family care ($12, $0-1200), homecare ($2, $0-330) and other ($8, $0-250), with the total averaging $213 ($0-5230). Imputed travel mileage costs added $372 ($0-6180). Most patients were well served by the current healthcare programmes. In multivariate analysis, variables influencing several OOPC categories were: tumour site, hospitalization, age, and number of clinic trips. Travel costs proved the most problematic, with patients under 65 years and without insurance more likely to have high OOPC. Education and income were not reliable predictors for high OOPC. Many of these costs were for items not traditionally covered by public healthcare financing systems, raising important issues around defining 'medically necessary' care and the role of government.

The economic value of a new insulin preparation, Humalog Mix 25. Measured by a willingness-to-pay approach.

OBJECTIVE: To measure the economic value of a new insulin formulation consisting of rapid-acting insulin lispro and intermediate-acting neutral protamine lispro in a 25:75 ratio (Humalog Mix 25). DESIGN AND SETTING: A cost-benefit analysis using a consumer-based willingness-to-pay (WTP) approach was used. The study sample consisted of 80 Canadian taxpayers randomly selected from Ontario and Quebec. After background information on the differences between Humalog Mix 25 and human 30/70 insulin were presented, respondents were asked what their preferred product would be if they were diagnosed with diabetes mellitus. Respondents were then asked the maximum premium that they would pay per month in the form of a user's fee for the insulin of their choice. STUDY PERSPECTIVE: Canadian taxpayer perspective. MAIN OUTCOME MEASURES AND RESULTS: The WTP survey instrument was simple to administer and easily understood by participants. Approximately 84% of the sample of taxpayers preferred to use Humalog Mix 25 rather than human 30/70 insulin and were willing to pay for it (p = 0.012). They were willing to pay a mean of $Can35.28 [95% confidence interval (CI): $Can27.50 to $Can43.07] per month for the benefits offered by Humalog Mix 25, which was at least 2-fold higher than the incremental monthly cost of the drug (1999 values). CONCLUSIONS: The results of the study revealed that Canadians prefer to use Humalog Mix 25 instead of human 30/70 insulin, and they would be willing to pay for it. Compared with other drugs, this overall net gain suggests that Humalog Mix 25 represents good value for money and should be considered for reimbursement by government formularies and other third-party payers.

Choices of methodology in pharmacoeconomics studies.

OBJECTIVES: The goal of this paper is to evaluate the comparative value of economic methodologies in assessing the benefit of a new cytoprotective agent (amifostine) delivered before cisplatin/cyclophosphamide in the treatment of ovarian cancer. BACKGROUND: Data from a randomized controlled multinational multicenter ovarian cancer trial were used as the basis for a retrospective pharmacoeconomic analysis. Trial results demonstrated amifostine had no significant effect on oncolytic efficacy, but side effect profiles improved for febrile neutropenia (absolute risk reduction [ARR] 11%), neurotoxicity (ARR 11%), and nephrotoxicity (ARR 26%). Although, the methodology most commonly used in this type of analysis is cost utility (CU), we investigated a "willingness to pay" (WTP) approach. RESEARCH DESIGN SUBJECTS: Four pharmacy managers were given an informal telephone interview to assess their preferences. Two managers understood, and preferred, the CU data. The others, who had no education or training on CU principles, preferred WTP data. All managers understood the outputs from WTP studies. RESULTS/MEASURES: WTP for reductions in febrile neutropenia, neurotoxicity, and nephrotoxicity were collected from 50 healthy volunteers and measured against the cost of delivering the new therapy. Results revealed WTP values of $141 per year for reductions in febrile neutropenia, $86 per year for reductions in neurotoxicity, and $71 per year for reductions in nephrotoxicity. The base case analysis showed that amifostine was cost neutral ($350 net cost, CI = -850 to +1551). CONCLUSIONS: The results were well-received by decision-makers. This manager survey illustrates that the methodologic choice should be determined not only by the nature of the comparison, but also by the stakeholder the data is meant to influence.

Assessment of articular cartilage thickness of the humeral head: MR-anatomic correlation in cadavers.

OBJECTIVE: The purpose of our study was to evaluate several commonly used MR sequences to determine how accurately each demonstrates the thickness of the articular cartilage of the humeral head. MATERIALS AND METHODS: Ten cadaveric shoulders (age at death, 58-92 years; mean, 79 years) were imaged with fat-suppressed transaxial T1-weighted spin-echo three-dimensional gradient-recalled sequences, both before and after injection of 12 ml of diluted gadopentetate dimeglumine. Articular cartilage was measured to the nearest 10th of a millimeter on the MR images and corresponding anatomic sections. RESULTS: Cartilage could not be differentiated from surrounding structures in 14 of 112 locations (13%) on the spin-echo images obtained without contrast material, in 4 of 112 locations (4%) on the spin-echo images obtained with contrast material, in 4 of 112 locations (4%) on the gradient-echo images obtained without contrast material, and in 6 of 112 locations (5%) on the gradient-echo images obtained with contrast material. Mean true cartilage thickness was 1.23 mm (SD, 0.52 mm). The mean MR-anatomic differences (absolute values) were 0.38 mm for the spin-echo images obtained without contrast material, 0.42 mm for the spin-echo images obtained with contrast material, 0.49 mm for the gradient-echo images obtained without contrast material, and 0.37 mm for the gradient-echo images obtained with contrast material. There was a tendency to overestimate thin cartilage and to underestimate thick cartilage. CONCLUSION: Several of the routinely used MR sequences, with and without intraarticular contrast medium, may cause errors in the assessment of the articular cartilage of the humeral head. Some of these errors result from either insufficient contrast between cartilage and surrounding structures or inadequately concentrated contrast medium.