Intravenous ketamine for treatment-resistant depression patients who have failed to respond to transcranial magnetic stimulation: A case series.

BACKGROUND: For individuals with treatment-resistant depression (TRD), transcranial magnetic stimulation (TMS) has become a well-established approach. In the past decade, intravenous (IV) racemic ketamine has also emerged as a potential treatment for TRD. Currently, little data is available on the clinical effects of IV racemic ketamine in TRD patients who experienced TMS-failure. METHODS: Twenty-one (21) TRD patients who had failed to respond to a standard course of high-frequency left-dorsolateral prefrontal cortex TMS were subsequently scheduled to received IV racemic ketamine infusions. The IV racemic ketamine protocol consisted of 0,5 mg/kg infusions over 60 min, 3 times a week over 2 weeks. RESULTS: Treatment was safe with minimal side-effects. Mean baseline MADRS score was 27.6 ± 6.4 (moderate depression), decreasing down to 18.6 ± 8.9 (mild depression) post-treatment. Mean percent improvement was 34.5 % ± 21.1 from baseline to post-treatment. Paired sample t-test showed significant MADRS score decrease pre- to post-treatment [t(20) = 7.212, p < .001]. Overall, four (4) patients (19.0 %) responded and two (2) of those achieved remission (9.5 %). LIMITATIONS: Limitations of this case series include its retrospective and uncontrolled open-label nature, the lack of self-rating and standardized adverse events questionnaires, as well as follow-ups beyond the immediate treatment period. CONCLUSIONS: Novel ways to increase the clinical effects of ketamine are being explored. We discuss potential combination approaches of ketamine with other modalities to augment its effects. Given the global burden of TRD, novel approaches are needed to curb the current mental health epidemic around the world.

HTA challenges for appraising rare disease interventions viewed through the lens of an institutional multidimensional value framework.

INTRODUCTION: Evaluating rare disease interventions poses challenges for HTA agencies, including uncertainties and ethical issues and tensions. INESSS has recently adopted a Statement of Principles and Ethical Foundations which proposes a multidimensional approach to value appraisal as well as five principles to frame the evaluation process. AREAS COVERED: Our aim was to identify and analyze HTA challenges for appraising interventions for rare diseases, using the Statement's approach to value appraisal as an analytical framework, and outline how the Statement's principles can help address these challenges. Challenges, covering a diversity of aspects, were identified by leveraging institutional experience in diverse domains of expertise and consolidated through narrative literature review. Challenges were categorized by value dimension (clinical, populational, economic, organizational, and sociocultural), which allowed to pinpoint how each challenge affects the ability to appraise the value of an intervention. Key ethical tensions across dimensions were also identified. Specific approaches to addressing these challenges - related to knowledge mobilization and integration, deliberation, and recommendation-making - were outlined on the basis of the principles promulgated in the Statement. EXPERT OPINION: A multidimensional approach can be fruitful for analyzing challenges for appraising the value of rare disease interventions and help guide approaches to tackle them.

Transcranial magnetic stimulation and intravenous ketamine combination therapy for treatment-resistant bipolar depression: A case report.

About a third of patients suffering from major depression develop treatment-resistant depression (TRD). Although repetitive transcranial magnetic stimulation (rTMS) and intravenous ketamine have proven effective for the management of TRD, many patients remain refractory to treatment. We present the case of a patient suffering from bipolar TRD. The patient was referred to us after failure to respond to first-and second-line pharmacotherapy and psychotherapy. After minimal response to both rTMS and ketamine alone, we attempted a combination rTMS and ketamine protocol, which led to complete and sustained remission. Various comparable and complimentary mechanisms of antidepressant action of ketamine and rTMS are discussed, which support further study of this combination therapy. Future research should focus on the feasibility, tolerability, and efficacy of this novel approach.

Patient and Citizen Participation in the Identification of Ethical Considerations Aiming to Address Uncertainty in the Evaluation of Promising Interventions in a Pandemic Context.

Since the beginning of the COVID-19 pandemic, numerous studies have been conducted to identify interventions that could contribute to alleviating the burden it has caused. The Institut national d'excellence en santé et en services sociaux (INESSS) has played a key role in informing the government of Québec regarding the evaluation of specific pandemic-related interventions. This process took place in a context characterized by a sense of urgency to assess and recommend potential interventions that could save lives and reduce the effects of the disease on populations and healthcare systems, which increased the pressure on the regulatory agencies leading these evaluations. While some of the interventions examined were considered promising, results from COVID-19 studies often led to uncertainty regarding their efficacy or safety. Regulatory agencies evaluating the value of promising interventions thus face challenges in deciding whether these should be made available to the population, particularly when assessing their benefit-risk balance. To shed light on these challenges, we identified underlying ethical considerations that can influence such an assessment. A rapid literature review was conducted in February 2021, to identify the main challenges associated with the benefit-risk balance assessment of promising interventions. To reinforce our understanding of the underlying ethical considerations, we initiated a discussion among various social actors involved in critical thinking surrounding the evaluation of promising interventions, including ethicists, clinicians and researchers involved in clinical or public health practice, as well as patients and citizens. This discussion allowed us to create a space for exchange and mutual understanding among these various actors who contributed equally to the identification of ethical considerations. The knowledge and perspectives stemming from the scientific literature and those consulted were integrated in a common reflection on these ethical considerations. This allowed patients and citizens, directly affected by the evaluation of pandemic-related interventions and the resulting social choices, to contribute to the identification of the relevant ethical considerations. It also allowed for reflection on the responsibilities of the various actors involved in the development, evaluation, and distribution of promising interventions in a setting of urgency and uncertainty, such as that brought about by the COVID-19 pandemic.

Developing recommendations for the diagnosis and treatment of Lyme disease: the role of the patient's perspective in a controversial environment.

CONTEXT: The Ministry of Health in Québec requested the National Institute of Excellence in Health and Social Services to produce clinical and implementation recommendations for the prophylaxis, diagnosis, and treatment of Lyme disease. OBJECTIVES: (i) Describe the process of trialing different modalities of patient engagement as a means to integrate a diversity of patient perspectives and (ii) Describe the learning process of INESSS regarding the integration of the patient perspective. METHODOLOGY: All documents were analyzed, and a survey with all advisory committee members and semi-structured interviews with stakeholders were conducted. Each interview was transcribed verbatim and imported into QDA miner software for the purposes of analysis. Data analysis was carried out concurrently with data collection to allow for an iterative approach between data collection and analysis. RESULTS: Five methods to integrate the perspectives of patients were used: (i) interviews with patients, (ii) inclusion of patient partners within the advisory committee, (iii) literature review, (iv) focus groups with one patient association, and (v) feedback from patient associations on recommendations intended for decision makers and other targeted stakeholders. The patient partners influenced decisions by sharing their experiential knowledge. The patient interviews and the literature review added an in-depth perspective on the disease and experience with the healthcare system. The patient association members shared their perspectives and helped disseminate the recommendation to sustain a practice change. CONCLUSION: The combination of methods to collect and integrate patients' knowledge and patient associations' perspectives helped develop a comprehensive understanding of a controversial object of evaluation.

Co-construction of health technology assessment recommendations with patients: An example with cardiac defibrillator replacement.

CONTEXT: The National Institute of Excellence in Health and Social Services (INESSS), which functions as the Québec health technology assessment (HTA) agency, tested a new way to engage patients along with health-care professionals in the co-construction of recommendations regarding implantable cardioverter-defibrillator replacement. OBJECTIVE: The objective of this article was to describe the process of co-construction of recommendations and to propose methods of building best practices for patient involvement (PI) in HTA. DESIGN: Throughout the process, documents were collected and participant observations were made. Individual interviews were conducted with patients, health-care professionals and the INESSS scientific team, from January to March 2018. RESULTS: Three committees were established: an expert patient committee to reflect on patient experience literature; an expert health professional committee to reflect on medical literature; and a co-construction committee through which both patients and health-care professionals contributed to develop the recommendations. The expert patients validated and contextualized a literature review produced by the scientific team. This allowed the scientists to consider aspects related to the patient experience and to integrate the feedback from patients into HTA recommendations. The most important factor contributing to a positive PI experience was the structured methodology for selecting patient participants, and a key factor that inhibited the process was a lack of training in PI on the part of the scientific team. CONCLUSIONS: This experience demonstrates that it is possible to co-construct recommendations, even for technically complex HTA subjects, through a more democratic process than usual which led to more patient-focused guidance.

A framework for value-creating learning health systems.

BACKGROUND: Interest in value-based healthcare, generally defined as providing better care at lower cost, has grown worldwide, and learning health systems (LHSs) have been proposed as a key strategy for improving value in healthcare. LHSs are emerging around the world and aim to leverage advancements in science, technology and practice to improve health system performance at lower cost. However, there remains much uncertainty around the implementation of LHSs and the distinctive features of these systems. This paper presents a conceptual framework that has been developed in Canada to support the implementation of value-creating LHSs. METHODS: The framework was developed by an interdisciplinary team at the Institut national d'excellence en santé et en services sociaux (INESSS). It was informed by a scoping review of the scientific and grey literature on LHSs, regular team discussions over a 14-month period, and consultations with Canadian and international experts. RESULTS: The framework describes four elements that characterise LHSs, namely (1) core values, (2) pillars and accelerators, (3) processes and (4) outcomes. LHSs embody certain core values, including an emphasis on participatory leadership, inclusiveness, scientific rigour and person-centredness. In addition, values such as equity and solidarity should also guide LHSs and are particularly relevant in countries like Canada. LHS pillars are the infrastructure and resources supporting the LHS, whereas accelerators are those specific structures that enable more rapid learning and improvement. For LHSs to create value, such infrastructures must not only exist within the ecosystem but also be connected and aligned with the LHSs' strategic goals. These pillars support the execution, routinisation and acceleration of learning cycles, which are the fundamental processes of LHSs. The main outcome sought by executing learning cycles is the creation of value, which we define as the striking of a more optimal balance of impacts on patient and provider experience, population health and health system costs. CONCLUSIONS: Our framework illustrates how the distinctive structures, processes and outcomes of LHSs tie together with the aim of optimising health system performance and delivering greater value in health systems.

Addressing the affordability of cancer drugs: using deliberative public engagement to inform health policy.

BACKGROUND: Health system expenditure on cancer drugs is rising rapidly in many OECD countries given the costly new treatments and increased rates of use due to a growing and ageing population. These factors put considerable strain on the sustainability of health systems worldwide, sparking public debate among clinicians, pharmaceutical companies, policy-makers and citizens on issues of affordability and equity. We engaged Canadians through a series of deliberative public engagement events to determine their priorities for making cancer drug funding decisions fair and sustainable in Canada's publicly financed health system. METHODS: An approach to deliberation was developed based on the McMaster Health Forum's citizen panels and the established Burgess and O'Doherty model of deliberative public engagement. Six deliberations were held across Canada in 2016. Transcripts were coded in NVivo and analysed to determine where participants' views converged and diverged. Recommendations were grouped thematically. RESULTS: A total of 115 Canadians participated in the deliberative events and developed 86 recommendations. Recommendations included the review and regular re-review of approved drugs using 'real-world' evidence on effectiveness and cost-effectiveness; prioritisation of treatments that restore patients' independence, mental health and general well-being; ensuring that decision processes, results and their rationales are transparent; and commitment to people with similar needs receiving the same care regardless of where in Canada they live. CONCLUSIONS: The next steps for policy-makers should be to develop mechanisms for (1) re-reviewing effectiveness and cost-effectiveness data for all cancer drugs; (2) making disinvestments in cancer drugs that satisfy requirements relating to grandfathering and compassionate access; (3) ensuring fair and equitable access to cancer drugs for all Canadians; and (4) fostering a pan-Canadian approach to cancer drug funding decisions.

Dissemination of performance information and continuous improvement: A narrative systematic review.

PURPOSE: Developing a performance measure and reporting the results to support decision making at an individual level has yielded poor results in many health systems. The purpose of this paper is to highlight the factors associated with the dissemination of performance information that generate and support continuous improvement in health organizations. DESIGN/METHODOLOGY/APPROACH: A systematic data collection strategy that includes empirical and theoretical research published from 1980 to 2010, both qualitative and quantitative, was performed on Web of Science, Current Contents, EMBASE and MEDLINE. A narrative synthesis method was used to iteratively detail explicative processes that underlie the intervention. A classification and synthesis framework was developed, drawing on knowledge transfer and exchange (KTE) literature. The sample consisted of 114 articles, including seven systematic or exhaustive reviews. FINDINGS: Results showed that dissemination in itself is not enough to produce improvement initiatives. Successful dissemination depends on various factors, which influence the way collective actors react to performance information such as the clarity of objectives, the relationships between stakeholders, the system's governance and the available incentives. RESEARCH LIMITATIONS/IMPLICATIONS: This review was limited to the process of knowledge dissemination in health systems and its utilization by users at the health organization level. Issues related to improvement initiatives deserve more attention. PRACTICAL IMPLICATIONS: Knowledge dissemination goes beyond better communication and should be considered as carefully as the measurement of performance. Choices pertaining to intervention should be continuously prompted by the concern to support organizational action. ORIGINALITY/VALUE: While considerable attention was paid to the public reporting of performance information, this review sheds some light on a more promising avenue for changes and improvements, notably in public health systems.

Fostering deliberations about health innovation: what do we want to know from publics?

As more complex and uncertain forms of health innovation keep emerging, scholars are increasingly voicing arguments in favour of public involvement in health innovation policy. The current conceptualization of this involvement is, however, somewhat problematic as it tends to assume that scientific facts form a "hard," indisputable core around which "soft," relative values can be attached. This paper, by giving precedence to epistemological issues, explores what there is to know from public involvement. We argue that knowledge and normative assumptions are co-constitutive of each other and pivotal to the ways in which both experts and non-experts reason about health innovations. Because knowledge and normative assumptions are different but interrelated ways of reasoning, public involvement initiatives need to emphasise deliberative processes that maximise mutual learning within and across various groups of both experts and non-experts (who, we argue, all belong to the "publics"). Hence, we believe that what researchers might wish to know from publics is how their reasoning is anchored in normative assumptions (what makes a given innovation desirable?) and in knowledge about the plausibility of their effects (are they likely to be realised?). Accordingly, one sensible goal of greater public involvement in health innovation policy would be to refine normative assumptions and make their articulation with scientific observations explicit and openly contestable. The paper concludes that we must differentiate between normative assumptions and knowledge, rather than set up a dichotomy between them or confound them.