Frameworks for Health Technology Assessment at an Early Stage of Product Development: A Review and Roadmap to Guide Applications.

OBJECTIVES: Early health technology assessment (eHTA) can be used to evaluate and optimize a medical product's value proposition and to inform go/no-go decisions by using health economic modeling, literature scanning, and stakeholder preference studies at an early stage of development. eHTA frameworks offer high-level guidance on conducting this complex, iterative, and multidisciplinary process. The objective of this study was to review and summarize existing eHTA frameworks, understood as systematic approaches to guide early evidence generation and decision making. METHODS: Using a rapid review methodology, we identified all relevant studies published in English, French, and Spanish from PubMed/MEDLINE and Embase until February 2022. We only included frameworks relevant to the preclinical and early clinical (phase I) stages of medical product development. RESULTS: From 737 reviewed abstracts, 53 publications describing 46 frameworks were selected for inclusion and classified into categories based on their scope: (1) criteria frameworks, which provide an overview of eHTA; (2) process frameworks, which offer stepwise guidance for conducting eHTA, including preferred methods; and (3) methods frameworks, which provide detailed descriptions of specific eHTA methods. Most of the frameworks did not specify their target users or the specific stage of technology development. CONCLUSIONS: Despite some variability and gaps found across existing frameworks, the structure provided by this review helps inform eHTA applications. Remaining challenges are the frameworks' limited accessibility to users without a background in health economics, poor distinctions being made among early lifecycle stages and technology types, and the inconsistent terminology used to describe eHTA in different contexts.

Effectiveness of home-based pulmonary rehabilitation programs for patients with chronic obstructive pulmonary disease (COPD): systematic review.

BACKGROUND: Although pulmonary rehabilitation (PR) is considered a key component in managing chronic obstructive pulmonary disease (COPD) patients, uptake remains suboptimal. This systematic review aimed to determine the effectiveness of home-based PR (HBPR) programs for COPD patients. METHODS: A systematic review of scholarly literature published within the last 10 years from the conception of this project was conducted using internationally recognized guidelines. Search strategies were applied to electronic databases and clinical trial registries through March 2020 and updated in November 2021 to identify studies comparing HBPR with 'usual care' or outpatient pulmonary rehabilitation (OPR). To critically appraise randomized studies, the Cochrane Collaboration risk of bias tool (ROB) was used. The quality of non-randomized studies was evaluated using the ACROBAT-NRSI tool. The quality of evidence relating to key outcomes was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) on health-related quality of life (HRQoL), exacerbation frequencies, COPD-related hospital admissions, and program adherence. Three independent reviewers assessed methodologic quality and reviewed the studies. RESULTS: Twelve randomized controlled trials (RCTs) and 2 comparative observational studies were included. While considerable evidence relating to the effectiveness of HBPR programs for COPD patients exist, overall quality is low. There were no differences between HBPR and OPR in terms of safety, HRQoL, functional exercise capacity and health care resource utilization. Compared to usual care, functional exercise capacity seemed to significantly improve after HBPR. While patient compliance with HBPR is good, two factors appeared to increase the 'risk' of non-compliance: expectations of patients to 1) complete daily diaries/activity logs and 2) engage in solely unsupervised exercise sessions. CONCLUSION: The overall quality for most outcomes was low to very low; however, HBPR seems to offer comparable short-term benefits to OPR.

Effectiveness of remote home monitoring for patients with Chronic Obstructive Pulmonary Disease (COPD): systematic review.

BACKGROUND: Although remote home monitoring (RHM) has the capacity to prevent exacerbations in patients with chronic obstructive pulmonary disease (COPD), evidence regarding its effectiveness remains unclear. The objective of this study was to determine the effectiveness of RHM in patients with COPD. METHODS: A systematic review of the scholarly literature published within the last 10 years was conducted using internationally recognized guidelines. Search strategies were applied to several electronic databases and clinical trial registries through March 2020 to identify studies comparing RHM to 'no remote home monitoring' (no RHM) or comparing RHM with provider's feedback to RHM without feedback. To critically appraise the included randomized studies, the Cochrane Collaboration risk of bias tool (ROB) was used. The quality of included non-randomized interventional and comparative observational studies was evaluated using the ACROBAT-NRSI tool from the Cochrane Collaboration. The quality of evidence relating to key outcomes was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) on the following: health-related quality of life (HRQoL), patient experience and number of exacerbations, number of emergency room (ER) visits, COPD-related hospital admissions, and adherence as the proportion of patients who completed the study. Three independent reviewers assessed methodologic quality and reviewed the studies. RESULTS: Seventeen randomized controlled trials (RCTs) and two comparative observational studies were included in the review. The primary finding of this systematic review is that a considerable amount of evidence relating to the efficacy/effectiveness of RHM exists, but its quality is low. Although RHM is safe, it does not appear to improve HRQoL (regardless of the type of RHM), lung function or self-efficacy, or to reduce depression, anxiety, or healthcare resource utilization. The inclusion of regular feedback from providers may reduce COPD-related hospital admissions. Though adherence RHM remains unclear, both patient and provider satisfaction were high with the intervention. CONCLUSIONS: Although a considerable amount of evidence to the effectiveness of RHM exists, due to heterogeneity of care settings and the low-quality evidence, they should be interpreted with caution.

Robot-assisted coronary artery bypass surgery: a systematic review and meta-analysis of comparative studies.

BACKGROUND: Robot-assisted coronary bypass (RCAB) surgery has been proposed as an alternative to conventional coronary artery bypass grafting (C-CABG) for managing coronary heart disease, but the evidence on its performance compared to other existing treatments is unclear. The aim of this study was to assess, through a systematic review of comparative studies, the safety and clinical effectiveness of RCAB compared to C-CABG and other minimally invasive approaches for the treatment of coronary heart disease. METHODS: We conducted a systematic review of primary studies in the English-language literature comparing RCAB to existing treatment options (C-CABG, minimally invasive direct coronary artery bypass [MIDCAB] and port-access coronary artery bypass [PA-CAB]) following Cochrane Collaboration guidelines. Meta-analyses were performed where appropriate. RESULTS: We reviewed 13 studies: 11 primary studies of RCAB (v. C-CABG in 7, v. MIDCAB in 3 and v. PA-CAB in 1) and 2 multicentre database studies (RCAB v. non-RCAB). The overall quality of the evidence was low. Most studies showed no significant benefit of RCAB over other treatments in a majority of outcome variables. Meta-analyses showed that RCAB had lower rates of pneumonia or wound infection than C-CABG, and shorter intensive care unit length of stay than C-CABG or MIDCAB. Individual studies showed that RCAB had some better outcomes than C-CABG (ventilation time, transfusion, postoperative pain, hospital length of stay) or MIDCAB (transfusion, postoperative pain, time to return to normal activities, physical functioning and hospital length of stay). The review of the database studies showed that RCAB was statistically superior to non-RCAB approaches in postoperative pain, renal failure, transfusion, reoperation for bleeding, stroke and hospital length of stay; however, the difference between the 2 groups in several of these outcomes was small. CONCLUSION: Although the findings from this review of comparative studies of RCAB appear promising and suggest that RCAB may offer some benefits to patients, in the absence of randomized controlled trials, these results should be interpreted cautiously.

CONTEXTE: Le pontage aortocoronarien assisté par robot (PACAR) a été proposé comme solution de rechange au pontage aortocoronarien classique (PACC) pour la prise en charge des coronaropathies, mais on manque de données probantes claires comparant son efficacité à celle d'autres traitements. La présente étude visait à évaluer, dans le cadre d'une revue systématique d'études comparatives, la sûreté et l'efficacité clinique du PACAR, comparativement à celles du PACC et d'autres interventions à effraction minimale visant le traitement des coronaropathies. MÉTHODES: Nous avons réalisé une revue systématique d'études primaires publiées en anglais comparant le PACAR à d'autres options thérapeutiques (PACC, pontage aortocoronarien direct à effraction minimale [PACDEM] et pontage aortocoronarien par voie percutanée [PACVP]) selon les lignes directrices de la Collaboration Cochrane, et avons réalisé des méta-analyses lorsque c'était approprié. RÉSULTATS: Nous avons retenu 13 études : 11 études primaires sur le PACAR (comparativement à 7 études sur le PACC, à 3 études sur le PACDEM et à 1 étude sur le PACVP) et 2 études multicentriques fondées sur des bases de données (PACAR contre tout autre type de PAC). Dans l'ensemble, les données probantes étaient considérées de faible qualité. Selon la plupart des études, le PACAR ne présentait aucun avantage significatif par rapport aux autres traitements, et ce, pour la majorité des issues. Les méta-analyses ont montré que le PACAR était associé à des taux de pneumonie et d'infection de la plaie plus faibles que le PACC, de même qu'à une durée d'hospitalisation en soins intensifs plus courte que le PACC et le PACDEM. Des études individuelles ont montré que le PACAR donnait lieu à de meilleures issues pour certains paramètres que le PACC (temps de ventilation, besoin de transfusion, douleur postopératoire et durée d'hospitalisation) et que le PACDEM (besoin de transfusion, douleur postopératoire, temps nécessaire pour la reprise des activités normales, fonctionnement physique et durée d'hospitalisation). La revue des études fondées sur des bases de données a indiqué que le PACAR était supérieur, sur le plan statistique, aux autres types de PAC en ce qui a trait à la douleur postopératoire, à l'insuffisance rénale, au besoin de transfusion, à la réalisation d'une autre chirurgie en raison de saignements, à l'accident vasculaire cérébral et à la durée d'hospitalisation; cependant, pour plusieurs de ces paramètres, les différences entre les 2 groupes étaient petites. CONCLUSION: Bien que les résultats de cette revue d'études comparatives sur le PACAR semblent prometteurs et laissent penser que cette intervention comporte des avantages pour les patients, ils devraient être interprétés avec prudence étant donné l'absence d'études cliniques randomisées.

A Systematic Review and Meta-Analysis of Robot-Assisted Mitral Valve Repair.

OBJECTIVE: Robot-assisted surgery is a minimally invasive approach for repairing the mitral valve. This study aimed to assess its safety and clinical efficacy when compared with conventional sternotomy, partial sternotomy, and right minithoracotomy. METHODS: A systematic review of peer-reviewed studies comparing robot-assisted mitral valve repair with conventional sternotomy, partial sternotomy, and right minithoracotomy was conducted following Cochrane Collaboration guidelines. Meta-analyses were performed where possible. RESULTS: The search strategy yielded 15 primary studies, of which 12 compared robot-assisted with conventional sternotomy, 2 compared robot-assisted with partial sternotomy, and 6 compared robot-assisted with right minithoracotomy. The overall quality of evidence was low, and there was a lack of data on long-term outcomes. Individual studies and pooled data demonstrated that robotic procedures were comparable to conventional sternotomy and other minimally invasive approaches with respect to the rates of stroke, renal failure, reoperation for bleeding, and mortality. Robot-assisted mitral valve repair was superior to conventional sternotomy with reduced atrial fibrillation, intensive care unit and hospital stay, pain, time to return to normal activities, and physical functioning at 1 year. However, robot-assisted mitral valve repair had longer cardiopulmonary, aortic cross-clamp, and procedure times compared with all other surgical approaches. CONCLUSIONS: Based on current evidence, robot-assisted mitral valve repair is comparable to other approaches for safety and early postoperative outcomes, despite being associated with longer operative times. Ideally, future studies will be randomized controlled trials that compare between robot-assisted surgery, conventional surgery, and other minimally surgery approaches focusing on hard clinical outcomes and patient-reported outcomes.

Factors associated with positive and negative recommendations for cancer and non-cancer drugs for rare diseases in Canada.

BACKGROUND: In Canada, reimbursement recommendations on drugs for common and rare diseases are overseen by the Canadian Agency for Drugs and Technologies in Health (CADTH) and made through the pan-Canadian Oncology Drug Review (pCODR) and the Common Drug Review (CDR). While the agency specifies information requirements for the review of drug submissions, how that information is used by each process to formulate final reimbursement recommendations, particularly on drugs for rare diseases (DRDs) in which per patient treatment costs are often high, is unclear. The purpose of this study was to determine which factors contribute to recommendation type for DRDs. METHODS: Information was extracted from CDR and pCODR recommendations on drugs for diseases with a prevalence < 1 in 2000 from January 2012 to April 2018. Data were tabulated and multiple logistic regression was applied to explore the association between recommendation type and the following factors: condition/review process (cancer vs non-cancer), year, prevalence, clinical effectiveness (improvements in surrogate, clinical and patient reported outcomes), safety, quality of evidence (availability of comparative data, consistency between population in trial and indication, and bias), clinical need, treatment cost, and incremental cost-effective ratio (ICER). Two-way interactions were also explored. RESULTS: A total of 103 recommendations were included. Eleven were resubmissions, all of which received a positive recommendation. Among new submissions (n = 92), DRDs that were safe or offered improvements in clinical or patient reported outcomes were more likely to receive positive reimbursement recommendations. No associations between recommendation type and daily treatment cost, cost-effectiveness, or condition (cancer or non-cancer) were found. CONCLUSIONS: Clinical effectiveness, as opposed to economic considerations or whether the drug is indicated for cancer or non-cancer, determine the type of reimbursement recommendation.