Grand Rounds 4: Modifications and Waivers of Informed Consent in Pragmatic Clinical Trials


Jason Karlawish, MD 

Learning Objectives

  1. Identify how consideration of ethical and regulatory issues in the design phase of an ePCT with PLWD can help make the study more pragmatic.
  2. Review the regulatory requirements for a waiver or alteration of informed consent and discuss related ethical considerations.
  3. Apply what we’ve covered to two case studies.

Watch the Webinar

Webinar Slides

Download the slides: IMPACT Grand Rounds February 20 2020.

Additional Resources

  • 45 CFR 46 – Protection of Human Subjects
  • Scott Kim and Frank Miller. “Waivers and alterations to consent in pragmatic clinical trials: Respecting the principle of respect for persons.” IRB: Ethics and Human Research. January-February 2016, Vol 38, issue 1.
  • January 31, 2008 SACHRP letter to HHS Secretary: Recommendations related to waiver of informed consent and interpretation of “minimal risk,” available at

New blog post on clustered randomized trials and the design effect

The latest blog post from Keith Goldfeld, DrPH, MS, MPA, member of the executive committee of the IMPACT Collaboratory Design and Statistics Core, discusses how the design effect could provide additional insight into cluster randomized trials in his most recent blog post. The ideas in this blog post were motivated in part by Goldfeld’s work with the IMPACT Collaboratory.

Gitlin’s Tailored Activity Program highlighted in Wall Street Journal

The Tailored Activity Plan (TAP),  a home-based occupational therapy intervention shown to reduce behavioral symptoms in people living with dementia and caregiver burden, was recently included in an article in the Wall Street Journal. The TAP program was developed by Laura Gitlin, PhD, FGSA, FAAN, Dean and distinguished professor at College of Nursing and Health Professions, at Drexel University and leader of the IMPACT Collaboratory Dissemination and Implementation Core and her colleagues. Read the full article at the Wall Street Journal at this link.

An Introduction to the NIA IMPACT Collaboratory

Richard J. Hodes, MD, Director of the National Institute of Aging and Partha Bhattacharyya, PhD, the IMPACT Collaboratory Project Officer and Program Director in the Division of Behavioral and Social Research, share their thoughts on the need for the IMPACT Collaboratory and the project goals.



An Introduction to the NIA IMPACT Collaboratory from NIA IMPACT Collaboratory on Vimeo.

Goldfeld discusses analyzing data from a stepped-wedge designed cluster randomized trial in a real-world context

Keith Goldfeld, DrPH, MS, MPA, member of the executive committee of the IMPACT Collaboratory Design and Statistics Core, recently discussed his work with the IMPACT Collaboratory on his blog, ouR data generation.

Goldfeld wrote about how to analyze data from a stepped-wedge designed cluster randomized trial. He said that this design can be an important tool to evaluate interventions in a real-world context, including research for the IMPACT Collaboratory in dementia and Alzheimers disease.

Read the full blog entry here:

Mitchell shares a look back at research in advanced dementia and links to her career

NIA IMPACT Collaboratory multiple principal investigator Susan Mitchell, MD, MPH, spoke at the February 4 Palliative and Advanced Illness Research (PAIR) Center Series at the Perelman School of Medicine at Pennsylvania University. Her talk, “Advanced Dementia: The Evolution of Research Informing Practice,” included a look at the overall body of work in advanced dementia and the evolution of her own research.

Mitchell described her research to date in three phases: Retrospective, Prospective, and Interventional, and described studies in each phase and how they contributed to the overall body of knowledge about advanced dementia. Mitchell concluded her talk with an introduction to the NIA IMPACT Collaboratory, describing how effectiveness and efficacy research continue the evolution of research in advanced dementia care.

To view the entire talk, please go to the PAIR Series site here: and begin the video at the 13:12 mark.

Mission Moment: Marie Martinez Israelite, MSW

The mission of the NIA IMPACT Collaboratory is to build the nation’s capacity to conduct pragmatic clinical trials of interventions embedded within health care systems for people living with dementia and their care partners.   Our Mission Moments highlight the perspective of someone directly involved with dementia to remind us of the importance of our mission. In this Mission Moment, we hear from Marie Martinez Israelite, MSW, Director of Victim Services at the Human Trafficking Institute and care partner for her mother, a retired physician who is living with Alzheimer’s. Ms. Israelite spoke at the NIA IMPACT Steering Committee meeting in January 2020.



IMPACT Collaboratory Mission Moment: Marie Martinez Israelite from NIA IMPACT Collaboratory on Vimeo.

Harrison outlines the need for embedded pragmatic clinical trails and how IMPACT can help in AcademyHealth editorial

Jill Harrison, PhD, Executive Director for the IMPACT Collaboratory at Brown University, authored a blog post for AcademyHealth describing the need for embedded pragmatic clinical trails and how the IMPACT Collaboratory can help.

Harrison describes the rise in diagnoses of Alzheimer’s disease and related dementias as a global public health crisis and describes how embedded pragmatic clinical trials can help to gather real world data for clinical trials, and incorporate diverse stakeholders into study design. Read the full blog post on the AcademyHealth website.

IMPACT principal investigators share their vision of the project with LeadingAge

The NIA IMPACT Collaboratory’s multiple principal investigators, Susan L. Mitchell, PhD, MPH, and Vincent Mor, PhD, shared the vision and goals of the project with LeadingAge in an article from January 17.

“We are confident that the NIA IMPACT Collaboratory will transform the delivery, quality, and outcomes of care provided to Americans with dementia, and their caregivers, by accelerating the testing and adoption of evidence-based interventions within health care systems,” says Mitchell.

The article includes a description of the problem of Alzheimer’s disease and related dementias, as well as how the structure of the IMPACT Collaboratory will help researchers who seek to conducted embedded pragmatic clinical trials to combat these conditions.

IMPACT leaders hope their collaborative efforts will identify and validate evidence-based programs that can be adopted across PLWD communities and help people live a higher quality of life. “The goal,” concludes Mor, “is to reduce the suffering of persons living with dementia, reduce the burden on the caregivers, and ease the challenge of humanely meeting the needs of this difficult-to-serve population, while maintaining their dignity—and I am confident we can achieve this.”

Read the full article at LeadingAge here.

Registration open for statistical conference focused on cluster randomized clinical trials

IMPACT Steering Committee and Design and Statistics Core member Monica Taljaard, PhD, will be part of a panel at the 13th University of Pennsylvania Conference on Statistical Issues in Clinical Trials  on April 29th.  The conference will focus on challenges and opportunities in cluster randomized clinical trials. Registration is now open.