Sentinel IMPACT-AFib

Investigators from Multiple U.S. Organizations Collaborate on First Embedded Pragmatic Clinical Trial Using National Health Plans’ Data

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CTTI Project: Electronic Healthcare Data

Today, at the ESC Congress 2020 – The Digital Experience, a group of U.S. investigators from several organizations announced their collaborative findings from the Implementation of a randomized controlled trial to imProve treatment with oral AntiCoagulanTs in patients with Atrial Fibrillation (IMPACT-AFib), the first trial to use the U.S. Food and Drug Administration’s (FDA) FDA-Catalyst System network of electronic health data from a diverse group of national health plan data partners.

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Recent CTTI Publication Explores Educational Strategies for Increasing Use of Anticoagulants Among AFib Patients

Posted on by Hannah Faulkner

A new CTTI publication from collaborators including CTTI investigates the impact of educational mailings in increasing the use of oral blood thinners among patients with atrial fibrillation (AFib). For many of these patients, use of blood thinners can reduce their stroke risk by about 70%. Despite current guideline recommendations, only about half of eligible patients with AFib are routinely taking blood thinners, and patient interviews have revealed that patients are undereducated about stroke risk and the potential benefits of preventative blood thinner use. To explore solutions to this educational gap, the IMplementation of a randomized controlled trial to imProve treatment with oral AntiCoagulanTs in patients with Atrial Fibrillation (IMPACT-AFib) identified and sent educational mailings to a subset of eligible patients enrolled in health plans that participate in the FDA’s Sentinel System. The resulting paper, published in JAMA Network Open, found that these mailings were only minimally successful in increasing blood thinner use among AFib patients. These results indicate that more intensive educational interventions may be needed to address this problem. 

This trial was the first ever to leverage the FDA-Catalyst System, which combines data from interactions with patients and/or providers with data from the Sentinel Infrastructure. The collaboration included Aetna, Duke Clinical Research Institute, the Harvard Pilgrim Health Care Institute’s Department of Population Medicine, Harvard Pilgrim Health Care, HealthCore Anthem, Humana, Optum, and the FDA.  

CTTI Collaborates with Multiple U.S. Organizations on First Successful Embedded Trial Using National Health Plans’ Data

Posted on by Hannah Faulkner

Today, at the ESC Congress 2020 – The Digital Experience, a group of U.S. investigators from several organizations including CTTI announced their collaborative findings from the Implementation of a randomized controlled trial to imProve treatment with oral AntiCoagulanTs in patients with Atrial Fibrillation (IMPACT-AFib) trial.

CTTI worked with Aetna, Duke Clinical Research Institute, the Harvard Pilgrim Health Care Institute’s Department of Population Medicine, Harvard Pilgrim Health Care, HealthCore Anthem, Humana, Optum, and the FDA, as well as a patient representative, to plan and conduct this ground-breaking, 80,000-patient, randomized clinical study. This trial was the first ever to leverage the FDA-Catalyst System network of electronic health data, which consolidates data from a diverse group of national health plan data partners.

The study involved identifying patients with atrial fibrillation (AF) who were at high risk of stroke and not currently taking any type of oral anticoagulant (OAC). The goal of the study was to learn if mailing educational information to patients and their providers could incentivize patients to initiate important OAC prescribing discussions with their doctors.

“It is imperative to identify all patients with AF who are at risk of stroke, especially because strokes can be prevented with OAC,” said Sean Pokorney, co-principal investigator at Duke Clinical Research Institute, who presented the findings at the event. “The underuse of OAC is a significant public health priority, and also a priority of health plans like those participating in this study, which is why we were so eager to collaborate on IMPACT-AFib.”

Although it had never been done before, the study relied upon administrative health plan data and pharmacy dispensing data from multiple national health plans to identify eligible patients and randomize them to an early or delayed intervention, and to assess clinical outcomes.

The study results showed that it would take more than one educational mailing to achieve the desired outcome. Moreover, the study sets a foundation for future clinical trials in AF and other diseases as an example of how the FDA-Catalyst System can help to conduct trials using new and resourceful methods. The goal is for solutions like this to help clinical trial stakeholders conduct future trials much faster than before.

“CTTI played a key role in the pre-work for this trial, proving the viability of running a large-scale trial using the FDA-Catalyst platform,” added Pamela Tenaerts, executive director at CTTI. “The study is a successful proof of concept of embedding a randomized clinical trial into a claims system, while confirming in a large scale experiment that the use of educational interventional approaches in medicine might be limited. We believe that all future clinical trials should maximally leverage available clinical and nonclinical data to minimize collection of necessary trial specific data, and the IMPACT-AFib trial is a fantastic example of that; it serves as a strong model for future research.”

Read the full press release.

IMPACT-AFib Shares Successes and Lessons Learned from Use of Single IRB

Posted on by Hannah Faulkner

IMPACT-AFib (IMplementation of a randomized controlled trial to imProve treatment with oral AntiCoagulanTs in patients with Atrial Fibrillation) is a nationwide pragmatic clinical trial launched in 2017 by collaborators including CTTI. IMPACT-AFib is the first trial conducted under FDA-Catalyst, which incorporates the infrastructure of the FDA’s Sentinel System and enables direct contact with health plan members and providers. To help facilitate large-scale interventional research more efficiently, the collaborators followed CTTI’s recommendations of using a single institutional review board (sIRB).

The study team shared that the use of an sIRB had many positive results, including reducing study start-up time and alleviating administrative burden and costs on sites.

The study team also shared lessons that were learned through the process of using an sIRB:

  • In a multi-center trial, each site has unique requirements, which must be taken into account by study leadership when identifying an sIRB that all sites will find acceptable. Selecting an sIRB that has national experience and is accustomed to dealing with different regulations across states is helpful. In addition, choosing an sIRB that many or all sites have used in the past expedites reliance agreements required between each site and the sIRB.
  • Certain approaches can increase the efficiency of the sIRB approval process and reduce administrative burden for sites. For example, the team behind IMPACT-AFib expedited the process by submitting the initial protocol application to the sIRB that applied to all five sites. They then provided each site a template for the site submissions, noting items that might need to be adjusted according to site-specific considerations.
  • Specific considerations around trial design, such as pragmatic studies leveraging claims data, should be taken into account when submitting to an sIRB. For example, sites for this study are virtual – with patient contact via mailings from their health plans – rather than contacting potential participants in-person at traditional clinical trial sites such as clinics or hospitals.
  • Using an sIRB expedites the amendment process because only one submission is required, which is reviewed and approved for all sites.

Historically, each site’s local IRB has reviewed a trial’s protocol separately in multi-center trials, which results in lengthy approval processes, duplicative work, and differing protocol or informed consent changes among sites. The use of sIRBs can improve the quality and efficiency of multi-center trials by improving oversight and streamlining the review process.

Understanding of sIRB implementation has recently become even more critical; in 2018, the NIH began to require the use of an sIRB for all multi-center trials funded by the NIH, and by 2020, all U.S. institutions involved in U.S.-based cooperative research will be required to use an sIRB.

CTTI has championed the adoption of sIRB review for nearly a decade, developing recommendations and resources to address barriers and assist in the implementation of sIRBs. CTTI is also supporting an NIH workgroup to develop a comprehensive plan for assessing the NIH’s new sIRB policy.

Learn more about the IMPACT-AFib trial on ClinicalTrials.gov.

Article Outlines Lessons Learned from First Large Pragmatic Trial Using Sentinel

Posted on by Lorri Bingham

A new article in Clinical Trials, co-authored by CTTI, outlines lessons learned from the planning phase of the implementation of a randomized controlled trial to improve treatment with oral anticoagulants in patients with Atrial Fibrillation (IMPACT-AFib) trial, the first large pragmatic clinical trial that used the Sentinel infrastructure. This work is part of CTTI’s larger effort to advance trials that use real-world data sources.

The FDA’s Sentinel System uses electronic health records (EHR) and insurance claims from 18 health plans and delivery systems covering about 45 million individuals enrolled in commercial health plans, in addition to 22 million Medicare recipients.

The IMPACT-AFib trial, launched in 2017 by collaborators including CTTI, identified patients with atrial fibrillation who were at high risk of stroke, and randomized them to either an early or delayed intervention. The Sentinel System helped the trial team assess the size of the potential trial population, examine baseline measurements, and determine there were significant gaps in care, which showed there was a need for the trial.

In selecting participants for the trial and conducting other planning analyses, the trial team used Sentinel’s common data model and reusable analytic programs, which accelerated the planning and budgeting for the trial while keeping member-level data safe.

The IMPACT-AFib team also considered limitations introduced by Sentinel, including the potential for misclassification due to the use of administrative claims data. Other lessons learned for developing health plan-based clinical trials include using a single IRB, involving patient representatives in protocol design, and timing the start of the trial and mailing of materials around open enrollment and other health plan initiatives.

Learn more about CTTI’s other work to increase the appropriate use of real-world data sources and real-world evidence in clinical trials for regulatory submission.

Public and Stakeholders Encouraged to Comment on Protocol for Innovative Clinical Trial

Posted on by Lorri Bingham

SENTINEL IMPACT-AFIB DRAFT PROTOCOL POSTED

The draft protocol for an innovative pragmatic clinical trial examining educational methods for improving medication utilization in patients with atrial fibrillation (AFib) has been posted on Sentinel Initiative website. This draft protocol is now available for public comment and feedback as part of process that seeks to engage all potential stakeholders in study development and implementation.

The Sentinel IMPACT-AFib study grew out of findings from a pilot program in which CTTI, through its Electronic Healthcare Data project, evaluated the feasibility of using data from FDA’s Sentinel System to conduct clinical trials. IMPACT-AFib marks the first time the Sentinel System has been used to support a randomized pragmatic clinical trial—not only by serving as a primary source for study data, but also by helping study organizers to identify potential participants.

Atrial fibrillation affects more than 5 million people in the United States. It is a serious condition in which the upper chambers of the heart beat with an irregular rhythm. More common among persons aged 65 years or older, AFib increases a person’s risk of stroke by up to five times and contributes to an estimated 130,000 deaths annually in the United States alone. Although AFib can be treated effectively with a number of different oral anticoagulant (OAC) medications, many of the people who stand to benefit from these therapies do not receive them.

Find out more about AFib and the background of the Sentinel IMPACT AFib trial by clicking here to access a CTTI webinar and slides.

CTTI Acknowledged for Contributing to FDA Sentinel Program in Applied Clinical Trials News Article

Posted on by Lorri Bingham

The Food and Drug Administration’s (FDA) Sentinel program was launched in 2008 and has been a considerable investment for the FDA, as indicated by Janet Woodcock in a recent Applied Clinical Trials news article. The Sentinel system is an important part of routine safety surveillance for pharmaceuticals and other medical products. The FDA plans to expand use of the Sentinel system to public health and quality improvement activities as well as effectiveness research in its “Guardian” system.

CTTI supported FDA efforts to explore the potential for using the Sentinel database beyond safety surveillance previously; CTTI and FDA’s Mini-Sentinel jointly published a report describing the capability and willingness of Mini-Sentinel’s Data Partners to collaborate in a variety of types of randomized trials, using the Mini-Sentinel (now Sentinel) Distributed Dataset. CTTI and Sentinel are now collaborating to design and implement a trial based on findings in the report. As mentioned in the recent Applied Clinical Trials news article, CTTI will facilitate the development and execution of a protocol for a randomized trial (IMPACT-AF) to study an educational intervention to improve the appropriate use of anti-coagulation for atrial fibrillation. This trial is a proof of concept study intended to determine whether it is possible to conduct a trial within the “Guardian” system. CTTI is proud to support the FDA’s efforts to expand their safety monitoring system to become a national resource with broader applications, specifically in more real-world clinical studies.