clinical trials

January 24, 2020: Cardiovascular Trials Over 2 Decades: Progress on Pragmatism? (Justin A. Ezekowitz, MBBCh, MSc)

Posted on by Gina Uhlenbrauck

Speaker

Justin A. Ezekowitz, MBBCh, MSc
Professor, Department of Medicine
Co-Director, Canadian VIGOUR Centre
Director, Cardiovascular Research, University of Alberta
Cardiologist, Mazankowski Alberta Heart Institute

Topic

Cardiovascular Trials Over 2 Decades: Progress on Pragmatism?

Keywords

Pragmatic clinical trials; PRECIS-2; Cardiovascular trials; Enrollment of women

Key Points

  • Pragmatic clinical trials are “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” (Califf & Sugarman, 2015).
  • This study examined how pragmatic or explanatory cardiovascular (CV) randomized controlled trials are; whether the level of pragmatism in CV trials has changed over 2 decades; and whether the proportion of women enrolled in CV trials has changed over 2 decades.
  • No clinical trial is completely explanatory or pragmatic. In this study, trials that scored higher on pragmatism (using the PRECIS-2 tool) had more sites, a larger sample size, longer follow up, and mortality as a primary endpoint.

Discussion Themes

Randomized controlled trials that were published in general medicine journals scored higher in pragmatism than those published in CV journals. Pragmatism has increased over time in CV trials.

While women account for ~45% of the burden of CV diseases, they are underrepresented in CV randomized controlled trials, with less than one-third of trial participants. There was no difference between pragmatic trials and other trials in terms of women’s enrollment.

Initiatives that focus on patient, clinician, and trial design factors are needed to address the gender gap in trial enrollment.

Read more about the PRECIS-2 tool in the Living Textbook, and Dr. Ezekowitz’s research in Trends in the Explanatory or Pragmatic Nature of Cardiovascular Clinical Trials Over 2 Decades (JAMA Cardiology, 2019).

Tags
#pctGR, @Collaboratory1

January 8, 2020: Registration Opens for 13th Annual Conference on Statistical Issues in Clinical Trials

Posted on by Damon Seils

Registration opened on January 1 for the 13th Annual University of Pennsylvania Conference on Statistical Issues in Clinical Trials. The theme of this year’s conference is “Cluster Randomized Clinical Trials: Challenges and Opportunities.”

The conference will be held on April 29 at the Smilow Center for Translational Research on the campus of the University of Pennsylvania Perelman School of Medicine in Philadelphia. Cosponsors include the American Statistical Association, the Society for Clinical Trials, and the National Institute of Statistical Sciences.

During the methods portion of the program, NIH Collaboratory investigator David Murray will present “Overview: Innovations in the Design and Analysis of Group- or Cluster-Randomized Trials.” The program also includes presentations on the uses of network- and individual-level information in design and analysis, the complexity introduced by noncompliance, current issues in stepped-wedge designs, and various applications of statistical techniques in cluster randomized studies.

Registration is required for this daylong event.

December 13, 2019: Reissuance of Funding Opportunity Announcement for HEAL Initiative/PRISM Coming January 2020

Posted on by Gina Uhlenbrauck

The National Center for Complementary and Integrative Health (NCCIH), with other NIH Institutes, Centers, and Offices, intends to reissue Funding Opportunity Announcement (FOA) HEAL Initiative: Pragmatic and Implementation Studies for the Management of Pain To Reduce Opioid Prescribing (PRISM) (UG3/UH3 Clinical Trial Optional).

This RFA solicits applications for phased cooperative research applications to conduct efficient, large-scale pragmatic or implementation trials to improve pain management and reduce the unnecessary use of opioid medications in the health care delivery setting. The re-issuance of the FOA will prioritize the following areas for pragmatic trials to integrate multimodal or multiple interventions that have demonstrated efficacy into health care systems or implement health care system changes to improve adherence to evidence-based guidelines:

  • Pain management in emergency departments, dental clinics, primary care, and hospitals
  • Chronic overlapping pain conditions
  • Pain management in individuals at risk of or with opioid use disorder
  • Pain management in those with co-occurring mental health disorders
  • Noncancer pain management in persons with medical comorbid conditions

The FOA is expected to be published in January 2020 with an expected application due date in March 2020.

The announcement is part of the NIH Heal (Helping to End Addiction Long-term) Initiative, which was created in April 2018 in an effort to speed scientific solutions for addressing the national opioid public health crisis.

 

December 13, 2019: New ePCT Training Materials Focus on Nephrology Research

Posted on by Gina Uhlenbrauck

Presentations from a recent seminar offered by the NIH Collaboratory in partnership with the American Society of Nephrology are now available on the Living Textbook. The seminar, Embedded Pragmatic Clinical Trials: Accelerating Evidence Generation in Nephrology, was held at ASN Kidney Week 2019. The sessions provide an introduction to concepts in the design of embedded pragmatic clinical trials (ePCTs), with a focus on interventions that are relevant to the nephrology research community.

Visit the NIH Collaboratory Training Resources to download the presentations.

November 1, 2019: NIH Collaboratory: Looking Back, Looking Forward (Adrian Hernandez, MD, MHS, Lesley Curtis, PhD, Kevin Weinfurt, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Adrian F. Hernandez, MD, MHS
Professor of Medicine
Vice Dean for Clinical Research
Duke University School of Medicine

Lesley H. Curtis, PhD
Chair and Professor
Department of Population Health Sciences
Duke University School of Medicine
Interim Executive Director, Duke Clinical Research Institute

Kevin Weinfurt, PhD
Professor and Vice Chair of Research
Department of Population Health Sciences
Duke University School of Medicine

Topic

NIH Collaboratory: Looking Back, Looking Forward

Keywords

Embedded pragmatic clinical trials; ePCTs; NIH Collaboratory; Health care systems research; NIH Collaboratory Trials; Living Textbook; HEAL Initiative; Coordinating Center; Research dissemination; Learning health systems; Real-world evidence

Key Points

Discussion Themes

How can we harmonize the different ideas about what it is to be “pragmatic” for NIH study sections, IRBs, and DSMB reviews? For example, if your DSMB isn’t knowledgeable about PCTs, you could end up with a very explanatory trial.

A willingness to share imperfections is an important part of learning and helps the clinical trial ecosystem evolve.

An important future topic would be how the NIH Collaboratory and PCORnet fit together.

Read more about the NIH Collaboratory Program and the Living Textbook of Pragmatic Clinical Trials.

Tags
#pctGR, #PragmaticTrials, @Collaboratory1, @texhern, @lmhcurtis, @KevinWeinfurt

October 30, 2019: Baseline Covariate Imbalance Influences Treatment Effect Bias in Cluster Randomized Trials

Posted on by Damon Seils

In a study supported by the NIH Collaboratory, researchers found that imbalance in individual-level baseline covariates influences bias in the observed treatment effect in cluster randomized trials. Using race as an example, the study highlights the importance of reducing covariate imbalance in the design stage of cluster randomized trials and of using statistical analysis techniques to minimize the resulting bias.

The innovative study, published in Contemporary Clinical Trials, used computer simulation models validated by real-data simulations from a large clinical trial to examine the influence of baseline covariate imbalance on treatment effect bias. They found that bias was proportional to the degree of baseline covariate imbalance and the covariate effect size. In the simulations, trials with larger numbers of clusters had less covariate imbalance. Statistical models that adjusted for important baseline confounders were more effective than unadjusted models in minimizing bias.

The authors recommend several design approaches and statistical analysis techniques for both reducing covariate imbalance and minimizing bias. Using the results of available prior data can help researchers identify important baseline confounders when designing cluster randomized trials.

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.

October 11, 2019: Objecting to Experiments that Compare Two Unobjectionable Policies or Treatments: Implications for Comparative Effectiveness and Other Pragmatic Clinical Trials (Michelle Meyer, PhD, JD)

Posted on by Gina Uhlenbrauck

Speaker

Michelle N. Meyer, PhD, JD
Assistant Professor & Associate Director, Research Ethics
Center for Translational Bioethics & Health Care Policy
Faculty Co-Director, Behavioral Insights Team
Steele Institute for Health Innovation, Geisinger

Topic

Objecting to Experiments that Compare Two Unobjectionable Policies or Treatments: Implications for Comparative Effectiveness and Other Pragmatic Clinical Trials

Keywords

A vs B trials; Comparative effectiveness research; Clinical equipoise; Randomization; Learning health system

Key Points

  • Healthcare delivery systems often have an ethical obligation to experiment in order to determine the effects of their policies and treatments on stakeholders. A/B experiments conducted within health systems are intended to increase quality and safety, decrease waste or lower costs, and reduce inequity and injustice.
  • The “A/B effect” is the approval of untested policies or treatments (A or B) being universally implemented but disapproval of randomized experiments (A/B tests) to determine which of those policies or treatments is superior.
  • Experimentation aversion may be an important barrier to evidence-based practice.

Discussion Themes

Do you think the objection to random assignment is related to a sense that it is not “random?”

A potential solution to the “A/B effect” is to let patients be partners in improving healthcare by explaining that “we don’t know if A or B is better. Would you be willing to help us find out?”

Read Dr. Meyer and colleagues’ open access article in the journal Proceedings of the National Academy of Sciences (May 2019): Objecting to experiments that compare two unobjectionable policies or treatments.

Tags
#pctGR, @Collaboratory1

October 11, 2019: Guiding Good Choices for Health (GGC4H) Pragmatic Trial Enrolls First Participant

Posted on by Gina Uhlenbrauck

The GGC4H NIH Collaboratory Trial, now in its implementation phase, has begun enrollment of study participants. Congratulations to Drs. Kuklinski, Sterling, and Catalano and the entire GGC4H study team!

GGC4H is a cluster-randomized trial that is testing the feasibility and effectiveness of implementing Guiding Good Choices—a universal evidence-based anticipatory guidance curriculum for parents of early adolescents—in three large, integrated healthcare systems serving socioeconomically diverse families. In prior community trials, the Guiding Good Choices curriculum has been shown to prevent adolescent substance use, depressive symptoms, and delinquent behavior. This study offers an opportunity to test the intervention’s effectiveness with respect to improving adolescent behavioral health outcomes when implemented at scale in pediatric primary care within a pragmatic trial.

Read more about GGC4H:

GGC4H NIH Collaboratory Trial

PI Interview

PCT Grand Rounds webinar

October 4, 2019: Ascertaining Death and Hospitalization Endpoints: The TRANSFORM-HF Experience (Eric Eisenstein, DBA, Kevin Anstrom, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Eric L. Eisenstein, DBA
Associate Professor in Medicine
Duke University School of Medicine

Kevin J. Anstrom, PhD
Professor of Biostatistics and Bioinformatics
Director of Biostatistics, Duke Clinical Research Institute
Duke University School of Medicine

Topic

Ascertaining Death and Hospitalization Endpoints: The TRANSFORM-HF Experience

Keywords

Clinical endpoints: Ascertaining death; Hospitalization; TRANSFORM-HF; National Death Index

Key Points

  • When patient deaths occur outside the care setting, the cause of death may not be reliably documented. For researchers, the challenges of measuring deaths include the lack of a national death data source and incomplete or hard-to-access sources.
  • The death identification and adjudication process differs for explanatory versus pragmatic trials, and has implications for how death endpoints are acquired and measured.
  • The TRANSFORM-HF pragmatic trial is comparing the effects of treatment strategies on long-term outcomes for hospitalized patients with heart failure. The primary study endpoint is all-cause mortality, which is ascertained and verified using a hybrid approach at the clinical site and call center, and includes searching the National Death Index data.

Discussion Themes

What are the tradeoffs in making endpoint ascertainment more simple?

If using a hybrid death data collection strategy, how are discrepancies adjudicated?

Use of call centers that coordinate follow-up patient contact and data collection is a valid approach that ensures a single point of contact for patients or proxies and care providers. This approach should also be supplemented with redundant data sources.

Read more in the Living Textbook about Using Death as an Endpoint and Inpatient Endpoints in Pragmatic Clinical Trials.

Tags
#pctGR, @Collaboratory1, @DCRINews

September 20, 2019: Designing & Testing the Future of Home-based Cervical Cancer Screening: Results from a Collaborative Academic-Embedded Delivery System Pragmatic Randomized Trial (Rachel L. Winer, PhD; Diana S.M. Buist, PhD, MPH)

Posted on by Gina Uhlenbrauck

Speakers

Rachel L. Winer, PhD
University of Washington
School of Public Health
Department of Epidemiology

Diana S.M. Buist, PhD, MPH
Kaiser Permanente Washington Health Research Institute

Topic

Designing & Testing the Future of Home-based Cervical Cancer Screening: Results from a Collaborative Academic-Embedded Delivery System Pragmatic Randomized Trial

Keywords

Embedded pragmatic clinical trial; Cervical cancer screening; Human papilloma virus

Key Points

  • The aim of the Home-Based Options to Make Screening Easier (HOME) pragmatic randomized trial was to compare the effectiveness of 2 approaches to increasing cervical cancer screening among women 30-64 years of age who are overdue for cervical cancer screening.
  • Challenges of embedded pragmatic trials reported by the study team include:
    • Discussions with lab, primary care, OB/GYN, and prevention and outreach teams
    • Negotiation about the target population
    • Aligning with evolving clinical guidelines
    • Engaging multiple clinical champions
    • Extensive back and forth with IRB for approval
  • The study team also conducted semi-structured interviews to understand women’s attitudes, emotional responses, and informational needs after receiving a positive kit result and completing recommended follow up.

Discussion Themes

Were you able to assess the impact of this intervention on the clinic staff?

To help move the field forward, there is a need for more publications and more education of peer reviewers and funders about the challenges of conducting embedded pragmatic trials.

Read more about the HOME pragmatic trial design and suggestions for how to improve the promise of embedded pragmatic trials.

Tags

#pctGR, @Collaboratory1