June 6, 2023: INSPIRE NIH Collaboratory Trial Principal Investigators Share Update at Annual Steering Committee Meeting

In an interview at the annual NIH Pragmatic Trials Collaboratory Steering Committee meeting in Bethesda, Maryland, Richard Platt, MD, MS (co–principal investigator) and Shruti Gohil, MD, MPH (lead investigator) of the INSPIRE NIH Collaboratory Trial shared the status of the trials, discussed recent lessons learned, described the impact they hope their trials will have on the future of healthcare, and reflected on the impact the NIH Collaboratory has had on their trials thus far.

Status Update

Headshot of Dr. Richard Platt
Richard Platt, MD

Shruti Gohil, MD, MPH

INSPIRE (or Intelligent Stewardship Prompts to Improve Real-Time Empiric Antibiotic Selection for Patients) is implementing 2 separate cluster-randomized trials to study the effectiveness of a patient/infection/hospital-specific clinical decision support program in improving antibiotic prescribing for non–critically ill patients who are hospitalized with abdominal infections or skin and soft tissue infections. The purpose of the trials is to reduce unnecessary broad-spectrum antibiotic use in non–intensive care unit inpatients.

The 12-month trial is currently in month 5, and the team has already seen a downward inflection in broad-spectrum antibiotic use.

Lessons Learned

Due to the urgent public health threat of antibiotic resistance, healthcare systems are actively seeking ways to support clinicians in judicious antibiotic prescribing. As a result, although the target recruitment was 60 hospitals out of approximately 200, 92 hospitals at HCA Healthcare requested enrollment.

"We have the privilege of being with a health system that has a strong leadership structure that is patient-safety oriented, and quality improvement is a top-notch priority," Gohil said, describing the unusual overenrollment.

The INSPIRE team determined that the trial could be shortened from 18 months to 12 by using all 92 hospitals.

"We determined that the higher number of hospitals wanting to participate gave us the opportunity to understand the usefulness of this decision support tool as quickly as possible and honor the commitment of the partner health system," Platt said. "Their view is, if it works, we want to use it everywhere as soon as possible," he said.

Impact of the Trial on Real-World Healthcare

Dr. Gohil explained that she hopes not only to reduce unnecessary prescribing of broad-spectrum antibiotics, but also to learn about how digital health can transform healthcare and its delivery.

“We have a tool that not only flags a low-risk patient, but is doing it based on data from the [electronic medical record] system, and is calculating risk specific to a patient, specific to a disease, and specific to a type of bacteria, and one that is unique to a hospital. It captures all that information and presents it to a clinician to make good judgments about antibiotic selection,” Gohil said. She hopes this work will be a step towards future systems that could be “savvy enough and real-time enough deliver high precision care tailored for individual patients as  part of an embedded learning system.”

Impact of the NIH Pragmatic Trials Collaboratory on INSPIRE

The INSPIRE intervention includes a clinical decision support tool to help clinicians make a guideline-concordant decision on antibiotic use based on a patient's personalized risk. At the time of the trial’s launch, the FDA introduced a new guidance on Clinical Decision Support Software to support determinations regarding whether a software would be considered a device and therefore subject to FDA oversight.

“It was really helpful to have the Ethics and Regulatory Core do a deep dive with us on the FDA guidance on clinical decision support and help determine that our software was not considered a device,” Platt said.

The INSPIRE NIH Collaboratory Trial is supported within the NIH Pragmatic Trials Collaboratory by a grant from the National Institute of Allergy and Infectious Diseases (NIAID).

All of the materials from the 2023 Steering Committee meeting are now available.

August 31, 2022: New Section of Living Textbook Addresses Evaluating Fitness for Use of Real-World Data Sources

A new section of the NIH Pragmatic Trials Collaboratory’s Living Textbook of Pragmatic Clinical Trials discusses challenges associated with Evaluating Fitness for Use of real-world data for trials. The section uses a case study from the Harmony Outcomes EHR Ancillary Study (eHARMONY) to describe lessons learned and to provide recommendations for studies considering incorporating real-word data as a data source.

Among the lessons learned were:

  • Standalone clinical research sites had very little extractable EHR data about patients.
  • Most lab results and medications were either not extractable or not mapped to a useful terminology.
  • Many sites did not have the ability to transform their data into a common format and had to send rudimentary data extracts to the ancillary study coordinating center. Sites participating in other research networks, such as PCORnet, had no difficulty with this task.

For more, read the chapter or watch the Grand Rounds presentation Leveraging RWD in a Multinational Trial: Results from the other eHARMONY 

Podcast July 8, 2022: FDA Draft Guidance on Real-World Evidence (John Concato, MD, MS, MPH)

This podcast continues the discussion with Dr. John Concato as he discusses the FDA draft guidance on real-word evidence. Click on the recording below to listen to the podcast.

Want to hear more? View the full Grand Rounds presentation.

For alerts about new episodes, subscribe free on Apple Podcasts or SoundCloud. Read the transcript.

June 24, 2022: FDA Draft Guidance on Real-World Evidence (John Concato, MD, MS, MPH)

Speaker

John Concato, MD, MS, MPH
Associate Director for Real-World Evidence Analytics
Office of Medical Policy (OMP)
Center for Drug Evaluation and Research (CDER)
Food and Drug Administration (FDA)

 

 

Keywords

Big data; Real-word evidence; Real-world data; 21st Century Cures Act; FDA Draft Guidance

 

Key Points

  • Big Data, a term first used in the 1990s, leverages modern technology to increase the quantity, forms, speed, and capability to manipulate large-scale data. Real-world data (RWD) is a term with specific regulatory implications referring to health care data routinely collected from a variety of sources. Real-world evidence (RWE) is clinical evidence derived from analysis of RWD regardless of study design.
  • Terminology is important in research work, and we should strive to be as precise as possible with the terminology we use.
  • With the 21st Century Cures Act of 2016, the FDA established a program to evaluate the potential use of real-world evidence to support new indications for drugs and satisfy post-approval study requirements.
  • In 2021, the FDA issued 4 draft guidance documents for Real-world data and Real-world evidence intended to guide the selection and management of data sources to appropriately address the study question and support decision-making for drug and biological products.

Discussion Themes

– Could real-world data sources be certified and preclude the need for submission of source data on a study specific basis? From the FDA point-of-view, while reliability can be more readily evaluated and would tend to be more stable, the relevance to a particular study could not be determined as easily.

– While there can be a reflex that says we can never be sure about major confounding, it should not be the miasma of the 21st century. A thoughtful approach that considers the characteristics that matter is the best approach.

 

Read Dr. Concato’s publication Randomized, observational, interventional, and real-world—What’s in a name? and the FDA Draft Guidance for RWD/RWE.

Tags

#pctGR, @Collaboratory1

June 22, 2022: FDA’s Draft Guidance on Real-World Evidence to Be Featured in Grand Rounds

Headshot of Dr. John ConcatoIn this Friday’s PCT Grand Rounds, Dr. John Concato of the US Food and Drug Administration will present “FDA Draft Guidance on Real-World Evidence.” The Grand Rounds session will be held on Friday, June 24, 2022, at 1:00 pm eastern.

Dr. Concato is the associate director for real-world evidence analytics in the Office of Medical Policy in the FDA’s Center for Drug Evaluation and Research.

Join the online meeting.

May 9, 2022: FDA Leaders Offer Perspective on Real-World Data and Real-World Evidence

FDA leaders Dr. John Concato and Dr. Jacqueline Corrigan-Curay published a perspective piece in the New England Journal of Medicine encouraging researchers to be more explicit and specific about the types of real-world data (RWD) they are using to generate real-world evidence (RWE).

The article, “Real-World Evidence — Where Are We Now?,” cautions that the terms RWD and RWE are too often used interchangeably and inconsistently in describing research and that this imprecision has led to confusion and an inability to assess the impact of RWD and RWE. The authors described 2 misconceptions about RWD and RWE. The first is that RWD is “new” when in fact real world sources of information have always existed; what is new is how researchers are able to access the information. The second misconception is that “a simple dichotomy between randomized, controlled trials (RCTs) and observational studies delineates the entire landscape of study design.” In fact, the authors write, the important distinction in study design is often interventional vs non-interventional.

The authors recommend precision in describing how RWD is incorporated into a variety of study designs to generate regulatory-grade RWE and cited recent examples of FDA approvals that were made possible by RWD. They also describe how the COVID-19 pandemic is changing perceptions about the potential of RWD and RWD.

Read the full article.

August 27, 2021: Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock: the DOREMI trial (Benjamin Hibbert, MD, PhD)

Speaker

Benjamin Hibbert, MD, PhD
Clinician Scientist and Interventional Cardiologist
University of Ottawa Heart Institute

Topic

Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock: the DOREMI trial

Keywords

Randomized pragmatic clinical trial; Milrinone; Dobutamine; CAPITAL DOREMI; Cardiogenic Shock; Evidenced based research

Key Points

  • Many therapies in cardiology and critical care are based on lower quality data, creating a large knowledge gap between the therapies used and the evidence to support their use.
  • Powerful randomized clinical trials are needed to evaluate and support the therapies used in clinical care.
  • Cardiogenic Shock, a common presentation with a mortality rate of 40% to 50%, has limited effective therapies and very limited data to support the therapies that are used.
  • The CAPITAL DOREMI trial was a double-blind randomized pragmatic clinical trial focused on the hypotheses that Milrinone would reduce the composite primary outcome compared to Dobutamine.
  • No significant differences were found between Milrinone and Dobutamine, and selection of one therapy over the other could be based on physician comfort and preference.
  • A future trial, CAPITAL DOREMI-2, will investigate the use of an inotrope vs placebo for Cardiogenic Shock.

Discussion Themes

Are medical physicians so anxious to help their desperately ill patients that they gravitate toward doing something, even when there isn’t high quality evidence that it helps?

The therapies used by critical care physicians do not always have a great foundation of evidence. As a field, critical care physicians should be developing this evidence base with pragmatic clinical trials.

Read more about Dr. Hibbert’s work with the CAPITAL DOREMI study.

Tags

#pctGR, @Collaboratory1

July 23, 2021: Long Term COVID Patient Engagement: Best Practices Informed By Patients’ Experiences Seeking Medical Care (Diana Berrent, JD; Natalie Lambert, PhD; Nick Guthe)

Speakers

Diana Berrent, JD
Survivor Corps, Founder

Natalie Lambert, PhD
Associate Research Professor
Indiana University School of Medicine

Nick Guthe
Survivor Corps Member and Advisor

Topic

Long Term COVID Patient Engagement: Best Practices Informed By Patients’ Experiences Seeking Medical Care

Keywords

Long-term COVID; COVID-19 symptoms; Survivor Corps; Patient-centered outcomes; Real-world evidence; Patient engagement

Key Points

  • Survivor Corps is a 170,000 member grassroots organization founded in 2020 to support and educate people with COVID-19 and those who continue to experience long-lasting symptoms of COVID-19.
  • People who experience long-term, after-effects of COVID-19 report feeling alone and desperate due to the difficult and dissatisfying medical care they receive and their medical provider’s lack of knowledge about long-term COVID.
  • Long-term COVID patients want to be heard and believed by medical professionals who are thorough in their examination and testing methods.
  • Survivor Corps advocates for crucial research to be done on the symptoms that cause the most human pain and suffering, and not just the symptoms that are experienced most frequently.
  • COVID-19 research can be done at a faster pace if we engage citizen-scientists and quickly release NIH research funding.
  • The life-or-death struggles of people with long-term COVID illustrate the need to treat this condition as an emergency medical situation—the same as we would treat an acute case of COVID-19.

Discussion Themes

The CDC guidelines are the first-step, interim guidance; however, no treatment options have been offered. Another iteration of these guidelines needs to be released soon.

We know from people who have experienced long-lasting effects of COVID-19 that the condition can be debilitating and devastating—patients are in urgent need of understanding and help.

Medical professionals should focus on real-word evidence to develop patient-centered outcomes.

Read more about Survivor Corps, Dr. Lambert’s research, the report from the Survivor Corps COVID-19 ‘Long Hauler’ Symptom Survey, and physician resources.

Tags

#pctGR, @Collaboratory1, @Survivor_Corps

July 19, 2021: COVID-19 Grand Rounds Will Feature Survivor Corps and the Use of Real-World Evidence From Citizen-Scientists

Survivor Corp logo

In this Friday’s COVID-19 Grand Rounds session, Diana Berrent, Natalie Lambert, and Nick Guthe of Survivor Corps will present “Long Term COVID Patient Engagement: Best Practices Informed By Patients’ Experiences Seeking Medical Care.” The Grand Rounds session will be held on Friday, July 23, at 1:00 pm eastern. Join the online meeting.

Survivor Corps is an online community of 170,000 patients affected by COVID-19 and their families and friends. The advocacy group is using its members’ collective experience to build a repository of data sets and research tools to support COVID-19 research, including studies of post-COVID conditions, or “long COVID.” The group seeks to fill the gap between real-world evidence and scientific research to advance understanding of the disease and patients’ healthcare options.

“We have been sort of the canary in the COVID coal mine from the beginning,” said Berrent, who founded Survivor Corps in March 2020 after becoming one of the first people in the United States to be diagnosed with COVID-19.

Berrent will be joined during Grand Rounds by Survivor Corps research director Dr. Natalie Lambert and by Nick Guthe, a Survivor Corps member and adviser.

Survivor Corps’s website, which has been selected by the US Library of Congress for inclusion in the nation’s Coronavirus Web Archive, serves as a hub to provide support, information, and education about COVID-19, connect patients to researchers, and facilitate the nation’s COVID-19 response.

The NIH Collaboratory Coordinating Center is using its popular Grand Rounds platform to share late-breaking research and promote resources in support of clinical researchers affected by the COVID-19 public health emergency. For previous COVID-19 Grand Rounds, and more news and resources related to the COVID-19 public health emergency, see the COVID-19 Resources page.