Personalized benefit‐risk assessments combining clinical trial and real‐world data provide further insights into which patients may benefit most from therapy: Demonstration for a new oral antiplatelet therapy

2019 ◽  
Vol 28 (4) ◽  
pp. 443-451 ◽  
Author(s):  
Cathy Anne Pinto ◽  
Tommi Tervonen ◽  
Kevin Marsh ◽  
Dimitra Lambrelli ◽  
Anna Schultze ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Antiplatelet Therapy ◽  
Real World ◽  
Risk Assessments ◽  
Real World Data ◽  
World Data

The rate of tumor growth, g, as a biomarker for overall survival (OS) in prostate cancer (PC) in clinical trials as well as in real-world data from the Veterans Administration Medical Centers (VAMCs).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5074-5074
Author(s):  
Harshraj Leuva ◽  
Mengxi Zhou ◽  
Julia Wilkerson ◽  
Keith Sigel ◽  
Ta-Chueh Hsu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Clinical Trials ◽  
Tumor Growth ◽  
Real World ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Real World Data ◽  
World Data

5074 Background: Novel assessments of efficacy are needed to improve determination of treatment outcomes in clinical trials and in real-world settings. Methods: Cancer treatments usually lead to concurrent regression and growth of the drug-sensitive and drug-resistant fractions of a tumor, respectively. We have exploited novel methods of analysis that assess these two simultaneous processes and have estimated rates of tumor growth ( g) and regression ( d) in over 30,000 patients (pts) with diverse tumors. Results: In prostate cancer (PC) we have analyzed both clinical trial and real-world data from Veterans. Using clinical trial data from 6819 pts enrolled in 15 treatment arms we have established separately and by combining all the data that g correlates highly (p<0.0001) with overall survival (OS) – slower g associated with better OS. In PC, abiraterone (ABI) and docetaxel (DOC) are superior to placebo, prednisone and mitoxantrone. ABI (median g =0.0017) is superior to DOC ( g=0.0021) in first line (p=0.0013); and ABI in 2nd line ( g=0.0034) is inferior to ABI in 1st line ( g=0.0017; p<0.0001). Finally, using combined clinical trial data as a benchmark we could assess the efficacy of novel therapies in as few as 30-40 patients. Amongst 7457 Veterans, the median g on a taxane ( g=0.0022) was similar to that from clinical trials ( g=0.0012). Although only 258 Veterans received cabazitaxel (CAB), g values for CAB ( g=0.0018) and DOC ( g=0.0023) were indistinguishable (p=0.3) consistent with their identical mechanism of action. Finally, outcomes with DOC in African American (AA) ( g=0.00212) and Caucasian ( g=0.00205) Veterans were indistinguishable (p=0.9) and comparable across all VAMCs. Conclusions: The rate of tumor growth, g, is an excellent biomarker for OS both in clinical trials and in real-world settings. g allows comparisons between trials and for large trial data sets to be used as benchmarks of efficacy. Real-world outcomes in the VAMCs are similar to those in clinical trials. In the egalitarian VAMCs DOC efficacy in PC is comparable in AA and Caucasian Veterans -- indicating inferior outcomes reported in AAs are likely due to differential health care access, not differences in biology.

Tumor response and growth rate of nivolumab treatment in advanced gastric cancer: Real-world data from a large observational/translational study, JACCRO GC-08 (deliver trial).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4527-4527
Author(s):  
Ryohei Kawabata ◽  
Yasuhiro Sakamoto ◽  
Eisuke Inoue ◽  
Atsushi Ishiguro ◽  
Yusuke Akamaru ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Growth Rate ◽  
Tumor Growth ◽  
Real World ◽  
Fold Increase ◽  
Real World Data ◽  
World Data ◽  
Translational Study ◽  
Before And After

4527 Background: Nivolumab (Nivo) demonstrated survival benefit in previously treated gastric cancer (GC) patients (pts), with a response rate (RR) of 11% and a disease control rate (DCR) of 40% (Kang YK, et al. Lancet 2017). There are few real-world data of Nivo and its predictive markers are needed in GC. It has been demonstrated that some tumors grow rapidly after Nivo treatment, but the proportion is uncertain. Methods: DELIVER trial was a prospective, multicenter, observational/translational study which assessed pts with advanced GC treated with Nivo alone and ECOG Performance Status (PS) 0-2 (UMIN000030850). The aims were to evaluate the efficacy and safety of Nivo in real world, and to discover novel host-related immune-biomarkers (gut microbiome, genetic polymorphism, gene expression, and metabolome) using fecal and blood samples which were collected before and after Nivo treatment. The RR, DCR, progression-free survival, overall survival, and tumor growth rate (TGR) were estimated as the efficacy. The response was evaluated by first imaging based on RECIST version 1.1. The TGR was calculated as a percentage increase in tumor volume during 1 month (Champiat et al. Clin Cancer Res 2017). Results: A total of 501 pts was enrolled in this study from Mar 2018 to Aug 2019, and 487 pts were evaluable for analysis (median age 70-y, 71% male, ECOG PS0/1/2 42%/44%/14%, tub/por/sig 45%/41%/5%, 21% HER2-pos, 42% pts with ascites). The DCR was 39.2% (95%CI 34.9-43.7) in evaluable pts. In 282 pts with measurable lesions, the RR was 6.7% (95%CI 4.1-10.3) and DCR was 36.5%. Sub-analysis by patient background indicated that DCR was 41% for PS0, 42% for PS1, and 24% for PS2. In addition, the DCR was lower in pts with ascites compared to those without ascites (28.6% vs. 47.0%, p= 0.005). The TGR decreased after introduction of Nivo in 124 (56.6%) of 219 evaluable pts for TGR; however, 20.5% pts were identified as experiencing hyper-progressive disease (HPD) which was defined as a ≥2-fold increase of the TGR before and after Nivo. When defining HPD as a ≥2-fold increase of tumor growth kinetics ratio and 50% increase of tumor burden, 9.6% pts experienced it. Conclusions: The real-word data of the large observational trial showed a comparable DCR to that of clinical trial in advanced GC treated with Nivo. This trial revealed the tumor behavior and some pts who experienced rapid tumor growth after Nivo treatment in clinical practice; biomarkers for HPD and the definition should be established. Clinical trial information: UMIN000030850 .

scholarly journals Peak Inspiratory Flow Rate in COPD: An Analysis of Clinical Trial and Real-World Data

2021 ◽  
Vol Volume 16 ◽  
pp. 933-943
Author(s):  
Martin Anderson ◽  
Kathryn Collison ◽  
M Bradley Drummond ◽  
Melanie Hamilton ◽  
Renu Jain ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Flow Rate ◽  
Real World ◽  
Inspiratory Flow ◽  
Inspiratory Flow Rate ◽  
Real World Data ◽  
World Data ◽  
Peak Inspiratory Flow ◽  
Peak Inspiratory Flow Rate

scholarly journals Clinical trial and ‘real-world’ data support switching from a bio-originator to its biosimilar

2019 ◽  
Vol 79 (4) ◽  
pp. e44-e44 ◽  
Author(s):  
Jonathan Kay ◽  
Thomas Dörner ◽  
Paul Emery ◽  
Tore K Kvien ◽  
Ferdinand C Breedveld
Keyword(s):  
Clinical Trial ◽  
Real World ◽  
Real World Data ◽  
World Data ◽  
Data Support

Neoadjuvant chemoradiation (NCRT) for esophageal (EC) or gastroesophageal junction cancer (GEJC): A Canadian single institution real-world experience using the CROSS trial regimen.

2019 ◽  
Vol 37 (27_suppl) ◽  
pp. 25-25
Author(s):  
Sidra Khalid ◽  
Wilma M. Hopman ◽  
Beatrice Preti ◽  
Anna T. Tomiak ◽  
Kiran Virik
Keyword(s):  
Clinical Trial ◽  
Real World ◽  
Gastroesophageal Junction ◽  
Trial Protocol ◽  
Single Institution ◽  
Real World Data ◽  
Trimodality Therapy ◽  
World Data ◽  
The Real ◽  
The Cross

25 Background: NCRT followed by surgery per the CROSS trial regimen is an accepted standard of care in the treatment of EC and GEJC. When treatments are used in the real-world setting, there are often patient, treatment and potential outcome differences compared to the original clinical trial. The study aim was to assess the real-world application and outcomes of the CROSS trial protocol. Methods: A retrospective chart review was undertaken of 83 patients (pts) with EC or GEJC who were treated from June 2012 to June 2018 with CRT. 65 pts were with NCRT intent to proceed to surgery. Pts’ demographics, clinical, pathological, treatment and surgical characteristics were assessed and exploratory analyses were conducted to review these factors and outcomes. Analyses included Chi-square, t-tests and Kaplan-Meier. Results: For pts who underwent NCRT (n = 65): median age was 68 yrs (range 52-80), male 79%, adenocarcinoma 82%, median (m) tumor length 5 cm, GERD 43%, clinical stage II/III 95%, and BMI > 30 in 37%. 80% completed CRT with RT ≥ 41.4 Gy; of these 88% had ≥ 50.4 Gy. Delay/interruption in chemotherapy occurred in 46% and in RT 37%. Pts who underwent surgery were younger (p = 0.04) and weighed more (p = 0.05). mOS was 37 months (M) v 14 M in those who started CRT ≤ 8 weeks (w) from diagnosis v > 8 w (p = 0.10). The median time from CRT to surgery was 8.9 w. 40 pts had surgery with a complete response in 38% and a R0 resection in 98%. Postoperative major and minor complications occurred in 67%. Those < 75 yrs v ≥ 75 yrs had a mOS of 32 M v 15 M respectively (log rank p = 0.46). 25 pts did not get surgery; 28% was due to death/progression. Pts who proceeded to surgery had a mOS of 35 M v 12 M in pts who did not go to surgery (log rank p = 0.002). Further correlative outcome data will be presented. Conclusions: Real-world data in our center showed patient, tumor and treatment differences compared to the CROSS trial protocol. Despite the broadening of eligibility and treatment criteria, survival in a single institution setting is maintained with trimodality therapy compared to NCRT alone. Real-world data is of value in the assessment of therapeutic validity of clinical trial data.

Estimate of Real-World Medical Costs Avoidance When New Oral Anticoagulants Are Used Vs. Standard Therapy for the Treatment of Patients with Venous Thromboembolism in the U.S

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 687-687
Author(s):  
Alpesh N Amin ◽  
Amanda Bruno ◽  
Jeffrey Trocio ◽  
Jay Lin ◽  
Melissa Lingohr-Smith
Keyword(s):  
Clinical Trial ◽  
Medical Cost ◽  
Real World ◽  
Standard Therapy ◽  
Clinical Trial Data ◽  
Medical Costs ◽  
Trial Data ◽  
Real World Data ◽  
World Data ◽  
Event Rates

Abstract Introduction: Clinical trials have demonstrated that the new oral anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban are noninferior to standard therapies for treatment of acute symptomatic venous thromboembolism (VTE). We have previously published the medical costs avoided when NOACs are used instead of standard therapies based on rates of clinical events reported in clinical trials. However, the rates of recurrent VTE and major bleeding (MB) in the real-world settings may differ from those from the clinical trials. In this study, we estimated the real-world medical cost avoidance from a U.S. payer perspective when NOACs are used instead of standard therapy for the treatment of patients with VTE. Methods: Reduction of real-world event rates of recurrent VTE and MB were obtained by applying rate reductions observed in clinical studies to the Worcester population. Incremental annual medical costs among patients with VTE and MB from a U.S. payer perspective were obtained from the literature or healthcare claims databases and inflation adjusted to 2013 costs. Differences in total medical costs associated with clinical endpoints for patients treated with NOACs vs. standard therapy were then estimated. One-way univariate and Monte Carlo sensitivity analyses were additionally carried out. Univariate analysis varied the estimates of the clinical event rates between the ranges of confidence intervals and the estimates of event costs ±30% when such confidence intervals were not reported. Ten thousand cycles of Monte-Carlo simulations were used for additional sensitivity analysis where all model parameters were allowed to vary simultaneously. Results: Real-world event rates of recurrent VTE and MB in the Worcester VTE study were 11.2% and 10.8% respectively. Differences in real-world event rates of recurrent VTE among VTE patients treated with NOACs instead of standard therapy were estimated at -1.80% for apixaban, -1.23% for rivaroxaban, -2.02% for edoxaban, and 1.02% for dabigatran. Differences in real-world event rates of MB among VTE patients treated with NOACs instead of standard therapy were estimated at -7.48% for apixaban, -4.97% for rivaroxaban, -1.73% for edoxaban, and -2.57% for dabigatran. Based on the real-world data, the annual total medical cost avoidances vs. standard therapy were greatest for VTE patients treated with apixaban (-$4,440 per patient year-ppy), followed by those treated with rivaroxaban (-$2,971 ppy), edoxaban (-$1,957 ppy), and dabigatran (-$572 ppy). In comparison to data previously reported based on clinical trials, these medical cost avoidances are substantially greater for any of the NOACs vs. standard therapy (Table). The medical cost avoidances remained consistent under univariate (one-way) sensitivity. Additionally, the mean cost estimates of 10,000 random cycles of Monte-Carlo simulations for each of the NOACs were similar to the default estimated medical cost avoidances, demonstrating the robustness of the model estimates. Conclusions: Based on real-world data, when any of the evaluated NOACs are used instead of standard therapy for treatment of patients with acute VTE annual medical costs are reduced. In the real-world setting, the use of NOACs vs. standard therapy is predicted to be associated with even greater annual medical cost reductions than that previously estimated based on clinical trial data. Of the NOACs, apixaban has the greatest real-world medical cost avoidance, as its use is associated with substantial reductions in both VTE and MB event rates. Abstract 687. Table 1 Estimates of Medical Cost Differences Among VTE Patients Treated with NOACs vs. Standard Therapy Based on Clinical Trial Data vs. Real-World Data Outcome Apixaban ($/patient-yr) Rivaroxaban ($/patient-yr) Edoxaban ($/patient-yr) Dabigatran ($/patient-yr) Recurrent VTE* Clinical trial data -$252 -$132 -$197 $114 Real-world data -$1,047 -$717 -$1,173 $595 Major bleedings* Clinical trial data -$572 -$354 -$109 -$195 Real-world data -$3,392 -$2,254 -$784 -$1,167 Total Medical Cost* Clinical trial data -$824 -$486 -$306 -$80 Real-world data -$4,440 -$2,971 -$1,957 -$572 *Negative values mean the NOAC is associated with lower total medical cost vs. standard therapy. Disclosures Amin: Bristol-Myers Squibb, Pfizer: Consultancy. Off Label Use: Apixaban and edoxaban for the indication of VTE. Bruno:Bristol-Myers Squibb: Employment, Equity Ownership. Trocio:Pfizer: Employment, Equity Ownership. Lin:Bristol-Myers Squibb, Pfizer: Consultancy, Research Funding. Lingohr-Smith:Bristol-Myers Squibb, Pfizer: Consultancy, Research Funding.

scholarly journals P2.07-044 Thyroid Disfunction in Advanced NSCLC Patients Treated with Nivolumab out of Clinical Trial: A Real-World Data Analysis

2017 ◽  
Vol 12 (11) ◽  
pp. S2432
Author(s):  
R. Palmero ◽  
J.C. Ruffinelli ◽  
E. Alanya ◽  
J.A. Marin ◽  
M. Ferrer ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Data Analysis ◽  
Real World ◽  
Advanced Nsclc ◽  
Real World Data ◽  
World Data ◽  
Nsclc Patients
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