Clinical trials

December 18, 2019: National Institute on Aging IMPACT Collaboratory Launches Grand Rounds Series and New Website

Posted on by Gina Uhlenbrauck

The National Institute on Aging (NIA) IMbedded Pragmatic Alzheimer’s disease (AD) and AD Related Dementias (AD/ADRD) Clinical Trials (IMPACT) Collaboratory has launched a new website highlighting the project.

The IMPACT Collaboratory recently invited applications for pilot grant funding for projects that aim to generate preliminary data necessary to design and conduct full-scale embedded pragmatic clinical trials of nonpharmacologic interventions for persons living with Alzheimer’s disease and related dementias and/or their caregivers. Pilot grants will help IMPACT Collaboratory’s mission to build the nation’s capacity to conduct pragmatic clinical trials of interventions embedded within health care systems for people living with dementia and their caregivers.

Since the IMPACT Collaboratory started this September, the program has been hard at work launching its new website, as well as a series of specialized Grand Rounds focused on the topic of pragmatic research in the area of Alzheimer’s disease and related dementias.

IMPACT Collaboratory Grand Rounds occur the 3rd Thursday of each month at 12 noon ET. Join the next webinar on Thursday, December 19, “Stepped Wedge Cluster Trials: What, How, And When?,” by Monica Taljaard, PhD, Senior Scientist, Ottawa Hospital Research Institute and Associate Professor, University of Ottawa from the IMPACT Collaboratory Design and Statistics Core.

Following in the footsteps of the NIH Collaboratory, the IMPACT Collaboratory has also launched a podcast series to correspond with its Grand Rounds Series. Both the Grand Rounds webinar recordings and accompanying podcasts for all the sessions are available on the website.

Those interested in getting updates about the IMPACT Collaboratory can also join the program’s mailing list .

December 13, 2019: Reissuance of Funding Opportunity Announcement for HEAL Initiative/PRISM Coming January 2020

Posted on by Gina Uhlenbrauck

The National Center for Complementary and Integrative Health (NCCIH), with other NIH Institutes, Centers, and Offices, intends to reissue Funding Opportunity Announcement (FOA) HEAL Initiative: Pragmatic and Implementation Studies for the Management of Pain To Reduce Opioid Prescribing (PRISM) (UG3/UH3 Clinical Trial Optional).

This RFA solicits applications for phased cooperative research applications to conduct efficient, large-scale pragmatic or implementation trials to improve pain management and reduce the unnecessary use of opioid medications in the health care delivery setting. The re-issuance of the FOA will prioritize the following areas for pragmatic trials to integrate multimodal or multiple interventions that have demonstrated efficacy into health care systems or implement health care system changes to improve adherence to evidence-based guidelines:

  • Pain management in emergency departments, dental clinics, primary care, and hospitals
  • Chronic overlapping pain conditions
  • Pain management in individuals at risk of or with opioid use disorder
  • Pain management in those with co-occurring mental health disorders
  • Noncancer pain management in persons with medical comorbid conditions

The FOA is expected to be published in January 2020 with an expected application due date in March 2020.

The announcement is part of the NIH Heal (Helping to End Addiction Long-term) Initiative, which was created in April 2018 in an effort to speed scientific solutions for addressing the national opioid public health crisis.

 

December 13, 2019: New ePCT Training Materials Focus on Nephrology Research

Posted on by Gina Uhlenbrauck

Presentations from a recent seminar offered by the NIH Collaboratory in partnership with the American Society of Nephrology are now available on the Living Textbook. The seminar, Embedded Pragmatic Clinical Trials: Accelerating Evidence Generation in Nephrology, was held at ASN Kidney Week 2019. The sessions provide an introduction to concepts in the design of embedded pragmatic clinical trials (ePCTs), with a focus on interventions that are relevant to the nephrology research community.

Visit the NIH Collaboratory Training Resources to download the presentations.

July 2, 2019: New Living Textbook Section on Inpatient Endpoints in Pragmatic Clinical Trials

Posted on by Karen Staman

A new section in the Living Textbook describes the considerations for using “real-world” data for inpatient-based event ascertainment. There are many sources for acquiring this information, and they have different time lags in their availability and varying degrees of error and bias. In order to use inpatient endpoints in pragmatic clinical trials, these factors must be understood during the design, conduct, and analysis phases of an embedded pragmatic clinical trial.

“The pragmatic trial community needs to collectively determine which endpoints are relevant for pragmatic trials, how they can be measured and validated, and how the accuracy of these measurement methods may impact hypothesis testing sample size estimates.” —Eisenstein et al 2019

Topics in the chapter include:

  • Pragmatic trial inpatient endpoints
  • Inpatient event data sources
  • Patient-reported data
  • Secondary data sources: EHR
  • Secondary data sources: claims
  • Case studies: ICD-Pieces, TRANSFORM-HF, ADAPTABLE, and TRANSLATE ACS
  • Data source accuracy

 

May 17, 2019: The VITamin D and OmegA-3 TriaL (VITAL): Design and Results of a Large Pragmatic Trial (JoAnn E. Manson, MD, DrPH)

Posted on by Gina Uhlenbrauck

Speaker

JoAnn E. Manson, MD, DrPH
Chief, Division of Preventive Medicine, Brigham and Women’s Hospital
Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health
Harvard Medical School
Professor, Department of Epidemiology
Harvard T.H. Chan School of Public Health

Topic

The VITamin D and OmegA-3 TriaL (VITAL): Design and Results of a Large Pragmatic Trial

Keywords

Pragmatic clinical trial; Dietary supplements; Primary prevention; Mail-based randomized clinical trial; Cancer prevention; Cardiovascular disease prevention; vitamin D; Omega-3 fatty acids

Key Points

  • The VITAL pragmatic trial evaluated the effects of dietary supplements (vitamin D and omega-3) on reducing risk for developing cancer, heart disease, and stroke in the general population.
  • Study recruitment involved nationwide and targeted mailings, media reports, advertising, and brochures. Retention included participant newsletters, incentive gifts, and honoraria.
  • Findings included that neither omega-3s nor vitamin D significantly reduced the primary endpoints of major cardiovascular disease events or total invasive cancer. Omega-3s did reduce total myocardial infarction by 28%, with greatest reductions in those with low dietary fish intake and in African Americans.

Discussion Themes

VITAL’s hybrid design—remote or mail-based intervention plus serial in-clinic visits in a sample—has advantages in promoting quality and cost-efficiency.

Next steps for VITAL include continued follow-up for 5 years; genetic studies; and fostering new ancillary studies through nationwide collaborations.  

Visit the VITAL study website and read more about the results of VITAL (Manson et al., New Engl J Med, 2019)

Tags

#dietarysupplements, #pctGR, @Collaboratory1

May 16, 2019: NIH Collaboratory Investigators Author Recommendations for Responding to Guideline or Policy Changes That Affect Ongoing Pragmatic Trials

Posted on by Karen Staman

A new perspective article by NIH Collaboratory investigators describes the unique, unexpected challenges researchers face when clinical practice guidelines and policies change during the conduct of a pragmatic clinical trial (PCT). The article was published online this week in Clinical Trials.

The NIH Collaboratory Trials are PCTs that test interventions to address urgent public health problems. They involve hundreds to thousands of participants and generally include usual care as a control arm. During the course of these years-long trials, clinical practice guidelines and policies changed due to new evidence from observational studies, small trials, and shifting expert opinion. Such changes can have profound effects on usual care and, therefore, threaten the ability of the PCTs to address the questions they were designed to answer. Investigators must strike a balance between the primary ethical obligation to protect patients by adhering to new best-practice guidelines and policy and the secondary, yet crucial, obligation to develop high-quality evidence to improve care.

“PCTs are an important means of producing high-quality evidence needed to better inform clinical practice. However, when guidelines or reimbursement policies change during the conduct of a PCT, the ethical obligation to gather information to develop evidence-based practices may conflict with the primary ethical obligation to participants.” — Curtis et al, Clinical Trials, 2019

Based on their aggregate experience with the NIH Collaboratory, the authors provide broad recommendations and strategies for overcoming these challenges, including protecting the well-being of patients; involving stakeholders, health system leaders, and the entity charged with data and safety monitoring; and actively monitoring changes and site-level responses to them. If changes to the standard of care are merited, investigators should provide equal opportunity and support for the recommended changes. Finally, during the design phase, investigators should communicate with the entities charged with creating guidelines to see what is needed and to anticipate possible future changes.

“The ability to appropriately address the tension between modifications to clinical guidelines and the need to generate quality evidence to support those guidelines is a crucial consideration for the fulfilment of a learning health system.” — Curtis et al, Clinical Trials, 2019

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

Posted on by Gina Uhlenbrauck

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)

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

January 4, 2019: TRANSFORMing Research for Patients With Heart Failure (Robert Mentz, MD, Kevin Anstrom, PhD, Eric Eisenstein, DBA, Stephen Greene, MD, Eric Velazquez, MD)

Posted on by Gina Uhlenbrauck

Speakers

Robert J. Mentz, MD
Associate Professor of Medicine
Duke University School of Medicine

Kevin J. Anstrom, PhD
Professor of Biostatistics and Bioinformatics
Director of Biostatistics, Duke Clinical Research Institute
Duke University School of Medicine

Eric Eisenstein, DBA
Associate Professor in Medicine
Duke University School of Medicine

Stephen J. Greene, MD
Fellow, Division of Cardiology and Duke Clinical Research Institute
Duke University School of Medicine

Eric J. Velazquez. MD, FACP, FACC, FASE, FAHA
Robert W. Berliner Professor of Medicine, Yale University
Chief, Cardiovascular Medicine, Yale New Haven Hospital
Physician-in-Chief, Heart and Vascular Center, Yale New Haven Health

Topic

TRANSFORMing Research for Patients With Heart Failure

Keywords

Pragmatic clinical trial; Heart failure; PRECIS-2; Hospitalization; TRANSFORM-HF; Clinical equipoise; Electronic health records; National Heart, Lung, and Blood Institute (NHLBI)

Key Points

  • The traditional approach to conducting clinical trials is unsustainable in many respects, including operational complexities, low enrollment rates, high costs, and failure to leverage existing resources. Incorporating pragmatic elements in the design of trials may improve efficiencies and conduct.
  • TRANSFORM-HF is a pragmatic trial evaluating torsemide versus furosemide treatment for long-term clinical outcomes among patients hospitalized for heart failure. Study randomization is 1:1, and the primary endpoint is all-cause mortality.
  • Advantages of trials with pragmatic designs include real-world effectiveness; broad patient/provider groups; reduced number and complexity of visits; streamlined data collection; potential for faster results; and results that will be more generalizable.

Discussion Themes

The clinical question involving starting a treatment (Should we start with furosemide or torsemide?) versus switching a treatment (Should we attempt to switch patients from furosemide to torsemide?) would seem to lead to different study designs.

While the peer review process for funding TRANSFORM-HF was challenging and required modifying the approach, it ultimately led to a better design.

Read more about PRECIS-2 domains along the explanatory-pragmatic continuum of a clinical trial in the Living Textbook.

Tags

#HeartFailure, #pctGR, @Collaboratory1, @robmentz, @SJGreene_md, @YaleCardiology, @ericjvelazquez

December 3, 2018: FDA Calls for Comments on Proposed Rule to Allow Exceptions to the Requirement for Informed Consent in Minimal-Risk Research

Posted on by Karen Staman

The Food and Drug Administration (FDA) is proposing a rule to allow for a waiver or alteration of informed consent for clinical investigations posing no more than minimal risk to human participants. This rule would align FDA regulations with the Common Rule, reduce burden and costs for Institutional Review Boards, and be expected to lead to advances in healthcare.

“We expect benefits in the form of healthcare advances from minimal risk clinical investigations and from harmonization of FDA’s informed consent regulations with the Common Rule’s provision for waiver of informed consent for certain minimal risk research.” —  Federal Register /Vol. 83, No. 221

Currently, FDA allows a waiver or alteration of consent only in life-threatening situations. If aligned with the Common Rule, a waiver or alteration would be allowed if the IRB finds and documents that 1) the research involves no more than minimal risk, 2) the rights and welfare of subjects will not be adversely affected, 3) the research could not practicably be carried out without a waiver, and 4) the participants will be provided with additional pertinent information after completion of the trial.

Comments on the proposed rule are due by January 14, 2019.