November 3, 2020: Disseminating Trial Results: We Can Have Faster and Better

Healthcare cover imageNIH Collaboratory investigators Drs. Greg Simon, Rachel Richesson, and Adrian Hernandez published an opinion piece in Healthcare arguing that clinical trials investigators should align their dissemination processes with industry-sponsored trials to favor speed, and that years-long delays in dissemination reduce the relevance of clinical research.

“Delays reduce the ability for researchers to apply trial findings to new research questions, impede clinicians from having the most up-to-date information, and perhaps most importantly, are a disservice to patients who could benefit from the information.”

The authors use experiences with pragmatic trials supported by the NIH Collaboratory to explore faster dissemination of results, and suggest the following solutions:

  • Real-time access to outcome data
  • Continuous data curation and cleaning
  • Immediate data analysis
  • Rapid reporting of trial results

Much change is needed to reach these goals. The authors suggest that by modeling processes after industry-sponsored trials, researchers may be able to improve the speed and quality of results reporting.

“Cultural incentives are aligned in industry sponsored trials to favor speed: readiness for generalizing topline results is considered valuable to shareholders, and the culture encourages a system where data are liquid, available, and continuously cleaned and curated, such that topline results can be reported within a timespan of two weeks rather than two years.”

As part of the NIH Collaboratory’s commitment to dissemination and sharing, all NIH Collaboratory Trials are expected to share data and resources, and topline results are reported in our weekly Grand Rounds Webinars.

 

January 16, 2020: NIH Collaboratory Investigators Describe Key Elements of Successful Distributed Research Networks

Members of the NIH Collaboratory Distributed Research Network (DRN) have helped build DRNs for the Sentinel System, the NIH Collaboratory, and the National Patient-Centered Clinical Research Network (PCORnet). In a new article published online in Contemporary Clinical Trials Communications, they describe the key elements of successful DRNs, as well as methods, challenges, and solutions encountered in using DRNs to support different phases of randomized, multisite clinical research.

“…[DRNs] are a vital component for trials that use real-world data to generate real-world evidence. Given their access to larger and more diverse populations, as well as health systems with a variety of care practices, DRN-based trials have the potential to produce more generalized results.” —Marsolo et al. 2020

DRNs enable the use of real-world data by repurposing electronic health record (EHR) and claims data for research. However, the use of these data to create evidence is “complicated by lack of uniformity in data collection, a fragmented healthcare system, and the imperative to protect research participants.”

The NIH Collaboratory DRN can support observational studies of comparative effectiveness and safety, prospective data collection, and randomized clinical trials. For more, see the list of publications and presentations.

July 3, 2019: New Article Describes the Public’s Beliefs Regarding Responsibility to Participate in Research

Findings from a new article suggest that the majority of patients do not feel a personal responsibility to participate in clinical research. In the article, Kevin Weinfurt, Li Lin, and Jeremy Sugarman report the results of a national survey of nearly 3000 people regarding their attitudes towards research responsibilities as well as their trust in doctors, healthcare systems, and medical research. Ethical frameworks for learning health systems have suggested that patients have a responsibility to contribute to learning activities, including research. The findings from this survey suggest that most patients in the U.S. do not currently endorse such a responsibility.

“These data provide a useful snapshot of the public’s views toward the obligation to participate in research. It is unclear how, if at all, these views will shift with increased efforts to create mature learning health systems. And if such views do not shift, it is uncertain what that would mean for the success of learning health systems.” —Kevin Weinfurt, PhD

Read the full article: Public Views Regarding the Responsibility of Patients, Clinicians, and Institutions to Participate in Research in the U.S.

For more on alternate approaches to consent, see the Living Textbook Chapter on Consent, Disclosure, and Non-Disclosure

April 26, 2019: The VERITAS Trial: Virtual Exercise Rehabilitation at the Intersection of Evidence, Implementation, and Policy (Janet Prvu Bettger, ScD)

Speaker

Janet Prvu Bettger, ScD, FAHA
Associate Professor
Duke Department of Orthopaedic Surgery
Duke Clinical Research Institute

Topic

The VERITAS Trial: Virtual Exercise Rehabilitation at the Intersection of Evidence, Implementation, and Policy

Keywords

Rehabilitation; Virtual physical therapy; Patient outcomes; Physical therapy; Orthopaedic surgery; Total knee replacement; Digital technology; Telehealth

Key Points

  • The VERITAS trial evaluated the effects of physical therapy–supported virtual exercise compared with traditional home- or clinic-based physical therapy after total knee replacement. Outcome measures included 90-day health service use costs; patient-centered outcomes; and differential improvement from 6 weeks to 3 months.
  • The Center for Connected Health Policy found that while most states currently have established telehealth policies for primary care providers, these often do not include physical or occupational therapists.
  • Tele-rehabilitation facilitates communication between the patient and physical therapist in real time. The VERA™ technology provides a virtual physical therapist assistant for patients and clinicians, offering a digital interface that includes patient education, longitudinal functional assessments, telehealth video conferencing, personalized exercises, and remote monitoring of patient progress.

Discussion Themes

Study results support effectiveness and safety hypotheses: that tele-rehabilitation is noninferior to traditional physical therapy with respect to range of motion, walking speed, pain, or rehospitalization. However, it was not shown that the intervention is noninferior with respect to falls after hospital discharge.

Because virtual physical therapy interventions can save total costs, prevent readmissions, and improve mobility, it will be important to expand access to tele-rehabilitation and to advance policies that include physical therapists.

Read more about the VERITAS project and at ClinicalTrials.gov.

Tags

#telehealth, #pctGR, @Collaboratory1

April 5, 2019: The ENGAGES Pragmatic Trial and the Power of Negative Thinking (Michael S. Avidan, MBBCh)

Speaker

Michael S. Avidan, MBBCh
Dr. Seymour and Rose T. Brown Professor of Anesthesiology
Chief, Division of Clinical and Translational Research
School of Medicine, Department of Anesthesiology
Washington University in St. Louis

Topic

The ENGAGES Pragmatic Trial and the Power of Negative Thinking

Keywords

Pragmatic clinical trial; Surgery; Electroencephalography; EEG-guided anesthesia; Postoperative delirium; Older patients; Patient-centered outcomes; ENGAGES

Key Points

  • The ENGAGES pragmatic trial evaluated whether electroencephalogram-guided anesthetic administration decreases postoperative delirium incidence in older patients undergoing major surgery.
  • Delirium is a disturbance in consciousness or change in cognition for a short period of time as a consequence of a medical illness. 25% to 50% of older adults experience delirium after major surgery, and the number is even higher for ICU patients.
  • The ENGAGES trial found that, among older adults undergoing major surgery, EEG-guided anesthetic administration, compared with usual care, did not decrease the incidence of postoperative delirium.

Discussion Themes

Aside from the intensity of patient follow-up and the expertise needed to deliver the EEG-guided protocol, the ENGAGES study fulfilled the criteria for a pragmatic clinical trial as shown in PRECIS-2 ratings.

Clinicians participating in ENGAGES were not researchers but carried out the intervention on the ground. They understood the appeal of it and found it easy to implement.

With respect to study findings, instead of referring to “negative” or “null” findings, why not say, “this is what we found and these are interesting findings.”

Learn more about the results of the ENGAGES trial in JAMA (Feb 2019).

Tags

#delirium, #pctGR, @Collaboratory1, @WUSTL_med

November 13, 2018: Summary of Workshop on Pragmatic Trials of Therapeutic A vs B Interventions Now Available

The NIH Collaboratory recently convened a workshop to explore embedded pragmatic clinical trials comparing two or more therapeutic medical interventions. These “A vs B” trials are meant to test existing, viable treatment alternatives where there is uncertainty about which treatment is best in which populations. There are unique barriers that make these types of pragmatic trials especially challenging to implement. For the workshop, a panel of experts gathered to discuss challenges and solutions regarding partnering with healthcare systems to conduct the trials, unique legal and ethical issues, and design and operational considerations. The summary of the workshop is now available: Workshop Summary: Embedded Pragmatic Clinical Trials of Therapeutic A vs. B Interventions

 

Additional Resources:

Embedded pragmatic clinical trials of therapeutic A vs. B interventions workshop videocast.

 

September 7, 2018: Spotlight on a New NIH Collaboratory Trial: HiLo

Kidney transplantation is the preferred treatment for patients with end-stage renal disease (ESRD), but an insufficient organ supply renders dialysis the only viable treatment option for most patients. Though clinical outcomes among patients receiving dialysis have improved modestly in recent years, annual rates of hospitalization and mortality remain unacceptably high, and quality of life is poor. Poor outcomes are driven primarily by increased risk of cardiovascular disease (CVD), but interventions that improve outcomes in the general population by targeting traditional CVD risk factors have mostly failed in patients with ESRD. Current clinical practice guidelines advocate aggressive treatment of high serum phosphate to near-normal levels using dietary phosphate binders and restrictive diets. The benefits of this approach, however, are unproven, the optimal serum phosphate target remains unknown, and potential harms of aggressive treatment have not been definitively identified.

The Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo) plans to address these clinically important questions in a large, pragmatic, cluster-randomized trial that will evaluate the effects of liberalizing the serum phosphate target (“Hi”) versus maintaining aggressive phosphate control (“Lo”) for patients receiving treatment with maintenance hemodialysis.

 “The question at hand is something we grapple with on a daily basis in every dialysis facility across the country. Either answer will be important new information that will help us do a better job taking care of patients and hopefully improve their quality of life.”

HiLo is led by Myles Wolf, MD, of Duke University with support from the National Institute of Diabetes and Digestive and Kidney Diseases. Read more about HiLo.

October 11, 2017: New grant awarded to Dr. Jeffrey Jarvik and his team of investigators to promote pragmatic musculoskeletal clinical research

Congratulations to Dr. Jeffrey Jarvik and his colleagues at the University of Washington for their recent grant award to establish the Core Center for Clinical Research (CCCR). The initiative will promote pragmatic, multi-institutional clinical research on musculoskeletal conditions, such as the diagnosis and treatment of back pain. The new center—the UW Center for Clinical Learning, Effectiveness And Research (CLEAR)—will investigate the effectiveness of interventions such as imagining tests, physical therapy, opioids, spine injections, and spine surgery, as well as approaches for implementation.  The National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) are funding the 5-year, $3.7 million initiative, which will include pragmatic and comparative effectiveness trials and Core groups, including:

  • The Methodology Core, led by Patrick J. Heagerty PhD, Chair of the Department of Biostatistics, and Sean Mooney PhD, Professor of Biomedical Informatics and Chief Research Information Officer
  • The Resource Core, led by Janna Friedly MD, Associate Professor of Rehabilitation Medicine, and Danielle Lavallee PharmD PhD, Research Associate Professor of Surgery

Dr. Jarvik is a Professor of Radiology at University of Washington and the Principal Investigator the Collaboratory NIH Collaboratory Trial, the Lumbar Imaging with Reporting of Epidemiology (LIRE) trial.

 

PCORnet Posts Aspirin Study Protocol for Public Review and Comment


PCORnetThe National Patient-Centered Clinical Research Network (PCORnet) has recently made a draft protocol for its first randomized clinical trial available for stakeholder review. Researchers, clinicians, patients and the public are all invited to read the current draft of the study protocol and provide comments and feedback.

The ADAPTABLE Study (PDF), which will investigate whether lower- or higher-dose aspirin is better for preventing heart attack and stroke in patients at risk for heart disease, is PCORnet’s first randomized pragmatic clinical trial. Designed to leverage PCORnet’s Clinical Data Research Networks (CDRNs) and Patient-Powered Research Networks (PPRNs), the trial will serve as twofold purpose: answering a clinical question of direct importance for patients, families, and healthcare providers, and serving as a demonstration of PCORnet’s capabilities in conducting clinical research on a national scale.

Links to the proposed study protocol, a survey tool for capturing feedback, and other information about ADAPTABLE Study, including press releases, fact sheets, and infographics, are available at the link below:

ADAPTABLE: The Aspirin Study

Follow PCORnet on Twitter @PCORnetwork for updates on the ADAPTABLE #ClinicalTrial


Patient-Reported Outcomes Workshop Report Available


Tools for ResearchIn January of 2015, the NIH HCS Collaboratory’s Patient-Reported Outcomes (PRO) Core Group convened a 2-day workshop in Baltimore devoted to identifying barriers and possible solutions to the use of NIH-supported PRO tools in comparative-effectiveness research (CER).

Findings from the meeting, which include case study presentations and reflections from multiple stakeholders representing the research, clinical, and patient communities, were distilled into a summary document available from the NIH Collaboratory Knowledge Repository at the link below:

The workshop summary is also available on the Living Textbook’s “Tools for Research” section, under “Patient-Reported Outcomes White Paper.