All posts by Karen Staman

New article compares different approaches for notification and authorization in pragmatic clinical research

July 6, 2017Comparative Effectiveness Research, Informed Consent, Notification and Authorization, Pragmatic clinical trials, Regulatory issuesAuthorization, Bioethics, Comparative effectiveness research, Ethics, Informed consent, Notification, Pragmatic clincal trialKaren Staman

Dr. Kevin Weinfurt and colleagues in the Regulatory/Ethics Core of the NIH Collaboratory recently published an article in the American Journal of Bioethics regarding how acceptable different approaches to notification and authorization are to potential participants in pragmatic research. The authors conducted a series of interviews using 24 different hypothetical scenarios reflecting different types of studies and approaches to notification and authorization.

Key findings:

People have significant difficulty understanding 1) randomization and 2) that all the data are collected during routine care, and no extra visits or tests are required.
For some types of pragmatic research, many of the respondents viewed
- Active alternatives to written consent—such as oral consent—as acceptable.
- Less active approaches to notification—such as no notification ahead of time or broad notification—as unacceptable.
When using written consent in cases where researchers are testing accepted medical interventions that have known clinical risks but with no incremental risks of participating in the research, it was acceptable to omit the clinical risks from the consent documents, thereby shortening the forms.
A significant portion (28-49%) of respondents would decline to participate regardless of notification approach, which could lead to non-trivial consent bias (in other words, there could be significant differences in people who decline vs people who agree to participate).

Based on these findings, the authors suggest alternate approaches to notification and authorization should be further developed and tested.

Read the full article here.

New article from the Collaboratory’s PRO core presents first-hand experiences and practical approaches to initiating and implementing PROs

June 12, 2017Clinical outcomes, Patient-Centered Outcomes Research, Patient-Reported OutcomesClinical trials, NIH Collaboratory, Patient-reported outcomesKaren Staman

In a new article in eGems, the NIH Health Care Systems Research Collaboratory’s Patient-Reported Outcomes (PRO) Core gathered first-hand experiences on the incorporation of PROs for both care and research. The Core uses case studies from seven programs to present practical approaches for initiating and implementing PROs. The article includes tips on instrument selection, methods for integrating PRO collection into clinical workflow, consideration for user experience, and methods to monitor and assess data quality.

Read the full article: Case Studies from the Clinic: Initiating and Implementing Patient-Reported Outcome Measures

Use of Data from Electronic Health Records to Customize Medical Treatments

January 12, 2017Data analysis, Data quality, Electronic health recordsData quality, Electronic health records, Precision medicineKaren Staman

In a recent segment on NPR’s Morning Edition, commentators discuss the potential of using electronic health records to customize medical treatments.

Dr. Harlan Krumholz, a professor of medicine at Yale University, says comparing data in electronic health records with genomic information holds great promise for customizing individual treatments, but he warns that the quality of data collected in the medical record is not research quality. While researchers are making a positive start with initiatives such as the Precision Medicine Initiative (re-branded as the All of Us research program), medicine still has a long way to go to fully realize the potential of these data.

Dr. Harlan Krumholz will be presenting at an upcoming NIH Collaboratory Grand Rounds on January 13 from 1:00 – 2:00 p.m. ET. “What’s Next: People-Powered Knowledge Generation from Digital Health Data.” Join the meeting here.

The full article and audio can be found on NPR Shots, an online channel for health stories from the NPR Science Desk.

FDA releases draft guidance for using electronic health records in clinical research

May 24, 2016Data privacy, Data quality, Data sharing, Data standards, Electronic health records, Policy, Regulatory issuesData sharing, Data standards, FDAKaren Staman

The FDA has released a Draft Guidance for Industry to facilitate the use of data from electronic health record (EHRs) in clinical investigations. The draft guidance provides recommendations on how to use EHRs as a source of data for research, ensure data quality and integrity, and satisfy the FDA’s inspection, recordkeeping, and record retention requirements. An additional goal of the draft guidance is to promote interoperability, or the ability to exchange and use information between EHR systems that capture information during patient care visits and electronic data capture (EDC) systems that support clinical investigations. Sponsors of clinical research must also consider whether there are any reasonably foreseeable risks involved in using the EHR for research—such as an increased risk of data breaches—that should be disclosed in the informed consent document.

Read the full draft guidance here.

FDA Cites Collaboratory as Part of a National System for Generating Clinical Evidence

May 6, 2016Clinical trials, Comparative Effectiveness Research, Data sharing, Data standards, Pragmatic clinical trialsClinical trials, Comparative effectiveness, Data sharing, Data standards, Dissemination, NIH Collaboratory, PCORnet, Pragmatic clinical trialKaren Staman

In a recent post on the FDA’s “FDA Voice” blog, Associate Deputy Commissioner Rachel Sherman and Commissioner Robert Califf describe how to overcome barriers to data sharing and create a successful national system for medical evidence generation (or “EvGen”). To foster new approaches for creating clinical evidence the authors suggest 3 principles:

“1. There must be a common approach to how data is presented, reported and analyzed and strict methods for ensuring patient privacy and data security.

2. Rules of engagement must be transparent and developed through a process that builds consensus across the relevant ecosystem and its stakeholders.

3. To ensure support across a diverse ecosystem that often includes competing priorities and incentives, the system’s output must be intended for the public good and be readily accessible to all stakeholders.”

Drs. Sherman and Califf point to substantial pioneering work being done in secondary use of data, in which data collected for clinical care are “secondarily” used for research, including projects currently underway through the NIH Collaboratory, PCORnet, and other initiatives and networks. The experience gained from these groundbreaking efforts should provide a foundation for a national system for evidence generation.

Read the full post here.

ABATE Infection Study Team Releases Training Video

May 2, 2016Cluster Randomized Trials, Comparative Effectiveness Research, Research toolsABATE Trial, Cluster randomized trial, Demonstration Project, DisseminationKaren Staman

The Active Bathing to Eliminate (ABATE) Infection trial was conducted in nearly 200 non-critical care hospital units across the United States. The ABATE study team developed a training video to teach nurses and nursing assistants how to approach patients to administer a bath with a topical antiseptic agent containing chlorhexidine (CHG), or help patients take a shower using the liquid CHG soap. If the results of the trial demonstrate a reduction in unit-attributable infections or multi-drug resistant organism (MDRO) burden for the intervention units, this video could be used to train nurses and staff to implement CHG bathing in healthcare systems around the nation.

The ABATE trial (ClinicalTrials.gov #NCT02063867) is a large-scale, cluster-randomized pragmatic clinical trial (PCT) designed to assess a bathing approach for reducing multidrug-resistant organisms and hospital-associated infections (HAIs) in patients hospitalized in non-critical care units. Patients were bathed either according to the hospital unit’s usual care procedures (the control group) or bathed with a topical antiseptic agent containing chlorhexidine (CHG; the intervention group). Patients in the intervention group could shower using liquid CHG soap and a mesh sponge, or have a self-assisted or nurse-assisted bed bath using the CHG cloths. If a patient in the intervention group was colonized with, infected with, or had a recent history of methicillin-resistant Staphylococcus aureus (MRSA), the antibiotic mupirocin was additionally administered nasally for 5 days.

The investigators hypothesize that this regimen will reduce the burden of vancomycin-resistant enterococci (VRE) and Staphylococcus aureus (MRSA) in these units and translate to a reduction in overall bloodstream and urinary tract infections. They will also evaluate its ability to reduce antibiotic-resistant gram-negative bacteria and Clostridium difficile.

The ABATE Infection Trial has been conducted in hospitals in the Hospital Corporation of America (HCA) health system and is an NIH Health Care Systems Research Collaboratory UH3 Demonstration Project supported by the National Institutes of Allergy and Infectious Diseases (NIAID) and the Common Fund at the National Institutes of Health. This video was created and scripted for the trial by study investigators and filmed by Sage Products, LLC.

Watch the training video here.

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

March 11, 2016Clinical trials, Cluster Randomized Trials, Pragmatic clinical trials, Randomized controlled trialsABATE Trial, Cluster randomized trials, Demonstration Project, NIH Collaboratory, pragmatic clinical trialsKaren Staman

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.

Journal Editors Propose New Requirements for Data Sharing

February 4, 2016Data sharing, Research reporting standards, Writing and PublishingData sharing, DisseminationKaren Staman

On January 20, 2016, the International Committee of Medical Journal Editors (ICMJE) published an editorial in 14 major medical journals in which they propose that clinical researchers must agree to share the deidentified data set used to generate results (including tables, figures, and appendices or supplementary material) as a condition of publication in one of their member journals no later that six months after publication. By changing the requirements for manuscripts they will consider for publication, they aim to ensure reproducibility (independent confirmation of results), foster data sharing, and enhance transparency. To meet the new requirements, authors will need to include a plan for data sharing as a component of clinical trial registration that includes where the data will be stored and a mechanism for sharing the data.

Evolving Standards for Data Reporting and Sharing

As early as 2003, the National Institutes of Health published a data sharing policy for research funded through the agency, stipulating that “Data should be made as widely and freely available as possible while safeguarding the privacy of participants, and protecting confidential and proprietary data.” Under this policy, federally funded studies receiving over $500,000 per year were required to have a data sharing plan that describes how data will be shared, that shared data be available in a usable form for some extended period of time, and that the least restrictive method for sharing of research data is used.

In 2007, Congress enacted the Food and Drug Administration Amendments Act. Section 801 of the Act requires study sponsors to report certain kinds of clinical trial data within a specified interval to the ClinicalTrials.gov registry, where it is made available to the public. Importantly, this requirement applied to any study classified as an “applicable clinical trial” (typically, an interventional clinical trial), regardless of whether it was conducted with NIH or other federal funding or supported by industry or academic funding. However, recent academic and journalistic investigations have demonstrated that overall compliance with FDAAA requirements is relatively poor.

In 2015, the Institute of Medicine (now the National Academy of Medicine) published a report that advocates for responsible sharing of clinical trial data to strengthen the evidence base, allow for replication of findings, and enable additional analyses. In addition, these efforts are being complemented by ongoing initiatives aimed at widening access to clinical trial data and improving results reporting, including the Yale University Open Data Access project (YODA), the joint Duke Clinical Research Institute/Bristol-Myers Squibb Supporting Open Access to clinical trials data for Researchers initiative (SOAR), and the international AllTrials project.

Responses to the Draft ICMJE Policy

The ICMJE recommendations are appearing in the midst of a growing focus on issues relating to the integrity of clinical research, including reproducibility of results, transparent and timely reporting of trial results, and facilitating widespread data sharing, and the release of the draft policy is amplifying ongoing national and international conversations taking place on social media and in prominent journals. Although many researchers and patient advocates have hailed the policy as timely and needed, others have expressed concerns, including questions about implementation and possible unforeseen consequences.

The ICMJE is welcoming feedback from the public regarding the draft policy at www.icmje.org and will continue to collect comments through April 18, 2016.

Resources

Journal editors publish editorial in 14 major medical journals stipulating that clinical researchers must agree to share a deidentified data set: Sharing clinical trial data: A proposal from the International Committee of Medical Journal Editors (Annals of Internal Medicine version). January 20, 2016.

A New England Journal of Medicine editorial in which deputy editor Dan Longo and editor-in-chief Jeffrey Drazen discuss details of the ICJME proposal: Data sharing. January 21, 2016.

A follow-up editorial in the New England Journal of Medicine by Jeffrey Drazen: Data sharing and the Journal. January 25, 2016.

Editorial in the British Medical Journal: Researchers must share data to ensure publication in top journals. January 22, 2016.

Commentary in Nature from Stephan Lewandowsky and Dorothy Bishop: Research integrity: Don’t let transparency damage science. January 25, 2016.

National Public Radio interview on Morning Edition: Journal editors to researchers: Show everyone your clinical data with Harlan Krumholz. January 27, 2016.

Institute of Medicine (now the National Academy of Medicine) report advocating for responsible sharing of clinical trial data: Sharing clinical trial data: maximizing benefits, minimizing risk. National Academies Press, 2015.

Rethinking Clinical Trials Living Textbook Chapter, Acquiring and using electronic health record data, which describes the use of data collected in clinical practice for research and the complexities involved in sharing data. November 3, 2015.

NIH Health Care Systems Research Collaboratory data sharing policy. June 23, 2014.

Commentary from Richard Platt and Joakim Ramsberg in New England Journal of Medicine on challenges of data sharing from healthcare systems research. April 20, 2016.

List of International Committee of Medical Journal Editors (ICMJE) member journals.

New Lessons Learned Document Draws on Experiences of Demonstration Projects

January 21, 2016Electronic health records, Institutional review boards, Pragmatic clinical trials, Regulatory issues, Research toolsElectronic health records, Guidance documents, Healthcare systems interactions, NIH Collaboratory, Pragmatic clinical trial, pragmatic clinical trials, Research regulations, Study designKaren Staman

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.

Rethinking Clinical Trials®

A Living Textbook of Pragmatic Clinical Trials