December 7, 2018: Cluster Randomized Trials in Health Care Delivery Systems: Lessons from STIC2IT (Niteesh K. Choudhry, MD, PhD)

Speaker

Niteesh K. Choudhry, MD, PhD
Professor, Harvard Medical School
Executive Director, Center for Healthcare Delivery Sciences, Brigham and Women’s Hospital

Topic

Cluster Randomized Trials in Health Care Delivery Systems: Lessons from STIC2IT

Keywords

STIC2IT; Pragmatic clinical trial; Learning health system; Cluster randomization; Medication adherence; Telepharmacy; Electronic health record; Stakeholder engagement

Key Points

  • STIC2IT, a pragmatic, cluster-randomized trial, evaluated a telepharmacy intervention to improve medication adherence for people with chronic diseases.
  • Pragmatic aspects of STIC2IT included outcomes assessed using routinely collected data, cluster randomization by physician practice, intention-to-treat analysis, and use of the EHR to collect research data.
  •  While medication adherence did improve in the STIC2IT intervention group, secondary clinical outcomes did not improve. Future trials within health systems should incorporate multilevel engagement across the health system, physicians and staff, and patients.

Discussion Themes

It is important to do ongoing outreach at the health system leadership level to ensure understanding and commitment to the study and keep providers aware of the trial. Study teams should be mindful of the priorities of their partner health system.

Using the EHR for research data required some upfront work building special modules and generating custom reports.

For more information on conducting PCTs in health delivery systems, visit the Living Textbook chapter on engaging stakeholders and building partnerships.

Tags

@Collaboratory1, #pctGR, #HarvardMed, #telepharmacy

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

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.

November 16, 2018: Primary Palliative Care for Emergency Medicine (PRIM-ER) (Corita Grudzen, MD, MSHS)

Speaker

Corita R. Grudzen, MD, MSHS, FACEP
Vice Chair for Research
Associate Professor of Emergency Medicine and Population Health
Ronald O. Perelman Department of Emergency Medicine
NYU School of Medicine

Topic

Primary Palliative Care for Emergency Medicine (PRIM-ER)

Keywords

PRIM-ER; Emergency department; Palliative care; Demonstration project; Pragmatic trial; Stepped-wedge study design; Clinical decision support; Best practice alerts; Advance care planning

Key Point

  • The PRIM-ER trial is a pragmatic, cluster-randomized, stepped wedge Demonstration Project that will implement primary palliative care in emergency medicine across a diverse group of 35 emergency departments (EDs).
  • PRIM-ER’s clinical decision support intervention is tailored to each ED site. The study aims to enable system, organizational, and provider change in the emergency department workflow.
  • The study team is identifying and preparing site champions by conducting communication skills training in serious illness for emergency physicians and staff using the EM Talk program.

Discussion Themes

It is important to consider sustainability of the intervention during the planning phase of the trial. Plan for staff turnover and how new staff will be educated and oriented to the intervention.

The volume and sophistication of best practice alerts (BPAs) received by physicians varies across U.S. emergency departments. Alert “fatigue” can be a concern.

For more information on the PRIM-ER Demonstration Project, visit the PRIM-ER website on the Living Textbook.

Tags

@Collaboratory1, #pctGR, #EmergencyMedicine

October 19, 2018: A New Path Forward for Using Decentralized Clinical Trials (Jeffry Florian, PhD, Annemarie Forrest, Penny Randall, MD, MBA)

Speakers

Jeffry Florian, PhD
Clinical Analyst, Office of New Drugs
FDA Center for Drug Evaluation and Research (CDER)

Annemarie Forrest
Clinical Trials Transformation Initiative (CTTI)

Penny Randall, MD, MBA
VP and Global Therapeutic Head, CNS
IQVIA

Topic

A New Path Forward for Using Decentralized Clinical Trials

Keywords

Decentralized clinical trials; Telemedicine; Mobile health; Clinical Trials Transformation Initiative; FDA

Key Points

  • Decentralized clinical trials (DCTs) are defined as those executed through telemedicine, mobile, or local healthcare providers (HCPs), using procedures that vary from the traditional clinical trial model; for example, shipping investigational medical product directly to the trial participant.
  • DCTs are not “all or nothing.” They exist in a broad continuum and can expand the reach of traditional clinical trial sites.
  • Potential benefits of DCTs apply to all trials in all disease areas but may offer particular advantages in rare diseases, where patients are generally limited in number or are highly geographically dispersed.
  • Mobile HCP training is similar to that required for standard investigative sites: Good clinical practice, protocol-specific training, human subject protections, data protection, and clinical trial billing.

Discussion Themes

Will a decentralized trial lead to less diverse patient populations as participants will need to be technology literate and have access to technology?

Decentralized clinical trial safety monitoring plans should not be held to a higher standard than with traditional trials unless merited by a particular circumstance. It is important to develop protocol-specific safety monitoring and communication escalation plans.

Download CTTI’s recommendations for decentralized clinical trials.

Tags

#telemedicine #pctGR, @PCTGrandRounds, @Collaboratory1, @CTTI_Trials @IQVIA_global @US_FDA

September 28, 2018: Assessing and Reducing Risk of Re-identification When Sharing Sensitive Research Datasets (Greg Simon, MD, MPH, Deven McGraw, JD, MPH, Khaled El Emam, PhD)

Speakers

Gregory Simon MD, MPH
Investigator, Kaiser Permanente Washington Health Research Institute

Deven McGraw, JD, MPH, LLM
General Counsel & Chief Regulatory Officer, Ciitizen

Khaled El Emam, PhD
Department of Pediatrics, University of Ottawa
Children’s Hospital of Eastern Ontario Research Institute

Topic

Assessing and Reducing Risk of Re-identification When Sharing Sensitive Research Datasets

Keywords

Clinical trials; Research ethics; Data security; Data sharing; Sensitive research data; De-identified data

Key Points

  • The cycle of risk de-identification involves setting a risk threshold, measuring the risk, evaluating the risk, and applying transformations to reduce the risk.
  • The Safe Harbor method of de-identification (removal of 18 categories of data) is a legal minimum standard that does not take context into account, and may not be sufficient when sharing sensitive data publicly.
  • A higher standard for de-identification is the “Expert Determination” method, whereby an expert with contextual knowledge of the broader data ecosystem can determine whether the risk is “not greater than very small.”
  • With increasing concern about the risks of sensitive data sharing, it is important to be transparent with data participants and continue to build trust for data uses.

Discussion Themes

When is a dataset safe for sharing? What is the risk of re-identification, and how can we reduce the risk? Consider who you are releasing the data to and what other kinds of data might they have access to that could potentially lead to re-identification.

For more information on the de-identification of protected health information, visit the U.S. Department of Health and Human Services’s Guidance Regarding Methods for De-identification of Protected Health Information in Accordance with the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule.

The Health Information Trust Alliance de-identification framework identifies 12 criteria for a successful de-identification program and methodology.

Tags

#pctGR, #PragmaticTrials, #HealthData, @HealthPrivacy @Collaboratory1, @PCTGrandRounds

October 1, 2018: Meeting Minutes from NIH Collaboratory’s Regulatory/Ethics Core Discussions with the New Demonstration Projects

Meeting minutes and supplementary materials are available that summarize discussions related to the ethics and regulatory issues associated with each of the new UG3 Demonstration Projects. These discussions, which took place by teleconference, included representation from study principal investigators and study teams, members of the NIH Collaboratory Regulatory/Ethics Core, NIH staff, and NIH Collaboratory Coordinating Center personnel as well as some IRBs responsible for oversight of the projects.

September 14, 2018: Advancing the Use of Mobile Technologies for Data Capture & Improved Clinical Trials (John Hubbard, PhD, Barry Peterson, PhD, Cheryl Grandinetti, PharmD)

Speakers

John Hubbard, PhD
Healthcare Strategic Advisory Board
Genstar Capital

Barry Peterson, PhD
Independent Consultant

Cheryl Grandinetti, PharmD
Office of Compliance, Office of Scientific Investigations, Division of Clinical Compliance Evaluation
Center for Drug Evaluation and Research
Food and Drug Administration

Topic

Advancing the Use of Mobile Technologies for Data Capture & Improved Clinical Trials

Keywords

Clinical trials; Mobile health technologies; Clinical Trials Transformation Initiative; CTTI; FDA; Data integrity

Key Points

  • The goal of CTTI’s Mobile Clinical Trials program is to develop evidence-based recommendations that affect the widespread adoption and use of mobile technology in clinical trials for regulatory submission.
  • Potential benefits of using mobile technology include higher quality, patient-centric endpoints and fewer barriers to participation in clinical trials.
  • Data access issues to consider before selecting a mobile technology include:
    • How will the data generated by the mobile technology be accessed and used by the manufacturer?
    • What data will be provided by the manufacturer to the sponsor?
  • The mobile era creates new data security demands.

Discussion Themes

CTTI’s recommendations aim to help sponsors determine the right device to use, how to write the protocol for remote data capture, and how to protect and analyze the data.

Know what you want to measure before selecting the mobile technology. The appropriateness of the selection should be justified through verification and validation processes.

Ensure the authenticity, integrity, and confidentiality of data over its entire lifecycle.

To reduce risk in large trials, conduct feasibility studies before full implementation.

Visit CTTI for more recommendations and resources for mobile clinical trials.

 

Tags

@CTTI_Trials, @PCTGrandRounds, #MobileTech, #pctGR

September 7, 2018: NIH Collaboratory: Research Transformation in Progress (Adrian Hernandez MD, MHS, Kevin Weinfurt, PhD, Lesley Curtis, PhD)

Speakers

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

Kevin Weinfurt, PhD
Professor and Vice Chair for Research
Department of Population Health Sciences
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

Topic

NIH Collaboratory: Research Transformation in Progress

Keywords

Clinical trials; Research studies; Healthcare delivery; Clinical care; embedded pragmatic clinical trials; ePCTs; Peer-reviewed journals; Demonstration projects; NIH funding

Key Points

  • The goal of the NIH Collaboratory is to strengthen the national capacity to implement cost-effective large-scale research studies that engage healthcare delivery organizations as research partners.
  • Embedded pragmatic clinical trials bridge research into clinical care.
  • The NIH Collaboratory has contributed to 80 publications about embedded pragmatic trials in peer-reviewed journals.
  • Six new demonstration projects were recently added to the NIH Collaboratory portfolio:
    • Improving Advance Care Planning in Oncology: A Pragmatic, Cluster-Randomized Trial Integrating Patient Videos and Clinician Communication Training (ACP PEACE)
    • Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo)
    • Pragmatic Trial of Parent-Focused Prevention in Pediatric Primary Care: Implementation and Adolescent Health Outcomes in Three Health Systems (GGC4H: Guiding Good Choices for Health)
    • Pragmatic Trial of User-Centered Clinical Decision Support to Implement Emergency Department-Initiated Buprenorphine for Opioid Use Disorder (EMBED)
    • Personalized Patient Data and Behavioral Nudges to Improve Adherence to Chronic Cardiovascular Medications (Nudge)
      Primary Palliative Care for Emergency Medicine (PRIM-ER)

Discussion Themes

The NIH Collaboratory is addressing many of the challenges and logistical barriers to conducting pragmatic clinical trials embedded in healthcare systems. There is still progress to be made in explaining the value and benefit of embedded PCTs (ePCTs) to healthcare leadership.

The NIH Collaboratory workshops have had a positive impact and have increased NIH’s interest in supporting the conduct of ePCTs.

Determining how pragmatic clinical trials can be conducted more routinely will be critical to their impact.

 

Tags

@texhern, @lmhcurtis, @PCTGrandRounds, #pctGR #ClinicalResearch, #researchstudies, #clinicaltrials, #clinicalcare, #peerreviewed

September 7, 2018: Spotlight on a New Demonstration Project: HiLo

Kidney transplantation is the preferred treatment for patients with end-stage renal disease (ESRD), but an insufficient organ supply renders dialysis the only viable treatment option for most patients. Though clinical outcomes among patients receiving dialysis have improved modestly in recent years, annual rates of hospitalization and mortality remain unacceptably high, and quality of life is poor. Poor outcomes are driven primarily by increased risk of cardiovascular disease (CVD), but interventions that improve outcomes in the general population by targeting traditional CVD risk factors have mostly failed in patients with ESRD. Current clinical practice guidelines advocate aggressive treatment of high serum phosphate to near-normal levels using dietary phosphate binders and restrictive diets. The benefits of this approach, however, are unproven, the optimal serum phosphate target remains unknown, and potential harms of aggressive treatment have not been definitively identified.

The Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo) plans to address these clinically important questions in a large, pragmatic, cluster-randomized trial that will evaluate the effects of liberalizing the serum phosphate target (“Hi”) versus maintaining aggressive phosphate control (“Lo”) for patients receiving treatment with maintenance hemodialysis.

 “The question at hand is something we grapple with on a daily basis in every dialysis facility across the country. Either answer will be important new information that will help us do a better job taking care of patients and hopefully improve their quality of life.”

HiLo is led by Myles Wolf, MD, of Duke University with support from the National Institute of Diabetes and Digestive and Kidney Diseases. Read more about HiLo.

September 4, 2018: Spotlight on a New Demonstration Project: PRIM-ER

In the United States, half of persons 65 years and older have an emergency department visit in the last month of life, and three-quarters have an emergency department visit in the last 6 months of life. Admissions to intensive care units by emergency clinicians are on the rise, especially for older patients. Meanwhile, three-quarters of older adults with serious illness have thought about end-of-life care, and only 12% want life-prolonging care.

The Primary Palliative Care for Emergency Medicine (PRIM-ER) pragmatic clinical trial will address this gap in the delivery of goal-directed emergency care of older adults. PRIM-ER will implement primary palliative care in a diverse group of 35 emergency departments. The trial will test the hypothesis that older patients with serious, life-limiting illness who receive care from clinicians with primary palliative care skills are less likely to be admitted to inpatient settings, are more likely to be discharged home or to palliative care service, and will have higher home health and hospice use, fewer inpatient days and intensive care unit admissions at 6 months, and longer survival than patients receiving care before implementation of the intervention.

“Giving emergency nurses, physician assistants, doctors the knowledge and skills they need to better care for patients with serious illness will ease symptom burden, improve quality of life, and get patients to the places where they want to be at the end of life.”

As a new addition to the NIH Collaboratory’s family of innovative Demonstration Projects, the PRIM-ER trial will feature evidence-based, multidisciplinary primary palliative care education; simulation-based workshops on communication in serious illness; clinical decision support, and provider audit and feedback.

PRIM-ER is led by principal investigator Dr. Corita Grudzen of New York University with support from the National Institute on Aging and the National Center for Complementary and Integrative Health. Watch a video interview with Dr. Grudzen, and read more about PRIM-ER.