Is Canada Moving towards a More Agile Regulatory Approval and Reimbursement Process with a Shifting Role for Real-World Evidence (RWE) for Oncology Drugs?

Canada is known to have a complex pathway for new drug approval and reimbursement, resulting in delayed access for patients with serious and life-threatening diseases, such as cancer. Several recent publications from key stakeholders, including patients, physicians and policymakers, highlight patient helplessness, physician frustrations and policymakers entangled in a massive network of bureaucracy unable to make headway. Several quantitative and qualitative assessments using time from regulatory approvals to successful reimbursements confirm long review times and high rejection rates for oncology drugs, especially those receiving conditional approvals.

Timeliness of Health Technology Assessments and Price Negotiations for Oncology Drugs in Canada.

Purpose: To evaluate whether time targets for Canadian Agency for Drugs and Technologies in Health (CADTH) reimbursement reviews and pan-Canadian Pharmaceutical Alliance (pCPA) price negotiations are being achieved for oncology drugs.

Materials And Methods: Recommendations, dates of submission and publication, and indications for oncology medicines issued between January 2014 and December 2023 were recorded from CADTH's reimbursement reports webpage. The date any negotiation began and the date it was completed (successfully or not), or when a decision was made not to pursue negotiation was extracted from the pCPA's webpage.

New Anticancer Drugs: Reliably Assessing "Value" While Addressing High Prices.

Countries face challenges in paying for new drugs. High prices are driven in part by exploding drug development costs, which, in turn, are driven by essential but excessive regulation. Burdensome regulation also delays drug development, and this can translate into thousands of life-years lost.

Access to Oncology Medicines in Canada: Consensus Forum for Recommendations for Improvement.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients' access to best care.

Canadians Need Improved Access to Drugs for Rare Diseases, Not More Denial.

Sirrs et al. (2023a) discuss what they consider "explosive growth" (p. 11) in the research and development (R&D) and commercialization of expensive drugs for rare diseases (DRDs).

Health technology assessment and price negotiation alignment for rare disorder drugs in Canada: Who benefits?

Background: Since 2014, the Canadian Agency for Drugs and Technologies in Health (CADTH), which performs health technology assessments for all federal, provincial and territorial government drug programs (except Quebec's) and the pan-Canadian Pharmaceutical Alliance (pCPA), which conducts price negotiations with manufacturers for all government drug programs, have been aligning their processes.

Objective: To examine trends in CADTH recommendations for non-oncology drugs for rare disorders (DRDs) released between 2014 and 2021, results of pCPA negotiations for the same drugs, and listings in government drug plans to assess who benefits from the alignment.

Results: Recommendations were positive in 87% of the reviews, although all included clinical criteria for use and/or economic conditions.

Leading Causes of Mortality and Prescription Drug Coverage in Canada and New Zealand.

Canada may soon see the introduction of a national pharmaceutical insurance system. New Zealand has a government-funded healthcare system used by all residents that operates within a tight cost-containment budget. The objective of this analysis was to compare the main mortality causes in Canada and New Zealand and examine listings in current Canadian provincial public drug plans and the New Zealand national drug formulary.

National Pharmacare in Canada: Equality or Equity, Accessibility or Affordability Comment on "Universal Pharmacare in Canada: A Prescription for Equity in Healthcare".

Canada's federal government intends to take steps to implement national pharmacare so that all Canadians have prescription drug coverage they need at an affordable price. Relatively limited funds have so far been pledged to support national pharmacare, which raises the question: what kind of program is envisioned? Since the government has already introduced regulations intended to reduce new drug prices drastically, national pharmacare seems likely to be a basic system designed to assist low-income Canadians with accessing primary care medicines. What Canadians actually need is a system that provides access to the medicine considered appropriate by the patient and their healthcare provider for the patient's specific condition.

Regulatory approval and public drug plan listing of new drugs for rare disorders in Canada and New Zealand.

A previous assessment of the alignment of health technology assessments and price negotiations for new drugs for rare disorders in Canada completed between 2014 and 2018 demonstrated that it is working for governments but has yet to lead to improved access in a timely manner for all appropriate patients in all provinces. In this analysis, drugs for rare and ultra-rare disorders with a completed price negotiation or no negotiation between 2014 and 2018 in Canada, and their reimbursement recommendations and listings in Canadian public drug programs are compared with their regulatory approval in New Zealand and listing in the New Zealand National Formulary. The results show that pharmaceutical manufacturers generally seek regulatory approval for rare disorder drugs in Canada before New Zealand, and fewer rare disorder medicines receive regulatory approval in New Zealand.

Alignment of health technology assessments and price negotiations for new drugs for rare disorders in Canada: Does it lead to improved patient access?

A previous assessment of submissions for rare disorder drugs made to the Canadian Agency for Drugs and Technologies in Health (CADTH) found that, from 2012, all positive recommendations included criteria advocating a price reduction. Since 2016, CADTH and the pan-Canadian Pharmaceutical Alliance (pCPA), which conducts drug price negotiations with manufacturers for all public drug programs, have aligned their processes. This analysis examined drugs for rare and ultra-rare disorders (DRDs and DURDs)-prevalence of ≤20 to >2 and ≤2 per 100,000, respectively-with a completed pCPA negotiation or no negotiation between 2014 and 2018, together with their reimbursement recommendations and listings in public drug programs.

Response to Letter to the Editor.

Author's response to comments from Dr Lexchin's Letter to the Editor regarding our article.

Comparison of numbers and timing of new medication regulatory approvals in Canada and New Zealand.

The Canadian federal government has proposed significant revisions to the way its patented medicines price regulator assesses the excessiveness of medication prices that are to take effect in 2019. The changes have the potential to decrease Canada's attractiveness as a market for innovative medicines. The objective of this analysis was to compare the number of new drugs given regulatory approval in Canada between 2002 and 2017 with the number in New Zealand and, of those approved in both countries, to compare approval dates.

Canadian, European and United States new drug approval times now relatively similar.

The objectives of this analysis were to assess whether consistency in Health Canada's (HC's) approval times identified in 2011 has been sustained and to compare HC's approval times with those of the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Between 2002 and 2016, 460 new drugs were approved by at least one of the agencies: 351 (76.3%), 319 (69.

Healthcare Databases for Drug Safety Research: Data Validity Assessment Remains Crucial.

Administrative healthcare utilization databases are frequently used either individually or as a component of aggregated data for evaluating drug safety issues without taking into account their known deficiencies. All too often insufficient evidence is provided about their validity for the purposes for which they are used. The assessment of data validity is a key constituent that should be included in drug safety research studies and should take a broad multifaceted approach that encompasses both diagnostic and drug exposure data.

Promoting adherence to medicines: possible lessons for Canada?

Non-adherence to medication regimens is a major issue that can negatively impact patient health and wastes health care system resources. This commentary considers whether approaches to strategies undertaken in Israel to promote adherence could be viable in Canada. The structure of the Canadian health care system and budgetary constraints make new initiatives similar to those in Israel seem unlikely in Canada without some compelling stimulus.

Health technology assessment of new drugs for rare disorders in Canada: impact of disease prevalence and cost.

Background: Authors from the Canadian Agency for Drugs and Technologies in Health (CADTH) presented an analysis of submissions to the Common Drug Review (CDR) between 2004 and February 3, 2016 for drugs for rare disorders (disorders with a prevalence of <50 per 100,000).

Objective: The aim of this analysis was to examine the same CDR submissions to evaluate whether the negative reimbursement recommendation rate, clinical evidence of efficacy and statements concerning the drug's cost in the CDR reports varied with the prevalence of the disorder treated by the drug grouped into three decreasing categories: <50 to >10, ≤10 to >1, and ≤1 per 100,000.

Results: As the prevalence of the treated disorder decreased, the median daily cost of the drug, the negative recommendation rate and the proportion of submissions with statements in the CDR reports highlighting the cost of the drug increased, while the proportion of submissions with acceptable evidence of clinical efficacy decreased.

Drug safety: withdrawn medications are only part of the picture.

In a research article published in BMC Medicine, Onakpoya and colleagues provide a historical review of withdrawals of medications for safety reasons. However, withdrawn medications are only one part of the picture about how regulatory agencies manage drug risks. Moreover, medications introduced before the increased pre-marketing regulations and post-marketing monitoring systems instituted after the thalidomide tragedy have little relevance when considering the present drug safety picture because the circumstances under which they were introduced were completely different.

Health Canada's use of priority review status for drugs for unmet needs.

The processes for granting priority review status to new drug submissions in Canada and the United States are not exactly the same, but reasonable concordance should be expected since the selection criteria are similar in the two countries. This study compared new therapeutic drugs approved by both Health Canada and the Food and Drug Administration (FDA) between 2000 and 2014 to evaluate concordance on priority review status. New therapeutic drugs approved in both countries totalled 301; 86 (28.

Review of the quality of observational studies of the association between rosiglitazone and acute myocardial infarction.

Background: Following the publication of a meta-analysis reporting a risk of acute myocardial infarction (AMI) with rosiglitazone that led to severe restrictions being placed on its use, several observational studies of the association were reported. The lifting of restrictions in the United States in 2013 makes a review of these studies pertinent.

Objective: To evaluate the quality of population-based observational studies of the rosiglitazone-AMI association.

New drug approval times and safety warnings in the United States and Canada, 1992-2011.

Background: New drug approvals in the US and Canada were reviewed in short-term studies in the 1990s. A database of drugs approved in both countries between 1992 and 2011 exists allowing for a longer time horizon to assess trends.

Objective: To compare review times of drugs approved in the US and Canada over the 20-year period and their duration on the respective markets until any serious safety risk arose.

Rosiglitazone use and associated adverse event rates in Canada between 2004 and 2010.

Background: We examined the change in the use of rosiglitazone-containing products (RCPs) Canada-wide between 2004 and 2010 and whether the rates of adverse events in association with RCP therapy in Canadian patients changed in this period to better understand the real world use of RCP medications and as part of a regulatory commitment by GlaxoSmithKline to Health Canada to assess whether there was an impact of a risk communication on cardiac safety.

Methods: RCP utilization data were obtained from IMS Brogan's longitudinal de-identified patient database (known as LRx) that tracks prescription activity using store-based data collection from pharmacies in all Canadian provinces. Adverse events (AEs), serious adverse events (SAEs) and cardiac AEs associated with RCP use in Canadian patients between April 2004 and December 2010 were identified from GlaxoSmithKline's AE database and, using the LRx data, rates per 100,000 patients were estimated.