study design

August 21, 2020: Adaptive Platform Trials: Scalable from Breast Cancer to COVID (Laura Esserman, MD, MBA)

Posted on by Gina Uhlenbrauck

Speaker

Laura Esserman, MD, MBA
Director, UCSF Carol Franc Buck Breast Care Center
Alfred A. de Lorimier Endowed Chair in General Surgery
Professor of Surgery and Radiology, UCSF

Topic

Adaptive Platform Trials: Scalable from Breast Cancer to COVID

Keywords

COVID-19; Adaptive platform trial; Study design; Learning healthcare system; Collaborative research

Key Points

  • Adaptive trial design is an innovative, collaborative approach with the potential to maximize learning about treatments so as to prioritize therapeutic agents and drive better patient outcomes.
  • Adaptive platform trials are designed to identify early endpoints that can be captured in the course of care. Multiple agents are evaluated simultaneously, and those with a potential for big impact are advanced quickly.
  • As a “learning engine,” adaptive platform trials could be used to accelerate high-impact treatments for COVID-19 and future pandemics.

Discussion Themes

Essential to an adaptive platform trial are checklists of data and nimble EHR tools that evolve as the disease evolves.

What is the process to monitor for and make the decision to modify the standard of care backbone?

Read more about adaptive platform trials at the I-SPY Trials website and a recent Grand Rounds presentation, Optimized Learning While Doing: The REMAP-CAP Adaptive Platform Trial.

Tags

#pctGR, @Collaboratory1

August 14, 2020: Learning While Sprinting: A One-Year Retrospective from the NOHARM Pragmatic Trial (Jon Tilburt, MD; Andrea Cheville, MD)

Posted on by Gina Uhlenbrauck

Speakers

Jon Tilburt, MD
Professor of Medicine and Biomedical Ethics
Mayo Clinic

Andrea Cheville, MD
Professor of Physical Medicine and Rehabilitation
Mayo Clinic

Topic

Learning While Sprinting: A One-Year Retrospective from the NOHARM Pragmatic Trial

Keywords

PRISM; NIH Heal Initiative; NOHARM; Postoperative care; Nonpharmacologic pain care (NPPC); Stepped wedge; Cluster-randomized trial; Electronic health records (EHRs); Patient engagement; Clinical decision support

Key Points

  • The Nonpharmacologic Options in Postoperative Hospital-based and Rehabilitation Pain Management (NOHARM) NIH Collaboratory Trial is completing its pilot phase. This embedded, stepped-wedge PCT will test a sustainable strategy in perioperative, nonpharmacologic pain management that preserves patient function, honors patient values, and maintains the availability of opioids as a last resort.
  • NOHARM is a pragmatic, EHR-integrated intervention that bundles a portal-based conversation guide that captures patient preferences for postsurgical pain care and a clinician-directed decision support tool.
  • Nonpharmacologic pain care management options include walking, yoga, tai chi, acupressure, massage, meditation, and relaxation.

Discussion Themes

Opioids are insufficient in postsurgical care. Guidelines recommend nonpharmacologic pain care (NPPC), but there have not been studies showing how to make NPPC more viable.

The COVID-19 pandemic caused disruption in scheduled surgeries and also air travel, which precluded on-the-ground support at two study sites. However, the team was able to adjust recruitment methods during the pilot phase.

What was the team’s proactive process in working with the IRB in order to obtain a waiver of consent?

The NOHARM intervention has sustained high-level institutional support despite the impact of COVID-19.

Read more about the NOHARM NIH Collaboratory Trial.

Tags

#pctGR, @Collaboratory1

August 19, 2020: NIH Collaboratory COVID-19 Grand Rounds Series Puts Spotlight on Adaptive Platform Trials

Posted on by Damon Seils

Photo of Dr. Laura EssermanIn this week’s COVID-19 Grand Rounds session, Dr. Laura Esserman of the University of California, San Francisco will present “Adaptive Platform Trials: Scalable From Breast Cancer to COVID.” The Grand Rounds session will be held on Friday, August 21, at 1:00 pm eastern. Join the online meeting.

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.

Previous COVID-19 Grand Rounds:

For more news and resources related to the COVID-19 public health emergency, see the COVID-19 Resources page.

August 11, 2020: Grand Rounds Webinar Discusses the Democratization of Medical Research

Posted on by Gina Uhlenbrauck

A recent Grand Rounds webinar presented by C. Michael Gibson, MS, MD, described how open access, patient empowerment, social media, and digital health are transforming clinical trials. Dr. Gibson is a professor of medicine at Harvard Medical School and president and CEO of Baim and PERFUSE Research Institutes.

Among the key points:

  • The COVID-19 pandemic has been a call to arms to physicians to combat not only the virus but the misinformation.
  • As the internet is replacing the printing press, “copyleft” is replacing copyright in this new open-access era. It is a participatory community with bidirectional flow of information through social media.
  • Health data does not equal health care. Patients are looking to physicians to curate health information.
  • In this new world of clinical research, patients are enrolling in virtual trials via a phone app and will be followed up online through claims data and patient-reported outcomes.
  • Patient-empowered trials have the potential to provide more generalizable study results and to lead to patient-specific predictions through use of artificial intelligence.

Watch the complete webinar and download the slides.

Read more in The Democratization of Medical Research and Education Through Social Media: The Potential and the Peril (Gibson, JAMA Cardiology, 2017) and learn about the Heartline Study as an example of a “giga trial.”

August 7, 2020: The Democratization of Medicine: Open Access, Social Media, AI, Apps, and Empowering the Patient as the Future of Clinical Research (C. Michael Gibson, MS, MD)

Posted on by Gina Uhlenbrauck

Speaker

C. Michael Gibson, MS, MD
Professor of Medicine
Harvard Medical School
President and CEO
Baim and PERFUSE Research Institutes

Topic

The Democratization of Medicine: Open Access, Social Media, AI, Apps, and Empowering the Patient as the Future of Clinical Research

Keywords

Clinical research; Open access; Social media; Artificial intelligence; Heartline study; WikiDoc; WikiPatient

Key Points

  • As the internet is replacing the printing press, “copyleft” is replacing copyright in the open-access era. It is a participatory community with bidirectional flow of information through social media.
  • Health data does not equal health care. Patients are looking to physicians to curate health information from huge volumes of data.
  • Social media and open access during the COVID-19 pandemic has meant that physicians are citizen journalists, innovators, activists, and educators.
  • In this new world, patients are enrolling in virtual trials via a phone app and will be followed up online through claims data and patient-reported outcomes.

Discussion Themes

The COVID-19 pandemic has been a call to arms to clinicians to combat not only the virus but the misinformation. As educators we must set the path and not allow uninformed people to take control.

Enabling patient-empowered trials has the potential for more generalizable study results and can lead to patient-specific predictions through use of artificial intelligence.

How do we validate the quality of open-access data and reports that are not peer-reviewed?

How can we diminish the hazards of skewed research outcomes arising from trial participant conversations on social media?

Read more from C. Michael Gibson in The Democratization of Medical Research and Education Through Social Media: The Potential and the Peril (JAMA Cardiology 2017).

Tags

#pctGR, @Collaboratory1

July 24, 2020: TENS in Fibromyalgia: From Fundamental Neurobiology to Pragmatic Trial (Leslie J. Crofford, MD; Kathleen Sluka, PT, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Leslie J. Crofford, MD
Wilson Family Chair and Professor of Medicine
Vanderbilt University Medical Center

Kathleen Sluka, PT, PhD
Kate Daum Research Professor
Department of Physical Therapy and Rehabilitation Science
University of Iowa

Topic

TENS in Fibromyalgia: From Fundamental Neurobiology to Pragmatic Trial

Keywords

Fibromyalgia; Musculoskeletal pain; Neuropathic pain; Transcutaneous electrical nerve stimulation (TENS); Physical therapy; Nonpharmacologic pain treatment; PRISM; Patient-reported outcomes (PROs)

Key Points

  • Fibromyalgia (FM) is a condition of widespread pain that is worsened with physical activity. It involves chronic musculoskeletal and visceral pain and is often accompanied by fatigue, depression, or anxiety.
  • Transcutaneous electrical nerve stimulation (TENS) is a technique that uses a device to deliver an electric impulse through the skin. Treatment with TENS has been shown to improve resting and movement-evoked pain and fatigue.
  • While physical therapists generally are trained in the use of TENS, the technique remains underused in clinical practice.
  • The goal of the FM TIPS pragmatic trial is to determine, in a real-world clinical setting, whether physical therapy combined with TENS for patients with FM is more effective than physical therapy alone. The study is being piloted in 24 sites across 5 physical therapy health systems.

Discussion Themes

While COVID-19 has had an impact on piloting the FM TIPS study, some kind of physical therapy will be possible through telemedicine. Other challenges include that conducting embedded research in physical therapy clinics is new, and there are multiple different EHR systems in use across the partnering clinics.

The recently published results from Fibromyalgia Activity Study With TENS (FAST) showed that TENS can be safely used in addition to other treatments to improve pain and fatigue in women with fibromyalgia in the setting of a randomized controlled trial.

Read more about the Fibromyalgia TENS in Physical Therapy Study (FM TIPS) NIH Collaboratory Trial and watch a brief interview with the PIs of the study.

FM TIPS is one of the NIH HEAL Initiative’s PRISM (Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing) studies.

Tags

#pctGR, @Collaboratory1

July 27, 2020: ADAPTABLE Roundtable Produces Consensus Statement on Capturing Patient-Reported Health Data in Clinical Trials

Posted on by Damon Seils

A new report from an NIH Collaboratory roundtable discussion held in 2017 discusses considerations for the capture of patient-reported health (PRH) data in clinical trials. The report is part of an effort by the ADAPTABLE Supplement project team “to address best practices for capturing PRH data in pragmatic studies and optimal analytic approaches for integrating PRH with other data sources.”

The statement was published online ahead of print this month in Healthcare.

The new consensus statement is the second report from the ADAPTABLE roundtable. A statement published in February offered guidance for the analysis and integration of PRH data in clinical trials.

ADAPTABLE, the first major randomized comparative effectiveness trial conducted by the National Patient-Centered Clinical Research Network (PCORnet), seeks to determine the optimal dose of aspirin therapy for secondary prevention of atherosclerotic cardiovascular disease. The trial relies on both existing EHR data sources and PRH data.

This work was supported by a supplemental grant award to the NIH Collaboratory Coordinating Center from the National Center for Complementary and Integrative Health.

June 30, 2020: Special Issue of JAGS Features NIA IMPACT Collaboratory’s Work on Embedded Pragmatic Trials and Dementia Care

Posted on by Karen Staman

Members of the National Institute on Aging (NIA) IMPACT Collaboratory (Imbedded Pragmatic Alzheimer’s Disease [AD] and AD-Related Dementias [AD/ADRD] Clinical Trials) recently contributed 10 articles to a special issue of the Journal of the American Geriatrics Society. The articles support the IMPACT Collaboratory’s mission to “build the nation’s capacity to conduct ePCTs within healthcare systems for people living with dementia and their caregivers.”

The NIA IMPACT Collaboratory was modeled after the NIH Collaboratory; it has Working Group Cores to help advance the mission and support pilot and NIH Collaboratory Trials. The Cores include Administration, Design and Statistics, Dissemination and Implementation, Health Care Systems, Health Equity, Patient/Caregiver Reported Outcomes, Pilot Studies, Regulation and Ethics, Stakeholder Engagement, Technical Data, and Training.

Each of the Cores contributed an article to the special issue to describe how they are working to improve the quality and effectiveness of ePCTs for people living with dementia and their care partners.

The full list of articles (below) also includes an introductory article by leadership of the NIA IMPACT Collaboratory, Drs. Susan Mitchell, Vincent Mor, Ellen McCarthy, and Jill Harrison.

  • Embedded Pragmatic Trials in Dementia Care: Realizing the Vision of the NIA IMPACT Collaboratory
  • Achieving Health Equity in Embedded Pragmatic Trials for People Living with Dementia and Their Family Caregivers
  • Building a National Program for Pilot Studies of Embedded Pragmatic Clinical Trials in Dementia Care
  • Training the Workforce to Conduct Embedded Pragmatic Clinical Trials to Improve Care for People Living with Dementia and Their Caregivers
  • Dissemination and Implementation of Evidence-Based Dementia Care Using Embedded Pragmatic Trials
  • Ethical and Regulatory Issues for Embedded Pragmatic Trials Involving People Living with Dementia
  • Transforming Dementia Care Through Pragmatic Clinical Trials Embedded in Learning Healthcare Systems
  • Using Healthcare Data in Embedded Pragmatic Clinical Trials among People Living with Dementia and Their Caregivers: State of the Art
  • Selecting Outcomes to Ensure Pragmatic Trials Are Relevant to People Living with Dementia
  • Engaging Stakeholders in the Design and Conduct of Embedded Pragmatic Clinical Trials for Alzheimer’s Disease and Alzheimer’s Disease–Related Dementias
  • Statistical Considerations for Embedded Pragmatic Clinical Trials in People Living with Dementia

Drs. Mitchell and Mor are also co–principal investigators of the Pragmatic Trial of Video Education in Nursing Homes (PROVEN), an NIH Collaboratory Trial. See the Living Textbook for more on the NIH Collaboratory Core Working Groups and NIH Collaboratory Trials.

June 19, 2020: Living Textbook Grand Rounds Series: Part 4-Demystifying Biostatistical Concepts for Embedded Pragmatic Clinical Trials (Elizabeth Turner, PhD; Patrick Heagerty, PhD; David Murray, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Elizabeth Turner, PhD
Associate Professor
Department of Biostatistics & Bioinformatics
Duke Global Health Institute
Duke University  

Patrick Heagerty, PhD
Professor Department of Biostatistics
University of Washington  

David Murray, PhD
Associate Director for Prevention
Director, Office of Disease Prevention National Institutes of Health

Topic

Demystifying Biostatistical Concepts for Embedded Pragmatic Clinical Trials

Keywords

Embedded PCTs; Biostatistics; Trial design; Cluster-randomized trial (CRT); Stepped-wedge; Intraclass correlation coefficient; NIH Collaboratory Trial; Sample size; Individually randomized group treatment

Key Points

  • Focus on the research question, because that will drive the design, and the design will drive the analysis.
  • Select design features with analysis in mind, and collaborate early with a statistician. Weigh statistical choices against the challenges of implementation.
  • If possible, choose individual randomization. However, sometimes there is a strong rationale for choosing cluster/group randomization. Clustering must be accounted for in both design and analysis for CRTs and individually randomized group treatment (IRGT) trials.
  • The intraclass correlation coefficient (ICC) is a common measure of outcome clustering. Estimating the ICC is needed for study planning and power.
  • Increasing the number of clusters has more impact on power than increasing the number of patients per cluster.

Discussion Themes

With the move to virtual healthcare, the boundaries between clinic-based clusters have become more fluid. What approaches should trials use to describe contamination and estimate the impact of contamination on outcomes?

Read more about ICC in a Living Textbook resource and visit the Training Resources page for practical help on how to plan and conduct ePCTs.

Learn more in the Living Textbook about considerations for trial design and analysis for ePCTs.

Visit the NIH Collaboratory’s Biostatistics and Study Design Core webpage for more resources around design and analysis issues in ePCTs.

The NIH hosts a Research Methods Resources website with materials on this topic.

Tags

#pctGR, @Collaboratory1

June 22, 2020: NIH Offers Methods Webinar on Stepped-Wedge Cluster Randomized Trials

Posted on by Damon Seils

The NIH Office of Disease Prevention will continue its Methods: Mind the Gap webinar series on July 14 with “Overview of Statistical Models for the Design and Analysis of Stepped Wedge Cluster Randomized Trials.” Dr. Fan Li of Yale University, a longtime participant in the NIH Collaboratory’s Biostatistics and Study Design Core Working Group, will lead the webinar.

The Methods: Mind the Gap series explores research design, measurement, intervention, data analysis, and other methods of interest in prevention science. The July 14 session will address the stepped-wedge cluster randomized design, which has received increasing attention in pragmatic clinical trials (PCTs) and implementation science research. Since the design’s introduction, a variety of mixed-effects model extensions have been proposed for the design and analysis of PCTs. Dr. Li will provide a general model representation and discuss model extensions as alternative ways to characterize secular trends, intervention effects, and sources of heterogeneity. He will also review key model ingredients and clarify their implications for the design and analysis of stepped-wedge cluster randomized trials.

Register in advance to join the online presentation. Registration is required.