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


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


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


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.


#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


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)


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


Introducing the Digital Medicine Society


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.


#DigitalMedicine, #pctGR, @Collaboratory1, @_DiMeSociety

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


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


Open Science: Are We There Yet?


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?


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

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

June 28, 2019: Moving Beyond Return of Research Results to Return of Value (Consuelo Wilkins, MD, MSCI)


Consuelo H. Wilkins, MD, MSCI
Vice President for Health Equity, Vanderbilt University Medical Center
Executive Director, Meharry-Vanderbilt Alliance


Moving Beyond Return of Research Results to Return of Value


Health outcomes; Research results; Patient preferences; Value of information

Key Points

  • In returning value to research participants, results are shared with added context, are prioritized by each participant, include specific suggestions for relevant actions, and incorporate participant recommendations and preferences.
  • Data captured for research purposes, including EHR data, vital signs, and genetic data, can be repurposed and reoriented for study participants.
  • Participants are more likely to trust research if results are returned—and they are more likely to participate again.

Discussion Themes

We need to return study results that are informed by participants, and we need to design approaches for accessing and understanding results that participants will want to use.

We should think carefully about risk mitigation when returning research results for which there is a clear next step or action for the participant.

Read more about understanding what information is valued by research participants in a recent article by Dr. Wilkins and colleagues in Health Affairs.


#pctGR, @Collaboratory1, @drchwilkins, @vumchealth

Podcast June 26, 2019: Good Clinical Practice Guidance and Pragmatic Trials: Balancing the Best of Both Worlds in the Learning Health System (Robert Mentz, MD)

Podcast June 26: Good Clinical Practice Guidance and Pragmatic Trials: Balancing the Best of Both Worlds in the Learning Health System (Robert Mentz, MD)

In this episode of the NIH Collaboratory Grand Rounds podcast, Dr. Adrian Hernandez sits down with Dr. Rob Mentz to discuss balancing Good Clinical Practice Guidance and Pragmatic Trials in the Learning Health System. In the discussion, Dr. Mentz covers key challenges with good clinical practice (GCP), input from Dr. Rob Califf and others, and suggestions on how the scientific community should address the evolution of GCP versus the evolution of clinical trials.

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June 14, 2019: Good Clinical Practice Guidance and Pragmatic Trials: Balancing the Best of Both Worlds in the Learning Health System (Robert Mentz, MD)


Robert J. Mentz, MD, FACC, FAHA, FHFSA
Associate Professor
Director, Duke Cooperative Cardiovascular Society
Associate Program Director, Duke Cardiovascular Disease Fellowship
Duke University Medical Center and Duke Clinical Research Institute


Good Clinical Practice Guidance and Pragmatic Trials: Balancing the Best of Both Worlds in the Learning Health System


International Council for Harmonization (ICH); Good clinical practice (GCP); Learning health system; Pragmatic clinical trials; Institutional review board (IRB); Research oversight; Regulatory issues; Quality by design (QbD)

Key Points

  • Good clinical practice (GCP) guidance details the responsibilities, procedures, and recording that are necessary for appropriate trial conduct; for example, conducting the trial in accordance with an IRB-approved protocol with appropriate adverse event monitoring and reporting.
  • There is an urgent need to streamline randomized trials. Key obstacles are lack of transparency, lack of representativeness, and lack of evidence of competence.
  • In the United States, clinical investigators must abide by guidance from FDA, HHS, and ICH-GCP. Yet it is hard for investigators to keep track and to know how GCP applies to their study.
  • GCP as an overall construct is useful, but it does not deal well with issues particular to pragmatic trials or trials outside the FDA-regulated world.

Discussion Themes

With embedded pragmatic trials, informed consent is more nuanced. New considerations and approaches for consent have arisen since ICH GCP first came into effect.

Establishing quality by design will take time, effort, and educating IRBs to understand how QbD can be used to avoid errors in a trial and collect data that is fit-for-purpose.

It’s crucial that trials address an important question, answer that question reliably, and keep participants safe.

Read more about Dr. Mentz’s study of GCP and pragmatic trials.


#pctGR, @Collaboratory1, @RobMentz