regulatory issues

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 5, 2021: New Video Collection Highlights Advances in Electronic Health Records for Pragmatic Research

Posted on by Damon Seils

We are pleased to announce our new collection of short educational videos that highlight advances in the use of electronic health records (EHRs) in pragmatic clinical trials.

The videos are drawn from our 2020 EHR Workshop Grand Rounds Series, “Advances at the Intersection of Digital Health, Electronic Health Records and Pragmatic Clinical Trials.” The series highlighted advances in digital health, new approaches and evolving standards for EHRs, and implications for researchers conducting pragmatic trials. Experts discuss the evolving regulatory context for EHRs, national policy priorities, and innovative uses of EHRs in several NIH Collaboratory Trials.

Video topics include:

Visit the EHR Workshop Video Modules page for access to all of the new videos.

September 22, 2020: New Article Highlights Ethical and Regulatory Challenges of Conducting PCTs

Posted on by Gina Uhlenbrauck

Cover of Ethics & Human ResearchA recent article in Ethics & Human Research describes the experience and management of regulatory noncompliance during the conduct of a large, multisite embedded pragmatic clinical trial (ePCT). The Trauma Survivors Outcomes and Support (TSOS), an NIH Collaboratory Trial, was a stepped-wedge, cluster-randomized clinical trial of a collaborative care intervention for injured patients with symptoms of posttraumatic stress disorder in 25 level 1 trauma centers in the United States. The article, Ethical and Regulatory Concerns in Pragmatic Clinical Trial Monitoring and Oversight, was coauthored by members of the TSOS study team, the Collaboratory’s Ethics and Regulatory Core, and colleagues.

The authors describe how the study encountered variabilities in participant tracking across sites, which led to a study-wide internal audit and corrective action. The study team implemented a revision of the participant tracking system and retrained site staff in new procedures. Based on the lessons learned, the authors offer recommendations for future PCTs and relevant stakeholders, including institutional review boards, data safety and monitoring boards, institutions, and trial sponsors.

Among the recommendations:

  • Use a single IRB of record to streamline regulatory processes and reduce variability among research sites.
  • Standardize research procedures but allow for real-world flexibility; this could include real-time, workflow-integrated study logging that captures and documents provider turnover and regulatory training compliance.
  • Implement thorough, specific, and practical training in procedures, especially around participant enrollment and tracking.
  • Ensure that research procedures, monitoring and oversight plans, and training are study specific to account for unique issues, contexts, and needs.

Thoughtful planning, communication, and development and dissemination of standardized procedures remain hallmarks of successful research operations both to advance biomedical research and to ensure appropriate safeguards for its participants. –Roberts et al.

July 31, 2020: Using Real-World Data to Plan Eligibility Criteria and Enhance Recruitment: Actionable Recommendations and Resources from the Clinical Trials Transformation Initiative (Sudha Raman, PhD, MA; John Sheehan, PhD, MBA, RPh)

Posted on by Gina Uhlenbrauck

Speakers

Sudha Raman, PhD, MA
Assistant Professor
Department of Population Health Sciences
Duke University

John Sheehan, PhD, MBA, RPh
Senior Director, Value and Evidence (HEOR) Neuroscience
Janssen Scientific Affairs, LLC

Topic

Using Real-World Data to Plan Eligibility Criteria and Enhance Recruitment: Actionable Recommendations and Resources from the Clinical Trials Transformation Initiative

Keywords

Clinical Trials Transformation Initiative (CTTI); Real-world data (RWD); Recruitment planning; EHR; Eligibility criteria; Fit-for-purpose data

Key Points

  • Real-world data (RWD) are data relating to patient health status and/or the delivery of health care routinely collected by a variety of sources.
  • CTTI provides recent recommendations, resources, and case studies that highlight actionable tools and best practices for evaluating and using real-world data (RWD) in clinical trial recruitment activities:
    • General principles for using RWD
    • Using RWD to plan eligibility criteria
    • Using RWD to support recruitment
    • Enhancing RWD capabilities for the research enterprise
  • Using RWD from data sources such as electronic health records and claims data brings challenges for completeness, accuracy, and generalizability of the data.
  • RWD holds the potential to increase patient eligibility and enrollment as well as reduce recruitment timelines.

Discussion Themes

Insights from RWD should be sought early in the product lifecycle and include context from patients and sites.

One challenge of RWD data sources is finding appropriate databases for the disease area of interest, especially for trials of rare diseases.

Are there lessons learned about when using RWD becomes prohibitive or too expensive?

Read and download CTTI’s recommendations for using RWD. Learn more about FDA’s guidance for real-world data and real-world evidence. A publication is available about the health plan recruitment method used in the ADAPTABLE aspirin study.

Tags

#pctGR, @Collaboratory1

May 8, 2020: Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials: Real World Evidence: Contemporary Experience and Future Directions (Patrick Heagerty, PhD, Jacqueline Corrigan-Curay, JD, MD, Joshua C. Denny, MD, MS)

Posted on by Gina Uhlenbrauck

Speakers

Guest Moderator:
Patrick J. Heagerty, PhD
Professor, Department of Biostatistics, University of Washington

Panel:
Jacqueline Corrigan-Curay, JD, MD
Director of CDER’s Office of Medical Policy (OMP)
U.S. Food and Drug Administration (FDA)

Joshua C. Denny, MD, MS, FACMI
Chief Executive Officer, All of Us Research Program, NIH

Topic

Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials: Real World Evidence: Contemporary Experience and Future Directions

Keywords

Electronic health records; Real-world evidence; RWE; Real-world data; RWD; FDA; All of Us; Phenotypes; Regulatory; Fit-for-use data; Digital heath

Key Points

  • To create quality clinical/research records, we must design for multiuse by integrating standards-based tools in the EHR to bring together health care and research. 
  • Quality real-world evidence cannot be built without quality real-world data. With greater efficiencies in data capture, randomization with real-world data provides a pathway for reliable—and persuasive—real-world evidence.

Discussion Themes

Patient-generated health data is part of FDA’s MyStudies Application, designed to facilitate the input of real-world data directly by patients, which can be linked to electronic health data supporting traditional clinical trials, pragmatic trials, observational studies, and registries.

In assessing data quality we can ask, How does a data element travel from clinical care to a research data set?

The NIH’s All of Us program is building a diverse database that can inform thousands of studies on a variety of health conditions.

The All of Us study is tracking COVID-19 in its patients. Sites have identified their COVID-19 participants and relevant labs. Consent is obtained for future sharing of data.

Tags

#pctGR, @Collaboratory1

April 24, 2020: The RECOVERY Trial: A UK National Platform Trial of Potential Treatments for Patients Hospitalised with COVID-19 (Martin Landray, PhD, FRCP)

Posted on by Gina Uhlenbrauck

Speaker

Martin Landray, PhD, FRCP
Professor of Medicine & Epidemiology
Nuffield Department of Population Health
University of Oxford, UK

Topic

The RECOVERY Trial: A UK National Platform Trial of Potential Treatments for Patients Hospitalised with COVID-19

Keywords

Coronavirus; Virus pandemic; COVID-19; SARS-CoV-2; RECOVERY Trial; Randomized trial; Epidemiology

Key Points

  • Between March 10 and April 3, 2020, the RECOVERY team developed the protocol, obtained regulatory and ethics approval, and enrolled 1,000 patients.
  • COVID-19 presents an unprecedented clinical challenge to the health system, staff, and patients. Even moderate effects from this study will be worthwhile in the generation of robust evidence.
  • RECOVERY follow up will involve linkage to national data sources for vital status and death certificates; coded hospital episode statistics (diagnoses, procedures); intensive care audit data and SARS-CoV-2 PCR laboratory results; and primary care and national outpatient prescribing data.

Discussion Themes

Informed consent for participants in the RECOVERY trial consists of a 2-page information sheet and single form written in plain language.

The urgency of this pandemic requires everyone to focus on what matters and leave orthodoxy, habits, and traditional practices behind. Our mindset has been altered by the COVID-19 disruptions and this public health crisis of extraordinary proportion.

For more information, visit the RECOVERY Trial website.

Tags
#pctGR, #COVID19, @Collaboratory1

March 31, 2020: Engagement in PCTs: Considerations from the Collaboratory’s Ethics and Regulatory Core

Posted on by Gina Uhlenbrauck

A new document from the Ethics and Regulatory Core is available that provides considerations around determining which individuals or groups are engaged in research in pragmatic clinical trials (PCTs). Developed for investigators designing and conducting PCTs as well as institutional review boards overseeing them, the document introduces these questions in relation to research subjects, study team members, and service providers:

  • Which individuals/groups are included in the research?
  • Are these individuals/groups research subjects, study team members, or service providers?
  • Why does it matter how the individuals/groups are categorized for the research?

Download Engagement in Research for Pragmatic Clinical Trials.

 

March 24, 2020: Impacts of COVID-19 on the Conduct of Clinical Trials

Posted on by Gina Uhlenbrauck

In a recent PCT Grand Rounds, Drs. Naggie, Hernandez, and Perakslis of Duke University discussed the impacts of the COVID-19 outbreak on the conduct of clinical trials. The panel described the status of COVID-19, its impact on trials currently begin conducted, some key questions to consider, and potential solutions and approaches. A brief Q&A followed the presentation.

View the video and download the slides from the webinar.

Recent news announcements are available at NIH Announces Guidance for Clinical Trials Affected by COVID-19 Emergency and NIH Shares COVID-19 Guidance and Resources for Applicants and Recipients.

March 20, 2020: Clinical Trials in the Time of COVID-19 (Susanna Naggie, MD; Adrian Hernandez, MD, MHS; Eric Perakslis, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Susanna Naggie, MD
Associate Dean for Clinical Research Initiatives and Regulatory Affairs
Duke University School of Medicine

Adrian F. Hernandez, MD, MHS
Professor of Medicine
Vice Dean for Clinical Research
Duke University School of Medicine

Eric Perakslis, PhD
Rubenstein Fellow
Duke University

Topic

Clinical Trials in the Time of COVID-19

Keywords

Infectious disease; Coronavirus; Pandemic response; COVID-19; Population health; Clinical trials; Human subject protections; Contingency measures; Vaccine; Contact tracing

Key Points

Discussion Themes

Do you anticipate that statisticians will need to account for period effect in later analysis of data (pre/post COVID-19)?

Are there lessons learned from the last epidemics, for example H1N1 or Ebola? How can we deal with global pandemics in the future?

What about clinical trials in the elderly population, given that they are the most vulnerable to the coronavirus and may not be as good with technology as younger participants?

Would it be possible to set up a multisite telehealth-based outbreak learning health unit?

Recent news announcements are available at NIH Announces Guidance for Clinical Trials Affected by COVID-19 Emergency and NIH Shares COVID-19 Guidance and Resources for Applicants and Recipients.

Johns Hopkins University maintains a live website of Coronavirus COVID-19 Global Cases.

Tags
#pctGR, @Collaboratory1, @texhern, @snaggie1, @DukeForge, @eperakslis

March 13, 2020: Impact of Regulatory Guidance on Evaluating Cardiovascular Risk of New Glucose-Lowering Therapies to Treat Type 2 Diabetes Mellitus–Lessons Learned and Future Directions (Abhinav Sharma, MD, PhD; Christopher Granger, MD)

Posted on by Gina Uhlenbrauck

Speakers

Abhinav Sharma, MD, PhD
Assistant Professor of Medicine
McGill University

Christopher B. Granger, MD, FAHA, FACC
Professor of Medicine
Director, Cardiac Intensive Care Unit
Duke University Medical Center

Topic

Impact of Regulatory Guidance on Evaluating Cardiovascular Risk of New Glucose-Lowering Therapies to Treat Type 2 Diabetes Mellitus–Lessons Learned and Future Directions

Keywords

Type 2 diabetes; Regulatory; Cardiovascular risk; Food and Drug Administration; FDA; Patient outcomes; Anti-hyperglycemic medications

Key Points

  • The hallmark of type 2 diabetes mellitus is insulin resistance and relative insulin deficiency. Ninety percent of all cases of diabetes are type 2 diabetes, and the diagnosis can occur at any age.
  • While people with type 2 diabetes can often initially manage their condition through exercise and diet, over time most people will require oral drugs or insulin.
  • Strategies are needed reduce the burden of cardiovascular outcomes in patients with diabetes.
  • In 2008, the U.S. Food and Drug Administration (FDA) issued guidelines for sponsors to demonstrate that their anti-hyperglycemic medications do not increase the risk of cardiovascular disease. In March 2020, the FDA updated the guidance in a draft for comment: Type 2 Diabetes Mellitus: Evaluating the Safety of New Drugs for Improving Glycemic Control Guidance for Industry.

Discussion Themes

Is the cardiovascular protection of some anti-hyperglycemic drugs independent of the effect on blood glucose?

How can regulators, industry, academia, payers, and patient advocacy groups assure that evidence generation to improve care is incentivized without undue regulatory burdens?

Should post-marketing studies include comparative effectiveness pragmatic trials in order to improve translation into clinical practice?

Read more on this topic from Sharma and colleagues in a recent publication in Circulation.

Tags
#pctGR, @Collaboratory1