November 20, 2017: NIH Collaboratory Core Working Group Interviews: Reflections from the Regulatory/Ethics Core

We recently asked Drs. Jeremy Sugarman and Kevin Weinfurt, Co-chairs of the Regulatory/Ethics Core, to reflect on the first 5 years of the Core as well as on the challenges ahead. The regulatory and ethical landscape for pragmatic clinical trials was not well defined when the Core began 5 years ago, and the Core helped to map and navigate the emerging landscape to enable the implementation of Demonstration Projects in ways that satisfied ethical and regulatory criteria.

“The Core’s work has led to the creation of a substantial body of scholarship contributing to the ongoing policy and ethics debates about pragmatic clinical trials.” – Drs. Sugarman and Weinfurt

Download the interview (PDF).

November 17, 2017: ICD-Pieces: From Planning to Performance

Speakers

Miguel A. Vazquez, MD
Professor of Medicine
Clinical Chief Nephrology Division
University of Texas Southwestern Medical Center

George Oliver, MD
Vice President Clinical Informatics
Parkland Center for Clinical Innovation

Topic

ICD-Pieces: From Planning to Performance

Keywords

Pragmatic clinical trial; Multiple chronic conditions; Diabetes; Hypertension; Chronic kidney disease; Pieces™; Parkland Center for Clinical Innovation; PCCI; University of Texas Southwestern Medical Center; Electronic health records

Key Points

  • ICD-Pieces is a pragmatic clinical trial conducted in 4 large, diverse healthcare systems, including a Veterans Affairs (VA) system.
  • This study is evaluating a collaborative care model for improving the management of 3 chronic conditions: diabetes, hypertension, and chronic kidney disease. This model of care combines a novel IT platform, primary care practitioners, and site practice facilitators.
  • The study is conducted with the aid of clinical decision support tools, previsit planning, performance monitoring, and outcomes ascertainment through EHR data and claims data.

Discussion Themes

It is essential to engage key stakeholders early and throughout the pragmatic trial to sustain enthusiasm for the trial’s outcomes. In ICD-Pieces, it was especially important to engage with individual healthcare practitioners to facilitate and simplify their workflow. The study team also collaborated with medical directors and other leaders at the participating healthcare systems.

Practice facilitators at each study site served as a link between the study team and the healthcare system operations.

As with many real-world pragmatic trials, ICD-Pieces needed to address some turnover of key study participants, including principal investigators, practice facilitators, and IT staff.

For More Information

Read more about the ICD-Pieces trial in the Living Textbook: http://bit.ly/2j1qkJu

Dr. Vazquez discusses lessons learned in ICD-Pieces: http://bit.ly/2zx8tEY

Visit the ICD-Pieces Demonstration Project page: http://bit.ly/2zQE1my

For more on dissemination, implementation & sustainability for ICD-Pieces: http://bit.ly/2A6zL5A

Tags

#pctGR, #chronicdisease, @PCTGrandRounds, @Collaboratory1, @PCORnetwork, @UWMedicine, @PCCIpieces

November 3, 2017: Dr. Miguel Vazquez Shares Lessons From the Improving Chronic Disease Management with Pieces (ICD-Pieces) Trial

In this interview, Dr. Miguel Vazquez gives an update on the first years of the Improving Chronic Disease Management with Pieces (ICD-Pieces) trial. Dr. Vazquez discussed the status of his trial, challenges and surprises, and advice he has for new investigators.

“Try to really learn from others who have done this—even if you are the first one doing your specific trial with your specific questions. It was helpful for us to learn from the other Collaboratory projects; they had already faced some problems, and we were able to anticipate and develop solutions proactively.” – Dr. Miguel Vazquez

Read more from Dr. Vazquez in the full interview (PDF).

October 18, 2017: NIH Collaboratory Core Working Group Interviews: Reflections from the Biostatistics and Study Design Core

We recently asked Dr. Liz DeLong, Chair of the Biostatistics and Study Design Core, to reflect on the first 5 years of the Core’s work and the challenges ahead. She says the biggest impact of the Core has been working with the individual Demonstration Projects to provide a sounding board to discuss statistical challenges. Further, Core members have contributed to new knowledge through manuscripts that address key methodological issues related to pragmatic clinical trials. She’s hoping the Core will continue to push the boundaries of statistical methods in the coming years.

“The statisticians on the individual trials have not only developed excellent statistical methods for their own studies, but also contributed substantively to the Core.” Dr. Liz DeLong

Download the interview (PDF).

October 16, 2017: NIH Collaboratory Core Working Group Interviews: Reflections from the Stakeholder Engagement Core

At the NIH Collaboratory Steering Committee meeting in May 2017, we asked Ellen Tambor, a member of the Stakeholder Engagement Core, to reflect on the first 5 years of the Core’s work and the challenges ahead. She says it’s key for stakeholder engagement to take place throughout the entire healthcare system, from leadership to the frontline providers and staff. And, because of the nature of pragmatic trials conducted in clinical settings, engagement is essential from the early stages through trial completion. Tambor also suggests asking two questions to ensure the right people are involved throughout pragmatic research: Who is going to use the evidence that results from the study? Who will help ensure that the study is implemented as seamlessly as possible?

“Pragmatic trials take stakeholder engagement to a new level of importance in terms of both the scope of engagement and the array of potential stakeholders.” Ellen Tambor

Download the interview (PDF).

October 10, 2017: NIH Collaboratory Core Working Group Interviews: Reflections from the Phenotypes, Data Standards, and Data Quality Core

At the NIH Collaboratory Steering Committee meeting in May 2017, we asked Drs. Rachel Richesson and W. Ed Hammond, Co-chairs of the Phenotypes, Data Standards, and Data Quality Core, to reflect on the first 5 years of their Core’s work and the challenges ahead.

Both were pleased with how the Core was able to provide guidelines for assessing data quality and the reporting of pragmatic trials, especially around issues with phenotypes and the use of electronic health record data. Future work in this area needs to advance the development of regulations and standards for the collection of clinical data to support learning healthcare systems.

“We’ve built a community in our Core that represents a diverse group of scientists and clinicians showing the many ways to look at data challenges.”
– Dr. Rachel Richesson

In Fall 2017, the Phenotypes, Data Standards, and Data Quality Core merged with the Electronic Health Records Core. The combined Core will continue to work on data standards and quality, and approaches to define clinical phenotypes and endpoints, extract information, and discover errors in data from healthcare systems.

Download the interview (PDF).

A PDF of the May 2017 interview with leaders of the Phenotypes Core Working Group.

NIH & FDA seek feedback on new clinical trial protocol template


As part of their ongoing effort to improve the speed and efficiency of conducting clinical trials, the NIH-FDA Joint Leadership Council has created a draft clinical trial protocol template. The template contains instructional and sample text intended to assist NIH-funded investigators in writing protocols for phase 2 or 3 clinical trials that require Investigational New Drug (IND) or Investigational Device Exemption (IDE) applications. Feedback is sought from investigators, investigator-sponsors, institutional review board members, and other stakeholders involved in protocol development and review.

Our goal is to provide an organized way for creative investigators to describe their plans so that others can understand them. – Dr. Pamela McInnes, NIH

Details on the rationale and development of the protocol template are on these blog posts:

Notice Number: NOT-OD-16-043. Responses accepted through April 17, 2016.

You can access the template document as well as a template shell, comment form, and other resources at NIH’s Clinical Research Policy website.

Recent Collaboratory Publications on Research Ethics


The American Journal of Bioethics has recently published three articles authored by members of the Regulatory/Ethics core group describing various questions related to research on medical practices:

  • Is shared decision making an appropriate analytic frame for research on medical practices (Sugarman 2015) discusses the role of shared decision making (SDM) in research on medical practices. The author cautions that “while SDM is in many ways similar to informed consent, there are some important differences, especially in the research setting.” This publication is freely accessible through PubMed Central.
  • Patients’ views concerning research on medical practices: implications for consent (Weinfurt et al. 2015) describes the results of focus group sessions that elicited a range of patients’ views and opinions about different types of research on usual medical practices. The authors state that “our data suggest that effective policy and guidance will involve balancing different patients’ interests and potentially different sets of interests for different types of research studies on usual medical practices.”
  • Ethics of research in usual care settings: data on point (Sugarman 2016) introduces a special five-article supplement in the American Journal of Bioethics, stating that the “growing empirical ethics literature regarding research in usual care settings provides data to inform conceptual and policy debates regarding this research and suggests areas that require further study.”

These publications were supported by a bioethics supplement awarded to the Regulatory/Ethics Core group by the NIH’s Office of the Director.


CTSA-PCORnet Webinar: A Central IRB Approach


The webinar copresented on March 2, 2016, by the Clinical and Translational Science Awards (CTSA) program and PCORnet is available as a video and slideset.

Petra Kaufmann, MD, MSc
Director, Office of Rare Diseases Research and Division of Clinical Innovation
National Center for Advancing Translational Sciences
National Institutes of Health

Rachael Fleurence, PhD
Program Director, CER Methods and Infrastructure Program
Patient-Centered Outcomes Research Institute

Sabune J. Winkler, JD
Director, Regulatory Affairs Operations
Harvard Catalyst

Webinar details:
March 2, 2016
3pm - 4pm ET
To join the WebEx, click here: http://bit.ly/1TGRTFS
Call-in number: 1-855-244-8681
Access code: 737 807 582

STOP CRC Trial: Analytic Challenges and Pragmatic Solutions


Investigators from the STOP CRC pragmatic trial, an NIH Collaboratory Demonstration Project, have recently published an article in the journal eGEMs describing solutions to issues that arose in the trial’s implementation phase. STOP CRC tests a program to improve colorectal cancer screening rates in a collaborative network of Federally Qualified Health Centers by mailing fecal immunochemical testing (FIT) kits to screen-eligible patients at clinics in the intervention arm. Clinics in the control arm provided opportunistic colorectal-cancer screening to patients at clinic visits in Year 1 and implemented the intervention in Year 2. In this cluster-randomized trial, clinics are the unit of analysis, rather than individual patients, with the primary outcome being the proportion of screen-eligible patients at each clinic who complete a FIT.

The team dealt with various challenges that threatened the validity of their primary analysis, one of which related to potential contamination of the primary outcome due to the timing of the intervention rollout: for control participants, the Year 2 intervention actively overlapped with the Year 1 control measurements. The other challenge was due to a lack of synchronization between the measurement and accrual windows. To deal with these issues, the team had to slightly modify the study design in addition to developing a few sensitivity analyses to better estimate the true impact of the intervention.

“While the nature of the challenges we encountered are not unique to pragmatic trials, we believe they are likely to be more common in such trials due to both the types of designs commonly used in such studies and the challenges of implementing system-based interventions within freestanding health clinics.” (Vollmer et al. eGEMs 2015)

The Publish EDM Forum Community publishes eGEMs (generating evidence & methods to improve patient outcomes) and provides free and open access to this methods case study. Readers can access the article here.