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)

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.

Tags
#pctGR, @Collaboratory1

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

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.

 

November 22, 2019: It’s Time to Learn From Patients Like Mine (Nigam H. Shah, MBBS, PhD)

Speaker

Nigam H. Shah, MBBS, PhD
Associate Professor of Medicine
Stanford University

Topic

It’s Time to Learn From Patients Like Mine

Keywords

Clinical informatics; Clinical data warehouse; Aggregate patient data; Consult service; Cohort search engine

Key Points

  • The “Green Button” service consists of software, data, and personnel. Multiple datasets are used in the analysis, along with a human filter.
  • The search engine can find matching patients by searching across diagnosis and procedure codes, concepts extracted from clinical notes, laboratory test results, vital signs, as well as visit types and duration of inpatient stays, and then compare their outcomes.
  • Questions that remain include:
    • Does having such a consult service change patient outcomes?
    • How could we enable such consults nationwide?
    • Could we automate such analyses to be “always on”?
    • Could we get such a “curbside consult” from multiple health systems?
    • Could patients benefit from having access to such reports?

Discussion Themes

Could this technology be applied in emergent, critical patient settings where the care is more diagnostic, and where predictive modeling using health system data could be helpful?

What’s missing from the data that would improve accuracy or relevance? For example, social, demographic, and environmental data.

Read more about Stanford’s Green Button clinical informatics consult project.

Tags
#pctGR, @Collaboratory1

November 1, 2019: NIH Collaboratory: Looking Back, Looking Forward (Adrian Hernandez, MD, MHS, Lesley Curtis, PhD, Kevin Weinfurt, PhD)

Speakers

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

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

Kevin Weinfurt, PhD
Professor and Vice Chair of Research
Department of Population Health Sciences
Duke University School of Medicine

Topic

NIH Collaboratory: Looking Back, Looking Forward

Keywords

Embedded pragmatic clinical trials; ePCTs; NIH Collaboratory; Health care systems research; Demonstration Projects; Living Textbook; HEAL Initiative; Coordinating Center; Research dissemination; Learning health systems; Real-world evidence

Key Points

Discussion Themes

How can we harmonize the different ideas about what it is to be “pragmatic” for NIH study sections, IRBs, and DSMB reviews? For example, if your DSMB isn’t knowledgeable about PCTs, you could end up with a very explanatory trial.

A willingness to share imperfections is an important part of learning and helps the clinical trial ecosystem evolve.

An important future topic would be how the NIH Collaboratory and PCORnet fit together.

Read more about the NIH Collaboratory Program and the Living Textbook of Pragmatic Clinical Trials.

Tags
#pctGR, #PragmaticTrials, @Collaboratory1, @texhern, @lmhcurtis, @KevinWeinfurt

October 11, 2019: Objecting to Experiments that Compare Two Unobjectionable Policies or Treatments: Implications for Comparative Effectiveness and Other Pragmatic Clinical Trials (Michelle Meyer, PhD, JD)

Speaker

Michelle N. Meyer, PhD, JD
Assistant Professor & Associate Director, Research Ethics
Center for Translational Bioethics & Health Care Policy
Faculty Co-Director, Behavioral Insights Team
Steele Institute for Health Innovation, Geisinger

Topic

Objecting to Experiments that Compare Two Unobjectionable Policies or Treatments: Implications for Comparative Effectiveness and Other Pragmatic Clinical Trials

Keywords

A vs B trials; Comparative effectiveness research; Clinical equipoise; Randomization; Learning health system

Key Points

  • Healthcare delivery systems often have an ethical obligation to experiment in order to determine the effects of their policies and treatments on stakeholders. A/B experiments conducted within health systems are intended to increase quality and safety, decrease waste or lower costs, and reduce inequity and injustice.
  • The “A/B effect” is the approval of untested policies or treatments (A or B) being universally implemented but disapproval of randomized experiments (A/B tests) to determine which of those policies or treatments is superior.
  • Experimentation aversion may be an important barrier to evidence-based practice.

Discussion Themes

Do you think the objection to random assignment is related to a sense that it is not “random?”

A potential solution to the “A/B effect” is to let patients be partners in improving healthcare by explaining that “we don’t know if A or B is better. Would you be willing to help us find out?”

Read Dr. Meyer and colleagues’ open access article in the journal Proceedings of the National Academy of Sciences (May 2019): Objecting to experiments that compare two unobjectionable policies or treatments.

Tags
#pctGR, @Collaboratory1

September 13, 2019: ADAPTABLE Recruitment and Follow-up: Health Plan Research Network Engagement (Kevin Haynes, PharmD, MSCE)

Speaker

Kevin Haynes, PharmD, MSCE
Principal Scientist
HealthCore, Inc.

Topic

ADAPTABLE Recruitment and Follow-up: Health Plan Research Network Engagement

Keywords

Real-world evidence; Real-world data; Study design; Claims data; ADAPTABLE; Patient recruitment; Pragmatic clinical trial; Electronic health record; Informed consent; Learning health system

Key Points

  • We need integrated EHR data and claims data in order to close evidence gaps in observational pharmacoepidemiology studies and comparative effectiveness trials.
  • The health plan claims data environment can be leveraged to support real-world evidence studies.
  • An integrated health plan network database can be a resource for data about eligibility, lab test results, and pharmacy claims. In a pragmatic clinical trial, using health plan data can provide a longitudinal electronic approach to endpoint ascertainment.

Discussion Themes

Have you had a chance to do any cost analysis of this high-volume, low-touch method of recruitment?

In the ADAPTABLE enrollment portal, it seems the biggest chunk of time (reading about the study) came before the screening questions. Do you think swapping the order might have improved enrollment?

Read more about the ADAPTABLE pragmatic trial.

Tags

#pctGR, @Collaboratory1, @HealthCoreRWE

September 13, 2019: HiLo Awarded Continuation From Planning to Implementation Phase

The investigators of HiLo, an NIH Collaboratory Demonstration Project, have received approval to move from the planning phase to the implementation phase of their study. Congratulations to Dr. Myles Wolf and the HiLo study team for their excellent work!

HiLo (Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis) is designed to answer the question of what is the optimal level of serum phosphate for patients with end-stage renal disease (ESRD) who are undergoing hemodialysis. In an effort to improve clinical outcomes, current practice guidelines advocate aggressive treatment of high blood phosphate to near normal levels using dietary phosphate binders and restrictive diets. Yet, the optimal phosphate target remains unknown, and potential harms of aggressive treatment have not been definitively identified. HiLo is the first formal clinical research study to evaluate this important question. The study team is planning the first wave of site activations with the goal of beginning enrollment at 10 dialysis centers in the Raleigh-Durham area in October or November.

We recently asked Dr. Wolf to reflect on the transition of the HiLo trial.

Were there any surprises during the study’s planning phase?

How much work was required to plan a large pragmatic trial! Fortunately, we have a superb team of investigators and study staff who are deeply invested in the trial, deep expertise at the Duke Clinical Research Institute, full engagement of our partners at DaVita and the University of Utah, invaluable insight from our Patient Ambassadors from the American Association of Kidney Patients, and unwavering support from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the NIH Collaboratory.

What is an example of a challenge that you were able to overcome with the help of a Core group?

The Ethics and Regulatory Core helped us work through unique challenges related to obtaining individual-level informed consent in a cluster-randomized trial. The Biostatistics and Study Design Core and a number of outside statistical consultants helped us identify a novel solution for designing and analyzing a primary outcome of the trial that best aligns with the study’s clinical goal.

“We hope that the experience we gained from HiLo related to application of novel methods for pragmatic trials will stimulate further innovation and enhance the design of future studies in our field, ultimately for the benefit of kidney patients.” – Dr. Myles Wolf, PI of HiLo

What other key challenges have you faced?

We learned from the Ambassadors on our Patients Advisory Group about how important it will be to convince dialysis facility staff and patients that it is justified and important for the study to reevaluate what has been dogma in ESRD treatment: that serum phosphate must be lowered aggressively. We have had to grapple with how to deploy an electronic process to obtain informed consent remotely—a first in U.S. dialysis studies—given that we will not have on-site study coordinators in the participating dialysis facilities. We also had to develop, refine, and defend our use of a newer statistical approach to HiLo’s primary hierarchical composite outcome of all-cause mortality and all-cause hospitalizations. The approach, which is gaining traction in other areas, has not been used in large-scale trials in nephrology. While the process of preparing for this trial was long and required substantial hard work from a large team of investigators and study staff, we hope that the experience we gained from HiLo related to application of novel methods for pragmatic trials will stimulate further innovation and enhance the design of future studies in our field, ultimately for the benefit of kidney patients.

What words of advice do you have for investigators conducting their first embedded PCT?

Get to know the people—patients and professionals—who need to be invested and will be affected by your study and its outcomes. Understand their interests and concerns even if it goes against what you think you know. These early conversations will help identify hurdles at a time when they can be readily addressed and the study enhanced. Be patient and be prepared to work, and work some more. And ask for more money … pragmatic plus more resources is still pragmatic!

Additional details about the study are on the HiLo website.

NIH Collaboratory Demonstration Projects begin with a 1-year, milestone-driven planning phase. Projects become eligible to move to the implementation phase after an administrative review of progress toward scientific milestones and feasibility requirements. Throughout the process, the project team interacts with the Core Working Groups and investigators from the other Demonstration Projects.

HiLo is supported within the NIH Collaboratory by a cooperative agreement from the NIDDK and receives logistical and technical support from the NIH Collaboratory Coordinating Center. Read more about HiLo in the Living Textbook, and learn more about the NIH Collaboratory Demonstration Projects.

September 11, 2019: Deadline Extended for Special Supplement Seeking Papers on Embedded Research

AcademyHealth

The submission deadline has been extended to October 28, 2019, for a special supplement on embedded health services research in Healthcare: The Journal of Delivery Science and Innovation, the partner journal of AcademyHealth. Embedded research is a critical part of the learning health system in mining and analyzing health system data to improve patient care while also providing generalizable findings to transform the health care system at large.

This special supplement is being supported by the Department of Veterans Affairs Health Services Research & Development and will be published in March 2020. It is expected to feature 10-12 peer-reviewed articles. Ultimately, the supplement will be a resource for those aiming to improve the relevance and use of health research to improve patient care.

For details on relevant topics and how to submit your paper online, visit the journal’s special issue page.

August 16, 2019: Introducing the Digital Medicine Society (Andy Coravos, MBA, Jen Goldsack, MS, MBA)

Speakers

Andy Coravos
CEO, Elektra Labs
Fellow, Harvard-MIT Center for Regulatory Science
Co-founder, Digital Medicine Society (DiMe)

Jen Goldsack, MS, MBA
Interim Executive Director, DiMe
Portfolio, Strategy & Ops, HealthMode

Topic

Introducing the Digital Medicine Society

Keywords

Digital medicine; Mobile health; Digital technologies; Wearable health devices; Connected devices; Cybersecurity

Key Points

  • Digital medicine is a rapidly evolving field that is by nature multidisciplinary and introduces new considerations for the healthcare community.
  • The Digital Medicine Society (DiMe) sits at the intersection of two communities: healthcare and technology. The Society is helping to move the field of digital medicine forward by developing a common language for diverse stakeholders from engineers and ethicists to payers and providers.
  • The U.S. healthcare system has strong protections for patients’ biospecimens like blood or genomic data, but what about digital specimens?

Discussion Themes

Are digital medical technologies worthy of the trust we place in them?

Should there be a Hippocratic Oath for manufacturers, organizations, and individuals delivering care through connected medical devices?

Read more about the emerging field of digital medicine and learn more about the Digital Medicine Society (DiMe), the professional home for those who practice and develop products in the digital era of medicine.

Tags

#DigitalMedicine, #pctGR, @Collaboratory1, @_DiMeSociety

August 9, 2019: Open Science: Are we there yet? (Adrian Hernandez, MD)

Speaker

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

Topic

Open Science: Are We There Yet?

Keywords

Open science; Data sharing; Secondary analyses; Research collaboration

Key Points

  • Open science involves the responsible sharing of research data for the purpose of scientific advancement, integrity, and transparency.
  • Various stakeholders have made progress toward sharing clinical trial data, including:
  • Guiding principles of open science include appropriate access to research information; proper oversight with minimum barriers to data access; maintaining utility of data; an expectation that results of shared data will similarly be shared; and acknowledgment of those who contribute original data.
  • Despite efforts at supporting open science, no academic institution has an open science policy yet.

Discussion Themes

Open science remains an important goal to build trust and expand knowledge.

Data sharing is not a traditional measure of academic success. What incentives would need to change in order to support open science?

Tags

#OpenScience, #DataSharing, #pctGR, @Collaboratory1, @texhern