January 19, 2018: New Research Methods Resources Website on Group- or Cluster-Randomized Studies

The National Institutes of Health (NIH) Office of Extramural Research has released new clinical trial requirements for grant applications and contract proposals due on or after January 25, 2018. In anticipation of these new requirements, the NIH modified the Application Guide and the Review Criteria to address methodological problems common to many clinical trials. As group- or cluster-randomization designs are increasingly common in both basic and applied research, the new Application Guide includes links to the new Research Methods Resources website, which provides resources for investigators considering these group- or cluster-randomized designs, including lists of NIH webinars, key references, and statements to help investigators prepare sound applications and avoid methodological pitfalls.

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.

New Lessons Learned Document Draws on Experiences of Demonstration Projects

The NIH Collaboratory’s Health Care Systems Interactions Core has published a document entitled Lessons Learned from the NIH Health Care Systems Research Collaboratory Demonstration Projects. The Principal Investigators of each of the Demonstration Projects shared their trial-specific experience with the Core to develop the document, which presents problems and solutions for initiation and implementation of pragmatic clinical trials (PCTs). Lessons learned are divided into the following categories: build partnerships, define clinically important questions, assess feasibility, involve stakeholders in study design, consider institutional review board and regulatory issues, and assess potential issues with biostatistics and the analytic plan.

Other tools available from the Health Care Systems Interactions Core include a guidance document entitled Considerations for Training Front-Line Staff and Clinicians on Pragmatic Clinical Trial Procedures and an introduction to PCTs slide set.

New Guidance Document on Training Front-Line Staff & Clinicians in PCTs

Tools for ResearchThe NIH Collaboratory’s Health Care Systems Interactions Core has published a guidance document entitled Considerations for Training Front-Line Staff and Clinicians on Pragmatic Clinical Trial Procedures. The purpose of this guidance is to help pragmatic clinical trial (PCT) teams plan training for study procedures that involve front-line clinicians and staff. The content was developed by drawing on trial-specific experience from the NIH Collaboratory Demonstration Projects. The document describes how training for PCTs will differ from training conducted for typical research studies, and includes a list of specific considerations, real-world examples, a checklist for PCT training design, and links to additional resources.

Other tools available from the Health Care Systems Interactions Core include an introduction to PCTs slide set.

New Biostatistical Guidance Document Available: Small-Sample Robust Variance Correction for GEE

Tools for ResearchThe NIH Collaboratory’s Biostatistics and Study Design Core has just published a new guidance document by Andrea Cook, PhD, of the Group Health Research Institute, on using small-sample robust variance correction for generalized estimating equations (GEE) for use in cluster-randomized trials. The document, which includes guidance on methods available in the SAS and Stata statistical analysis packages, is available directly from the NIH Collaboratory Knowledge Repository here (opens as PDF), or via the Biostatistical Guidance Documents page in the Living Textbook.

This guidance document is one in a series of research tools focused on detailed aspects of statistical design for conducting pragmatic clinical trials. Each document in this series provides a synthesis of current developments, discusses possible future directions, and, where appropriate, makes recommendations for application to pragmatic clinical research.

Mobile Health (mHealth) Research Platform to Launch

In recent health information technology news, the University of California, San Francisco (UCSF), has received a 5-year National Institutes of Health award to support its launch of a cardiovascular mHealth platform. The research platform, to be named Health ePeople, will build on the successes of UCSF’s Health eHeart Study, which began in 2013. That study, with more than 30,000 participants worldwide, uses the power of mobile technologies to collect cardiovascular data and patient-reported outcomes (PROs) from study participants.

The Health ePeople platform will advance mHealth by providing researchers with easy access to a large cohort of volunteers, along with a quick, affordable means for collecting their health data through mobile and wireless technologies. Though the platform will not be ready to enroll new participants for several months, people who want to participate in the cohort can sign up through the Health eHeart Study website.

For information and short videos on mHealth technologies, visit the Living Textbook’s chapter on mHealth and PROs.

Minimizing the Burden of Practical Research: Case Studies from the NIH Collaboratory

In a forthcoming article in Healthcare, Dr. Eric Larson and colleagues present practical advice based on case studies from the National Institutes of Health (NIH) Health Care Systems Research Collaboratory. Physician–scientists, health services researchers, and delivery system leaders provide insight from their experience launching a pragmatic clinical trial (PCT) as part of the Collaboratory.

The authors make 5 recommendations:

  • Establish a partnership from the get-go
  • Do a pilot project
  • Take advantage of existing hospital and health system infrastructure
  • Minimize the impact on clinical workflow
  • Remember that even high-priority research questions must be balanced with the systems’ greatest priority: providing good healthcare to patients.

The authors note that researchers need to be flexible and prepared to adjust the study design to the workflow and culture of the system.

Reference: Larson E, Tachibana C, Thompson E, et al. Trials without tribulations: Minimizing the burden of pragmatic research on healthcare systems. Healthcare. 2015; in press. doi:10.1016/j.hjdsi.2015.07.005

Watch Dr. Larson’s Grand Rounds Presentation from June 2013: Trials, Not Tribulations: Minimizing the Burden of Research on Health Care Systems

Patient-Reported Outcomes Workshop Report Available

Tools for ResearchIn January of 2015, the NIH HCS Collaboratory’s Patient-Reported Outcomes (PRO) Core Group convened a 2-day workshop in Baltimore devoted to identifying barriers and possible solutions to the use of NIH-supported PRO tools in comparative-effectiveness research (CER).

Findings from the meeting, which include case study presentations and reflections from multiple stakeholders representing the research, clinical, and patient communities, were distilled into a summary document available from the NIH Collaboratory Knowledge Repository at the link below:

The workshop summary is also available on the Living Textbook’s “Tools for Research” section, under “Patient-Reported Outcomes White Paper.

ClinicalTrials.gov Analysis Dataset Available from CTTI

Tools for ResearchAs part of a project that examined the degree to which sponsors of clinical research are complying with federal requirements for the reporting of clinical trial results, the Clinical Trials Transformation Initiative (CTTI) and the authors of the study are making the primary dataset used in the analysis available to the public. The full analysis dataset, study variables, and data definitions are available as Excel worksheets from the CTTI website and on the Living Textbook’s Tools for Research page.

CTSA Working Group Unveils Accelerated Clinical Trial Agreement

A persistent problem facing the clinical research enterprise is the difficulty of negotiating the terms of contracts under which clinical trials will be performed at individual clinical research sites. For many research centers, the process is complex and protracted, and can often contribute to substantial delay in study start-up.

However, the Clinical and Translational Science Award (CTSA) Master Contracts Working Group has recently developed a possible solution—the Accelerated Clinical Trial Agreement, or ACTA. The ACTA provides a standardized template for contracts between site investigators and study sponsors, one with the potential to expedite contracting and make the start-up process for clinical trials more efficient.

The ACTA, which has already been adopted by more than 50 research centers and individual is available, along with the Accelerated Confidential Disclosure Agreement (ACDA), from the CTSA’s Accelerated Research Agreements Initiative.

For further reading:


"Use Accelerated Clinical Trial Agreement (ACTA) to Expedite Study Start-Up" (Duke Translational Medicine Institute)

Clinical Trials Transformation Initiative - Site Metrics Project Summary

Cycle time metrics for multisite clinical trials in the United States