Canadian newspaper coverage on harm reduction featuring bereaved mothers: A mixed methods analysis.

A growing body of evidence suggests that news media which includes a sympathetic portrayal of a mother bereaved by substance use can increase public support for harm reduction initiatives. However, the extent to which such news media coverage occurs in Canada is unknown, and research has not documented how the news media in Canada covers such stories. We undertook a mixed-method secondary analyses of 5681 Canadian newspaper articles on harm reduction (2000-2016). Quantitative analyses described the volume and content of harm reduction reporting featuring a mother whose child's death was related to substance use while qualitative thematic analysis provided in-depth descriptions of the discourses underlying such news reporting. Newspaper articles featuring a mother whose child's death was related to substance use were rarely published (n = 63; 1.1% of total harm reduction media coverage during the study period). Deductive content analysis of these 63 texts revealed that coverage of naloxone distribution (42.9%) and supervised drug consumption services (28.6%) were prioritized over other harm reduction services. Although harm reduction (services or policies) were advocated by the mother in most (77.8%) of these 63 texts, inductive thematic analysis of a subset (n = 52) of those articles revealed that mothers' advocacy was diminished by newspaper reporting that emphasized their experiences of grief, prioritized individual biographies over structural factors contributing to substance use harms, and created rhetorical divisions between different groups of people who use drugs (PWUD). Bereaved mothers' advocacy in support of harm reduction programs and services may be minimized in the process of reporting their stories for newspaper readers. Finding ways to report bereaved mothers' stories in ways that are inclusive of all PWUD while highlighting the role of broad, structural determinants of substance use has the potential to shift public opinion and government support in favour of these life-saving services.

Asynchronous online focus groups for research with people living with amyotrophic lateral sclerosis and family caregivers: usefulness, acceptability and lessons learned.

BACKGROUND: People with amyotrophic lateral sclerosis (ALS) face disability- and travel-related barriers to research participation. We investigate the usefulness and acceptability of asynchronous, online focus groups (AOFGs) for research involving people affected by ALS (patients and family caregivers) and outline lessons learned. METHODS: The ALS Talk Project, consisting of seven AOFGs and 100 participants affected by ALS, provided context for this investigation. Hosted on the secure itracks Board™ platform, participants interacted in a threaded web forum structure. Moderators posted weekly discussion questions and facilitated discussion. Data pertaining to methodology, participant interaction and experience, and moderator technique were analyzed using itracks and NVivo 12 analytics (quantitative) and conventional content analysis and the constant-comparative approach (qualitative). RESULTS: There was active engagement within groups, with post lengths averaging 111.48 words and a complex network of branching interactions between participants. One third of participant responses included individual reflections without further interaction. Participants affirmed their co-group members, offered practical advice, and discussed shared and differing perspectives. Moderators responded to all posts, indicating presence and probing answers. AOFGs facilitated qualitative and quantitative data-gathering and flexible response to unanticipated events. Although total participation fell below 50% after 10-12 weeks, participants valued interacting with peers in an inclusive, confidential forum. Participants used a variety of personal devices, browsers, and operating systems when interacting on the online platform. CONCLUSIONS: This methodological examination of AOFGs for patient-centred investigations involving people affected by ALS demonstrates their usefulness and acceptability, and advances knowledge of online research methodologies. Lessons learned include: early identification of research goals and participant needs is critical to selecting an AOFG platform; although duration longer than 10-12 weeks may be burdensome in this population, participants were positive about AOFGs; AOFGs offer real world flexibility enabling response to research challenges and opportunities; and, AOGFs can effectively foster safe spaces for sharing personal perspectives and discussing sensitive topics. With moderators playing an important role in fostering engagement, AOFGs facilitated rich data gathering and promoted reciprocity by fostering the exchange of ideas and interaction between peers. Findings may have implications for research involving other neurologically impaired and/or medically vulnerable populations.

What do people affected by amyotrophic lateral sclerosis want from health communications? Evidence from the ALS Talk Project.

INTRODUCTION/AIMS: Health communication is central to effective, supportive amyotrophic lateral sclerosis (ALS) clinical care. Guidance for ALS communication is limited, focuses on diagnosis disclosure, and frequently relies on expert consensus and/or reviews. Patient-based evidence is needed to guide ALS health communication. We investigated how the experiences of ALS patients and family caregivers can inform effective communication practices from diagnosis to end-of-life. METHODS: Data were drawn from the ALS Talk Project, an asynchronous, online focus group study. Seven focus groups and five interviews (105 participants) were conducted. Data were qualitatively analyzed using directed content analysis and the constant-comparative approach. RESULTS: We found four primary themes: communication content, communication circumstances, information sufficiency, and communication manner. Data indicate participants relied on clinicians for medical information but also wanted practical information; health communication should attend to the circumstances within which conversations occur; information must be sufficient for individual needs, without overwhelming; and an empathetic, direct, and honest manner facilitated trust. Participants identified communication challenges and strategies to improve communication across major themes, including stepwise approaches and conversations tailored to individuals and their heterogeneous disease experiences. DISCUSSION: Healthcare professionals should discuss patient/caregiver communication preferences early in the therapeutic relationship, co-develop a communication agreement, and update the agreement in response to changing needs and disease progression. This will foster regular discussion of information needs and promote timely discussions of challenging topics, including advance care, while giving patients and families a sense of control. Findings may have implications for other neuromuscular disease and/or seriously ill populations.

Should Canada adopt managed access agreements in Canada for expensive drugs?

Drugs are increasingly authorized based on less mature evidence, leaving payors faced with significant clinical and cost-effectiveness uncertainties. As a result, payors must often choose between reimbursing a drug that may not turn out to be cost-effective (or may even be unsafe) or delaying the reimbursement of a drug that is cost-effective and offers clinical benefit to patients. Novel reimbursement decision models and frameworks, such as managed access agreements (MAAs), may address this decision challenge. Here, we provide a comprehensive overview of the legal limitations, considerations, and implications for adopting MAAs in Canadian jurisdictions. We begin with an overview of current drug reimbursement processes in Canada, terminology and definitions of the different types of MAAs, and select international experiences with MAAs. We discuss the legal barriers to MAA governance frameworks, design and implementation considerations, and legal and policy implications of MAAs. Finally, we provide recommendations to guide policy development for implementing MAAs in Canada, based on existing literature, international experience, and our legal analysis. We conclude that legal and policy barriers likely prevent the adoption of a pan-Canadian MAA governance framework. More feasible is a quasi-federal or provincial approach, building on existing infrastructure.

Lessons from Canada's notice of compliance with conditions policy for the life-cycle regulation of drugs.

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.

Can Managed Access Agreements Mitigate Evidentiary, Economic and Ethical Issues with Access to Expensive Drugs for Rare Diseases in the Canadian Context?

Expensive drugs for rare diseases (EDRDs) pose challenges for regulatory and reimbursement decision makers. Managed access agreements (MAAs), conditional reimbursement schemes that use a variety of price and evidence generation mechanisms to support value-based decision making, have the potential to address the evidentiary, economic and ethical issues associated with EDRDs. Several jurisdictions have successfully used MAAs to manage budget impact and evidentiary uncertainties, demonstrating the promise of this approach. We comment on the feasibility of adopting MAAs in Canada to address challenges associated with EDRDs. Adopting MAAs in the Canadian context requires attention to Canada's federated healthcare and drug coverage system and will require investing in robust data infrastructure and governance systems.

CAPTURE ALS: the comprehensive analysis platform to understand, remedy and eliminate ALS.

The absence of disease modifying treatments for amyotrophic lateral sclerosis (ALS) is in large part a consequence of its complexity and heterogeneity. Deep clinical and biological phenotyping of people living with ALS would assist in the development of effective treatments and target specific biomarkers to monitor disease progression and inform on treatment efficacy. The objective of this paper is to present the Comprehensive Analysis Platform To Understand Remedy and Eliminate ALS (CAPTURE ALS), an open and translational platform for the scientific community currently in development. CAPTURE ALS is a Canadian-based platform designed to include participants' voices in its development and through execution. Standardized methods will be used to longitudinally characterize ALS patients and healthy controls through deep clinical phenotyping, neuroimaging, neurocognitive and speech assessments, genotyping and multisource biospecimen collection. This effort plugs into complementary Canadian and international initiatives to share common resources. Here, we describe in detail the infrastructure, operating procedures, and long-term vision of CAPTURE ALS to facilitate and accelerate translational ALS research in Canada and beyond.

Amyotrophic lateral sclerosis (ALS) health charities are central to ALS care: perspectives of Canadians affected by ALS.

OBJECTIVE: Expert consensus guidelines recommend referral of people with amyotrophic lateral sclerosis (ALS) to ALS health charities for support. Limited research indicates that patients and families value interaction with these volunteer sector organizations. We investigated how patient support from Canadian ALS health charities (ALS Societies) is experienced by those affected by ALS, and whether patient-centered outcomes validate recommendations for referral. METHODS: Data were drawn from the ALS Talk Project, an asynchronous online focus group study. Patients and family caregivers were recruited from regions across Canada. Seven groups met online for 14 weeks between January and July 2020. Seventy-eight participants made statements about ALS Societies. Data were qualitatively analyzed using directed content analysis and the constant-comparative approach. RESULTS: Participants viewed ALS Societies as integral to the healthcare system. The Societies acted as patient navigators and filled perceived care gaps, including psychological support. They provided critical practical assistance, particularly equipment loans and peer support groups; comprehensive disease-related and real-life information; and personal connections. They facilitated knowledge of research, emerging therapies, and research opportunities. Delayed referral to ALS Society supports and information resources was a concern for some participants. CONCLUSIONS: ALS Societies provide patients with critical practical, informational, and emotional support and play an overarching role as patient/research navigators. Patient-centred outcomes support patient referral to ALS Societies. Communication about the services provided should be a standard component of clinical care, with choice of access left to individuals. Clinical conversations should be supplemented with information resources developed by these voluntary sector organizations.

A perspective on life-cycle health technology assessment and real-world evidence for precision oncology in Canada.

Health technology assessment (HTA) can be used to make healthcare systems more equitable and efficient. Advances in precision oncology are challenging conventional thinking about HTA. Precision oncology advances are rapid, involve small patient groups, and are frequently evaluated without a randomized comparison group. In light of these challenges, mechanisms to manage precision oncology uncertainties are critical. We propose a life-cycle HTA framework and outline supporting criteria to manage uncertainties based on real world data collected from learning healthcare systems. If appropriately designed, we argue that life-cycle HTA is the driver of real world evidence generation and furthers our understanding of comparative effectiveness and value. We conclude that life-cycle HTA deliberation processes must be embedded into healthcare systems for an agile response to the constantly changing landscape of precision oncology innovation. We encourage further research outlining the core requirements, infrastructure, and checklists needed to achieve the goal of learning healthcare supporting life-cycle HTA.

Do-It-Yourself and Commercial Automated Insulin Delivery Systems in Type 1 Diabetes: An Uncertain Area for Canadian Health-care Providers.

In the past century, since the discovery of insulin, methods of insulin delivery and glucose monitoring have advanced technologically. In particular, the introduction of insulin pumps, providing continuous subcutaneous insulin infusion (CSII), and continuous glucose monitors (CGMs) have been revolutionary for people living with type 1 diabetes. In this review, we have focussed on automated insulin delivery (AID) systems and discuss the implications of both approved and off-label options for the user and health-care providers. By pairing insulin pumps with CGM, AID systems facilitate automated adjustment in insulin delivery based on CGM readings. A subset of these have been developed commercially and were granted regulatory approval. In contrast, unregulated do-it-yourself AID systems, designed and set up by people living with type 1 diabetes and their families, have advanced rapidly and are gaining popularity worldwide. These patient-driven technologies have demonstrated impressive user self-reported improvements in glycemic control and quality of life, but have not been evaluated in any formal randomized controlled trials or by regulators. This presents challenging uncertainty for health-care providers, in addition to ethical and legal implications in supporting people with diabetes who wish to use these technologies. The current knowledge, opinions and practices relating to the use of AID systems across Canada are unknown. Gathering this information will highlight current practice and areas of knowledge gaps and concern and will assist in focussed education. This understanding is crucial to ensure people with type 1 diabetes using these systems have access to optimal, consistent and safe patient-centred care.

"I have such a hard time hitting myself, I thought it'd be easier": perspectives of hospitalized patients on injecting drugs into vascular access devices.

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.

Covid-19 threat and coping: application of protection motivation theory to the pandemic experiences of people affected by amyotrophic lateral sclerosis.

BACKGROUND: People with amyotrophic lateral sclerosis (ALS) are at high risk for severe outcomes from Covid-19 infection. Researchers exploring ALS and Covid-19 have focused primarily on system response and adaptation. Using Protection Motivation Theory, we investigated how people with ALS and family caregivers appraised and responded to Covid-19 threat, the 'costs' associated with pandemic response, and how health professionals and systems can better support people affected by ALS who are facing public health emergencies. METHODS: Data were drawn from the 'ALS Talk Project,' an asynchronous, moderated focus group study. Participants were recruited from regions across Canada. Seven groups met online over 14 weeks between January and July 2020. Fifty-three participants contributed to Covid-19 discussions. Data were qualitatively analyzed using directed content analysis and the constant-comparative approach. RESULTS: Participants learned about the Covid-19 pandemic from the media. They rapidly assessed their vulnerability and responded to Covid-19 threat by following recommendations from health authorities, information monitoring, and preparing for worst-case scenarios. Adopting protective behaviors had substantial response costs, including adaptations for medical care and home support workers, threatened access to advance care, and increased caregiver burden. Participants expressed need for ALS-specific, pandemic information from trusted health professionals and/or ALS health charities. Telemedicine introduced both conveniences and costs. Prior experience with ALS provided tools for coping with Covid-19. Threat and coping appraisal was a dynamic process involving ongoing vigilance and adaptation. Findings draw attention to the lack of emergency preparedness among participants and within health systems. CONCLUSIONS: Clinicians should engage ALS patients and families in ongoing discussions about pandemic coping, strategies to mitigate response costs, care pathways in the event of Covid-19 infection, and changing information about Covid-19 variants and vaccines. Healthcare systems should incorporate flexible approaches for medical care, leveraging the benefits of telemedicine and facilitating in-person interaction as needed and where possible. Research is needed to identify strategies to mitigate response costs and to further explore the interaction between prior experience and coping. Further study is also needed to determine how communication about emergency preparedness might be effectively incorporated into clinical care for those with ALS and other medically vulnerable populations.

The Importance of and Challenges with Adopting Life-Cycle Regulation and Reimbursement in Canada.

Regulatory and reimbursement decisions for drugs and vaccines are increasingly based on limited safety and efficacy evidence. In this environment, life-cycle approaches to evaluation are needed. A life-cycle approach grants market approval and/or positive reimbursement decisions based on an undertaking to conduct post-market clinical trials that address evidentiary uncertainties, relying on the collection and analysis of post-market data. In practice, however, both conditional regulatory and reimbursement decisions have proven problematic. Here we discuss some of the regulatory implications and unsettled ethical and pragmatic issues, taking lessons from the recent experiences of Israel in rapidly approving the Pfizer-BioNTech COVID-19 vaccine.

Communication About End of Life for Patients Living With Amyotrophic Lateral Sclerosis: A Scoping Review of the Empirical Evidence.

Background: Communication about end of life, including advance care planning, life-sustaining therapies, palliative care, and end-of-life options, is critical for the clinical management of amyotrophic lateral sclerosis patients. The empirical evidence base for this communication has not been systematically examined. Objective: To support evidence-based communication guidance by (1) analyzing the scope and nature of research on health communication about end of life for amyotrophic lateral sclerosis; and (2) summarizing resultant recommendations. Methods: A scoping review of empirical literature was conducted following recommended practices. Fifteen health-related and three legal databases were searched; 296 articles were screened for inclusion/exclusion criteria; and quantitative data extraction and analysis was conducted on 211 articles with qualitative analysis on a subset of 110 articles that focused primarily on health communication. Analyses summarized article characteristics, themes, and recommendations. Results: Analysis indicated a multidisciplinary but limited evidence base. Most reviewed articles addressed end-of-life communication as a peripheral focus of investigation. Generic communication skills are important; however, substantive and sufficient disease-related information, including symptom management and assistive devices, is critical to discussions about end of life. Few articles discussed communication about specific end-of-life options. Communication recommendations in analyzed articles draw attention to communication processes, style and content but lack the systematized guidance needed for clinical practice. Conclusions: This review of primary research articles highlights the limited evidence-base and consequent need for systematic, empirical investigation to inform effective communication about end of life for those with amyotrophic lateral sclerosis. This will provide a foundation for actionable, evidence-based communication guidelines about end of life. Implications for research, policy, and practice are discussed.

ISSCR Guidelines for Stem Cell Research and Clinical Translation: The 2021 update.

The International Society for Stem Cell Research has updated its Guidelines for Stem Cell Research and Clinical Translation in order to address advances in stem cell science and other relevant fields, together with the associated ethical, social, and policy issues that have arisen since the last update in 2016. While growing to encompass the evolving science, clinical applications of stem cells, and the increasingly complex implications of stem cell research for society, the basic principles underlying the Guidelines remain unchanged, and they will continue to serve as the standard for the field and as a resource for scientists, regulators, funders, physicians, and members of the public, including patients. A summary of the key updates and issues is presented here.

Conditional Drug Approval as a Path to Market for Oncology Drugs in Canada: Challenges and Recommendations for Assessing Eligibility and Regulatory Responsiveness.

International drug regulators use conditional drug approval mechanisms to facilitate faster patient access to drugs based on a lower evidentiary standard typically required of drug approvals. Faster and earlier access is justified by limiting eligibility to drugs intended for serious and life-threatening diseases and by requiring post-market evidence collection to confirm clinical benefit. One such mechanism in Canada, the Notice of Compliance with Conditions (NOC/c) policy, was introduced in 1998. Today, most of the drugs approved under the NOC/c policy are for oncology indications. We analyze oncology drugs approvals under the NOC/c policy to inform discussions of two tradeoffs applied to conditional drug approvals, eligibility criteria and post-market evidence. Our analysis informs recommendations for Canada's proposed regulatory reforms approach to conditional approvals pathways. Our analysis demonstrates that under the current policy, eligibility criteria are insufficiently defined, resulting in their inconsistent application by Health Canada. Regulatory responsiveness to post-market evidence from post-market clinical trial and foreign jurisdiction regulatory decisions is slow and insufficient. In the absence of sufficient regulatory responsiveness, physicians and patients must make clinical decisions without the benefit of the best available evidence. Together, our analysis of the two core tradeoffs in Canada's conditional drug approval provides insight to inform the further development of Canada's proposed agile regulatory approach to drugs and devices that will expand the use of terms and conditions.

Identifying and understanding factors that affect the translation of therapies from the laboratory to patients: a study protocol.

Background: The process of translating preclinical findings into a clinical setting takes decades. Previous studies have suggested that only 5-10% of the most promising preclinical studies are successfully translated into viable clinical applications. The underlying determinants of this low success rate (e.g. poor experimental design, suboptimal animal models, poor reporting) have not been examined in an empirical manner. Our study aims to determine the contemporary success rate of preclinical-to-clinical translation, and subsequently determine if an association between preclinical study design and translational success/failure exists. Methods: Established systematic review methodology will be used with regards to the literature search, article screening and study selection process. Preclinical, basic science studies published in high impact basic science journals between 1995 and 2015 will be included. Included studies will focus on publicly available interventions with potential clinical promise. The primary outcome will be successful clinical translation of promising therapies - defined as the conduct of at least one Phase II trial (or greater) with a positive finding. A case-control study will then be performed to evaluate the association between elements of preclinical study design and reporting and the likelihood of successful translation. Discussion: This study will provide a comprehensive analysis of the therapeutic translation from the laboratory bench to the bedside. Importantly, any association between factors of study design and the success of translation will be identified. These findings may inform future research teams attempting preclinical-to-clinical translation. Results will be disseminated to identified knowledge users that fund/support preclinical research.

Application of protection motivation theory to clinical trial enrolment for pediatric chronic conditions.

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.