study design

April 15, 2019: Registration Now Open for Workshop on the Design & Analysis of Embedded Pragmatic Clinical Trials (ePCT)

Posted on by Gina Uhlenbrauck

The NIH Health Care Systems Research Collaboratory is hosting a one-day workshop on the Design & Analysis of Embedded Pragmatic Clinical Trials (ePCTs) on May 2, 2019, in the Lister Hill Auditorium on the NIH Campus.

The workshop will include a series of moderated discussions that focus on issues of measuring trial outcomes from available data sources, potential randomization strategies, specific ePCT design considerations, and unique challenges associated with ePCTs. Panel discussions will utilize case examples from the Collaboratory repertoire and beyond to illustrate how clinical investigators and biostatisticians work to address research questions posed by specific trials.

The Workshop Website provides information on meeting logistics, agenda, and registration. There is also an option to attend the workshop remotely via the NIH Videoconference Center, and those details are also available at the Workshop Website.

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

Posted on by Gina Uhlenbrauck

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

March 29, 2019: ICD-Pieces: Lessons Learned in an Ongoing Trial (Miguel Vazquez, MD, George (Holt) Oliver, MD, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Miguel A. Vazquez, MD
Professor of Medicine
Clinical Chief Nephrology Division
UT Southwestern Medical Center

George (Holt) Oliver, MD, PhD
Vice President Clinical Informatics
Parkland Center for Clinical Innovation

Topic

ICD-Pieces: Lessons Learned in an Ongoing Trial

Keywords

Multiple chronic conditions; Chronic kidney disease; Hypertension; Diabetes; Pieces™; Electronic health record; Parkland Center for Clinical Innovation; Primary care; U.S. Department of Veterans Affairs

Key Points

  • Improving Chronic Disease Management with Pieces™ (ICD-Pieces) is an NIH Collaboratory Trial that is implementing a novel technology platform (Pieces) to enable the use of electronic health record data in the management of chronic kidney disease, diabetes, and hypertension within primary care practices.
  • The aim of the study is to reduce hospitalizations, emergency department visits, readmissions, and cardiovascular events and deaths for patients with multiple chronic conditions.
  • ICD-Pieces is employing centralized clinical decision support across 4 large, diverse healthcare systems in addition to the use of Practice Facilitators within primary care.

Discussion Themes

In embedded pragmatic clinical trials conducted in real-world settings, it is important to anticipate changes over the course of the study, which could involve changes at every level, from staff turnover to changes in national policies or standards.

As one of the largest healthcare providers in the world for patients with chronic kidney disease, the VA has been an effective healthcare system partner in the ICD-Pieces trial.

When partnering with healthcare systems, it is important to align goals and plan together, minimize disruption, anticipate and adapt to changes, and create a sustainable foundation for future studies.

Learn more about ICD-Pieces on their website.

Tags

#pctGR, @Collaboratory1

April 1, 2019: Pre-Conference Seminar on Essentials of ePCTs Offered at AcademyHealth’s June 2019 Annual Research Meeting in D.C.

Posted on by Gina Uhlenbrauck

The NIH Collaboratory is partnering with AcademyHealth to offer a full-day pre-conference seminar at the 2019 Annual Research Meeting in Washington, D.C. Essentials of Embedded Pragmatic Clinical Trials will provide an introduction to the investigative opportunities for embedded health systems research, along with strategies for conducting clinical trials that provide real-world evidence necessary to inform both practice and policy. Firsthand ePCT experiences and case studies from the NIH Collaboratory will support and illustrate the topics presented. Speakers will include program officers and senior staff from NIH Institutes and Centers and senior investigators from the NIH Collaboratory Trials and Coordinating Center.

Learning objectives include:

  • To clarify the definition of ePCTs and explain their utility.
  • To introduce attendees to the unique characteristics and challenges of designing, conducting, and implementing ePCTs within diverse health care systems.
  • To increase the capacity of health services researchers to address important clinical questions with ePCTs.
Seminar Details & Registration
Saturday, June 1, 2019
8 am to 5 pm
Walter E. Washington Convention Center
Washington, D.C.

March 13, 2019: PROVEN Publishes Study of Nursing Home Characteristics Associated With Implementation of an Advance Care Planning Video Intervention

Posted on by Gina Uhlenbrauck

The NIH Collaboratory Trial Pragmatic Trial of Video Education in Nursing Homes (PROVEN) is testing the effectiveness of a novel advance care planning (ACP) video education program in 360 nursing homes within 2 large nursing home healthcare systems. The investigators of PROVEN recently published a study that examines the characteristics of nursing homes associated with implementation of the video. They found that lower quality nursing homes (rated 1 star) had lower offer rates than higher quality nursing homes, suggesting that ongoing support might be necessary in these settings, as well as engagement with a local champion.

ACP is a process by which individuals define their future goals and preferences for medical treatment at the end of life and discuss these goals with their family and healthcare providers. ACP is especially important for nursing home residents, who often receive unnecessary care and experience burdensome transitions at the end of life. The ACP intervention in PROVEN is delivered by an onsite champion at the facility—usually a social worker with structured training in how and when to offer and show the ACP videos to residents and families.

 “These results have implications for future pragmatic trials in the NH [nursing home] setting because ongoing engagement between research and NH staff appears crucial for successful integration of interventions into routine clinical practice. Future research is needed to understand how to best engage NHs in implementation and encourage communication between NHs to share pragmatic strategies for improving clinical practice without the support of research staff.”

– Loomer et al. Journal of the American Medical Directors Association

March 8, 2019: Dietary Trials in Heart Failure: SODIUM-HF (Justin Ezekowitz, MBBCh, MSc)

Posted on by Gina Uhlenbrauck

Video not available

Speaker

Justin A. Ezekowitz, MBBCh, MSc
Professor, University of Alberta
Co-Director, Canadian VIGOUR Centre
Cardiologist, Mazankowski Alberta Heart Institute

Topic

Dietary Trials in Heart Failure: SODIUM-HF

Keywords

Multicenter clinical trial; Heart failure; Dietary sodium; Cardiovascular health; Clinical equipoise; Clinical guidelines; SODIUM-HF

Key Points

  • The SODIUM-HF trial is a multicenter, multinational dietary study evaluating the long-term effects of a low-sodium diet in patients with heart failure on a composite clinical outcome of all-cause mortality, cardiovascular (CV) hospitalizations, and CV emergency department visits.
  • The recommended amount of dietary sodium for patients with heart failure varies among the guidelines, ranging from no restriction to <2300mg per day.
  • Among the successes of the study are the important research question, a simple electronic case report form, engaged clinicians and staff, 100% remote monitoring, and a low administrative burden.

Discussion Themes

Sodium restriction is one of the most challenging things for patients to undertake as it affects their lifestyle significantly.

What is your perspective on the importance of a low-sodium diet for patients with heart failure, given that low sodium was shown to be harmful in some studies?

How do you balance wanting a pragmatic/practical intervention versus wanting a rigorous test of your hypothesis?

For more information on this study, visit the SODIUM-HF trial website and ClinicalTrials.gov.

Tags

#HeartFailure, #pctGR, @SodiumHF, @Collaboratory1, @JustinEzekowitz, @CVC_UAlberta

March 1, 2019: Approaches to Patient Follow-Up for Clinical Trials: What’s the Right Choice for Your Study? (Keith Marsolo, PhD)

Posted on by Gina Uhlenbrauck

Speaker

Keith Marsolo, PhD
Department of Population Health Sciences
Duke Clinical Research Institute
Duke University School of Medicine

Topic

Approaches to Patient Follow-Up for Clinical Trials: What’s the Right Choice for Your Study?

Keywords

Pragmatic clinical trial; Real-world data; Distributed research network; Electronic health records; EHR; Health data sources; Data standardization; Common data model; Fast Healthcare Interoperability Resources (FHIR); Application programming interface (API)

Key Points

  • Different sites have different capabilities and levels of sophistication around data. Clinical trial investigators should think from the beginning about the questions they want to answer and how much data is needed.
  • From different sources, such as the EHR, claims, or participant, data can be procured and provided in different ways, either by the patient, staff or clinician, or through IT and data experts.
  • PCTs with many sites may require a “patchwork quilt” of approaches for patient follow-up depending on the needs of the trial. Clinician-generated reports, direct from patients, and solutions involving application programming interfaces (APIs) are all good options for data exchange.

Discussion Themes

How do we think through the options for getting patient data where some sites may not be in the distributed research network or use a common data model?

Fast Healthcare Interoperability Resources (FHIR) is a draft standard describing data formats and elements and an application programming interface (API) for exchanging electronic health records. The FHIR interface requests data as an object, and for each defined domain it specifies allowable values and variables and predefines the information that you get out of the system.

Until data are collected/generated using the same standards/formats as the API, there will still be a need to understand the EHR-to-interface mapping.

For more information on using health data in embedded pragmatic clinical trials, visit the NIH Collaboratory’s EHR Core webpage.

Tags

#CommonDataModel, #RealWorldData, #FHIR, #pctGR, @Collaboratory1

February 21, 2019: Living Textbook Offers New Content on Design and Analysis of Pragmatic Clinical Trials

Posted on by Damon Seils

Members of the NIH Collaboratory’s Biostatistics and Study Design Core contributed 3 new sections to the Living Textbook exploring issues in the design and analysis of pragmatic clinical trials. The new sections offer insights into emerging issues in embedded pragmatic clinical trials and lessons learned from the NIH Collaboratory’s first round of NIH Collaboratory Trials.

  • The Designing to Avoid Identification Bias section addresses a type of selection bias that can occur in pragmatic clinical trials that use information from electronic health records to determine study population eligibility and in which the study intervention influences who undergoes screening or receives a diagnosis in clinical care.
  • The Alternative Cluster Randomized Designs section describes alternative design choices for cluster randomized trials and their implications for statistical power and sample size calculations. Modified cluster randomized designs, such as cluster randomization with crossover, may reduce the sample size required for a pragmatic clinical trial and may be particularly feasible in trials embedded in healthcare systems with electronic health records.
  • Case Study: STOP CRC Trial explores challenges in design and analysis that were faced in the Strategies and Opportunities to Stop Colorectal Cancer in Priority Populations (STOP CRC) trial, one of the NIH Collaboratory Trials. The case study illustrates how the study team dealt with pragmatic issues during the planning and conduct of the trial.

In addition to contributing content to the Living Textbook, the Biostatistics and Study Design Core works with the NIH Collaboratory Trials to address challenges in their statistical plans and study designs during the planning phase and to develop guidance and technical documents related to study design and biostatistical issues relevant to pragmatic clinical trials.

January 18, 2019: Pragmatic Trials in End-stage Renal Disease (ESRD): HiLo (Myles Wolf, MD, MMSc)

Posted on by Gina Uhlenbrauck

Speaker

Myles Wolf, MD, MMSc
Charles Johnson, MD, Professor of Medicine
Chief, Duke Nephrology
Duke University School of Medicine

Topic

Pragmatic Trials in End-stage Renal Disease (ESRD): HiLo

Keywords

Pragmatic clinical trial; HiLo; End-stage renal disease; ESRD; Kidney disease; Hypophosphatemia; Serum phosphate; Hemodialysis; A vs B trials; Clinical equipoise; National Institute of Diabetes and Digestive and Kidney Diseases; NIDDK

Key Points

  • With high event rates and few proven therapies, patients with end-stage renal disease (ESRD) are in desperate need of clinical innovation.
  • The NIH Collaboratory’s HiLo Trial is a pragmatic, multicenter, cluster-randomized, open-label, noninferiority outcomes trial that will compare effects of two different phosphate management strategies in patients with ESRD.
  • The study hypothesizes that, compared with strict phosphate control, less stringent control will yield noninferior rates of all-cause hospitalization among patients with ESRD undergoing hemodialysis, as well as reduce the risk of all-cause mortality, enhance markers of diet and nutrition, and improve quality of life.

Discussion Themes

Dialysis clinic dieticians will have a pivotal role in implementing HiLo. They have established a rapport with patients and are among the most motivated caregivers on dialysis teams.

Individual patient-level informed consent for the HiLo trial will be via internet-linked tablets, paper forms, and educational materials including a video. Benefits of obtaining consent include promoting adherence, direct study updates and newsletters to participants, and ability to collect additional data without involving onsite study staff.

HiLo will be the first definitive clinical trial-grade evidence for opinion-based guidelines for phosphate management. Thus, results of HiLo have the potential to rapidly influence ESRD clinical practice.

Read more about the HiLo NIH Collaboratory Trial in the Living Textbook.

Tags

#ESRD, #pctGR, @Collaboratory1, @DCRINews, @DukeKidney

January 22, 2019: New Self-Paced ePCT Training Course Available

Posted on by Gina Uhlenbrauck

The NIH Collaboratory is pleased to announce the availability of a new self-paced, 10-module introductory course on how to design, conduct, and disseminate embedded PCTs (ePCTs). This course presents condensed material from the inaugural ePCT Training Workshop held in 2018 and provides users with important things to know and do when designing an ePCT, along with helpful links to additional learning resources within the Living Textbook.

Also available in the Living Textbook are links to videocast workshops hosted by the NIH on a range of ePCT topics including:

  • Embedded PCTs of therapeutic A versus B interventions
  • Unique opportunities for disseminating, implementing, and sustaining evidence-based practices into clinical care
  • Ethical and regulatory issues of PCTs

For these and other ePCT resources, visit the Training Resources webpage.