Defining the current models of immunization of immunocompromised patients in Spain, and how to improve them: results of the CARABELA-IP initiative

Abstract

Objective

The CARABELA initiative for the immunocompromised patient (IP) aims to optimize the management of these patients by focusing on four specific objectives: (i) the description of care pathway phases (diagnosis, immunization, and follow-up) and management models for IPs in Spain; (ii) the identification of improvement areas in IP care and potential solutions; (iii) the definition of healthcare quality indicators; and (iv) the dissemination of these findings to enable reference centers to guide others in the management of IP.

Material and methods

The CARABELA-IP initiative was developed in three phases: (1) characterization, identifying immunization models, improvement areas, and potential solutions in five pilot centers; (2) validation, through a national multidisciplinary meeting and a Delphi survey to agree on healthcare quality indicators; and (3) dissemination and implementation strategies beyond pilot centers, with a digital Playbook designed to guide the evolution of IP care.

Results

Three immunization models were identified based on coordination among departments, highlighting the role of preventive medicine and public health departments and nursing. Nine improvement areas and 24 potential solutions were defined. Furthermore, 28 healthcare quality indicators were validated to monitor the evolution of the immunization models.

Conclusions

Coordinated, multidisciplinary strategies are needed to ensure appropriate immunization in the face of diverse and heterogeneous IP management strategies. CARABELA-IP proposes a comprehensive model encompassing the identification, stratification, and protocolized referral of IPs, and promoting the training of healthcare professionals and the education of patients and their household contacts.

Resumen

Objetivo

La iniciativa CARABELA-paciente inmunocomprometido (PI) busca optimizar el manejo de estos pacientes enfocándose en cuatro objetivos específicos: (i) la descripción de las diferentes fases del proceso asistencial (diagnóstico, inmunización y seguimiento) en PIs en España y sus diferentes modelos de manejo; (ii) la identificación de áreas de mejora en el cuidado de los PIs y las potenciales soluciones; (iii) la definición de indicadores de calidad asistencial; y (iv) la divulgación de estos resultados para que los centros de referencia guíen a otros en el manejo de los PIs.

Material y métodos

La iniciativa CARABELA-PI se desarrolló en tres fases: (1) caracterización, identificando modelos de inmunización, áreas de mejora y potenciales soluciones en cinco centros piloto; (2) validación de estos resultados, mediante una reunión nacional multidisciplinaria y una encuesta Delphi para consensuar indicadores de calidad asistencial; y (3) estrategias de divulgación e implementación más allá de los centros piloto, con un Playbook digital que guíe la evolución del manejo de los PIs.

Resultados

Se identificaron tres modelos de inmunización según la coordinación entre servicios, destacando el rol de Medicina Preventiva y Salud Pública y enfermería. Se definieron nueve áreas de mejora y 24 soluciones potenciales. Además, se validaron 28 indicadores de calidad asistencial para monitorizar la evolución de los modelos de inmunización.

Conclusiones

Se necesitan estrategias coordinadas y multidisciplinares para garantizar la adecuada inmunización frente a las diversas y heterogéneas estrategias de manejo de los PIs. CARABELA-PI propone un modelo integral que incluye la identificación, estratificación y derivación protocolizada de los PIs, y promover la formación del personal sanitario y la educación de pacientes y sus entorno de convivencia.

Introduction

An immunocompromised patient (IP) is defined as one with a weakened immune system that shows little or no response to infections, resulting in an enhanced risk for preventable infections and severe diseases.¹ Frail IPs account for about a third of all intensive care unit admissions and numbers have increased notably over the years. Their prognosis and morbidity and mortality are tightly related not only with their underlying diseases or treatments but also, importantly, with the severe infections to which they are susceptible.^2–8 Optimal protection against infections in this vulnerable population is therefore crucial. This normally involves immunization plans that include a wide variety of vaccines/monoclonal antibodies against pneumococcus, influenza, COVID-19, human papillomavirus, varicella-zoster virus, herpes zoster, hepatitis A and B, diphtheria, tetanus, pertussis, Haemophilus influenzae type b, measles, rubella, mumps, meningococcal disease, and poliomyelitis.^9–11

Several definitions of the IP refer to the origin of their altered immune system,¹ including frail populations; patients with hematological malignancies; individuals receiving a transplant (either of solid organs or hematopoietic progenitors); people living with human immunodeficiency virus who had not been early diagnosed or those with advanced disease, with low CD4⁺ cells counts or with unsuppressed viral load; and patients with immune system-mediated inflammatory diseases (e.g., multiple sclerosis, rheumatoid arthritis, lupus, etc.) treated with corticosteroids at immunosuppressive doses (≥ 20 mg/day prednisone or equivalent for 14 days or more), immunosuppressors, or biological drugs; chronic kidney disease; nephrotic syndrome or those on dialysis; primary immunodeficiencies; anatomic or functional asplenia; or solid organ cancers needing chemotherapy.^1,11–13

Among the multiple IP definitions available, the characteristics of hematological patients may be representative. The immune system of these patients can be exhausted, rendering different immune cells incapable of responding to external threats and ultimately compromising patient survival.^14,15 These patients present with haematologic malignancies such as multiple myeloma, lymphoproliferative pathologies or monoclonal gammopathies that require severely immunosuppressive chemotherapy, and the possibility of a therapy based on anti-CD20, anti-CD19, anti-CD38 or anti-BCMA monoclonal antibodies, tyrosine kinase, TNF or BCL2 inhibitors, or CAR-T cells. These patients may also be receiving treatment with high-dose corticosteroids (> 20 mg/day prednisone or equivalent for more than 2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressors, and other biological drugs with immunosuppressive or immunomodulatory effects.^{1,11–13,16–23}

Heterogeneity in identifying an IP is a major challenge when designing a standardized, protocolized immunization plan, given the range of IP clinical profiles and the participation of several medical specialties in their management. Further challenges in establishing individualized immunization plans in IPs include the diverse management strategies and the lack of standard procedures in referring patients from the medical departments where their immunocompromised status is identified to preventive medicine and public health departments (PMPHD).

Awareness of the importance of immunization still remains poor. Aside from the difficulties described in establishing proper immunization plans for IPs, there is a risk that neither their household contacts nor the healthcare professionals managing them are properly vaccinated. This may be because household contacts have not been immunized according to clinical practice guidelines and have not received vaccines against influenza or COVID-19,^9–11 among others. Furthermore, the coverage of healthcare professionals is also low, generally due to a lack of accessibility and awareness.^24–26

Similar to other CARABELA initiatives aimed at transforming the current management of different diseases and clinical situations,²⁷ CARABELA-IP is a collaborative initiative that deepens our understanding of how patients with diseases of the immune system are identified and managed in Spain. The scientific societies involved in this initiative (XXX1 XXX2, XXX3, and XXX4), together with XXX5, have developed a guide for optimizing current Spanish healthcare immunization processes to enable the establishment of coordinated and protocolized strategies to improve the identification, stratification and referral of IP, while also promoting the training of healthcare professionals and the education of patients and their household contacts. In relation to all these, the initiative focused on four specific goals: (i) characterization of the immunization process in IP in Spain, in order to standardize management in an efficient, professional-coordinated manner; (ii) identification of solutions addressing improvement areas throughout the healthcare process, aimed at providing an integrated approach and improving the patient quality of life and experience; (iii) definition of healthcare quality indicators to monitor the impact of the improvement; and (iv) dissemination of the initiative's results, which will surely guide the optimization of IP management in Spain.

Material and methods

The CARABELA-IP initiative was designed as a three-phase process during which several Scientific Committee validation meetings were held, starting in May 2024, in line with the general CARABELA methodology²⁷ (Fig. 1). This Scientific Committee consisted of healthcare professionals from different regions in Spain, each with varying levels of experience in IP management, therefore being representative of the Spanish healthcare ecosystem. Phase 1 (characterization) was developed in an initial meeting aimed at modeling an evidence-based, optimal immunization process. That is, the Scientific Committee defined an “ideal” care process to be followed when immunizing IP, based on clinical practice guidelines and daily clinical practice. This healthcare process was also summarized in three phases: diagnosis, immunization, and follow-up. Diagnosis was understood as the identification of the IP or patients eligible for immunosuppressive treatment, either by the department prescribing this need or by a proactive action from PMPHD. Immunization was classified as follows: pharmacological primary prophylaxis if it is needed, followed by serology tests and referral to PMPHD for initial patient evaluation, establishment of a personalized vaccination/immunization plan for both the patient and their household contacts, and finally immunization procedures. After all these steps, the final follow-up phase was based on the definition of a personalized plan. Details of the processes occurring throughout these three phases are listed in Fig. 2. Furthermore, 10 variables related to IP management in Spain (Table 1) were identified, enabling the definition of three distinct immunization models for these patients. Through the conduction of structured workshops, a process mapping exercise was then followed at each site to describe their own immunization models and to identify improvement areas and potential solutions in relation to the “ideal” model.

Figure 1.

Summary of CARABELA-IP methodology and results. IPs: immunocompromised patients; KPI: key performance indicator.

Figure 2.

Description of the healthcare process. PMPHD: preventive medicine and public health departments.

Table 1.

Criteria for the characterization of immunization models.

Criteria⁎	Description
PMPHD specialized nursing team	Dedicated nursing team responsible for administering immunization and educating and continuously monitoring patients
Coordination and communication between departments involved in immunization	Coordination between PMPHD and support nursing staff involved in patient immunization
Patient identification and referral protocols	Clear protocols for the rapid identification of IP, facilitating timely referral to PMPHD
Multidisciplinary approach	Specific plans that guarantee a coordinated and multidisciplinary immunization approach
Virtual patient consultations	Online tool enabling frequent and accessible patient follow-up
Proactive patient identification	Strategies enabling early identification of IP across all departments
Urgent patient referral pathway	Streamlined referral process to PMPHD for rapid, effective, and personalized immunization
Patient coding and records	Labelling and maintaining updated records for the identification and tracking of IP
Immunization indicators	Clear metrics to assess immunization levels in both healthcare professionals and IP
Professional training	Continuous training for the healthcare professionals involved in managing IP

IP: immunocompromised patient; PMPHD: preventive medicine and public health departments.

⁎

In addition to these criteria, a broad criterion was taken into account: the availability and implementation of identification/referral protocols.

The next phase (validation) consisted of a multidisciplinary national meeting, held on 17 September 2024, in which the healthcare processes, improvement areas and potential solutions identified were validated and prioritized and healthcare quality indicators were defined. Healthcare quality indicators were further validated through a Delphi survey, the results of which were validated by the CARABELA-IP Scientific Committee.

Finally, in phase 3 (dissemination and implementation), a Playbook was generated in which all the CARABELA-IP data were included as a guideline for developing IP management across Spain. This Playbook is a digital platform that facilitates workshops across different hospitals throughout Spain beyond the pilot centers. By using it, the most appropriate model for each hospital is analyzed while identifying center-specific improvement areas and potential solutions to be implemented.

Results

Characterization of the immunization models of the immunocompromised patient

After examining clinical practice guidelines and daily clinical practice, various immunization models were identified (Fig. 3). In model 1, immunization is coordinated by the PMPHD together with the PMPHD nursing staff. This involves the adequate identification and referral of IPs from all the healthcare departments responsible for their management. Model 2 resembles the first but lacks protocolized coordination between PMPHD and other departments, in which a range of identification and referral protocols are in place. Finally, model 3 is characterized by immunization procedures performed by nursing staff independently of PMPHD and/or primary care. This last model lacks dedicated nursing support from PMPHD, and no identification or referral protocols are available.

Figure 3.

Immunization models in the management of immunocompromised patients identified by CARABELA-IP. IP: immunocompromised patient; HC: hospital care; KPI: key performance indicator; MR: medical record; PC: primary care; PMPHD: preventive medicine and public health departments.

Improvement areas and potential solutions

Nine improvement areas were described for the defined immunization models. Of these, 24 potential solutions emerged (see top 10 listed in Table 2) that could contribute to the continuous improvement and optimization of each immunization process. These improvement areas and solutions were classified into six categories: (i) resources; (ii) protocols; (iii) professional training; (iv) patient education; (v) technology; and (vi) organization. The improvement areas were prioritized according to their impact on daily clinical practice and the feasibility of implementing them. The defined solutions were also prioritized on the basis of their impact and how quickly they could be put in place.

Table 2.

Top 10 solutions within the CARABELA-IP initiative.

1. To develop a standardized, protocolized process on the basis of which PMPHD can share new recommendations for immunization

2. To establish a protocol for fast-track referral of IP to PMPHD

3. To create an accessible vaccination process for hospital staff

4. To review and update existing protocols for identification, referral, and serology of IP, and to disseminate them within the hospital

5. To define a workflow for proactive identification and immunization for current and potential IP, and to define a referral list toward PMPHD

6. To designate representatives within the hospital and primary care responsible for coordinating IP referral and immunization, in collaboration with PMPHD and hospital and primary care managers

7. To train hospital and primary care professionals on identifying, referring, and immunizing/vaccinating IP, as well as their household contacts and the healthcare professionals managing them

8. To train nursing staff on IP immunization recommendations

9. To create identification, stratification and PMPHD referral protocols aimed at IP and patients liable to receive immunosuppression

10. To establish a protocol in which hospital pharmacy and PMPHD will be involved in reviewing and validating immunosuppressive therapies

IP: immunocompromised patient; PMPHD: preventive medicine and public health departments

Validation of the results in the national meeting and identification of indicators

A total of 101 family and community medicine and nursing, hematology, hospital pharmacy, intensive care medicine, internal medicine, nephrology, neurology, PMPHD, and pulmonology professionals from 59 centers participated in the multidisciplinary national meeting. In this meeting, 28 healthcare quality indicators were identified that would be used to objectively measure the progress of the centers with regard to the different immunization models. Sixty-five specialists in IP management participated in the two-round Delphi survey in which these indicators were finally validated.

The healthcare quality indicators on which there was consensus were divided into three main categories: (i) structural indicators, addressing material and human resources and available infrastructure needed in the management of IP; (ii) healthcare process indicators, measuring the adequacy of all the established healthcare processes; and (iii) result indicators, assessing the effectiveness (healthcare outcomes), efficiency, and quality of care (patient security, continuity of care, equity, etc.). All final indicator definitions are listed in Table 3.

Table 3.

List of healthcare quality indicators presented and Delphi-validated in the CARABELA-IP multidisciplinary national meeting.

Structural indicators
Indicator	Description
IP identification and referral protocols	Existence of a protocol for identifying and referring IP candidates for immunization from various departments to PMPHD (Yes/No)
Rapid referral	Existence of a fast-track referral procedure from different departments to PMPHD (Yes/No)
Training on immunization	Existence of a training plan for primary and hospital care professionals on vaccines and IP, including updates on current and future immunization alternatives (Yes/No)
EHR coding	Availability of EHR registries and coding systems to categorize IP (Yes/No)
EHR immunization alerts	Presence of EHR visual alerts to inform immunization needs based on patient profile and prescription history (Yes/No)
Absenteeism alerts to PMPHD	Presence of visual EHR alerts for reporting patient missed appointments in PMPHD (Yes/No)
Digital patient support tool	Availability of a digital tool/resource for patients to address immunization-related questions (Yes/No)
Vaccination coverage dashboard	Existence of a dashboard to monitor vaccination coverage among IP (Yes/No)^a
Primary care involvement in vaccination of IP household contacts	Existence of a protocol for involving primary care in vaccinating household contacts of IP (Yes/No)
Patient satisfaction surveys	Implementation of patient satisfaction and experience surveys (Yes/No)
Nursing consultation availability	Availability of nursing consultations within PMPHD (Yes/No)
Process Indicators
Indicator	Description
Prophylactic assessment in origin departments	Percentage of IP evaluated for prophylactic suitability in their origin departments
Pre-referral serology	Percentage of IP for whom serology is requested in their origin services before referral to PMPHD
Referral rates	Percentage of IP referred from origin departments to PMPHD for immunization^b
Time from IP identification to initial consultation in PMPHD	Average time from identification of an immunocompromised patient to a first consultation in PMPHD (days)^b
Time from IP identification to immunization	Average time from identification to initial vaccination/immunization (days)^b
Time from urgent referral to PMPHD to immunization	Average time from urgent referral to immunization in PMPHD (days)^b
Vaccination in PMPHD	Percentage of IP referred to PMPHD who receive vaccines/immunization in these departments^b
Proactive IP identification in PMPHD	Percentage of IP proactively identified by PMPHD^c
Follow-up consultation in PMPHD	Percentage of IP seen in PMPHD who receive a follow-up consultation in these departments^c
Results Indicators
Prophylactic suitability by immunodeficiency type	Percentage of IP receiving prophylaxis in origin departments in line with their immunodeficiency
Vaccination/immunization coverage	Percentage of IP properly vaccinated/immunized, considering patient-personalized timings, types of vaccine/immunization, and dose numbers
Coverage for household contacts	Percentage of IP household contacts properly vaccinated
Coverage among professionals	Percentage of healthcare professionals who receive vaccination^d
Annual influenza vaccination in PMPHD	Percentage of IP seen by PMPHD who receive an annual influenza vaccine
Annual COVID-19 vaccination in PMPHD	Percentage of IP seen by PMPHD who receive an annual COVID-19 vaccine
IP and household contact education on vaccination importance	Percentage of IP and corresponding household contacts who receive education on the importance of vaccination
Patient satisfaction	Percentage of IP satisfied with the care received

EHR: electronic health records; IP: immunocompromised patient; PMPHD: preventive medicine and public health departments.

a

Implies the need to define different indicators per patient type.

b

Implies aggregated, department- and pathology-based analyses.

c

Implies aggregated and pathology-based analyses.

d

Implies department-based analyses.

Discussion

The management of IPs is subject to several challenges, ranging from the identification of the patients themselves, which is difficult due to the widely differing clinical situations, to the proper referral from origin departments toward PMPHD in order to achieve immunization against preventable infections. In this scenario, CARABELA-IP initiative not only sought the coverage of unmet medical or prevention needs but also aimed to establish an integral immunization model guaranteeing a standardized, efficient, and coordinated process.

The identification of three immunization models will help the centers classify their own processes in order to determine the improvement they would like or are able to achieve (that is, improvement within the same immunization model or advancement to another). This method will foster a standardized immunization process characterized by healthcare coordination across the different levels and departments involved in the management of IP, by identifying and solving the improvement areas detected in each of the models defined. The three immunization models differ from each other in terms of the involvement of healthcare professionals managing IP. This is particularly applicable to the role of PMPHD and the nursing staff collaborating in the immunization of these patients, whose participation has historically been described as paramount in the context of some specific complications in IPs.²⁸

The definition of integral and integrated communication and coordination models and the protocolized identification, stratification, and referral of IPs to PMPHD are crucial to ensure personalized, efficient, optimized and early immunization. Establishing individualized pharmacological prophylaxis plans will help reduce and prevent infections and complications normally associated with IPs.^29–31 All these approaches will address the unmet needs of PMPHD^32,33; the availability of a single, electronic medical history flagging an IP, for example, will ensure their comprehensive and coordinated management (from patient identification to post-immunization follow-up), by not only the PMPHD but also other pertinent professionals.

Training for professionals on IP management is essential for promoting awareness of the importance of immunization/vaccination of patients, their household contacts, and the healthcare professionals themselves,^34–36 especially when we know that IP management is the responsibility of a significant number of medical specialties, including cardiology, dermatology, gastroenterology, hematology, hospital pharmacy, infectious diseases, internal medicine, medical oncology, nephrology, neurology, ophthalmology, PMPHD, primary care, pulmonology, and rheumatology, among others. Training, therefore, as highlighted in the results of the improvement areas, potential solutions and healthcare quality indicators of the CARABELA-IP initiative, must include updated information on the different kinds of patients and the current recommendations and immunization schedules.⁹ These initiatives will also serve to improve patient identification, referral, and immunization, thus reducing the incidence of preventable infections. Patients and their household contacts should also be educated and empowered using clear, updated and accessible resources, as proper immunization results in a better quality of life.^9,11,37 The CARABELA-IP initiative has underlined the importance of the proper immunization of household contacts and healthcare professionals who come into contact with IPs and the need for implementing appropriate immunization processes to protect IPs against infections.

The initiative's primary limitation was the absence of a quantitative methodology, although the definition of healthcare quality indicators is important for assessing immunization processes related to organization, structure, resources, and engagement of IP and household contacts. Besides, another potential limitation relates to the difficulty to extrapolate the initiative's results to the broad Spanish healthcare ecosystem. However, the participating centers were selected taking this potential limitation into account, and each of them represented a different scenario regarding the region in Spain where IP are immunized and the daily clinical experience with these patients.

Conclusions

The strengths of this initiative include the participation of a considerable number of healthcare professionals representing almost all the medical specialties involved in IP management. By means of the dissemination, implementation, and regional refinement of the findings described, CARABELA-IP, as an evolving initiative, will foster multidisciplinary coordination and communication strategies, taking into account all the healthcare levels in order to overcome current barriers in identifying and managing IP. It will guide the definition and development of continuous training programs to improve the knowledge and attitudes of healthcare professionals responsible for IP management, and overall, this integral and integrated approach will contribute to the improvement of IP healthcare in Spain.

Disclosure of the use of generative AI and AI-assisted technologies in the process of writing

During the elaboration of this manuscript, the authors used ChatGPT to improve legibility and language. After using this tool, the authors reviewed and edited the content when needed, assuming all the responsibilities regarding the manuscript's contents.

CRediT authorship contribution statement

All authors (Jaime Pérez, Manuel García de la Vega, Gregorio Montes, Inmaculada Mediavilla, José Francisco Soto, Luciano Escudero, Marta Eva González, Victoria Nartallo, and María Fernández-Prada) equally contributed to conceptualization and writing (original draft preparation and writing and review and editing). All authors, including those participating in the CARABELA-IP Scientific Committee equally, contributed to writing (final draft review). All authors have read and agreed to the published version of the manuscript.

Funding

This work was funded by AstraZeneca Farmacéutica Spain.

Acknowledgements

The authors acknowledge the participation of all the professionals attending the national multidisciplinary meeting of the CARABELA-IP initiative, and all those involved in the pilot phase, from Hospital Universitario Álvaro Cunqueiro (Vigo, Galicia), Hospital Universitario y Politécnico La Fe (Valencia, Comunidad Valenciana), Hospital Universitario Príncipe de Asturias (Alcalá de Henares, Comunidad de Madrid), Hospital Universitario Parc Taulí (Sabadell, Cataluña), and Hospital Universitario Reina Sofía (Córdoba, Andalucía).

Medical writing support under the guidance of the authors was provided by Javier Arranz-Nicolás, PhD, and Beatriz Albuixech, PhD, from Medical Statistics Consulting (MSC), Valencia, Spain, in accordance with Good Publication Practice guidelines (DeTora, L M. et al. Ann Intern Med. 2022).