TRANSLATION OF CLINICAL TRIAL TO REAL WORLD PRACTICE: CAN SACUBITRIL-VALSARTAN BE SAFELY TITRATED TO TARGET DOSE, 97/103MG BI-DAILY, IN CLINICAL PRACTICE AND WHAT BASELINE CHARACTERISTICS PREDICT SUCCESSFUL TITRATION?

2019 ◽  
Vol 73 (9) ◽  
pp. 704
Author(s):  
Alexander Dashwood ◽  
Cassandra Vale ◽  
Shaaheen Laher ◽  
Haunnah Rheault ◽  
Scott Mckenzie ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Practice ◽  
Real World ◽  
Target Dose ◽  
Baseline Characteristics

scholarly journals Developing real-world comparators for clinical trials in chemotherapy-refractory patients with gastric cancer or gastroesophageal junction cancer

2019 ◽  
Vol 23 (1) ◽  
pp. 133-141 ◽  
Author(s):  
Ian Chau ◽  
Dung T. Le ◽  
Patrick A. Ott ◽  
Beata Korytowsky ◽  
Hannah Le ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Real World ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Eligibility Criteria ◽  
Asian Patients ◽  
Baseline Characteristics

Abstract Background There are few third-line or later (3L+) treatment options for advanced/metastatic (adv/met) gastric cancer/gastroesophageal junction cancers (GC/GEJC). 3L+ Nivolumab demonstrated encouraging results in Asian patients in the ATTRACTION-2 study compared with placebo (12-month survival, 26% vs 11%), and in Western patients in the single-arm CheckMate 032 study (12-month survival, 44%). This analysis aimed to establish comparator cohorts of US patients receiving routine care in real-world (RW) clinical practice. Methods A 2-step matching process generated RW cohorts from Flatiron Health’s oncology database (January 1, 2011–April 30, 2017), for comparison with each trial: (1) clinical trial eligibility criteria were applied; (2) patients were frequency-matched with trial arms for baseline variables significantly associated with survival. Median overall survival (OS) was calculated by Kaplan–Meier analysis from last treatment until death. Results Of 742 adv/met GC/GEJC patients with at least 2 prior lines of therapy, matching generated 90 US RW ATTRACTION-2-matched patients (median OS: 3.5 months) versus 163 ATTRACTION-2 placebo patients (median OS: 4.1 months), and 100 US RW CheckMate 032-matched patients (median OS: 2.9 months) versus 42 CheckMate 032 nivolumab-treated patients (median OS: 8.5 months). Baseline characteristics were generally similar between clinical trial arms and RW-matched cohorts. Conclusions We successfully developed RW cohorts for comparison with data from clinical trials, with comparable baseline characteristics. Survival in US patients receiving RW care was similar to that seen in Asian patients receiving placebo in ATTRACTION-2; survival with nivolumab in CheckMate 032 appeared favorable compared with US RW clinical practice.

scholarly journals Effectiveness of Tocilizumab in Patients with Rheumatoid Arthritis Is Unaffected by Comorbidity Burden or Obesity: Data from a US Registry

2020 ◽  
Vol 47 (10) ◽  
pp. 1464-1474 ◽  
Author(s):  
Dimitrios A. Pappas ◽  
Carol J. Etzel ◽  
Margaux Crabtree ◽  
Taylor Blachley ◽  
Jennie Best ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Body Mass Index ◽  
Clinical Practice ◽  
Disease Activity ◽  
Real World ◽  
Obesity Status ◽  
Comorbidity Burden ◽  
Comorbidity Index ◽  
Baseline Characteristics ◽  
High Comorbidity

ObjectiveComorbidity burden and obesity may affect treatment response in patients with rheumatoid arthritis (RA). Few real-world studies have evaluated the effect of comorbidity burden or obesity on the effectiveness of tocilizumab (TCZ). This study evaluated TCZ effectiveness in treating RA patients with high versus low comorbidity burden and obesity versus nonobesity in US clinical practice.MethodsPatients in the Corrona RA registry who initiated TCZ were stratified by low or high comorbidity burden using a modified Charlson Comorbidity Index (mCCI) and by obese or nonobese status using body mass index (BMI). Improvements in disease activity and functionality after TCZ initiation were compared for the above strata of patients at 6 and 12 months after adjusting for statistically significant differences in baseline characteristics.ResultsWe identified patients with high (mCCI ≥ 2; n = 195) and low (mCCI < 2; n = 575) comorbidity burden and patients categorized as obese (BMI ≥ 30; n = 356) and nonobese (BMI < 30; n = 449) who were treated with TCZ. Most patients (> 95%) were biologic experienced and about one-third of patients received TCZ as monotherapy, with no significant differences between patients by comorbidity burden or obesity status. Improvement in disease activity and functionality at 6 and 12 months was similar between groups, regardless of comorbidity burden or obesity status.ConclusionIn this real-world analysis, TCZ was frequently used to treat patients with high comorbidity burden or obesity. Effectiveness of TCZ did not differ by comorbidity or obesity status.

Assessing real-world clinical response in patients with multiple myeloma (MM): A survey of the literature.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19260-e19260
Author(s):  
Daniel Lane ◽  
Andrew D. Norden ◽  
Andrew J. Belli ◽  
Ching-Kun Wang
Keyword(s):  
Clinical Trial ◽  
Clinical Practice ◽  
Real World ◽  
English Language ◽  
Complete Response ◽  
Protein Electrophoresis ◽  
Mandatory Reporting ◽  
Routine Clinical Practice ◽  
Cell Transplant ◽  
Strict Adherence

e19260 Background: A recent study (Foster, Tromanhauser et al. 2019) utilizing Electronic Health Record (EHR) data found that patients with MM rarely have both serum protein electrophoresis (SPEP) and 24-hour urine protein electrophoresis (UPEP) documented in routine clinical practice settings. These elements are necessary to classify response using the International Myeloma Working Group (IMWG) consensus criteria. It could be hypothesized that adding the additional requirements for bone marrow biopsy necessary to confirm a complete response would further reduce the rate of strict adherence to the IMWG criteria in the real world (RW). Clinicians are however assessing response and progression in RW settings and often report these assessments in published literature. In this study, we survey the literature to determine how RW response is being captured and reported outside of the clinical trial setting. Methods: A systematic search was performed using Medline 2010-2019. Using a standardized grading system, English language articles were evaluated that utilized EHR data from routine clinical practice to report RW response in patients with active MM. Registry based and/or pragmatic observational studies were excluded as many had mandatory reporting procedures in place. Studies were then categorized based on methods of assessing response, progression and use of IMWG criteria. Results: The majority of studies grade 1 studies identified (21/25) utilized best response achieved based on treating physician-documented assessment and either did not specify the use of IMWG(10/21) criteria or explicitly stated they did not use conventional criteria (11/21). Progression event capture and reporting varied greatly with many using physician-documented progression, change in regimen, addition of additional agents to existing regimen, stem cell transplant, or an individually created algorithm. Conclusions: Our findings suggest that there is a need for further research on objective techniques for the assessment of RW progression and response in patients with MM. Additionally, validation of an approach that utilizes partial adherence to IMWG criteria would help in the ability to compare findings across clinical trial and RW settings. This validation work is under way, and preliminary results will be reported at the meeting.

scholarly journals Baseline characteristics of patients with transthyretin amyloid cardiomyopathy enrolled in a tafamidis expanded access programme

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M H Rozenbaum ◽  
I Ionescu ◽  
M Clausen ◽  
M Lopez ◽  
M B Sultan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Real World ◽  
Nyha Class ◽  
Class I ◽  
Wild Type ◽  
Real World Data ◽  
Expanded Access Programme ◽  
Access Programme ◽  
Baseline Characteristics ◽  
Amyloid Cardiomyopathy

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and ultimately fatal disease caused by the accumulation of amyloid fibrils in the heart muscle. Tafamidis, currently the only approved drug for the treatment of ATTR-CM, demonstrated reduced mortality and cardiovascular-related hospitalisations in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). Real-world data in patients with ATTR-CM, including patient characteristics, are scarce. Here we analysed the baseline characteristics of patients enrolled in an expanded access programme (EAP) for tafamidis. Initiated in 2018, this tafamidis EAP allows access to tafamidis for patients who have exhausted all standard-of-care options and are not eligible for a clinical trial. Purpose To examine baseline characteristics of patients with ATTR-CM enrolled in a tafamidis EAP. Methods All patients enrolled in this tafamidis EAP from the start (May 2018) until November 2020 were included. To be eligible for inclusion, patients had to have documentation of the following: genetic testing for transthyretin amyloidosis (TTR sequencing); ATTR-CM diagnosis, including the criteria used; exclusion of light chain amyloidosis; and current medical/cardiac status, including New York Heart Association (NYHA) functional classification. Patients were grouped for analysis purposes in the following NYHA classes: I–II, &gt;II–III, and &gt;III–IV. Results A total of 700 patients (88.7% male) from 20 countries were enrolled over 2.6 years. Mean age was 76.2 years in males and 76.6 years in females. Of 518 patients with a recorded genotype, 87.5% were wild-type (89.6% male) and 12.5% hereditary (73.8% male). In males and females, respectively, mean age was 77.0 and 79.4 years in wild-type patients, and 66.2 and 69.3 years in variant patients. The NYHA class distribution is shown in the Figure. The greatest proportion of patients was considered NYHA class I–II. The proportion of patients considered NYHA class I–II was lower in the first half of the data collection period (Months 0–15, 55.3%) compared with the latter half (Months 15–30, 59.4%). In 254 patients with baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) data, the median NT-proBNP level was 2784.5 pg/mL (NYHA class I–II, 2408.5 pg/mL; NYHA class &gt;II–III, 3165.0 pg/mL). Conclusions These are the first multi-country, real-world data evaluating baseline characteristics of patients with ATTR-CM enrolled in an EAP. It is of interest that, compared with the ATTR-ACT population, this patient group was older and had a greater proportion of wild-type patients. As a higher percentage of patients with less severe disease was enrolled in the latter half of data collection, these data also suggest a potential shift over time to earlier diagnosis of ATTR-CM. This analysis provides insight into the characteristics of real-world patients with ATTR-CM. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Pfizer Figure 1. Baseline NYHA class distribution

Challenges in Using Real-World Clinical Practice Records for Retrospective Validation of Clinical Trial Data: Lessons Learned

2016 ◽  
Vol 111 ◽  
pp. S324-S325
Author(s):  
Sunanda V. Kane ◽  
Anita Afzali ◽  
Doug Wolf ◽  
Ira Shafran ◽  
Matthew A. Ciorba ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Practice ◽  
Real World ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Lessons Learned

Characteristics of adult multiple myeloma patients receiving carfilzomib in a U.S. community oncology setting.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19517-e19517
Author(s):  
Robert M. Rifkin ◽  
Rohan Medhekar ◽  
Khalid Mezzi ◽  
Kathleen Aguilar ◽  
Thomas Wilson ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Real World ◽  
Older Patients ◽  
Patient Characteristics ◽  
Refractory Multiple Myeloma ◽  
Female Patients ◽  
Community Oncology ◽  
The Us ◽  
Baseline Characteristics

e19517 Background: Carfilzomib (K) is indicated for treatment of relapsed or refractory multiple myeloma (MM). We studied the characteristics of patients receiving K in the US Oncology Network’s (USON) EHR database. Methods: Patients ≥18 years who received a K-containing regimen between 11/01/2013-02/29/2016, were not in a clinical trial, and had ≥2 visits at a USON clinic were eligible. Baseline characteristics were compared between patients who received a K-based doublet, triplet or other regimen (monotherapy or >3 treatments). Results: Of the 718 patients who received a K-based regimen during the study period, 219 (30.5%) had doublet regimens, 287 (40.0%) received triplet regimens and 212 (29.5%) received other regimens; 494 (68.8%) received regimens with ≥3 therapies. Mean age was 69.7 and 64.7 years among patients on doublets and triplets, respectively. A higher proportion of female patients received doublets (53.0%) (Table). There were no differences in ISS stage or number of comorbidities across patients receiving doublets, triplets, or other regimens. Conclusions: In this real-world analysis of K-regimens, a majority of patients received triplet regimens. Older patients received doublet regimens more frequently. The influence of regimen on outcomes controlling for patient characteristics and prior treatments among MM patients receiving K-based regimens should be studied. [Table: see text]

scholarly journals A Novel Case Study of the Use of Real-World Evidence to Support the Registration of an Osteoporosis Product in China

2021 ◽  
Author(s):  
Neal E. Storm ◽  
Wen Chang ◽  
Tzu-Chieh Lin ◽  
Jeff L. Lange ◽  
Brian Bradbury ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Hong Kong ◽  
Clinical Practice ◽  
Real World ◽  
Controlled Trial ◽  
Real World Evidence ◽  
Study Results ◽  
Global Clinical Trial ◽  
Clinical Trial Program

AbstractOn June 23, 2020, Prolia® (denosumab) was approved by the National Medical Products Administration (NMPA) in the People’s Republic of China as the first monoclonal antibody for the treatment of postmenopausal women with osteoporosis at high risk of fractures. Its brand name in Chinese is 普罗力, a transliteration from the English name “Prolia”, which has an implied meaning of “to give strength to everyone”— a suitable name for a potent anti-resorptive therapy. The approval was supported by a novel marketing authorization application (MAA) that included data from Prolia’s global clinical trial program establishing favorable efficacy and safety, augmented by results from a real-world evidence (RWE) study confirming the effectiveness and safety of Prolia in clinical practice within Taiwan and Hong Kong. Key constructs for this registration-quality RWE study included the fit-for-purpose assessment of data quality, methodology and quantitative assessment of potential biases, good practices of study conduct, and reproducibility of results. Using data from clinical practice in Taiwan and Hong Kong to evaluate the benefits versus risks of Prolia treatment in ethnic Chinese women with postmenopausal osteoporosis, the RWE study results for effectiveness were comparable to efficacy demonstrated in the global clinical trial program and results for safety were consistent with the incidence observed in global post-marketing safety studies. While RWE is often used to monitor postmarket safety of drug products, support health insurance coverage decisions, and inform clinicians on real-world use of medicines, it has not been widely used to support regulatory approval for new medicines in lieu of clinical bridging studies in countries where such studies are required. Well-conducted registrational RWE studies can play a pivotal role in complementing the totality of evidence presented in an MAA. The benefits of such an approach include avoiding the collection of additional placebo-controlled trial data in populations where adequate ethnic characterization of efficacy, effectiveness, and safety may already exist from postmarketing sources, and accelerate access for patients to innovative medicines in important regions. Here, we describe a regulatory case study of a novel MAA incorporating RWE that provided important evidence to confirm the benefit:risk of a new drug and facilitated a label expansion to a new patient population.

PP81 Real World Data: The Early Access To Medicines Scheme Catches The Worm

2019 ◽  
Vol 35 (S1) ◽  
pp. 53-53
Author(s):  
Adam Hall ◽  
Lok Wan Liu ◽  
Richard Macaulay ◽  
Sean Walsh
Keyword(s):  
Clinical Trial ◽  
Clinical Practice ◽  
Real World ◽  
Clinical Trial Data ◽  
Access To Medicines ◽  
Trial Data ◽  
Real World Data ◽  
World Data ◽  
Early Access ◽  
Nice Guidance

IntroductionThe Early Access to Medicines Scheme (EAMS) aims to provide access to medicines prior to market authorization for patients with severe, life-threatening diseases who do not have adequate treatment options. An EAMS designation enables the potential collection of United Kingdom-specific real world evidence (RWE) prior to health technology assessment (HTA) by the National Institute for Health and Care Excellence (NICE). This research evaluates whether RWE is being gathered through the EAMS and utilized to support HTA submissions.MethodsAll EAMS designations as of 7 November 2018 were identified from the Medicines and Healthcare products Regulatory Agency website. For products with final NICE guidance, all publicly-available NICE documentation was reviewed.ResultsSixteen product and indication pairings with an EAMS designation were identified, with 12 having received final NICE guidance (11 were recommended, 3 were recommended for temporary reimbursement via the Cancer Drugs Fund, and 2 were not recommended). Of the 11 recommended products, seven had references to the number of patients or sites with product access through the EAMS, but only one (dupilumab for atopic dermatitis) had detailed data collected during the EAMS period. The manufacturer of dupilumab reported baseline demographics and disease characteristics from a cohort of 35 patients treated under the EAMS to inform the generalizability of trial populations for clinical practice. Follow-up results from this cohort demonstrated that real-world data on dupilumab effectiveness was comparable with the clinical trial data, despite a higher proportion of patients in the real-world cohort receiving immunosuppressant therapy, which makes improvements in efficacy harder to achieve. The committee also noted that the RWE presented supported the understanding of dupilumab's long-term clinical effectiveness and informed assumptions for the economic model.ConclusionsTo date, the majority of products receiving an EAMS designation have not presented RWE at NICE reappraisal. The case of dupilumab illustrated how RWE collected through the EAMS can be used to reduce uncertainty around how clinical trial data can be translated into clinical practice. In the future, RWE may increasingly be used to help inform NICE decisions.

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