research methods

December 18, 2019: NIH Collaboratory Shares New Findings and Fresh Insights in 2019

Posted on by Damon Seils

NIH Collaboratory researchers in 2019 continued to generate new knowledge and research methods in pragmatic clinical trials. Their work included insights from the Coordinating Center and Core Working Groups, large-scale analyses of data from the NIH Collaboratory Distributed Research Network, and results and innovative methodological approaches from the NIH Collaboratory Trials.

So far this year, the NIH Collaboratory has produced nearly 3 dozen articles in the peer-reviewed literature, including the primary results of the ABATE Infection trial, confirmation by the TiME trial of the feasibility of embedding large pragmatic trials in clinical care, and more:

NIH Collaboratory Coordinating Center

NIH Collaboratory Distributed Research Network

ABATE Infection NIH Collaboratory Trial

EMBED NIH Collaboratory Trial

PPACT NIH Collaboratory Trial

PRIM-ER NIH Collaboratory Trial

PROVEN NIH Collaboratory Trial

SPOT NIH Collaboratory Trial

STOP CRC NIH Collaboratory Trial

TiME NIH Collaboratory Trial

TSOS NIH Collaboratory Trial

December 6, 2019: Millions More People, Stronger Collaborations: The New and Improved NIH Collaboratory Distributed Research Network (Richard Platt, MD, Kevin Haynes, PharmD, Denise Boudreau, PhD, Jerry Gurwitz, MD, Christopher Granger, MD)

Posted on by Gina Uhlenbrauck

Speakers

Richard Platt, MD, MS
Professor and Chair
Harvard Medical School
Department of Population Medicine

Kevin Haynes, PharmD, MSCE
Principal Scientist
HealthCore

Denise Boudreau, PhD
Senior Scientific Investigator
Kaiser Permanente Washington Health Research Institute

Jerry H. Gurwitz, MD
Professor of Medicine, Family Medicine and Community Health, and Population & Quantitative Health Sciences
University of Massachusetts Medical School
Executive Director, Meyers Primary Care Institute

Christopher B. Granger, MD
Professor of Medicine
Duke University

Topic

Millions More People, Stronger Collaborations: The New and Improved NIH Collaboratory Distributed Research Network

Keywords

Embedded clinical research; Distributed research network; Administrative claims data; Multisite research; Sentinel System; Electronic health data; National registries; Common data model; Curated research data

Key Points

  • The NIH Collaboratory Distributed Research Network (DRN) enables investigators funded by the NIH and other not-for-profit sponsors to collaborate with investigators based in health plans that participate in the FDA’s Sentinel System.
  • Examples from an array of real-world research studies highlight strengths of conducting collaborative research using the DRN.
  • Among the DRN’s attributes are the abilities to embed a randomized clinical trial in real-world clinical settings, to direct outreach to providers and patients/families, and to determine feasibility with high accuracy to allow confidence in planning of ambitious clinical trials.

Discussion Themes

The DRN is optimized for multicenter research and depends on partnerships. It was developed to enable productive research collaborations.

How do investigators who are not embedded in participating health systems learn to work effectively in the DRN?

Read more about the NIH Collaboratory’s DRN.

Tags
#pctGR, @Collaboratory1, @DeptPopMed, @HealthCoreRWE

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

Posted on by Gina Uhlenbrauck

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; NIH Collaboratory Trials; 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 18, 2019: Playing with FHIR–Innovative Use Cases for the New REDCap EHR Integration Module (Paul Harris, PhD)

Posted on by Gina Uhlenbrauck

Speaker

Paul A. Harris, PhD
Director, Office of Research Informatics
Professor of Biomedical Informatics, Biostatistics, and Biomedical Engineering
Vanderbilt University Medical Center

Topic

Playing with FHIR–Innovative Use Cases for the New REDCap EHR Integration Module

Keywords

Fast Healthcare Interoperability Resources; FHIR; Data interoperability; Electronic health record; EHR; Electronic data capture; Clinical data; Research informatics

Key Points

  • REDCap (Research Electronic Data Capture) is a robust, web-based data exchange platform developed at Vanderbilt to assist the research community in implementation efforts.
  • The REDCap consortium has more than a million users. The platform is available at no cost to academic, nonprofit, and government organizations who join the consortium.
  • Innovative use cases are being conducted with REDCap and an Epic EHR system to increase data flow and remove dependency on a data warehouse.

Discussion Themes

How can we harmonize the REDCap approach with PCORnet’s common data model (CDM)?

FHIR is an HL7 standard for exchanging healthcare information electronically. Another use case integrates FHIR to democratize EHR extraction methods to improve efficiency in multisite clinical data collection.

How can researchers manage many-to-one mapping; for example, if the electronic case report form (CRF) has one field value but there are many values in the record?

Read more about the REDCap project.

Tags
#pctGR, @Collaboratory1

October 15, 2019: Postdoctoral Fellowship in the Ethics and Regulatory Aspects of Pragmatic Clinical Trials at Johns Hopkins

Posted on by Gina Uhlenbrauck

The Johns Hopkins Berman Institute of Bioethics invites applications for a Postdoctoral Fellowship in the Ethics and Regulatory Aspects of Pragmatic Clinical Trials. This position includes pursuing independent research, working alongside faculty members involved with the ethics and regulatory aspects of large-scale pragmatic clinical trials (PCTs), and participating in the Hecht-Levi Postdoctoral Fellowship in Bioethics. The postdoctoral fellow is expected to pursue one or more projects addressing the ethics and regulatory aspects of PCTs in collaboration with Berman Institute faculty members. The Fellow will actively engage with the Ethics and Regulatory Core of the NIH Health Care Systems Research Collaboratory and the Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) Resource Coordinating Center.

Qualifications: Applications are welcome from candidates who will have an MD, PhD, or JD or their equivalent by the start date of the fellowship. Applicants should not have completed their terminal degree more than 3 years before the start date of the appointment. Physicians should not have completed a formal residency training program more than 3 years by the start date of the appointment.

Start date: September 1, 2020.

Terms of Appointment: The fellowship is guaranteed for 1 year with the expectation of a second year of funding, contingent on review. Applicants may not be employed by another institution and are expected to be in residence for the duration of the appointment.

How to apply: For details on how to apply see: https://bioethics.jhu.edu/education-training/fellowships/#fellowship-pragmatic. Applications must be submitted by December 16, 2019.

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)

Posted on by Gina Uhlenbrauck

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

October 4, 2019: Ascertaining Death and Hospitalization Endpoints: The TRANSFORM-HF Experience (Eric Eisenstein, DBA, Kevin Anstrom, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Eric L. Eisenstein, DBA
Associate Professor in 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

Topic

Ascertaining Death and Hospitalization Endpoints: The TRANSFORM-HF Experience

Keywords

Clinical endpoints: Ascertaining death; Hospitalization; TRANSFORM-HF; National Death Index

Key Points

  • When patient deaths occur outside the care setting, the cause of death may not be reliably documented. For researchers, the challenges of measuring deaths include the lack of a national death data source and incomplete or hard-to-access sources.
  • The death identification and adjudication process differs for explanatory versus pragmatic trials, and has implications for how death endpoints are acquired and measured.
  • The TRANSFORM-HF pragmatic trial is comparing the effects of treatment strategies on long-term outcomes for hospitalized patients with heart failure. The primary study endpoint is all-cause mortality, which is ascertained and verified using a hybrid approach at the clinical site and call center, and includes searching the National Death Index data.

Discussion Themes

What are the tradeoffs in making endpoint ascertainment more simple?

If using a hybrid death data collection strategy, how are discrepancies adjudicated?

Use of call centers that coordinate follow-up patient contact and data collection is a valid approach that ensures a single point of contact for patients or proxies and care providers. This approach should also be supplemented with redundant data sources.

Read more in the Living Textbook about Using Death as an Endpoint and Inpatient Endpoints in Pragmatic Clinical Trials.

Tags
#pctGR, @Collaboratory1, @DCRINews

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

Posted on by Gina Uhlenbrauck

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

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

Posted on by Gina Uhlenbrauck

Speaker

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

Topic

Moving Beyond Return of Research Results to Return of Value

Keywords

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.

Tags

#pctGR, @Collaboratory1, @drchwilkins, @vumchealth

June 20, 2019: EMBED Investigators Discuss Progress and Transition to Implementation Phase

Posted on by Gina Uhlenbrauck

At the May 2019 meeting of the NIH Collaboratory Steering Committee, we talked with Drs. Ted Melnick and Gail D’Onofrio of EMBED, an NIH Collaboratory Trial, to hear about progress and challenges during the UG3 planning phase. The goal of EMBED is to test whether implementation of a user-centered clinical decision support system increases adoption of initiation of buprenorphine/naloxone into the routine emergency care of patients with opioid use disorder. In the UG3 phase, the study team put in place the infrastructure of a pragmatic, multicenter, parallel, group-randomized health IT intervention. EMBED recently transitioned to the UH3 implementation phase and plans to launch the intervention at 20 sites across 5 healthcare systems in August 2019.

“With EMBED, we’re trying to take evidence-based research and implement it to improve practice. EMBED is both a research and patient care project.”

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

The first surprise came at last year’s Steering Committee meeting, when we met with the Biostatistics and Study Design Core. They encouraged us to change our original study design from stepped-wedge to group-randomized, which we did. We think this advice led to a stronger study. The main reason for this is the group-randomized design’s ability to better account for temporal changes. Since our intervention is being conducted in the middle of an opioid crisis, there are potentially other concurrent interventions that could make it difficult to determine the effect of our intervention. The group-randomized design should give us better insight into whether our intervention is driving behavior change in treating patients with opioid use disorder.

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

In addition to design advice from the Biostatistics Core, we received expert guidance from the Ethics and Regulatory Core, who helped us prepare for the central IRB process. The Core’s input was essential to how we developed our protocol’s waiver of informed consent, data handling, and protection of patient privacy. We were able to demonstrate to the IRB that our approach was logical and informed. We think this helped the IRB “get it” and allowed us to more efficiently address patient privacy issues in a vulnerable population across multiple healthcare systems.

What other key challenges have you faced?

One challenge was on the IT side with electronic health record (EHR) integration, which required more customization than we initially planned. How we work with EHR vendors is evolving, and we’ve found good partners so that we can integrate across different systems. This has strengthened our intervention so that it is perceived as more universal than one designed only for a specific EHR system.

Another challenge is the general under-resourcing of healthcare delivery systems for pragmatic research. We found that, regardless of budget, getting approval from system leadership for an IT change is often not enough—what is needed is figuring out who is going to make the change, how much time is involved, and whether the team has the bandwidth to complete the task. You cannot underestimate the degree of difficulty a change poses to a health system that is still struggling to get the clinical side of things right.

The way a study is framed to leadership is important—understand what’s motivating them to participate and move a project forward. With EMBED, we’re trying to take evidence-based research and implement it to improve practice. EMBED is both a research and patient care project. We need to impress upon leadership that we can improve patient outcomes and we’ll pay for it, but we need their help and support in navigating the process through the institution.

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

  • Study teams should think about potential barriers from the beginning and find solutions quickly.
  • Make sure that health system leadership discusses your project with those on the ground.
  • Enlist the experts your study needs for each site. In our case, we needed both an IT expert for the operational side and a clinical expert, or we couldn’t have moved the project forward.
  • Recognize that there are trade-offs in pragmatic design and remember that you’re working with health systems in which your intervention will need to be replicated.
  • Make your intervention sustainable and easily usable by the clinician, without the need for research or other additional staff.

EMBED is supported within the NIH Collaboratory by a cooperative agreement from the National Institute on Drug Abuse and receives logistical and technical support from the NIH Collaboratory Coordinating Center. Read more about EMBED in the Living Textbook, and learn more about the NIH Collaboratory Trials.