Influenza

Grand Rounds January 9, 2026: Pragmatic Care Embedded Randomization: Insights From the KP-VACCINATE Megatrial (Ankeet S. Bhatt, MD, MBA, ScM)

Posted on by Sophia Ramirez

Speaker

Ankeet S. Bhatt, MD, MBA, ScM
Cardiologist, Kaiser Permanente San Francisco Medical Center
Research Scientist, Kaiser Permanente Northern California Division of Research
Assistant Professor, Kaiser Permanente Bernard J. Tyson School of Medicine
Adjunct Professor, Stanford University School of Medicine

Keywords

Vaccination; Learning Health System; Implementation Science; Nudges; Influenza; Cardiovascular

Key Points

  • Every year, influenza leads to over 500,000 deaths and 3-5 million severe cases globally. It increases the risk of cardiovascular (CV) events like myocardial infarction and heart failure. Though health guidelines strongly recommend annual influenza vaccination, rates remain suboptimal globally and persistent inequities exist. There’s an urgent need for novel, effective, and scalable strategies to improve influenza vaccination rates.
  • The KP-VACCINATE trial is one of the largest ever conducted, randomizing over 3.6 million patients in under 30 days. It included several pragmatic elements, such as coordination with existing vaccine promotion efforts; randomization performed by operational health system teams; and endpoint capture fully embedded in the electronic health record.
  • The study team assessed the effect of a cardiovascular-focused nudge communication on influenza vaccination rates and found that there was no effect. Despite the negative results, the trial establishes that pragmatic and rapid randomization of communication strategies is operationally feasible at scale with routine healthcare workflows in the US.

Discussion Themes

The study team targeted a larger-than-usual population in order to 1) demonstrate the feasibility of randomization within a large-scale health system, and 2) be well-powered for subgroup analyses that could help tailor future interventions.

Dr. Bhatt viewed the negative result as an illustration of the importance of design and context for interventions based in behavioral science, rather than an indication that nudges are ineffective.

Future directions may include involvement of the broader care team, with primary care providers and specialty providers playing a potentially critical role in nudging patients towards vaccine uptake.

Grand Rounds May 30, 2025: Embedding Randomization Into Clinical Care in Learning Healthcare Systems: Insights From the KP-VACCINATE Trial (Ankeet S. Bhatt, MD, MBA, ScM)

Posted on by Sophia Ramirez

Speaker

Ankeet S. Bhatt, MD, MBA, ScM
Cardiologist, Kaiser Permanente San Francisco Medical Center
Research Scientist, Kaiser Permanente Northern California Division of Research
Adjunct Professor, Stanford University School of Medicine

Keywords

Nudges; Behavioral Science; Vaccination; Influenza; Implementation Science

Key Points

  • Implementation science is the scientific study of methods and strategies that facilitate the uptake of evidence-based practice and research into regular use by practitioners and policymakers.
  • While many implementation science interventions have targeted patients and providers, relatively few have been scaled at the system level with the ability to be replicated in other healthcare delivery systems. Dr. Bhatt’s team was interested in using a cyclical framework to address this gap in the evidence.
  • Behavioral science emerged as a promising area for this project. In recent years, the practice of employing nudges – subtle changes in design that can impact human behavior without restricting choice – has gained traction in the tech sector and in the public eye more broadly.
  • Dr. Bhatt’s team had worked with a group of Danish researchers on a sequence of nationwide clinical trials: NUDGE-FLU, NUDGE-FLU-2, and NUDGE-FLU-CHRONIC. These trials improved influenza vaccination rates in Denmark through randomization to different behavioral science-informed messaging strategies.
  • Vaccination rates in the U.S. have been stagnant for many years, and most systems are not reaching the minimum target of 70% compliance. Dr. Bhatt’s team, inspired by the NUDGE trials’ success, launched the Kaiser Permanente VACCination Improvement with Nudge-based CardiovAscular Targeted Engagement (KP-VACCINATE) Trial.
  • KP-VACCINATE is a fully embedded, randomized clinical trial assessing the effectiveness and timing of cardiovascular-focused nudge communication when it comes to vaccine uptake in a diverse U.S. population. It was developed in collaboration with Danish partners from the NUDGE trials and will be one of the largest clinical trials ever completed.
  • At the time of presentation, KP-VACCINATE was an ongoing, a 4-arm, 1:1:1:1 randomized clinical trial. The primary outcome is influenza vaccination rates assessed with 6 co-primary outcomes. Patients in Arm 1 receive nudges at Touchpoints 1 & 2; patients in Arm 2 receive nudges at Touchpoint 1; patients in Arm 3 receive nudges at Touchpoint 2; and patients in Arm 4 receive usual care.
  • This model is embedded in an integrated healthcare delivery system and may be readily transferable to other areas of patient, clinician, and health system engagement. Seamless collaboration between the research and operational teams was paramount for stakeholder engagement, implementation, and subsequent analysis.

Discussion Themes

In the interest of pragmatic systemwide inclusion, inclusion criteria were broad and most exclusion criteria pertained to an inability to receive health care system outreach. They also allowed for local adaptation to a unified protocol.

One barrier to conducting this kind of research is that not all healthcare systems are receptive to A/B randomization. When socializing KP-VACCINATE with operational teams, Dr. Bhatt pointed out that many health systems already conduct this kind of testing, albeit informally. Healthcare operates on incomplete evidence; decisions are made based on an integration of clinician judgement and the data we have on hand. This approach could improve systems’ ability to assess these strategies and integrate them into usual care.