FDA’s Oncology Center for Excellence Pilots Project Orbis: A framework for concurrent submission and review of oncology products among international partners.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14125-e14125
Author(s):  
Dianne Spillman ◽  
Shaily Arora ◽  
Rajesh Venugopal ◽  
Bradley Scott ◽  
Sarah Golding ◽  
...  
Keyword(s):  
Cancer Therapeutics ◽  
The United States ◽  
Lymphocytic Leukemia ◽  
Health Science ◽  
Therapeutic Good Administration ◽  
Pilot Program ◽  
Regulatory Review ◽  
Regulatory Pathways ◽  
Health Canada ◽  
Oncology Center

e14125 Background: Cancer therapeutics often receive FDA approval months to years before regulatory submission to other countries. [i] Registrational trials in oncology are increasingly international, with many patients enrolled outside of the United States. Harmonizing access to new global standards of treatment may facilitate optimal design and conduct of global clinical trials. Methods: In May 2019, the Oncology Center for Excellence launched Project Orbis in collaboration with the Australian Therapeutic Good Administration (TGA) and Health Canada. The aim of this initiative is to provide a framework for concurrent submission and review of oncology products among international partners to facilitate global access. Results: The first Project Orbis was a collaborative review of a supplemental application for lenvatinib and pembrolizumab for patients with advanced endometrial cancer. This review also deployed other OCE regulatory review tools including the Real-Time Oncology Review (RTOR) pilot program, which can streamline the submission of data prior to the completion and submission of the entire application, and its accompanying Assessment Aid, to facilitate discussions among regulatory agencies. Lenvatinib and pembrolizumab was approved on September 17, 2019, in conjunction with the TGA and Health Canada, three months prior to the FDA goal date. FDA, TGA, and Health Canada issued a second action under Project Orbis on November 21, 2019, with the approval of acalabrutinib for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Several other products are under international review as part of this pilot program and a summary of timelines and outcomes will be described. Conclusions: Project Orbis is an innovative OCE initiative that leverages the Center’s longstanding communication and collaboration with international regulators. This pilot program facilitates concurrent submission and review of oncology products among global regulatory health agencies. Continued efforts under Project Orbis will build on the initial success to incorporate additional global partners including Swissmedic and Singapore’s Health Science Authority. [i] The Centre for Innovation in Regulatory Science (CIRS). R&D Briefing 70 New drug approvals in six major authorities 2009-2018: Focus on Facilitated Regulatory Pathways and Orphan Status

scholarly journals Maximizing Regulatory Review Efficiency: The Evolution of the FDA OCE RTOR Pilot

2022 ◽  
Author(s):  
Ya Grace Gao ◽  
Samantha Roberts ◽  
Allison Guy
Keyword(s):  
Real Time ◽  
Drug Application ◽  
Priority Review ◽  
Pilot Program ◽  
Regulatory Review ◽  
Oncology Review ◽  
The Us ◽  
Complex Features ◽  
Study Designs ◽  
Oncology Center

AbstractTo promote the efficient review of oncology drug applications, the US Food and Drug Administration (FDA) Oncology Center of Excellence (OCE) launched the Real-Time Oncology Review (RTOR) pilot program in 2018. RTOR allows FDA to review individual sections of eCTD modules of a drug application for oncology drugs in contrast to requiring the applicant to submit complete modules or the complete application before review is initiated. Initially, the program accepted only supplemental applications with simple study designs and easily interpretable endpoints, but the scope has since been expanded to include applications for New Molecular Entities (NME), and other applications with more complex features. Though many applicants experience faster approvals under RTOR, it is difficult to isolate the effect of the RTOR program on review timelines as its contribution is masked by other expedited programs like priority review and breakthrough therapy designation (BTD). This article discusses the expanded scope of RTOR, its interplay with other OCE initiatives to modernize regulatory review, summarizes Genentech’s experiences in planning RTOR submissions from February 2019 to July 2021, and provides considerations for the future of the program.

The Oxford Handbook of Integrative Health Science

2018 ◽  
Keyword(s):  
Adult Life ◽  
The United States ◽  
Sociodemographic Factors ◽  
Population Based ◽  
Health Science ◽  
National Study ◽  
Integrative Health ◽  
Social Structural ◽  
Research Population ◽  
Psychosocial Influences

This handbook signals a paradigm shift in health research. Population-based disciplines have employed large national samples to examine how sociodemographic factors contour rates of morbidity and mortality. Behavioral and psychosocial disciplines have studied the factors that influence these domains using small, nonrepresentative samples in experimental or longitudinal contexts. Biomedical disciplines, drawing on diverse fields, have examined mechanistic processes implicated in disease outcomes. The collection of chapters in this handbook embraces all such prior approaches and, via targeted questions, illustrates how they can be woven together. Diverse contributions showcase how social structural influences work together with psychosocial influences or experiential factors to impact differing health outcomes, including profiles of biological risk across distinct physiological systems. These varied biopsychosocial advances have grown up around the Midlife in the United States (MIDUS) national study of health, begun over 20 years ago and now encompassing over 12,000 Americans followed through time. The overarching principle behind the MIDUS enterprise is that deeper understanding of why some individuals remain healthy and well as they move across the decades of adult life, while others succumb to differing varieties of disease, dysfunction, or disability, requires a commitment to comprehensiveness that attends to the interplay of multiple interacting influences. Put another way, all of the disciplines mentioned have reliably documented influences on health, but in and of themselves, each is inherently limited because it neglects factors known to matter for health outside the discipline’s purview. Integrative health science is the alternative seeking to overcome these limitations.

The Roles of Twin Studies and Modern Genomic Technologies in Integrative Health Science

2018 ◽  
pp. 34-46
Author(s):  
Robert F. Krueger ◽  
Susan C. South
Keyword(s):  
Allostatic Load ◽  
Twin Studies ◽  
Transcriptional Response ◽  
The United States ◽  
Health Science ◽  
Research Strategies ◽  
Integrative Health ◽  
Genomic Technologies ◽  
Health And Illness ◽  
Modern Genomic

This chapter focuses on genetically informative research design and strategy in integrative health science (IHS). A feature of IHS is studying individual differences in health outcomes together and in a multidisciplinary manner. The chapter focuses on the advantages of using genetically informative research strategies for IHS. Genetically informative strategies are tools to enrich inferences within the IHS paradigm. They help parse the meaning of observed associations between exposures and outcomes. Two strategies are considered for the Midlife in the United States study : (1) Gene × Environment interactions and (2) correlations between education and allostatic load. A strategy likely to be employed in IHS research involves using segments of RNA to understand mechanisms underlying health and illness, focusing on the conserved transcriptional response to adversity (CTRA). The conclusion is that IHS and genetically informative research strategies are natural allies in understanding origins of health and illness in the population at large.

Creating Intersectional Subjects: A Critical Discourse Analysis of Health Science Breastfeeding Research

2021 ◽  
pp. 233264922098109
Author(s):  
Shannon K. Carter ◽  
Ashley Stone ◽  
Lain Graham ◽  
Jonathan M. Cox
Keyword(s):  
United States ◽  
Discourse Analysis ◽  
Black Women ◽  
Critical Discourse Analysis ◽  
The United States ◽  
Health Science ◽  
Policy Implications ◽  
Critical Discourse ◽  
Race Disparities ◽  
Breastfeeding Policy

Reducing race disparities in breastfeeding has become a health objective in the United States, spurring research aimed to identify causes and consequences of disparate rates. This study uses critical discourse analysis to assess how Black women are constructed in 80 quantitative health science research articles on breastfeeding disparities in the United States. Our analysis is grounded in critical race and intersectionality scholarship, which argues that researchers often incorrectly treat race and its intersections as causal mechanisms. Our findings reveal two distinct representations. Most commonly, race, gender, and their intersection are portrayed as essential characteristics of individuals. Black women are portrayed as a fixed category, possessing characteristics that inhibit breastfeeding; policy implications focus on modifying Black women’s characteristics to increase breastfeeding. Less commonly, Black women are portrayed as a diverse group who occupy a social position in society resulting from similar social and material conditions, seeking to identify factors that facilitate or inhibit breastfeeding. Policy implications emphasize mitigating structural barriers that disproportionately impact some Black women. We contribute to existing knowledge by demonstrating how dominant health science approaches provide evidence for health promotion campaigns that are unlikely to reduce health disparities and may do more harm than good to Black women. We also demonstrate the existence of a problematic knowledge set about Black women’s reproductive and infant feeding practices that is both ahistorical and decontextualized.

Safety-Related Postmarketing Modifications of Drugs for Hematological Malignancies

2019 ◽  
Vol 143 (1) ◽  
pp. 73-77
Author(s):  
Anat Gafter-Gvili ◽  
Ariadna Tibau ◽  
Pia Raanani ◽  
Daniel Shepshelovich
Keyword(s):  
Hematological Malignancies ◽  
New Drugs ◽  
Priority Review ◽  
Regulatory Review ◽  
Regulatory Pathways ◽  
The Us ◽  
Black Box Warnings ◽  
Accelerated Approval ◽  
Drug Approvals ◽  
Approved Drugs

The prevalence of safety-related postmarketing label modifications of medications for hematological malignancies is unknown. We identified 35 new drugs indicated for hematological malignancies approved by the US Food and Drug Administration between January 1999 and December 2014. Characteristics of supporting trials and safety-related label modifications from approval to December 2017 were collected from drug labels. Regulatory review and approval pathways were also collected. New drug approvals were supported by trials with a median of 167 patients (interquartile range 115–316). All drugs were approved based on surrogate endpoints. Twenty-seven drug approvals (77%) were not supported by randomized controlled trials. All drugs received orphan drug designation, and most were granted fast track designation, priority review, and accelerated approval (83, 74, and 60%, respectively). A total of 28 drugs (80%) had postmarketing safety-related label modifications. Additions to black box warnings, contraindications, warnings and precautions, and common adverse reactions were identified in 31, 11, 77, and 46% of drugs, respectively. Five drugs (14%) were permanently or temporarily withdrawn from the US market. Drugs for hematological malignancies are often approved based on limited evidence through expedited regulatory pathways with incomplete safety profiles. Hematologists should be vigilant for unrecognized side effects when prescribing newly approved drugs.

scholarly journals Chronic Lymphocytic Leukemia: A Rare Cause of Pathological Fracture of the Femur

2017 ◽  
Vol 5 (4) ◽  
pp. 232470961773513 ◽  
Author(s):  
Parita Soni ◽  
Nidhi Aggarwal ◽  
Anand Rai ◽  
Vivek Kumar ◽  
Kamholz Stephan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Chronic Lymphocytic Leukemia ◽  
Endotracheal Intubation ◽  
Pathological Fracture ◽  
The United States ◽  
Left Knee ◽  
Lymphocytic Leukemia ◽  
Initial Presentation ◽  
Richter’S Transformation ◽  
Richter's Transformation

The incidence rate of chronic lymphocytic leukemia (CLL) in the United States is approximately 0.005%; men are at slightly higher risk than women. Bony involvement or pathological fracture rarely occurs in CLL, and it may be the initial presentation. An 85-year-old woman presented with acute respiratory failure secondary to pneumonia. Symptomatology included dyspnea. She was found to have pathological fracture of the femur caused by CLL. The diagnosis of CLL had been made 6 years previously, but the patient had refused therapy. On admission, the patient required endotracheal intubation, mechanical ventilation, and admission to the medical intensive care unit. Endotracheal intubation extubation was successful after 48 hours. The patient then complained of severe left knee pain. Bone radiograph and femoral computed tomography scan revealed acute pathological fracture of the left distal femur. There was no history of trauma. The fracture was stabilized with extension lock splint. Pathological fracture in patients with CLL is associated with hypercalcemia, Richter’s transformation, or multiple myeloma. This patient exemplifies the fact that pathological fracture can be caused by CLL in the absence of hypercalcemia, Richter’s transformation, or multiple myeloma and can be the initial presentation of CLL.

Abstract WP365: STARS PLUS Patient Transition Pilot Program

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Alexandra Graves ◽  
Angie West ◽  
Miranda N Bretz ◽  
Marie Welch ◽  
Lynn Toth ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Stroke Prevention ◽  
Recurrent Stroke ◽  
Age Groups ◽  
The United States ◽  
Lifestyle Changes ◽  
Older Age ◽  
Stroke Survivors ◽  
Pilot Program

Background: As the leading cause of adult disability and the fourth leading cause of death in the United States, stroke prevention strategies are imperative. Arguably equal attention should be given towards both primary and secondary prevention of stroke. While much is known about medications and lifestyle changes to prevent recurrent stroke, additional research is needed to effectively ensure stroke survivors are following the recommended guidelines. Research shows that support after discharge from the hospital post-stroke is frequently inadequate. Purpose: The purpose of the Steps Against Recurrent Stroke (STARS) Plus Patient Transition Pilot Program was to design and deliver a program to facilitate optimal recovery for stroke survivors and prevent recurrent stroke. The program began at discharge from the hospital and continued through the first year of rehabilitation and recovery. Patients could opt in based on perceived benefits of support with medication management, timed educational mailings and calls about stroke recovery and recurrent stroke prevention. Results: Twelve hospitals participated; 261 patients enrolled and contact was established with 193. Outcomes were gathered based on patient self-report of health status using the Standard Form 12 (SF-12) Health Survey at 30, 90, 180 and 360 days. A total of 72 patients completed each follow-up in the full 12 months of the program. A dependent sample t-test was completed comparing participants’ 30 and 360 day follow-up scores. Results demonstrated an overall increase in subjective pain. A repeated MANOVA was conducted to compare 30 and 360 day SF-12 scores across age and subscales. Results revealed that those in the younger and older age groups reported poorer health outcomes. Conclusion: STARS Plus Program found no statistically significant change in perceived health benefits, although the majority found the program to be beneficial. Future programs should consider targeting pain management in all ages and education targeted at younger and older age groups, as they reported poorer health outcomes. The findings from this program should contribute to the guidance and insight for others developing transitional interventions for stroke survivors.

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