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CONTENT TYPE, Foundational (Intro Level), MAPS Members Only, CAPABILITIES & COMPETENCIES, FOCUS AREA, Content Hub, ACCESS, Evidence Generation, Evidence Generation

Essentials of Real World Evidence (RWE)

This Powerpoint offers a comprehensive overview of Real World Evidence (RWE) and its evolving use in the biopharmaceutical industry.

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January 12, 2021/by Medical Affairs Professional Society
https://medicalaffairs.org/wp-content/uploads/2021/01/Essentials-RWE-Featured.png 321 845 Medical Affairs Professional Society https://medicalaffairs.org/wp-content/uploads/2020/07/logo-medical.png Medical Affairs Professional Society2021-01-12 14:51:512021-01-12 15:11:01Essentials of Real World Evidence (RWE)
CONTENT TYPE, Foundational (Intro Level), Content HUB Featured, CAPABILITIES & COMPETENCIES, Business Knowledge, Open Access, FOCUS AREA, Content Hub, ACCESS, Evidence Generation, Podcasts

Creating an HEOR Function Within Medical Affairs

AlphaGroup HEOR

MAPS explores Health Economics and Outcomes Research (HEOR): Why a Medical Affairs organization needs an HEOR function and how to build this capability.

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January 11, 2021/by Medical Affairs Professional Society
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CONTENT TYPE, Foundational (Intro Level), MAPS Members Only, CAPABILITIES & COMPETENCIES, FOCUS AREA, Content Hub, ACCESS, Customer Engagement & Scientific Comms, Evidence Generation, Leadership & Management, On-Demand Webinars

Do’s and Don’ts of Visual Communication and Data Visualization

Data Visualization OD Featured

In this Medical Affairs webinar, founder and CEO of Killer Visual Strategies, Amy Balliett, helps you master data visualization best practices.

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December 16, 2020/by Medical Affairs Professional Society
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CONTENT TYPE, Foundational (Intro Level), CAPABILITIES & COMPETENCIES, Open Access, FOCUS AREA, Content Hub, ACCESS, Evidence Generation, Evidence Generation, Podcasts

History of Real-World Evidence Prior to the 21st Century Cures Act

RWE 2 Featured

Medical Affairs thought leaders discuss the Pre-21st Century Cures Act uses of Real World Evidence (RWE) in regulatory decision-making.

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November 16, 2020/by Medical Affairs Professional Society
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CONTENT TYPE, CAPABILITIES & COMPETENCIES, Open Access, FOCUS AREA, Content Hub, ACCESS, Evidence Generation, Evidence Generation, Podcasts

The Application of Real-World Evidence in Regulatory Decision Making

RWE Regulatory Podcast Featured

Cerise James, MD, moderates this podcast in which Neil Belson, JD, discusses Real World Evidence and its impact to the biopharmaceutical industry.

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October 20, 2020/by Medical Affairs Professional Society
https://medicalaffairs.org/wp-content/uploads/2020/10/RWE-Regulatory-Podcast-Featured.png 321 845 Medical Affairs Professional Society https://medicalaffairs.org/wp-content/uploads/2020/07/logo-medical.png Medical Affairs Professional Society2020-10-20 12:11:442020-11-18 14:41:11The Application of Real-World Evidence in Regulatory Decision Making
CONTENT TYPE, Foundational (Intro Level), Content HUB Featured, Elevate Magazine, CAPABILITIES & COMPETENCIES, Open Access, FOCUS AREA, Compliance, Content Hub, ACCESS, Evidence Generation, Evidence Generation

Contemporary Applications of Real-World Evidence in Regulatory Decision Making: A Case Series Review

REW Regulatory Featured

Download the full article here

 

By Robert Honigberg, MBA, MD, MS&T Consulting, LLC

Neil Belson, JD, Law Office of Neil A Belson, LLC

 

EXECUTIVE SUMMARY

The 21st Century Cures Act, enacted in 2016, requires the U.S. Food and Drug Administration (FDA) to assess the use of Real-World Evidence (RWE) for applications that include new drug indications and satisfying post-approval drug study requirements. RWE can contribute to showing that a drug or medical device is safe and effective, within the context of the FDA’s “totality of evidence approach” for evaluating regulatory submissions. The FDA has approved both drugs and medical devices based on regulatory submissions which have included RWE.

KEY WORDS: Real-World Data (RWD), Real-World Evidence (RWE), totality of evidence, FDA

INTRODUCTION

The 21st Century Cures Act (2016) requires the U.S. Food and Drug Administration (FDA) to assess the use of Real-World Evidence (RWE) for applications that include new drug indications and satisfying post-approval1,2. The FDA issued a final guidance document for medical devices in 2017, in which the Agency stated that the applicant could use Real-World Data (RWD) to support regulatory determinations under the right conditions3. While the FDA has not yet followed up with a guidance for pharmaceutical products, their 2018 Framework for FDA’s Real-World Evidence Program outlined the potential applications of RWE for regulatory decision-making regarding the effectiveness of marketed products4. In the instance of an original approval for a product, the FDA recommended that an evidence package could contain three types of studies: clinical pharmacology, non-clinical toxicology, and clinical studies. However, for post-marketing labeling changes (i.e., use in a new population or a new indication), the evidence package could include prior submitted evidence and new evidence, traditionally represented by randomized clinical studies but also RWE studies. What is important for Medical Affairs and Regulatory teams to understand is that regardless of study type, setting, or design, the FDA does not have to evaluate one study type (i.e., Randomized Clinical Trial (RCT)) only when making regulatory decisions. Instead, the FDA uses a totality of evidence approach, examining all available evidence in the regulatory materials submitted including the quality of the studies and context of the manufacturer’s request4.

“While Real-World Evidence analysis will not replace the randomized controlled trial, it already has been used as effective support data for drug and device labeling changes and for rare disease submissions.”

Bob Honigberg MD

Several applications for labeling expansions and other regulatory approvals have successfully incorporated RWD and RWE. The purpose of this Elevate article is to provide regulatory examples of how various companies have negotiated with the FDA and successfully utilized RWE within regulatory submissions.

 

Real World Evidence divider

APPROACHES TO RWE REGULATORY SUBMISSIONS

Regulatory submissions that involve the submission of RWD can come from data sources that routinely collect health-related information such as claims data, electronic health records, patient reported outcomes (questionnaires and devices), registries, as well as public and private databases. The use of RWE implies the analyses of RWD through applied research methods, such as for historical controls, or other types of analyses using records that were initially collected from sources other than randomized clinical trials. It is important to first target an opportunity where the use of RWE will add to the “totality of evidence.” The role of RWD and RWE has been especially useful for rare diseases as well as for the expansion of labeling to a more broad or newly defined sub-population, and the evolution of procedural medical device techniques. Using a “totality of evidence” approach, one can determine if the new evidence from RWD sources or RWE analyses can add to the existing evidence to create a new evidence package that has value from a clinical and regulatory perspective.

A White Paper prepared in December 2019 by the Duke Margolis Center for Health Policy5 examined non-traditional study designs which have used RWE, including open-label, single-arm studies, retrospective observational and case series, retrospective cohort studies using RWD sources, non-inferiority studies, RWE-generated historical controls, the use of concurrent control groups, and the use of post-market surveillance and registry data. Table 1 is an adapted summary of examples of approvals and labeling changes for drugs using evidence generated from these non-traditional studies. This article discusses three pharmaceutical case examples in this communication: Ibrance for male breast cancer, Invega Sustenna for schizoaffective disorder and Brineura for treatment of a form of Batten disease. The article also examines the label expansion of a medical device based on RWE to include a minimally-invasive approach to aortic valve replacement using Transcatheter Aortic Valve Replacement (TAVR).

 

Ibrance (Pfizer) for Male Breast Cancer Indication

Ibrance (Palbociclib) was approved for metastatic breast cancer in 2019. The approval was based on two large randomized controlled trials (the PALOMA studies) in women and supported by clinical pharmacology and non-clinical toxicology studies. Evidence for clinical benefit in male breast cancer was noted from post-marketing reports, insurance claims data and electronic health records. Male breast cancer is a rare condition with a high unmet need for treatment; there were approximately 2,500 new cases and 500 deaths in 2019. The FDA submission included evidence derived from RWD sources including: the IQVIA insurance database, Flatiron Health breast cancer database, and the Pfizer global safety database. The FDA noted in its approval letter that “Given the extensive established efficacy and safety of the use of Palbociclib in women observed in randomized controlled trials, the additional RWE data provided in this application for the use in men, modest as it is, does support the expansion of the Palbociclib indication to provide for the treatment of men with metastatic breast cancer.”6

 

TAVR device procedure (Edwards Lifesciences)

In 2011, the FDA approved the Sapien 3 device for TAVR, a novel approach that provided a minimally invasive alternative to open heart surgery for clinically appropriate patients. Post-marketing surveillance requirements included the collection of data in over 100,000 procedures in the Transcatheter Valve Therapy Registry, which included a subset in 600 patients that underwent the valve-in-valve variant of the procedure. Although this procedural variant was considered off-label, the valve-in-valve procedure was shown to be an improvement as it allowed the new valve to be placed inside the diseased valve. The FDA evaluated the clinical and functional data for this procedure from the registry to expand the indication for the TAVR-enabling device. The FDA announced that even though the United States had been only the 42nd country to approve the original TAVR device, through the use of creative regulatory procedures the United States became the first country to approve the new indication.

 

Invega Sustenna (Janssen) for a more Broad and Inclusive Indication for Schizoaffective Disorder

Invega Sustenna (paliperidone palmitate) is a centrally active anti-psychotic and the only once-monthly long-acting injectable (LAI) for schizoaffective disorder. There have been several expansions to the label since its original approval in 2006 for acute schizophrenia. In 2018, a labeling change was approved related to the time to treatment failure compared to oral anti-psychotics using an unconventional clinical trial design that was more representative of the disease population. Prior RCTs had excluded adult subjects with recent incarceration or substance abuse from the trial. The PRIDE trial, which was a randomized open-label pragmatic trial, recruited many subjects from jail-release programs, homeless shelters and soup kitchens. The trial was able to build on the existing evidence provided by published RCTs and include a broader and more representative population using an unconventional RWE clinical trial design that not only showed a time to treatment failure benefit but also a medication adherence benefit compared to oral anti-psychotics.

 

Brineura (Biomarin) as a treatment for Batten Disease

The FDA’s approval of Brineura (cerliponase alfa) in 2017 as a treatment for a form of Batten disease, is an example of the agency comparing a “single-arm” clinical study of a prospective drug treatment against a natural history “control” obtained from RWD. This use of natural history “controls” in single-arm clinical studies of prospective treatments for rare diseases has historically been among the most common uses of RWD to support regulatory approvals7. Brineura, an enzyme replacement therapy, was the first FDA-approved treatment for slowing the progressive loss of walking ability in patients with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2). CLN2 disease is a rare inherited disorder which occurs in approximately two to four of every 100,000 U.S. live births. Signs and symptoms in the late infantile form of this disease typically begin between ages two and four. Individuals with this condition often require use of a wheelchair by late childhood and typically do not survive past their teens. The clinical trial which established Brineura’s efficacy was a non-randomized, single-arm dose escalation clinical study in 22 symptomatic pediatric patients. The “control” or comparator was a group of 42 untreated CLN2 patients from a natural history cohort (an independent historical control group). Patients treated with Brineura suffered fewer declines in walking ability compared to the untreated patients in the natural history cohort.8

Real World Evidence divider

SUMMARY AND CONCLUSION

The 21st Century Cures Act directed FDA to evaluate the use of Real-World Data (RWD) and Real-World Evidence (RWE) in regulatory submissions. The objective of this Elevate article is to examine some of the approaches accepted by the FDA for using RWE to obtain regulatory approvals for drugs and devices. It is important to select new indication and expansion targets where there is an opportunity for RWE analysis to credibly add to the existing evidence base using a “totality of evidence” approach.

“While our understanding of the potential applications of RWE and the appropriate standards for its use is still evolving, RWE will almost certainly have an increasingly important role in future regulatory submissions for drugs and medical devices.”

Neil Belson JD

Real World Evidence divider

1

PRODUCT

SPONSOR

DISEASE

STUDY DESIGN

Bavencio (avelumab)

Pfizer and Merck KGaA

Metastatic merkel cell CA

Open-label single-arm multicenter trial
RWE-generated historical control as benchmark

2

Blincyto (blinatumomab)

Amgen

B-cell precursor ALL

Open-label single-arm multicenter trial
RWE-generated historical control

3

Brineura (cerliponase alfa)

Biomarin

Infantile Batten Disease

Non-randomized single-arm dose-escalation study Non-randomized comparison with natural history cohort

4

Carbaglu (carglumic acid)

Recordati Rare Diseases

Hyper-ammonemia

Retrospective unblinded uncontrolled case series

5

Cordarone (amio darone HCl tabs)

Sanofi

Arrhythmia

Retrospective open-label self-controlled study

6

Ibrance

Pfizer

Male breast cancer

Retrospective cohort study using HER data, insurance billing data, and post-marketing studies

7

Inactivated polio vaccine

NFIP (March of Dimes)

Polio

Randomized blinded placebo-controlled trial with additional observed controls

8

Intravenous ganciclovir

Exela Pharma Sciences

AIDS and CMV retinitis

Retrospective non-randomized study

9

Invega Sustenna (paliperidone palmitate)

Janssen

Schizophrenia, schizoaffective disorder

Prospective randomized open-label active-controlled parallel-group trial

10

Luthathera (lutetium Lu 177 dotatate)

Advanced Accelerator Applications (Novartis)

Somatostatin receptor positive GEP-NETs

Randomized open-label, active-controlled multicenter trial Retrospective study

Real World Evidence divider

REFERENCES

  1. Public Law 114–255—Dec. 13, 2016, 130 STAT. 1033, Sec. 3022.
  2. Belson, N. Regulatory Applications of Real-World Evidence. Journal of Precision Medicine, March-April 2018. Accessed October 6, 2020.
  3. U.S. Department of Health and Human Services, Food and Drug Administration, Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices. Issued August 31, 2017. Accessed October 6, 2020.
  4. U.S. Food and Drug Administration. Framework for FDA’s Real-World Evidence Program. U.S. Department of Health & Human Services: December 2018. Accessed October 6, 2020.
  5. Mahendraratnam, H. Adding Real-World Evidence to a Totality of Evidence Approach for Evaluating Marketed Product Effectiveness. Published December 19, 2019. Duke Margolis Center for Health Policy. Accessed October 6, 2020.
  6. CENTER FOR DRUG EVALUATION AND RESEARCH. Approval Package for: APPLICATION NUMBER: 207103Orig1s008. 2019.
  7. Belson, N. FDA’s Historical Use of Real-World Evidence. Update Magazine, August-September 2018. Accessed October 6, 2020.
  8. FDA approves first treatment for a form of Batten disease. (2017). Accessed October 6, 2020.
October 20, 2020/by Medical Affairs Professional Society
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CONTENT TYPE, Elevate Magazine, CAPABILITIES & COMPETENCIES, Open Access, FOCUS AREA, Content Hub, ACCESS, Evidence Generation, Evidence Generation, Strategic Vision, Medical Communications

The Future of Medical Affairs: A Conversation with Beat Sümegi, SVP Medical, Sanofi

Sumegi Featured

MAPS speaks with Beat Sümegi, SVP Medical with Sanofi, about major areas of change and the need to help Medical Affairs professionals build new skills to succeed in this world of increased responsibility and opportunity.

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October 1, 2020/by Medical Affairs Professional Society
https://medicalaffairs.org/wp-content/uploads/2020/10/Sumegi-Featured.png 321 845 Medical Affairs Professional Society https://medicalaffairs.org/wp-content/uploads/2020/07/logo-medical.png Medical Affairs Professional Society2020-10-01 11:47:072020-10-22 12:07:23The Future of Medical Affairs: A Conversation with Beat Sümegi, SVP Medical, Sanofi
CONTENT TYPE, Content HUB Featured, CAPABILITIES & COMPETENCIES, Open Access, FOCUS AREA, Content Hub, ACCESS, Evidence Generation, Evidence Generation, On-Demand Town Halls, Strategic Vision, Medical Communications

Global Town Hall: An Opportunity for Medical Affairs Strategic Leadership During the Pandemic and Beyond

GTH Evidence Dissemination Featured

Medical Affairs thought leaders Q&A on topics including virtual congresses, digital platforms, and pre-print scientific publications.

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September 23, 2020/by Medical Affairs Professional Society
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Open Access, COVID-Related, Evidence Generation, Field Medical, On-Demand Town Halls

Global Town Hall: An Opportunity for Medical Affairs Strategic Leadership During the Pandemic and Beyond

1

OVERVIEW:

The COVID-19 pandemic is affecting Medical Affairs professionals around the world, and each team is responding in different ways. During this live Global Town Hall, we will discuss how Medical Affairs can continue to function during the COVID-19 pandemic, as well as share industry best practices and consider how Medical Affairs could change post-COVID-19. Through patient-focus and peer-to-peer relationships with HCPs, Medical Affairs professionals have a unique role in ensuring the safe and effective use of medicines, vaccines and medical devices, and are also positioned to bring invaluable insights from the field into ongoing R&D. By strengthening our understanding within the pharmaceutical industry of how Medical Affairs can support HCPs and patients in these times, this Town Hall will explore how the role of Medical Affairs can be expanded to maintain quality in a rapidly evolving clinical environment, helping to achieve industry-wide alignment on the issue and potentially saving lives.

 

Join this webinar for insights from industry-leading experts. This series including follow-on webinars will equip MAPS members and MA professionals worldwide with the tools to fulfill the opportunity for Medical Affairs strategic leadership during the Covid-19 pandemic and beyond.

 

MAPS Members have access to view and download the slides from this presentation. 

CLICK HERE TO VIEW AND DOWNLOAD SLIDES IN THE COMMUNITY PORTAL

 

 

SPEAKERS:

Rachele Berria

Vice President and Medical Head, US BioPharmaceuticals

AstraZeneca

 

Eric Mortensen

Head Gastrointestinal Clinical Development, R&D

Janssen Immunology

 

Tamas Koncz

Chief Medical Officer, Inflammation and Immunology

Pfizer

 

Isma Benattia

VP, Europe Medical Affairs

Amgen

 

Terry Griesing

VP, Head of North America Medical Affairs, Internal Medicine

Pfizer

 

Ann Hartry

VP, HEOR

Lundbeck

 

Audrey Krolicki

Senior Director, Head of Scientific Publications

Astellas

 

Danie du Plessis

Executive VP Medical Affairs

Kyowa Kirin International

 

AGENDA

Time Title speaker
9:00–9:10 EDT The Opportunity for Medical Affairs Strategic Leadership Chair: Tamas Koncz
9:10–9:20 EDT Evidence Generation: Ensuring Speed and Quality During
Rapid Decision-Making
Ann Hartry
9:20–9:30 EDT Evidence Dissemination: The New World of Publications and Virtual Congresses Audrey Krolicki
9:30–10:05 EDT Audience Q&A and Panel Discussion

What has changed for Field Medical? What hasn’t changed?

What are the needs now, and in the future?

How can the return-to-field be balanced with continued virtual interactions?

What are the key adaptive strategies, innovations and practices?

Full Expert Panel
10:05–10:15 EDT Closing: The Opportunity for MA is Here and Now Tamas Koncz

 

July 28, 2020/by Medical Affairs Professional Society
https://medicalaffairs.org/wp-content/uploads/2020/08/1.png 321 845 Medical Affairs Professional Society https://medicalaffairs.org/wp-content/uploads/2020/07/logo-medical.png Medical Affairs Professional Society2020-07-28 15:00:292020-09-22 14:47:51Global Town Hall: An Opportunity for Medical Affairs Strategic Leadership During the Pandemic and Beyond
MAPS Members Only, Evidence Generation, Evidence Generation, On-Demand Webinars

Contemporary Practices for Data Generation Strategies: Design, Implementation, and Communication of New Evidence

16

Join this Webinar to better understand contemporary practices for data generation strategies; describe how to design data generation strategies, implementation of the strategies, and how to communicate new evidence; and describe how real-world evidence may be utilized to support product value including regulatory label change.

Read more
June 15, 2020/by Medical Affairs Professional Society
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