study design

March 12, 2021: Lessons Learned from the Gates MRI Virtual COVID-19 Trial (Mohamed Bassyouni, PharmD; Jintanat Ananworanich, MD, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Mohamed Bassyouni, PharmD
Product Development Program Leader
Bill and Melinda Gates Medical Research Institute
Cambridge, MA
 
Jintanat Ananworanich, MD, PhD
Clinical Development Leader
Bill and Melinda Gates Medical Research Institute
Cambridge, MA

Topic

Lessons Learned from the Gates MRI Virtual COVID-19 Trial

Keywords

COVID-19; Virtual trial; Gates Medical Research Institute (MRI); Underserved populations; Health outcomes; Treatment safety and efficacy; Decentralized trial

Key Points

  • The goal of this study was to conduct a randomized controlled, adaptive platform trial to evaluate safety and efficacy of interventions for high-risk people with mild COVID-19 disease.
  • A key feature of the virtual trial was the development of a “COVID trial in a box.” This innovative method involved a single shipment of the study materials—including the study drug, lab sample kits, pulse oximeter, and PPE—directly to study participants’ homes.
  • The study evaluated multiple strategies for participant identification and outreach. Challenges included finding a better approach to engage minority communities; having better access for potential participants to be screened for COVID-19; increasing participation in the elderly population.

Discussion Themes

100% remote trials are possible and are especially crucial during a pandemic.

How did the study use social medial for virtual screening?

Did you do exit interviews with participants to get feedback on outreach and study design? 

Were alternatives to eConsent offered to patients who may have had technical difficulty with electronic apps or platforms?

Read more at the Gates Medical Research Institute website.

Tags

#pctGR, @Collaboratory1

February 26, 2021: Calibrating Real-World Evidence Against RCT Evidence: Early Learnings from RCT-DUPLICATE (Sebastian Schneeweiss, MD, ScD)

Posted on by Gina Uhlenbrauck

Speaker

Sebastian Schneeweiss, MD, ScD
Chief, Division of Pharmacoepidemiology and Pharmacoeconomics
Department of Medicine, Brigham and Women’s Hospital
Professor of Medicine, Harvard Medical School
Professor in Epidemiology, Harvard T.H. Chan School of Public Health

Topic

Calibrating Real-World Evidence Against RCT Evidence: Early Learnings from RCT-DUPLICATE

Keywords

Real-world evidence (RWE); Randomized controlled trials (RCTs); Epidemiology; Emulation; Fit-for-purpose data

Key Points

  • While RCTs are an accepted research study design to establish the efficacy of medical products, RWE studies can complement the evidence generated by RCTs, as well as expand the line of inquiry around population, endpoints, treatment patterns, and comparators.
  • The RCT-DUPLICATE study aimed to understand and improve the validity of RWE studies for regulatory decision making. One objective was to identify factors that predictably increase the validity of such studies.
  • In RCT-DUPLICATE, RWE studies were designed to emulate 20 target RCTs. The regulatory-standard RCTs for replication underwent feasibility checks and quality assessments.
  • With data that are fit-for-purpose and proper design and analysis, nonrandomized RWE studies usually come to the same conclusion as the RCT about a drug’s treatment effect.
  • In any emulation, despite best efforts, there will remain differences in population, measurement, and drug use. Data fit-for-purpose and study design choices are the most important considerations for emulation success.

Discussion Themes

Initial findings of RCT-DUPLICATE identify circumstances when RWE may offer causal insights in situations where RCT data are either not available or cannot be quickly or feasibly generated.

Can this approach be used to predict results for a new entity?

It will be useful to establish a repository of case studies to increase the predictability of future RWE studies; increase the use of common methodological approaches to emulate target trials; and point out areas that are currently difficult to address with RWE.

Read more about RCT-DUPLICATE in Circulation.

Tags

#pctGR, @Collaboratory1

February 12, 2021: Leveraging RWD in a Multinational Trial: Results from the Other eHARMONY [HARMONY Outcomes EHR Ancillary Study] (Lesley Curtis, PhD, Bradley Hammill, PhD, Sudha Raman, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Lesley Curtis, PhD
Professor in Population Health Sciences
Department of Population Health Sciences
Duke University School of Medicine
 
Bradley Hammill, DrPH
Associate Professor in Population Health Sciences
Department of Population Health Sciences
Duke University School of Medicine
 
Sudha Raman, PhD
Assistant Professor in Population Health Sciences
Department of Population Health Sciences
Duke University School of Medicine

Topic

Leveraging RWD in a Multinational Trial: Results from the Other eHARMONY (HARMONY Outcomes EHR Ancillary Study)

Keywords

Electronic health records; eHARMONY; Real-world data; DataMart; Common data model; Data sensitivity/specificity

Key Points

  • While the electronic health record (EHR) is a rich source of clinical data, the fitness of EHR data for use in high-quality clinical research has not been rigorously evaluated.
  • The HARMONY trial aimed to determine the effect of albiglutide, when added to standard blood glucose lowering therapies, on major cardiovascular events in patients with type 2 diabetes mellitus. eHARMONY was an ancillary study conducted alongside the HARMONY trial, with these objectives:
    • Understand how EHR data are used to facilitate trial recruitment and what the barriers are to that use
    • Evaluate the fitness of real-world data (RWD) data for use in populating baseline characteristics in the electronic case report form
    • Evaluate the fitness of RWD data for use in identifying clinical endpoints
  • In the eHARMONY study, assessing data quality and fitness of a site’s EHR data was often not possible. Among the lessons learned were:
    • Each strategy required ongoing feasibility assessment
    • Standalone clinical research sites had very little (extractable) EHR data about patients
    • Lab results and medications were either not extractable or not mapped to a useful terminology
    • Many sites did not participate because they knew they could not perform this work, and many sites that promised to do this work could not deliver

Discussion Themes

What structural and behavioral factors have you encountered? For example, a healthcare system might not provide a particular service, or a healthcare system provides the service but people might choose to receive it elsewhere.

What about the overall cost of the trial? Has anything changed over the last 5 years—or are we consigned to spend hundreds of millions on outcome trials?

To realize the potential of real-world data in clinical trials, be mindful of the actual context of the trial, and (1) keep it simple, (2) collect only the data you need for the question at hand, and (3) remember that clinical research is not the priority for healthcare systems.

It is also essential for studies to report what does not work.

Read more about how real-world data (RWD) and real-world evidence (RWE) are playing an increasing role in health care decisions.

Tags

#pctGR, @Collaboratory1

February 5, 2021: Generating High-Quality Evidence During a Pandemic: The Brazilian COALITION Experience (Renato Lopes, MD, MHS, PhD)

Posted on by Gina Uhlenbrauck

Speaker

Renato D. Lopes, MD, MHS, PhD
Professor of Medicine
Division of Cardiology
Duke University Medical Center
Duke Clinical Research Institute
Brazilian Clinical Research Institute

Topic

Generating High-Quality Evidence During a Pandemic: The Brazilian COALITION Experience

Keywords

COVID-19; Patient outcomes; Cardiology; Randomized clinical trials; COALITION; Levels of evidence

Key Points

  • The SARS-CoV-2 infection affects the cardiovascular system and is associated with complications such as myocardial ischemia, myocarditis, arrhythmias, and thromboembolic events. These manifestations result mainly from the intense systemic inflammatory response and disorders of the coagulation system. 
  • The COALITION collaborative includes several major Brazilian hospitals and research networks with the aim of accelerating multicenter randomized controlled trials that generate high-quality evidence to guide the treatment of patients with COVID-19.
  • To move toward a world in which most clinical decisions are supported by high-quality evidence requires structural changes in the clinical trials ecosystem.

Discussion Themes

How did you overcome contractual and regulatory concerns to execute your trials?

Instead of “publish or perish,” it should be “collaborate or perish.” Collaboration is the key to surviving in modern academic medicine.

Read more about the need for high-quality evidence to treat COVID-19 patients in Anticoagulation in COVID-19: It Is Time for High-Quality Evidence (J Am Coll Cardiol, 2020)

Tags

#pctGR, @Collaboratory1

February 8, 2021: Meeting Minutes are Available from the Ethics and Regulatory Core Discussions with the PRISM NIH Collaboratory Trials

Posted on by Gina Uhlenbrauck

Meeting minutes, supplementary materials, and updates are available that summarize recent discussions related to the ethics and regulatory issues associated with the six PRISM NIH Collaboratory Trials:

These discussions, which took place by teleconference, included representation from study principal investigators and study teams, members of the NIH Collaboratory Ethics and Regulatory Core, NIH staff, and NIH Collaboratory Coordinating Center personnel as well as some IRBs responsible for oversight of the projects.

January 29, 2021: The COVID-19 Citizen Science Study (Gregory M. Marcus, MD, MAS)

Posted on by Gina Uhlenbrauck

Speaker

Gregory M. Marcus, MD, MAS
Professor of Medicine
University of California, San Francisco

Topic

The COVID-19 Citizen Science Study

Keywords

Eureka digital research platform; COVID-19 infections; Mobile health; Risk factors; Citizen science; Geolocation; Participant engagement

Key Points

  • Eureka is an NIH-supported digital research platform built to use mobile health technology to combat the novel coronavirus, focusing on identifying risk factors for infection, transmission, and severity of disease that may inform best practices.
  • Eureka is also intended to serve as a platform for collaborating investigators to answer their own research questions.
  • As a citizen science project, any adult with a smartphone can participate and contribute information. Nearly 50,000 participants have enrolled to date.

Discussion Themes

The COVID-19 Citizen Science website provides data visualizations that show how people answered the survey questions. A study blog through the app is used to translate key information to participants.

Will this project be collaborating with other entities that are potentially overlapping in terms of their COVID-19 applications?

Best practices in mHealth include keeping it simple, avoiding over-explaining, listening to participants, and providing a feedback pathway.

Learn more about the Eureka platform. The smartphone app is available under the name “UCSF Eureka Research.”

Tags

#pctGR, @Collaboratory1  

January 25, 2021: Grand Rounds Podcast with Dr. Emily O’Brien on HERO-TOGETHER is Available

Posted on by Gina Uhlenbrauck

In the latest episode of the NIH Collaboratory Grand Rounds podcast, Dr. Adrian Hernandez and Dr. Emily O’Brien continue the discussion about the HERO-TOGETHER initiative that aims to understand how healthcare workers do after receiving the COVID-19 vaccination. The full January 8 Grand Rounds webinar with Dr. O’Brien is also available.

January 15, 2021: How CTTI & the Clinical Trials Community Have Risen to Meet the Challenge of the COVID-19 Pandemic (Pamela Tenaerts, MD, MBA; Sara Calvert, PharmD; Leanne Madre, JD, MHA)

Posted on by Gina Uhlenbrauck

Speakers

Pamela Tenaerts, MD, MBA
Executive Director
Clinical Trials Transformation Initiative

Sara Calvert, PharmD
Senior Project Manager
Clinical Trials Transformation Initiative

Leanne Madre, JD, MHA
Directory of Strategy
Clinical Trials Transformation Initiative

Topic

How CTTI & the Clinical Trials Community Have Risen to Meet the Challenge of the COVID-19 Pandemic

Keywords

Clinical Trials Transformation Initiative (CTTI); Best practices; COVID-19 treatment trials; RECOVERY Trial; Digital health technology; Decentralized clinical trials

Key Points

  • During 2020, CTTI conducted a series of intensive surveys, discussions, and collaborations across the clinical trials ecosystem, which shaped the creation of public webinars, a Best Practices for Conducting Trials During the COVID-19 Pandemic playbook, and a searchable, real-time AACT COVID-19 Trials Spreadsheet, among other efforts.

  • CTTI’s efforts helped the research community successfully navigate the challenges associated with adjusting trials that were underway when the pandemic hit, as well as launching new trials for COVID-19 treatments.

  • Among the best practices for conducting clinical trials during the pandemic: keep participants informed, perform ongoing risk-benefit assessment, adjust study startup and enrollment based on current risks, pivot to remote study visits, and switch to remote monitoring.

Discussion Themes

Because of the COVID-19 pandemic, there is more momentum toward digital health technology and decentralized clinical trials.

With the pandemic, we are seeing trial results go straight to practice, bypassing input from the clinical community at large—will this continue after the pandemic?

To what extent do you think the IRB/research oversight sphere might be permanently reshaped by the pandemic’s impact on the conduct of clinical trials? 

Read more about CTTI’s efforts around clinical trials during the COVID-19 pandemic.

Tags

#pctGR, @Collaboratory1

January 8, 2021: HERO-TOGETHER: Building Vaccine Confidence With Long-Term Outcomes Data (Emily O’Brien, PhD)

Posted on by Gina Uhlenbrauck

Speaker

Emily O’Brien, PhD
Associate Professor
Duke Clinical Research Institute
Duke University School of Medicine
Department of Population Health Sciences

Topic

HERO-TOGETHER: Building Vaccine Confidence With Long-Term Outcomes Data

Keywords

Vaccine development; COVID-19; Pandemic: Vaccine hesitancy; HERO-TOGETHER; Healthcare workers; Clinical outcomes: Observational study

Key Points

  • According to the World Health Organization, vaccine hesitancy refers to the delay in acceptance of, or refusal of, vaccines despite availability of vaccination services.

  • Vaccine hesitancy is complex and context specific, varying across time, place, and vaccines. It is influenced by factors such as complacency, convenience, and confidence. Hesitancy occurs on a continuum, from acceptance of all vaccines, to acceptance but doubt, to vaccine delayers, refusers, and deniers.

  • HERO-TOGETHER is a prospective, observational, multicenter cohort study of 20,000 adult U.S. healthcare workers who received a COVID-19 vaccine within the past 60 days. The study will collect data from participants that includes their experience with receiving the vaccine, medical history, unexpected medical care, safety events, and quality of life.

Discussion Themes

There is no universal best practice to address vaccine hesitancy in all its contexts. Locally tailored and multicomponent approaches will be needed.

How has the political environment influenced the hesitancy around receiving the COVID-19 vaccine?

What are your approaches to evaluating vaccine safety? What about safety for women during child-bearing years?

Read more about the HERO-TOGETHER study.

Tags

#pctGR, @Collaboratory1