scholarly journals P477 Assessment of treatment sequence and real-world outcomes in patients with Ulcerative Colitis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S466-S467
Author(s):  
J Chen ◽  
Y Zhao ◽  
T Liu ◽  
N Candela ◽  
K Lasch
Keyword(s):  
Ulcerative Colitis ◽  
Laboratory Test ◽  
Real World ◽  
International Classification Of Diseases ◽  
Research Database ◽  
Treatment Sequence ◽  
Real World Data ◽  
Optimal Position ◽  
The Impact ◽  
Treatment Sequences

Abstract Background Several therapies are available to manage moderately to severely active ulcerative colitis (UC); however, little is known about the impact of treatment sequence on patient outcomes. Using real-world data, we assessed the outcomes of patients treated with different UC treatment sequences in routine clinical practice in the USA with the aim of determining the optimal position of vedolizumab within the current UC treatment paradigm. Methods This analysis used deidentified claims and clinical data from the Optum Research Database between 2016 and 2019. Patients diagnosed with UC were identified using International Classification of Diseases, Tenth Revision codes, and UC treatments were identified using National Drug Codes. Two scenarios of treatment sequences were analysed: with (S1) or without (S2) the inclusion of immunomodulator (IM) therapy (Table). Patients were matched on baseline age, sex and race using nearest neighbour propensity score matching. Outcomes, including colectomy-related procedure, disease flare defined as a relevant diagnostic/imaging procedure, UC-related hospitalization, UC-related laboratory test abnormality and all-cause death, were described for each of the treatment sequences (Figure 1). Results Of a total of 143 678 patients diagnosed with UC, 3291 were treated with vedolizumab and an IM and/or an anti-tumour necrosis factor (TNF) therapy. Patients who received vedolizumab before an IM and/or anti-TNF therapy (S1a and S2a) had better outcomes than those who received vedolizumab after one or both of these therapies, including a numerically lower rate of UC-related hospitalizations, colectomies, disease flares, UC-related laboratory test abnormalities and all-cause death (Figures 2 and 3). Conclusion Given the increasing number of therapies available for the management of UC, it is important to understand the impact of treatment sequence on outcomes. Clinical trial evidence suggests that patients with UC may experience better outcomes when vedolizumab is used prior to anti-TNF therapy. This observation is consistent with the findings of this analysis of real-world outcomes in patients with UC who received treatments in different sequences. Owing to the nature of the data, the population could not be stratified by disease activity. Future work will aim to further characterize outcomes associated with different treatment sequences in patients with moderately to severely active UC and include newly available therapies.

scholarly journals P535 Optimising vedolizumab in treatment sequences for Crohn’s disease: Results from a simulation model using real-world evidence

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S509-S509
Author(s):  
E Louis ◽  
A Nikolaou ◽  
M Litkiewicz ◽  
C Agboton ◽  
S Wang ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Simulation Model ◽  
Clinical Response ◽  
Real World ◽  
Treatment Sequence ◽  
Real World Evidence ◽  
Patient Reported ◽  
The Impact ◽  
Treatment Sequences

Abstract Background With the availability of biologic therapies for treating Crohn’s disease (CD) there are limited data to inform optimal treatment decisions. Vedolizumab (VDZ), an anti-integrin antibody that selectively targets lymphocyte migration to the gut, was approved in 2014 for the treatment of moderate-to-severe CD. We developed a model based on real-world evidence (RWE) to examine the effect of different positioning for VDZ in CD treatment sequences on clinical outcomes. Methods A Markov sequential model was developed to identify the optimal position of VDZ within a sequence of CD therapies that included corticosteroids (CS), 2 biologics and best supportive care. Three sequences were compared: VDZ as first biologic (first position), second and last biologic among anti-TNFs and ustekinumab as alternate biologic treatments. To test the behaviour of the model, VDZ was also positioned before CS (Position 0, off label). Model inputs were informed using published RWE. At each position in the treatment sequence, patients achieving clinical response or remission during induction continued on maintenance; patients on maintenance could lose clinical response or remission; patients who did not achieve response during induction or lost response during maintenance (including after dose escalation) moved to the next position of the sequence after a treatment-free interval. Surgery, development of intestinal malignancy/lymphoma, and discontinuation of treatment due to serious adverse events or death could occur at each sequence position. VDZ sequences were compared and ranked based on quality-adjusted life years (QALYs), patient-reported outcomes (PRO2/3) derived from CDAI scores, or proportion of patients undergoing surgery by the end of the 10-year time horizon for model simulation. Probabilistic sensitivity analysis (PSA) evaluated the impact of model inputs uncertainty on the outcomes. Results For QALYs, PRO2/3, and rates of surgery, VDZ early in the treatment sequence was the optimal positioning strategy (Table). Using QALYs as the ranking criterion, VDZ before CS was the optimal sequence yielding 5.19 QALYs and incremental QALYs of 0.7, 0.20, and 0.20 versus the second-, third- and fourth-line strategy, respectively. The ranking of VDZ in treatment sequences was preserved when PRO2/3 or surgery were used as ranking criteria. In 1,780/2,000 PSA iterations (89%), VDZ before CS or as first biologic yielded the highest QALYs vs. other sequence positions. Conclusion The results of this simulation model using real-world evidence clearly indicate that positioning VDZ earlier in the treatment sequence may yield better patient outcomes in terms of QALYs, PROs and rates of surgery.

scholarly journals NCDB Analysis of Melanoma 2004–2015: Epidemiology and Outcomes by Subtype, Sociodemographic Factors Impacting Clinical Presentation, and Real-World Survival Benefit of Immunotherapy Approval

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1455
Author(s):  
Sunny R. K. Singh ◽  
Sindhu J. Malapati ◽  
Rohit Kumar ◽  
Christopher Willner ◽  
Ding Wang
Keyword(s):  
Metastatic Melanoma ◽  
Metastatic Disease ◽  
Real World ◽  
Care Delivery ◽  
Sociodemographic Factors ◽  
P Value ◽  
Real World Data ◽  
Factors Associated ◽  
Improvement In Survival ◽  
The Impact

Background: The incidence of invasive melanoma is rising, and approval for the first immune checkpoint inhibitor (ICI) to treat metastatic melanoma occurred in 2011. We aim to describe the epidemiology and outcomes in recent years, sociodemographic factors associated with the presence of metastasis at diagnosis, and the real‐world impact of ICI approval on survival based on melanoma subtype and race. Methods: This is a retrospective analysis of the National Cancer Database (NCDB) from the years 2004–2015. The primary outcome was the overall survival of metastatic melanoma by subtype. Secondary outcomes included sociodemographic factors associated with the presence of metastasis at diagnosis and the impact of treatment facility type and ICI approval on the survival of metastatic melanoma. Results: Of the 419,773 invasive melanoma cases, 93.80% were cutaneous, and 4.92% were metastatic at presentation. The odds of presenting with metastatic disease were higher in African Americans (AA) compared to Caucasians (OR 2.37; 95% CI 2.11–2.66, p < 0.001). Treatment of metastatic melanoma at an academic/research facility was associated with lower mortality versus community cancer programs (OR 0.75, 95 % CI 0.69–0.81, p-value<0.001). Improvement in survival of metastatic melanoma was noted for Caucasians after the introduction of ICI (adjusted HR 0.80, 95% CI 0.78–0.83, p < 0.001); however, this was not statistically significant for AA (adjusted HR 0.80, 95% CI 0.62–1.02, p‐value = 0.073) or ocular cases (HR 1.03, 95% CI 0.81–1.31, p‐value 0.797). Conclusion: Real‐world data suggest a 20% improvement in survival of metastatic melanoma since the introduction of ICI. The disproportionately high odds of metastatic disease at presentation in AA patients with melanoma suggest the need for a better understanding of the disease and improvement in care delivery.

PIN83 The COVID-19 Research Database: Building One of the Largest PRO Bono Real-World DATA Repositories

2021 ◽  
Vol 24 ◽  
pp. S121
Author(s):  
A. Talwai ◽  
V. Wing ◽  
Y. Itzkovich ◽  
A. Galaznik ◽  
A. Chatterjee ◽  
...  
Keyword(s):  
Real World ◽  
Research Database ◽  
Real World Data ◽  
Data Repositories ◽  
World Data ◽  
Pro Bono

PD-0776 A Bayesian approach to evaluate the impact of change in IGRT protocol using real world data

2021 ◽  
Vol 161 ◽  
pp. S608
Author(s):  
I. Fornacon-Wood ◽  
H. Mistry ◽  
C. Johnson-Hart ◽  
J.P.B. O’Connor ◽  
C. Faivre-Finn ◽  
...  
Keyword(s):  
Bayesian Approach ◽  
Real World ◽  
Real World Data ◽  
World Data ◽  
The Impact

scholarly journals A Comparison of the Randomized Clinical Trial Efficacy and Real-World Effectiveness of Tofacitinib for the Treatment of Inflammatory Bowel Disease: A Cohort Study

2019 ◽  
Author(s):  
Vivek A. Rudrapatna ◽  
Benjamin S. Glicksberg ◽  
Atul J. Butte
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Real World ◽  
Controlled Trials ◽  
Real World Data ◽  
Eligibility Criteria ◽  
Primary Endpoints ◽  
Three Phase

AbstractBackgroundReal-world data are receiving attention from regulators, biopharmaceuticals and payors as a potential source of clinical evidence. However, the suitability of these data to produce evidence commensurate with randomized controlled trials (RCTs) and the best practices in their use remain unclear. We sought to compare the real-world effectiveness of Tofacitinib in the treatment of IBD against efficacy rates published by corresponding RCTs.MethodsElectronic health records at the University of California, San Francisco (UCSF) were queried and reviewed to identify 86 Tofacitinib-treated IBD patients through 4/2019. The primary endpoint was treatment effectiveness. This was measured by time-to-treatment-discontinuation and by the primary endpoints of RCTs in Ulcerative Colitis (UC) and Crohn’s Disease (CD). Endpoints were measured and analyzed following a previously published protocol and analysis plan.Findings86 patients (68 with UC, 18 with CD) initiated Tofacitinib for IBD treatment. Most of the data needed to calculate baseline and follow-up disease activity indices were documented within the EHR(77% for UC, 91% for CD). Baseline characteristics of the UCSF and RCT cohorts were similar, except for a longer disease duration and 100% treatment failure of Tumor Necrosis Factor inhibitors in the former. None of the UCSF cohort would have met the RCT eligibility criteria due to multiple reasons.The rate of achieving the RCT primary endpoints were highly similar to the published rates for both UC(16%, P=0·5) and CD (38%, P=0·8). However, treatment persistence was substantially higher: 69% for UC (week 52) and 75% for CD (week 26).InterpretationAn analysis of routinely collected clinical data can reproduce published Tofacitinib efficacy rates, but also indicates far greater treatment durability than suggested by RCTs including possible benefit in CD. These results underscore the value of real-world studies to complement RCTs.FundingThe National Institutes of Health and UCSF Bakar InstituteResearch in ContextEvidence before this studyTofacitinib is the most recently approved treatment for Ulcerative Colitis. Data related to treatment efficacy for either IBD subtype is generally limited, whether from controlled trials or real-world studies. A search of clinicaltrials.gov was performed in January 2019 for completed phase 2 or 3, interventional, placebo-controlled clinical trials matching the terms “Crohn’s Disease” OR “Ulcerative Colitis” in the conditions field, and matching “Placebo” AND “Tofacitinib” OR “CP-690,550”) in the Interventions field. We identified three Phase 3 trials for UC (OCTAVE trials, all initially reported in a single article in 2016) and three Phase 2 trials of CD (two published in the same article in 2017, one reported in 2014). The Phase 3 UC trials reported 57·6% pooled clinical response rate in the Tofacitinib-assigned groups after 8 weeks (induction), and a 37·5% pooled remission rate among eligible induction trial responders in the Tofacitinib-assigned groups at 52 weeks. The 2017 CD trial reported a 70·8% pooled rate of response or remission in the Tofacitinib-assigned groups after 8 weeks, and a 47·6% pooled rate of response or remission among enrolled induction-trial responders at 26 weeks. A bias assessment of both UC and CD trials indicated a high risk of attrition bias and unclear risk of bias related to conflicts of interest. We also performed a search of pubmed.gov in January 2019 using search terms (“Colitis” OR “Crohn’s”) AND (“Tofacitinib” OR “CP-690,550”) OR “real-world” to identify cohort studies of Tofacitinib efficacy in routine clinical practice. No studies meeting these criteria were identified.Added value of this studyThis is one of the early studies to closely compare the results of clinical trials with the continuously-updated data captured in the electronic health records, and the very the first to assess the efficacy-effectiveness gap for Tofacitinib. We found that none of the patients treated at our center thus far would have qualified for the clinical trial based on published eligibility criteria. We found that the drug appeared to perform similarly to its efficacy when using the endpoints reported in clinical trials, but treatment persistence was significantly greater than would have been expected from the reported trial outcomes: 69% for UC at week 52 and 75% for CD at week 26.Implications of all the available evidenceTofacitinib is an effective treatment for the Ulcerative colitis and may be efficacious for Crohn’s disease. Controlled trials may not be representative of real-world cohorts, may not be optimally designed to identify efficacious drugs, and may not accurately predict patterns of use in clinical practice. Further studies using real-world data as well as methods to enable their proper use are needed to confirm and continuously monitor the efficacy and safety of drugs, both for on- and off-label use.

Assessment and design of real world driving cycles targeted to the calibration of vehicles with electrified powertrain

2021 ◽  
pp. 146808742110387
Author(s):  
Stylianos Doulgeris ◽  
Zisimos Toumasatos ◽  
Maria Vittoria Prati ◽  
Carlo Beatrice ◽  
Zissis Samaras
Keyword(s):  
Real World ◽  
Simulation Models ◽  
Cost Effective ◽  
Operational Parameters ◽  
Virtual Design ◽  
Passenger Cars ◽  
Real World Data ◽  
Vehicle Simulation ◽  
Driving Cycles ◽  
The Impact

Vehicles’ powertrain electrification is one of the key measures adopted by manufacturers in order to develop low emissions vehicles and reduce the CO2 emissions from passenger cars. High complexity of electrified powertrains increases the demand of cost-effective tools that can be used during the design of such powertrain architectures. Objective of the study is the proposal of a series of real-world velocity profiles that can be used during virtual design. To that aim, using three state of the art plug-in hybrid vehicles, a combined experimental, and simulation approach is followed to derive generic real-world cycles that can be used for the evaluation of the overall energy efficiency of electrified powertrains. The vehicles were tested under standard real driving emissions routes, real-world routes with reversed order (compared to a standard real driving emissions route) of urban, rural, motorway, and routes with high slope variation. To enhance the experimental activities, additional virtual mission profiles simulated using vehicle simulation models. Outcome of the study consists of specific driving cycles, designed based on standard real-world route, and a methodology for real-world data analysis and evaluation, along with the results from the assessment of the impact of different operational parameters on the total electrified powertrain.

scholarly journals Indirect costs associated with ulcerative colitis: a systematic literature review of real-world data

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Joelle Constantin ◽  
Petar Atanasov ◽  
Daniel Wirth ◽  
Andras Borsi
Keyword(s):  
Ulcerative Colitis ◽  
Sick Leave ◽  
Indirect Costs ◽  
Cochrane Library ◽  
Real World Data ◽  
Eligibility Criteria ◽  
Productivity Costs ◽  
Productivity Losses ◽  
The Impact

Abstract Background The economic burden of ulcerative colitis (UC), specifically related to indirect costs, is not extensively documented. Understanding and quantifying it is required by health care decision makers. Aim To assess the impact of indirect costs of UC in observation studies. Method A systematic literature search was conducted in MEDLINE®, Embase® and Cochrane Library to capture all relevant publications reporting outcomes on absenteeism, presenteeism and productivity losses in moderate to severe UC. Eligibility criteria for inclusion into the review were established using a predefined PICOS scheme. All costs were adjusted to 2017 currency values (USD dollars, $). Results In total, 18 studies reporting data on indirect costs were included in the analysis. Absenteeism costs were classified into three categories: sick leave, short-term and long-term disability. Most of the studies captured absenteeism costs related specifically to sick leave, which was experienced on average by 10 to 24% patients with UC. Only three studies captured presenteeism costs, as these are difficult to measure, however costs ranged from 1602 $ to 2947 $ per patient year. The proportion of indirect costs accounted for 35% of total UC costs (Total UC costs were defined as the sum of healthcare costs, productivity costs and out-of-pocket costs). Discussion A limited number of studies were identified describing the indirect costs in patients with moderate to severe UC. Insufficient data on different components of costs allowed a limited analysis on the impact of indirect costs in patients with UC. Further studies are needed to gain an understanding of the influence of UC on patients’ functional abilities.

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