scholarly journals Validating Direct Oral Anticoagulants (DOAC) for Use in Children By the Throm-PED Doac Registry of the International Pediatric Thrombosis Network

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1063-1063
Author(s):  
Susanne Holzhauer ◽  
Christoph Male ◽  
Paul Monagle ◽  
Mohammadreza Bordbar ◽  
Heleen van Ommen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Renal Disease ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Chronic Medical Conditions ◽  
Medical Conditions ◽  
Efficacy And Safety ◽  
Real World Data ◽  
World Data ◽  
International Pediatric

Abstract Background: A growing number of randomized clinical trials (RCTs) provide promising data on pharmacokinetics/ pharmacodynamics, efficacy and safety of DOAC in children and the first DOACs have recently been approved for treatment of thromboembolism in children. Based on the risk benefit profiles published so far, we expect DOACs to be widely used for treatment and prophylaxis of thrombosis in children. The strict inclusion criteria for participation in the RCTs limit their generalizability, particularly to those with more serious acute and chronic medical conditions that account for a significant proportion of pediatric VTE patients in clinical practice. Real world data complements evidence from randomized clinical trials, and is urgently needed to improve patient care. Aim: To obtain efficacy and safety data of DOACs in a large and heterogeneous pediatric patient collectives. To expand the knowledge on treatment strategies and outcomes across different risk profiles and comorbidities including cancer and renal disease. Study Design: An international, multicentre, prospective observational cohort study imbedded in the Throm-PED Registry of the International Pediatric Thrombosis Network (IPTN). Parameters included at baseline are age, gender, height, weight, thrombosis type, thrombosis location, risk factors, underlying medical conditions and comedication. Primary outcomes include 1) thrombus progression or recurrence and 2) bleeding (major, clinically relevant non major including menorrhagia) and 3) mortality. Outcomes are assessed every 3 months for a total of 12 months. Additional variables include self-reported adherence, comedication, chemotherapy, DOAC drug levels, measures of renal function and dose adjustments on children with chronic medical conditions including renal disease and cancer. Study population : Patients from 0-21 years with thromboembolic disease treated with DOACs who are enrolled in the IPTN Throm-PED Registry. Results: As of June 30, 2021 82 patients from 10 centers have been enrolled. The majority of patients were at least 12 years old (Figure 1). 66% suffered from venous thrombosis. With about 30% each, pulmonary embolism or thrombosis of the lower extremities were reported most commonly. In this cohort the majority of patients received Rivaroxaban (80%), followed by Apixaban and Edoxaban. Risk factors were manifold, including patients with cancer (13%) and renal disease (4%). Of the 33 patients with follow-up reported at 3 months, bleeding was reported in 3 (9%) of patients during treatment with a DOAC, and thrombosis progression was reported in 2 (6%) (Table 1). Summary: This initial real world data, as expected, demonstrates reduced efficacy and more bleeding than noted in published trials, however numbers are small. Further real world data collection is essential to identify specific patient groups at risk of worse outcome with DOACs and to understand drug interactions and dose adjustments. Data on younger age groups are required. IPTN registry is an important framework to collect real world data that can then be explored in clinical trials. Figure 1 Figure 1. Disclosures Raffini: CSL Behring: Consultancy; Genentech: Consultancy; HEMA Biologics: Consultancy; Bayer: Consultancy; XaTek: Consultancy.

scholarly journals Application of Real-World Data to External Control Groups in Oncology Clinical Trial Drug Development

2022 ◽  
Vol 11 ◽  
Author(s):  
Timothy A. Yap ◽  
Ira Jacobs ◽  
Elodie Baumfeld Andre ◽  
Lauren J. Lee ◽  
Darrin Beaupre ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Real World ◽  
External Control ◽  
Control Group ◽  
Precision Oncology ◽  
Efficacy And Safety ◽  
Control Groups ◽  
Real World Data ◽  
World Data

Randomized controlled trials (RCTs) that assess overall survival are considered the “gold standard” when evaluating the efficacy and safety of a new oncology intervention. However, single-arm trials that use surrogate endpoints (e.g., objective response rate or duration of response) to evaluate clinical benefit have become the basis for accelerated or breakthrough regulatory approval of precision oncology drugs for cases where the target and research populations are relatively small. Interpretation of efficacy in single-arm trials can be challenging because such studies lack a standard-of-care comparator arm. Although an external control group can be based on data from other clinical trials, using an external control group based on data collected outside of a trial may not only offer an alternative to both RCTs and uncontrolled single-arm trials, but it may also help improve decision-making by study sponsors or regulatory authorities. Hence, leveraging real-world data (RWD) to construct external control arms in clinical trials that investigate the efficacy and safety of drug interventions in oncology has become a topic of interest. Herein, we review the benefits and challenges associated with the use of RWD to construct external control groups, and the relevance of RWD to early oncology drug development.

scholarly journals Health Canada & Canadian Society for Pharmaceutical Sciences - Use of Real World Data/Evidence to Inform Regulatory Decision Making

2020 ◽  
Vol 23 ◽  
pp. 1s-47s
Author(s):  
Real World Data Workshop Group CSPS/Health Canada
Keyword(s):  
Health Care ◽  
Decision Making ◽  
Clinical Trials ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Regulatory Agencies ◽  
Real World Data ◽  
World Data ◽  
Regulatory Decision ◽  
Health Canada

Real world data (RWD) and real world evidence (RWE) are playing increasing roles in health-care decisions. Real world data are routinely employed to support reimbursement and coverage decisions for drugs and devices. More recently, clinical trials incorporating pragmatic designs and observational studies are considered to supplement traditional clinical trials (e.g., randomized clinical trials). Regulatory agencies and large co-operative groups including academia and industry are exploring whether leveraging big databases such as electronic medical records and claims databases can be used to garner clinical insights extending beyond those gained from randomized controlled studies. Whether RWE can ultimately replace or improve traditional clinical trials is the big question. The workshop held on December 3, 2019 at Health Canada included presenters from regulatory agencies, industry and academia. Health Canada, US FDA and European Medicine Agency presented current thinking, draft frameworks and guidance available in the public domain. While the three agencies might be at different stages of utilizing RWE for regulatory decision making, the consensus is not whether RWE would be used but when and how it can be incorporated into regulatory decision making while maintaining a high evidentiary bar. The complexity of data sourcing, curating databases, aligning on common data models, illustrated by high-profile work conducted as part of Sentinel, DSEN, OHDSI and Duke-Margolis initiatives, was presented and discussed during the workshop, creating great learning opportunities for the attendees. The design and analysis of RWE studies were compared and contrasted to those of RCTs. While there are gaps, they are closing quickly as novel analytical methods are employed and innovative ways of curating data, including natural language processing and artificial intelligence, are explored.   This proceeding contains summaries of information presented by the speakers, including current highlights about the use of RWE in regulatory decision making. In the world where the uptake of “big data” in everyday life is happening at unprecedented speed, we can expect RWE to be a fast-moving area and with the potential for big impact in health-care decision making in the years to come.

scholarly journals P198 Efficacy and safety of secukinumab in ankylosing spondylitis: real-world data from Midlands Ankylosing Spondylitis Collaboration (MASC)

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Nibha Jain ◽  
Ramasharan Laxminarayan ◽  
Arumugam Moorthy ◽  
Roshan Amarasena ◽  
Natasha Cleaton ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Ankylosing Spondylitis ◽  
Clinical Improvement ◽  
Real World ◽  
Patient Choice ◽  
Efficacy And Safety ◽  
Real World Data ◽  
Data Set ◽  
World Data ◽  
Leicester Royal Infirmary

Abstract Background/Aims  Secukinumab is an interleukin-17 inhibitor has been found to be effective in the treatment of ankylosing spondylitis (AS) in studies, including phase 3 clinical trials, however these are conducted in highly selected patients and it is important to confirm the efficacy and safety in a real world data. Response to secukinumab should be assessed after 16-weeks and continued if there has been sufficient response to treatment according to the BASDAI and spinal VAS scores. Methods  This was a multicentre cross-sectional observational study in collaboration with Midland Ankylosing Spondylitis Collaboration. Consecutive baseline and 16th week data of all AS patients on Secukinumab from 2017 to 2019 were collected and analysed to assess treatment response. All data were compiled in excel sheets and analysed using Medcalc calculator. Data were collected from collaborative efforts of the Royal Wolverhampton NHS trust, Queen’s Hospital (Burton on Trent), Leicester Royal Infirmary and Robert Jones and Agnes Hunt hospital. Results  Total 92 patients with radiographic AS on standard dose of secukinumab were included at baseline and 88 were followed up till week 16. Mean age was 45.9(SD ± 15) (Median=44years) and 67% were male. Baseline Mean BASDAI was 7 (SD ± 1.7); Mean CRP was 16.6 (SD ± 11.2), Mean VAS was 7.6(SD ± 1.6). There was statistical significant change in BASDAI, VAS and CRP levels at week 16th. ΔBASDAI=2.2 (SD ± 2) (p = 0.002), ΔVAS=3.2 (SD ± 2.1) (p = 0.001), ΔCRP=6.9 (SD ± 17) (p = 0.03). At 16th week, 68% had clinical improvement while 4 patients discontinued therapy (2-colitis, 1-uveitis and 1-patient choice). 10% overall had some adverse effects with most common being upper respiratory tract infection. We also compared patients with previous anti-TNF exposure (TE) to Anti-TNF naïve (TN). 63% were in TE group vs 37% in TN. 69% of TE and 76% of TN showed clinical improvement at week 16.Mean ΔBASDAI was more in TN group vs TE (p = 0.01), however there was no difference in ΔVAS and ΔCRP levels. (p = 0.0 & p = 0.2 respectively). Conclusion  This multi-centre retrospective analysis found secukinumab to be clinically effective in 68% of patients with AS. There was significant improvement in BASDAI, VAS and CRP levels at week16. Compared to anti-TNF resistant patients, TNF-Naïve responded better to secukinumab, although both showed good clinical improvement. These findings support the use of secukinumab in the treatment of AS, as a first line therapy or for those who have failed anti-TNF therapy. Safety signals observed in the real-word data set were consistent with those seen in the clinical trials and the Summary of Product Characteristics. Disclosure  N. Jain: None. R. Laxminarayan: Honoraria; Honorarium from Novartis, Lilly, Pfizer and Abvie. A. Moorthy: Honoraria; Speaker and conference fee MSD, Novartis, Abbvie. R. Amarasena: None. N. Cleaton: None. G. Kakade: None. A. Gunawardane: None. T. Khan: None. H. Sapkota: None. N. Barkham: Grants/research support; research funding from Novartis, Eli Lilly, UCB.

scholarly journals CP2 - USING REAL WORLD DATA TO EXTRAPOLATE EVIDENCE FROM RANDOMIZED CLINICAL TRIALS

2018 ◽  
Vol 21 ◽  
pp. S5
Author(s):  
S.V. Wang ◽  
S. Schneeweiss ◽  
J.J. Gagne ◽  
T. Evers ◽  
C. Gerlinger ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Real World Data ◽  
World Data

scholarly journals Health Canada & Canadian Society for Pharmaceutical Sciences - Use of Real World Data/Evidence to Inform Regulatory Decision Making

2020 ◽  
Vol 23 ◽  
pp. 1s-47s
Author(s):  
Real World Data Workshop Group CSPS/Health Canada
Keyword(s):  
Health Care ◽  
Decision Making ◽  
Clinical Trials ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Regulatory Agencies ◽  
Real World Data ◽  
World Data ◽  
Regulatory Decision ◽  
Health Canada

Real world data (RWD) and real world evidence (RWE) are playing increasing roles in health-care decisions. Real world data are routinely employed to support reimbursement and coverage decisions for drugs and devices. More recently, clinical trials incorporating pragmatic designs and observational studies are considered to supplement traditional clinical trials (e.g., randomized clinical trials). Regulatory agencies and large co-operative groups including academia and industry are exploring whether leveraging big databases such as electronic medical records and claims databases can be used to garner clinical insights extending beyond those gained from randomized controlled studies. Whether RWE can ultimately replace or improve traditional clinical trials is the big question. The workshop held on December 3, 2019 at Health Canada included presenters from regulatory agencies, industry and academia. Health Canada, US FDA and European Medicine Agency presented current thinking, draft frameworks and guidance available in the public domain. While the three agencies might be at different stages of utilizing RWE for regulatory decision making, the consensus is not whether RWE would be used but when and how it can be incorporated into regulatory decision making while maintaining a high evidentiary bar. The complexity of data sourcing, curating databases, aligning on common data models, illustrated by high-profile work conducted as part of Sentinel, DSEN, OHDSI and Duke-Margolis initiatives, was presented and discussed during the workshop, creating great learning opportunities for the attendees. The design and analysis of RWE studies were compared and contrasted to those of RCTs. While there are gaps, they are closing quickly as novel analytical methods are employed and innovative ways of curating data, including natural language processing and artificial intelligence, are explored.   This proceeding contains summaries of information presented by the speakers, including current highlights about the use of RWE in regulatory decision making. In the world where the uptake of “big data” in everyday life is happening at unprecedented speed, we can expect RWE to be a fast-moving area and with the potential for big impact in health-care decision making in the years to come.

Using real-world cohorts to assess the generalizability and relevance of randomized clinical trials (RCTs).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6540-6540 ◽  
Author(s):  
Caroline Savage Bennette ◽  
Nathan Coleman Nussbaum ◽  
Melissa D. Curtis ◽  
Neal J. Meropol
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Standard Of Care ◽  
Real World Data ◽  
Eligibility Criteria ◽  
Relevance Score ◽  
World Data

6540 Background: RCTs are the gold standard for understanding the efficacy of new treatments, however, patients (pts) in RCTs often differ from those treated in the real-world. Further, selecting a standard of care (SOC) arm is challenging as treatment options may evolve during the course of a RCT. Our objective was to assess the generalizability and relevance of RCTs supporting recent FDA approvals of anticancer therapies. Methods: RCTs were identified that supported FDA approvals of anticancer therapies (1/1/2016 - 4/30/2018). Relevant pts were selected from the Flatiron Health longitudinal, EHR-derived database, where available. Two metrics were calculated: 1) a trial’s pt generalizability score (% of real-world pts receiving treatment consistent with the control arm therapy for the relevant indication who actually met the trial's eligibility criteria) and 2) a trial’s SOC relevance score (% of real-world pts with the relevant indication and meeting the trial's eligibility criteria who actually received treatment consistent with the control arm therapy). All analyses excluded real-world pts treated after the relevant trial’s enrollment ended. Results: 14 RCTs across 5 cancer types (metastatic breast, advanced non-small cell lung cancer, metastatic renal cell carcinoma, multiple myeloma, and advanced urothelial) were included. There was wide variation in the SOC relevance and pt generalizability scores. The median pt generalizability score was 63% (range 35% - 88%), indicating that most real-world pts would have met the RCT eligibility criteria. The median SOC relevance score was 37% (range 15% - 74%), indicating that most RCT control arms did not reflect the way trial-eligible real-world pts in the US were actually treated. Conclusions: There is great variability across recent RCTs in terms of pt generalizability and relevance of SOC arms. Real-world data can be used to inform selection of control arms, predict impact of inclusion/exclusion criteria, and also assess the generalizability of the results of completed trials. Incorporating real-world data in planning and interpretation of prospective clinical trials could improve accrual and enhance relevance of RCT outcomes.

scholarly journals Real-World Data for Planning Eligibility Criteria and Enhancing Recruitment: Recommendations from the Clinical Trials Transformation Initiative

2021 ◽  
Author(s):  
Scott R. Evans ◽  
Dianne Paraoan ◽  
Jane Perlmutter ◽  
Sudha R. Raman ◽  
John J. Sheehan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Real World Data ◽  
Eligibility Criteria ◽  
World Data ◽  
Study Planning ◽  
Efficiency And Effectiveness ◽  
Multi Stakeholder ◽  
Functional Teams ◽  
Data Driven Decisions

AbstractThe growing availability of real-world data (RWD) creates opportunities for new evidence generation and improved efficiency across the research enterprise. To varying degrees, sponsors now regularly use RWD to make data-driven decisions about trial feasibility, based on assessment of eligibility criteria for planned clinical trials. Increasingly, RWD are being used to support targeted, timely, and personalized outreach to potential trial participants that may improve the efficiency and effectiveness of the recruitment process. This paper highlights recommendations and resources, including specific case studies, developed by the Clinical Trials Transformation Initiative (CTTI) for applying RWD to planning eligibility criteria and recruiting for clinical trials. Developed through a multi-stakeholder, consensus- and evidence-driven process, these actionable tools support researchers in (1) determining whether RWD are fit for purpose with respect to study planning and recruitment, (2) engaging cross-functional teams in the use of RWD for study planning and recruitment, and (3) understanding patient and site needs to develop successful and patient-centric approaches to RWD-supported recruitment. Future considerations for the use of RWD are explored, including ensuring full patient understanding of data use and developing global datasets.

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