research methods

April 6, 2020: Convening Pain Management Expertise in the Patient-Centered Outcomes Core: An Interview With Dr. Kevin Weinfurt

Posted on by Gina Uhlenbrauck

The Collaboratory recently interviewed Kevin Weinfurt, PhD, co-chair of the Patient-Centered Outcomes Core working group, to hear about the Core’s plans for supporting the PRISM Demonstration Projects. In this video, Dr. Weinfurt says one challenge for embedded trials of pain is in obtaining high-quality, complete patient-reported outcome data on pain intensity and functioning. Along with other national initiatives focused on pain research, such as the NIH-DoD-VA Pain Management Collaboratory, a chief task of the Core will be to look at efforts to harmonize pain outcomes across studies.

“The Core serves as a convener of expertise in pain management within the Collaboratory. We keep an eye on issues across the Demonstration Projects that might also be of interest to the broader pragmatic trial community.”

Read more about the work of the Patient-Centered Outcomes Core, and view other interviews about the HEAL Initiative and PRISM Demonstration Projects.

March 27, 2020: Living Textbook Grand Rounds Series: Part 3-Tips for Putting Together a Successful PCT Grant Application (Wendy Weber, ND, PhD, MPH)

Posted on by Gina Uhlenbrauck

Speaker

Wendy Weber, ND, PhD, MPH
Branch Chief, Clinical Research Branch
Division of Extramural Research
National Center for Complementary and Integrative Health (NCCIH)

Topic

Tips for Putting Together a Successful PCT Grant Application

Keywords

Pragmatic clinical trials; Embedded PCTs; Healthcare systems; NIH; Scientific officers; Funding opportunity announcement; Request for application

Key Points

  • Investigators interested in developing a compelling grant application for a pragmatic clinical trial (PCT) should consider these tips:
    • First, confirm that a PCT is the best study design to answer your research question.
    • From the NIH’s 27 Institutes and Centers, find the one that matches your disease area, organ system, or stage of life—and talk with the program official.
    • Also find the right funding opportunity announcement (FOA) and tailor your application to address all the FOA-specific instructions and review criteria.
  • Do not assume that the study panel is going to understand what pragmatic means; they may have a completely different definition. It is important that you get on the same page early in the application.
  • In your application, make sure you justify the research, include pilot data, address potential overlaps, reduce complexity, ensure the aims will advance the field, choose expert personnel for a multidisciplinary team, link data collection and analysis to aims, and justify the use of multiple sites and sample size.

Discussion Themes

For some urgent clinical problems, a PCT may be the only study design that can answer the research question.

Phased awards can be helpful. Determine the key elements of your trial to test in the planning phase. It’s important to “fail quickly”—not in the implementation phase. Applicants should identify milestones in the planning phase that will help convince reviewers their study will be feasible.

Because PCTs take place in changing conditions and real-world healthcare settings, they are not necessarily easier to implement than a traditional efficacy trial.

For more information, visit the Living Textbook’s Developing a Compelling Grant Application.

Tags
#pctGR, @Collaboratory1

March 30, 2020: New Living Textbook Chapter Describes Ways to Monitor Intervention Fidelity and Adaptations During the Conduct of ePCTs

Posted on by Gina Uhlenbrauck

The new Monitoring Intervention Fidelity and Adaptations chapter of the Living Textbook was developed to introduce how to evaluate changes that may be encountered while conducting an embedded pragmatic clinical trial (ePCT). For example, a health system might experience competing clinical initiatives; turnover in leadership, clinicians, or staff; changes in technologies; new clinical practice guidelines; or regulatory changes.

The chapter offers strategies for study teams to anticipate, monitor, and document adaptations to the intervention in order to support study analysis and set the stage for dissemination and implementation of successful interventions in other healthcare settings. The chapter was developed by experts from the Collaboratory’s Health Care Systems Interactions Core, along with principal investigators conducting ePCT Demonstration Projects.

Topics include:

  • Anticipating changes that might impact intervention fidelity
  • Frameworks to assist in monitoring fidelity and adaptations
  • Strategies and case examples from the NIH Collaboratory Demonstration Projects
  • Pointers to additional resources

We encourage you to explore this new content.

 

March 20, 2020: Clinical Trials in the Time of COVID-19 (Susanna Naggie, MD; Adrian Hernandez, MD, MHS; Eric Perakslis, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Susanna Naggie, MD
Associate Dean for Clinical Research Initiatives and Regulatory Affairs
Duke University School of Medicine

Adrian F. Hernandez, MD, MHS
Professor of Medicine
Vice Dean for Clinical Research
Duke University School of Medicine

Eric Perakslis, PhD
Rubenstein Fellow
Duke University

Topic

Clinical Trials in the Time of COVID-19

Keywords

Infectious disease; Coronavirus; Pandemic response; COVID-19; Population health; Clinical trials; Human subject protections; Contingency measures; Vaccine; Contact tracing

Key Points

Discussion Themes

Do you anticipate that statisticians will need to account for period effect in later analysis of data (pre/post COVID-19)?

Are there lessons learned from the last epidemics, for example H1N1 or Ebola? How can we deal with global pandemics in the future?

What about clinical trials in the elderly population, given that they are the most vulnerable to the coronavirus and may not be as good with technology as younger participants?

Would it be possible to set up a multisite telehealth-based outbreak learning health unit?

Recent news announcements are available at NIH Announces Guidance for Clinical Trials Affected by COVID-19 Emergency and NIH Shares COVID-19 Guidance and Resources for Applicants and Recipients.

Johns Hopkins University maintains a live website of Coronavirus COVID-19 Global Cases.

Tags
#pctGR, @Collaboratory1, @texhern, @snaggie1, @DukeForge, @eperakslis

February 28, 2020: Preparing for the Unknown: Conducting Pragmatic Research in Real-World Contexts

Posted on by Gina Uhlenbrauck

Speakers

Vincent Mor, PhD
Florence Pirce Grant University Professor
Department of Health Services Policy & Practice
Brown University School of Public Health

Leah Tuzzio, MPH
Research Associate
Kaiser Permanente Washington Health Research Institute

Jeffrey (Jerry) G. Jarvik MD MPH
Professor, Radiology, Neurological Surgery and Health Services
Adjunct Professor, Pharmacy and Orthopedics & Sports Medicine
University of Washington

Topic

Preparing for the Unknown: Conducting Pragmatic Research in Real-World Contexts

Keywords

Embedded research; Implementation; Healthcare systems; Nursing homes; Radiology reports; Electronic health records; Data collection; Pragmatic clinical trials

Key Points

  • Early engagement between study teams and health system leaders and staff can help ease the embedded intervention into the clinical workflow. Consider, for example, who will deliver the intervention and how difficult it will be to implement.
  • In the pilot phase, show that you can implement the intervention effectively. For example, demonstrate that you can collect the outcome data you will need within the pilot’s time frame. Ensure that your study questions are important to the partner healthcare system.

Discussion Themes

It is essential to anticipate, identify, and make a plan to address changes in the healthcare system as your trial is being conducted.

Among the NIH Collaboratory Trials, many have good measures of how much site-to-site variation there is, which helps to understand what the preconditions are for high levels of implementation.

Use the pilot study to maximize acceptability, maintain affordability, and consider the scalability of the intervention.

These topics and more are on the Living Textbook of Pragmatic Clinical Trials. Plan to hear the next topics in the Living Textbook Grand Rounds series.

Tags
#pctGR, @Collaboratory1

February 21, 2020: New Video Interviews Highlight Goals of the NIH HEAL Initiative and PRISM NIH Collaboratory Trials

Posted on by Gina Uhlenbrauck

Recently, the Collaboratory Coordinating Center conducted video interviews describing the critical work being done in the NIH HEAL Initiative program to address the national opioid crisis. As part of this program, the PRISM (Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing) NIH Collaboratory Trials present exciting new possibilities for answering important questions along with unique challenges.

Drs. Rebecca Baker and Wendy Weber discuss the aims of the HEAL Initiative, including:

  • Leveraging expertise across all NIH institutes and centers to enhance pain management and improve prevention and treatment strategies for opioid use disorder and addiction
  • Generating evidence to help clinicians and patients make the right treatment decisions

 

Drs. Meyers, Hernandez, and Weber discuss aspects of collaborating with the four PRISM NIH Collaboratory Trials, including:

  • Leveraging broad expertise in the Collaboratory program to support embedded healthcare systems research in pain management
  • Developing new understanding across different care models such as physical therapy, surgery, acupuncture therapy, and primary care settings
  • Learning about patient-reported outcomes that will be the most meaningful to establish best practices in pain management

Learn more about the PRISM NIH Collaboratory Trials on their webpages:

  • AcuOA: Pragmatic Trial of Acupuncture for Chronic Low Back Pain in Older Adults
  • FM TIPS: Fibromyalgia TENS in Physical Therapy Study
  • NOHARM: Non-pharmacological Options in Postoperative Hospital-Based and Rehabilitation Pain Management
  • OPTIMUM: Group-based mindfulness for patients with chronic low back pain in the primary care setting

February 11, 2020: ADAPTABLE Roundtable Produces Consensus Statement on Analysis and Integration of Patient-Reported Data in Clinical Trials

Posted on by Damon Seils

A roundtable discussion organized by the NIH Collaboratory in 2017 has produced consensus findings on the analysis and integration 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 consensus statement was published online ahead of print this month in the Journal of the American Medical Informatics Association.

The report discusses strengths and limitations of PRH data, approaches for ascertaining and classifying study end points, and methods for addressing incompleteness, data alignment, and data concordance. Roundtable participants used experiences from the ADAPTABLE trial as a case study to inform their discussions.

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.

January 31, 2020: Living Textbook Grand Rounds Series Part 1: Pragmatic Clinical Trials: How Do I Start? (Lesley H. Curtis, PhD, Greg Simon, MD, MPH)

Posted on by Gina Uhlenbrauck

Speakers

Greg Simon, MD, MPH
Senior Investigator
Kaiser Permanente Washington Health Research Institute

Lesley H. Curtis, PhD
Chair and Professor
Department of Population Health Sciences
Duke University School of Medicine
Interim Executive Director, Duke Clinical Research Institute

Topic

Pragmatic Clinical Trials: How Do I Start?

Keywords

Pragmatic clinical trials; PRECIS-2; Real-world evidence; Health systems research; Stakeholders; Clinical workflow; Study team

Key Points

  • Embedded pragmatic clinical trials (ePCTs) are large, efficient studies conducted in the real world that provide evidence for adoption of an intervention into clinical practice.
  • ePCTs are conducted in partnership with healthcare systems, use streamlined procedures and existing infrastructure, and answer important medical questions. However, high relevance to real-world decision-making can sometimes come at the expense of trial efficiency.
  • The PRECIS-2 scores are not absolute virtues; rather, the tool helps researchers determine if their trial is fit for purpose based on their study question.
  • For greater generalizability, ePCTs should be conducted in a diverse range of patients, and study results should be reported transparently.

Discussion Themes

How might we support health systems that serve more diverse populations to participate in a pragmatic clinical trial?

What concerns might be voiced by health system leaders regarding potential reputational risk of a PCT, and perhaps downstream issues about the results publication?

The question “Can everyone do this study?” is different from “Can everyone believe the research results?”

To see upcoming topics in the Living Textbook Grand Rounds series, download the flyer and share with your colleagues and institution. To learn more about the fundamentals of designing and launching a successful ePCT visit the Living Textbook.

January 24, 2020: Cardiovascular Trials Over 2 Decades: Progress on Pragmatism? (Justin A. Ezekowitz, MBBCh, MSc)

Posted on by Gina Uhlenbrauck

Speaker

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

Topic

Cardiovascular Trials Over 2 Decades: Progress on Pragmatism?

Keywords

Pragmatic clinical trials; PRECIS-2; Cardiovascular trials; Enrollment of women

Key Points

  • Pragmatic clinical trials are “designed for the primary purpose of informing decision-makers regarding the comparative balance of benefits, burdens and risks of a biomedical or behavioral health intervention at the individual or population level” (Califf & Sugarman, 2015).
  • This study examined how pragmatic or explanatory cardiovascular (CV) randomized controlled trials are; whether the level of pragmatism in CV trials has changed over 2 decades; and whether the proportion of women enrolled in CV trials has changed over 2 decades.
  • No clinical trial is completely explanatory or pragmatic. In this study, trials that scored higher on pragmatism (using the PRECIS-2 tool) had more sites, a larger sample size, longer follow up, and mortality as a primary endpoint.

Discussion Themes

Randomized controlled trials that were published in general medicine journals scored higher in pragmatism than those published in CV journals. Pragmatism has increased over time in CV trials.

While women account for ~45% of the burden of CV diseases, they are underrepresented in CV randomized controlled trials, with less than one-third of trial participants. There was no difference between pragmatic trials and other trials in terms of women’s enrollment.

Initiatives that focus on patient, clinician, and trial design factors are needed to address the gender gap in trial enrollment.

Read more about the PRECIS-2 tool in the Living Textbook, and Dr. Ezekowitz’s research in Trends in the Explanatory or Pragmatic Nature of Cardiovascular Clinical Trials Over 2 Decades (JAMA Cardiology, 2019).

Tags
#pctGR, @Collaboratory1

January 17, 2020: Assessment of the Human Systemic Absorption of Sunscreen Active Ingredients: FDA-Sponsored Randomized Clinical Trial (Murali Matta, MPharm, PhD)

Posted on by Gina Uhlenbrauck

Speaker

Murali Matta, MPharm, PhD
Bioanalytical Lead
Division of Applied Regulatory Science
Office of Clinical Pharmacology
Food and Drug Administration

Topic

Assessment of the Human Systemic Absorption of Sunscreen Active Ingredients: FDA-Sponsored Randomized Clinical Trial

Keywords

FDA; Sunscreen; Randomized controlled trial; Regulatory; Data analysis

Key Points

  • The active ingredients in nonprescription sunscreen products are organic chemicals, some of which have been shown to be absorbed through human skin with detectable levels in the blood or urine.
  • It is important that randomized clinical trials be conducted to better understand the clinical significance of systemic exposure to sunscreen products.
  • In this trial, all active ingredients in all tested products exhibited systemic exposures above the threshold for potentially waiving some nonclinical toxicology studies for sunscreens.

Discussion Themes

Do the observed differences in the sunscreen concentration depend on the application type; for example, spray versus lotion versus cream?

While additional toxicology data are needed, the results of this study do not indicate that individuals should refrain from the use of sunscreen.

Is there opportunity for collaboration with other organizations including private physician-scientists to conduct larger population studies with consumers?

Read more about Dr. Matta’s study at Shedding New Light on Sunscreen Absorption and in a recent JAMA publication.

Tags
#pctGR, @Collaboratory1, @US_FDA