Biologics in Plaque Psoriasis

Health Canada has approved 11 biologics for the treatment of adults with moderate-to-severe plaque psoriasis (PsO). These biologics can be divided into 2 groups based on mechanisms of action and market authorization dates: Old-generation biologics (5): include anti–tumour necrosis factor (TNF) agents (etanercept, adalimumab, infliximab, and certolizumab pegol) and an anti-interleukin (IL)-12/IL-23 inhibitor (ustekinumab) which were approved in Canada before 2010. New-generation biologics (6): include anti-IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) and anti-IL-23 inhibitors (guselkumab, tildrakizumab, and risankizumab) which were approved in Canada in 2015 or later. Patent protection has expired for infliximab, certolizumab, and ustekinumab. There is no valid data protection status for all 5 older generation biologics. However, only 3 of the old-generation biologics have biosimilar versions (adalimumab, etanercept, and infliximab) that are available in the Canadian market. Biosimilar versions for adalimumab and etanercept were marketed for PsO approximately 3 years to 4 years after their initial Notice of Compliance was issued, respectively. This delay can be attributed to various factors, including litigation and global agreements between manufacturers. Despite the expiry of data and patent protection for both ustekinumab and certolizumab, no biosimilar versions are available in Canada. Data protection for both biologics expired more than 4 years ago, and the patents have expired in 2021. A lack of a biosimilar entrant in Canada could be attributed to various factors, including clinical trial development based on exclusivity timelines in the US, where data protection is 4 years longer for biologics versus Canada. CADTH has reviewed 3 of 5 of the old-generation biologics and all 6 of the new-generation biologics; all drugs received similar CADTH Canadian Drug Expert Committee (CDEC) recommendations. The clinical programs of most of the new-generation biologics included direct evidence demonstrating superiority or statistically significantly higher efficacy outcomes compared with the active comparator of the old-generation biologics. The clinical trials for new-generation biologics also incorporated more stringent primary outcome measures. The old-generation biologics predated the pan-Canadian Pharmaceutical Alliance (pCPA) process (except for certolizumab), which could imply disparate product listing agreements across public drug plans for these drugs. The only biologics not included on any public formularies are certolizumab, guselkumab, and tildrakizumab (although tildrakizumab has yet to begin pCPA negotiations). Listing status for biologics fell under restricted benefit, but differed in terms of active (e.g., review through special authorization forms) versus passive (e.g., Limited Use codes in Ontario) procedures across public drug plans. Moreover, 3 public drug plans employed 2-tiered formularies (i.e., Alberta, Manitoba, and Correctional Services Canada) which required a trial of new-generation biologics or old-generation biosimilars before reimbursement of old-generation originators. Utilization patterns of old- versus new-generation biologics within the Ontario Public Drug Programs demonstrated that a significant proportion of new patients were treated with old-generation biologics (54% in 2019 and 37% in 2020) despite the availability of multiple new-generation biologics. In conclusion, formulary management is warranted for biologics for PsO given the significant utilization of old-generation originators in the current context of delayed marketing of their biosimilar versions for PsO and their reimbursement predating the pCPA process. New-generation biologics underwent pCPA negotiations and direct evidence was submitted that demonstrated superiority versus old-generation biologic active comparators, which may ultimately prove to be a greater value for patients and payers.

Examining the Prevalence, Nutritional Quality and Marketing of Foods with Voluntary Nutrient Additions in the Canadian Food Supply

Foods with voluntary nutritional additions are a fast-growing sector of the global food industry. In Canada, while the addition of nutrients to foods has been regulated through fortification regulations, parallel policies which aim to encourage product innovation have also allowed for the voluntary addition of nutrients and other novel ingredients to ‘supplemented’ and ‘functional’ foods. Concerns have been raised that the consumption of these products may have negative repercussions on population health, such as high nutrient intakes inappropriate for certain population subgroups (e.g., children) and the shifting of dietary patterns to include more unhealthy foods. The aim of this study was to evaluate the prevalence, nutritional quality, and marketing characteristics of foods with added nutrients in the Canadian market. We found many nutritionally-enhanced foods contained high levels of nutrients beyond recommended intakes, despite these nutrients having no evidence of inadequacy in the Canadian population. Additionally, a large proportion of foods with added nutrients had poor nutrient profiles (were deemed ‘less healthy’ than their non-enhanced counterparts) and carried heavy marketing on their labels, regardless of their nutritional quality. Taken together these findings raise concerns about foods with voluntary nutrient additions and suggest the need to further investigate consumer attitudes and decision-making towards these foods.

Stability of Compounded Digoxin Solution 0.05 mg/mL for Injection

Background: In 2015, commercial pediatric digoxin injection 0.05 mg/mL was discontinued, leaving only one adult concentration (0.25 mg/mL) for injection on the Canadian market. No published studies have documented the chemical stability over a long period of time of a diluted solution of digoxin for injection. Objective: The aim of this study was to assess the chemical stability of 2 digoxin injection formulations 0.05 mg/mL diluted in 2 vehicles stored at 5°C or a 25°C. Methods: The compounded solution of digoxin 0.05 mg/mL for injection was prepared with digoxin 0.25 mg/mL after dilution in 2 different vehicles, normal saline, and a compounding of the commercial vehicle. Half of the compounding products were stored in 2 mL transparent glass vials at 25°C and the other half at 5°C. Chemical stability was evaluated by HPLC–UV analysis on days 0, 14, 30, 60, 90, 120, 150, 180 for each temperature conditions. In addition, samples were tested for organoleptic change, presence of particular matter as well as sterility. Results: For all tested preparations, the concentration of digoxin remained above 90.0% of the initial concentration throughout the 180-day study. Furthermore, no organoleptic change was observed; particulate matter assessment was in acceptable range; and sterility specifications were met. Conclusions: Digoxin 0.05 mg/mL obtained with a dilution of digoxin 0.25 mg/mL by normal saline or a copy of the commercial vehicle remained stable for at least 180 days at 5°C and 25°C.

An investigation of corporate responsibility & sustainability goals in the Canadian commercial real estate and construction sector

This thesis investigates the potential integration of leading Corporate Responsibility and Sustainability (CR&S) goals across selected Commercial Real Estate (CRE) firms, key anchor tenants, and construction companies within the Canadian market as they relate to office building assets. Current literature provides limited observations and analysis on CR&S within the CRE sector, particularly for the Canadian market. In order to address this gap and advance the principles of CR&S across the Canadian CRE sector, the research provides a comprehensive qualitative content analysis of publically available CR&S reports, along with interviews conducted with subject matter experts in the sector. Reduction of energy, water and waste consumption, along with associated GHG emissions have been identified as leading elements driving environmental resource management, which in turn is identified as the founding base for integrating CR&S goals across the Canadian CRE market. In addition to uncovering leading CR&S goals, the study identified market differentiators and regulatory compliance as key CR&S motivators, along with leading tracking and implementation measures for CR&S goals, and their associated internal and external barriers to integrating CR&S goals. Ultimately, the study provides an academic contribution in identifying environmental resource management as a base for CR&S integration across the Canadian CRE sector.

An investigation of corporate responsibility & sustainability goals in the Canadian commercial real estate and construction sector

This thesis investigates the potential integration of leading Corporate Responsibility and Sustainability (CR&S) goals across selected Commercial Real Estate (CRE) firms, key anchor tenants, and construction companies within the Canadian market as they relate to office building assets. Current literature provides limited observations and analysis on CR&S within the CRE sector, particularly for the Canadian market. In order to address this gap and advance the principles of CR&S across the Canadian CRE sector, the research provides a comprehensive qualitative content analysis of publically available CR&S reports, along with interviews conducted with subject matter experts in the sector. Reduction of energy, water and waste consumption, along with associated GHG emissions have been identified as leading elements driving environmental resource management, which in turn is identified as the founding base for integrating CR&S goals across the Canadian CRE market. In addition to uncovering leading CR&S goals, the study identified market differentiators and regulatory compliance as key CR&S motivators, along with leading tracking and implementation measures for CR&S goals, and their associated internal and external barriers to integrating CR&S goals. Ultimately, the study provides an academic contribution in identifying environmental resource management as a base for CR&S integration across the Canadian CRE sector.

Book publishing in Canada, 1945-2010: ownership and control of the Canadian market

"This essay sets out to trace the structure of the Canadian publishing industry in light of the policies that have allowed and enabled the survival of an indigenous Canadian publishing industry. Specifically, it explores the history of government intervention in the Canadian publishing industry through the Investment Canada Act in its three formualations: Federal Investment Revenue Agency Act (FIRA), enacted from 1974 to 1985; the Baie Comeau policy, from 1985 to 1992; and the Revised Investment Canada Act, from 1992 to the present. The Investment Canada Act in each of these formulation was the crucial policy designed to protect and encourage Canadian ownership of the publishing industry. This study then assesses the impact of these policies on the ownership and size of Canadian publishers"--From the introduction, page 3.

Book publishing in Canada, 1945-2010: ownership and control of the Canadian market

"This essay sets out to trace the structure of the Canadian publishing industry in light of the policies that have allowed and enabled the survival of an indigenous Canadian publishing industry. Specifically, it explores the history of government intervention in the Canadian publishing industry through the Investment Canada Act in its three formualations: Federal Investment Revenue Agency Act (FIRA), enacted from 1974 to 1985; the Baie Comeau policy, from 1985 to 1992; and the Revised Investment Canada Act, from 1992 to the present. The Investment Canada Act in each of these formulation was the crucial policy designed to protect and encourage Canadian ownership of the publishing industry. This study then assesses the impact of these policies on the ownership and size of Canadian publishers"--From the introduction, page 3.

How competitive is the Canadian residential broadband market? A study of Canadian internet service providers and their regulatory environment

This paper offers a detailed assessment of the state of competition in the Canadian residential broadband market. After examining barriers to entry, the nature of rivalry in pricing and services, and the extent to which competitors can develop a sustainable position in the market, it concludes that the Canadian market does not foster effective competition. Canadian consumers do not have access to a range of differentiated services, and there is little innovation in the market. The paper offers some suggestions on ways to increase competitiveness in the broadband market, and concludes that changes to the current market structure are required to enable the development of more innovative broadband services in Canada.

How competitive is the Canadian residential broadband market? A study of Canadian internet service providers and their regulatory environment

This paper offers a detailed assessment of the state of competition in the Canadian residential broadband market. After examining barriers to entry, the nature of rivalry in pricing and services, and the extent to which competitors can develop a sustainable position in the market, it concludes that the Canadian market does not foster effective competition. Canadian consumers do not have access to a range of differentiated services, and there is little innovation in the market. The paper offers some suggestions on ways to increase competitiveness in the broadband market, and concludes that changes to the current market structure are required to enable the development of more innovative broadband services in Canada.

Companies’ statements about drugs withdrawn from the Canadian market: A descriptive analysis

BACKGROUND: Companies often defending their products when there are concerns about their safety and/or effectiveness. OBJECTIVE: This study looks at drugs removed from the Canadian market from 1990 onward and examines how companies responded. METHODS: This descriptive analysis used a previously published article and a hand search of a Government of Canada website to generate a list of drugs withdrawn from Canada from 1990 onwards. For each product the following information was extracted: brand-name, generic name, company, date of withdrawal and evidence base for withdrawal. Google and Factiva searches were used to identify sources containing statements from the company about the withdrawal. Statements were independently graded by two people into the following categories: company agrees with the withdrawal; drug could be used safely with certain precautions; company may reintroduce the drug; company disagrees with the withdrawal. Searches were carried out between September 15–20, 2020. RESULTS: There were 22 drugs for which there were company statements. In 10 statements, the companies disagreed with the decision to withdraw the drug and in 7 they agreed with the decision. In the other 5 cases they felt that the drug could have been kept on the market with restrictions (2 cases) or they might reintroduce the drug (3 cases). The level of evidence for the withdrawal did not seem to influence the companies’ position. CONCLUSION: In 15 out of 22 cases, the company either disagreed with the decision to withdraw the drug or felt that the drug should continue to be available to Canadian patients.