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 NIH has issued a final policy requiring the use of a single institutional review board (sIRB) for multi-site non-exempt human subjects research funded by the NIH. The policy will take effect May 25, 2017.
According to the policy announcement, “while the NIH anticipates that that there will be challenges associated with implementation, we expect these to be short-lived. Once the transition to the new way of operating is made, the benefits of widespread use of sIRBs will outweigh any costs and, ultimately, reduce burdens to the research process.”
In proposals submitted to the NIH, applicants will be expected to include a plan identifying the sIRB that will serve as the IRB of record for all study sites. It will be the applicants’ responsibility to assure that the sIRB is qualified to serve. NIH acceptance of the submitted plan will be incorporated as a term and condition in the award. Awardees will be responsible for ensuring that the authorization agreements between IRBs (“reliance agreements”) are in place.
According to the policy, “The additional costs associated with sIRB review may be charged to grants or contracts as direct costs, provided that such costs are well-justified and consistently treated as either direct or indirect costs according to applicable cost principles in the NIH Grants Policy Statement and the FAR 31.202 (Direct Costs) and FAR 31.203 (Indirect Costs).”
Before the policy takes effect, the NIH will be issuing guidance and resources to assist with implementation.
In the systematic review, the researchers found that imaging findings of spine degeneration are present in high proportions of asymptomatic individuals, and these findings increase with age. Thus, many degenerative features found on spine imaging are likely part of normal aging. Given that advanced imaging is increasingly used in the evaluation of patients with lower back pain, knowing the prevalence of degenerative findings in asymptomatic individuals can help clinicians and patients when interpreting imaging findings.
The LIRE pragmatic trial is testing the insertion of these epidemiologic benchmarks into lumbar spine imaging reports with the goal of reducing subsequent tests and treatments, including MRI and CT, opioid prescriptions, spinal injections, or surgery.
On Tuesday, May 10, 2016, the NIH Collaboratory invites you to view a public webcast of the workshop, Ethical and Regulatory Issues of Pragmatic Clinical Trials.
This workshop will include several topics from a series of articles discussing regulatory and ethical issues related to the conduct of pragmatic clinical trials. Panelists from the NIH Collaboratory pragmatic trial Demonstration Projects, along with experts in the areas of informed consent, vulnerable populations, IRBs, data monitoring committees, and privacy issues, will participate in moderated discussion using case examples from the NIH Collaboratory.
Ethics of research in usual care settings: data on point (Sugarman 2016) introduces the special five-article supplement, stating that the “growing empirical ethics literature regarding research in usual care settings provides data to inform conceptual and policy debates regarding this research and suggests areas that require further study.”
Patients’ views concerning research on medical practices: implications for consent (Weinfurt et al. 2015) describes the results of focus group sessions that elicited a range of patients’ views and opinions about different types of research on usual medical practices. The authors state that “our data suggest that effective policy and guidance will involve balancing different patients’ interests and potentially different sets of interests for different types of research studies on usual medical practices.”
The patient’s perspective on the need for informed consent for minimal risk studies: Development of a survey-based measure (Kaplan et al. 2016) describes development and testing of a survey to assess patient preferences for and understanding of consent in quality assessment activities. The authors state, “as efforts to improve care and accelerate the implementation of effective interventions continue to challenge the understanding and practical boundaries of informed consent, in addition to ethical analysis, more careful studies of understanding patients’ and other stakeholders’ perspectives on these boundaries are needed in order to develop appropriate policies.”
A new article published in Circulation by a group of authors from the Duke Clinical Research Institute describes tensions between pragmatic clinical trial design and Good Clinical Practice (GCP) guidelines, which were established in 1996 to help ensure the safety of participants in clinical trials and the validity of trial findings. Pragmatic clinical trials (PCTs) are designed to test interventions in real-world settings and populations rather than under highly controlled conditions, and thus rely on simplified procedures, such as those used for screening, informed consent, and participant follow-up.
The authors concede that many PCT features appear to be at odds with GCP guidance, which has arguably led to improvements in the consistency and quality of trial conduct. However, they also note data suggesting that the intensive approach to monitoring and documentation fostered by GCP may ultimately increase trial cost and complexity by emphasizing minutia that “may direct focus away from critical aspects of trial conduct.”
The authors go on to suggest that GCP guidance should be updated to account for a growing proportion of research that incorporates aspects of pragmatic trial design and is conducted with data gathered from electronic health records and registries. They also offer a path forward for pragmatic research under current GCP guidelines by outlining strategies for areas that include participant enrollment, monitoring, study visits, participant follow-up, and documentation.
The authors conclude that collaborative efforts from trial sponsors, regulators, clinical trialists, and patients will be necessary to realign the guidance with contemporary trial conduct while preserving its central goal of protecting trial participants.
LIRE is studying the effect of inserting epidemiologic benchmarks for common imaging findings into lumbar spine imaging reports being delivered to primary care physicians. The primary goal is to measure whether the intervention reduces subsequent spine-related tests and treatments. All outcomes are captured passively through the electronic health record. The authors state that if successful, such a low-cost intervention could potentially be applied to diagnostic tests for other conditions. LIRE has a projected sample size of more than 160,000 patients across an estimated >2000 primary care physicians at 4 health systems. Enrollment will continue through 2016.
“LIRE is a pragmatic cluster randomized trial of a minimal-risk intervention that we believe can serve as a model for future pragmatic trials.”
(Jarvik JG, et al. Contemp Clin Trials 2015)
A new research toolavailable on the Living Textbook provides an overview of RxNorm and explores the application of some of its associated tools in the research setting. RxNorm is a free, publicly available resource from the National Library of Medicine that provides “normalized” names and unique identifiers that make it possible to clearly identify a given drug. This allows information about medications to be exchanged across electronic health records (EHRs). In fact, the Office of the National Coordinator designated use of RxNorm as a criterion for EHR certification of interoperability and Stage 2 Meaningful Use.
Earlier this year, the NIH Collaboratory conducted a series of interviews with the principal investigators of its first round of pragmatic clinical trial Demonstration Projects. These projects completed a pilot phase before scaling up to full implementation in 2014-2015. The purpose of the interviews was to share challenges and lessons learned that may help future pragmatic trials. The interviews have now been archived on the Living Textbook: