Tania Bubela

Background: Targeted treatment or immunotherapy may yield increased, durable responses for melanoma patients. Whether patient-level benefits translate to population health is unknown. This study sought to estimate patient and population impacts of a cancer control policy that reimbursed multigene panel testing and pembrolizumab for metastatic melanoma in British Columbia, Canada. Methods: This retrospective study examined a population-based cohort of 721 adults diagnosed with metastatic melanoma in British Columbia who received single or multigene testing between 2013 and 2018. We determined patient-level policy impacts using 1:1 genetic algorithm matching of policy-affected patients with historical control patients and Kaplan–Meier analysis and inverse probability of censoring weighted regression of 2-year health-care costs and survival times. For population-level effects, we applied interrupted time-series analysis on monthly health-care system expenditures and mortality rates, estimating autoregressive integrated moving average and generalized least squares Poisson regressions. Results: Matched cohort analysis (control patients, n = 154; intervention patients, n = 154) found mean cumulative patient-level cost increases of CAD$53 963 (95% confidence interval [CI] = $35 641 to $72 621; P < .001) and increased survival times of 111 days (95% CI = 44 to 166 days; P < .001) over 2 years. Higher patient-level systemic therapy spending of CAD$48 890 (95% CI = $31 110 to $66 910; P < .001) drove overall cost differences. Population-interrupted time-series analysis detected an immediate, sustained increase in mean monthly health-care expenditures of CAD$1921 (95% CI = $935 to $2908; P < .001) per patient. Higher overall spending did not coincide with population-level mortality changes. Conclusions: The policy of reimbursing multigene testing and pembrolizumab produced patient survival improvements, but selectivity of response prevented population mortality improvement. Health-care system costs statistically significantly increased at the patient and population levels.

Tania Bubela and colleagues examine how fragmented responsibilities and accountability for public health data hindered Canada’s pandemic response

Innovative health technologies are not well regulated under current pathways, leading regulators to adopt contextual, life-cycle regulatory models, which authorize drugs based on earlier clinical evidence subject to the conduct of post-market trials that confirm clinical benefit and safety. In this paper, we evaluate all drugs authorized in Canada under the Notice of Compliance with conditions (NOC/c) policy from 1998 to 2021 to analyze its function, identify challenges and areas for improvement, and make recommendations to inform Health Canada’s regulatory reforms. We analyzed a sample of 148 drugs authorized between 1998 and 2021, including characteristics about the pre- and post-market clinical trials, finding that most NOC/c authorizations are based on one, single-arm clinical trial using a surrogate endpoint. Post-market trials are more likely to be randomized, Phase III trials but mostly use surrogate endpoints. Based on our findings, we recommend increasing decision-making transparency throughout the regulatory process, developing comprehensive eligibility criteria for selecting appropriate health technologies, modernizing pre-market evidence requirements, adopting a more active role in designing post-market trials, and utilizing automatic expiry, stronger penalties, and ongoing disclosure of the status of post-market trials to promote compliance.

Background: Hospital patients who use drugs may require prolonged parenteral antimicrobial therapy administered through a vascular access device (VAD). Clinicians’ concerns that patients may inject drugs into these devices are well documented. However, the perspectives of patients on VAD injecting are not well described, hindering the development of informed clinical guidance. This study was conducted to elicit inpatient perspectives on the practice of injecting drugs into VADs and to propose strategies to reduce associated harms. Methods: Researchers conducted a focused ethnography and completed semi-structured interviews with 25 inpatients at a large tertiary hospital in Western Canada that experiences a high rate of drug-related presentations annually. Results: A few participants reported injecting into their VAD at least once, and nearly all had heard of the practice. The primary reason for injecting into a VAD was easier venous access since many participants had experienced significant vein damage from injection drug use. Several participants recognized the risks associated with injecting into VADs, and either refrained from the practice or took steps to maintain their devices while using them to inject drugs. Others were uncertain how the devices functioned and were unaware of potential harms. Conclusions: VADs are important for facilitating completion of parenteral antimicrobial therapy and for other medically necessary care. Prematurely discharging patients who inject into their VAD from hospital, or discontinuing or modifying therapy, results in inequitable access to health care for a structurally vulnerable patient population. Our findings demonstrate a need for healthcare provider education and non-stigmatizing clinical interventions to reduce potential harms associated with VAD injecting. Those interventions could include providing access to specialized pain and withdrawal management, opioid agonist treatment, and harm reduction services, including safer drug use education to reduce or prevent complications from injecting drugs into VADs.

Regulatory, ethical and pragmatic issues of life-cycle regulatory and reimbursement approaches are discussed, taking lessons from the recent experiences of Isra

Background: Parents of children living with chronic but manageable conditions hope for improved therapies or cures, including Advanced Therapy Medicinal Products (ATMPs). Multiple pediatric clinical trials for ATMPs are underway, but the risk profile of ATMPs for chronic conditions is largely unknown and likely different than for terminal pediatric illnesses. Applying Protection Motivation Theory modified to the context of pediatric ATMP clinical trial enrollment, our study analyses information needs of parents of children living with chronic manageable conditions: Type 1 Diabetes (T1D) or Inherited Retinal Diseases (IRD).Methods: We conducted semi-structured interviews with 15 parents of children living with T1D and 14 parents of children living with an IRD about: a) family background and the diagnostic experience; b) awareness of gene and stem cell therapy research and clinical trials for T1D and IRD; c) information sources on trials and responses to that information; d) attitudes to trial participation, including internationally; e) understanding of trial purpose and process; and f) any experiences with trial participation. We then discussed a pediatric ATMP clinical trial information sheet, which we developed with experts. We applied directed qualitative content analysis, based on PMT, to examine the information preferences of parents in deciding whether to enrol their children in stem cell or gene therapy clinical trials.Results: Parents balanced trial risks against their child’s ability to cope with the chronic condition. The better the child’s ability to cope with vision impairment or insulin management, the less likely parents were to assume trial risks. Conversely, if the child struggled with his/her vision loss, parents were more likely to be interested in trial participation, but only if the risks were low and likelihood for potential benefit was high.Conclusions: Fear of adverse events as part of threat appraisal was the predominant consideration for parents in considering whether to enroll their child living with a manageable, chronic condition in a pediatric clinical trial of an ATMP. This consideration outweighed potential benefits and severity of their child’s condition. Parents called for available safety data and fulsome communication processes that would enable them to make informed decisions about clinical trial enrolment on behalf of their children.

Background: Health care system decision makers face challenges in allocating resources for screening, diagnosis and treatment of hepatitis C. Approximately 240,000 individuals are infected with the hepatitis C virus (HCV) in Canada. Populations most affected by HCV include Indigenous people, people who inject drugs, immigrants and homeless or incarcerated populations as well as those born between 1946 and 1965. Curative but expensive drug regimens of novel direct acting antivirals (DAAs) are available. We aim to identify social values from academic literature for inclusion in health technology assessments. Methods: We conducted a scoping review of academic literature to identify and analyze the social values and evidence-based recommendations for screening, diagnosis and treatment of HCV in Canada. After applying inclusion/exclusion criteria, we abstracted: type of intervention(s), population(s) affected, study location, screening methods, diagnostics and treatments. We then abstracted and applied qualitative codes for social values. We extracted social value statements and clustered them into one of 4 categories: (1) equity and justice, (2) duty to provide care, (3) maximization of population benefit, and (4) individual versus community interests. Results: One hundred and eighteen articles met our inclusion criteria on screening, diagnosis and treatment of HCV in Canada. Of these, 54 (45.8%) discussed screening, 4 (3.4%) discussed diagnosis and 60 (50.8%) discussed treatment options. Most articles discussed the general population and other non-vulnerable populations. Articles that discussed vulnerable populations focused on people who inject drugs. We coded 1243 statements, most of which fell into the social value categories of equity and justice, duty to provide care and maximization of population benefit. Conclusion: The academic literature identified an expanded set of social values to be taken into account by resource allocation decision makers in financially constrained environments. In the context of hepatitis C, authors called for greater consideration of equity and justice and the duty to provide care in making evidence-based recommendations for screening, diagnosis and treatment for different populations and in different settings that also account for individual and community interests.

In the event of the current COVID-19 pandemic and in preparation for future pandemics, open science can support mission-oriented research and development, as well as commercialization. Open science shares skills and resources across sectors; avoids duplication and provides the basis for rapid and effective validation due to full transparency. It is a strategy that can adjust quickly to reflect changing incentives and priorities, because it does not rely on any one actor or sector. While eschewing patents, it can ensure high-quality drugs, low pricing, and access through existing regulatory mechanisms. Open science practices and partnerships decrease transaction costs, increase diversity of actors, reduce overall costs, open new, higher-risk/higher-impact approaches to research, and provide entrepreneurs freedom to operate and freedom to innovate. We argue that it is time to re-open science, not only in its now restricted arena of fundamental research, but throughout clinical translation. Our model and attendant recommendations map onto a strategy to accelerate discovery of novel broad-spectrum anti-viral drugs and clinical trials of those drugs, from first-in-human safety-focused trials to late stage trials for efficacy. The goal is to ensure low-cost and rapid access, globally, and to ensure that Canadians do not pay a premium for drugs developed from Canadian science.