Speaker

Tor Biering-Sørensen, MD, PhD, MPH
Professor in Translational Cardiology and Pragmatic Randomized Trials
Head of Center for Translational Cardiology and Pragmatic Randomized Trials
Department of Biomedical Sciences
Faculty of Health and Medical Sciences
University of Copenhagen
Head of Cardiovascular Non-Invasive Imaging Research Laboratory
Department of Cardiology
Copenhagen University Hospital – Herlev and Gentofte

Keywords

DANFLU-1, Pragmatic Clinical Trials

Key Points

• The Danish Nationwide Registries include the Danish Patient Registry (a registry of every inpatient and outpatient contact in the Danish free-for-all public healthcare system); the Danish Medicines Registry (a registry of every filed prescription at any pharmacy in Denmark including information on pill strength, pack size, etc.); and the Danish Registry of Causes of Death (a registry of long-term clinical outcomes including hospitalizations, outpatient visits, procedures, prescriptions, mortality). Denmark also has registries tracking socioeconomic data such as income and level of education and other types of data that can be linked together for study.

• Denmark also has a mandatory electronic mailbox (e-BOKs) system that is required for all Danish citizens older than 18 and is linked to each citizen’s social security number. The system is used by approximately 5.8 million people, representing more than 95% of the population. The system is used for priority communications from government agencies, hospitals, banks, and others, and allows for rapid delivery of recruitment letters and implementation interventions

• The national registries can be used to identify potential study participants who meet specific criteria and the e-BOKs system allows researchers to easily send invitations to potential participants, as well as follow up communications. Researchers can track participants through their medical records regardless of location and through the national registries. This infrastructure can be used to conduct pragmatic Phase II trials, large-scale pragmatic RCTs, such as DANFLU, and nationwide implementation trials.

• The COlchicine Hypertension Trial (COHERENT) is a pragmatic Phase II trial that looked at only hypertension by using registry data to identify patients that receive at least two hypertension drugs. The DECODE trial used registry data to identify patients with chronic kidney disease.

• The DANFLU-1 trial is a large-scale pragmatic RCT that looked at high-dose vs standard-dose flu vaccine to test whether high-dose vaccines might reduce hospitalizations among the elderly, age 65 and older. The DANFLU-1 trial evaluated the feasibility of integrating an individually randomized trial into routine seasonal influenza vaccination practice using administrative health registries for data collection. 34,000 study invitations were sent out and 12,551 participants consented and were randomized in the study. One hypothesis-generating outcome was that participants randomized for the high-dose vaccine had a 64% lower risk for hospitalization than the standard-dose vaccine.

• With the success of DANFLU-1, the team is launching the fully powered DANFLU-2 trial, which will be conducted the next two years, randomizing 208,000 patients over two flu seasons. The team will send out 800,000 invitations. Hospitalization of flu is the primary outcome.

• The NUDGE-FLU trial is a nationwide implementation study that will randomize all Danish citizens above 65 who receive a free vaccine by Danish government. 1.2 million citizens will be randomized to receive 10 different communications. The aim is to test communication strategies for optimizing the update of the flu vaccine. Another trial is called NUDGE-DM using the same system for identifying patients with diabetes to test communication strategies for optimizing the use of guideline directed medical therapy for T2D patients with established CVD

Discussion Themes

-I was struck by the number of people that were approached and joined the DANFLU study. For most trials it’s 2-4%. What was the type of engagement; were people aware clinicians were involved? These are participants who are already in the vaccine company’s registry. They have been vaccinated and were seeking the flu vaccine. We would not expect this recruitment rate in other trials.

–What clinicians are involved in the trial? It wasn’t the intention to bypass clinicians but the only ones involved are in the study lab and with the vaccine company. We are bypassing the normal ways because we are not in the hospitals. We are using the vaccine clinics where it’s nurses who are administering the vaccine at clinics in all of the cities, not just at hospitals. During the vaccine season they have pop-ups. We can do this work cheaply because we are not using local sites, we are not paying participants. The DANFLU-1 trial was close to $1.5 million U.S. dollars.

-These one-time interventions, like vaccines, contact people, deliver intervention, what about chronic care that is needed for a trial where more monitoring is needed? You can always use the system to identify potential candidates and then guide them to the local cardiology, kidney department. To keep the cost down, we are thinking about how to use vaccine clinics. It was the first try at testing the systems, so now we are testing whether mailing out potential interventions or using the vaccine clinics where they have to go in to draw a blood sample

Learn more

Read about DANFLU-1.

Tags

#pctGR, @Collaboratory1