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.
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.
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.
The Department of Health and Human Services and 15 other agencies have announced revisions to the Federal Policy for the Protection of Human Subjects, otherwise known as the Common Rule. The final rule can be found here and will be officially published in the Federal Register on January 19, 2017.
The changes to the rule that will have a significant impact on the conduct of pragmatic clinical trials and embedded research include:
New requirements regarding the information that must be given to patients as part of the informed consent process, including
Key information that is most important to the subject and likely to help a patient (or legal representative) make a decision about participation
An opportunity to discuss the information
An approach that emphasizes the fostering of overall understanding (as opposed to specific length requirements)
Allowing the use of broad consent for the use of identifiable information or identifiable biospecimens for other research studies (other than the proposed one) for
Storage and maintenance for secondary research use
Secondary research (including future uses)
New exempt categories of research based on risk profile
A requirement for U.S.-based institutions engaged in cooperative research to use a single Institution Review Board (IRB)
A removal of the requirement for continuing review of ongoing research for studies that undergo expedited review.
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.
The National Institutes of Health’s Office of Disease Prevention (ODP) has just released a free, self-paced online course on designing and analyzing pragmatic and group-randomized trials. The course, which is presented by ODP Director Dr. David Murray, includes a series of seven video presentations plus slide sets, reference materials, and guided activities.
Course segments typically last 25 to 35 minutes. Presentations can be accessed individually and include the following topics:
A new funding opportunity announcement from the NIH solicits applications to support Demonstration Projects that include an efficient, large-scale pragmatic clinical trial. Trials must be conducted across two or more health care systems (HCS) and must be conducted as part of the NIH HCS Research Collaboratory supported through the NIH Common Fund. Awards made through this FOA will initially support a one-year milestone-driven planning phase (UG3), with possible rapid transition to the second implementation phase (UH3) for a pragmatic trial Demonstration Project.
The NIH Collaboratory Demonstration Project, Lumbar Imaging with Reporting of Epidemiology (LIRE), has completed enrollment as of September 30, 2016. LIRE is a pragmatic, cluster-randomized trial testing the effectiveness of inserting epidemiologic benchmarks into lumbar spine imaging reports for reducing subsequent tests and treatments for back pain. Given the rate of age-related, incidental imaging findings in individuals without back pain, many follow-up interventions for back pain based on imaging results are unnecessary. With back pain as one of the most common reasons for doctor visits, this inexpensive intervention has the potential for a large public health impact. The trial will continue to follow subjects for up to 2 years after enrollment using data from the electronic health record, but no new subjects will be enrolled.
Congratulations to the LIRE study team on this important milestone!
The ABATE Infection trial, an NIH Collaboratory project led by Dr. Susan Huang, is featured in the September 12 Health section of the Wall Street Journal. The article describes several studies aimed at preventing the hospital-associated infection MRSA (methicillin-resistant Staphylococcus aureus).
In the Reduce MRSA trial, published in 2013, Dr. Huang’s team demonstrated that treating ICU patients with a germ-fighting soap plus a nasal antibiotic ointment, an approach called “universal decolonization,” was superior to standard approaches in preventing MRSA infections. The ABATE Infection trial examines similar approaches to decolonization for all patients in non–critical care medical and surgical units, comparing the use of an antiseptic bath and nasal ointment to standard bathing and showering. More than 1 million showers and baths were taken over the course of the study, which has now completed enrollment. Data from ABATE are currently being analyzed, with the results expected to inform whether this strategy is effective in reducing hospital-associated infections.
“These are preventable infections and we should be able to drive them down to zero.” Susan Huang, MD
On Friday of last week, the US Department of Health and Human Services published a long-awaited final rule (PDF) that governs the registration and data reporting for clinical trials with ClinicalTrials.gov. The final rule and an accompanying complementary policy issued by the National Institutes of Health (NIH) represents the formal codification and clarification of requirements first described in Section 801 of the 2007 Food and Drug Administration Amendments Act (FDAAA). These requirements oblige research sponsors or other responsible parties to register most kinds of clinical trials with an accepted, publicly available registry (such as ClinicalTrials.gov) and to report certain key data about the trial design, study population, and outcomes.
However, despite the enactment of FDAAA in 2008, compliance with many of its requirements has generally been poor, as both scholarly investigations and media reports have documented. Although registration of trials has improved during this interval, possibly due to many scientific journals refusing to publish reports from unregistered studies, basic summary data (including information about adverse events) from many clinical trials have gone unreported in the ClinicalTrials.gov registry, with academic researchers being among the worst offenders for late reporting or failure to report. In addition, although Section 801 of FDAAA includes penalties for not meeting reporting obligations, no enforcement actions have yet been taken.
The final rule, which goes into effect in January of 2017, clarifies reporting requirements and responsibilities, provides checklists for research sponsors, establishes penalties for failing to fulfill reporting obligations in a timely fashion, and obligates sponsors to furnish the full research protocol to ClincalTrials.gov. Importantly, the HHS rules and NIH policy also articulate new standards for gathering and reporting data about the race and ethnicity of trial participants—information that has often been lacking from many trials datasets.
The NIH Collaboratory has developed a tool to assist authors in the complete and transparent reporting of their pragmatic clinical trials (PCTs). In the PCT Reporting Template, users will find descriptions of reporting elements based on CONSORT guidance as well as on expertise from the NIH Collaboratory Demonstration Projects and Core working groups.
Particularly relevant to PCTs are recommendations on how to report the use of data from electronic health records. Other elements of importance to PCTs include reporting wider stakeholder engagement, monitoring for unanticipated changes in study arms, and specific approaches to human subjects protection. The template contains numerous links to online material in the Living Textbook, CONSORT, and the Pragmatic–Explanatory Continuum Indicator Summary tool known as PRECIS-2.
This resource is intended to assist authors in developing primary journal publications. It will be updated over time as new best practices emerge for the transparent reporting of PCTs.
Please note: this document opens as an Adobe PDF. If you do not have software that can open a PDF, click here to download a free version of Adobe Acrobat Reader.
This work was supported by a cooperative agreement (U54 AT007748) from the NIH Common Fund for the NIH Health Care Systems Research Collaboratory. The views presented in this document are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
Originally published on September 1, 2016.
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