US teens remain at risk of developing human papillomavirus (HPV)-related cancers due to inadequate HPV vaccine uptake, despite strong endorsement in clinical guidelines and substantial intervention efforts by healthcare providers and public health entities. A strong recommendation from a clinician has been identified as the most powerful facilitator of HPV vaccine uptake, yet less than half of parents of pre-teens for whom routine HPV vaccination is recommended by the CDC's Advisory Committee on Immunization Practices receive an HPV vaccine recommendation from their providers. Unfortunately, training clinicians in effective HPV vaccine communication alone produces only a small improvement in vaccination rates. In order to develop effective interventions for improving HPV vaccine uptake, there is a critical need to understand the full range of multilevel factors influencing providers' likelihood and effectiveness in a strong recommendation (secondary outcome). Previous studies have demonstrated the complexity of barriers to HPV vaccination, including their multilevel, multi-factorial nature and heterogeneity across communities and practice settings; as reflected in our and others' data. However, most intervention studies display two limitations: 1) many are single level and single component (e.g., parent education only), leaving many barriers unaddressed; and 2) most address pre-selected barriers using pre-specified interventions that are fixed for all sites. This "prescribed" approach ignores differences in barriers across sites (due to varying context, culture, etc.), and likely leaves key local barriers unaddressed. These interventions have mostly shown modest and inconsistent success. Current thinking in implementation science suggests that significant improvement in HPV vaccination rates will require synergistic, multi-level, multi-component interventions tailored to the local context and barriers.

The study goal is to evaluate the effectiveness of three implementation strategies (local-tailored, prescribed strategy, and usual care) to improve HPV vaccination rates among children 9-12 years old. Study Aims A1) Examine baseline associations between patient-, provider-, and clinic-level factors and variations in (a) HPV vaccination rates; (b) the quality of the provider recommendation; and (c) the impact of provider recommendation on vaccine uptake. A2) Conduct a cluster RCT comparing the effectiveness of a "tailored" multilevel implementation strategy to a "prescribed" multilevel implementation strategy and to usual care in improving HPV vaccination rates (primary outcome) and strengthening the provider recommendation (secondary outcome). Sub-aim: Conduct cost-effectiveness analyses of the implementation strategies based on the RCT results. A3) Study mechanisms of the effect of the implementation strategies to understand the interaction between the intervention, local context, and participant experience combined with quantitative measures. Study Descriptions: In this study, we are using a 3-arm cluster randomized controlled trial (RCT) to compare: (1) An innovative "local-tailored" implementation strategy, engaging local care teams, using local barrier assessment and barrier-driven local tailoring of interventions versus (2) A "prescribed" strategy, that involves pre-specified interventions addressing pre-selected vaccination barriers, guided by the 4 Pillars for Practice Transformation Program versus (3) Usual care - there are no research-led activities. This study will examine two theses: (a) interventions need to be multilevel and multi-component, and (b) local barrier assessment and intervention tailoring with the engagement of local teams (who are familiar with the local context) are needed to increase the uptake of the HPV vaccine.

Clinics will be randomized into one of the three groups. Prior to randomization, clinics will be matched in triads on key attributes that may be associated with implementation success (e.g. geographic location, Consolidated Framework for Implementation Research (CFIR) constructs, membership, race/ethnicity, and baseline HPV vaccine coverage) using a SAS algorithm. The three clinics matched in a triad will be most like each other in these attributes. Within each triad, the three clinics will then be randomized to determine which receives the local-tailored strategy ( 20 clinics) vs prescribed ( 20 clinics) vs usual care (20 clinics). The study subjects will include pediatric physicians, nurses, and other clinical staff. We will also include other non-clinical individuals, such as department administrators. The outcome of interest is: improving HPV vaccination rates (primary outcome) and strengthening provider recommendations (secondary outcome). We will also examine assess other outcome measures such as HPV vaccine series completion rate in children 9-12 years, time taken to recommend the HPV vaccine (provider-centered outcome); perceived comfort/distress in discussing HPV vaccination with parents (provider-centered outcome), parent satisfaction with HPV vaccine communication (parent-centered outcome) and sustainment of interventions (system-centered outcomes). Study data will be obtained through collection electronic medical record extraction, patient surveys, and semi-structured interviews. The analysis will follow an intent-to-treat (ITT) strategy using a log-binomial or Robust Poisson model. Content analysis will be used to evaluate the qualitative data collected. We will use the Consolidated Framework for Implementation Research (CFIR) and the Multilevel Influences on the Cancer Care Continuum (MICC) to inform our overall study approach and provide rigor and structure to our analyses.