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OBJECTIVE: Evidence on re-appraisals of health technologies in Germany is limited, and for rare disease treatments (RDTs) the Federal Joint Committee follows different processes (limited or regular) depending on whether an annual revenue threshold has been exceeded. Our objective is to better understand (re)-appraisal processes and their outcomes for RDTs in Germany. METHODS: We analysed appraisal documents of 55 RDT indications for which an initial appraisal and a re-appraisal were conducted between 2011 and 2023. We extracted information for the type of evidence, the risk of bias, the availability of additional evidence, and the change in the maturity of survival data as proxies for evidence quality. Specifically, we reviewed the reasons for conducting re-appraisals; examined how evidence quality and the clinical benefit rating (CBR) differed between initial appraisals and re-appraisals; and explored the association between evidence quality and (i) the CBR and (ii) the change in the CBR following re-appraisal. RESULTS: Most re-appraisals were conducted because the annual revenue threshold was exceeded, or the initial appraisal resolution was time-limited. Almost all initial appraisals used the limited process, while the majority of re-appraisals used the regular process. The CBR increased in only nine and decreased in 21 of 55 re-appraisals. There was some evidence that re-appraisals with an accepted randomised controlled trial were significantly more likely to achieve a higher CBR. CONCLUSIONS: Findings confirmed that reasons and processes for conducting re-appraisals of RDTs in Germany differ. Further, high CBRs in re-appraisals were not common and evidence quality in initial appraisals and re-appraisals was limited.
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BACKGROUND AND OBJECTIVE: This study aimed to assess the cost-effectiveness of two regimens regarded as the standard of care for the treatment of newly diagnosed, transplant-ineligible multiple myeloma in Singapore: (1) daratumumab, lenalidomide, and dexamethasone and (2) bortezomib, lenalidomide, and dexamethasone. Additionally, it aimed to explore potential strategies to manage decision uncertainty and mitigate financial risk. METHODS: A cost-effectiveness analysis from the healthcare system perspective was conducted using a partitioned survival model to estimate lifetime costs and quality-adjusted life years (QALYs) associated with daratumumab-based treatment and the bortezomib-based regimen. The analysis used data from the MAIA and SWOG S0777 trials and incorporated local real-world data where available. Sensitivity analyses were performed to evaluate the robustness of the findings, and a risk analysis was conducted to analyze various payer strategies in terms of their payer strategy and uncertainty burden (P-SUB), which account for the decision uncertainty and the additional cost of choosing a suboptimal intervention. RESULTS: The incremental cost-effectiveness ratio (ICER) for daratumumab, lenalidomide, and dexamethasone (DRd) compared with bortezomib, lenalidomide, and dexamethasone (VRd) was US $90,364 per QALY gained. The results were sensitive to variations in survival for DRd, postprogression treatment costs, cost of hospice care, and hazard ratio for progression-free survival. The scenarios explored indicated that structural assumptions, such as the time horizon of the analysis, significantly influenced the results due to uncertainties arising from immature trial data and treatment efficacy over time. Among the various payer strategies compared, an upfront price discount for daratumumab emerged as the best approach with the lowest P-SUB at US $14,708. CONCLUSION: In conclusion, this study finds that daratumumab as a first-line treatment for myeloma exceeds the cost-effectiveness threshold considered in this evaluation. An upfront price reduction is the recommended strategy to manage uncertainties and mitigate financial risks. These findings highlight the importance of targeted payer strategies to address specific types and sources of uncertainty.
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BACKGROUND: Patients experiencing myocardial infarction (MI) remain at high risk of future major adverse cardiovascular events (MACE). While low-dose colchicine and spironolactone have been shown to decrease post-MI MACE, more data are required to confirm their safety and efficacy in an unselected post-MI population. Therefore, we initiated the CLEAR SYNERGY (OASIS 9) trial to address these uncertainties. METHODS: The CLEAR SYNERGY trial is a 2 × 2 factorial randomized controlled trial of low-dose colchicine 0.5 mg daily versus placebo and spironolactone 25 mg daily versus placebo in 7,062 post-MI participants who were within 72 hours of the index percutaneous coronary intervention (PCI). We blinded participants, healthcare providers, research personnel, and outcome adjudicators to treatment allocation. The primary outcome for colchicine is the first occurrence of the composite of cardiovascular death, recurrent MI, stroke, or unplanned ischemia-driven revascularization. The coprimary outcomes for spironolactone are (1) the composite of the total numbers of cardiovascular death or new or worsening heart failure and (2) the first occurrence of the composite of cardiovascular death, new or worsening heart failure, recurrent MI or stroke. We finished recruitment with 7,062 participants from 104 centers in 14 countries on November 8, 2022, and plan to present the results in the fall of 2024. CONCLUSIONS: CLEAR SYNERGY is a large international randomized controlled trial that will inform the effects of low-dose colchicine and spironolactone in largely unselected post-MI patients who undergo PCI. (ClinicalTrials.gov Identifier: NCT03048825).
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OBJECTIVES: Accurate risk stratification of patients with stage II and III colorectal cancer (CRC) prior to treatment selection enables limited health resources to be efficiently allocated to patients who are likely to benefit from adjuvant chemotherapy. We aimed to investigate the cost-effectiveness of a recently developed deep learning-based prognostic method, Histotyping, from the perspective of the Norwegian healthcare system. METHODS: Two partitioned survival models were developed to assess the cost-effectiveness of Histotyping for two treatment cohorts: patients with CRC stage II and III. For each of the two cohorts, Histotyping was used for risk stratification to assign adjuvant chemotherapy and was compared with the standard of care (SOC) (adjuvant chemotherapy to all patients). Health outcomes measured in the model were quality-adjusted life years (QALYs) and life years (LYs) gained. Deterministic and probabilistic sensitivity analyses were performed to determine the impact of uncertainty. Scenario analyses were performed to assess the impact of the parameters with the greatest uncertainty. RESULTS: Risk-stratifying patients with CRC stage II and III using Histotyping was dominant (less costly and more effective) compared to SOC. In patients with CRC stage II, the net monetary benefit of Histotyping was 270,934 Norwegian kroners (NOK) (year of valuation is 2021), and the net health benefit of Histotyping was 0.99. In stage III, the net monetary benefit of Histotyping was 195,419 NOK, and the net health benefit of Histotyping was 0.71. CONCLUSIONS: Risk-stratifying patients with CRC using Histotyping prior to the administration of adjuvant chemotherapy is likely to be a cost-effective strategy in Norway.
Subject(s)
Colorectal Neoplasms , Cost-Benefit Analysis , Deep Learning , Quality-Adjusted Life Years , Humans , Colorectal Neoplasms/economics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/diagnosis , Norway , Prognosis , Chemotherapy, Adjuvant/economics , Neoplasm Staging , Risk Assessment , Biomarkers, Tumor , Male , FemaleABSTRACT
OBJECTIVES: This study aims to identify how real-world data (RWD) have been used in single technology appraisals (STAs) of cancer drugs by the National Institute for Health and Care Excellence (NICE). DESIGN: Cross-sectional study of NICE technology appraisals of cancer drugs for which guidance was issued between January 2011 and December 2021 (n=229). The appraisals were reviewed following a published protocol to extract the data about the use of RWD. The use of RWD was analysed by reviewing the specific ways in which RWD were used and by identifying different patterns of use. PRIMARY OUTCOME MEASURE: The number of appraisals where RWD are used in the economic modelling. RESULTS: Most appraisals used RWD in their economic models. The parametric use of RWD was commonly made in the economic models (76% of the included appraisals), whereas non-parametric use was less common (41%). Despite widespread use of RWD, there was no dominant pattern of use. Three sources of RWD (registries, administrative data, chart reviews) were found across the three important parts of the economic model (choice of comparators, overall survival and volume of treatment). CONCLUSIONS: NICE has had a long-standing interest in the use of RWD in STAs. A systematic review of oncology appraisals suggests that RWD have been widely used in diverse parts of the economic models. Between 2011 and 2021, parametric use was more commonly found in economic models than non-parametric use. Nonetheless, there was no clear pattern in the way these data were used. As each appraisal involves a different decision problem and the ability of RWD to provide the information required for the economic modelling varies, appraisals will continue to differ with respect to their use of RWD.
Subject(s)
Antineoplastic Agents , Technology Assessment, Biomedical , Humans , Cross-Sectional Studies , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/economics , United Kingdom , Models, Economic , Medical Oncology , Neoplasms/therapy , Cost-Benefit AnalysisABSTRACT
OBJECTIVE: This study examined the application, feasibility, and validity of supervised learning models for text classification in appraisals for rare disease treatments (RDTs) in relation to uncertainty, and analyzed differences between appraisals based on the classification results. METHODS: We analyzed appraisals for RDTs (n = 94) published by the National Institute for Health and Care Excellence (NICE) between January 2011 and May 2023. We used Naïve Bayes, Lasso, and Support Vector Machine models in a binary text classification task (classifying paragraphs as either referencing uncertainty in the evidence base or not). To illustrate the results, we tested hypotheses in relation to the appraisal guidance, advanced therapy medicinal product (ATMP) status, disease area, and age group. RESULTS: The best performing (Lasso) model achieved 83.6 percent classification accuracy (sensitivity = 74.4 percent, specificity = 92.6 percent). Paragraphs classified as referencing uncertainty were significantly more likely to arise in highly specialized technology (HST) appraisals compared to appraisals from the technology appraisal (TA) guidance (adjusted odds ratio = 1.44, 95 percent CI 1.09, 1.90, p = 0.004). There was no significant association between paragraphs classified as referencing uncertainty and appraisals for ATMPs, non-oncology RDTs, and RDTs indicated for children only or adults and children. These results were robust to the threshold value used for classifying paragraphs but were sensitive to the choice of classification model. CONCLUSION: Using supervised learning models for text classification in NICE appraisals for RDTs is feasible, but the results of downstream analyses may be sensitive to the choice of classification model.
Subject(s)
Rare Diseases , Technology Assessment, Biomedical , Adult , Child , Humans , Uncertainty , Rare Diseases/drug therapy , Bayes Theorem , Technology Assessment, Biomedical/methods , Cost-Benefit AnalysisABSTRACT
BACKGROUND: In ST-segment elevation myocardial infarction (STEMI), complete revascularization with percutaneous coronary intervention (PCI) reduces major cardiovascular events compared with culprit-lesion-only PCI. Whether age influences these results remains unknown. METHODS: COMPLETE was a multinational, randomized trial evaluating a strategy of staged complete revascularization, consisting of angiography-guided PCI of all suitable nonculprit lesions, versus a strategy of culprit-lesion-only PCI. In this prespecified subgroup analysis, treatment effect according to age (≥65 years vs <65 years) was determined for the first coprimary outcome of cardiovascular (CV) death or new myocardial infarction (MI) and the second coprimary outcome of CV death, new MI, or ischemia-driven revascularization (IDR). Median follow-up was 35.8 months (interquartile range [IQR]: 27.6-44.3 months). RESULTS: Of 4,041 patients randomized in COMPLETE, 1,613 were aged ≥ 65 years (39.9%). Higher event rates were observed for both coprimary outcomes in patients aged ≥ 65 years comparted with those aged < 65 years (11.2% vs 7.9%, HR 1.49, 95% CI 1.22-1.83; 14.4% vs 11.8%, HR 1.28, 95% CI 1.07-1.52, respectively). Complete revascularization reduced the first coprimary outcome in patients ≥ 65 years (9.7% vs 12.5%, HR 0.77; 95% CI, 0.58-1.04) and < 65 years (6.7% vs 9.1%, HR 0.72; 95% CI, 0.54-0.96)(interaction P = .74). The second coprimary outcome was reduced in those ≥ 65 years (HR 0.56, 95% CI, 0.43-0.74) and < 65 years (HR 0.48, 95% CI, 0.37-0.61 (interaction P = .37). A sensitivity analysis was performed with consistent results demonstrated using a 75-year threshold (albeit attenuated). CONCLUSIONS: In patients with STEMI and multivessel CAD, complete revascularization compared with culprit-lesion-only PCI reduced major cardiovascular events regardless of patient age and could be considered as a revascularization strategy in older adults.
Subject(s)
Coronary Artery Disease , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Aged , Humans , Coronary Artery Disease/therapy , Myocardial Infarction/surgery , Myocardial Infarction/etiology , Myocardial Revascularization/methods , Percutaneous Coronary Intervention/methods , ST Elevation Myocardial Infarction/therapy , Treatment Outcome , Middle AgedABSTRACT
BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is associated with high morbidity and mortality worldwide. Simple electrocardiogram (ECG) tools, including ST-segment resolution (STR) have been developed to identify high-risk STEMI patients after primary percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: We evaluated the prognostic impact of STR in the ECG lead with maximal baseline ST-segment elevation (STE) 30-60 minutes after primary PCI in 7,654 STEMI patients included in the TOTAL trial. Incomplete or no STR was defined as < 70% STR and complete STR as ≥ 70% STR. The primary outcome was the composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock, or new or worsening New York Heart Association (NYHA) class IV heart failure at 1-year follow-up. RESULTS: Of 7,654 patients, 42.9% had incomplete or no STR and 57.1% had complete STR. The primary outcome occurred in 341 patients (10.4%) in the incomplete or no STR group and in 234 patients (5.4%) in the complete STR group. In Cox regression analysis, adjusted hazard ratio for STR < 70% to predict the primary outcome was 1.56 (95% confidence interval 1.32-1.89; P < .001) (model adjusted for all baseline comorbidities, clinical status during hospitalization, angiographic findings, and procedural techniques). CONCLUSION: In a large international study of STEMI patients, STR < 70% 30-60 minutes post primary PCI in the ECG lead with the greatest STE at admission was associated with an increased rate of the composite of cardiovascular death, recurrent MI, cardiogenic shock, or new or worsening NYHA class IV heart failure at 1-year follow-up. Clinicians should pay attention to this simple ECG finding.
Subject(s)
Heart Failure , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Prognosis , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/surgery , ST Elevation Myocardial Infarction/etiology , Percutaneous Coronary Intervention/adverse effects , Shock, Cardiogenic/etiology , Myocardial Infarction/diagnosis , Myocardial Infarction/surgery , Electrocardiography , Heart Failure/etiology , Treatment OutcomeABSTRACT
BACKGROUND: In the COMPLETE trial (Complete Versus Culprit-Only Revascularization to Treat Multivessel Disease After Early PCI for STEMI), a strategy of complete revascularization reduced the risk of major cardiovascular events compared with culprit-lesion-only percutaneous coronary intervention in patients presenting with ST-segment-elevation myocardial infarction (STEMI) and multivessel coronary artery disease. Patients with diabetes have a worse prognosis following STEMI. We evaluated the consistency of the effects of complete revascularization in patients with and without diabetes. METHODS: The COMPLETE trial randomized a strategy of complete revascularization, consisting of angiography-guided percutaneous coronary intervention of all suitable nonculprit lesions, versus a strategy of culprit-lesion-only percutaneous coronary intervention (guideline-directed medical therapy alone). In prespecified analyses, treatment effects were determined in patients with and without diabetes on the first coprimary outcome of cardiovascular death or new myocardial infarction and the second coprimary outcome of cardiovascular death, new myocardial infarction, or ischemia-driven revascularization. Interaction P values were calculated to evaluate whether there was a differential treatment effect in patients with and without diabetes. RESULTS: Of the 4041 patients enrolled in the COMPLETE trial, 787 patients (19.5%) had diabetes. The median HbA1c (glycated hemoglobin) was 7.7% in the diabetes group and 5.7% in the nondiabetes group. Complete revascularization consistently reduced the first coprimary outcome in patients with diabetes (hazard ratio, 0.87 [95% CI, 0.59-1.29]) and without diabetes (hazard ratio, 0.70 [95% CI, 0.55-0.90]), with no evidence of a differential treatment effect (interaction P=0.36). Similarly, for the second coprimary outcome, no differential treatment effect (interaction P=0.27) of complete revascularization was found in patients with diabetes (hazard ratio, 0.61 [95% CI, 0.43-0.87]) and without diabetes (hazard ratio, 0.48 [95% CI, 0.39-0.60]). CONCLUSIONS: Among patients presenting with STEMI and multivessel disease, the benefit of complete revascularization over a culprit-lesion-only percutaneous coronary intervention strategy was consistent regardless of the presence or absence of diabetes.
Subject(s)
Coronary Artery Disease , Diabetes Mellitus , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Diabetes Mellitus/diagnosis , Myocardial Infarction/therapy , Percutaneous Coronary Intervention/adverse effects , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , Treatment OutcomeABSTRACT
OBJECTIVES: The National Institute for Health and Care Excellence (NICE) recently completed a review of its methods for health technology assessment, involving a 2-stage public consultation. We appraise proposed methodological changes and analyze key decisions. METHODS: We categorize all changes proposed in the first consultation as "critical," "moderate" or "limited" updates, considering the importance of the topic and the degree of change or the level of reinforcement. Proposals were followed through the review process, for their inclusion, exclusion, or amendment in the second consultation and the new manual. RESULTS: The end-of-life value modifier was replaced with a new "disease severity" modifier and other potential modifiers were rejected. The usefulness of a comprehensive evidence base was emphasized, clarifying when nonrandomized studies can be used, with further guidance on "real-world" evidence developed separately. A greater degree of uncertainty was accepted in circumstances when evidence generation raised challenges, in particular for children, rare diseases, and innovative technologies. For some topics, such as health inequality, discounting, unrelated healthcare costs, and value of information, significant changes were possibly warranted, but NICE decided not to make any revisions at present. CONCLUSION: Most of the changes to NICE's health technology assessment methods are appropriate and modest in impact. Nevertheless, some decisions were not well justified and further research is needed on several topics, including investigation of societal preferences. Ultimately, NICE's role of protecting National Health Services resources for valuable interventions that can contribute toward improving overall population health must be safeguarded, without accepting weaker evidence.
Subject(s)
Health Status Disparities , Technology Assessment, Biomedical , Child , Humans , Cost-Benefit Analysis , Uncertainty , United KingdomABSTRACT
BACKGROUND: The prognostic significance of Q waves and T-wave inversions (TWI) combined and separately in STEMI patients undergoing primary PCI has not been well established in previous studies. METHODS: We included 7,831 patients from the TOTAL trial and divided the patients into categories based on Q waves and TWIs in the presenting ECG. The primary outcome was a composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock or new or worsening NYHA class IV heart failure within one year. The study evaluated the effect of Q waves and TWI on the risk of primary outcome and all-cause death, and whether patient benefit of aspiration thrombectomy differed between the ECG categories. RESULTS: Patients with Q+TWI+ (Q wave and TWI) pattern had higher risk of primary outcome compared to patients with Q-TWI- pattern [33 (10.5%) vs. 221 (4.2%); adjusted hazard ratio (aHR) 2.10; 95% CI, 1.45-3.04; p<0.001] within 40-days' period. When analyzed separately, patients with Q waves had a higher risk for the primary outcome compared to patients with no Q waves in the first 40 days [aHR 1.80; 95% CI, 1.48-2.19; p<0.001] but there was no additive risk after 40 days. Patients with TWI had a higher risk for primary outcome only after 40 days when compared to patients with no TWI [aHR 1.63; 95% CI, 1.04-2.55; p=0.033]. There was a trend towards a benefit of thrombectomy in patients with the Q+TWI+ pattern. CONCLUSIONS: Q waves and TWI combined (Q+TWI+ pattern) in the presenting ECG is associated with unfavourable outcome within 40-days. Q waves tend to affect short-term outcome, while TWI has more effect on long-term outcome.
Subject(s)
Heart Failure , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Prognosis , ST Elevation Myocardial Infarction/diagnosis , ElectrocardiographyABSTRACT
BACKGROUND: The optimal strategy to prevent no-reflow in ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI) is unknown. AIMS: We aimed to examine the effect of thrombectomy on the outcome of no-reflow in key subgroups and the adverse clinical outcomes associated with no-reflow. METHODS: We performed a post hoc analysis of the TOTAL Trial, a randomised trial of 10,732 patients comparing thrombectomy versus PCI alone. This analysis utilised the angiographic data of 1,800 randomly selected patients. RESULTS: No-reflow was diagnosed in 196 of 1,800 eligible patients (10.9%). No-reflow occurred in 95/891 (10.7%) patients randomised to thrombectomy compared with 101/909 (11.1%) in the PCI-alone arm (odds ratio [OR] 0.95, 95% confidence interval [CI]: 0.71-1.28; p-value=0.76). In the subgroup of patients who underwent direct stenting, those randomised to thrombectomy compared with PCI alone experienced less no-reflow (19/371 [5.1%] vs 21/216 [9.7%], OR 0.50, 95% CI: 0.26-0.96). In patients who did not undergo direct stenting, there was no difference between the groups (64/504 [12.7%] vs 75/686 [10.9%)], OR 1.18, 95% CI: 0.82-1.69; interaction p-value=0.02). No-reflow patients had a significantly increased risk of experiencing the primary composite outcome (cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA Class IV heart failure) at 1 year (adjusted hazard ratio 1.70, 95% CI: 1.13-2.56; p-value=0.01). CONCLUSIONS: In patients with STEMI treated by PCI, thrombectomy did not reduce no-reflow in all patients but may be synergistic with direct stenting. No-reflow is associated with increased adverse clinical outcomes.
Subject(s)
Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/surgery , Myocardial Infarction/therapy , Percutaneous Coronary Intervention/adverse effects , Treatment Outcome , Shock, Cardiogenic/etiology , Coronary Angiography/adverse effectsABSTRACT
BACKGROUND: Mortality remains high in patients with ST-segment-elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS), and early reperfusion has been shown to improve outcomes. We analyzed the association between first medical contact (FMC)-to-percutaneous coronary angiography time with mortality and major adverse cardiovascular events among patients with STEMI with and without CS. METHODS: We performed a retrospective analysis of the Vancouver Coastal Health Authority STEMI registry, including all patients with STEMI who received primary percutaneous coronary angiography between January 1, 2010, and December 31, 2020, and stratified them by presence or absence of CS at hospital arrival. The primary outcome was in-hospital mortality, the secondary outcome was in-hospital major adverse cardiovascular events, defined as a composite of the first occurrence of mortality, cardiac arrest, heart failure, intracerebral hemorrhage, cerebrovascular accident, or reinfarction. Mixed effects logistic regression with restricted cubic splines was used to estimate the relationships between FMC-to-device time and the outcomes in the CS and non-CS groups. RESULTS: 2929 patients were included, 9.4% (n=275) had CS. Median FMC-to-device time was 113.5 (interquartile range, 93.0-145.0) and 103.0 (interquartile range, 85.0-130.0) minutes for patients with CS and without CS, respectively. More patients with CS had FMC-to-device times above guideline recommendations (76.6% versus 54.1%, P<0.001). Between 60 and 90 minutes, for each 10-minute increase in FMC-to-device time, absolute mortality for patients with CS increased by 4% to 7%, whereas for patients without CS, it increased by <0.5%. CONCLUSIONS: Among patients with STEMI undergoing primary percutaneous coronary angiography, reperfusion delays among patients with CS are associated with significantly worse outcomes. Strategies to reduce FMC-to-device times for patients with STEMI presenting with CS are required.
Subject(s)
Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/etiology , Shock, Cardiogenic/therapy , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , Retrospective Studies , Risk Factors , Treatment Outcome , Reperfusion , Percutaneous Coronary Intervention/adverse effects , Hospital MortalityABSTRACT
Background: The Vancouver Coastal Health (VCH) ST-elevation myocardial infarction (STEMI) program aimed to increase access to primary percutaneous coronary intervention (PPCI) and reduce first-medical-contact-to-device times (FMC-DTs). We evaluated the long-term program impact on PPCI access and FMC-DT, and overall and reperfusion-specific in-hospital mortality. Methods: We analyzed all VCH STEMI patients between June 2007 and November 2019. The primary outcome was the proportion of patients receiving PPCI over 4 program implementation phases over 12 years. We also evaluated overall changes in median FMC-DT and the proportion of patients achieving guideline-mandated FMC-DT, in addition to overall and reperfusion-specific in-hospital mortality. Results: A total of 3138 of 4305 VCH STEMI patients were treated with PPCI. PPCI rates increased from 40.2% to 78.7% from 2007 to 2019 (P < 0.001). From phase 1 to 4, median FMC-DT improved from 118 to 93 minutes (percutaneous coronary intervention [PCI]-capable hospitals, P < 0.001) and from 174 to 118 minutes (non-PCI-capable hospitals, P < 0.001), with a concomitant increase in those achieving guideline-mandated FMC-DT (35.5% to 66.1%, P < 0.001). Overall in-hospital mortality was 9.0% (P = 0.20 across phases), with mortality differing significantly by reperfusion strategy (4.0% fibrinolysis, 5.7% PPCI, 30.6% no reperfusion therapy, P < 0.001). Mortality significantly decreased from phase 1 to phase 4 at non-PCI-capable centres (9.6% to 3.9%, P = 0.022) but not at PCI-capable centres (8.7% vs 9.9%, P = 0.27). Conclusions: A regional STEMI program increased the proportion of patients who received PPCI and improved reperfusion times over 12 years. Although no statistically significant decrease occurred in overall regional mortality incidence, mortality incidence was decreased for patients presenting to non-PCI-capable centres.
Contexte: Le programme sur l'infarctus du myocarde avec élévation du segment ST (STEMI) de la régie régionale de santé Vancouver Coastal Health (VCH) visait à améliorer l'accès à des interventions coronariennes percutanées primaires (ICPP) et à réduire le temps entre le premier contact médical et l'intervention. Nous avons évalué les effets à long terme du programme sur l'accès aux ICPP, sur le temps entre le premier contact médical et l'intervention, ainsi que sur le taux global de mortalité hospitalière et le taux de mortalité hospitalière lié à la reperfusion. Méthodologie: Nous avons analysé les cas de tous les patients admis au programme STEMI de la VCH entre juin 2007 et novembre 2019. Le critère d'évaluation principal était la proportion de patients recevant une ICPP pendant les 4 phases du programme, qui se sont étalées sur 12 ans. Nous avons aussi évalué la variation totale du temps médian entre le premier contact médical et l'intervention, et de la proportion de patients chez qui le temps recommandé entre le premier contact médical et l'intervention a été respecté ainsi que la variation du taux global de mortalité hospitalière et du taux de mortalité hospitalière lié à la reperfusion. Résultats: Au total, 3138 des 4305 patients du programme STEMI de la VCH ont été traités par une ICPP. Les taux d'ICPP sont passés de 40,2 % à 78,7 % entre 2007 et 2019 (p < 0,001). De la phase 1 à la phase 4 du programme, le temps médian entre le premier contact médical et l'intervention s'est amélioré, passant de 118 minutes à 93 minutes (hôpitaux en mesure d'effectuer une intervention coronarienne percutanée [ICP]; p < 0,001) et de 174 à 118 minutes (hôpitaux n'étant pas en mesure d'effectuer une ICP; p < 0,001), avec une augmentation du nombre de personnes pour qui le temps recommandé entre le premier contact médical et l'intervention a été respecté (35,5 % à 66,1 %; p < 0,001). Le taux global de mortalité hospitalière était de 9,0 % (p = 0,20 pour toutes les phases), et le taux de mortalité hospitalière lié à la reperfusion différait de manière significative selon la stratégie adoptée (fibrinolyse : 4,0 %; ICPP : 5,7 %; aucune reperfusion : 30,6 %; p < 0,001). Le taux de mortalité a diminué de manière significative entre la phase 1 et la phase 4 dans les centres qui n'étaient pas en mesure d'effectuer une ICP (9,6 % à 3,9 %; p = 0,022), mais pas dans les centres en mesure d'effectuer une ICP (8,7 % c. 9,9 %; p = 0,27). Conclusions: Le programme STEMI régional a permis d'augmenter la proportion de patients qui ont reçu une ICPP et d'améliorer les temps de reperfusion sur 12 ans. Bien qu'aucune diminution statistiquement significative n'ait été observée quant au taux global de mortalité dans la région, le taux de mortalité a diminué chez les patients se présentant dans un centre qui n'était pas en mesure d'effectuer une ICP.
ABSTRACT
INTRODUCTION: The National Institute for Health and Care Excellence (NICE) in England has appraised three treatments for spinal muscular atrophy (SMA), namely, nusinersen, onasemnogene abeparvovec, and risdiplam. As rare disease treatments (RDTs) commonly face challenges in health technology assessment (HTA) processes due to their clinical and economic uncertainties, an in-depth review of these appraisals is useful to enable a deeper understanding of economic modeling considerations for SMA. AREAS COVERED: This review is a detailed analysis of NICE appraisals for SMA and aims to compare the economic modeling evidence from the three RDTs. This is done by examining differences and similarities and by discussing critical outstanding issues across the economic evaluations of the appraisals. EXPERT OPINION: This article aims to contribute to the development of evidence that can be used as guidance to inform resource allocation decisions for RDTs for SMA, but also to be a resource about approaches for the generation, analysis and interpretation of economic modeling evidence for RDTs more broadly.
Subject(s)
Muscular Atrophy, Spinal , Rare Diseases , Humans , Rare Diseases/drug therapy , Models, Economic , Muscular Atrophy, Spinal/drug therapy , Cost-Benefit Analysis , EnglandABSTRACT
BACKGROUND: India contributes 15% of the total global maternal mortality burden. An increasing proportion of these deaths are due to Pregnancy Induced Hypertension (PIH), Gestational Diabetes Mellitus (GDM), and anaemia. This study aims to evaluate the effectiveness of a tablet-based electronic decision-support system (EDSS) to enhance routine antenatal care (ANC) and improve the screening and management of PIH, GDM, and anaemia in pregnancy in primary healthcare facilities of Telangana, India. The EDSS will work at two levels of primary health facilities and is customized for three cadres of healthcare providers - Auxiliary Nurse Midwifes (ANMs), staff nurses, and physicians (Medical Officers). METHODS: This will be a cluster randomized controlled trial involving 66 clusters with a total of 1320 women in both the intervention and control arms. Each cluster will include three health facilities-one Primary Health Centre (PHC) and two linked sub-centers (SC). In the facilities under the intervention arm, ANMs, staff nurses, and Medical Officers will use the EDSS while providing ANC for all pregnant women. Facilities in the control arm will continue to provide ANC services using the existing standard of care in Telangana. The primary outcome is ANC quality, measured as provision of a composite of four selected ANC components (measurement of blood pressure, blood glucose, hemoglobin levels, and conducting a urinary dipstick test) by the healthcare providers per visit, observed over two visits. Trained field research staff will collect outcome data via an observation checklist. DISCUSSION: To our knowledge, this is the first trial in India to evaluate an EDSS, targeted to enhance the quality of ANC and improve the screening and management of PIH, GDM, and anaemia, for multiple levels of health facilities and several cadres of healthcare providers. If effective, insights from the trial on the feasibility and cost of implementing the EDSS can inform potential national scale-up. Lessons learned from this trial will also inform recommendations for designing and upscaling similar mHealth interventions in other low and middle-income countries. CLINICALTRIALS: gov, NCT03700034, registered 9 Oct 2018, https://www. CLINICALTRIALS: gov/ct2/show/NCT03700034 CTRI, CTRI/2019/01/016857, registered on 3 Mar 2019, http://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=28627&EncHid=&modid=&compid=%27,%2728627det%27.
Subject(s)
Diabetes, Gestational , Prenatal Care , Female , Pregnancy , Humans , Prenatal Care/methods , Pregnant Women , Primary Health Care , India , Randomized Controlled Trials as TopicABSTRACT
HIGHLIGHTS: This article compares the relative preferences from stated preference (SP) questions requiring ordered categorical versus discrete choice responses. The approaches were contrasted for blood donation service characteristics that offer opportunities to donate blood.The estimates of relative preferences for alternative blood donation service characteristics were similar between the 2 forms of SP approach.This study illustrates how SP survey questions can be formulated to provide responses on an ordered categorical scale and to estimate marginal rates of substitution between different attributes, which can be compared with those derived from discrete choice experiment (DCE) choices.The article highlights the potential value of considering alternative choice framings rather than relying solely on DCEs.
Subject(s)
Blood Donors , Choice Behavior , Humans , Surveys and Questionnaires , Patient PreferenceABSTRACT
OBJECTIVES: The Cancer Drugs Fund (CDF) in England uses managed access agreements to facilitate additional data collection to address uncertainties identified in the appraisals of new drugs. This study reviews the uncertainties highlighted in the original appraisals where recommendations "to use within the CDF" were made and how additional data were used to address these uncertainties in the CDF review appraisals where final decisions on routine commissioning were made. METHODS: The first 24 drugs exiting the 2016 CDF were included in this review. The information about uncertainty and the use of newly collected data were extracted from the original appraisals and the CDF review appraisals. The additional data used in the CDF review appraisals, distinguishing between clinical trial data and real-world data (RWD), were reviewed to assess the extent to which the additional data were able to reduce the original uncertainties. RESULTS: The recommendation that the drug be routinely commissioned was made in 87.5% of re-appraisals. Uncertainty stemming from immaturity of the survival data in clinical trials was frequently found in appraisals. Later follow-up of clinical trials was used to address this uncertainty, whereas limited use was made of RWD. The Systemic Anti-Cancer Therapy (SACT) dataset is the most frequently used source of RWD. SACT data were mostly used in review appraisals to support the clinical outcomes based on later follow-up of trial participants and to inform modelling of subsequent treatments or treatment duration. CONCLUSIONS: While additionally collected RWD attracted attention when the 2016 CDF was introduced, RWD have not been widely used in CDF review appraisals and (to date) have done little to reduce uncertainty. Experience with these appraisals has highlighted the importance of longer follow-up of clinical trials and the relatively limited role of RWD, in general, and of SACT data in particular.