Special Issue Published on Ethical & Regulatory Complexities of Pragmatic Clinical Trials


Tools for ResearchA new series of 12 articles published in a special issue of the journal Clinical Trials addresses ethical and regulatory challenges particular to pragmatic clinical research. Pragmatic clinical trials are designed to efficiently provide answers to important clinical questions, yet they present special challenges in conforming to the ethical and regulatory guidelines that were developed for more traditional clinical research. The special issue describes these challenges and begins to outline possible solutions that will protect the rights and welfare of research participants while allowing pragmatic clinical trials to gather much-needed evidence for informing healthcare decisions. An introductory article is followed by 11 articles addressing individual topics, such as alteration of informed consent, privacy, gatekeepers, and defining minimal risk research. The effort was funded by the NIH Health Care Systems Research Collaboratory, with additional support from the Patient-Centered Outcomes Research Institute (PCORI), and involved diverse groups of stakeholders, including researchers, patient advocates, bioethicists, and regulatory experts. Robert M. Califf, MD, and Jeremy Sugarman, MD, MPH, were editors of the special issue.

For more information:


PCORnet Posts Aspirin Study Protocol for Public Review and Comment


PCORnetThe National Patient-Centered Clinical Research Network (PCORnet) has recently made a draft protocol for its first randomized clinical trial available for stakeholder review. Researchers, clinicians, patients and the public are all invited to read the current draft of the study protocol and provide comments and feedback.

The ADAPTABLE Study (PDF), which will investigate whether lower- or higher-dose aspirin is better for preventing heart attack and stroke in patients at risk for heart disease, is PCORnet’s first randomized pragmatic clinical trial. Designed to leverage PCORnet’s Clinical Data Research Networks (CDRNs) and Patient-Powered Research Networks (PPRNs), the trial will serve as twofold purpose: answering a clinical question of direct importance for patients, families, and healthcare providers, and serving as a demonstration of PCORnet’s capabilities in conducting clinical research on a national scale.

Links to the proposed study protocol, a survey tool for capturing feedback, and other information about ADAPTABLE Study, including press releases, fact sheets, and infographics, are available at the link below:

ADAPTABLE: The Aspirin Study

Follow PCORnet on Twitter @PCORnetwork for updates on the ADAPTABLE #ClinicalTrial


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.


Groundbreaking Suicide Prevention Trial has Enrolled Initial Patients

March 5, 2015

Dr. Greg Simon and the Suicide Prevention Team have enrolled the first participants in the Pragmatic Trial of Population-Based Programs to Prevent Suicide Attempt. This groundbreaking study was developed by researchers at Group Health Cooperative in Seattle, Washington, Health Partners Medical Group in Minnesota, and Kaiser Permanente of Colorado, in collaboration with patients who have experienced suicidal thoughts or survived suicide attempts themselves.

Over 9 million adults in the United States experience suicidal thoughts, and more than 1 million adults attempt suicide each year. However, patients at risk for suicidal behavior are not routinely identified, and successful interventions for depression and suicide are not routinely implemented. New evidence suggests that patients who report frequent thoughts of death or self-harm on a commonly-used depression questionnaire are at higher risk for suicide attempt and death over the following year.

This study aims to address the significant problem of suicide by identifying patients who are at risk for suicidal behavior and testing two suicide prevention strategies. Patients at participating institutions will complete a standard depression severity questionnaire during routine clinical care, and the results will be stored in their electronic health records (EHR). Investigators will use the responses in the EHR to identify at-risk individuals, and once identified, the patients will be randomly assigned to either usual care or to two treatment programs. The first is a collaborative care-management approach; the second is an online skills training program called “Now Matters Now,” which is designed to help people manage painful emotions and stressful situations.

Over the next 5 years, the team plans to enroll 19,500 adult patients. The study is an NIH Collaboratory Demonstration Project being overseen by the National Institute of Mental Health (NIMH).

Congratulations to Dr. Simon and his team for their achievement!

 

Office for Human Research Protections Releases Draft Guidance on Disclosing Risks in Standard-of-Care Research


On October 20, 2014 the Office for Human Research Protections (OHRP) released a draft guidance on how to apply the Department of Health and Human Services (HHS) regulations on protecting human subjects (45 CFR Part 46) who participate in research studies intended to evaluate risks of treatments or procedures commonly used by healthcare professionals and recognized as “standard of care.” In standard-of-care research (or comparative effectiveness research), participants are randomized to receive one of two (or more) treatments that are accepted by medical experts as appropriate treatments for a given disease or condition.

Because treatments assigned to some participants might be different than the treatments they would have been assigned if they were not participating in the study, and the risks associated with one treatment might be different from the risks associated with another treatment, the OHRP recommends that these risks be fully described to potential participants as a part of the informed consent process.

Click here for the full draft guidance: Draft Guidance on Disclosing Reasonably Foreseeable Risks in Research Evaluating Standards of Care

The Institute of Medicine is planning a two-day public workshop in December to discuss human subjects protections in standard-of-care research. Click here for more information.​


 

Collaboratory Phenotypes, Data Standards, and Data Quality Core Releases Data Quality Assessment White Paper


The NIH Collaboratory’s Phenotypes, Data Standards, and Data Quality Core (now the Electronic Health Records Core) has released a new white paper on data quality assessment in the setting of pragmatic research. The white paper, titled Assessing Data Quality for Healthcare Systems Data Used in Clinical Research (V1.0) provides guidance, based on the best available evidence and practice, for assessing data quality in pragmatic clinical trials (PCTs) conducted through the Collaboratory. Topics covered include an overview of data quality issues in clinical research settings, data quality assessment dimensions (completeness, accuracy, and consistency), and a series of recommendations for assessing data quality. Also included as appendices are a set of data quality definitions and review criteria, as well as a data quality assessment plan inventory.

The full text of the document can be accessed through the “Tools for Research” tab on the Living Textbook or can be downloaded directly here (PDF).


PCORnet: “Not your father’s clinical trial network”


“PCORnet: Turning a Dream Into Reality,” an editorial published online this week in the Journal of the American Medical Informatics Association, details the promises of the National Patient-Centered Clinical Research Network (PCORnet):

“Providing accurate answers based on the highest levels of scientific evidence for the majority of unresolved clinical questions is a revolutionary dream shared by patients, providers, payers, health plans, researchers, and policy makers alike. PCORnet, the National Patient-Centered Clinical Research Network, promises a transformative platform that will turn this revolutionary dream into reality.”

The authors describe PCORnet’s patient-centered vision and how its transformative clinical research will be carried out through a national research network. This “network of networks” is designed to include a large, highly representative population. PCORnet will first work to establish data architecture and standards and address key policy questions, followed by the conduct of its first pragmatic clinical trial slated to begin in September 2015.

Editorial authors include NIH Director Dr. Francis Collins, Kathy L. Hudson, PhD, and Josephine P. Briggs, MD.


Grand Rounds (4-4-2014): Defining Denominator Populations Within and Across Complex Health Systems

Update:

Archived video and slides from the April 4 Grand Rounds are now available on the NIH Collaboratory Grand Rounds webpage.


This Friday’s NIH Collaboratory Grand Rounds (“Defining Denominator Populations Within and Across Complex Health Systems”) will be presented by Greg Simon, MD, MPH, of the Group Health Research Institute. Dr. Simon is the principal investigator for the NIH Collaboratory Demonstration Project “Pragmatic Trial of Population-Based Programs to Prevent Suicide Attempt” (detailed description available here).

The Grand Rounds presentation will take place from 1:00-2:00 PM Eastern time on Friday, April 4. Archived video and slide sets from the presentation will be available early the following week; links to archived material will be provided in an update to this post.


LIRE Pragmatic Clinical Trial Begins Randomization


One of the NIH Collaboratory’s initial Demonstration Projects, the Lumbar Image Reporting with Epidemiology (LIRE) study, has begun randomization in early April. The LIRE trial is designed to test whether inserting additional epidemiological information into the lumbar spine imaging reports of patients being treated for lower back pain can help both doctors and patients to better understand and interpret the reports. This in turn could help doctors avoid subjecting patients to unnecessary tests and procedures.

LIRE is a cluster randomized trial, which means that instead of randomizing individual patients, whole clinics (one at the Henry Ford Health System in Detroit; one at Group Health Cooperative in Seattle, with more to follow) are randomly assigned to provide either the experimental treatment or the control treatment to patients.

Cluster-randomized trials offer a number of advantages, including the avoidance of certain kinds of bias that can effect the outcome of a study, but they also raise special issues that can require careful consideration.

The principal investigator of the LIRE trial is Dr. Jeffrey Jarvik  of the University of Washington. You can read more about the LIRE trial here.


STOP CRC Study Featured on NPR Health Blog


The Strategies and Opportunities to Stop Colon Cancer in Priority Populations (STOP CRC) study was recently featured on National Public Radio’s Shots Blog, which is devoted to coverage and discussion of health and healthcare issues.

Picture of U.S. stop sign.
Public-domain image via Wikimedia Commons.

STOP CRC, which is exploring innovative approaches for increasing colon cancer screening rates among low-income and minority populations, is one of the seven UH2 pilot projects supported by the NIH Collaboratory. The demonstration phase of the project will be conducted within a pair of health centers that are part of OCHIN, a community-based network of Federally Qualified Health Centers.

More information about about STOP CRC is available here.