Tag Archives: pragmatic clinical trials

Active Bathing to Eliminate (ABATE) Infection Trial Completes Intervention Phase

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The Active Bathing to Eliminate (ABATE) Infection trial (ClinicalTrials.gov #NCT02063867) has completed its intervention phase—the first NIH Health Care Systems Research Collaboratory UH3 Demonstration Project to reach this major milestone. The large-scale, cluster-randomized pragmatic clinical trial (PCT) was designed to assess an approach for reducing multidrug-resistant organisms and hospital-associated infections (HAIs) in nearly 200 non-critical care hospital units affiliated with Hospital Corporation of America (HCA) across the United States.

Susan Huang, MD, MPH
ABATE study PI Dr. Susan Huang

The ABATE study is led by principal investigator Dr. Susan Huang of the University of California, Irvine, who stated “We are elated to reach the successful completion of the trial thanks to an incredible investigative team at HCA, Harvard Pilgrim Health Care, Rush University, the University of Massachusetts Amherst, and UC Irvine. We look forward to what the trial data will tell us and hope that we can continue to find effective ways to protect patients from infection.”

In the ABATE study, patients hospitalized in non-critical care units were bathed either according to the hospital unit’s usual care procedures (the control group) or bathed with the topical antibacterial agent chlorhexidine (plus nasal administration of the antibiotic mupirocin for those patients who were colonized or infected with, or had a history of methicillin-resistant Staphylococcus aureus [MRSA] [the intervention group]). The study investigators will compare the number of unit-attributable, multidrug-resistant organisms in clinical cultures between the study arms; these organisms include vancomycin-resistant enterococci (VRE), MRSA, and gram-negative bacteria. In addition, the investigators will compare the number of unit-attributable infections in the bloodstream and urinary tract (all pathogens) and Clostridium difficile infections. Cultures were collected at baseline and post intervention and will be assessed to determine whether resistance emerged to decolonization products.

“We are elated to reach the successful completion of the trial thanks to an incredible investigative team at HCA, Harvard Pilgrim Health Care, Rush University, the University of Massachusetts Amherst, and UC Irvine.We look forward to what the trial data will tell us and hope that we can continue to find effective ways to protect patients from infection.”

Healthcare-associated infections caused by common bacteria, including MRSA and VRE, are a leading cause of preventable illness and death in the United States and are associated with upward of $6.5 billion in annual healthcare costs. Although these bacteria normally live on the skin or in the nose, under certain circumstances they can cause serious or even life-threatening infections. Hospitalized patients who are ill or who have weakened immune systems are especially at risk for such infections. Because these pathogens are resistant to many antibiotics, they can be difficult to treat.

In intensive care units (ICUs), reducing the amount of such bacteria (a process referred to as decolonization) by treating patients’ skin with chlorhexidine and their noses with mupirocin ointment has been shown to reduce MRSA infections and all-cause bacteremias. However, relatively little is known about the effects of decolonization in hospital settings outside of critical care units, although this is where the majority of such infections occur. The ABATE trial, in contrast, is testing its bathing and decolonization strategy in adult medical, surgical, oncology, and step-down units (pediatric, psychology, peri-partum, and bone marrow transplantation units were excluded).

Over the course of the study, more than a million showers and baths were taken, and all sites have completed the intervention. The next steps for the ABATE investigators are to finish strain collection over the coming weeks, and then clean, validate, and analyze the data over the coming months.

Resources: NIH Health Care Systems Collaboratory Demonstration Project. Active Bathing to Eliminate (ABATE) Infection trial. 2014. Available at: https://www.nihcollaboratory.org/demonstration-projects/Pages/ABATE.aspx. Accessed February 2, 2015.

Huang SS, Septimus E, Moody J, et al. Randomized Evaluation of Decolonization vs. Universal Clearance to Eliminate Methicillin-Resistant Staphylococcus aureus in ICUs (REDUCE MRSA Trial). 2012. Available at: https://idsa.confex.com/idsa/2012/webprogram/Paper36049.html. Accessed December 15, 1024.

Huang SS, Septimus E, Kleinman K, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med 2013;368:2255–2265. PMID: 23718152. doi: 10.1056/NEJMoa1207290.

New Lessons Learned Document Draws on Experiences of Demonstration Projects

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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 Living Textbook Chapter on Acquiring and Using Electronic Health Record Data for Research

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Topic ChaptersMeredith Nahm Zozus and colleagues from the NIH Collaboratory’s Phenotypes, Data Standards, and Data Quality Core have published a new Living Textbook chapter about key considerations for secondary use of electronic health record (EHR) data for clinical research.

In contrast to traditional randomized controlled clinical trials where data are prospectively collected, many pragmatic clinical trials use data that were primarily collected for clinical purposes and are secondarily used for research. The chapter describes the steps a prospective researcher will take to acquire and use EHR data:

  • Gain permission to use the data. When a prospective researcher wishes to use data, a data use agreement (DUA) is usually required that describes the purpose of the research and the proposed use of the data. This section also describes use of de-identified data and limited data sets.
  • Understand fundamental differences in context. Data collected in routine care settings reflect standard procedures at an individual’s healthcare facility, and are not collected in a standard, structured manner.
  • Assess the availability of health record data. Few assumptions can be made about what is available from an organization’s healthcare records; up-front, detailed discussions about data element collection over time at each facility is required.
  • Understand the available data. A secondary data user must understand both the data meaning and the data quality; both can vary greatly across organizations and affect a study’s ability to support research conclusions.
  • Identify populations and outcomes of interest. Because healthcare facilities are obligated to provide only the minimum necessary data to answer a research question, investigators must identify the needed patients and data elements with specificity and sensitivity to answer the research question given the available data.
  • Consider record linkage. Studies using data from multiple records and sources will require matching data to ensure they refer to the correct patient.
  • Manage the data. The investigator is responsible for receiving, managing, and processing data and must demonstrate that the data are reproducible and support research conclusions.
  • Archive and share the data after the study. Data may be archived and shared to ensure reproducibility, enable auditing for quality assurance and regulatory compliance, or to answer other questions about the research.

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

Informed Consent, Institutional review boards, Pragmatic clinical trials, Regulatory issues, , , , , ,

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

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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

Clinical outcomes, Clinical trials, Comparative Effectiveness Research, Patient-Centered Outcomes Research, Patient-Reported Outcomes, Pragmatic clinical trials, Research tools, , , , , , , , , ,

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

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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

Comparative Effectiveness Research, Informed Consent, Pragmatic clinical trials, Regulatory issues, , , ,

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

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The NIH Collaboratory’s Phenotypes, Data Standards, and Data Quality 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).

New Living Textbook Chapter – Learning Healthcare Systems

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A new Living Textbook topic chapter, “Learning Healthcare Systems,” has just been published. The topic includes background information on the creation and evolution of the concept of the learning healthcare system and the key attributes that define such systems, as described by the Institute of Medicine:

A learning healthcare system is [one that] is designed to generate and apply the best evidence for the collaborative healthcare choices of each patient and provider; to drive the process of discovery as a natural outgrowth of patient care; and to ensure innovation, quality, safety, and value in health care [1].

Also included in the topic chapter are ethical and regulatory implications for learning healthcare systems, patient and public engagement, the application of electronic heatlh records and other information technology, logistical and organizational challenges to bulding learning healthcare systems, and early examples of such systems in practice.

Reference

1. Institute of Medicine. The Learning Healthcare System: Workshop Summary. Olsen L, Aisner D, McGinnis JM, eds. Washington, DC: National Academies Press; 2007. Available at: http://www.iom.edu/Reports/2007/The-Learning-Healthcare-System-Workshop-Summary.aspx. Accessed April 4, 2014.