study design

September 11, 2020: Launching CONNECTS: Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (Gordon Bernard, MD; Sonia Thomas, DrPH)

Posted on by Gina Uhlenbrauck

Speakers

Gordon R. Bernard, MD
CONNECTS ACC Science Unit P
Professor of Medicine
Executive Vice President for Research
Senior Associate Dean for Clinical Science
Vanderbilt University Medical Center

Sonia Thomas, DrPH
CONNECTS ACC Principal Investigator
Senior Research Statistician
RTI International

Topic

Launching CONNECTS: Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies

Keywords

COVID-19; CONNECTS; NHLBI; Collaborative research; Data sharing; Adaptive trials; Data standardization; ACTIV; Therapeutic agent prioritization

Key Points

  • The Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (CONNECTS) is a research partnership coordinated by the Research Triangle Institute, Vanderbilt University Medical Center, and the National Heart, Lung, and Blood Institute (NHLBI) of the NIH.
  • CONNECTS aims to build on existing clinical research networks to better understand the risk of severe illness from COVID-19 and to identify therapies that will slow or halt the disease progression and speed recovery. Studies will enroll participants with health conditions that are known to increase their risk for severe complications from COVID-19.
  • The immediate goal is to design and implement master protocol-driven adaptive clinical trials, including outpatient, inpatient, and recovering master protocols.
  • CONNECTS is part of a larger ecosystem in the Department of Health and Human Services that includes the FDA, CDC, BARDA, Operation Warp Speed, and NIH. More than 34 trial networks and 1,000 sites are participating in CONNECTS.

Discussion Themes

Are the CONNECTS resources, such as the common data elements manual, draft protocols, and case report forms, publicly available?

In your effort to reach underrepresented communities, have you considered collaborating with Historically Black Colleges and Universities (HBCUs), particularly those that conduct health research?

While COVID-19 is providing you with plenty to focus on, do you see the potential for sustainability of CONNECTS beyond this pandemic?

Read more about CONNECTS.

Tags

#pctGR, @Collaboratory1

August 31, 2020: Newly Validated Sample Size Formula Detects Heterogeneity of Treatment Effect in Cluster Randomized Trials

Posted on by Damon Seils

Cover of Statistics in MedicineIn a study supported by the NIH Collaboratory, researchers developed and validated a new sample size formula for detecting heterogeneity of treatment effect in cluster randomized trials. The work was published this month in Statistics in Medicine.

Cluster randomization is frequently used in pragmatic clinical trials embedded in healthcare systems. Although cluster randomized trials are typically designed to evaluate the overall treatment effect in a study population, investigators are increasingly interested in studying differential treatment effects among subgroups.

The NIH Collaboratory investigators used extensive computer simulations to validate the new formula. They illustrate the procedure in a dataset from a large clinical trial.

In a previous study published last year, the same research team used computer simulation models validated by real-data simulations to reveal the influence of baseline covariate imbalance on treatment effect bias.

This work was supported within the NIH Collaboratory by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director, and by a research supplement from the NIH Common Fund to promote diversity in health-related research.

August 27, 2020: Chapter on Acquiring Real-World Data Added to the Living Textbook

Posted on by Karen Staman

The NIH Collaboratory this week published a new chapter of its Living Textbook of Pragmatic Clinical Trials. The chapter, “Acquiring Real-World Data,” outlines strategies for obtaining real-world data for use in research.

“Real-world data” include data relating to the health status of a patient or the delivery of healthcare services. Common sources include electronic health records (EHRs), administrative claims, patient-reported outcomes, patient-generated health data, medical product and device registries, and databases relating to environmental factors or social determinants of health. Real-world data can support a number of activities in pragmatic clinical trials, such as patient identification and recruitment, monitoring of outcomes, and ascertainment of endpoints.

The new chapter includes the following sections:

The new chapter updates a previous resource, one of the most popular on the Living Textbook, based on work by experts in the NIH Collaboratory’s Electronic Health Records Core Working Group.

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.