Grand Rounds Archive

Grand Rounds July 7, 2023: Implementing Virtual Strategies Across an Integrated Healthcare System: The IMPLEMENT-HF Study (Ankeet S. Bhatt, MD, MBA, ScM)

Posted on by Elizabeth Mccamic

Speaker

Ankeet S. Bhatt, MD, MBA, ScM
Associate Physician, Kaiser Permanente San Francisco Medical Center
Research Scientist, Kaiser Permanente Northern California Division of Research

Keywords

Heart Failure, Implementation Science, IMPLEMENT-HF

Key Points

  • There are 4 drugs that modify 5 pathways, renin-angiotensin inhibition, neprilysin inhibition, SNS inhibition, aldosterone inhibition, and SGLT2 inhibition, that are the mainstays for treatment of heart failure with reduced ejection fraction (HFrEF).
  • In modeling exercises, optimal implementation of these therapies, such as an ARNI, a beta blocker, an MRA, and an SGLT2 inhibitor, compared to conventional therapy (an ACEi or ARB plus a beta blocker) is estimated to afford more than 6 years of survival in a typical 55-year-old patient. This is compelling evidence that patients with HFrEF should be treated with this combination of therapies, but less than 5% of patients on are optimal guideline therapies for this condition.
  • There is renewed interest in implementation science in cardiometabolic care to better understand optimal pathways for delivering these therapies in patients with HFrEF.
  • The daily workflow consisted of a daily electronic health record (EHR) query that identified patients who had heart failure with reduced ejection fraction, who were admitted for any cause within sites in the healthcare system. Patients went through a screening by a study physician for eligibility. The physician-pharmacist team developed recommendations using an algorithm that was supported by the ACC, AHA clinical practice guidelines. They made only one suggestion a day for how to optimize the patient’s care, such as initiation of one therapy or an up titration of an existent therapy. The recommendations were communicated in the EHR as a note and the primary team received a page notification. The recommendations were at the discretion of the primary provider.
  • There were substantial improvements in the intervention group of the pilot study and improved guideline medical therapy that indicated that the virtual nudge strategy might be beneficial and scalable to multiple entities within an integrated healthcare system.
  • For the IMPLEMENT-HF Pivotal Study, 200 hospitalized patients were enrolled at 3 hospital sites in one integrated health care system, where patients either received the virtual care team intervention or usual care. The study team assessed the change in medical therapy from hospital admission to hospital discharge by assigning a guideline directed in-hospital medical therapy score.
  • As compared to usual care, a virtual care team-guided strategy improved medical therapy optimization in hospitalized HFrEF patients across multiple hospitals in an integrated healthcare system. Benefits were consistent across most subgroups, including hospitalizations for non-HF indications and de-novo HF presentations.

Learn more

Read about the IMPLEMENT-HF study in JACC.

Discussion Themes

–How diverse were the settings where this was tested? The study team was interested in testing in a setting outside of a large academic hospital. Salem Hospital is affiliated with the health care system but is a community-based hospital. We need to test in systems that might have an enhanced usual care arm. Would this provide incremental value?

-What is going on at Mass General? It hasn’t been implemented in usual care yet but we hope that it will happen. There are a lot of programs that are aimed at this type of intervention at Kaiser but not one with a virtual intervention. It is something we are looking at seriously to see if we can run a small-scale version of this to see if it would be effective.

Tags

#pctGR, @Collaboratory1

Grand Rounds June 16, 2023: BeatPain Utah: Partnering With Community Health Centers Within a Socio-Technical Framework (Julie Fritz, PT, PhD, FAPTA; Guilherme Del Fiol, MD, PhD)

Posted on by Damon Seils

Speakers

Julie Fritz, PT, PhD, FAPTA
Distinguished Professor, Department of Physical Therapy & Athletic Training
Associate Dean for Research, College of Health
University of Utah

Guilherme Del Fiol, MD, PhD
Professor, Biomedical Informatics
University of Utah

Keywords

Community Health Centers; Low Back Pain; Physical Therapy Modalities; Primary Care; Telemedicine

Key Points

  • Clinical practice guidelines support nonpharmacologic care as first-line management of low back pain. However, persons in low-income and rural communities have significantly higher odds of receiving a prescription opioid for a new back pain diagnosis.
  • Use of nonpharmacologic pain treatments is lower in rural settings and for persons of Hispanic/Latino ethnicity. Many of these communities are served by federally qualified health centers that often lack options to provide accessible nonpharmacologic alternatives.
  • Clinical research can exacerbate disparities, because clinical trials typically are based in urban, academic medical centers, underrepresent diverse populations, and overlook community engagement strategies in trial planning and design.
  • BeatPain Utah, an NIH Pragmatic Trials Collaboratory Trial, is an embedded pragmatic clinical trial comparing the effectiveness of nonpharmacologic intervention strategies for patients with back pain seeking care in federally qualified health centers in Utah. The interventions include a telehealth strategy that provides a brief pain teleconsult along with phone-based physical therapy, and an adaptive strategy that provides the brief pain teleconsult first, followed by phone-based physical therapy among patients who are nonresponsive to treatment.
  • BeatPain Utah is using the Community-Engaged Dissemination and Implementation (CEDI) framework, which considers both social and technical factors in the implementation of health IT strategies, decentralizes the research methods and procedures, and grounds the implementation in a systematic, iterative mapping of how both clinic staff and patients interact with health IT.
  • Although there is evidence of a significant divide in the implementation of advanced health IT functions, low-resource settings can adopt advanced health IT with some assistance. Moreover, there is considerable opportunity to reduce inequities through increased adoption of telehealth strategies, given that 96% of people in low-resource communities have at least a text and voice phone.

Discussion Themes

  • Motivating patients to engage in self-management of health conditions is a challenge, irrespective of whether the intervention is delivered in person or remotely.
  • Designing interventions that can meet everyone’s needs can be a challenge in a study that involves rural/urban and racial/ethnic diversity. Implementation mapping at the beginning of the design process is key. This includes direct assessment of patients’ needs, such as by interviewing patients who seek care in the partnering clinics to understand their expectations and how they would think about a mode of care delivery, like telehealth, that is unfamiliar to them.
  • Another crucial element of the health equity–focused model is ensuring that the question at the heart of the research is of value to the clinics and their leadership. For every trial, one of the first important tasks is to reach out to the community health center leadership and see if they are interested. The clinic’s priorities should drive the design of the trial. “We have to be very accommodating to the needs of each [community health center] and respect their needs.”
  • How quickly can these types of studies proceed from trial completion to release of results? Especially in studies involving chronic conditions, having long-term follow-up data to answer the core effectiveness question in a hybrid trial means there could be a long wait for results. Researchers must also be prepared to consider the question of sustaining a service that many clinics in the study have come to rely on, even before the results are available.

Tags

#pctGR, @Collaboratory1

Grand Rounds June 30, 2023: Decentralized Trials – From Guidance to Reality & What’s Left (Adrian Hernandez, MD, MHS; Pamela Tenaerts, MD, MPH; Craig Lipset, MPH)

Posted on by Lauren Stewart

Speaker

Adrian Hernandez, MD, MHS
Director, Duke Clinical Research Institute

Pamela Tenaerts, MD, MPH
Chief Scientific Officer, Medable

Craig Lipset, MPH
Co-Chair, Decentralized Trials & Research Alliance

 

Keywords

Decentralized; Guidance; FDA; Clinical trials

 

Key Points

  • Decentralized clinical trials (DCTs) are regular clinical trials in which all activities take place at locations other than traditional trial sites. Over the past several years, a variety of factors have accelerated the need for decentralized trials, including the push to make trials more accessible, the increased speed of science, the possibility of environmentally conscious trials, and the need to be flexible in a rapidly changing world.
  • During the COVID-19 pandemic, several regulatory authorities around the world introduced guidance on DCTs. There has been a growing sense of hesitancy about whether regulators will remain equally receptive to these decentralized methods when the pandemic recedes. The Food and Drug Administration (FDA) issued a draft guidance in May 2023 that provided guidance about the conduct of decentralized clinical trials. This guidance and others in development in other markets act as an important countermeasure to ensuring sustained adoption and implementation of DCTs.
  • The FDA draft guidance includes guidance around rules and expectations for topics, including patient safety and data integrity, location stipulations, rules for health care providers, telehealth versus in-person protocol, digital health technology, trial operations, management and supervision, consent, and investigational product (IP) administration. Additional considerations are needed for the data management plan, monitoring plan, safety plan, task log, and case report forms in the FDA draft guidance.
  • The European Medicines Agency (EMA) released a separate guidance around DCTs in December 2022. While similar to the FDA draft guidance, the EMA guidance differs slightly in its emphasis and lack of certain topics. For instance, there is no discussion of the role of the health care provider in the DCTs, but it emphasizes the importance of patient voice. The EMA guidance also features an extensive discussion on the need for investigator oversight.
  • The key remaining issues for DCTs include clarification around the roles and responsibilities of health care providers as well as principal investigator (PI) oversight and responsibility. All trials are different, but it’s important to ask the right questions and be clear in the protocol.
  • As IRBs and ethics committees review of DCTs, they can use newly developed recommendations for what should be submitted and discussions that should occur once the appropriate documents are submitted.
  • DCTs are not only more convenient for trial participants, but they often provide a positive return on investment for the trial itself. The DCT space is evolving and will require more commentary on guidance, sharing research, and effective implementation.

Learn more

Read more about Decentralized Clinical Trials.

Discussion Themes

-As an early adopter of DCTs, could you share your experience and perspective on these issues? DCTs can make things easier for patients and the research more efficient. It can also contribute to providing more inclusive trials in solving some of the access issues that exist in healthcare and clinical trials. There are a lot of gray areas within the FDA guidance, but the key is to work together to address these challenges and ambiguities in order to ensure the safety and needs of the patients, while generating the knowledge necessary to further the trials.

-What is your response to questions surrounding the issue of adverse event reporting issue? A lot of questions on this topic have to do with the role of the health care provider as it relates to event reporting. The idea that health care providers in our communities may have data about an adverse event is not necessarily new, and health care providers are often aware of an adverse event very early on. Interstate licensing and our own institution’s policies are issues that still need to be addressed in terms of oversight and responsibilities. In some ways, health care providers are the same as any other data instrument in the trial – they are external data sources that come back to the investigator for safety and quality review.

Tags

#pctGR, @Collaboratory1

Grand Rounds June 23, 2023: Improving Delivery of Care for Chronic Kidney Disease, Diabetes and Hypertension (Miguel A. Vazquez, MD and George Oliver, MD, PhD)

Posted on by Hannah Webster

Speakers

Miguel A. Vazquez, MD
Robert Toto, MD
University of Texas Southwestern Medical Center
Dallas, TX

George Oliver, MD, PhD
Parkland Center for Clinical Innovation
Dallas, TX

Keywords

ICD-Pieces, pragmatic clinical trial, chronic kidney disease, type 2 diabetes, hypertension

Key Points

  • ICD-Pieces, an NIH Collaboratory Trial, was a cluster randomized, pragmatic clinical trial testing an intervention that used an electronic health record–based algorithm and practice facilitators in 141 primary care practices.
  • The study team randomly assigned more than 11,000 adults to receive either the intervention or usual care. The study population was diverse—20% were Black and almost 20% were Hispanic or Latino—representative of the population with chronic kidney disease, type 2 diabetes, and hypertension in the United States.
  • In the intervention group, the study team used an algorithm to identify patients in the electronic health record in real time.
  • Practice facilitators worked with the participating primary care providers and patients in the intervention group to meet blood pressure targets, promote use of appropriate medications, achieve goals for blood glucose control, and engage in other guideline-directed care. The intervention period lasted 12 months. The primary outcome was hospitalization for any reason.
  • The hospitalization rate was similar between the intervention group and the usual care group. Rates of key secondary outcomes, such as emergency department visits and cardiovascular events, were also similar between the groups.
  • The study team successfully completed study in 4 different health systems with a variety of EHR systems. The intervention was delivered with a high degree of fidelity, showing the feasibility of the study approach.
  • Engaging multiple stakeholders is key. Technology is helpful but not sufficient; delivery of the intervention required sustained effort.

Discussion Themes

- A more sustained intervention, greater engagement with pharmacists, and use of more patient-facing technology would have added to the success of intervention delivery.

- The longer the trial duration, the more complicated the challenges with site-level staff turnover, unanticipated changes in institutional policies and procedures, and changes in technology and EHR systems.

Tags

#pctGR, @Collaboratory1

Grand Rounds June 9, 2023: Emulating Randomized Clinical Trials with Non-randomized Real-world Evidence Studies: Results From The RCT DUPLICATE Initiative (Shirley V. Wang, PhD)

Posted on by Lauren Stewart

Speaker

Shirley V. Wang
Associate Professor
Division of Pharmacoepidemiology and Pharmacoeconomics
Brigham and Women’s Hospital
Harvard Medical School

 

Keywords

Pragmatic Clinical Trials; Emulation; Design; Database Study; Replicate

 

Key Points

  • RCT DUPLICATE is a series of methods NIH Collaboratory Trials with the the goal of understanding when and how database studies can support regulatory decision making. The first aim of the project is to use healthcare databases to emulate the design of 30 completed trials and predict the results of 7 ongoing trials. The goal with this aim is to determine if the same conclusion can be drawn from a database study and a trial. The second aim is to test the transparent and reproducible process with the FDA to evaluate Real World Evidence (RWE) studies. The third aim is to evaluate factors that predict concordance between the trials and the databases.
  • The study team used three predefined binary agreement metrics that they applied to each trial. They also used correlation coefficients to summarize agreement across the trial emulations.
  • The results showed that when the emulated trials were more pragmatic, the ability to closely emulate the trial design and obtain similar results was higher. However, when attempting to emulate a trial that had more explanatory design features, such as a run in or strict measures in place to ensure prolonged adherence, it was more difficult to disentangle whether the diversions in results were due to design emulation differences, which are differences between randomized controlled trials (RCT) and RWE, or biases, which are differences between RWE treatment arms.
  • In any trial emulation, researchers encounter design emulation differences in addition to potential sources of bias. The emulation differences in this trial included inclusion-exclusion criteria of the trial, population distribution, quality of the comparator emulation, outcome emulation, placebo control, in-hospital start time of medication, loading dose or dose titration protocol during follow-up, delayed effect with a long follow-up window, run-in window, discontinuation of maintenance therapy at randomization, and robustness of findings.
  • The team created an exploratory indicator that split the trials into two categories: those with fewer design emulation differences and those with more substantive design emulation differences. For trials with fewer emulation challenges, there was a closer agreement in agreement metrics. For trials with more emulation challenges, the correlation was low and results diverged more. The real benefit of database studies is the opportunity to generate evidence that is complementary to trials as well as to explore relevant clinical questions in which, for a variety of reasons, a trial cannot be conducted.
  • When the team was able to emulate the design and analysis closely, database studies often drew similar conclusions as trials. It is more challenging to emulate trials that are designed with many constraints to show effects under ideal conditions. The team saw greater success when replicating results of trials with more pragmatic design features.
  • When evaluating when and how RWE studies complement RCTs, it’s important to consider the target trial design that would best match the need or questions of the end users.

Discussion Themes

–What’s next for this initiative? Ongoing work we’re tackling is understanding that the methods and validity of trial emulation using EHR data or EHR-linked claims instead of claims data alone, as we used for these 32 trial emulations. We’ve also launched a spin-off project called ENCORE which is focused on emulating oncology trials using oncology specialty EHR data.

–What are you interested in on the analytic front regarding this topic? In general, I feel that the design trumps analytics in this case. We’re getting through the study design and making sure we’re asking the right questions. A lot of these analytics are about dealing with confounding in a better way, but if you can’t get the design right, then the analytics aren’t going to be closer.

-How do we teach our students and colleagues how to use the target trial framework and use these emulation approaches to advance our comparative effectiveness studies? It’s useful to lay out the parameters, or all of the questions to define the estimate for the target trial, whether hypothetical or real. Then lay out the same parameters you’re intending to set next to the real-world data. In our case, we color-coded these parameters and made a decision on whether it was feasible to continue or not based on whether it was possible to answer that same question. It’s a great approach to directly compare the parameters to see what question you’re truly asking.

Tags

#pctGR, @Collaboratory1

Grand Rounds June 2, 2023: PROACT Xa and The Wizard of Oz: Behind the Curtain of a Pragmatic Decentralized Clinical Trial (John Alexander, MD, MHS)

Posted on by Elizabeth Mccamic

Speaker

John Alexander, MD, MHS
Professor of Medicine/Cardiology
DCRI/Duke University

 

Keywords

PROACT Xa, Aortic Valve Replacement, Warfarin, Apixaban, Pragmatic Clinical Trial

 

Key Points

  • In the PROACT Xa trial, researchers wanted to learn if patients with an On-X mech valve implanted in the aortic position can be maintained on a factor Xa inhibitor (Apixaban) with a safe level of thromboembolic events compared to standard warfarin.
  • The trial was designed to randomize 1,000 patients who had an On-X aortic valve replacement at least 3 months prior to randomization with either a standard dose of Apixaban (5mg) or continued warfarin (the standard of care). The primary endpoint was composite of valve thrombosis or valve-related thromboembolism, and the primary safety endpoint was major bleeding. The drugs were administered open label and all patients were given a low dose of aspirin. The trial took place at 64 sites, and randomized 863 patients.
  • Sites were selected based on their On-X AVR volume, and the study leveraged the surgeon/patient relationship for recruitment. The study used remote enrollment, and there was also a centralized outreach to patients with On-X AVR by mail to all U.S. patients with a link to clinicaltrials.gov to learn more about the study. Several sites could enroll patients from outside of their system, based on regional or state requirements from local IRBs.
  • The study drug was mailed directly to participants, and at the end of the trial participants were instructed to destroy the drug. The price for Apixaban was $600 per bottle/$6M, and the price for warfarin was $50K. Follow up was conducted with a standardized script to ascertain events, and medical records were collected for event adjudication.
  • On Sept. 21, 2022, the PROACT Xa  DSMB recommended stopping enrollment and transitioning patients off of the study drug due to an observed excess in thromboembolic events in the Apixaban arm compared to the warfarin arm. Enrollment was stopped and all enrolled patients were contact to transition off of the study drug and back onto standard of care warfarin.
  • Of the total 863 enrolled patients, 20 on Apixaban had a valve thrombosis or valve-related thromboembolism event, compared to 6 events in the warfarin arm. The study determined that Apixaban was not non-inferior to warfarin for the prevention of valve thrombosis or valve-related thromboembolism and resulted in more thromboembolic events than warfarin in patients with an On-X mechanical aortic valve.

Learn more

Read about the PROACT Xa study.

Discussion Themes

-What was your impression of the challenges imposed for doing this trial? Tracy Wang: It is safe to say that none of us predicted COVID, and it hit pretty soon after we started enrollment. We never had to make too many procedural operations because everything was set up as much as possible for remote recruitment. The pragmatic elements were already in place so when COVID happened the main thing that had the biggest impact on our study was the shortage of study coordinators that effected every trial, and a few of our study sites went under due to difficulty of staffing and sustaining a research enterprise. We never had an amendment to the protocol.

-How are you taking it forward now that you are at PCORI? Tracy Wang: What lessons learned are your taking forward at PCORI? There are several things that are going to be in the PCORI rubric. We have a strong focus on comparative effectiveness and looking at critical health decisions. We are trying to do more of that and ask the more impactful questions to help patients and stakeholders make critical decisions in their care. From a funder’s perspective, trials of this size and impact can be done for prices that are not in the $200-300 million range. A lot of this has to do with the infrastructure, PROACT tapped into a unique device infrastructure.

-Since you demonstrated that a couple sites were able to care for subjects in any location, would you say more about the value that the additional separate clinical sites provided? John Alexander: One of the things we did in PROACT X-a is we allowed flexibility. There were sites that did no remote consent or enrollment. We said that was fine. Then others did remote. At times they changed their mind, based on other people doing it. There were some sites that allowed remote within a specific region. There were 2 sites that would take patients from anywhere in the U.S. It was very individualized.  Tracy Wang: Until there is more widespread experience in supporting decentralized trials, I do think there’s still value to the “local” clinical sites and certainly more patient familiarity and comfort.

Tags

#pctGR, @Collaboratory1

Grand Rounds May 19, 2023: Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis After a Fracture (Robert O’Toole, MD)

Posted on by Elizabeth Mccamic

Speaker

Robert O’Toole, MD
Chief of Orthopaedics, R Adams Cowley Shock Trauma Center
Head, Division of Orthopaedic Trauma
Department of Orthopaedics
Director, Clinical Research, Department of Orthopaedics
University of Maryland School of Medicine

 

Keywords

Pragmatic trials, orthopedic surgery, orthopedic trauma, Venous thromboembolism

 

Key Points

  • Venous thromboembolism (VTE) is a potentially fatal complication after orthopedic trauma. Prophylaxis (chemical or mechanical) reduces risk deep vein thrombosis (DVT) by around 50%. The North American guideline is to give Low Molecular Weight Heparin (LMWH) in cases of orthopedic trauma for VTE prophylaxis.
  • Aspirin is now the most commonly used VTE prophylaxis for Arthroplasty patients, in which Aspirin and LMWH are both safe and effective prophylaxis options.
  • Aspirin as an oral pill is a less expensive and easier option for the orthopedic trauma population, which has a high proportion of uninsured patients. Researchers aimed to test the safety and effectiveness of Aspirin use as prophylaxis in orthopedic trauma cases.
  • A pilot study, called the ADAPT trial, demonstrated feasibility, similar in-patient compliance and similar post-discharge adherence for the 2 options.
  • Through the Patient-Centered Outcomes Research Institute (PCORI), the team conducted a Discrete Choice Experiment (DCE), which highlighted patient concern for risk of death compared to risk of complication. This inspired the research team to shift the primary outcome to death.
  • Aspirin vs. Low Molecular Weight Heparin for Thromboprophylaxis: A Randomized Clinical Trial of Over 12,000 Orthopedic Trauma Patients (PREVENT CLOT) was conducted through METRC at 21 centers across the country.
  • The primary hypothesis was that all-cause mortality is non-inferior with Aspirin compared to LMWH among orthopedic trauma patients. The study required an FDA exemption because Aspirin is not approved for this indication. The pragmatic randomized control trial was designed from a hospital policy perspective.
  • Adult patients who fit the inclusion criteria were randomized at the patient level and stratified by treatment site. Patients and clinicians were non-blinded.
  • The primary outcome was all-cause mortality. Secondary outcomes were pulmonary embolism-related death, non-fatal pulmonary embolism, and DVT. Secondary safety outcomes were bleeding events, wound complications, and surgical site infections.
  • The study found that Aspirin is non-inferior to LMWH in preventing all-cause mortality after orthopedic trauma. There were similar results in the secondary outcomes, except LMWH showed lower risk of distal DVT. Therefore, it can be considered an acceptable option when clinicians, patients and hospital consider these data.
  • Using the Win Ratio, which strategically considers the primary outcome as well as secondary outcomes like patient satisfaction, the researchers found that Aspirin was still acceptable even among higher-risk patients.

 

Discussion Themes

-Researchers decided to use a two-arm study with only Aspirin because of its low cost and its use in orthopedic arthroplasty.

-While people may be interested in specific subpopulations or outcomes, the confidence interval is not adjusted for multiple comparisons, so slicing the data could risk spurious findings.

-Clinician buy-in and understanding the social component of clinical work was essential to the pragmatic trial.

-The research team did not run into institutional barriers in the trial, likely because of the opportunity of Aspirin to be a much lower cost option if proven safe and effective.

Tags

#pctGR, @Collaboratory1

Grand Rounds May 12, 2023: Design and Pragmatic Trial of COACH: A Patient Portal/EHR Information System for Home Blood Pressure Monitoring in Hypertension (Richelle J. Koopman, MD, MS)

Posted on by Elizabeth Mccamic

Speaker

Richelle J. Koopman, MD, MS
Jack M. and Winifred S. Colwill Professor and Vice Chair
Department of Family and Community Medicine
University of Missouri

 

Keywords

Electronic Health Record, Pragmatic Clinical Trial

 

Key Points

  • Patients bring patient-generated home blood pressure data into the clinical workflow. It is difficult to enter and create visualizations of this data in the electronic health record (EHR), so the research team developed an EHR data visualization of home blood pressure from data entered via the patient portal.
  • Starting in 2015, researchers held 10 focus groups with patients, family medicine and general internal medicine physicians and 1 CMIO. Researchers assessed the effect of the data visualization on patient risk perception and the interaction of health literacy, numeracy, and graph literacy with the data visualization.
  • The team’s goals were to design for the primary care setting because 85% of hypertension care is in this setting. The team wanted the visualization designed for shared decision making, with an emphasis on patient information needs and comprehension and physician information needs and workflow. The visualization needed to have an intuitive design, and the team was cognizant of how data visualization can affect decision making.
  • The data visualization started with a basic list of information needed, including systolic and diastolic data; clinic and home data; raw data numbers, effect of medications on blood pressure; goal ranges; out of range values; customizable goal ranges; patient burden of entry; data variability relative to control, and contextual life event data. From there, the team iterated based on patient-physician needs, resulting in the COACH (Collaborative Oriented Approach to Controlling High Blood Pressure) app.
  • Later this year, the study team will launch the COACH trial, a pragmatic clinical trial with 550 adult primary care patients with uncontrolled hypertension who are portal users. The trial will take place across 3 sites, University of Missouri, OHSU, and Vanderbilt and across 2 EHR platforms, EPIC and Oracle. The primary outcome is blood pressure at 6 months. The trial is doing a consolidated framework for implementation research to understand the preferred workflows and concerns for patients and physicians.

 

Discussion Themes

-Who provided the text support for the app and how were they resourced and trained? We specified adverse events that were largely hypotension, ER visits and hospitalizations. We are evaluating the usability of the app. At MU we have a collaboratory called the Tiger Institution that does programming. They estimated 5,000 hours to put it in the EHR, and they did it for free. We are paying now. It works in the Oregon EPIC EHR, and we are working on translating it to Vanderbilt.

–Can you speak to sustainability and what you are doing with billing codes? It was data that was sitting there without alerts in our system. We need to have some way to create a better actionable alert. There is billing potential here. There are mechanisms to bill for home blood pressure monitoring for Medicare. The sustainability comes from being able to bill for these services and keeping it lean in messaging.

–What about the patients who are not in the portal? That is definitely a problem. At MU and OHSU we are at about 80-90%. You can access the portal from desktop and phones. Lots of people have smartphones but they do not have the portal. Vanderbilt has a plan for bridging this gap through care managers.

Tags

#pctGR, @Collaboratory1

Grand Rounds May 5, 2023: All of Us Research Program: Improving Health Through Diverse Technology, Huge Cohorts, and Precision Medicine (Joshua C. Denny, MD, MS)

Posted on by Elizabeth Mccamic

Speaker

Joshua C. Denny, MD, MS
CEO, All of Us Research Program

 

Keywords

Precision Medicine, All of Us Research Program

 

Key Points

  • The mission of the All of Us Research Program is to accelerate health research and medical breakthroughs, enabling individualized prevention, treatment, and care for all of us.  The program will nurture partnerships for decades with at least a million participants who reflect the diversity of the U.S.; deliver one of the largest, richest biomedical datasets that is broadly available and secure; and catalyze an ecosystem of communities, researchers, and funders who make All of Us an indispensable part of research.
  • Participation in All of Us is open to all and reflects the rich diversity of the U.S. Participants are partners, and trust will be earned through transparency. Participants have access to their information, data will be access broadly for research purposes, and security and privacy will be of highest importance. The program will be a catalyst for positive change in research.
  • All of Us started in 2016 by asking communities what is important to them. The program held 77 listening studios in 17 cities with 654 community members. More than 631,000 participants have enrolled in All of Us with continued growth. More than 80% of All of Us participants are underrepresented in biomedical research.
  • Returning value is a key part of the program. Participants shared that genetic information is a type of information they want to get back. All of Us also provides back survey data, EHR and claims data, ongoing study updates, aggregate results, scientific findings, and opportunities to be contacted for other research opportunities.
  • All of Us has a philosophy to get data to researchers quickly. The Research Workbench data browser is available with no log in and you get aggregate results. The Researcher Workbench is a cloud-based central resource with a passport access model. It is currently open to U.S. nonprofits and nonprofit/for-profit academic and healthcare organizations.
  • By the end of 2026, the goal is to reach 1 million participants who reflect the diversity of the U.S., cover the lifespan, and have shared all baseline elements. Of these participants, 500,000 participate in ongoing data donation opportunities. All of Us will expand the data available for participants, launch ancillary studies as a core and scalable capability, establish a diverse global community of 10,000 researchers, and incorporate participant return of value into data collections and assess its impact.
  • All of Us is currently working on developing a pediatric population and will soon be launching 2 modules looking at mental health and well-being.

 

Discussion Themes

-From a researcher perspective, how do researchers leverage All of Us and how should the costs be included in grants and funding opportunities? New researchers get $300 of free credits which will handle a lot of EHR access. At the NIH we are recognizing that we want this to be part of people’s grants. We are a platform, so we do not have awards open that support science. Those funds would come from NIH.

–How can one use this for prospective studies? We are thinking about this as the future of these studies. We are not at the capability yet where we can open this up. We want to make sure that we are not an off ramp for clinical trials. We want trials to adhere to our core values and have the data come back to our ecosystem. We are looking forward to supporting more.

Tags

#pctGR, @Collaboratory1

Grand Rounds April 28, 2023: Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation: An Embedded Cluster-crossover Trial (Matthew W. Semler, MD, MSc)

Posted on by Elizabeth Mccamic

Speaker

Matthew W. Semler, M.D., M.Sc.
Assistant Professor of Medicine and Biomedical Informatics
Medical Director, VICTR Center for Learning Healthcare
Vanderbilt University Medical Center

 

Keywords

Pragmatic Clinical Trials, Cluster-crossover Trial

 

Key Points

  • More than 3 million adults receive invasive mechanical ventilation each year in the U.S. and providing mechanical ventilation to critically ill adults involved titrating the fraction of inspired oxygen (FiO2) to maintain arterial oxygenation. Yet, even though millions of patients have received oxygen during mechanical ventilation in clinical care for decades, the oxygen target that optimizes outcomes has been unknown.
  • There are 3 basic approaches to oxygenation targets in clinical care. There is an approach that targets values in the low end of the range commonly seen in critical care (about 88-92% range of SpO2 values), an approach that targets a middle range (92-96% SpO2), or an approach that targets values at the higher end of the range (96-100% SpO2).
  • Each approach has theoretical pros and cons, with oxygen levels on the higher end providing a larger buffer against hypoxia but might increase exposure to hyperoxymia while oxygen levels in the lower range might minimize those risks but might not provide as big a buffer against hypoxia, and oxygen levels in the middle of the range might avoid the risk of hyperoxia and hypoxia or might intermittently expose patients to both sets. Because of the lack of data about these 3 approaches, the recommended targets vary among 3 international guidelines.
  • In 2017 the study team developed a pilot trial with the aim of determining the effect of lower intermediate and higher SpO2 targets on clinical outcomes for mechanically validated critically ill adults.
  • The pilot trial was a pragmatic, unblinded, cluster-randomized, cluster-crossover trial that began in April 2018, paused from April 1-May 31, 2020 due to the COVID-19 pandemic, and concluded on Aug. 31, 2021. Study sites were in the emergency department and medical intensive care unit at Vanderbilt University. All adults in the medical ICU or in the ED with planned medical ICU admission were eligible and enrolled at the time of the first receipt of invasive mechanical ventilation.
  • All patients in the ED and ICU were assigned together to an SpO2 target. Every 2 months, the ED and ICU switched together between SpO2 targets in a sequence generated by computerized randomization using permuted blocks of 3 to minimize impact on seasonal variation of changes over time. There was a washout period the last 7 days of each two-month period. The trial was conducted under waiver of informed consent.
  • For the intervention, respiratory therapists titrated FiO2 to achieve SpO2 beginning within 15 minutes of initiation of mechanical ventilation and ending at discontinuation from mechanical ventilation or transfer. If a clinician, patient, or family member determined that an oxygenation target other than the assigned target would be best for the patient, that target was used and the reason was recorded.
  • The primary outcome was ventilator-free days, the number of days alive and free of mechanical ventilation through study day 28. The secondary outcome was in-hospital mortality. The sample size was 2,250 patients over 36 months.
  • The pilot trial found that for mechanically ventilated critically ill adults, clinical outcomes do not differ between lower, intermediate, and higher SpO2 targets. This was also true for all prespecified subgroups, and the 3 target groups did not differ for the secondary, exploratory, and safety outcomes.

 

Discussion Themes

-What was the experience doing these repeated crossovers? I think this is philosophically something that our ICU is used to when we don’t know what the right treatment is for a patient. That culture is very deep in our ICU and we benefited from it. The amount of education and interaction with clinical personnel at the start of the trial and at the first crossover is huge to help understand why we are doing this. By the second half of the trial, our team is available but everyone knows what and why we are doing it. For this type of trial all of the work happens in the first 3 months and then it is more streamlined?

–How many times were patients not included because the clinician had a good idea of the target for the patient. About 5% of patients developed a condition where the clinician knew what the target should be. For many patients, this did not happen. It was important to us that clinicians exercise their autonomy when they had the evidence needed to provide treatment

Tags

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