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ARCHIVED – What is a Pragmatic Clinical Trial
Section 2
The Embedded Pragmatic Clinical Trial Ecosystem – ARCHIVED
Definition of a Pragmatic Clinical Trial
According to Califf and Sugarman (2015), there are “three key attributes of PCTs: (1) an intent to inform decision-makers (patients, clinicians, administrators, and policy-makers), as opposed to elucidating a biological or social mechanism; (2) an intent to enroll a population relevant to the decision in practice and representative of the patients or populations and clinical settings for whom the decision is relevant; and (3) either an intent to (a) streamline procedures and data collection so that the trial can focus on adequate power for informing the clinical and policy decisions targeted by the trial or (b) measure a broad range of outcomes. Given these attributes, a common-sense definition for a PCT would thus be as follows: Designed for the primary purpose of informing decision-makers regarding the comparative balance of benefits, burdens and risks of a biomedical or behavioral health intervention at the individual or population level."
Watch the video module: What Are Pragmatic Clinical Trials?
Embedded PCTs Bridge Clinical Care and Research
To achieve generalizable results in an efficient manner, ePCTs commonly take place in the settings where patients already receive their usual clinical care. In contrast with traditional RCTs, the intention is to avoid the need for a separately constructed infrastructure with specially trained research staff responsible for data collection. For a broader, more representative population, eligibility criteria are minimized and recruitment expanded to potentially all eligible individuals receiving care in the participating setting. Intervention delivery, participant follow-up, and adherence protocols are more flexible and closely align with usual care in order to understand the real-world implications of the intervention. Arguably, many of these pragmatic qualities occur along a spectrum, with some trials being more pragmatic than others (Thorpe et al. 2009).
NIH Collaboratory Trials
To explore the potential of ePCTs and establish best practices, the NIH Pragmatic Trials Collaboratory supports the design and implementation of the NIH Collaboratory Trials, which are ePCTs that address questions of major public health importance (Table).
Table. NIH Collaboratory Trials
| Trial |
Goal | Population and Setting | Unit of Randomization |
|---|---|---|---|
| ABATE Infection
Active Bathing to Eliminate Infection (NCT02063867) |
Evaluate the use of universal chlorhexidine bathing plus targeted nasal decolonization for methicillin-resistant Staphylococcus aureus carriers in hospitalized patients outside the intensive care unit | 339,902 patients in 194 non–critical care units in 53 hospitals | Cluster randomization by hospital |
| ACP PEACE
Advance Care Planning: Promoting Effective and Aligned Communication in the Elderly (NCT03609177) |
Test whether clinician communication skills training and patient video decision aids increase completion of advance care planning | Patients 65 years and older with advanced cancer in 36 oncology clinics in 3 healthcare systems | Stepped-wedge, cluster randomized trial |
| AIM-CP
Adapting and Implementing a Nurse Care Management Model to Care for Rural Patients With Chronic Pain (NCT06407115) |
Adapt and test a nurse care management model to provide comprehensive coordinated care for patients with chronic pain in rural communities | Adults with chronic pain in primary care clinics in 6 rural-serving healthcare systems in 2 practice-based research networks | Type 2 hybrid effectiveness-implementation trial with individual-level randomization |
| ARBOR-Telehealth
Advancing Rural Back Pain Outcomes Through Rehabilitation Telehealth (NCT06471920) |
Improve patient-centered outcomes and decrease opioid use among patients with chronic low back pain living in rural communities | Adults with chronic low back pain in primary care clinics in a healthcare system serving rural communities | Type 1 hybrid effectiveness-implementation trial with individual-level randomization |
| BackInAction
Pragmatic Trial of Acupuncture for Chronic Low Back Pain in Older Adults |
Evaluate the safety and effectiveness of acupuncture in older adults with chronic low back pain | 789 adults aged 65 years and older with chronic low back pain in 4 performance sites | Individual-level randomization |
| BeatPain Utah
Nonpharmacologic Pain Management in Federally Qualified Health Center Primary Care Clinics |
Improve pain management and reduce reliance on opioids for patients with chronic back pain in federally qualified health centers in Utah | Adults with chronic back pain in federally qualified health centers in Utah | Type 1 hybrid effectiveness-implementation trial with individual-level randomization |
| BEST-ICU
Behavioral Economic and Staffing Strategies to Increase Adoption of the ABCDEF Bundle in the ICU (NCT06184945) |
Build and evaluate behavioral economic and implementation science theory-based interventions fostering ABCDEF bundle adoption and improving the clinical outcomes of critically ill adults | Critically ill adults on mechanical ventilation in 12 intensive care units in 3 hospitals | Stepped-wedge, cluster randomized trial |
| Chat 4 Heart Health
Using Artificially Intelligent Text Messaging Technology to Improve American Heart Association’s Life’s Simple 7 Health Behaviors |
Evaluate the implementation and effectiveness of 3 automated patient communication approaches for self-management support to improve control of cardiovascular disease risk factors defined by the American Heart Association’s Life’s Simple 7 Risk Factors | Patients in 3 federally qualified health centers | Individual-level randomization |
| EMBED
Pragmatic Trial of User-Centered Clinical Decision Support to Implement Emergency Department-Initiated Buprenorphine for Opioid Use Disorder (NCT03658642) |
Test the effectiveness of user-centered computerized clinical decision support on rates of emergency department–initiated buprenorphine/naloxone and referral for ongoing medication-assisted treatment in patients with opioid use disorder | 5047 patients with opioid use disorder under the care of 599 attending physicians in 18 emergency department clusters across 4 healthcare systems in 5 states | Cluster randomization by emergency department |
| FM TIPS
Fibromyalgia TENS in Physical Therapy Study (NCT04683042) |
Test the feasibility and effectiveness of adding transcutaneous electrical nerve stimulation (TENS) nonpharmacologic treatment for pain and fatigue in patients with fibromyalgia (FM) | Approximately 6000 patients with fibromyalgia in 24 routine physical therapy clinics in 6 healthcare systems in rural and urban settings | Cluster randomization by clinic |
| GGC4H
Pragmatic Trial of Parent-Focused Prevention in Pediatric Primary Care: Implementation and Adolescent Health Outcomes in Three Health Systems (NCT04040153) |
Test the feasibility and effectiveness of implementing a universal evidence-based anticipatory guidance curriculum (Guiding Good Choices) for parents of early adolescents | 3 large integrated healthcare systems with 75 pediatric primary care practices serving 3600 families with adolescents aged 11 to 12 years | Cluster randomization by pediatrician within clinic |
| GRACE
Hybrid Effectiveness-Implementation Trial of Guided Relaxation and Acupuncture for Chronic Sickle Cell Disease Pain (NCT04906447) |
Determine the effectiveness of guided relaxation and acupuncture compared with usual care in decreasing pain and opioid use for patients with sickle cell disease | Adults with sickle cell disease in 3 large healthcare systems | Cluster randomization |
| HiLo
Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (NCT04095039)
|
Test the effects of liberalizing the serum phosphate target (“Hi”) versus maintaining aggressive phosphate control (“Lo”) | Approximately 4400 patients with end-stage renal disease receiving maintenance hemodialysis at 100 sites in 2 large dialysis provider organizations | Cluster randomization |
| I CAN DO Surgical ACP
Improving Completion, Accuracy, and Dissemination of Surgical Advance Care Planning (NCT06090552) |
Use a model of expanded advance care planning as the foundation to support advance care planning engagement in older adults undergoing surgery | Patients 65 years and older, or with serious illness, who are referred for major elective surgery in 3 healthcare systems | Individual-level randomization |
| ICD-Pieces
Improving Chronic Disease management with Pieces (NCT02587936) |
Improve care for patients with chronic kidney disease, diabetes, and hypertension by using a novel technology platform (Pieces) that uses the electronic health record to identify patients and by assigning practice facilitators within primary care practices or community medical homes | 11,182 patients with coexisting chronic kidney disease, type 2 diabetes, and hypertension in 141 primary care practices in 4 healthcare systems | Stratified cluster randomization of clinical practices within healthcare systems |
| IMPACt-LBP
Implementation of the American College of Physicians Guideline for Low Back Pain |
Evaluate the effect of first-contact patient referral to physical therapists and doctors of chiropractic; determine if initial contact with these “primary spine practitioners” will improve physical function, decrease pain, and decrease opioid prescriptions in patients with a primary complaint of low back pain | Adults with low back pain in 3 academic healthcare systems | Cluster randomized trial |
| INSPIRE
Intelligent Stewardship Prompts to Improve Real-Time Empiric Antibiotic Selection for Patients (NCT05423743 and NCT05423756) |
Improve physicians’ choice of antibiotics for patients hospitalized with abdominal, skin, or soft tissue infections by reducing the unnecessary use of extended-spectrum antibiotics | Hospitalized adults with abdominal, skin, or soft tissue infection in 90 hospitals | Cluster randomized trial |
| iPATH
Implementing Scalable, Patient-Centered Team-Based Care for Adults with Type 2 Diabetes and Health Disparities (NCT06251323) |
Refine and test an innovative practice transformation strategy to improve type 2 diabetes for NIH-designated priority populations | 12 clinics in federally qualified health centers in 4 regions | Stepped-wedge, cluster randomized, type 2 hybrid effectiveness-implementation trial |
| LIRE
Lumbar Image Reporting with Epidemiology (NCT02015455)
|
Determine if inserting epidemiological benchmarks (essentially representing the normal range) into lumbar spine imaging reports reduces subsequent tests and treatments | 250,401 patients with low back pain in 98 clinics in 4 healthcare systems | Cluster randomization by clinic; stepped-wedge, one-way crossover design |
| MOMs Chat & Care Study
Maternal Outcomes Program: Testing Integrated Maternal Care Model Approaches to Reduce Disparities in Severe Maternal Morbidity (NCT06335381) |
Test the effectiveness of an integrated care model approach at 2 different levels of intensity designed to facilitate timely, appropriate care for high-risk Black birthing people and reduce risk for severe maternal morbidity | Black/African American pregnant adults at high risk for severe maternal morbidity in 1 obstetrics practice site | Individual-level randomization |
| NOHARM
Nonpharmacologic Options in Postoperative Hospital-based and Rehabilitation Pain Management (NCT04570371)
|
Evaluate the feasibility of EHR-embedded patient- and clinician-facing decision support for nonpharmacologic pain care after surgery | Approximately 54,000 postoperative patients in 22 practice clusters in 4 large integrated healthcare systems | Cluster randomization by practice cluster |
| Nudge
Personalized Patient Data and Behavioral Nudges to Improve Adherence to Chronic Cardiovascular Medications (NCT03973931) |
Use pharmacy refill data to test effectiveness of medication reminder nudges delivered to patients’ mobile phones, and test an interactive chat bot mechanism that optimizes content | 14,700 patients with chronic cardiovascular conditions who take medications in 3 large integrated healthcare systems | Individual-level randomization |
| OPTIMUM
Group-Based Mindfulness for Patients With Chronic Low Back Pain in the Primary Care Setting (NCT04129450) |
Evaluate a group-based mindfulness program (mindfulness-based stress reduction) for patients with chronic low back pain within primary care | Approximately 450 patients with chronic low back pain in primary care clinics in 3 large healthcare systems | Individual-level randomization |
| PPACT
Pain Program for Active Coping and Training (NCT02113592) |
Help patients adopt self-management skills for chronic pain, limit use of opioid medications, and identify factors amenable to treatment in the primary care setting | 850 patients with chronic pain on long-term opioid therapy in 3 staff model health plans; 106 clusters of primary care providers | Cluster-randomization by primary care provider |
| PRIM-ER
Primary Palliative Care for Emergency Medicine (NCT03424109) |
Test effectiveness of primary palliative care education, training, and technical support for emergency medicine | Patients 66 years and older with serious life-limiting illness in 35 emergency departments (4983 providers) | Cluster randomization; stepped-wedge design |
| PROVEN
Pragmatic Trial of Video Education in Nursing Homes (NCT02612688) |
Determine if showing advanced care planning videos in nursing homes affects the rates of hospitalization | 166,196 patients with comorbid conditions in 359 nursing homes in 2 nursing home healthcare systems serving long-stay (>12 months) patients | Cluster randomization by nursing home |
| RAMP
Reaching Rural Veterans: Applying Mind-Body Skills for Pain Using a Whole Health Telehealth Intervention |
Improve pain management and reduce opioid use among rural patients in the VA system | Veterans with chronic pain living in rural areas in the VA healthcare system | Type 2 hybrid effectiveness-implementation trial with individual-level randomization |
| SPOT
Suicide Prevention Outreach Trial (NCT02326883) |
Compare outcomes in patients who receive care-management or online skills training for suicide prevention versus usual care | 18,889 individuals at elevated risk for suicide in 4 large healthcare systems | Individual-level randomization |
| STOP CRC
Strategies and Opportunities to Stop Colon Cancer in Priority Populations (NCT01742065) |
Improve the rates of colorectal cancer screening by mailing fecal immunochemical testing tests to patients at federally qualified health centers | 41,193 adults eligible for colorectal screening in 26 federally qualified health center clinics in 8 health centers | Cluster randomization by clinic |
| TAICHIKNEE
Remote Tai Chi for Knee Osteoarthritis: An Embedded Pragmatic Trial |
Test a remote tai chi mind-body program in multiple healthcare systems’ outpatient practices using web-based technology, designed to improve patient centered outcomes of symptomatic knee osteoarthritis | Adults with a clinical diagnosis of knee osteoarthritis in 20 to 25 clinics in 4 healthcare systems in 4 geographic regions | Individually randomized group treatment trial |
| TiME
Time to Reduce Mortality in End-Stage Renal Disease (NCT02019225) |
To determine whether increasing hemodialysis session duration reduces mortality and hospitalization rates for patients receiving maintenance hemodialysis care | 7035 adults who had initiated treatment with maintenance hemodialysis within the previous 120 days in 266 dialysis units operated by 2 dialysis provider organizations | Cluster randomization by dialysis facility |
| TSOS
Trauma Survivors Outcomes and Support (NCT02655354) |
To coordinate care and improve outcomes for trauma survivors with post-traumatic stress disorder (PTSD) and comorbidity and to provide the American College of Surgeons with multisite pragmatic trial evidence that could further inform regulatory policy | 635 hospitalized adult survivors of physical injury with PTSD and comorbidity in 25 level 1 trauma centers | Cluster randomization by trauma center; stepped-wedge design |
Extending the Reach of the ePCT Ecosystem
PCORnet
The National Patient-Centered Clinical Research Network (PCORnet) links multiple integrated health systems and ‘‘patient-powered’’ networks to conduct comparative effectiveness research and explore questions about conditions, care, and outcomes that matter most to patients and their families. PCORnet consists of clinical data research networks and patient-powered research networks that are linked through a distributed research network (DRN) to facilitate multi-site, observational, and interventional research (Fleurence et al. 2014). The DRN harnesses data from the electronic health record for research, allows each participating organization to maintain physical and operational control over their data, and minimizes the transfer of individual-level clinical data (Fleurence et al. 2014). PCORnet’s first PCT is ADAPTABLE: the Aspirin Study (Johnston et al. 2016).
Pain Management Collaboratory
The Pain Management Collaboratory (PMC) is jointly supported by the National Institutes of Health (NIH), Department of Defense (DoD), and Veterans Affairs (VA). The program aims to develop the capacity to implement cost-effective large-scale pragmatic clinical research in military and veteran health care delivery organizations focusing on nonpharmacologic approaches to pain management and other comorbid conditions. The PMC supports 11 NIH Collaboratory Trials addressing such clinical areas as chronic low back pain, postoperative pain, and behavioral treatments for pain, among others.
National Institute on Aging (NIA) IMPACT Collaboratory
The NIA IMPACT Collaboratory aims to increase the nation’s capacity to conduct pragmatic clinical trials embedded within healthcare systems for people living with dementia and their caregivers. The NIA IMPACT Collaboratory is funding 1-year pilot studies that are meant to generate the preliminary data necessary to design and conduct full-scale ePCTs that will be funded through other grant mechanisms such as the NIH or other sources.
Real-World Data and Real-World Evidence
We believe that when the term "real-world evidence" is used, the primary attribute that distinguishes it from other kinds of evidence is related to the context in which the evidence is gathered—in other words, in clinical care and home or community settings as opposed to research-intensive or academic environments. (Sherman et al. 2016)
ePCTs can also be viewed within the context of recent discussions about real-world data (RWD) and real-world evidence (RWE). RWD is data relating to patient health status or the delivery of healthcare routinely collected from a variety of sources, such as electronic health records (EHRs), claims and billing activities, product and disease registries, patient-generated data, and data gathered from sources that can inform on health status (FDA). RWE is the clinical evidence regarding the usage and potential benefits or risks of a medical product derived from analysis of real-world data. RWE can be generated by different study designs or analyses, including but not limited to, randomized trials, including large simple trials, pragmatic trials, and observational studies (prospective and/or retrospective).
- For more on the role of RWD and RWE in ePCTs, read Real World Evidence: Mobile Health in the Living Textbook.
- In Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials: Real World Evidence: Contemporary Experience and Future Directions, a PCT Grand Rounds webinar, a panel discusses how quality real-world evidence cannot be built without quality real-world data.
In late 2021, the FDA issued 4 draft guidances for real-world data and real-world evidence intended to guide the selection and management of data sources to appropriately address study questions and support decision-making for drug and biological products. These draft guidances include:
- Real-World Data: Assessing Electronic Health Records and Medical Claims Data To Support Regulatory Decision-Making for Drug and Biological Products
- Data Standards for Drug and Biological Product Submissions Containing Real-World Data
- Real-World Data: Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products Guidance for Industry
- Considerations for the Use of Real-World Data and Real-World Evidence To Support Regulatory Decision-Making for Drug and Biological Products
Dr. John Concato, Associate Director for Real-World Evidence Analytics with the Food and Drug Administration (FDA), discusses this FDA guidance in the June 24, 2022 PCT Grand Rounds Webinar titled “ FDA Draft Guidance on Real-World Evidence,” and the July 14, 2022 Grand Rounds Podcast.
SECTIONS
sections
- Why Are We Talking About Pragmatic Trials? – ARCHIVED
- The Embedded Pragmatic Clinical Trial Ecosystem – ARCHIVED
- Differentiating Between RCTs, PCTs, and Quality Improvement Activities – ARCHIVED
- Pragmatic Elements: An Introduction to PRECIS-2- ARCHIVED
- PRECIS-2 Case Study – ARCHIVED
- Key Considerations for PCTs – ARCHIVED
- Additional Resources – ARCHIVED
REFERENCES
Califf RM, Sugarman J. 2015. Exploring the ethical and regulatory issues in pragmatic clinical trials. Clin Trials. 12:436–441. doi:10.1177/1740774515598334.
Fleurence RL, Curtis LH, Califf RM, Platt R, Selby JV, Brown JS. 2014. Launching PCORnet, a national patient-centered clinical research network. J Am Med Inform Assoc. 21:578–582. doi:10.1136/amiajnl-2014-002747.
Johnston A, Jones WS, Hernandez AF. 2016. The ADAPTABLE Trial and Aspirin Dosing in Secondary Prevention for Patients with Coronary Artery Disease. Curr Cardiol Rep. 18:81. doi:10.1007/s11886-016-0749-2.
Sherman RE, Anderson SA, Dal Pan GJ, et al. 2016. Real-World Evidence - What Is It and What Can It Tell Us? N Engl J Med. 375:2293-2297. doi:10.1056/NEJMsb1609216. PMID: 27959688.
Thorpe KE, Zwarenstein M, Oxman AD, et al. 2009. A pragmatic-explanatory continuum indicator summary (PRECIS): a tool to help trial designers. J Clin Epidemiol. 62:464–475. doi:10.1016/j.jclinepi.2008.12.011. PMID: 19348971.
current section : The Embedded Pragmatic Clinical Trial Ecosystem – ARCHIVED
- Why Are We Talking About Pragmatic Trials? – ARCHIVED
- The Embedded Pragmatic Clinical Trial Ecosystem – ARCHIVED
- Differentiating Between RCTs, PCTs, and Quality Improvement Activities – ARCHIVED
- Pragmatic Elements: An Introduction to PRECIS-2- ARCHIVED
- PRECIS-2 Case Study – ARCHIVED
- Key Considerations for PCTs – ARCHIVED
- Additional Resources – ARCHIVED