Search Results (46)

The COVID-19 pandemic exposed the urgent need for scalable, reliable telemedicine tools to manage mild cases remotely and avoid overburdening healthcare systems. This study evaluates StepCare, a remote monitoring medical device, during the first pandemic wave at a single center in Spain. Among 35 patients monitored, StepCare showed high clinical reliability, aligning with physician assessments in 90.4% of cases. Patients and clinicians reported excellent usability and satisfaction. The system improved workflow efficiency, reducing triage time by 25% and associated costs by 84%. These results highlight StepCare’s value as a scalable, patient-centered solution for remote care during health crises. Full article

Highly effective modulator therapy (HEMT) has been available for adults and young adults aged 12 years and over with cystic fibrosis for approximately 5 years, with real-world evidence (RWE) emerging that confirms the significant impacts of these novel medications in older patient groups. As licensing has been extended to younger children (2 years and above in some jurisdictions), we summarize the clinical experience of these medications in pre-school and school-aged children and compare how changes in the objective markers of the disease can be elucidated in younger children. We also discuss the different incidences and severity of side effect profiles, the efforts to mediate these in younger children, and the particular challenges in introducing novel medications into pediatrics. We speculate on the use of HEMT in younger infants and its potential use in prenatal care. Full article

Obsessive–compulsive disorder (OCD) has an estimated prevalence between 1 and 2.3%. Existing treatments may not be suitable or effective for all people with OCD, and there is increasing interest in whether these individuals may benefit from the use of cannabis-based medical products (CBMPs). We document the characteristics of 257 people reporting a diagnosis of OCD within Project T21, a study of medical cannabis patients, and examined whether the use of prescribed cannabinoids improves quality of life. Individuals with OCD were prescribed an average of 2.2 CBMPs, with most products classified as THC-dominant flowers (73.7%). Three months after initiating treatment, there were substantial improvements in quality of life (Cohen’s d = 0.48; 95% CI = 0.29–0.65), general health (Cohen’s d = 0.43; 95% CI = 0.26–0.61), mood/depression (Cohen’s d = 0.85; 95% CI = 0.65–1.04), and sleep (Cohen’s d = 0.61; 95% CI = 0.43–0.79). There was a corresponding reduction in anxiety symptoms among the subsample who completed the GAD-7 (Cohen’s d = 1.14; 95% CI = 0.84–1.44). Eight individuals (5.7%) reported a total of 14 adverse effects, with the majority of these (57%) being described as mild. Given emerging evidence that those with OCD can benefit from CBMPs, coupled with the increased availability of these unlicensed products internationally, there is a need for more research, including clinical trials, to identify those who may benefit most from the use of these medicines. Full article

Background: Sources and evidence cited to inform payer coverage decisions on pharmacogenomic (PGx) testing in psychiatry are presently underexplored. Methods: We conducted a qualitative and quantitative assessment of publicly available coverage policies from 14 US payers, examining the number and both the type and source of citations across policies and coverage decisions. Payers were classified as for-profit or mutual fund versus non-profit or government, and their coverage decisions were categorized as either coverage (limited or specified) or no coverage. Results: Among 32 unique sources cited, peer-reviewed literature as a single source was most frequently cited across all policies. Of 207 peer-reviewed papers cited across all policies, 40% (n = 83) were psychiatry-specific real-world evidence (RWE) studies. No statistically significant relationships were observed when comparing variance in the number of citations per policy by payer type (p = 0.22) or coverage decision (p = 0.75; unadjusted variance of 61.25 and an adjusted variance of 60.98 for both comparisons). For-profit or mutual fund payers and/or payers providing no coverage cited systematic reviews and non-randomized controlled cohort RWE studies most often. Non-profit or government payers and/or payers providing coverage cited case series or case-control RWE studies most often. Six psychiatry-specific RWE studies and contributions from 13 distinct sources were often cited, regardless of payer type or coverage decision. Conclusions: RWE, among several sources, are cited in many forms and to varying degrees among payers providing coverage decisions for PGx testing in psychiatry, with coverage determinations being largely based on how certain payers interpret evidence on the clinical value of testing. Full article

Background: Soft-tissue sarcomas (STSs) represent a heterogeneous group of malignancies with widely varying treatment responses and biological behaviors. While spontaneous necrosis (present at diagnosis) is recognized in established sarcoma grading systems, the prognostic significance of therapy-induced necrosis remains uncertain. Inconsistent definitions, methodological variability, and clinical confounders further complicate the interpretation of necrosis as an independent prognostic marker. Methods: This communication synthesizes findings from an international, multidisciplinary webinar hosted by the Sarcoma Academy, critically assessing the utility of therapy-induced necrosis in STS management. Discussions encompassed surgical, pathological, oncological, and radiological perspectives, emphasizing how necrosis is defined, measured, and contextualized in patient care. Results: Heterogeneity in STS subtypes, varied treatment protocols, and sampling inconsistencies challenge the prognostic value of post-treatment necrosis. While substantial necrosis may sometimes signal effective therapy, it can also reflect the tumor’s aggressive nature. The panel underscored the utility of measuring the percentage of viable tumor cells, rather than necrosis alone, to obtain a more standardized and reproducible measure of therapy response. Emerging approaches—such as radiomics, molecular profiling, immune-based analyses, and real-world evidence (RWE) protocols—offer promising avenues for refining prognostication and guiding personalized therapy in STS. Conclusions: A focus solely on therapy-induced necrosis is insufficient to predict outcomes in STS. Instead, a multidisciplinary framework—combining standardized pathology protocols, quantification of viable tumor cells, advanced imaging, and innovative clinical trial designs—can better capture both treatment effects and underlying tumor biology. Future collaborative studies and hybrid trial methodologies are needed to determine which STS subgroups gain the most from intensified treatments aimed at maximizing necrosis, and how to balance such interventions with surgical considerations, toxicity, and overall patient well-being. Full article

The 2025 EuDial Consensus systematically compared hemodiafiltration (HDF) to high-flux hemodialysis (HD), highlighting HDF’s superior removal of middle-molecular-weight uremic toxins, potential survival advantages, and immunomodulatory properties. High-Volume HDF (HVHDF), defined by a substitution volume exceeding 23 L per session, was associated with improved cardiovascular outcomes, reduced infection-related mortality, and decreased systemic inflammation. Background/Objectives: Nevertheless, the consensus refrains from endorsing HDF as the standard of care, citing insufficient evidence to prevent sudden cardiac death, reduce intradialytic hypotension, or significantly lower hospitalization rates compared to HD. Methods: This review critically evaluates the EuDial Consensus, highlighting its methodological strengths while noting potential limitations stemming from an exclusive reliance on randomized controlled trials (RCTs). The exclusion of real-world evidence (RWE) and mechanistic studies may have led to an underestimation of HDF’s broader clinical benefits, particularly in cardiovascular stability, inflammation control, and anemia management. Results: Multiple studies have demonstrated HDF’s capacity to enhance immune function, improve erythropoiesis, and increase the clearance of beta-2 microglobulin (β2M) and other pro-inflammatory toxins. Furthermore, the CONVINCE trial’s economic analysis supports HDF’s cost-effectiveness, especially when considering improved survival and reduced dependency on erythropoiesis-stimulating agents. Conclusions: Future research should integrate RWE and mechanistic insights to better define HDF’s therapeutic potential, particularly concerning anemia control, infection mitigation, and hemodynamic stability. While the EuDial Consensus provides valuable clinical guidance, its conclusions should be contextualized within a broader and evolving evidence base. Given its multidimensional benefits, post-dilution HVHDF is increasingly viewed as a preferred renal replacement therapy modality, warranting wider adoption in clinical practice. Full article

Background/Objectives: Obesity is a chronic, progressive, recurrent disease associated with impaired health, affecting an increasing proportion of the population worldwide. Newer-generation incretin-based therapies (IBTs) (liraglutide, semaglutide, and tirzepatide) have shown greater efficacy than older anti-obesity medications. This systematic literature review provides an overview of the evidence on the symptomatic adverse events (AEs) and patient-reported outcomes of IBTs to facilitate clinical decision-making. Methods: A systematic search was conducted using a predefined search strategy to identify controlled trials and real-world evidence (RWE) studies assessing IBTs. Results: Among 4414 publications identified, 81 (>400,000 participants) were included. Liraglutide (n = 49), semaglutide (n = 34), and tirzepatide (n = 7) were used in 48 clinical and 33 RWE studies. Gastrointestinal (GI) AEs were most common: placebo-subtracted incidences were 5–39% for nausea, −7–39% for diarrhea, 2–31% for constipation, 0–26% for vomiting, and 2–20% for abdominal pain, with no clear difference across IBTs. Most AEs were mild or moderate and mainly occurred during dose escalation. Quality of life outcomes were reported in 27 publications and generally showed improvements with IBTs. Conclusions: This study confirms that GI AEs are common with IBTs. Clinicians should keep the AE profile of IBTs in mind and consider where additional preventative measures may be required. Full article

Introduction and Aim: Stage III Non-Small Cell Lung Cancer (NSCLC) has a poor prognosis, with median survival ranging from 9 to 34 months. The PACIFIC trial demonstrated that durvalumab after platinum-based chemoradiotherapy (CRT) improves overall survival (OS) and progression-free survival (PFS). This review evaluates real-world evidence (RWE) on durvalumab’s efficacy and safety, focusing on patient characteristics, prognostic factors, treatment protocols, and outcomes beyond progression. Materials and Methods: A literature search of PubMed, Embase, and Google Scholar identified 49 observational studies published from January 2017 to August 2024 on unresectable stage III NSCLC. Clinical trials, early-stage disease, and alternative treatments were excluded. Results: Compared to the PACIFIC trial, real-world patients were older, had poorer ECOG performance (≥2), and more comorbidities like COPD. Despite this, durvalumab provided consistent survival benefits. Positive prognostic factors included non-squamous histology, high PD-L1 expression, and timely durvalumab initiation (≤42 days post-CRT). Most radiotherapy regimens mirrored PACIFIC (54–66 Gy). Concomitant CRT was used in 90% of cases, with sequential CRT for frail patients. Chemotherapy regimens varied. Immune-mediated pneumonitis was a major adverse event, with incidence rates between 15% and 100%. Severe cases led to treatment discontinuation, impacting survival. Treatment beyond progression remains uncertain, with limited benefits from immunotherapy rechallenge. Conclusions: RWE supports durvalumab’s efficacy, emphasizing the need for personalized treatment strategies and further research to improve long-term outcomes. Full article

Background: Diabetic ketoacidosis (DKA), a life-threatening complication, can occur in individuals with type 2 diabetes during illness, stress, or medication use. This study examines DKA signals in type 2 diabetes, focusing on sodium–glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl-peptidase-4 (DPP-4) inhibitors. Methods: DKA reports from Q1 2019 to Q3 2024 were retrieved from the FDA Adverse Event Reporting System (FAERS). Associations between primary exposure and outcomes were ascertained using four key metrics: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and Information Component (IC). Results: SGLT2 inhibitors exhibited the higher DKA risk in 2019–2021 (ROR: 314.86 [95% CI 301.76–328.53], PRR of 245.69 [95% CI 235.47–256.36], IC of 6.90, and EBGM of 120), declining in 2022–2024. GLP-1 receptor agonists showed an ROR increase from 2.88 [95% CI 2.56–3.25] in 2019–2021 to 4.64 [95% CI 4.06–5.29] in 2022–2023, slightly declining to 3.95 [95% CI 3.27–4.74] in 2024. DPP-4 inhibitors exhibited a steady ROR rise from 6.81 [95% CI 5.52–8.40] in 2019–2021 to 8.57 [95% CI 6.24–11.76] in 2022–2023 and further to 11.02 [95% CI 6.71–18.10] in 2024. PRR, EBGM, and IC values followed similar trends. The age groups 41–60 and 61–91 years were the most affected, with hospitalization at its highest rate for DPP4-inhibitors in Q1–Q3 of 2024. Hospitalizations were also observed with GLP-1 receptor agonists and SGLT2 inhibitors. Life-threatening events and fatalities were also reported, with physicians contributing to most reports. Conclusions: DKA signals were observed for all three drug classes, particularly among elderly patients, highlighting the need for careful monitoring, especially during periods of illness or stress. However, the risk was higher in the SGLT2 inhibitor group than in the other groups. Full article

Randomized controlled trials (RCTs) are the gold standard for testing the safety and efficacy of new drugs and biologicals. The US Food and Drug Administration (FDA) has proactively improved the trial designs to make them scientifically rational while avoiding unnecessary human exposure. Several new guidelines by the FDA have come in 2024 that address consolidating the RCTs with the Real-World Evidence (RWE) trials, decentralizing the testing platforms, and allowing the point-of-use clinicians to participate. However, the issue of placebo control remains, which is part of RCTs, and it should be reduced or removed given the organic impact of placebo that compounds the efficacy evaluation (explanatory trials), as opposed to effectiveness trials (pragmatic trials), which measure the degree of beneficial effects in “real-world” clinical settings. Additionally, clinical trials with low study power should be allowed, and when the proof of bioavailability at the site of action is not present, it should be removed. It is advised that the FDA issue a comprehensive guideline to consolidate its several guidelines and consider the role of placebo in making drug development a more affordable exercise while meeting the requirement to minimize the abuse of humans in such trials. Full article

Canada is known to have a complex pathway for new drug approval and reimbursement, resulting in delayed access for patients with serious and life-threatening diseases, such as cancer. Several recent publications from key stakeholders, including patients, physicians and policymakers, highlight patient helplessness, physician frustrations and policymakers entangled in a massive network of bureaucracy unable to make headway. Several quantitative and qualitative assessments using time from regulatory approvals to successful reimbursements confirm long review times and high rejection rates for oncology drugs, especially those receiving conditional approvals. A consensus forum of 18 Canadian oncology clinicians recently voiced frustration with the process and inability to deliver guideline-supported efficacious therapies to their patients. This manuscript compares data extracted from publicly available data sources from 2019 to June 2024 to previous publications. Methods: Public databases from Health Canada, the Canadian Agency for Drugs and Technologies in Health (CADTH), which is in the process of changing to Canada’s Drug Agency, and the pan-Canadian Pharmaceutical Alliance (pCPA) were reviewed and the data collected were analyzed with descriptive statistics. Results: From the data, three trends emerge, (i) an increasing number of oncology drugs are receiving conditional approvals from Health Canada, (ii) the percentage of conditionally approved oncology drugs receiving positive reimbursement recommendations from CADTH is still low but appears to be improving, but delays in access are now contingent upon pCPA deciding whether to negotiate price and then the duration of any negotiation, and (iii) real-world evidence is no longer part of the decision-making for conditional approvals. A slight increase in the positive endorsement of RWE used to support CADTH recommendations was observed. Conclusions: The lack of timely access to oncology drugs hurts Canadian patients. While a small trend of improvement appears to be emerging, longer-term data collection is required to ensure sustained patient benefits. Full article

The future directions in leveraging real-world evidence (RWE) and real-world data (RWD) in the field of lymphoma, as compared to traditional experimental clinical trials, are poised to significantly impact research methodologies, treatment strategies, and patient care. Current methods of clinical trials involve a well-controlled design and patient selection bias. Integrating RWE and RWD with experimental clinical trials offers a multifaceted approach to understanding lymphoma and enhancing patient outcomes. In this review, we discuss how RWE has helped shape lymphoma clinical trials, and we compare and evaluate evidence obtained from real-world lymphoma studies/databases with that obtained from clinical trials. We also discuss methods for utilizing surrogate endpoints to facilitate clinical trials and expedite drug development. RWE can be leveraged to bridge the gap between data obtained from clinical trial populations and the broader patient population encountered in clinical practice, by highlighting differences in outcomes and the need for effective treatment strategies across diverse patient groups. Full article

The use of real-world data (RWD) for healthcare decision-making is complicated by concerns regarding whether RWD is fit-for-purpose or is of sufficient validity to support the creation of credible RWE. An efficient mechanism for screening the quality of RWD is needed as regulatory agencies begin to use real-world evidence (RWE) to inform decisions about treatment effectiveness and safety. First, we provide an overview of RWD and RWE. Data quality frameworks (DQFs) in the US and EU were examined, including their dimensions and subdimensions. There is some convergence of the conceptual DQFs on specific assessment criteria. Second, we describe a list of screening criteria for assessing the quality of RWD sources. The curation and analysis of RWD will continue to evolve in light of developments in digital health and artificial intelligence (AI). In conclusion, this paper provides a perspective on the utilization of RWD and RWE in healthcare decision-making. It covers the types and uses of RWD, data quality frameworks (DQFs), regulatory landscapes, and the potential impact of RWE, as well as the challenges and opportunities for the greater leveraging of RWD to create credible RWE. Full article

The mpox 2022 outbreak was declared a public health emergency in July 2022. In August 2022, the MVA–BN vaccine received emergency use authorization in the United States (US) to target at-risk groups. This study (EUPAS104386) used HealthVerity’s administrative US healthcare data to generate real-world evidence for MVA–BN vaccine effectiveness and safety to prevent mpox disease in men who have sex with men (MSM) and transgender women, the most affected population during the 2022 mpox outbreak. Fully vaccinated subjects (two doses ≥ 28 days apart) were initially matched with five unvaccinated subjects on calendar date, age, US region, and insurance type. Subjects were followed from index date (14 days after the second dose) until death or data end to ascertain mpox occurrence. After propensity score adjustment, the MVA–BN vaccine effectiveness against mpox disease was 89% (95% CI: 12%, 99%) among those fully vaccinated; attenuated to 64% (95% CI: 40%, 78%) among those with any dose and 70% (95% CI: 44%, 84%) for those with only a single dose. One pericarditis adverse event of special interest was observed when the risk window was extended to 28 days. These results contribute to the totality of evidence supporting the favorable benefit/risk profile of the MVA–BN vaccine. Full article

Background: Real-world evidence (RWE) can reinforce clinical trial evidence in health technology assessment (HTA). Objectives: Review HTA bodies’ (HTAbs) requirements for RWE, real uses, and acceptance across seven countries (Brazil, Canada, France, Germany, Italy, Spain, and the United Kingdom) and outline recommendations that may improve acceptance of RWE in efficacy/effectiveness assessments and appraisals processes. Methods: RWE requirements were summarized based on HTAbs’ guidelines. Acceptance by HTAbs was evaluated based on industry experience and case studies. Results: As of June 2022, RWE methodological guidelines were in place in three of the seven countries. HTAbs typically requested analyses based on local data sources, but the preferred study design and data sources differed. HTAbs had individual submission, assessment, and appraisal processes; some allowed early meetings for the protocol and/or results validation, though few involved external experts or medical societies to provide input to assessment and appraisal. The extent of submission, assessment, and appraisal requirements did not necessarily reflect the degree of acceptance. Conclusion: All the countries reviewed face common challenges regarding the use of RWE. Our proposals address the need to facilitate collaboration and communication with industry and regulatory agencies and the need for specific guidelines describing RWE design and criteria of acceptance throughout the assessment and appraisal processes. Full article