Retrospective observational cohort study on innovation in oncology and progress in survival: how far have we gotten in the two decades of treating patients with advanced non-small cell lung cancer as a single population?

We assessed the impact of new antineoplastic agents on the overall survival (OS) of advanced non-small cell lung cancer (aNSCLC) patients followed up until 2012. Multivariate regression models were run for OS (outcome) and four proxies for innovation (exposure): Index (InnovInd, for SEER-Research data 1973–2012) and three levels of aggregation of Mean Medication Vintage, i.e. Overall (MMVOverall), using data aggregated at the State Level (MMVState), and using patient-level data (MMVPatient) using data from the US captured in SEER-Medicare 1991–2012. We derived Hazard ratios (HR) from Royston-Parmar models and odds ratios (OR) from a logistic regression on 1-year OS. Including 164,704 patients (median age 72 years, 56.8% stage IV, 61.8% with no comorbidities, 37.8% with adenocarcinoma, 22.9% with squamous-cell, 6.1% were censored). One-year OS improved from 0.22 in 1973 to 0.39 in 2012, in correlation with InnovInd (r = 0.97). Ten new NSCLC drugs were approved and 28 more used off-label. Regression-models results indicate that therapeutic innovation only marginally reduced the risk of dying (HROverall = 0.98 [0.98–0.98], HRMMV-Patient = 0.98 [0.97–0.98], and HRMMV-State = 0.98 [0.98–0.98], and slightly improved 1-year survival (ORMMV-Overall = 1.05 95%CI [1.04–1.05]). These results were validated with data from the Swedish National Health Data registers. Until 2013, aNSCLC patients were treated undifferentiated and the introduction of innovative therapies had statistically significant, albeit modest, effects on survival. Most treatments used off-guidelines highlight the high unmet need; however new advancements in treatment may further improve survival

Real-World Evidence in Healthcare Decision Making : Global trends and case studies from Latin America

Objectives: Real-world evidence (RWE) is increasingly used to inform health technology assessments (HTAs) for resource allocation, which are valuable tools for emerging economies such as in America. However, the characteristics and uses in South America are unknown. This study aims to identify sources, characteristics and uses of RWE in Argentina, Brazil, Colombia and Chile, and evaluate the context-specific challenges. The implications for future regulation and responsible management of RWE in the region are also considered. Methods: A systematic literature review, database mapping, and targeted grey literature search were conducted to identify the sources and characteristics of RWE. Findings were validated by key opinion leaders attending workshops in four South American countries. Results: A database mapping exercise revealed 407 unique databases. Geographic scope, database type, population and outcomes captured were reported. Characteristics of National Health Information Systems show efforts to collect interoperable data from service providers, insurers and government agencies, but that initiatives are hampered by fragmentation, lack of stewardship and resources. RWE is mainly used in South America for pharmacovigilance and as pure academic research, but less so for HTA decision-making or pricing negotiations and not at all to inform early access schemes. Conclusions: The quality of data collected in real-world in the case-study countries varies and RWE is not consistently used in healthcare decision-making. Authors recommend that future studies monitor the impact of digitalisation, and the potential effects of access to RWE on the quality of patient care

Impact of COVID-19 on immunocompromised populations during the Omicron era:insights from the observational population-based INFORM study

Background Immunocompromised individuals are not optimally protected by COVID-19 vaccines and potentially require additional preventive interventions to mitigate the risk of severe COVID-19. We aimed to characterise and describe the risk of severe COVID-19 across immunocompromised groups as the pandemic began to transition to an endemic phase. Methods COVID-19-related hospitalisations, intensive care unit (ICU) admissions, and deaths (01/01/2022-31/12/2022) were compared among different groups of immunocompromised individuals vs the general population, using a retrospective cohort design and electronic health data from a random 25% sample of the English population aged ≥12 years (Registration number: ISRCTN53375662). Findings Overall, immunocompromised individuals accounted for 3.9% of the study population, but 22% (4585/20,910) of COVID-19 hospitalisations, 28% (125/440) of COVID-19 ICU admissions, and 24% (1145/4810) of COVID-19 deaths in 2022. Restricting to those vaccinated with ≥3 doses of COVID-19 vaccine (∼84% of immunocompromised and 51% of the general population), all immunocompromised groups remained at increased risk of severe COVID-19 outcomes, with adjusted incidence rate ratios (aIRR) for hospitalisation ranging from 1.3 to 13.1. At highest risk for COVID-19 hospitalisation were individuals with: solid organ transplant (aIRR 13.1, 95% confidence interval [95% CI] 11.2–15.3), moderate to severe primary immunodeficiency (aIRR 9.7, 95% CI 6.3–14.9), stem cell transplant (aIRR 11.0, 95% CI 6.8–17.6), and recent treatment for haematological malignancy (aIRR 10.6, 95% CI 9.5–11.9). Results were similar for COVID-19 ICU admissions and deaths. Interpretation Immunocompromised individuals continue to be impacted disproportionately by COVID-19 and have an urgent need for additional preventive measures beyond current vaccination programmes. These data can help determine the immunocompromised groups for which targeted prevention strategies may have the highest impact. Funding This study was funded by AstraZeneca UK

Real-world outcomes in oncology : assessing the value of rewardable innovation

Recent years have seen a remarkable expansion of therapeutic options available for many forms of cancer. Evidence for the efficacy of these treatments have mainly come from randomized controlled trials, however questions often remain regarding the actual use, effectiveness and value of innovative therapies when used under the circumstances of routine clinical practice. In this thesis, we aim to assess the value and contribution of new oncology treatments for common cancers (lung, prostate, and breast) in early and/or advanced stages, based on data generated under ‘real world’ conditions in routine care. In paper I, we conducted a systematic review and mapping of the availability of real-world data (RWD) and use of evidence generated from such data (RWE), with focus on four South American countries. Findings were validated through workshops with regional experts. We identified 407 unique databases, and reported details included geographic scope, database type, population, and outcomes captured. The quality of RWD varied across countries, and we found that RWE was not consistently used to inform health care decision making. The main use of RWE was for pharmacovigilance studies, and to lesser extent for health technology assessment and for pricing decisions. In Paper II, we investigated therapeutic innovation in the care of patients diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) in the US between 1991 and 2012. Based on data from SEER-Medicare, we examined the association between the degree of innovation (measured as an innovation index or mean medication vintage) and overall survival. Results indicated that therapeutic innovation was associated with only a slightly improved 1-year survival (odds ratio (OR): 1.05 [95% confidence interval (CI): 1.04–1.05]). Paper III described the occurrence of comorbidities in patients with NSCLC based on national registry data from Sweden during 2006–2013. Comorbidities that may be associated with prognosis, disease progression or share risk factors with NSCLC were identified and assessed before and after the NSCLC diagnosis. 3,834 NSCLC patients were compared with 15,332 matched controls. The comorbidity prevalence at baseline was significantly higher in NSCLC patients with an OR of 2.44 (95% CI: 2.27–2.63), and the incidence rate ratio (IRR) of newly diagnosed comorbidities during the year after diagnosis was 32.5 (95% CI: 31.0– 34.2). In Paper IV, we described treatment patterns in patients with metastatic castration-resistant prostate cancer (mCRPC) based on health insurance data from Germany for the period January 2013 to December 2015. 447 patients were continuously enrolled for 12 months before being started on treatment with abiraterone, cabazitaxel, docetaxel, or enzalutamide. Over 70 distinct treatment pathways were identified. Abiraterone was the most commonly prescribed while cabazitaxel was the least commonly prescribed therapy. Abiraterone patients also had longest treatment duration. Paper V aimed to estimate the life-cycle value of trastuzumab for early (EBC) and metastatic (MBC) breast cancer in Sweden. Aggregate data on trastuzumab-treated patients from national registries was combined with data from RCTs and economic studies in Markov models to estimate overall survival, lifetime costs, and quality-adjusted life years (QALYs). Over 15,000 patients have been treated with trastuzumab, generating 25,844 life-years and 13,437 QALYs gained, at a monetary value of 8.7 trillion SEK. In conclusion, based on RWD, we found that innovative oncology therapies have delivered value in the care of patients with advanced or metastatic NSCLC, metastatic CRPC, and early or metastatic HER2+ BC, and other based on RWE over the past decades. However, this was not true for all new medicines introduced and the benefit derived from their use was not uniform. RWE can support value assessment of innovation, mainly in dimensions beyond therapeutic benefit

Prevalence, Characteristics, Management and Outcomes of Patients with Heart Failure with Preserved, Mildly Reduced, and Reduced Ejection Fraction in Spain

Objective: To estimate the prevalence, incidence, and describe the characteristics and management of patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF) in Spain. Methods: Adults with ≥1 inpatient or outpatient HF diagnosis between 1 January 2013 and 30 September 2019 were identified through the BIG-PAC database. Annual incidence and prevalence by EF phenotype were estimated. Characteristics by EF phenotype were described in the 2016 and 2019 HF prevalent cohorts and outcomes in the 2016 HF prevalent cohort. Results: Overall, HF incidence and prevalence were 0.32/100 person-years and 2.34%, respectively, but increased every year. In 2019, 49.3% had HFrEF, 38.1% had HFpEF, and 4.3% had HFmrEF (in 8.3%, EF was not available). Compared with HFrEF, patients with HFpEF were largely female, older, and had more atrial fibrillation but less atherosclerotic cardiovascular disease. Among patients with HFrEF, 76.3% were taking renin-angiotensin system inhibitors, 69.5% beta-blockers, 36.8% aldosterone antagonists, 12.5% sacubitril/valsartan and 6.7% SGLT2 inhibitors. Patients with HFpEF and HFmrEF took fewer HF drugs compared to HFrEF. Overall, the event rates of HF hospitalization were 231.6/1000 person-years, which is more common in HFrEF patients. No clinically relevant differences were found in patients with HFpEF, regardless EF (50- < 60% vs. ≥60%). Conclusions: >2% of patients have HF, of which around 50% have HFrEF and 40% have HFpEF. The prevalence of HF is increasing over time. Clinical characteristics by EF phenotype are consistent with previous studies. The risk of outcomes, particularly HF hospitalization, remains high, likely related to insufficient HF treatment

Evolution of economic burden of heart failure by ejection fraction in newly diagnosed patients in Spain

Abstract Objective To describe healthcare resource utilization (HCRU) and costs, in patients with newly diagnosed heart failure (HF) according to ejection fraction (EF) in Spain. Methods Retrospective cohort study that analyzed anonymized, integrated and computerised medical records in Spain. Patients with ≥ 1 new HF diagnosis between January 2013 and September 2019 were included and followed-up during a 4-year period. Rates per 100 person-years of HCRU and costs were estimated. Results Nineteen thousand nine hundred sixty-one patients were included, of whom 43.5%, 26.3%, 5.1% and 25.1% had HF with reduced, preserved, mildly reduced and unknown EF, respectively. From year 1 to 4, HF rates of outpatient visits decreased from 1149.5 (95% CI 1140.8–1159.3) to 765.5 (95% CI 745.9–784.5) and hospitalizations from 61.7 (95% CI 60.9–62.7) to 15.7(14.7–16.7) per 100 person-years. The majority of HF-related healthcare resource costs per patient were due to hospitalizations (year 1–4: 63.3–38.2%), followed by indirect costs (year 1–4: 12.2–29.0%), pharmacy (year 1–4: 11.9–19.9%), and outpatient care (year 1–4: 12.6–12.9%). Mean (SD) per patient HF-related costs decreased from 2509.6 (3518.5) to 1234.6 (1534.1) Euros (50% cost reduction). At baseline, 70.1% were taking beta-blockers, 56.3% renin-angiotensin system inhibitors, 11.8% mineralocorticoid receptor antagonists and 8.9% SGLT2 inhibitors. At 12 months, these numbers were 72.3%, 65.4%, 18.9% and 9.8%, respectively. Conclusions Although the economic burden of HF decreased over time since diagnosis, it is still substantial. This reduction could be partially related to a survival bias (sick patients died early), but also to a better HF management. Despite that, there is still much room for improvement

Additional file 1 of Healthcare resource utilization and costs among patients with heart failure with preserved, mildly reduced, and reduced ejection fraction in Spain

Additional file 1: Supplementary Table 1. Definition of the variables (codes)