Search Results (24)

Background/Objectives: Associations between scores on tests of sensory integration functions demonstrated in numerous studies over six decades have contributed to the development of Ayres Sensory Integration^® (ASI) theory and practice. Understanding these “patterns” aids therapists in their interpretation of assessment results, ensuring appropriate and effective intervention. This study aimed to describe and discuss published research on identified patterns related to constructs in the Ayres Sensory Integration^® approach. Methods: Arksey and O’Malley’s framework and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews Checklist were used. The literature review search was guided by the following criteria: population (children aged from 3 years to 12 years and 11 months), context (the literature within ASI), and concept (sensory integration patterns). Data were sourced from the following databases: CHINAL, ProQuest (Health & Medical Complete), SABINET, Web of Science, PubMed, OpenGreyEU, Greylit.org, and CADTH GreyMatters. There was no date constraint, and all available data were collected. Results: After reviewing 998 peer-reviewed articles, 17 articles met the inclusion criteria. Data extraction, charting, and analysis indicating a clear pattern of assessments were used to determine the sensory integration patterns. Similarities and differences between sensory integration patterns were found over time, in different diagnostic groups and different settings. Conclusions: The ASI approach is based on detailed research on the development of assessment instruments used for evaluation and sensory integration patterns used for interpretation of the assessment results. This research has been conducted over the past 60 years and contributes to an evidence-based therapeutic approach. Full article

Background: Chronological age is an imprecise proxy for cognitive aging. The Cognitive Age Delta (CAD)—the difference between predicted cognitive age and chronological age—offers a scalable, individualized marker of functional brain aging. We examined determinants of CAD in cognitively unimpaired (CU) adults stratified by Alzheimer’s disease (AD) and vascular biomarkers. Methods: We analyzed 177 CU participants from the Gipuzkoa Alzheimer Project (Basque Country, Northern Spain) classified as amyloid-negative/vascular-negative (CUA−V−, n = 140), amyloid-positive (CUA+, n = 23), or vascular-positive (CUV+, n = 14) using CSF and MRI criteria; vascular burden was defined as Fazekas ≥ 2 on T2-FLAIR or ≥4 microbleeds on SWI, excluding non-traumatic superficial siderosis and established ischemic lesions. MRI was used solely for vascular classification. Associations with demographic, genetic, lifestyle, and reserve measures were tested with General Linear Models. Results: CAD did not differ across biomarker groups (Kruskal–Wallis H(2) = 0.17, p = 0.91). Median (IQR) CAD values were 0.28 (−4.13, 4.69) for CUA−V−, −0.14 (−3.15, 2.87) for CUA+, and 0.77 (−2.22, 3.76) for CUV+, indicating comparable distributions. Higher vocabulary scores (proxy of cognitive reserve) related to a younger cognitive age in CUA−V− (β = −1.39, p < 0.001) and CUA+ (β = −2.08, p = 0.054). In CUA+, greater sedentary time—particularly computer-based sitting—was also associated with lower CAD (daily sitting β = −2.13, p = 0.009; workday computer sitting β = −2.32, p = 0.015). CAD showed no associations with CSF Aβ42, p-tau or t-tau, APOE ε4 load, or vascular risk factors (all p > 0.05). Conclusions: CAD captures interindividual resilience-related variability beyond classical AD biomarkers. Vocabulary, a marker of lifelong enrichment, emerged as a robust determinant of a younger cognitive age, while amyloid and vascular pathology exerted limited influence at preclinical stages. These findings support CAD as a sensitive, scalable endpoint for identifying protective factors and guiding personalized prevention in early Aging. Full article

Background/Objectives: The purpose of this study was to systematically review the potential effects of a pregnant woman’s excessive gestational weight gain on adverse perinatal outcomes affecting the mother and the fetus/neonate. Methods: Medline/PubMed, Scopus, CADTH Grey Matters and National Archive of PhD Theses were systematically searched for all relevant studies published. Assessments of the risk of bias in the included studies were made according to the tool “The Newcastle–Ottawa Scale (NOS)”. Results: Five publications met all the inclusion criteria and were included in this review. The risk of bias in all the included studies was low. One study supports the detrimental effect of excessive gestational weight gain on the risk of gestational diabetes mellitus, one study on the risk of preterm birth, five studies on the risk of macrosomia-high birthweight of the neonate, three studies on the risk of a large-for-gestational-age neonate, three studies on the risk of hypertensive disorders of pregnancy, one study on the risk of gestational hypertension and preeclampsia, five studies on the risk of delivery by cesarean section and one study on the risk of neonatal hypoglycemia requiring treatment. One study supports the beneficial effect of excessive gestational weight gain on the risk of preterm birth, two studies on the risk of a small-for-gestational-age neonate and two studies on the risk of low birthweight of the neonate. Conclusions: The study presents the most recent and strong evidence regarding the negative effect of excessive gestational weight gain on most adverse perinatal outcomes. However, excessive gestational weight gain has a beneficial effect in a very limited number of outcomes. Full article

Medical oncology is a rapidly evolving field, with new medications being discovered yearly, contributing to increased survival rates. However, accessing drugs in a timely manner can be challenging. In Quebec, Canada, a physician can prescribe an unlisted anticancer treatment through a regulated pathway under exceptional circumstances. We conducted a quality improvement study describing the outcomes of incurable cancer patients receiving unlisted anticancer therapy at the Jewish General Hospital between 2018 and 2019. Though our study did not include a comparator arm, unlisted anticancer therapies were associated with interesting median progression-free survival (11 months) and overall survival (25 months). Moreover, a large proportion of treatments, 44%, were subsequently reimbursed in the province of Quebec. Given the delay in anticancer drug reimbursement, this pathway is essential for timely access to oncology drugs. Such ‘special access’ programs will likely become increasingly important as precision medicine becomes the standard of practice. 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

Niraparib was recently funded in Canada for the maintenance treatment of ovarian cancer following platinum-based chemotherapy. However, the drug’s safety profile in the real world remains uncertain. We conducted a cohort study to describe the patient population using niraparib and the proportion that experienced adverse events between June 2019 and December 2022 in four Canadian provinces (Ontario, Alberta, British Columbia [BC], and Quebec). We used administrative data and electronic medical records from Ontario Health, Alberta Health Services, and BC Cancer, and registry data from Exactis Innovation. We summarized baseline characteristics using descriptive statistics and reported safety outcomes using cumulative incidence. We identified 514 patients receiving niraparib. Mean age was 67 years and most were initiated on a daily dose of 100 or 200 mg/day. Grade 3/4 anemia, neutropenia, and thrombocytopenia occurred in 11–16% of the cohort. In Ontario, the three-month cumulative incidence of grade 3/4 thrombocytopenia was 11.6% (95% CI, 8.3–15.4%), neutropenia was 7.1% (95% CI, 4.6–10.4%), and anemia was 11.3% (95% CI, 8.0–15.2%). Cumulative incidences in the remaining provinces were similar. Initial daily dose and proportions of hematological adverse events were low in the real world and may be related to cautious prescribing and close monitoring by clinicians. Full article

New oncology drugs undergo detailed review prior to public funding in a single-payer healthcare system. The aim of this study was to assess how cancer drug review times impact funding recommendations. Drugs reviewed by the pan-Canadian Oncology Drug Review (pCODR) between the years 2012 and 2020 were included. Data were collected including Health Canada approval dates, initial and final funding recommendations, treatment intent, drug class, clinical indications, and incremental cost-effectiveness ratios (ICER). Univariable and multivariable analyses were used to determine the association between funding recommendations and review times. Of the 164 applications submitted, 130 received a positive final recommendation. Median time from Health Canada (HC) approval to final recommendation was longer for drugs indicated for the treatment of gastrointestinal (GI) and lung cancer compared to breast, genitourinary (GU), and other tumours (205 vs. 198 vs. 111 vs. 129 vs. 181 days, respectively; Kruskal–Wallis p = 0.0312). Drugs with longer review times were more likely to receive a negative pCODR recommendation, even when adjusting for tumour type, drug class, and intent of therapy (157 vs. 298 days; Wilcoxon p = 0.0003, OR 1.002 95% CI [1.000–1.004].). There was no association between funding recommendation and tumour type or class of drug. The exploration of factors associated with variance in review times will be important in ensuring timely patient access to cancer drugs. Full article

New therapies in a publicly funded healthcare system are first appraised by health technology assessment agencies that provide funding recommendations to the payers. Treatment with Chimeric Antigen Receptor-T cell (CAR-T) therapy is revolutionizing the management of patients with relapsed/refractory aggressive B-cell lymphoma by providing an effective alternative to the standard of care. Yet, the implementation of CAR-T treatment has a substantial impact on the healthcare system due to its high cost, complex manufacturing process, and requirement for highly specialized services and expertise. CAR-T Cells, as a “living drug”, are fundamentally different from usual medications, and their approvals and funding recommendations pose unique challenges to the health technology agency. In this paper, we explore the specific challenges that face the health technology agencies in reviewing reimbursement recommendations for CAR-T therapy. We take a Canadian perspective and use CAR-T treatment of relapse/refractory aggressive B-cell lymphoma as an example. Full article

The addition of pertuzumab to neoadjuvant trastuzumab and chemotherapy for women with early-stage, high-risk, HER2+ breast cancer has been observed to lead to higher pathologic complete response rates (pCR), and improved event-free survival compared to trastuzumab and chemotherapy alone. Based on available data, neoadjuvant pertuzumab is recommended by ESMO, ASCO, and NICE as well as by a Canadian Consensus Guideline Group. We discuss the implications for Canadian patients with HER2+ early breast cancer due to a second and final negative funding decision by the Canadian Agency for Drugs and Technologies in Health (CADTH) related to neoadjuvant pertuzumab. This decision will have adverse impacts for up to 1 in 6 women receiving neoadjuvant therapy for high-risk HER2+ breast cancer, due to suboptimal pCR rates and higher risks of invasive breast cancer recurrent events, resulting in the need for more toxic adjuvant therapy. Full article

Real-world evidence (RWE) is health and outcomes data generated from a patient’s journey through the health care system or disease process (i.e., real-world data). RWE is now having an increasingly important role in regulatory/reimbursement decisions. This article examines reimbursement recommendations by the Canadian Agency for Drugs and Technology in Health (CADTH) on oncology drugs approved between 2019 and 2021. Oncology drugs with a Summary Basis of Decision (SBD) for original marketing approvals were used to generate a corresponding list of CADTH final clinical recommendations for review. Of the 45 oncology drugs approved by Health Canada, CADTH granted positive funding recommendations to all 11 drugs that had priority review approvals. Two of the 17 drugs with standard reviews did not file to CADTH and 3 received a negative recommendation. Of the 17 drugs with Notice of Compliance with Conditions (NOCc) status, three were not filed to CADTH and four were under active reviews. Of the ten completed NOCc reviews, all contained RWE from sponsors and six received a negative decision on their first review. No significant differences in review times were found between the three approval statuses. Regulatory approval status appeared to influence reimbursement outcomes in Canada and evaluation of 10 NOCc approvals provided little insight regarding robustness of RWE required for more favorable considerations. Full article

Publicly funded healthcare systems, including those in Canada, the United Kingdom (UK), and Australia, often use health technology assessment (HTA) to inform drug reimbursement decision-making, based on dossiers submitted by manufacturers, and HTA agencies issue publicly available reports to support funding recommendations. However, the level of information reported by HTA agencies in these reports may vary. To provide insights on this issue, we describe and assess the reporting of economic methods in recent oncology HTA recommendations from the Canadian Agency for Drugs and Technologies in Health (CADTH), National Institute for Health and Care Excellence (NICE), and Pharmaceutical Benefits Advisory Committee (PBAC). Publicly available HTA recommendations and reports for oncology drugs issued by CADTH over a 2-year period, 2019–2020, were identified and compared with the corresponding HTA documents from NICE and the PBAC. Reporting of key model characteristics and attributes, survival analysis methods, methodological criticisms, and re-assessment of the economic results were characterized using descriptive statistics. Dichotomous differences in the methodological criticisms observed between the three agencies were assessed using Cochran’s Q tests and substantiated using pairwise McNemar tests. Chi-squared tests were used to assess the dichotomous differences in the reporting of methods and explore the potential relationships between categorical variables, where appropriate. HTAs published by CADTH, NICE, and the PBAC consistently reported a broad spectrum of descriptive information on the economic models submitted by manufacturers. While common economic evaluation attributes were well-reported across the three HTA agencies, significant differences in the reporting of survival analysis methods and methodological criticisms were observed. NICE consistently reported more comprehensive information, compared to either CADTH or PBAC. Despite these differences, broadly similar recommendation rates were observed between CADTH and NICE. The PBAC was found to be more restrictive. Based on our 2-year sample of oncology, the HTAs published by CADTH matched with the corresponding HTAs from NICE and PBAC; we observed important variations in the reporting of economic evidence, especially technical aspects, such as survival analysis, across the three agencies. In addition to guidelines for HTA submissions by manufacturers, the community of HTA agencies should also have common standards for reporting the results of their assessments, though the information and opinions reported may differ. Full article

Background: Canada has a publicly funded healthcare system with a complex drug funding process. After Health Canada approval to market a drug, the pan-Canadian Oncology Drug Review (pCODR) (now renamed the CADTH reimbursement review) makes a non-binding funding recommendation to the Canadian provinces (except Quebec), which each then decide whether the drug will be publicly funded. We identified the determinants of funding in this process. Methods: We analyzed drugs for advanced lung (n = 15), breast (n = 8), colorectal (CRC) (n = 7), melanoma (n = 10), and neuroendocrine (NET) (n = 3) cancers undergoing the funding decision process from 2011 to 2019. Determinants of funding assessed in the model included list price, cancer type, drug class, and pCODR recommendation. The primary outcome was the correlation between list price and time to funding (TTF: Health Canada approval to first provincial funding). Secondary outcomes included an exploratory analysis of predictors of drug funding. Results: We analyzed 43 drugs: targeted agents 72%, immunotherapy 20%, chemotherapy 7%. A total of 72% were funded in at least one province. Median TTF was 379 days (IQR 203–601). Median list price (28-day course) was CAD 8213 (IQR CAD 5391–9445). Higher list price was not correlated with TTF (correlation coefficient −0.20, p = 0.28). There was no association between list price and pCODR recommendation or the decision to fund in at least one province. A positive pCODR recommendation correlated with the provinces’ funding decisions (p < 0.001), where 89% of drugs with a positive recommendation were funded and 100% of drugs with a negative recommendation were not funded. Tumor type was predictive of TTF (p < 0.001): CRC drugs were the slowest at a median of 2541 days (IQR 702–4379), and NETs were the quickest at a median of 0 days (IQR 0–502). Cancer type predicted decision to fund in at least one province (p = 0.005), with funding for 100% of NET drugs at the high end and 29% of CRC drugs at the low end. Drug class was predictive of TTF (p = 0.01): 465 days (IQR 245–702) for targeted agents, 443 days (IQR 298–587) for chemotherapy, and 339 days (IQR 164–446) for immunotherapy. Conclusions: Determinants of drug funding included cancer type, drug class, and pCODR recommendation but not list price. Factors other than cost were more heavily weighted in the funding decisions of cancer drugs in Canadian provinces. Full article

We undertook an analysis of the Canadian Agency for Drugs and Technologies in Health (CADTH)’s health technology assessments (HTAs) of systemic therapies for solid tumour indications to determine if a mechanism to re-evaluate HTA decisions is needed based on the level of certainty supporting the original recommendation. To measure the certainty in the evidence, we analysed if: (1) overall survival (OS) was the primary endpoint in the pivotal trial, (2) median OS was available at the time of the recommendation, and (3) the expert review committee explicitly identified gaps in the evidence. There were 96 drugs approved by Health Canada that met our eligibility criteria between 1 January 2017 and 31 October 2021. Median OS was not estimable at the time of the recommendation in 57% of the positive recommendations, and the uncertainty in the magnitude of clinical benefit was identified by the expert review committee in 21% of the positive recommendations. There is uncertainty at the time of the HTA recommendation for many drugs, and thus a need to implement a process to re-evaluate drugs in Canada to allow patients timely access to promising therapies while ensuring long-term value of therapies to patients and the healthcare system. Full article