Study design Archives - Page 2 of 4 - Rethinking Clinical Trials

February 18, 2022: Building a Resource: The Process of Developing a Trans-stakeholder Framework to Enable Pediatric Drug Development (Perdita Taylor-Zapata, MD)

Posted on February 23, 2022July 9, 2025 by terren.green@duke.edu

Speaker

Perdita Taylor-Zapata, MD
Best Pharmaceuticals for Children Act (BPCA) Program Lead and NICHD Program Officer
Obstetric and Pediatric Pharmacology and Therapeutics Branch
National Institute of Child Health and Human Development

Keywords

NIH Best Pharmaceuticals for Children Act; Pediatric Trial Network; Trial design; Pediatric drug development

Key Points

The current model for pediatric drug development can be slow and neglect neonates and rare pediatric conditions.

The NIH Best Pharmaceuticals for Children Act (BPCA) allows the NIH to conduct clinical trials with off-patent drugs in children.

Goals of the BPCA program include developing novel trial designs and including diverse and understudied populations.

A new framework to enable pediatric drug development could identify resources to assist in drug development, identify areas in need of further research, provide a pathway for integrating approaches, and connect pediatric researchers.

The BPCA went through a rigorous systematic approach to develop a comprehensive resource listing for best practices for pediatric drug trials.

Discussion Themes

Most data collected through the opportunistic model presented is PK data to determine dosing so that a more traditional drug trial can be conducted in the future.

With the right infrastructure in place, such as the Pediatric Trials Network, can substantially improve time to conduct trials.

Read more about the BPCA and their commitment to diversity in pediatric drug trials.

Tags

#pctGR, @Collaboratory1

February 11, 2022: Great Power and Great Responsibility: Machine Learning in Clinical Research (E. Hope Weissler, MD, MHS; Erich Huang, MD, PhD)

Posted on February 14, 2022March 31, 2022 by terren.green@duke.edu

Speakers

E. Hope Weissler, MD, MHS
Resident, Vascular and Endovascular Surgery
Duke University School of Medicine

Erich Huang, MD, PhD
Chief Science and Innovation Officer, Onduo

Topic

Great Power and Great Responsibility: Machine Learning in Clinical Research

Keywords

Machine Learning; Artificial Intelligence; Data Liquidity; Data Storage; HL7FHIR

Key Points

Machine learning may address issues that have reduced the efficiency and effectiveness of clinical research and help clinical research projects reach their full potential.

Machine learning may improve the pragmatism of research, decreasing costs and time it takes to conduct a research study.

Machine learning can be used to canvas the literature, hypothesize drug-target interactions, propose new therapeutics, and analyze highly dimensional research output.

Effects of machine learning are up to us and could potentially reduce the pragmatism of research if applied indiscriminately. Machine learning could produce overly selected study participant groups, too closely managing adherence, and using ultra-high-touch follow-up methods.

Data Liquidity refers to the ease with which data can be transferred or exchanged. This depends largely on the manner in which the data is stored.

Some forms of data are liquid than others due to privacy, security, and ethical concerns.

Discussion Themes

A lot of emphasis is currently being placed on the mobile/wearable device area, but an equally important area to develop in machine learning is patient identification and recruitment.

Is data ever really de-identified? Should data be owned by the patient? Why is health data treated differently than consumer data? Privacy regulation is difficult and needs to be addressed further by Congress in the future.

Read more about Dr. Weissler and Dr. Huang’s machine learning in clinical research.

Tags

#pctGR, @Collaboratory1

February 4, 2022: SPIRRIT-HFpEF: Opportunities and Challenges in a Large Registry-Based Randomized Clinical Trial(Adam DeVore, MD, MHS; Lars Lund, MD, PhD)

Posted on February 7, 2022March 31, 2022 by terren.green@duke.edu

Speakers

Adam DeVore, MD, MHS
Associate Professor of Medicine
Duke University Medical Center
Duke Clinical Research Institute

Lars Lund, MD, PhD
Professor of Cardiology
Karolinska Institutet
Karolinska University Hospital

Topic

SPIRRIT-HFpEF: Opportunities and Challenges in a Large Registry-based Randomized Clinical Trial

Keywords

Heart Failure; SPIRRIT-HFpEF; Randomized clinical trial; Spironolactone; Eplerenone; Swedish Heart Failure Registry (SwedeHF)

Key Points

The SPIRRIT-HFpEF trial, conducted Sweden and the US, was a randomized pragmatic clinical trial of spironolactone or eplerenone in heart failure.

Death from heart disease is decreasing while death from Heart Failure is increasing.

The SPIRRIT-HFpEF trial focused on improving the trajectory for the growing heart failure population.

Patients treated with Spironolactone had a modest but not statistically significant improvement over placebo, but total hospitalizations were less.

Patients with a lower ejection fraction were more likely to benefit than patients with a higher ejection fraction.

The Swedish Heart Failure Registry (SwedeHF) has been collecting data from HF patients since 2000.’

Discussion Themes

The hardest aspect of a clinical trial is recruitment and enrollment. Patients are spread out over the health care system. The challenge is getting staff and personnel to do the work of screening and prescreening.

In the SPIRRIT-HFpEF, the drawbacks of not blinding were small and the costs of blinding would have been huge.

Learn more about the SPIRRIT-HFpEF trial and the Swedish Heart Failure Registry. Read about the SPIRRIT-HFpEF trial results.

Tags

#pctGR, @Collaboratory1

January 27, 2022: Grand Rounds Podcast Now Available, Featuring Dr. Chris Lindsell on Selecting Outcomes for Outpatient Trials

Posted on January 27, 2022February 21, 2024 by terren.green@duke.edu

Headshot of Dr. Christopher John Lindsell In the latest episode of the NIH Collaboratory Grand Rounds podcast, Dr. Christopher Lindsell and Dr. Adrian Hernandez continue the discussion about research outcomes and the importance of understanding stakeholder perspectives in choosing the correct outcomes for outpatient trials.

The full January 14 Grand Rounds webinar with Dr. Lindsell is also available.

December 10, 2021: Decentralized Trials: Naughty or Nice? (Adrian F. Hernandez, MD, MHS)

Posted on December 15, 2021March 31, 2022 by terren.green@duke.edu

Speaker

Adrian F. Hernandez, MD, MHS
Executive Director, Duke Clinical Research Institute
Vice Dean, Duke University School of Medicine

Topic

Decentralized Trials: Naughty or Nice?

Keywords

Decentralized trials; Study design; Implementation; Patient engagement; Patient-reported data

Key Points

Decentralized trials have been occurring since the start of the internet and mobile devices to reach people where they are and collect data in places we were not able to in the past.

One key problem decentralized trials can help solve is the gap between those who wish to participate in research and those who actually do participate. Clinical trial deserts and lack of broadband widen the gap between those who wish to participate and those who are able.

Decentralized trials attempt to capture data remotely instead of at a site and virtually(patient-reported) rather than recorded by study personnel.

COVID-19 flipped the model for clinical trial visits from that of site-based visits and care to home based, virtual visits and care.

Enrollment can be a challenge for decentralized trials and requires engagement campaigns at various timepoints in the study to achieve desired enrollment numbers.

Decentralized trials can help ensure inclusion of diverse communities in your study population.

The HeartLine study, CHIEF-HF study, HERO-Together study, and ACTIV-6 study are taking advantage of various technologies to decentralize study design.

Discussion Themes

Decentralized methods may improve recruitment, but may not improve retention. We may need a hybrid model to keep a patient engaged.

Decentralized methods may require decisions about what data we should collect and what we could collect, but don’t need.

Tags

#pctGR, @Collaboratory1

November 19, 2021: Exploring Approaches in Using Digital and Mobile Health in Patient-oriented Research: Pearls and Pitfalls (Anish K. Agarwal MD, MPH MS)

Posted on November 22, 2021March 31, 2022 by terren.green@duke.edu

Speaker

Anish K. Agarwal MD, MPH MS
Assistant Professor of Emergency Medicine
Clinical Innovation Manager, Penn Medicine Center for Health Care Innovation
University of Pennsylvania, Perelman School of Medicine

Topic

Exploring Approaches in Using Digital and Mobile Health in Patient-oriented Research: Pearls and Pitfalls

Keywords

Mobile health; Digital health; Patient-oriented research; Study design

Key Points

Digital and mobile health is a rapidly evolving field that integrates with the electronic health records in both low and high tech ways.

Dr. Agarwal conducted a randomized control trial of overweight veterans who had daily access to a smartphone or tablet. These participants were sent a wearable device to collect step count data.

An important consideration for studies using mobile health technology is participant access to a smart or mobile device. 85% of Americans have access to a Smartphone where 97% have access to a mobile device that can receive texts. 20% use a smartwatch.

Mobile methods are just tools to support overall study design.

Dr. Agrawal conducted a study on post-operative opioid prescribing and use. Data was gathered from participants via text messaging systems.

Simple text messages that are more conversational in nature are received better by the participant. Links in text messages should be limited. It’s important for participants to understand the privacy and security of their communications and data. Nudge a participant with a text at the right time to avoid being overbearing.

Discussion Themes

Let patients know that SMS is not secure, and frame questions to avoid patients sending HIPAA covered data via text.

A good relationship with your institutions Privacy and Safety office is fundamental to navigating IRB regulations for research with digital and mobile devices.

Tags

#pctGR, @Collaboratory1

October 29, 2021: Embedding Pragmatic Trials into Emergency and Critical Care (Matthew W. Semler, MD, MSc; Jonathan D. Casey, MD, MSc)

Posted on November 3, 2021 by terren.green@duke.edu

Speakers

Matthew W. Semler, MD, MSc
Assistant Professor
Vanderbilt University Medical Center

Jonathan D. Casey, MD, MSc
Assistant Professor
Vanderbilt University Medical Center

Topic

Embedding Pragmatic Trials into Emergency and Critical Care

Keywords

Pragmatic clinical trials; Study design; Comparative effectiveness trials; Treatment effect; SMART trial; PreVent trial; Exception from Informed Consent (EFIC)

Key Points

Emergency medical clinicians are faced with common decisions in everyday practice with little to no data from randomized clinical trials to help inform their decisions.

Four barriers to comparative effectiveness trials in a critical care setting are a brief therapeutic window, patients with multiple co-morbidities, the inability of the patient to consent to research, and analyzing average treatment effect rather than individual treatment effect.

The PreVent Trial studied the use of bag-mask ventilation to prevent hypoxemia for patients who had been administered anesthesia in preparation for intubation.

Efficient, pragmatic trial procedures that don’t delay treatment enable comparative effectiveness randomized clinical trials to be conducted effectively.

After 50 years of debate about bag-mask ventilation during this interval period, the PreVent Trial found that bag-mask ventilation cut the rate of hypoxemia by 50% without affecting aspiration.

The SMART Trial was a cluster-randomized, multiple-crossover trial of fluid management that studied patient outcomes when Balanced Crystalloids were used versus Saline solution.

The large sample size of over 15,000 patients provided the SMART trial with the power to detect that a balanced crystalloid fluid prevented Major Adverse Kidney Events in 1% of patients compared to Saline solution. /li>

Exception from Informed Consent (EFIC), implemented in 1996 allows trials in emergency situations of the condition is life-threatening, existing treatments are unproven or unsatisfactory, and research involves no more than minimal risk.

Analyzing Individual Treatment Effects will allow clinical providers to tailor their decisions to their individual patient.

Discussion Themes

Clinical equipoise poses a challenge for comparative effectiveness trials.

Key to getting buy-in from clinician stakeholders is explaining the importance of the research to the patient.

Read more about PreVent trial and the SMART trial.

Tags

#pctGR, @Collaboratory1

October 22, 2021: The STAMP Trial: Increasing Engagement in Advance Care Planning and Lessons Learned from Partnering with Community Ambulatory Practices (Terri R. Fried, MD)

Posted on October 26, 2021July 9, 2025 by terren.green@duke.edu

Speaker

Terri R. Fried, MD
Section Chief, Geriatrics
Professor of Medicine
Yale School of Medicine
Attending Physician
VA Connecticut Healthcare System

Topic

The STAMP Trial: Increasing Engagement in Advance Care Planning and Lessons Learned from Partnering with Community Ambulatory Practices

Keywords

STAMP Trial; Advance Care Planning; ACP; Patient engagement; Cluster randomized trial

Key Points

The STAMP (Sharing and Talking about My Preferences) Trial is a cluster randomized controlled trial aimed at increasing engagement in Advanced Care Planning (ACP).

The STAMP Trial first aimed to re-conceptualize advance care planning (ACP) to achieve the ultimate goal of enabling the patient or surrogate to make decisions in a future moment rather than making decisions in advance. In this way, ACP is a flexible act of communication that allows for in-the-moment advice of a patients care providers about the nuances of a particular clinical situation.

ACP is a Health Behavior that involves stages of change. The STAMP Trial uses a 10 minute survey to assess how ready a patient is to start the ACP communication process.

Patients are given ACP materials based on their stage of readiness as assessed by the survey.

Results showed a small increase in ACP planning for groups randomized to the study interventions, but that small increase applied over large numbers of patients could have a significant impact on the number of people participating in ACP.

Discussion Themes

Cluster randomized trial design is complex unless you are working with an intervention that is implemented in a whole health care system rather than individual patients.

Determining a denominator in a cluster randomized trial at the patient level was very difficult.

Read more about Dr. Fried’s work on the STAMP Trial.

Tags

#pctGR, @Collaboratory1

October 15, 2021: The Impact of Community Masking on COVID-19: A Cluster-Randomized Trial in Bangladesh (Jason Abaluck, PhD)

Posted on October 21, 2021 by terren.green@duke.edu

Speaker

Jason Abaluck, PhD
Professor of Economics
Yale School of Management

Topic

The Impact of Community Masking on COVID-19: A Cluster-Randomized Trial in Bangladesh

Keywords

COVID-19; Cluster-randomized trial; Masking; Community spread; NORM model

Key Points

Dr. Abaluck’s cluster-randomized trial on the impact of community masking in ~350,000 adults in 600 villages of Bangledesh aimed to answer 2 questions: What strategies or interventions will increase mask-wearing? and What is the impact of mask wearing intervention on COVID-10?

There are two major differences between the existing randomized trials of mask wearing for flu and the impact of community masking in Bangladesh trial. The first issue is the existing trials were randomized individually not by communities so you cannot evaluate weather masks act as source control. The second issue with the existing trials is the discrepancy between the number of people who attest to wearing a mask and the number who actually wore a mask.

The impact of community masking in Bangladesh trial used the NORM model to increase mask wearing. The NORM model distributes masks at No-cost, Offers information about why mask wearing is important, Reinforces mask wearing by having mask promoters give free masks and information in public places, and Modeling by trusted community leaders wearing masks and endorsing mask wearing.

The NORM model more than tripled mask usage(13% usage increased to 42%), increased physical distancing, and had a sustained impact that lasted at least 10 weeks.

Communities where the NORM model was employed saw a 9% reduction in symptomatic COVID-19 infections.

Mask wearing showed a greater reduction in COVID-19 among the elderly.

Discussion Themes

The NORM model would have different efficacy rates in different cultures and communities.

You can get some people to wear a mask by just distributing the masks in public places and asking them to wear them.

Masks are not an all-or-nothing protection. Masks have a dose-reduction effect and that dose-reduction translates into a transmission effect.

Read more about the Dr. Abaluck’s work on masking and COVID-19 in the recently published Discussion Paper.

Tags

#pctGR, @Collaboratory1, @Jabaluck

October 8, 2021: Lessons Learned and Patient Partnership in ADAPTABLE (Schuyler Jones, MD; Madelaine Faulkner Modrow, MPH)

Posted on October 11, 2021March 31, 2022 by terren.green@duke.edu

Speakers

Schuyler Jones, MD
Associate Professor of Medicine
Duke University School of Medicine

Madelaine Faulkner Modrow, MPH
Program Director
Department of Epidemiology and Biostatistics
University of California, San Francisco

Topic

Lessons Learned and Patient Partnership in ADAPTABLE

Keywords

Patient engagement; Pragmatic clinical trial; Aspirin; ADAPTABLE; Study design; Stakeholder engagement; Recruitment

Key Points

ADAPTABLE is a pragmatic clinical study of 15,000 patients to examine a simple, everyday decision, whether to take 81mg or 325mg of aspirin daily, to identify if that decision could prevent heart attacks.

ADAPTABLE used both pragmatic and personalized approaches to participant recruitment.

Pragmatic recruitment involves broad-based email and social media outreach to a large pool of potential subjects. This method of recruitment was lower cost, less time intensive, and faster paced than personalized recruitment.

Personalized recruitment involves traditional in-clinic or phone call personal outreach to potential participants. This method of recruitment was higher cost, time intensive, and slower paced than personalized recruitment.

ADAPTABLE learned a critical lesson in patient engagement: in-clinic enrollment was much higher at 81% of those approached versus e-communication enrollment at 35% of those contacted.

Key principles of patient engagement include trust and partnership, respect and listening, empowering patients to find solutions, and value and design the trial for the patient experience.

Discussion Themes

We are moving from a traditional model of research to a relational model with participants coming together with researchers and forming a kind of social contract where a participant’s voice is valued in the research process.

We have lessons left to learn in order to fully utilize technology for patient engagement including how to use broad outreach methods to increase enrollment of diverse populations.

Patients continue to look to their clinician or doctor for advice on whether to participate in a clinical trial. Trusted contacts will continue to play an important role in the recruitment process.

Tags

#pctGR, @Collaboratory1