Embedded PCTs tend to be larger and more broadly generalizable than QI initiatives and may generate high-quality evidence for care and clinical practice guidelines. However, QI initiatives may address the same high-impact health questions, and if they co-occur with ePCTs, they may dilute or confound the ability to detect differences. Therefore, for ePCTs to be rigorous, study teams must monitor, adapt, and respond to QI during the design and implementation of the trail (Tuzzio et al. 2021).

In an article (Tuzzio et al. 2021), NIH Collaboratory investigators shared their experience with this challenge, and we excerpt a few of the case studies below.

Competing QI initiatives may impact the ability to measure the primary outcome

For the ABATE trial (Huang et al. 2019), hospitals were required to report any new QI initiatives or other new interventions being considered or launched throughout the trial, and the Steering Committee assessed these initiatives weekly. When a potential competing intervention was noted, hospitals were asked to delay the QI initiatives until the trial was over, or to drop from the trial. During the 21-month trial, 196 QI interventions were identified, with 67 (34%) deemed to directly compete with trial outcomes. Three sites dropped from the trial (two in the control group and one in the intervention group) to pursue a competing intervention.

QI activities during recruitment of an ePCT can create confusion among participants and clinicians

The PPACT study tested cognitive behavioral therapy interventions to improve chronic pain among those receiving long-term opioid therapy (DeBar et al. 2022). The study was conducted in the primary care setting, and simultaneous QI efforts that appeared similar to the PPACT intervention caused unexpected confusion for frontline clinicians (Tuzzio et al. 2021). Additionally, potential participants were concerned that their chronic opioid treatment might be reduced or eliminated, and to alleviate these fears, the investigators intensified orientation efforts for potential participants.

Health systems that are early adopters of evidence are quick to change practice and have many QI activities

The PRIM-ER research team collaborated with early adopter emergency departments that were prioritizing palliative care initiatives and had physician and nurse champions (Grudzen et al. 2019). While these motivated sites were expected to be successful at implementing a complex intervention, they also implemented other related programs, which could have impacted the outcomes of the trial. The research team monitored QI initiatives at the site level and negotiated with clinical leadership to delay or replace palliative initiatives with PRIM-ER activities. The team hoped to support and encourage local QI while also ensuring the outcomes of the trial were the result of the intervention and not parallel programs.

Late adopters may be slow to implement evidence into care and to implement research interventions

The TiME trial tested a longer dialysis session duration (4.25 hours) versus usual care (non-trial directed session duration) for patients with end-stage renal disease (Dember et al. 2019). Observational studies demonstrated associations between longer session durations and improved patient survival. During facility selection, it was apparent that some dialysis provider organizations were already increasing hemodialysis session durations, which could decrease the difference in session durations between the intervention and usual care facilities. To counter this, the study team decided to restrict enrollment to “late-adopter” facilities that had not already implemented longer session durations. This approach had the unintended effect of enriching the trial for facilities that had less enthusiasm to change practice, and thus, less willingness to broadly adopt the TiME intervention as routine care during the conduct of the trial.

A mix of early and late adopters poses various challenges

For the STOP CRC trial, there were distinct differences between the implementation of the intervention at different Federally Qualified Health Centers: implementation success varied from 21% to 82%. Some clinics assigned to the control arm (usual care) did not want to wait to start the intervention. They believed that providing colorectal cancer screening kits would improve care, so they were more likely to give out kits at routine clinic visits. Conversely, some sites in the intervention arm were slow to mail the kits. This difference in implementation diluted the ability to detect changes due to the STOP CRC intervention, thereby decreasing the overall intervention effectiveness. However, the active intervention was still significantly more effective than usual care (Coronado et al. 2018).

Both ePCTs and QI happen within the same context and aim to improve patient care, and therefore, they are inherently interconnected. Routine collaboration with healthcare system partners can help align research and QI to support high-quality, patient-centered care.

For more information, see the Living Textbook Chapters on Advice from Health Care System Leadership,  Building Partnerships to Ensure a Successful Trial, and Monitoring Intervention Fidelity and Adaptations.