study design

December 11, 2020: PREVENTABLE: Starting a Pragmatic Trial in a Pandemic (Karen Alexander, MD; Schuyler Jones, MD)

Posted on by Gina Uhlenbrauck

Speakers

Karen P. Alexander, MD
Professor of Medicine/Cardiology
Duke University School of Medicine

W. Schuyler Jones, MD
Associate Professor of Medicine/Cardiology
Duke University School of Medicine

Topic

PREVENTABLE: Starting a Pragmatic Trial in a Pandemic

Keywords

Heart disease; Dementia; Cholesterol; Statins; Pragmatic trial; National Heart, Lung, and Blood Institute; National Institute on Aging; Mild cognitive impairment

Key Points

  • More than half of older adults (age 75+) in the United States have cognitive impairment or frailty or both.
  • PREVENTABLE is one of the largest research studies in older adults. The purpose is to learn if taking a statin could help older adults live well for longer by preventing dementia, functional decline, or heart disease.
  • The study medication (statin) is mailed directly to participants’ homes. Study sites are part of the research infrastructure within PCORnet and Veterans Affairs (VA).
  • Pragmatic aspects of the trial include the study question: Do statins work in practice for outcomes that matter most to older adults? Also, enrollment is telehealth-enabled, and consent is electronic (e-Consent).

Discussion Themes

How did the study team work with IT to make the EHR system changes (eg, tools and workflow) needed to conduct the research?

Are older participants able to interact well with the technology used in the trial?

Are there special considerations embedded within the study to encourage the retention of study participants?

Read more about the PREVENTABLE study.

Tags

#pctGR, @Collaboratory1

November 20, 2020: Drug Development in Kidney Disease: Proceedings from a Multi-Stakeholder Panel (Daniel Edmonston, MD)

Posted on by Gina Uhlenbrauck

Speaker

Daniel Edmonston, MD
Medical Instructor
Duke University School of Medicine

Topic

Drug Development in Kidney Disease: Proceedings from a Multi-Stakeholder Panel

Keywords

Chronic kidney disease (CKD); Dialysis; Evidence-based medicine; Electronic health records; Think Tank

Key Points

  • Only 5 percent of treatment recommendations for kidney disease reach a Grade A level of evidence.
  • In 2019, the DCRI convened a panel to address the urgent need for evidence-based treatments for kidney disease. “Accelerating Drug Development for Chronic Kidney Disease and End-Stage Renal Disease” included stakeholders from regulatory agencies, kidney societies, patient advocacy organizations, academia, and industry.
  • Key discussions explored the uses of interconnected data and site research networks, pragmatic and adaptive trial designs, robust surrogate endpoints, real-world data, and methods to improve the generalizability of trial results and uptake of approved drugs for kidney-related diseases.

Discussion Themes

Since there is more than one therapeutic agent showing promise for CKD, how should evidence be generated to understand the right combination of agents?

Could the principles laid out in the FDA Patient Focused Drug Development guidance be applied in these trials to ensure the patient perspective is included?

What are your thoughts on whether to focus on enrolling early CKD patients—some of whom will not progress—or patients later in the course of disease, when disease modification may be more challenging?

Read more about the Think Tank in a special report in the American Journal of Kidney Disease.

Tags

#pctGR, @Collaboratory1

November 13, 2020: Pragmatic and Explanatory Attitudes to RCTs: Using the PRECIS-2 Tool to Describe the Design of the MyTEMP Trial (Ahmed Al-Jaishi, PhD; Amit Garg, MD, PhD, Merrick Zwarenstein, MBBCh, MSc, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Ahmed Al-Jaishi, PhD (candidate)
Health Research Methodology
McMaster University

Amit Garg, MD, PhD
Professor, Department of Medicine
Epidemiology & Biostatistics
Western University, London, Canada
Senior Core Scientist, Site Director, and Program Lead
ICES Western Kidney Dialysis & Transplantation Research Program, London, Canada
Nephrologist, London Health Sciences Centre
Victoria Hospital, London, Canada

Merrick Zwarenstein, MBBCh, MSc, PhD
Professor, Department of Family Medicine
Epidemiology & Biostatistics
Western University, London, Canada
Senior Core Scientist
ICES Western Primary Care & Health Systems Research Program, London, Canada

Topic

Pragmatic and Explanatory Attitudes to RCTs: Using the PRECIS-2 Tool to Describe the Design of the MyTEMP Trial

Keywords

Pragmatic trials; PRECIS-2; Canadian Institutes of Health Research (CIHR); Study design; External validity

Key Points

  • Randomized controlled trial (RCT) intentions (attitudes) can be described as: pragmatic intentions provide evidence for decision-makers to choose between interventions, whereas explanatory intentions test a hypothesis about a mechanism.
  • Pragmatic and explanatory trials are not a dichotomy; a good trial design matches the intention of the trial.
  • Trials can be designed with both internal validity and external validity.
  • Different trial intentions, design choices, conclusions, and recommendations lead to different usefulness for decision-making.

Discussion Themes

Can you comment on the retrospective use of PRECIS-2 to dichotomize trials as pragmatic or explanatory?

What suggestions do you have to improve the labeling of trials as explanatory versus pragmatic, since both types are randomized controlled trials (RCTs)?

Read more about the PRECIS-2 tool and the CONSORT statement for pragmatic trials.

Tags

#pctGR, @Collaboratory1

November 6, 2020: Appendectomy Versus Antibiotics for Appendicitis–Early Results from the CODA Trial (David R. Flum, MD, MPH)

Posted on by Gina Uhlenbrauck

Speaker

David R. Flum
Professor, Surgery, Health Services, and Pharmacy
Associate Chair for Research, Department of Surgery
University of Washington

Topic

Appendectomy Versus Antibiotics for Appendicitis–Early Results from the CODA Trial

Keywords

Appendectomy; Antibiotic therapy; CODA Collaborative; Comparative effectiveness research; Patient-centered outcomes research; Pragmatic clinical trial; Noninferiority; PCORI

Key Points

  • The CODA (Comparing Outcomes of Drugs and Appendectomy) Collaborative involved 25 sites across 14 states. The Co-PIs included surgeons and emergency medicine physicians.
  • The CODA pragmatic trial aimed to inform the health decision for appendicitis treatment by asking two research questions:
    • Are antibiotics as effective as appendectomy for appendicitis?
    • Which patients are most likely to have a successful outcome with antibiotics?
  • Instead of appendectomy, the intervention group received antibiotics intravenously for 24 hours followed by pills for a  total of 10 days. The primary outcome in the trial was 30-day health status, as assessed with the European Quality of Life-5 Dimensions questionnaire.
  • The patients who received antibiotics cared about outcomes such as “Am I going to feel better,” followed by “Is it safe,” and “Will I return to work sooner?”

Discussion Themes

Antibiotics for appendicitis can be a good choice for some but not all. Decision-makers must weigh patient characteristics, preferences, and circumstances.

Can you comment on the relative “disappearance” of appendicitis during the COVID-19 pandemic? 

Based on your results, how would you counsel a patient (or parent) in the emergency department with a diagnosis of appendicitis?

Will there eventually be a biomarker that’s predictive for appendectomy?

Read more about CODA results in the New England Journal of Medicine.

Tags

#pctGR, @Collaboratory1

October 30, 2020: Lessons from Virtual Trials in Time of a Pandemic: Minnesota Hydroxychloroquine Experience (David Boulware, MD, MPH)

Posted on by Gina Uhlenbrauck

Speaker

David R. Boulware MD, MPH
Professor of Medicine
Infectious Disease & International Medicine
Department of Medicine
University of Minnesota

Topic

Lessons from Virtual Trials in Time of a Pandemic: Minnesota Hydroxychloroquine Experience

Keywords

COVID-19; Patient-reported outcomes (PROs); Hydroxychloroquine; Epidemiology; Virtual trials

Key Points

  • These virtual randomized controlled trials evaluated hydroxychloroquine as a post-exposure prophylaxis, pre-emptive early treatment, and pre-exposure prophylaxis for COVID-19.
  • The trial of post-exposure prophylaxis employed patient-reported outcomes around COVID-19 symptoms and severity as well as side effects of hydroxychloroquine.
  • Enrollment and screening of eligible participants was automated through a REDCap survey.

Discussion Themes

Being a virtual trial, were there concerns about practicing medicine “across state lines?”

There has been a mix of science and politics over the course of the COVID-19 pandemic. Because your trial had substantial media coverage, how did the publicity affect enrollment?

Many big strategy questions can be studied virtually. What changes do you see for trials during future pandemics?

Read reports of these virtual trials in New England Journal of Medicine, Annals of Internal Medicine, and the medRxiv preprint server.

Tags

#pctGR, @Collaboratory1

October 9, 2020: Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo) (Myles Wolf, MD)

Posted on by Gina Uhlenbrauck

Speaker

Myles Wolf, MD, MMSc
Division of Nephrology, Department of Medicine
Duke Clinical Research Institute
Duke University School of Medicine

Topic

Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo)

Keywords

End-stage renal disease; Hemodialysis; Serum phosphate; Patient-centered outcomes; NIDDK; Electronic health record; Cluster randomization; eConsent

Key Points

  • High serum phosphate is a ubiquitous complication in end-stage renal disease (ESRD), a serious illness that affects ~500,000 people in the United States. However, evidence is lacking for the best approach to reducing high phosphate that benefits survival in patients.
  • The hemodialysis setting is ideal for conducting a pragmatic trial because of an accessible study population, frequent clinical encounters, granular and uniform data collection via electronic health record (EHR), and the many unanswered questions about major aspects of dialysis care.
  • Pragmatic features of HiLo include:
    • Real-world setting
    • Cluster randomization
    • Broad entry criteria
    • Electronic informed consent
    • No traditional on-site study staff
    • Remote site monitoring
    • Outcomes based on EHR with no adjudication

Discussion Themes

The HiLo Ambassadors, a patient advisory group, have contributed to HiLo study materials including the protocol, informed consent form, eConsent script, informational videos, FAQs, flyer, and website content. They are providing strategies to help patients successfully participate and stay in the trial.

Dieticians are critical to the success of HiLo as they directly interact with dialysis patients and are among the most motivated caregivers on dialysis teams.

The onset of the COVID-19 pandemic came after the first week of HiLo site activation, causing a pause of trial activities and enrollment at the dialysis facilities.

What will success look like for the HiLo trial? A clear, proven answer to the question of higher versus lower target.

Read more about HiLo trial at the study website and the NIH Collaboratory Trials page.

Tags

#pctGR, @Collaboratory1

October 6, 2020: Four PRISM NIH Collaboratory Trials Awarded Continuation From Planning to Implementation Phase

Posted on by Gina Uhlenbrauck

The NIH Collaboratory is pleased to announce that the four PRISM NIH Collaboratory Trials received approval to transition from the planning phase to the implementation phase of their studies. These embedded PCTs (ePCTs) are directly addressing the U.S. opioid crisis and exploring fundamental questions of pain management using nonpharmacologic treatments.

Congratulations to the PIs and study teams for their excellent work!

BackInAction: Pragmatic Trial of Acupuncture for Chronic Low Back Pain in Older Adults

Karen Sherman, PhD, MPH
Photo of Lynn DeBar, principal investigator of PPACT
Lynn DeBar, PhD, MPH

BackInAction is conducting a three-arm pragmatic trial of older adults who have chronic low back pain to evaluate acupuncture versus usual care. The study will compare a standard 12-week course of acupuncture, an enhanced course of acupuncture (12-week standard course, plus 12-week maintenance course), and usual care to assess back-related function at 26 weeks.

 

 

 

 

FM TIPS: Fibromyalgia TENS in Physical Therapy Study

Kathleen Sluka, PT, PhD
Leslie Crofford, MD

The aim of FM TIPS is to demonstrate the feasibility of adding transcutaneous electrical nerve stimulation (TENS) to the treatment of patients with fibromyalgia in a real-world physical therapy setting, and to determine if adding TENS to physical therapy reduces pain, increases adherence to physical therapy, and allows patients with fibromyalgia to reach their specific functional goals with less medication use.

 

 

 

NOHARM: Nonpharmacologic Options in Postoperative Hospital-based and Rehabilitation Pain Management

Photo of Andrea Cheville, co–principal investigator of NOHARM
Andrea Cheville, MD
Jon Tilburt, MD

NOHARM is a stepped-wedge cluster-randomized trial that is testing a sustainable system-wide strategy for perioperative pain management using nonpharmacologic options in a manner that preserves patient function, honors patient values, and maintains availability of opioids as a last resort.

 

 

 

 

OPTIMUM: Group-based Mindfulness for Patients with Chronic Low Back Pain in the Primary Care Setting

Natalia Morone, MD

OPTIMUM aims to evaluate the impact of an innovative, group-based mindfulness program for patients with chronic low back pain in a real-life clinical setting. Mindfulness is effective for the treatment of chronic low back pain, yet remains underutilized as it has not been regularly woven into the outpatient clinical setting.

 

 

 

 

The PRISM program (Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing) is a component of the NIH’s Helping to End Addiction Long-term (HEAL) Initiative. The NIH Collaboratory serves as the PRISM Resource Coordinating Center and is supported by the National Center for Complementary and Integrative Health. Support is also provided by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director.

September 11, 2020: Launching CONNECTS: Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (Gordon Bernard, MD; Sonia Thomas, DrPH)

Posted on by Gina Uhlenbrauck

Speakers

Gordon R. Bernard, MD
CONNECTS ACC Science Unit P
Professor of Medicine
Executive Vice President for Research
Senior Associate Dean for Clinical Science
Vanderbilt University Medical Center

Sonia Thomas, DrPH
CONNECTS ACC Principal Investigator
Senior Research Statistician
RTI International

Topic

Launching CONNECTS: Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies

Keywords

COVID-19; CONNECTS; NHLBI; Collaborative research; Data sharing; Adaptive trials; Data standardization; ACTIV; Therapeutic agent prioritization

Key Points

  • The Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (CONNECTS) is a research partnership coordinated by the Research Triangle Institute, Vanderbilt University Medical Center, and the National Heart, Lung, and Blood Institute (NHLBI) of the NIH.
  • CONNECTS aims to build on existing clinical research networks to better understand the risk of severe illness from COVID-19 and to identify therapies that will slow or halt the disease progression and speed recovery. Studies will enroll participants with health conditions that are known to increase their risk for severe complications from COVID-19.
  • The immediate goal is to design and implement master protocol-driven adaptive clinical trials, including outpatient, inpatient, and recovering master protocols.
  • CONNECTS is part of a larger ecosystem in the Department of Health and Human Services that includes the FDA, CDC, BARDA, Operation Warp Speed, and NIH. More than 34 trial networks and 1,000 sites are participating in CONNECTS.

Discussion Themes

Are the CONNECTS resources, such as the common data elements manual, draft protocols, and case report forms, publicly available?

In your effort to reach underrepresented communities, have you considered collaborating with Historically Black Colleges and Universities (HBCUs), particularly those that conduct health research?

While COVID-19 is providing you with plenty to focus on, do you see the potential for sustainability of CONNECTS beyond this pandemic?

Read more about CONNECTS.

Tags

#pctGR, @Collaboratory1

August 31, 2020: Newly Validated Sample Size Formula Detects Heterogeneity of Treatment Effect in Cluster Randomized Trials

Posted on by Damon Seils

Cover of Statistics in MedicineIn a study supported by the NIH Collaboratory, researchers developed and validated a new sample size formula for detecting heterogeneity of treatment effect in cluster randomized trials. The work was published this month in Statistics in Medicine.

Cluster randomization is frequently used in pragmatic clinical trials embedded in healthcare systems. Although cluster randomized trials are typically designed to evaluate the overall treatment effect in a study population, investigators are increasingly interested in studying differential treatment effects among subgroups.

The NIH Collaboratory investigators used extensive computer simulations to validate the new formula. They illustrate the procedure in a dataset from a large clinical trial.

In a previous study published last year, the same research team used computer simulation models validated by real-data simulations to reveal the influence of baseline covariate imbalance on treatment effect bias.

This work was supported within the NIH Collaboratory by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director, and by a research supplement from the NIH Common Fund to promote diversity in health-related research.

August 27, 2020: Chapter on Acquiring Real-World Data Added to the Living Textbook

Posted on by Karen Staman

The NIH Collaboratory this week published a new chapter of its Living Textbook of Pragmatic Clinical Trials. The chapter, “Acquiring Real-World Data,” outlines strategies for obtaining real-world data for use in research.

“Real-world data” include data relating to the health status of a patient or the delivery of healthcare services. Common sources include electronic health records (EHRs), administrative claims, patient-reported outcomes, patient-generated health data, medical product and device registries, and databases relating to environmental factors or social determinants of health. Real-world data can support a number of activities in pragmatic clinical trials, such as patient identification and recruitment, monitoring of outcomes, and ascertainment of endpoints.

The new chapter includes the following sections:

The new chapter updates a previous resource, one of the most popular on the Living Textbook, based on work by experts in the NIH Collaboratory’s Electronic Health Records Core Working Group.