Real-world data for marginal zone lymphoma patients in the French REALYSA cohort: The REALMA study.

Marginal Zone Lymphoma (MZL) comprises three subtypes: extranodal MZL (EMZL), splenic MZL (SMZL) and nodal MZL (NMZL). Since clinical trials have limited representativeness, there is a need for real-world data (RWD) evidence in MZL. Real-world data in Lymphoma and survival in Adults (REALYSA) is a prospective multicentric French cohort of newly diagnosed lymphoma patients. This study consists of the first abstraction of MZL patients prospectively included in REALYSA between 12/2018 and 01/2021 with at least 1 year of follow-up. It provides a landscape description of clinical characteristics, initial workup, quality of life and first-line therapy performed in routine practice. Among 207 included patients, 122 presented with EMZL, 51 with SMZL and 34 with NMZL. At baseline, median age was 67 years (range 28-96), and patients reported a favorable global health status (75/100 (IQR 58,83)) - which was higher in NMZL and lower in SMZL patients (p = 0.006). 18FDG-PET/CT was frequently performed at initial workup (EMZL 72%, SMZL 73%, NMZL 85%). Active surveillance was the initial management for 58 (28%) patients. The most prescribed therapies were rituximab-chlorambucil in the EMZL population (30%), rituximab monotherapy in the SMZL population (37%) and R-CHOP (24%)/bendamustine-rituximab (15%) in the NMZL population. At end of first line, overall response rate was 93% among treated patients with 75% of complete response. This French nationwide study provided for the first time prospective RWD on clinical characteristics, initial management and treatment response of MZL patients.

Long-term treatment results of pembrolizumab monotherapy: reconsideration of immune checkpoint inhibitor monotherapy.

Objective: The extended outcomes of the KEYNOTE-024 study demonstrated a favorable 5-year overall survival (OS) rate of 31.9%. The present study investigated the outcomes of pembrolizumab monotherapy for advanced or recurrent non-small cell lung cancer (NSCLC) at our institution. Patient: The long-term outcomes of 102 patients with advanced or recurrent NSCLC treated with pembrolizumab monotherapy between March 2017 and December 2022 were retrospectively assessed. Results: This study included a total of 102 patients [mean age: 72 ± 9.6 years (range: 41-91 years), male/female=77/25; performance status (PS; 0, 1, 2, 3, 4)=49/38/15/0/0; smokers=91 (89%), non-squamous cell carcinoma/squamous cell carcinoma=66/36, PD-L1 tumor proportion score (TPS) ≥50%/1-49%=80/22, positive for EGFR mutation=5, advanced/postoperative recurrence=51/51, treatment line: first/second or later=81/21, treatment courses: median 8 (range: 1-39), objective response rate/disease control rate=44%/55%, immune-related adverse events (irAEs): 47, 5-year OS=34%]. On univariate analysis, PS, PD-L1 TPS, and irAEs were significant prognostic factors. On multivariate analysis, histology, PD-L1 TPS, and irAEs were significant prognostic factors. Conclusion: Pembrolizumab monotherapy demonstrated promising treatment outcomes for advanced or recurrent NSCLC, as evidenced by the significant association of PD-L1 TPS with irAEs and prognosis, suggesting its potential as a beneficial therapeutic option.

[Important statistical points for clinical research: from basics to applications].

Clinical research is conducted to investigate physicians' clinical questions and to clarify research hypotheses. When conducting clinical research, it is important to carefully consider the research design in advance. An optimal design that meets the objectives of the study and addresses practical implementation issues is desirable. Randomized comparisons during the final confirmatory phase may be the best tool for comparing treatments. However, not all clinical questions can be answered through randomized controlled trials. This article summarizes the basics of clinical study design and explains the role of randomization. It also introduces a propensity score-based method that has gained attention as a statistical method for comparing treatment groups when randomization is not feasible, and is increasingly being utilized in clinical research.

Is early-onset colorectal cancer an evolving pandemic? Real-world data from a tertiary cancer center.

BACKGROUND: Early onset Colorectal Cancer (EOCRC), defined as those diagnosed under the age of 50, has been increasing rapidly since 1970. UK data on EOCRC are currently limited and better understanding of the condition is needed. MATERIALS AND METHODS: A single-center retrospective study of patients with EOCRC treated over 9 years (2013-2021) at a large UK cancer center was performed. Clinicopathological features, risk factors, molecular drivers, treatment, and survival were analyzed. RESULTS: In total, 203 patients were included. A significant increase in cases was reported from 2018-2019 (n = 33) to 2020-2021 (n = 118). Sporadic EOCRC accounted for 70% of cases and left-sided tumors represented 70.9% (n = 144). Median duration of symptoms was 3 months, while 52.7% of the patients had de-novo metastatic disease. Progression-free survival after first-line chemotherapy was 6 months (95% CI, 4.85-7.15) and median overall survival (OS) was 38 months (95% CI, 32.86-43.14). In the advanced setting, left-sided primary tumors were associated with a median OS benefit of 14 months over right-sided primaries (28 vs 14 months, P = .009). Finally, primary tumor resection was associated with median OS benefit of 21 months compared with in situ tumors (38 vs 17 months, P < .001). CONCLUSIONS: The incidence of EOCRC is increasing, and survival outcomes remain modest. Raising public awareness and lowering the age for colorectal cancer screening are directions that could improve EOCRC clinical outcomes. There is also a need for large prospective studies to improve the understanding of the nature of EOCRC and the best therapeutic approaches.

FOUNTAIN: a modular research platform for integrated real-world evidence generation.

BACKGROUND: Real-world evidence (RWE) plays a key role in regulatory and healthcare decision-making, but the potentially fragmentated nature of generated evidence may limit its utility for clinical decision-making. Heterogeneity and a lack of reproducibility in RWE resulting from inconsistent application of methodologies across data sources should be minimized through harmonization. METHODS: This paper's aim is to describe and reflect upon a multidisciplinary research platform (FOUNTAIN; FinerenOne mUlti-database NeTwork for evidence generAtIoN) with coordinated studies using diverse RWE generation approaches and explore the platform's strengths and limitations. With guidance from an executive advisory committee of multidisciplinary experts and patient representatives, the goal of the FOUNTAIN platform is to harmonize RWE generation across a portfolio of research projects, including research partner collaborations and a common data model (CDM)-based program. FOUNTAIN's overarching objectives as a research platform are to establish long-term collaborations among pharmacoepidemiology research partners and experts and to integrate diverse approaches for RWE generation, including global protocol execution by research partners in local data sources and common protocol execution in multiple data sources through federated data networks, while ensuring harmonization of medical definitions, methodology, and reproducible artifacts across all studies. Specifically, the aim of the multiple studies run within the frame of FOUNTAIN is to provide insight into the real-world utilization, effectiveness, and safety of finerenone across its life-cycle. RESULTS: Currently, the FOUNTAIN platform includes 9 research partner collaborations and 8 CDM-mapped data sources from 7 countries (United States, United Kingdom, China, Japan, The Netherlands, Spain, and Denmark). These databases and research partners were selected after a feasibility fit-for-purpose evaluation. Six multicountry, multidatabase, cohort studies are ongoing to describe patient populations, current standard of care, comorbidity profiles, healthcare resource use, and treatment effectiveness and safety in different patient populations with chronic kidney disease and type 2 diabetes. Strengths and potential limitations of FOUNTAIN are described in the context of valid RWE generation. CONCLUSION: The establishment of the FOUNTAIN platform has allowed harmonized execution of multiple studies, promoting consistency both within individual studies that employ multiple data sources and across all studies run within the platform's framework. FOUNTAIN presents a proposal to efficiently improve the consistency and generalizability of RWE on finerenone.

Functional disability and disease activity are affected by social determinants of health in patients with rheumatoid arthritis.

BACKGROUND: The relationship between social determinants of health (SDH) and disease outcomes in rheumatoid arthritis (RA) is not well documented. METHODS: Data were extracted from the Ontario Best Practices Research Initiative (OBRI) registry for patients between January 2008 and April 2022. Adjusted mixed models analysis was used to investigate the effect of baseline SDH on disease activity (Clinical Disease Activity Index (CDAI)) and functional disability (Health Assessment Questionnaire-Disability Index (HAQ-DI)) 12 months after enrollment. The analyses were completed on multiple imputed data. RESULTS: There were 2651 patients with a mean age of 58.1 years (SD 12.9). The majority (77.8%) were female. Greater improvements in physical function were seen in patients who were full-time employed (difference = - 0.20; 95% CI - 0.28, - 0.11), part-time employed (difference = - 0.10; 95% CI - 0.19, - 0.02), or retired (difference = - 0.17; 95% CI - 0.25, - 0.08), compared to unemployed, those with highest income ($75,000 or more) (difference = - 0.23; 95% CI - 0.37, - 0.09). Caucasian was also associated with a positive impact on functional ability (difference = - 0.09; 95% CI - 0.17, - 0.02). In contrast, smokers had smaller improvements in physical function (difference = 0.07; 95% CI 0.002, 0.14). Interestingly, women had greater improvement in CDAI (difference = - 2.40; 95% CI - 3.29, - 1.51), while they reported less improving in their physical function (difference = 0.33; 95% CI 0.27-0.39). Achieving CDAI low disease activity/remission state was also more common in females. CONCLUSIONS: Our findings suggest that disease activity and functional disability are affected by different SDH factors. The effects of SDH should be better understood and addressed by rheumatologists to provide equitable healthcare for all patients with RA. Key points • This study explored a comprehensive panel of social determinants of health and their relationship to clinical outcomes. • Previously unreported factors such as employment status and income were found to influence clinical outcomes. • Our findings can help physicians to identify high-risk patients who may benefit from additional attention to their social background.

Burden of disease and cost of illness of infants less than 6 months of age hospitalised with respiratory syncytial virus in Denmark - a 10-year national register-based study.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of hospitalisation in infants aged ≤ 6 months in Western countries. Nearly 1,500 infants under six months of age are hospitalised with RSV annually in Denmark. This nationwide study describes the healthcare resource utilisation and costs related to RSV hospitalisation in this vulnerable age group. METHODS: RSV cases were identified in the Danish National Patient Register. Infants were included if they at the age of 0-5 months had a (1) respiratory related hospital admission (duration > 12 h), (2) within 10 days of a positive RSV test, (3) between January 2013 and December 2022. Each case was matched with five individuals never diagnosed with RSV on age, sex, region of residence, birth (pre/full term), number of siblings < 7 years old, and parents' education. An episode of RSV was defined as the seven days prior to hospitalisation to 30 days after initial hospitalisation. Study outcomes included contacts with hospital and primary care, and total healthcare costs defined as the sum cost of hospital care, primary care, and prescription medicine. Cost and contacts attributable to RSV was calculated in a diff-in-diff framework, as the difference between case and reference group. RESULTS: The study population comprised of 8,428 RSV cases and 41,725 reference individuals. Cases generated 1.58 (p < 0.001) attributable inpatient contacts, 0.84 (p < 0.001) outpatient contacts, and 1.19 (p < 0.001) primary care contacts during their RSV episode. An additional 0.6 (p < 0.001) inpatient, 1.08 (p < 0.001) outpatient and 2.42 (p < 0.001) primary care contacts were attributed to RSV in the year following the RSV episode. Total cost of an RSV episode was EUR 2,997 (p < 0.001) with an additional EUR 1,428 (p < 0.001) in the following year. CONCLUSION: RSV hospitalisations of infants are associated with substantial healthcare utilisation and costs. The same pattern was observed in the year following the RSV episode. If the new RSV prevention options are introduced nationwide, the overall burden of RSV is expected to be substantially reduced in the future.

Drug Review and Approval Policies Based on Real-world Evidence in China and the United States: A Comparative Study.

PURPOSE: The use of real-world evidence (RWE) in regulatory reviews and approvals is currently experiencing significant changes amid increasingly active discussions, primarily reflected in relevant policies, regulations, and guidance documents. However, disparities persist between China and the United States regarding the acceptance and formulation of policies for incorporating real-world data/evidence (RWD/E) in regulatory evaluation and authorization. Furthermore, the current policies lack specific operational details necessary for effective implementation and widespread adoption. METHODS: After conducting a systematic literature review and comparing relevant policies, regulations, and guidelines, as well as the related information published on their official websites, we analyze key aspects of RWE-based drug review and approval policies to highlight similarities and differences in these policies between China and the United States. FINDINGS: This paper reviews the frameworks and existing guidelines in China and the U.S., discussing similarities and differences observed in key policy aspects, including relevant definitions, data sources, data standards, data quality, and connectivity, information requirements, study design, personnel training, and communication, including an example of the application of RWE in drug review and approval processes. IMPLICATIONS: Further develop and refine RWE policies, encourage cooperation, and share best practices and successful examples to enhance the effectiveness of policy implementation and increase its social acceptance.

Comparison of the effectiveness of open, laparoscopic, and robotic-assisted radical prostatectomies based on complication rates: a retrospective observational study with administrative data from Switzerland.

BACKGROUND: Radical prostatectomies can be performed using open retropubic, laparoscopic, or robot-assisted laparoscopic surgery. The literature shows that short-term outcomes (in particular, inpatient complications) differ depending on the type of procedure. To date, these differences have only been examined and confirmed in isolated cases based on national routine data. METHODS: The data was based on the Swiss Medical Statistics from 2016 to 2018 from a national survey of administrative data from all Swiss hospitals. Cases with the coded main diseases neoplasm of the prostate (ICD C61) and the main treatments of laparoscopic (CHOP 60.5X.20) or retropubic (CHOP 60.5X.30) radical prostatectomies were included, resulting in a total sample size of 8,593 cases. RESULTS: A procedure-related complication occurred in 998 cases (11.6%). By surgical procedure, complication rates were 10.1% for robotic-assisted laparoscopic radical prostatectomy 9.0% for conventional laparoscopic radical prostatectomy and 17.1% for open retropubic radical prostatectomy (p < 0.001). Conventional and robotic-assisted laparoscopic radical prostatectomies had a significantly lower risk of complications than retropubic procedures. Moreover, the risk of a procedure-related complication was almost twice as high in cases operated on retropubically; however, no significant difference was found between conventional and robotic-assisted laparoscopic cases. DISCUSSION: The use of a surgical robot showed no advantages in radical prostatectomies regarding procedure-related during the hospital stay. However, both conventional and robotic-assisted laparoscopically operated radical prostatectomies show better results than open retropubic procedures. Further studies on the long-term course of patients based on claims data are needed to confirm the inherent benefits of surgical robots in tandem with them being increasingly employed in hospitals.

Regional diversity in drug-induced lung diseases among the USA, European Union, and Japan.

Background: Drug-induced lung disease (DILD) is a considerable and potentially fatal adverse event with poorly understood risk factors. Large-scale, data-driven analyses investigating regional discrepancies in DILD incidence are lacking. The aim of this study was to investigate the potential association among DILD prevalence, regional differences and other factors based on large-scale data base. Methods: This retrospective observational study analyzed spontaneous adverse event reports from the FDA Adverse Event Reporting System (FAERS) database between January 2010 and December 2020. Regional disparities in DILD incidence were assessed among reports from the United States of America (USA), the European Union (EU), and Japan (JP). Using multivariate logistic regression accounting for age, sex, and reporting years, we calculated the reporting odds ratios (RORs) with 95% confidence intervals. Subgroup analyses were performed for different types of anticancer agents, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and cytotoxic agents. Results: Regional differences in RORs were observed for anticancer drugs in reports from JP and the EU compared with those from the USA (JP, ROR 4.432; EU, ROR 1.291) and for non-anticancer drugs (JP, ROR 3.481; EU, ROR 1.086). Significantly higher RORs were observed for all anticancer drug regimens reported in JP than in the USA (TKIs, ROR 3.274; ICIs, ROR 2.170; ADCs, ROR 2.335; cytotoxic agents, ROR 3.989). The EU reports exhibited higher RORs for TKIs and cytotoxic agents than the USA reports, with no significant differences in ICIs or ADCs (TKIs, ROR 1.679; ICIs, ROR 1.041; ADCs, ROR 1.046; cytotoxic agents, ROR 1.418). Conclusion: The prevalence of DILD in JP, the EU, and the USA differed. These findings have important implications in evaluating the safety profiles of drugs and patient safety in drug development and clinical practice. This study is the first to identify regional differences in DILDs using a large global database.

Low to intermediate grade lung neuroendocrine tumours. A single centre real world experience.

INTRODUCTION: Lung neuroendocrine tumours (LNETs) are a rare heterogenous group of tumours whose incidence has been increasing. We investigated the diagnosis, treatment, and survival patterns of patients with low to intermediate grade LNETs. METHODS: A retrospective chart review of patients with low to intermediate grade LNETs, treated at a Canadian tertiary-level cancer centre was performed. RESULTS: We identified 59 patients. Most were G1or G2 and well or moderately differentiated. Forty-seven patients presented with local or locally advanced disease, of which 57.4 % received curative intent surgery. The rest were treated with definitive radiation, radical chemoradiation with platinum and etoposide, palliative chemotherapy with doxorubicin, or supportive care. The five-year overall survival (OS) for those treated surgically was 83 % versus 44 % in the non-surgical group. Metastatic disease was seen in 24/59 patients, with a five-year OS in patients with stage IV disease of 39 %. Of those with advanced or unresectable disease (n = 32), 21 received palliative systemic treatment with up to three lines of therapy. First-line treatment was most commonly chemotherapy with platinum/etoposide combination or somatostatin analogue therapy. Second-line treatment involved chemotherapy or targeted everolimus. PRRT was used once as a first-line and once as second-line therapy. Third-line included lanreotide or chemotherapy with capecitabine/temozolomide combination. CONCLUSION: Overall, patients with surgically resectable disease had a good five-year OS. However, inoperable or more advanced disease was associated with a poorer OS. Despite many treatment options, the sequence of treatments is poorly established. This highlights the need for further development and dissemination of evidence-based guidelines for LNET patients.

Optimizing tacrolimus dosing in Hispanic renal transplant patients: insights from real-world data.

Aim: Tacrolimus, an immunosuppressant used to prevent organ rejection in renal transplant patients, exhibits high inter-patient variability, necessitating therapeutic drug monitoring. Early post-transplant tacrolimus exposure in Hispanics is understudied. Although genotypic information is linked to pharmacokinetic differences, its clinical application remains limited. This study aimed to use a real-world data-driven, pharmacokinetic model-based approach for tacrolimus in Hispanics to determine a suitable initial dose and design an optimal dose titration strategy by simulations to achieve plasma trough concentration target levels of 10-12 ng/mL at the earliest. Methods: Sparse concentration-time data of tacrolimus were obtained from electronic medical records for self-identified Hispanic subjects following renal transplant. Rich pharmacokinetic literature data was leveraged to estimate structural pharmacokinetic model parameters, which were then fixed in the current analysis. Only apparent clearance was estimated with the sparse tacrolimus data and potential covariates were identified. Simulations of various starting doses and different dose titration strategies were then evaluated. Results: The analysis included 121 renal transplant patients with 2,215 trough tacrolimus concentrations. A two-compartment transit absorption model with allometrically scaled body weight and time-varying hematocrit on apparent clearance adequately described the data. The estimated apparent clearance was 13.7 L/h for a typical patient weighing 70 kg and at 30% hematocrit, demonstrating a 40% decrease in clearance compared to other patient populations. Model based simulations indicated the best initial dose for the Hispanic population is 0.1 mg/kg/day. The proposed titration strategy, with three dose adjustments based on trough levels of tacrolimus, increased the proportion of patients within the target range (10-12 ng/mL) more than 2.5-fold and decreased the proportion of patients outside the therapeutic window by 50% after the first week of treatment. Conclusion: Hispanic renal transplant population showed an estimated 40% decrease of apparent clearance in the typical patient compared to other populations with similar characteristics. The proposed dose adjustment attained the target range rapidly and safely. This study advocates for tailored tacrolimus dosing regimens based on population pharmacokinetics to optimize therapy in Hispanic renal transplant recipients.

Validation Assessment of Privacy-Preserving Synthetic Electronic Health Record Data: Comparison of Original Versus Synthetic Data on Real-World COVID-19 Vaccine Effectiveness.

PURPOSE: To assess the validity of privacy-preserving synthetic data by comparing results from synthetic versus original EHR data analysis. METHODS: A published retrospective cohort study on real-world effectiveness of COVID-19 vaccines by Maccabi Healthcare Services in Israel was replicated using synthetic data generated from the same source, and the results were compared between synthetic versus original datasets. The endpoints included COVID-19 infection, symptomatic COVID-19 infection and hospitalization due to infection and were also assessed in several demographic and clinical subgroups. In comparing synthetic versus original data estimates, several metrices were utilized: standardized mean differences (SMD), decision agreement, estimate agreement, confidence interval overlap, and Wald test. Synthetic data were generated five times to assess the stability of results. RESULTS: The distribution of demographic and clinical characteristics demonstrated very small difference (< 0.01 SMD). In the comparison of vaccine effectiveness assessed in relative risk reduction between synthetic versus original data, there was a 100% decision agreement, 100% estimate agreement, and a high level of confidence interval overlap (88.7%-99.7%) in all five replicates across all subgroups. Similar findings were achieved in the assessment of vaccine effectiveness against symptomatic COVID-19 Infection. In the comparison of hazard ratios for COVID 19-related hospitalization and odds ratio for symptomatic COVID-19 Infection, the Wald tests suggested no significant difference between respective effect estimates in all five replicates for all patient subgroups but there were disagreements in estimate and decision metrices in some subgroups and replicates. CONCLUSIONS: Overall, comparison of synthetic versus original real-world data demonstrated good validity and reliability. Transparency on the process to generate high fidelity synthetic data and assurances of patient privacy are warranted.

Monitoring Pregnancies Exposed to Galcanezumab for Migraine in a United States Administrative Claims Database.

PURPOSE: Galcanezumab is a calcitonin gene-related peptide monoclonal antibody indicated for migraine prevention in adults. Due to the long half-life of galcanezumab and the prevalence of migraine in women of childbearing age, galcanezumab exposure may occur during pregnancy. However, real-world use and safety of galcanezumab during pregnancy has not been fully described. To help fill this gap, galcanezumab has two ongoing pregnancy safety studies, one of which is an insurance claims database study. METHODS: This database study is actively identifying and following pregnancies exposed to galcanezumab using commercial claims from the Healthcare Integrated Research Database (HIRD). Patient accrual is planned from September 2018 to June 2026, with a final study report planned for December 2027. This study requires 430 galcanezumab-exposed pregnancies with linked infants to reach power for comparative analysis of major congenital malformations. RESULTS: Recent monitoring of patient accrual, including data from 28 September 2018 to 31 January 2023, identified 207 galcanezumab-exposed pregnancies in women with migraine in the HIRD, of which 110 were live births and 73 of which were linked to an infant. This represents an annual accrual rate of approximately 17 pregnancies linked to infants, which is substantially lower than the 55 required annually to reach target size within current regulatory-committed study timelines. CONCLUSIONS: The accrual of a sufficient number of galcanezumab-exposed pregnancies represents a substantial, but not uncommon, barrier to conducting comparative analyses in pregnancy studies. Potential solutions that would allow for timely dissemination of important safety information to patients and providers may be available.

Treatment of myasthenia gravis in france: A retrospective claims database study (STAMINA).

BACKGROUND: This study aimed to describe treatment patterns in patients with myasthenia gravis (MG) in France. METHODS: A retrospective cohort analysis was performed using the French National Health Data System (SNDS) database between 2008 and 2019. MG patients were identified using ICD-10 codes during hospitalization and/or long-term disease. We defined two adult subpopulations: a prevalent MG population of patients alive on 31/12/2019 and an incident population of newly identified patients with MG in 2012 and 2013. RESULTS: Among the 22,079 prevalent patients, 53.1% (n = 11,498) received at least one chronic MG treatment in 2019. Among these treated patients, 52.5% received Acetylcholinesterase inhibitors (AChEIs) only, 10.2% were treated with corticosteroids (CS) ± AChEIs, 7.3% with non-steroidal immunosuppressive treatments (NSIST) and CS, 24.2% with NSIST w/o CS, and 5.8% received immunoglobulin and/or plasma exchange. Among the 2,661 incident patients, 84.6% received at least one chronic MG treatment over the 6-year follow-up period, and among them, 79.0% had at least one treatment category change. During the first semester of follow-up, 28.1% of patients were treated with an immunomodulator (CS, NSIST). Among patients starting treatment with immunomodulator, the proportion of those treated with CS decreased from 35.3% at initiation to 10.9% at 6 years. CONCLUSION: This study illustrates the complexity of MG management. Significant CS sparing was observed over time. The frequent treatment changes especially in patients with an immunomodulator treatment reflect the high variability of the disease severity. The need for personalised treatment approaches in the management of MG to reduce the burden of disease remains.

Advances of artificial intelligence in predicting frailty using real-world data: A scoping review.

BACKGROUND: Frailty assessment is imperative for tailoring healthcare interventions for older adults, but its implementation remains challenging due to the effort and time needed. The advances of artificial intelligence (AI) and natural language processing (NLP) present a novel opportunity to harness real-world data (RWD) including electronic health records, administrative claims, and other routinely collected medical records for frailty assessments. METHODS: We followed the PRISMA-ScR guideline and searched Embase, Web of Science, and PubMed databases for articles that predict frailty using AI through RWD from inception until October 2023. We synthesized and analyzed the selected publications according to their field of application, methodologies employed, validation processes, outcomes achieved, and their respective limitations and strengths. RESULTS: A total of 23 publications were selected from the initial search (N=2067) and bibliography. The approaches to frailty prediction using RWD and AI were categorized into two groups based on the type of data utilized: 1) AI models using structured data and 2) NLP techniques applied to unstructured clinical notes. We found that AI models achieved moderate to high predictive performance in predicting frailty. However, to demonstrate their clinical utility, these models require further validation using external data and a comprehensive assessment of their impact on patients' health outcomes. Additionally, the application of NLP in frailty prediction is still in its early stages. Great potential exists to enhance frailty prediction by integrating structured data and clinical notes. CONCLUSION: The combination of AI and RWD presents significant opportunities for advancing frailty assessment. To maximize the advantages of these technological advances, future research is needed to rigorously address the challenges associated with the validation of AI models and innovative data integration.

Use of transportability methods for real-world evidence generation: a review of current applications.

Aim: To evaluate how transportability methods are currently used for real-world evidence (RWE) generation to inform good practices and support adoption and acceptance of these methods in the RWE context. Methods: We conducted a targeted literature review to identify studies that transported an effect estimate of the clinical effectiveness or safety of a biomedical exposure to a target real-world population. Records were identified from PubMed-indexed articles published any time before 25 July 2023 (inclusive). Two reviewers screened abstracts/titles and reviewed the full text of candidate studies to identify the final set of articles. Data on the therapeutic area, exposure(s), outcome(s), original and target populations and details of the transportability analysis (e.g., analytic method used, estimate transported, stated assumptions) were abstracted from each article. Results: Of 458 unique records identified, six were retained in the final review. Articles were published during 2021-2023, focused on the US/Canada context, and covered a range of therapeutic areas. Four studies transported an RCT effect estimate, while two transported effect estimates derived from real-world data. Almost all articles used weighting methods to transport estimates. Two studies discussed all transportability assumptions, and one evaluated the likelihood of meeting all assumptions and the impact of potential violations. Conclusion: The use of transportability methods for RWE generation is an emerging and promising area of research to address evidence gaps in settings with limited data and infrastructure. More transparent and rigorous reporting of methods, assumptions and limitations may increase the use and acceptability of transportability for producing robust evidence on treatment effectiveness and safety.

Real-life effectiveness of prehabilitation to improve postoperative outcomes in patients with colorectal cancer approaching surgery: A systematic review and meta-analyses of observational studies versus randomized controlled trials.

INTRODUCTION: Current evidence synthesis of prehabilitation studies in colorectal surgery is based on results of randomized controlled trials (RCT). Although RCTs are the gold standard for effectiveness research, observational studies probably better reflect real-life practice. The aims of the current study were to compare observational studies to RCTs regarding the association between prehabilitation and postoperative outcomes, and characteristics of included patients and interventions. METHODS: A systematic search was conducted in PubMed, Embase, and CINAHL (until September 2023). Observational studies and RCTs investigating prehabilitation before colorectal surgery and reporting postoperative complications and/or length of stay (LoS) were included. Two reviewers independently assessed the risk of bias using the Cochrane Risk of Bias 2 tool for RCTs and the Cochrane ROBINS-I tool for observational studies. Meta(regression)-analyses were performed for postoperative complications and LoS. RESULTS: Pooled results showed a statistically significant reduction in postoperative complications (OR 0.54; 95 % confidence interval (CI) 0.40 to 0.72) and LoS (mean difference (MD) -1.34 CI -2.57 to -0.12) after prehabilitation in observational studies but not in RCTs (complications OR 0.95; CI 0.53 to 1.72; LoS MD 0.16 CI -0.52 to 0.83). Patients included in observational studies were older and more often had an ASA score ≥3. In a meta-regression analysis, these characteristics were not statistically significantly associated with the main outcomes. CONCLUSION: Observational studies in a real-life setting showed that prehabilitation can reduce postoperative complications and LoS. To further explore the real-life effectiveness of prehabilitation, specific observational study designs, like a target emulation trial could be used.

Understanding the landscape and promoting the use of guides for real-world studies: A scoping review.

OBJECTIVE: To provide an overview of the existing guides for real-world studies (RWS). STUDY DESIGN AND SETTING: Scoping review: A systematic and snowball search of PubMed, Web of Science, CNKI, Wan Fang, and nine other official websites was conducted to identify guides for RWS published between January 1, 1990 and December 31, 2023. Two reviewers independently screened and extracted the data using a predefined form. Descriptive, quantitative, and qualitative summaries were also obtained. RESULTS: A total of 61 guides from PubMed (26, 42.6%), CNKI (9, 14.8%), and other websites (26, 42.6%) were included. Of these, 20 guides (32.8%) were developed through international collaboration, and 49 (80.3%) were published after 2016. Fifty-three (86.9%), six (9.8%), and four (6.6%) were methodological guides, reporting guidelines, and evaluation tools, respectively. These guides addressed observational studies (24, 39.3%), interventional studies (5, 8.2%), or both (22, 36.1%), that covered design (46, 75.4%), conduct (24, 39.3%), analysis (15, 24.6%), reporting (13, 21.3%), and evaluation (3, 4.9%). Only ten guides (16.4%) used both evidence-based and consensus-driven methods in their development. CONCLUSION: Existing RWS guides vary significantly in purpose, format, and content and are often tailored to specific contexts. However, improved guide development methods remain to be established. Researchers should carefully assess the scope, classification, and applicability of these guides, particularly at the beginning of the study, to ensure that they meet the needs of their specific research objectives.

Treatment patterns and patient journey in progressive pulmonary fibrosis: a cross-sectional survey.

BACKGROUND: For patients with interstitial lung diseases (ILDs) presenting with a progressive pulmonary fibrosis (PPF) phenotype, current knowledge of disease characteristics at diagnosis, patient journey, and treatment is limited. This study aimed to describe demographics and clinical experiences of patients presenting with PPF in a European real-world setting. METHODS: Data were analysed from the Adelphi Real World PPF-ILD Disease Specific Programme™, a cross-sectional survey of pulmonologists and rheumatologists in five European countries (France, Germany, Italy, Spain, United Kingdom) and internal medicine specialists (France) from April to October 2022. Physicians provided data for up to 12 consecutive patients with physician-confirmed ILD with a progressive phenotype other than idiopathic pulmonary fibrosis. Analyses were descriptive. RESULTS: Overall, 265 physicians reported on 1,335 patients. Mean (standard deviation) age at survey date was 60.4 (11.6) years, 91.2% were white, 58.1% female, 44.0% non-smokers. Most patients (63.3%) first consulted a primary care physician. There was a mean delay of 7.8 (22.7) months between first ILD symptom and healthcare professional visit, and another 7.7 (12.8) months to ILD diagnosis. At survey date, 47.7% of patients had physician-reported moderate ILD, 42.3% had mild ILD and 10.0% had severe ILD. Disease progression was reported in the 12 months prior to the survey for 19.5% of patients; of these, progression was based on worsening symptom in 27.3% and lung function decline in 25.8%. For patients experiencing symptoms prior to ILD diagnosis (72.8%), the most common symptoms were dyspnoea on exertion (80.5%) and cough (57.8%). Overall, 17.4% of patients were misdiagnosed prior to ILD diagnosis, with chronic obstructive pulmonary disease suspected in 39.2% of them. The most frequent comorbidities were anxiety (16.9%) and gastroesophageal reflux (15.5%). Although 77.8% of patients were receiving treatment for ILD at survey date, 15.6% of patients had never been prescribed treatment for ILD. CONCLUSIONS: This real-world study expands our understanding of patients, diagnostic delays and treatment gaps experienced by patients diagnosed with PPF in Europe. There was a mean delay of 15.5 months between first ILD symptoms and ILD diagnosis. Given the progressive nature of PPF, diagnostic delay may lead to poor outcomes, including shorter survival. TRIAL REGISTRATION: N/a.