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Special Issue "Access to Cancer Drugs in Canada"

A special issue of Current Oncology (ISSN 1718-7729).

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 22037

Special Issue Editor

Dr. Paul Wheatley-Price
E-Mail Website
Guest Editor
Department of Medicine, University of Ottawa; Medical Oncologist, The Ottawa Hospital Cancer Centre/Ottawa Hospital Research Institute; President of Lung Cancer Canada; Ottawa, ON, Canada
Interests: lung cancer; mesothelioma; advocacy

Special Issue Information

Dear Colleagues,

The therapeutic landscape in cancer has been changing rapidly for a century now since the emergence of radiotherapy in the early 1900s, and chemotherapy a few decades later. However, it seems as though the pace of progress has continued to accelerate as we rapidly have entered the era of novel chemotherapies and combinations, monoclonal antibodies, targeted therapies, immune checkpoint inhibitors, drug-antibody conjugates and more.

The regulatory processes in place to deal with the increasing numbers of effective drugs naturally needs to develop and progress too, reflecting and balancing the efficacies of new therapies, their place in treatment algorithms, the potential high price and cost-effectiveness, and the more nuanced discussions around value.

In this Special Issue of Current Oncology, manuscripts are invited to reflect on or educate about the challenges of the Canadian regulatory system, ranging from Health Canada, the Patented Medicines Prices Review Board (PMPRB), the Canadian Agency for Drugs and Technologies in Health (CADTH), who oversee the health technology assessment (HTA) and Reimbursement Reviews (formerly pan-Canadian Oncology Drug Review, or pCODR), to the pan Canadian Pharmaceutical Alliance (PCPA) that recommends a price to the territories and provinces.

These multiple steps in the regulatory process are changing, and often poorly understood by rank and file clinicians. This issue will seek to educate readers, and discuss the implications of change, the international context that Canada works in, the role of physicians as advocates or adjudicators, the pros and cons of a potential national pharmacare system, and debates around cost and value.

Manuscripts are invited that address these issues, or other issues that are considered relevant to the Special Issue title ‘Access to cancer drugs in Canada’.

Dr. Paul Wheatley-Price
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Current Oncology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (13 papers)

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Editorial

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Editorial
Access to Cancer Drugs in Canada
Curr. Oncol. 2022, 29(10), 7583-7586; https://doi.org/10.3390/curroncol29100598 - 12 Oct 2022
Viewed by 640
Abstract
Lung cancer, because of the multiple subtypes now identifiable and because of the myriad of new and effective therapies, provides fertile ground to highlight issues related to oncology drug access in Canada [...] Full article
(This article belongs to the Special Issue Access to Cancer Drugs in Canada)

Research

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Article
Determinants of the Cancer Drug Funding Process in Canada
Curr. Oncol. 2022, 29(3), 1997-2007; https://doi.org/10.3390/curroncol29030162 - 15 Mar 2022
Cited by 3 | Viewed by 1288
Abstract
Background: Canada has a publicly funded healthcare system with a complex drug funding process. After Health Canada approval to market a drug, the pan-Canadian Oncology Drug Review (pCODR) (now renamed the CADTH reimbursement review) makes a non-binding funding recommendation to the Canadian provinces [...] Read more.
Background: Canada has a publicly funded healthcare system with a complex drug funding process. After Health Canada approval to market a drug, the pan-Canadian Oncology Drug Review (pCODR) (now renamed the CADTH reimbursement review) makes a non-binding funding recommendation to the Canadian provinces (except Quebec), which each then decide whether the drug will be publicly funded. We identified the determinants of funding in this process. Methods: We analyzed drugs for advanced lung (n = 15), breast (n = 8), colorectal (CRC) (n = 7), melanoma (n = 10), and neuroendocrine (NET) (n = 3) cancers undergoing the funding decision process from 2011 to 2019. Determinants of funding assessed in the model included list price, cancer type, drug class, and pCODR recommendation. The primary outcome was the correlation between list price and time to funding (TTF: Health Canada approval to first provincial funding). Secondary outcomes included an exploratory analysis of predictors of drug funding. Results: We analyzed 43 drugs: targeted agents 72%, immunotherapy 20%, chemotherapy 7%. A total of 72% were funded in at least one province. Median TTF was 379 days (IQR 203–601). Median list price (28-day course) was CAD 8213 (IQR CAD 5391–9445). Higher list price was not correlated with TTF (correlation coefficient −0.20, p = 0.28). There was no association between list price and pCODR recommendation or the decision to fund in at least one province. A positive pCODR recommendation correlated with the provinces’ funding decisions (p < 0.001), where 89% of drugs with a positive recommendation were funded and 100% of drugs with a negative recommendation were not funded. Tumor type was predictive of TTF (p < 0.001): CRC drugs were the slowest at a median of 2541 days (IQR 702–4379), and NETs were the quickest at a median of 0 days (IQR 0–502). Cancer type predicted decision to fund in at least one province (p = 0.005), with funding for 100% of NET drugs at the high end and 29% of CRC drugs at the low end. Drug class was predictive of TTF (p = 0.01): 465 days (IQR 245–702) for targeted agents, 443 days (IQR 298–587) for chemotherapy, and 339 days (IQR 164–446) for immunotherapy. Conclusions: Determinants of drug funding included cancer type, drug class, and pCODR recommendation but not list price. Factors other than cost were more heavily weighted in the funding decisions of cancer drugs in Canadian provinces. Full article
(This article belongs to the Special Issue Access to Cancer Drugs in Canada)
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Article
Health Technology Assessment Process for Oncology Drugs: Impact of CADTH Changes on Public Payer Reimbursement Recommendations
Curr. Oncol. 2022, 29(3), 1514-1526; https://doi.org/10.3390/curroncol29030127 - 01 Mar 2022
Cited by 1 | Viewed by 2349
Abstract
Public reimbursement systems face the challenge of balancing provision of needed treatments and the reality of limited resources. Canada has a complex system for drug approval and public reimbursement, with jurisdiction divided between the federal government and the provinces/territories. A pivotal role is [...] Read more.
Public reimbursement systems face the challenge of balancing provision of needed treatments and the reality of limited resources. Canada has a complex system for drug approval and public reimbursement, with jurisdiction divided between the federal government and the provinces/territories. A pivotal role is that of health technology assessment (HTA), which relies primarily on health economic principles to analyze the value of drugs on a population health basis and make recommendations about public reimbursement. The Canadian Agency for Drugs and Technologies in Health (CADTH) provides recommendations to all provinces but Quebec. This article provides an overview of Canada’s approval and public reimbursement pathway, including the role of HTA and the economic principles on which it relies. Starting in late 2020, CADTH reduced the cost per quality-adjusted life year (QALY) threshold, the metric relied upon in making recommendations to public payers. An analysis of all 56 oncology drug final recommendations issued from January 2020 to January 2022 was conducted and confirms this reduction in the cost per QALY threshold. As a result of this threshold reduction, recommendations to the provinces include, in a number of cases, substantially greater price reductions. The potential implications for successful price negotiation with the pan-Canadian Pharmaceutical Alliance (pCPA), the public negotiating body for the provinces, are discussed. Full article
(This article belongs to the Special Issue Access to Cancer Drugs in Canada)
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Article
FDA Accelerated Approval for Malignant Hematology and Oncology Indications in the Canadian Environment
Curr. Oncol. 2022, 29(2), 402-410; https://doi.org/10.3390/curroncol29020036 - 18 Jan 2022
Cited by 1 | Viewed by 1492
Abstract
Accelerated approval (AA) by the FDA enables earlier access to promising new therapies. Health Canada has a similar process. Canada implemented a national health technology assessment (HTA) for reimbursement decisions in 2011. This study evaluated regulatory and funding timelines and decisions for FDA [...] Read more.
Accelerated approval (AA) by the FDA enables earlier access to promising new therapies. Health Canada has a similar process. Canada implemented a national health technology assessment (HTA) for reimbursement decisions in 2011. This study evaluated regulatory and funding timelines and decisions for FDA AA cancer therapies in Canada. The FDA’s AA of malignant hematology and oncology from January 2000–December 2019 was reviewed. Dates from Health Canada, HTA decisions and provincial listings were collected. There were 94 FDA AAs, two of which were subsequently withdrawn. Of the 92 AAs, 70 received full (46)/conditional (24) Health Canada approval, and 22 were not filed. Since the introduction of HTA, 31 out of 45 of Health Canada’s approved indications underwent HTA review: 18 received a positive recommendation conditional on cost-effectiveness, 8 were not recommended and 5 were withdrawn/suspended. The median time from the AA to any Health Canada approval is 9.4 months, from any Health Canada approval to HTA decision is 5.8 months and from HTA decision to the first formulary listing is 12.0 months. The access and timeline for the first formulary listing differences were observed between the USA and Canada due to the decision of pharmaceutical companies to submit (or not) to regulatory/HTA bodies, national procedural delays with different healthcare delivery models and submission timelines. This study demonstrates that there is delayed access to promising new therapies in Canada. Full article
(This article belongs to the Special Issue Access to Cancer Drugs in Canada)
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Article
Current Attitudes toward Unfunded Cancer Therapies among Canadian Medical Oncologists
Curr. Oncol. 2021, 28(6), 4748-4755; https://doi.org/10.3390/curroncol28060400 - 16 Nov 2021
Cited by 1 | Viewed by 1243
Abstract
Background: Despite successes in the development of innovative anticancer therapies, the fiscal and capacity restraints of the Canadian public healthcare system result in challenges with drug access. A meaningful proportion of systemic therapies ultimately do not receive public funding despite supporting clinical evidence. [...] Read more.
Background: Despite successes in the development of innovative anticancer therapies, the fiscal and capacity restraints of the Canadian public healthcare system result in challenges with drug access. A meaningful proportion of systemic therapies ultimately do not receive public funding despite supporting clinical evidence. In this study, we assessed Canadian medical oncologists’ current attitudes toward discussing publicly unfunded cancer treatments with patients and predictors of different practices. Methods: A web-based survey consisting of multiple choice and case-based scenarios was distributed to medical oncologists identified through the Royal College of Physicians and Surgeons of Canada directory. Results: A total of 116 responses were received. Almost all respondents reported discussing publicly unfunded treatments, including those who did so for Health Canada (HC) approved treatments (50%) and those who discussed off-label treatments (i.e., not HC approved) as guided by national guidelines (48%). Respondents in practice for over 15 years versus less than 5 years (OR 0.14, 95% CI 0.04–0.50, p = 0.002) and those who worked in a community practice versus comprehensive cancer center (OR 0.17, 95% CI 0.03–0.91, p = 0.04) were significantly less likely to discuss off-label treatment options with their patients. Almost half of respondents (47%) indicated that their institution did not permit the administration of unfunded treatments. Conclusions: There is variability in medical oncologists’ practices when it comes to discussing unfunded therapies. Given the limitations within Canada’s publicly funded healthcare system, physicians are faced with the challenge of navigating an increasingly complex balance between patient care and available resources. Engagement of relevant stakeholders and policy makers is crucial in the continued evaluation of Canada’s drug funding process. Full article
(This article belongs to the Special Issue Access to Cancer Drugs in Canada)
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Communication
Building a National Reassessment Process for Oncology Drugs: Lessons Learned by the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration through a Simulated Reassessment Exercise
Curr. Oncol. 2021, 28(6), 4645-4654; https://doi.org/10.3390/curroncol28060392 - 12 Nov 2021
Cited by 5 | Viewed by 1461
Abstract
The CanREValue Collaboration established the Reassessment & Uptake Working Group to develop a preliminary process to reassess funded cancer drugs in Canada. A simulated exercise was conducted to evaluate the proposed reassessment process using a real-world case. We invited 32 attendees including representatives [...] Read more.
The CanREValue Collaboration established the Reassessment & Uptake Working Group to develop a preliminary process to reassess funded cancer drugs in Canada. A simulated exercise was conducted to evaluate the proposed reassessment process using a real-world case. We invited 32 attendees including representatives from Health Canada and Health Technology Assessment (HTA) agencies, along with payers, clinicians, academics, and patient representatives. A case was developed using a real-world study on a publicly funded cancer drug. In facilitated group sessions, participants were asked to deliberate upon the evidence presented in the case to issue reassessment recommendations. Several themes were identified through the deliberation discussions. While the generalizability of real-world evidence (RWE) is perceived as a strength, trust in the RWE depends largely on the source of the real-world data. The attendees suggested several improvements to the proposed reassessment process including evidence requirement for reassessment, recommendation categories, and a priori study protocols. This exercise generated important insights on the evidence required for conducting reassessment and considerations for improvements of the proposed reassessment process. Building upon lessons from this exercise, future work would continue to refine the reassessment process as part of the overall CanREValue framework. Full article
(This article belongs to the Special Issue Access to Cancer Drugs in Canada)
Communication
Considerations for Developing a Reassessment Process: Report from the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration’s Reassessment and Uptake Working Group
Curr. Oncol. 2021, 28(5), 4174-4183; https://doi.org/10.3390/curroncol28050354 - 16 Oct 2021
Cited by 5 | Viewed by 2056
Abstract
The Canadian Real-world Evidence for Value in Cancer Drugs (CanREValue) Collaboration was established to develop a framework for generating and using real-world evidence (RWE) to inform the reassessment of cancer drugs following initial health technology assessment (HTA). The Reassessment and Uptake Working Group [...] Read more.
The Canadian Real-world Evidence for Value in Cancer Drugs (CanREValue) Collaboration was established to develop a framework for generating and using real-world evidence (RWE) to inform the reassessment of cancer drugs following initial health technology assessment (HTA). The Reassessment and Uptake Working Group (RWG) is one of the five established CanREValue Working Groups. The RWG aims to develop considerations for incorporating RWE for HTA reassessment and strategies for using RWE to reassess drug funding decisions. Between February 2018 and December 2019, the RWG attended four teleconferences (with follow-up surveys) and two in-person meetings to discuss recommendations for the development of a reassessment process and potential barriers and facilitators. Modified Delphi methods were used to gather input. A draft report of recommendations (to December 2018) was shared for public consultation (December 2019 to January 2020). Initial considerations for developing a reassessment process were proposed. Specifically, reassessment can be initiated by diverse stakeholders, including decision makers from public drug plans or industry stakeholders. The reassessment process should be modelled after existing deliberation and recommendation frameworks used by HTA agencies. Proposed reassessment outcome categories include maintaining status quo, revisiting funding criteria, renegotiating price, or disinvesting. Overall, these initial considerations will serve as the basis for future advancements by the Collaboration. Full article
(This article belongs to the Special Issue Access to Cancer Drugs in Canada)
Article
Describing Sources of Uncertainty in Cancer Drug Formulary Priority Setting across Canada
Curr. Oncol. 2021, 28(4), 2708-2719; https://doi.org/10.3390/curroncol28040236 - 17 Jul 2021
Cited by 4 | Viewed by 1486
Abstract
Over the years, there have been significant advances in oncology. However, the rate that therapeutics come to market has increased, while the strength of evidence has decreased. Currently, there is limited understanding about how these uncertainties are managed in provincial funding decisions for [...] Read more.
Over the years, there have been significant advances in oncology. However, the rate that therapeutics come to market has increased, while the strength of evidence has decreased. Currently, there is limited understanding about how these uncertainties are managed in provincial funding decisions for cancer therapeutics. We conducted qualitative interviews with six senior officials from four different Canadian provinces (British Columbia, Alberta, Quebec, and Ontario) and a document review of the uncertainties found in submissions to the pan-Canadian Oncology Drug Review (pCODR). Participants reported considerable uncertainty related to a lack of solid clinical evidence (early-phase clinical trials: generalizability, immature data, and the use of unvalidated surrogate outcomes). Proposed strategies to deal with the uncertainty included risk-sharing agreements, collection of real-world evidence (RWE), and ongoing collaboration between federal groups and provinces. The document review added to the reported uncertainties by classifying them into five main categories: trial validity, population, comparators, outcomes, and intervention. This study highlights how decision makers must deal with significant amounts of uncertainty in funding decisions for cancer drugs, most of which stems from methodological limitations in clinical trials. There is a critical need for transparent priority-setting processes and mechanisms to reevaluate drugs to ensure benefit given the high level of uncertainty of novel therapeutics. Full article
(This article belongs to the Special Issue Access to Cancer Drugs in Canada)

Review

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Review
The Pathway for New Cancer Drug Access in Canada
Curr. Oncol. 2022, 29(2), 455-464; https://doi.org/10.3390/curroncol29020041 - 21 Jan 2022
Cited by 1 | Viewed by 2525
Abstract
Cancer treatment has evolved significantly over the past decade with the emergence of a multitude of new treatments across cancer types. Alongside the pace of drug discovery, the cost of cancer drugs has also increased. In the face of this growth in development [...] Read more.
Cancer treatment has evolved significantly over the past decade with the emergence of a multitude of new treatments across cancer types. Alongside the pace of drug discovery, the cost of cancer drugs has also increased. In the face of this growth in development and spending, it is crucial to have an understanding of the processes and pressures new drugs navigate to get to the market in Canada. This paper is a review of the complex, multi-step regulatory and funding process undertaken by cancer drugs in Canada. It reviews the role of Health Canada, the Patented Medicine Prices Review Board, the Health Technology Assessment, the pan-Canadian Pharmaceutical Alliance, and finally, the provincial, territorial, and federal payers. Recent developments are highlighted. Strategies to minimize duplication of effort, improve timeliness, and increase efficiency are explored. The cancer drug regulatory and funding process in Canada is complex, and an understanding of the current system and ongoing evolution is essential. Full article
(This article belongs to the Special Issue Access to Cancer Drugs in Canada)
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Other

Opinion
Access Denied? The Unintended Consequences of Pending Drug Pricing Rules
Curr. Oncol. 2022, 29(4), 2504-2508; https://doi.org/10.3390/curroncol29040204 - 02 Apr 2022
Cited by 1 | Viewed by 1343
Abstract
The government of Canada now plans to bring into force new federal drug pricing regulations on 1 July 2022. We do not take issue with the goal of medication affordability, which is vital in healthcare the world over. Our concern is that the [...] Read more.
The government of Canada now plans to bring into force new federal drug pricing regulations on 1 July 2022. We do not take issue with the goal of medication affordability, which is vital in healthcare the world over. Our concern is that the new guidelines are being implemented without due consideration for three major unintended consequences: regulatory changes will lower the number of clinical trials for new medications in Canada, fewer clinical trials will mean lower research and development investments, and changes will reduce patients’ access to new medications. Access to effective medications is a cornerstone of healthcare for Canadian patients. As physicians, our duty to patient care demands that we tell the government to protect the right of Canadians to timely access to life-changing medicines. Full article
(This article belongs to the Special Issue Access to Cancer Drugs in Canada)
Viewpoint
Not All Canadian Cancer Patients Are Equal—Disparities in Public Cancer Drug Funding across Canada
Curr. Oncol. 2022, 29(3), 2064-2072; https://doi.org/10.3390/curroncol29030166 - 17 Mar 2022
Cited by 2 | Viewed by 1869
Abstract
Canada lacks a national drug insurance plan. The home province or territory of a patient determines which cancer drugs are available on the public formulary, who is eligible for public coverage and what portion of the financial burden of cancer care falls to [...] Read more.
Canada lacks a national drug insurance plan. The home province or territory of a patient determines which cancer drugs are available on the public formulary, who is eligible for public coverage and what portion of the financial burden of cancer care falls to the individual. This narrative review describes the current interprovincial disparities in access to cancer drugs across Canada. Health technology assessment (HTA) of drugs at a provincial and territory level is a closed process, does not necessarily follow the recommendations of national HTA and leads to further delays in drug access. The public coverage of take-home cancer drugs (THCDs) in Ontario and the Atlantic provinces is often fragmented, unnecessarily complex and a barrier to cancer drug access. Policy solutions to address inter-provincial formulary variation and poor access to THCDs are discussed. Full article
(This article belongs to the Special Issue Access to Cancer Drugs in Canada)
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Commentary
Is It Time to Commit to a Process to Re-Evaluate Oncology Drugs? A Descriptive Analysis of Systemic Therapies for Solid Tumour Indications Reviewed in Canada from 2017 to 2021
Curr. Oncol. 2022, 29(3), 1919-1931; https://doi.org/10.3390/curroncol29030156 - 10 Mar 2022
Cited by 1 | Viewed by 1327
Abstract
We undertook an analysis of the Canadian Agency for Drugs and Technologies in Health (CADTH)’s health technology assessments (HTAs) of systemic therapies for solid tumour indications to determine if a mechanism to re-evaluate HTA decisions is needed based on the level of certainty [...] Read more.
We undertook an analysis of the Canadian Agency for Drugs and Technologies in Health (CADTH)’s health technology assessments (HTAs) of systemic therapies for solid tumour indications to determine if a mechanism to re-evaluate HTA decisions is needed based on the level of certainty supporting the original recommendation. To measure the certainty in the evidence, we analysed if: (1) overall survival (OS) was the primary endpoint in the pivotal trial, (2) median OS was available at the time of the recommendation, and (3) the expert review committee explicitly identified gaps in the evidence. There were 96 drugs approved by Health Canada that met our eligibility criteria between 1 January 2017 and 31 October 2021. Median OS was not estimable at the time of the recommendation in 57% of the positive recommendations, and the uncertainty in the magnitude of clinical benefit was identified by the expert review committee in 21% of the positive recommendations. There is uncertainty at the time of the HTA recommendation for many drugs, and thus a need to implement a process to re-evaluate drugs in Canada to allow patients timely access to promising therapies while ensuring long-term value of therapies to patients and the healthcare system. Full article
(This article belongs to the Special Issue Access to Cancer Drugs in Canada)
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Opinion
Closing the Gaps to Timely Patient Access: Perspectives on Conditional Funding Models
Curr. Oncol. 2022, 29(2), 981-988; https://doi.org/10.3390/curroncol29020083 - 10 Feb 2022
Cited by 1 | Viewed by 1270
Abstract
The Canadian system for approval of new cancer drugs is complex with multiple steps. Health Canada grants a license for a drug to be marketed and prescribed. The Canadian Agency for Drugs and Technologies in Health (CADTH) and Institut national d’excellence en santé [...] Read more.
The Canadian system for approval of new cancer drugs is complex with multiple steps. Health Canada grants a license for a drug to be marketed and prescribed. The Canadian Agency for Drugs and Technologies in Health (CADTH) and Institut national d’excellence en santé et services sociaux (INESSS) make recommendations by way of health technology assessments (HTA). If positive, the latter then lead to confidential price negotiations at the pan-Canadian pharmaceutical alliance (pCPA), after which individual provinces and territories make a listing decision. Delays can occur at each stage, but post-HTA delays can be lengthy and unpredictable, denying or impeding access to an effective drug with the potential for devastating clinical outcomes. Conditional funding models have been adopted in a number of European countries with the goal of providing timely access to new medications in areas of unmet need, in advance of further steps in the reimbursement process. This manuscript discusses different stakeholder perspectives on conditional funding agreements—including a recent successful example of such a process in the UK—based on a panel discussion at the 2021 Canadian Association of Population Therapeutics (CAPT) Conference. Full article
(This article belongs to the Special Issue Access to Cancer Drugs in Canada)
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