Pragmatic and Observational Research最新文献

{"title":"Drug Repurposing in Crohn's Disease Using Danish Real-World Data.","authors":"Saeed Shakibfar, Kristine H Allin, Tine Jess, Maria Antonietta Barbieri, Vera Battini, Eva Simoncic, Julien Kirchgesner, Trond Ulven, Maurizio Sessa","doi":"10.2147/POR.S444569","DOIUrl":"https://doi.org/10.2147/POR.S444569","url":null,"abstract":"<p><strong>Aim: </strong>Drug repurposing, utilizing electronic healthcare records (EHRs), offers a promising alternative by repurposing existing drugs for new therapeutic indications, especially for patients lacking effective therapies. Intestinal fibrosis, a severe complication of Crohn's disease (CD), poses significant challenges, increasing morbidity and mortality without available pharmacological treatments. This article focuses on identifying medications associated with an elevated or reduced risk of fibrosis in CD patients through a population-wide real-world data and artificial intelligence (AI) approach.</p><p><strong>Methods: </strong>Patients aged 65 or older with a diagnosis of CD from 1996 to 2019 in the Danish EHRs were followed for up to 24 years. The primary outcome was the need of specific surgical procedures, namely proctocolectomy with ileostomy and ileocecal resection as proxies of intestinal fibrosis. The study explored drugs linked to an increased or reduced risk of the study outcome through machine-learning driven survival analysis.</p><p><strong>Results: </strong>Among the 9179 CD patients, 1029 (11.2%) underwent surgery, primarily men (58.5%), with a mean age of 76 years, 10 drugs were linked to an elevated risk of surgery for proctocolectomy with ileostomy and ileocecal resection. In contrast, 10 drugs were associated with a reduced risk of undergoing surgery for these conditions.</p><p><strong>Conclusion: </strong>This study focuses on repurposing existing drugs to prevent surgery related to intestinal fibrosis in CD patients, using Danish EHRs and advanced statistical methods. The findings offer valuable insights into potential treatments for this condition, addressing a critical unmet medical need. Further research and clinical trials are warranted to validate the effectiveness of these repurposed drugs in preventing surgery related to intestinal fibrosis in CD patients.</p>","PeriodicalId":20399,"journal":{"name":"Pragmatic and Observational Research","volume":"15 ","pages":"17-29"},"PeriodicalIF":8.9,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10894518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139973158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction Model with Validation for Polioseronegativity in Malnourished Children from Poliomyelitis Transmission High-Risk Area of the Democratic Republic of the Congo (DRC).","authors":"Guillaume Ngoie Mwamba, Michel Kabamba, Nicole A Hoff, Patrick K Mukadi, Kamy Kaminye Musene, Sue K Gerber, Megan Halbrook, Cyrus Sinai, Trevon Fuller, Arie Voorman, Paul Makan Mawaw, Oscar Luboya Numbi, Emile Okitolonda Wemakoy, Patricia N Mechael, Jean Jacques Muyembe Tamfum, Mala Ali Mapatano, Anne W Rimoin, Paul-Samson Lusamba Dikassa","doi":"10.2147/POR.S437485","DOIUrl":"10.2147/POR.S437485","url":null,"abstract":"<p><strong>Background: </strong>Malnutrition is identified as a risk factor for insufficient polio seroconversion in the context of a vaccine-derived poliovirus (VDPV) outbreak-prone region. In the Democratic Republic of Congo (DRC), underweight decreased from 31% (in 2001) to 26% (in 2018). Since 2004, VDPV serotype 2 outbreaks (cVDPV2) have been documented and were geographically limited around the Haut-Lomami and Tanganyika Provinces.</p><p><strong>Methods: </strong>To develop and validate a predictive model for poliomyelitis vaccine response in malnourished infants, a cross-sectional household study was carried out in the Haut-Lomami and Tanganyika provinces. Healthy children aged 6 to 59 months (n=968) were enrolled from eight health zones (HZ) out of 27, in March 2018. We performed a bivariate and multivariate logistics analysis. Final models were selected using a stepwise Wald method, and variables were selected based on the criterion p < 0.05. The association between nutritional variables, explaining polio seronegativity for the three serotypes, was assessed using the receiver operating characteristic curve (ROC curve).</p><p><strong>Results: </strong>Factors significantly associated with seronegativity to the three polio serotypes were underweight, non-administration of vitamin A, and the age group of 12 to 59 months. The sensitivity was 10.5%, and its specificity was 96.4% while the positive predictive values (PPV) and negative (PNV) were 62.7% and 65.3%, respectively. We found a convergence of the curves of the initial sample and two split samples. Based on the comparison of the overlapping confidence intervals of the ROC curve, we concluded that our prediction model is valid.</p><p><strong>Conclusion: </strong>This study proposed the first tool which variables are easy to collect by any health worker in charge of vaccination or in charge of nutrition. It will bring on top, the collaboration between the Immunization and the Nutritional programs in DRC integration policy, and its replicability in other low- and middle-income countries with endemic poliovirus.</p>","PeriodicalId":20399,"journal":{"name":"Pragmatic and Observational Research","volume":"14 ","pages":"155-165"},"PeriodicalIF":2.3,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10749540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Avelumab for Advanced Merkel Cell Carcinoma: Global Real-World Data on Patient Response and Survival.","authors":"Rishabh Lohray, Kritin K Verma, Leo L Wang, Dylan Haynes, Daniel J Lewis","doi":"10.2147/POR.S398151","DOIUrl":"10.2147/POR.S398151","url":null,"abstract":"<p><strong>Introduction: </strong>Avelumab is a programmed cell death-ligand 1 (PD-L1) inhibitor approved by the Food and Drug Administration for advanced Merkel cell carcinoma (MCC). Studies conducted in real-world settings have shed light on its effectiveness and safety in clinical settings.</p><p><strong>Areas covered: </strong>Real-world studies on avelumab for MCC from North and South America, Europe, and Asia have been presented in this review. Most studies are on patients over age 70 and have a male-predominant sex ratio. Overall response rates range from 29.1% to 72.1%, (disease control rate: 60.0-72.7%; complete response rate: 15.8%-37.2%; partial rate: 18.2-42.1%; stable disease: 7.1-30.9%; progressive disease: 7.1-40.0%) and median progression free survival ranges from 8.1 to 24.1 months depending on the population studied. Immunosuppressed patients appear to benefit from avelumab as well, with response rates equivalent to the general population. Patients receiving avelumab as a first-line agent tend to have better outcomes than those using it as a second-line therapy. Fatigue, infusion-related reactions, and dyspnea were some of the most common adverse events identified in real-world studies. Autoimmune hepatitis and thyroiditis were also observed.</p><p><strong>Conclusion: </strong>The use of avelumab as a safe and effective treatment option for advanced MCC is supported by real-world data, although additional study is required to assess long-term efficacy and safety outcomes.</p>","PeriodicalId":20399,"journal":{"name":"Pragmatic and Observational Research","volume":"14 ","pages":"149-154"},"PeriodicalIF":2.3,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult Severe Asthma Registries: A Global and Growing Inventory.","authors":"Breda Cushen,&nbsp;Mariko Siyue Koh,&nbsp;Trung N Tran,&nbsp;Neil Martin,&nbsp;Ruth Murray,&nbsp;Thendral Uthaman,&nbsp;Celine Yun Yi Goh,&nbsp;Rebecca Vella,&nbsp;Neva Eleangovan,&nbsp;Lakmini Bulathsinhala,&nbsp;Jorge F Maspero,&nbsp;Matthew J Peters,&nbsp;Florence Schleich,&nbsp;Paulo Pitrez,&nbsp;George Christoff,&nbsp;Mohsen Sadatsafavi,&nbsp;Carlos A Torres-Duque,&nbsp;Celeste Porsbjerg,&nbsp;Alan Altraja,&nbsp;Lauri Lehtimäki,&nbsp;Arnaud Bourdin,&nbsp;Christian Taube,&nbsp;Nikolaos G Papadopoulos,&nbsp;Csoma Zsuzsanna,&nbsp;Unnur Björnsdóttir,&nbsp;Sundeep Salvi,&nbsp;Enrico Heffler,&nbsp;Takashi Iwanaga,&nbsp;Mona Al-Ahmad,&nbsp;Désirée Larenas-Linnemann,&nbsp;Job F M van Boven,&nbsp;Bernt Bøgvald Aarli,&nbsp;Piotr Kuna,&nbsp;Cláudia Chaves Loureiro,&nbsp;Riyad Al-Lehebi,&nbsp;Jae Ha Lee,&nbsp;Nuria Marina,&nbsp;Leif Bjermer,&nbsp;Chau-Chyun Sheu,&nbsp;Bassam Mahboub,&nbsp;John Busby,&nbsp;Andrew Menzies-Gow,&nbsp;Eileen Wang,&nbsp;David B Price","doi":"10.2147/POR.S399879","DOIUrl":"10.2147/POR.S399879","url":null,"abstract":"<p><strong>Aim: </strong>The International Severe Asthma Registry (ISAR; http://isaregistries.org/) uses standardised variables to enable multi-country and adequately powered research in severe asthma. This study aims to look at the data countries within ISAR and non-ISAR countries reported collecting that enable global research that support individual country interests.</p><p><strong>Methods: </strong>Registries were identified by online searches and approaching severe asthma experts. Participating registries provided data collection specifications or confirmed variables collected. Core variables (results from ISAR's Delphi study), steroid-related comorbidity variables, biologic safety variables (serious infection, anaphylaxis, and cancer), COVID-19 variables and additional variables (not belonging to the aforementioned categories) that registries reported collecting were summarised.</p><p><strong>Results: </strong>Of the 37 registries identified, 26 were ISAR affiliates and 11 non-ISAR affiliates. Twenty-five ISAR-registries and 4 non-ISAR registries reported collecting >90% of the 65 core variables. Twenty-three registries reported collecting all optional steroid-related comorbidity variables. Twenty-nine registries reported collecting all optional safety variables. Ten registries reported collecting COVID-19 variables. Twenty-four registries reported collecting additional variables including data from asthma questionnaires (10 Asthma Control Questionnaire, 20 Asthma Control Test, 11 Asthma Quality of Life Questionnaire, and 4 EuroQol 5-dimension 5-level Questionnaire). Eight registries are linked to databases such as electronic medical records and national claims or disease databases.</p><p><strong>Conclusion: </strong>Standardised data collection has enabled individual severe asthma registries to collect unified data and increase statistical power for severe asthma research irrespective of ISAR affiliations.</p>","PeriodicalId":20399,"journal":{"name":"Pragmatic and Observational Research","volume":"14 ","pages":"127-147"},"PeriodicalIF":8.9,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/7f/por-14-127.PMC10595155.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50162638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an Asthma Exacerbation Risk Prediction Model for Conversational Use by Adults in England.","authors":"Constantinos Kallis,&nbsp;Rafael A Calvo,&nbsp;Bjorn Schuller,&nbsp;Jennifer K Quint","doi":"10.2147/POR.S424098","DOIUrl":"10.2147/POR.S424098","url":null,"abstract":"<p><strong>Background: </strong>Improving accurate risk assessment of asthma exacerbations, and reduction via relevant behaviour change among people with asthma could save lives and reduce health care costs. We developed a simple personalised risk prediction model for asthma exacerbations using factors collected in routine healthcare data for use in a risk modelling feature for automated conversational systems.</p><p><strong>Methods: </strong>We used pseudonymised primary care electronic healthcare records from the Clinical Practice Research Datalink (CPRD) Aurum database in England. We combined variables for prediction of asthma exacerbations using logistic regression including age, gender, ethnicity, Index of Multiple Deprivation, geographical region and clinical variables related to asthma events.</p><p><strong>Results: </strong>We included 1,203,741 patients divided into three cohorts to implement temporal validation: 898,763 (74.7%) in the training sample, 226,754 (18.8%) in the testing sample and 78,224 (6.5%) in the validation sample. The Area under the ROC curve (AUC) for the full model was 0.72 and for the restricted model was 0.71. Using a cut-off point of 0.1, approximately 27 asthma reviews by clinicians per 100 patients would be prevented compared with a strategy that all patients are regarded as high risk. Compared with patients without an exacerbation, patients who exacerbated were older, more likely to be female, prescribed more SABA and ICS in the preceding 12 months, have history of GORD, COPD, anxiety, depression, live in very deprived areas and have more severe disease.</p><p><strong>Conclusion: </strong>Using information available from routinely collected electronic healthcare record data, we developed a model that has moderate ability to separate patients who had an asthma exacerbation within 3 months from their index date from patients who did not. When comparing this model with a simplified model with variables that can easily be self-reported through a WhatsApp chatbot, we have shown that the predictive performance of the model is not substantially different.</p>","PeriodicalId":20399,"journal":{"name":"Pragmatic and Observational Research","volume":"14 ","pages":"111-125"},"PeriodicalIF":8.9,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10560745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41210162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tactical Considerations for Designing Real-World Studies: Fit-for-Purpose Designs That Bridge Research and Practice.","authors":"Nancy A Dreyer,&nbsp;Christina D Mack","doi":"10.2147/POR.S396024","DOIUrl":"https://doi.org/10.2147/POR.S396024","url":null,"abstract":"<p><p>Real-world evidence (RWE) is being used to provide information on diverse groups of patients who may be highly impacted by disease but are not typically studied in traditional randomized clinical trials (RCT) and to obtain insights from everyday care settings and real-world adherence to inform clinical practice. RWE is derived from so-called real-world data (RWD), ie, information generated by clinicians in the course of everyday patient care, and is sometimes coupled with systematic input from patients in the form of patient-reported outcomes or from wearable biosensors. Studies using RWD are conducted to evaluate how well medical interventions, services, and diagnostics perform under conditions of real-world use, and may include long-term follow-up. Here, we describe the main types of studies used to generate RWE and offer pointers for clinicians interested in study design and execution. Our tactical guidance addresses (1) opportunistic study designs, (2) considerations about representativeness of study participants, (3) expectations for transparency about data provenance, handling and quality assessments, and (4) considerations for strengthening studies using record linkage and/or randomization in pragmatic clinical trials. We also discuss likely sources of bias and suggest mitigation strategies. We see a future where clinical records - patient-generated data and other RWD - are brought together and harnessed by robust study design with efficient data capture and strong data curation. Traditional RCT will remain the mainstay of drug development, but RWE will play a growing role in clinical, regulatory, and payer decision-making. The most meaningful RWE will come from collaboration with astute clinicians with deep practice experience and questioning minds working closely with patients and researchers experienced in the development of RWE.</p>","PeriodicalId":20399,"journal":{"name":"Pragmatic and Observational Research","volume":"14 ","pages":"101-110"},"PeriodicalIF":8.9,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/35/por-14-101.PMC10541678.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41169171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Use of Immunotherapy for Hepatocellular Carcinoma.","authors":"Amir Sara, Samantha M Ruff, Anne M Noonan, Timothy M Pawlik","doi":"10.2147/POR.S397972","DOIUrl":"10.2147/POR.S397972","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide and accounts for 90% of all primary liver cancers. Chronic inflammation is the hallmark across most prevalent etiologies among which HBV is the leading cause worldwide (33%), followed by alcohol (30%), HCV (21%), other factors like non-alcoholic steatohepatitis linked to insulin resistance/metabolic syndrome, and obesity associated inflammation (16%). Deregulation of the tightly controlled immunological network leads to liver disease, including chronic infection, autoimmunity, and tumor development. While inflammation drives oncogenesis in the liver, HCC also recruits ICOS+ FOXP3+ Tregs and MDSCs and upregulates immune checkpoints to induce a state of immunosuppression in the tumor microenvironment. As such, research is focused on targeting and modulating the immune system to treat HCC. The Checkmate 040 and Keynote 224 studies established the role of immunotherapy in the treatment of patients with HCC. In Phase I and II trials, nivolumab and pembrolizumab demonstrated durable response rates of 15-20% and were subsequently approved as second-line agents after sorafenib. Due to the success of the IMbrave 150 and HIMALAYA trials, which examined the combination of atezolizumab/bevacizumab and tremelimumab/durvalumab, respectively, the FDA approved these regimens as first-time treatment options for patients with advanced HCC. The encouraging results of immunotherapy in the management of HCC has led researchers to evaluate if combination with locoregional therapies may result in a synergistic effect. Real-world studies represent an invaluable tool to assess and verify the applicability of clinical trials in the bedside setting with a more varied patient population. We herein review current real-life use of ICIs in the management of HCC and highlight some of the ongoing clinical trials that are expected to change current recommended first-line treatment in the near future.</p>","PeriodicalId":20399,"journal":{"name":"Pragmatic and Observational Research","volume":"14 ","pages":"63-74"},"PeriodicalIF":2.3,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bb/fc/por-14-63.PMC10455985.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10110092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Administrative Databases and Diagnostic Therapeutic and Assistance Paths -PDTA- in the Monitoring Treatment of Rheumatoid Arthritis: The Experience of ATS Pavia.","authors":"Giacomo M Bruno,&nbsp;Maria Chiara Valentino,&nbsp;Alessandra Brunetti,&nbsp;Sergio Di Matteo,&nbsp;Ivan Begovic,&nbsp;Edoardo Croce,&nbsp;Garifallia Sakellariou,&nbsp;Serena Bugatti,&nbsp;Pietro Perotti,&nbsp;Silvia Vecchio,&nbsp;Simona Migliazza,&nbsp;Roberto Langella,&nbsp;Giorgio L Colombo","doi":"10.2147/POR.S399221","DOIUrl":"https://doi.org/10.2147/POR.S399221","url":null,"abstract":"<p><strong>Background: </strong>The current flows of the SSN represent the set of interest whose interconnection alone justifies the current study. These flows can be interconnected with other sources, institutional or otherwise, in order to answer well-defined questions.</p><p><strong>Objective: </strong>The objective of the study is to verify, through the analysis of administrative databases, any differences in the consumption of health resources between biological off-patent originator drugs and biosimilars in real clinical practice, with particular reference to the rheumatology area.</p><p><strong>Methods: </strong>Through the use of assisted databases (BDA) of ATS Pavia we evaluated the differences in terms of consumption of health resources related to the different drugs under analysis. Annual and daily costs were calculated by total patient cost, stratified for different treatments, considering the sum of total costs for the prescriptions of drugs subject to the analysis. Another objective was to evaluate the adherence of the drugs of interest, by utilizing specific indicators (MPR).</p><p><strong>Results: </strong>A total of 145 patients were analyzed. Among enrolled patients, 26.9% of users were treated with a biosimilar drug, while 73.1% with a biologic originator. Adherence is higher if it is considered the population treated with biosimilar drugs (82.1%). Total cost (including drug prescriptions, hospitalizations, outpatient services, tests for any cause) during the observation period of 1 year is 14,274.08. 87.7% of the total is attributable to drugs. Non-hospitalized patients are the least expensive, whether they were treated with biologics or biosimilars.</p><p><strong>Conclusion: </strong>In our sample, biosimilar drugs tend to be underused: the treatment of a patient with a chronic autoimmune disease is a clinical process that involves many health professionals, and a criticality could also derive from the difficult communication between the various professional figures who get involved with the whole patient treatment.</p>","PeriodicalId":20399,"journal":{"name":"Pragmatic and Observational Research","volume":"14 ","pages":"29-38"},"PeriodicalIF":8.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cc/71/por-14-29.PMC10122854.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9431793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alignment of Physician-Stated vs Clinically Derived Reference Fibrosis Score in Patients with Non-Alcoholic Steatohepatitis: A Real-World European Survey.","authors":"Quentin M Anstee,&nbsp;Kate Hallsworth,&nbsp;Niall Lynch,&nbsp;Adrien Hauvespre,&nbsp;Eid Mansour,&nbsp;Sam Kozma,&nbsp;Juliana Bottomley,&nbsp;Gary Milligan,&nbsp;James Piercy,&nbsp;Victoria Higgins","doi":"10.2147/POR.S392320","DOIUrl":"https://doi.org/10.2147/POR.S392320","url":null,"abstract":"<p><strong>Objective: </strong>Stratifying disease severity in patients with non-alcoholic steatohepatitis (NASH) is essential for appropriate treatment and long-term management. Liver biopsy is the reference standard for fibrosis severity in NASH, but less invasive methods are used, eg, Fibrosis-4 Index (FIB-4) and vibration-controlled transient elastography (VCTE), for which reference thresholds for no/early fibrosis and advanced fibrosis are available. We compared subjective physician assessment of NASH fibrosis versus reference thresholds to understand classification in a real-world setting.</p><p><strong>Methods: </strong>Data were drawn from Adelphi Real World NASH Disease Specific Programme^TM conducted in France, Germany, Italy, Spain and UK in 2018. Physicians (diabetologists, gastroenterologists, hepatologists) completed questionnaires for five consecutive NASH patients presenting for routine care. Physician-stated fibrosis score (PSFS) based on available information was compared with clinically defined reference fibrosis stage (CRFS) determined retrospectively using VCTE and FIB-4 data and eight reference thresholds.</p><p><strong>Results: </strong>One thousand two hundred and eleven patients had VCTE (n = 1115) and/or FIB-4 (n = 524). Depending on thresholds, physicians underestimated severity in 16-33% (FIB-4) and 27-50% of patients (VCTE). Using VCTE ≥12.2, diabetologists, gastroenterologists and hepatologists underestimated disease severity in 35%, 32%, and 27% of patients, respectively, and overestimated fibrosis in 3%, 4%, and 9%, respectively (p = 0.0083 across specialties). Hepatologists and gastroenterologists had higher liver biopsy rates than diabetologists (52%, 56%, 47%, respectively).</p><p><strong>Conclusion: </strong>PSFS did not consistently align with CRFS in this NASH real-world setting. Underestimation was more common than overestimation, potentially leading to undertreatment of patients with advanced fibrosis. More guidance on interpreting test results when classifying fibrosis is needed, thereby improving management of NASH.</p>","PeriodicalId":20399,"journal":{"name":"Pragmatic and Observational Research","volume":"14 ","pages":"13-27"},"PeriodicalIF":8.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fa/3d/por-14-13.PMC9974948.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10853693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real World Data Studies of Antineoplastic Drugs: How Can They Be Improved to Steer Everyday Use in the Clinic?","authors":"Gincy George,&nbsp;Beth Russell,&nbsp;Anne Rigg,&nbsp;Anthony C C Coolen,&nbsp;Mieke Van Hemelrijck","doi":"10.2147/POR.S395959","DOIUrl":"https://doi.org/10.2147/POR.S395959","url":null,"abstract":"<p><p>There is a growing interest in real world evidence when developing antineoplastic drugs owing to the shorter length of time and low costs compared to randomised controlled trials. External validity of studies in the regulatory phase can be enhanced by complementing randomised controlled trials with real world evidence. Furthermore, the use of real world evidence ensures the inclusion of patients often excluded from randomised controlled trials such as the elderly, certain ethnicities or those from certain geographical areas. This review explores approaches in which real world data may be integrated with randomised controlled trials. One approach is by using big data, especially when investigating drugs in the antineoplastic setting. This can even inform artificial intelligence thus ensuring faster and more precise diagnosis and treatment decisions. Pragmatic trials also offer an approach to examine the effectiveness of novel antineoplastic drugs without evading the benefits of randomised controlled trials. A well-designed pragmatic trial would yield results with high external validity by employing a simple study design with a large sample size and diverse settings. Although randomised controlled trials can determine efficacy of antineoplastic drugs, effectiveness in the real world may differ. The need for pragmatic trials to help guide healthcare decision-making led to the development of trials within cohorts (TWICs). TWICs make use of cohorts to conduct multiple randomised controlled trials while maintaining characteristics of real world data in routine clinical practice. Although real world data is often affected by incomplete data and biases such as selection and unmeasured biases, the use of big data and pragmatic approaches can improve the use of real world data in the development of antineoplastic drugs that can in turn steer decision-making in clinical practice.</p>","PeriodicalId":20399,"journal":{"name":"Pragmatic and Observational Research","volume":"14 ","pages":"95-100"},"PeriodicalIF":8.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/de/c2/por-14-95.PMC10493103.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10284671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}