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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. We need system-wide reform that will enable less expensive, faster drug development. The speed with which COVID-19 vaccines and AIDS therapies were developed indicates this is possible if governments prioritize it. Countries also differ in how they value drugs, and generally, those willing to pay more have better, faster access. Canada is used as an example to illustrate how "incremental cost-effectiveness ratios" (ICERs) based on measures such as gains in "quality-adjusted life-years" (QALYs) may be used to determine a drug's value but are often problematic, imprecise assessments. Generally, ICER/QALY estimates inadequately consider the impact of patient crossover or long post-progression survival, therapy benefits in distinct subpopulations, positive impacts of the therapy on other healthcare or societal costs, how much governments willingly might pay for other things, etc. Furthermore, a QALY value should be higher for a lethal or uncommon disease than for a common, nonlethal disease. Compared to international comparators, Canada is particularly ineffective in initiating public funding for essential new medications. Addressing these disparities demands urgent reform.

There is an increasing demand for real-world data pertaining to the usage of cancer treatments, especially in settings where no standard treatment is specifically recommended. This study presents the first real-world analysis of third-line treatment patterns in HER2-positive metastatic breast cancer (mBC) patients in Canada. The purpose was to assess evolution of clinical practice and identify unmet needs in post-second-line therapy. Retrospective data from medical records of 66 patients who received third-line treatment before 31st October 2018, and data from 56 patients who received third-line treatment after this date, extracted from the Personalize My Treatment (PMT) cancer patient registry, were analyzed. In the first cohort, the study revealed heterogeneity in the third-line setting, with trastuzumab, lapatinib, and T-DM1 being the main treatment options. Even though data were collected before the wide availability of tucatinib, neratinib and trastuzumab deruxtecan in Canada, the PMT cohort revealed the emergence of new therapeutic combinations and a shift from lapatinib usage to T-DM1 choice was observed. These findings underscore the evolving nature of third-line treatment strategies in Canada, a facet that is intrinsically tied to the availability of new drugs. The absence of a consensus on post-second-line treatment highlights the pressing need for more efficient therapeutic alternatives beyond the currently available options. This study not only offers valuable insights into the present landscape of third-line treatment in Canada but validates the significance and effectiveness of the PMT registry as a tool for generating pan-Canadian real-world evidence in oncology and its capacity to provide information on evolution of therapeutic practices., Competing Interests: Author MG was employed by company Knight Therapeutics Inc. This study received funding from Knight Therapeutics Inc. Knight Therapeutics had the following involvement with the study: CR cohort patient selection design and review of the manuscript., (Copyright © 2023 Gambaro, Groleau, McNamara, Awan, Salem, Abdelsalam, St-Hilaire, Vincent, Carrier, MacKay, Provencher, Boudreau, Hamilou, Saad, Ferrario, Batist and Marques.)

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.

New drugs are expensive, in part due to excessive drug development costs. Governments are trying to reduce drug prices. This can delay access to effective agents. A country's access to new drugs correlates with prices they agree to pay. After Health Canada approves a drug, the Canadian Agency for Drug and Technologies in Health (CADTH) assesses it. CADTH's approval is usually contingent on it costing ≤CAD 50,000 per quality adjusted life year (QALY) gained. This value (unchanged from the 1970s) is inappropriately low. An inflation-adjusted CAD 50,000 1975 QALY should translate into a CAD 250,000 2021 QALY. CADTH's target also does not consider that drug development costs have risen much faster than inflation or that new precision therapies may only be used in small populations. In a separate process, proposals from the Patented Medicines Price Review Board (PMPRB) would decrease initial Canadian drug prices by 20%, but prices would fall further as sales increased, with ultimate price reductions of up to 80%. PMPRB claims its proposal would not reduce drug access, but multiple analyses strongly suggest otherwise. Government price controls target the symptom (high prices), not the disease. They translate into shortages without solving the problem. CADTH and PMPRB approaches both threaten access to effective drugs.

Canada's vast geography, and centralized delivery of cancer care and clinical trials create barriers for trial participation for patients in remote and rural settings. The development and implementation of a framework that enables safe and regulatory compliant trial participation through local healthcare providers would benefit Canadian patients, clinicians, trial sponsors and the health care system. To address this issue, representatives of Canada's cancer clinical trial community met to identify key challenges and develop recommendations for remote patient participation in trials. A structured literature review identified remote/rural trial delivery models. A panel of expert stakeholders reviewed the models and participated in a workshop to assess health system readiness, identify needed processes, tools and mechanisms, and develop recommendations for a Canadian framework for decentralized clinical trial conduct. The Canadian Remote Access Framework for clinical Trials (CRAFT) represents a risk-based approach used by site investigators to delegate responsibilities for a given trial to satellite health centres within a hub-and-spoke "trial cluster". The Framework includes specific recommendations to ensure research experience, capacity, regulatory compliance and patient safety. Canada's cancer care and telemedicine systems can be leveraged to enable broader access to clinical trials for patients who are geographically remote from cancer centres. CRAFT's risk-based framework is based on other successful models of remote trial patient management and is in the pilot implementation phase in Canada.

Introduction: Studies suggest that patients with cancer are more likely to experience severe outcomes from COVID-19. Therefore, cancer centres have undertaken efforts to care for patients with cancer in COVID-free units. Nevertheless, the frequency and relevance of nosocomial transmission of COVID-19 in patients with cancer remain unknown. The goal of this study was to determine the incidence and impact of hospital-acquired COVID-19 in this population and identify predictive factors for COVID-19 severity in patients with cancer., Methods: Patients with cancer and a laboratory-confirmed diagnosis of COVID-19 were prospectively identified using provincial registries and hospital databases between March 3rd and May 23rd, 2020 in the provinces of Quebec and British Columbia in Canada. Patient's baseline characteristics including age, sex, comorbidities, cancer type and type of anticancer treatment were collected. The exposure of interest was incidence of hospital-acquired infection defined by diagnosis of SARS-CoV-2 ≥ 5 days after hospital admission for COVID-unrelated cause. Co-primary outcomes were death or composite outcomes of severe illness from COVID-19 such as hospitalisation, supplemental oxygen, intensive-care unit (ICU) admission and/or mechanical ventilation., Results: A total of 252 patients (N = 249 adult and N = 3 paediatric) with COVID-19 and cancer were identified, and the majority were residents of Quebec (N = 233). One hundred and six patients (42.1%) received active anticancer treatment in the last 3 months before COVID-19 diagnosis. During a median follow-up of 25 days, 33 (13.1%) required admission to the ICU, and 71 (28.2%) died. Forty-seven (19.1%) had a diagnosis of hospital-acquired COVID-19. Median overall survival was shorter in those with hospital-acquired infection than that in a contemporary community-acquired population (27 days versus unreached, hazard ratio (HR) = 2.3, 95% CI: 1.2-4.4, p = 0.0006. Multivariate analysis demonstrated that hospital-acquired COVID-19, age, Eastern Cooperative Oncology Group status and advanced stage of cancer were independently associated with death., Interpretation: Our study demonstrates a high rate of nosocomial transmission of COVID-19, associated with increased mortality in both univariate and multivariate analysis in the cancer population, reinforcing the importance of treating patients with cancer in COVID-free units. We also validated that age and advanced cancer were negative predictive factors for COVID-19 severity in patients with cancer., Competing Interests: Conflict of interest statement BR and AE declare grant support from Astra Zeneca (grant number: N/A). Other authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Immune checkpoint inhibitors have revolutionized care for many cancer indications, with considerable effort now being focused on increasing the rate, depth, and duration of patient response. One strategy is to combine immune strategies (for example, ctla-4 and PD-1/L1-directed agents) to harness additive or synergistic efficacy while minimizing toxicity. Despite encouraging results with such combinations in multiple tumour types, numerous clinical challenges remain, including a lack of biomarkers that reliably predict outcome, the emergence of therapeutic resistance, and optimal management of immune-related toxicities. Furthermore, the selection of ideal combinations from the myriad of immune, systemic, and locoregional therapies has yet to be determined. A longitudinal network-based approach could offer advantages in addressing those critical questions, including long-term follow-up of patients beyond individual trials. The molecular cancer registry Personalize My Treatment, managed by the Networks of Centres of Excellence nonprofit organization Exactis Innovation, is uniquely positioned to accelerate Canadian immuno-oncology (io) research efforts throughout its national network of cancer sites. To gain deeper insight into how a pan-Canadian network could advance research in io combinations, Exactis invited preeminent clinical and scientific advisors from across Canada to a roundtable event in November 2017. The present white paper captures the expert advice provided: leverage longitudinal patient data collection; facilitate network collaboration and assay harmonization; synergize with existing initiatives, networks, and biobanks; and develop an io combination trial based on Canadian discoveries., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare the following interests outside the submitted work: VH is an employee of Exactis Innovation; RF is the ceo of Exactis Innovation; GB has received research funding from several pharmaceutical companies and is the cmo of Exactis Innovation; PKC has received fees as an advisory board member for Bristol–Myers Squibb, Merck, AstraZeneca, Pfizer, and Roche; HLM has received fees as an advisory board member for Merck, Spectrums, Syndax Pharmaceuticals, obi Pharma, Calithera, Roche, Lilly, Peregrine, TapImmune, Amgen, Puma, Pfizer, and Immunomedics, and has received research funding from Bristol–Myers Squibb, MedImmune, Ziopharm, Eli Lilly, and Merck; TMP has received advisory board member fees from Bristol–Myers Squibb, Merck, and Incyte, and a grant from Roche; RS has received honoraria from Pfizer, and honoraria or advisory board fees from Boehringer Ingelheim, AstraZeneca, Roche, Lundbeck, Bristol–Myers Squibb, Merck, AbbVie, and Takeda; MFS has received honoraria from Amgen; JS is a permanent member of the scientific advisory board of Surface Oncology and owns stock in Surface Oncology; DJS has received honoraria or consulting or advisory board fees from Roche, Boehringer Ingelheim, Novartis, Merck, AstraZeneca, Bristol–Myers Squibb, and Exactis, and scientific writing or clinical trials support from Boehringer Ingelheim, AstraZeneca, Novartis, Bristol–Myers Squibb, and Celgene; SV has received fees as an advisory board member for Amgen, Lilly, AstraZeneca, Novartis, Pfizer, and Roche, and is the co-founder and medical director of OncologyEducation.com (uncompensated). BM, DM, and SSS have no conflicts of interest to disclose.

Background: Colorectal Cancer Canada, in partnership with a Scientific Advisory Committee, is developing a Canadian Patient Group Pathway to Accessing Cancer Clinical Trials ("Pathway"). A central element of the Pathway is presented here-namely, a set of recommendations and tools aimed at each stakeholder group., Methods: A summary of the peer-reviewed and grey literature informed discussions at a meeting, held in June 2017, in which a cross-section of stakeholders reached consensus on the potential roles of patient groups in the cancer clinical trials process, barriers to accessing cancer clinical trials, best practice models for patient-group integration, and a process for developing the Pathway. Canadian recommendations and tools were subsequently developed by a small working group and reviewed by the Scientific Advisory Committee., Results: The major output of the consensus conference was agreement that the Clinical Trials Transformation Initiative (ctti) model, successfully applied in the United States, could be adapted to create a Canadian Pathway. Two main differences between the Canadian and American cancer clinical research environments were highlighted: the effects of global decision-making and systems of regulatory and funding approvals. The working group modified the ctti model to incorporate those aspects and to reflect Canadian stakeholder organizations and how they currently interact with patient groups., Conclusions: Developing and implementing a Canadian Pathway that incorporates the concepts of multi-stakeholder collaboration and the inclusion of patient groups as equal partners is expected to generate significant benefits for all stakeholders. The next steps to bring forward a proposed Pathway will involve engaging the broader cancer research community. Clinical trial sponsors will be encouraged to adopt a Charter recognizing the importance of including patient groups, and to support the training of patient groups through an independent body to ensure quality research partners. Integration of patient groups into the process of developing "real world" evidence will be advanced by a further consensus meeting being organized by Colorectal Cancer Canada for 6-7 November 2018., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conf licts of interest, and we declare the following interests: Colorectal Cancer Canada has received support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim Canada, Bristol–Myers Squibb, Eli Lilly Canada, Hoffmann–La Roche, Janssen, Merck Frosst Canada and Company, Novartis Pharma Canada, Pfizer Canada, Pharmascience; GB has contracted with multiple biopharma companies in clinical research programs and has collaborated with many in matching funds for major peer-reviewed grants, including Hoffman–La Roche, Merck, Pfizer, Bristol–Myers Squibb, Eli Lilly Canada, Esperas Pharma, Chorus, AstraZeneca, Novartis, and Amgen; DPR has accepted consulting fees, speaker fees, and honoraria from multiple biopharma companies, including AbbVie, Amgen, Janssen, Eli Lilly Canada, Merck, Novartis, Novo Nordisk, Pfizer, and Hoffman–La Roche; BioCanRx has received support from Turnstone Biologics, Merck, EMD Serono, Roche Pharma, General Electric, PeproTech, Immudex, Immunovaccine, Pall, Zymeworks, Beckman Coulter, AstraZeneca, Roche Diagnostics, GlaxoSmithKline, Affymetrix, Blueline Bioscience, Caprion Biosciences, PerkinElmer, BioLegend, PeproTech, and NanoString Technologies.

Advances in 'omics' technology and targeted therapeutic molecules are together driving the incorporation of molecular-based diagnostics into the care of patients with cancer. There is an urgent need to assess the efficacy of therapy determined by molecular matching of patients with particular targeted therapies. WINTHER is a clinical trial that uses cutting edge genomic and transcriptomic assays to guide treatment decisions. Through the lens of this ambitious multinational trial (five countries, six sites) coordinated by the Worldwide Innovative Networking Consortium for personalized cancer therapy, we discovered key challenges in initiation and conduct of a prospective, omically driven study. To date, the time from study concept to activation has varied between 19 months at Gustave Roussy Cancer Campus in France to 30 months at the Segal Cancer Center, McGill University (Canada). It took 3+ years to be able to activate US sites due to national regulatory hurdles. Access to medications proposed by the molecular analysis remains a major challenge, since their availability through active clinical trials is highly variable over time within sites and across the network. Rules regarding the off-label use of drugs, or drugs not yet approved at all in some countries, pose a further challenge, and many biopharmaceutical companies lack a simple internal mechanism to supply the drugs even if they wish to do so. These various obstacles should be addressed to test and then implement precision medicine in cancer., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Great advances in analytical technology coupled with accelerated new drug development and growing understanding of biological challenges, such as tumor heterogeneity, have required a change in the focus for biobanking. Most current banks contain samples of primary tumors, but linking molecular signatures to therapeutic questions requires serial biopsies in the setting of metastatic disease, next-generation of biobanking. Furthermore, an integration of multidimensional analysis of various molecular components, that is, RNA, DNA, methylome, microRNAome and post-translational modifications of the proteome, is necessary for a comprehensive view of a tumor's biology. While data using such biopsies are now regularly presented, the preanalytical variables in tissue procurement and processing in multicenter studies are seldom detailed and therefore are difficult to duplicate or standardize across sites and across studies. In the context of a biopsy-driven clinical trial, we generated a detailed protocol that includes morphological evaluation and isolation of high-quality nucleic acids from small needle core biopsies obtained from liver metastases. The protocol supports stable shipping of samples to a central laboratory, where biopsies are subsequently embedded in support media. Designated pathologists must evaluate all biopsies for tumor content and macrodissection can be performed if necessary to meet our criteria of >60% neoplastic cells and <20% necrosis for genomic isolation. We validated our protocol in 40 patients who participated in a biopsy-driven study of therapeutic resistance in metastatic colorectal cancer. To ensure that our protocol was compatible with multiplex discovery platforms and that no component of the processing interfered with downstream enzymatic reactions, we performed array comparative genomic hybridization, methylation profiling, microRNA profiling, splicing variant analysis and gene expression profiling using genomic material isolated from liver biopsy cores. Our standard operating procedures for next-generation biobanking can be applied widely in multiple settings, including multicentered and international biopsy-driven trials.

Objectives: To determine the association between self-rated health (SRH) and functional status, comorbidity, toxicity of treatment and mortality in older patients with newly-diagnosed cancer., Materials and Methods: Patients aged 65 and over, newly diagnosed were recruited at the Jewish General Hospital, Montreal, Canada. SRH and functional status [instrumental activities of daily living (IADL), basic activities of daily living (ADL), Eastern Cooperative Oncology Group performance status (ECOG PS), frailty markers and number of comorbid conditions] were evaluated prior to the start of treatment, and at 3, 6 and 12 months (SRH only). Treatment toxicity and mortality data were abstracted from the chart. Logistic regression was also used to examine the relationship between functional status, comorbidity and SRH at baseline. Logistic and Cox regression were used to examine the association between baseline SRH and treatment toxicity/time to death., Results: There were 112 participants enrolled on this study (median age 74.1). At baseline, 74 patients (66.1%) had a good SRH and 38 patients (33.9%) had poor SRH. Only an increasing number of comorbid conditions was associated with poor SRH at baseline in both univariate and multivariable analysis. We found no association between SRH and toxicity or mortality., Conclusion: A substantial proportion had poor SRH prior to and during cancer treatment. An increasing number of comorbidities was associated with poor SRH at baseline. SRH did not predict toxicity or mortality. Attention to comorbid conditions in older patients with cancer is warranted considering their impact on SRH in this population., (© 2013.)

Introduction: Older cancer patients are possibly at an increased risk of medication-related problems because, typically, they receive many medications during their cancer treatment, both for the cancer itself and for supportive care., Objectives: The aim of this study was to describe the number and severity of potential medication problems during treatment of cancer in the first year after diagnosis. We also sought to examine whether patients receiving systemic cancer treatment had more medication-related problems at 3, 6 and 12 months than those not receiving systemic cancer treatment., Methods: This was a prospective pilot cohort study on health and vulnerability in older newly diagnosed cancer patients with 1-year follow-up. The study was conducted at Segal Cancer Centre, Jewish General Hospital, Montreal, Canada. Of 156 eligible patients, 112 agreed to participate (response 71.8%). The patients were aged >or=65 years and were newly diagnosed with breast, colorectal or lung cancer, lymphoma or multiple myeloma. Patients were asked for permission to obtain their list of medications from their pharmacist. The cancer treatment information was abstracted from the medical chart. Vigilance Santé software was used to identify the presence, type and severity of potential medication problems., Results: The median number of medications was five at baseline, seven at 3 months and six at 6 and 12 months. At baseline, 247 potential medication problems were identified, followed by 273 at 3 months, 229 at 6 months and 188 at 12 months. About half of the patients at each follow-up had one or more moderate or severe potential medication problem. Patients receiving systemic cancer treatment had significantly fewer potential problems at 3 months than patients not receiving systemic cancer treatment, but no differences were observed at 6 and 12 months. The most common warnings were contraindications, interactions and miscellaneous warnings, and the cancer treatment was involved in 12% of all potential problems., Conclusion: This study showed that the majority of older newly diagnosed cancer patients take prescribed medication and about two-thirds have potential medication problems, of which about half are of at least moderate severity. The cancer treatment was involved in only a small proportion of all potential drug problems.

Background: Prescribing for older patients is challenging and complex. Cancer patients are at a considerable increased risk of drug-related problems because they typically receive a large number of medications during their cancer treatment, both for the cancer itself and for supportive care. Few studies have examined the scope of this problem in older newly diagnosed cancer patients., Objective: To investigate the number and severity of potential drug problems and factors associated with the occurrence of potential drug problems in older newly diagnosed cancer patients., Methods: This prospective pilot study was conducted in newly diagnosed cancer patients aged > or =65 years recruited in the Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada. Vigilance Santé software was used to identify the presence and type of potential drug problems. Logistic regression analyses were used to identify factors associated with the presence of one or more severe or moderately severe potential drug problems., Results: There were 112 participants with a mean age of 74.2 years, and 70% were women. A total of 103 patients (92%) were taking medications. The median number of medications per patient was 5 (interquartile range 3-9) and a total of 247 potential drug problems were identified. Sixty-four patients (62.1%) had a potential drug problem of any level of severity and 49 patients had a potential moderate/severe drug problem identified (47.6%). Two (0.8%) potential drug problems of the most severe level were identified, 122 warnings (49.4%) of all potential problems were of moderate severity and 123 warnings (49.8%) were at the least severe level. Factors associated with having one or more moderate/severe potential drug problems were taking five or more drugs and age > or =76 years., Conclusion: The majority of older newly diagnosed cancer patients in this study were taking at least one medication and the median number of medications per patient was 5. Published studies have shown that medication problems are common in community-dwelling older persons, but they are mostly of low severity. In this group of older newly diagnosed cancer patients, potential medication problems were also found to be common; however, half of the potential problems identified were of moderate severity.