This methodological, multiphase study comprises 2 main phases to develop and validate the PERSONAE scale for assessing the preparedness for self-monitoring and self-management of oral anticoagulation in adult patients. The protocol adheres to the “COnsensus-based Standards for the selection of health Measurement INstruments” (COSMIN) guidelines for instrument development [19].

Phase 1 focused on conceptualizing the PERSONAE scale through a developmental methodological approach involving 3 primary steps. First, a literature review was conducted to identify all relevant elements related to the preparedness for self-monitoring and self-management of oral anticoagulation (anticipated between May 2023 and July 2023). This review was recently published elsewhere [13]. Second, a consensus meeting among developers was held to examine the findings of the literature review and endorse its synthesis (anticipated time: September 2023). Finally, the situations representing patients’ preparedness will be operationalized, and an external panel of experts, including nurses, physicians, and pharmacists, will determine the face and content validity of the newly developed scale (anticipated time: October 2023). Phase 2 focused on the validation procedures. Initially, the PERSONAE scale, containing items with acceptable content validity, was used for cross-sectional data collection from January to May 2024. The Mokken scaling analysis (MSA) procedure will be used to assess how the items in the first version of the scale behave in response to varying levels of the theoretical latent trait (preparedness). MSA is preferred over exploratory factor analysis in this study as it allows selecting items with the highest scalability, leading to a brief, unidimensional measure computed in a single score. Once a stable unidimensional PERSONAE scale is developed, a second round of cross-sectional data collection was performed from June to September 2024 to cross-validate the plausible unidimensional structure of the scale.

In phase 1, a panel of 8-12 experts, comprising nurses, physicians, and pharmacists, evaluated the relevance and clarity of the proposed items derived from the literature review (content validity). The experts provided written consent to use their sociodemographic and professional characteristics for scientific reporting, as content validity is closely linked to the characteristics of the involved experts. This phase cannot be anonymous to ensure transparency, and variables such as sex, age, academic title, experience in studies testing content validity, and experience in oral anticoagulation were collected.

Once adequate content validity was established (December 2023), data collection commenced at the IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico [Institute for Research and Healthcare]) Policlinico San Donato, using 2 cross-sectional data collection rounds using web surveys. A convenience sampling procedure was used, disseminating the web surveys through social media campaigns, newsletters, and flyers of associations involving anticoagulated patients, such as “Associazione Italiana Cardiopatici Congeniti” (AICCA). Participants for the second round were selected based on the same approach, with communication to prevent overlapping responses from participants who completed the survey.

Quality control measures have been implemented to ensure the integrity and quality of the data collection process: automatic data validation checks are included in the survey software to ensure that all responses are complete and adhere to the required format; unique identifiers were used for each participant to prevent duplicate responses in the dataset; and after data collection, statistical analyses were performed to identify any outliers or inconsistencies in the responses, which were then reviewed for accuracy.

The sampling procedure will use a cloud-data recording system and web surveys disseminated through social media campaigns, newsletters, and flyers. The local study coordinator and the principal investigator will manage the sampling procedure following good clinical practice principles. An expected response rate of approximately 60% is anticipated, which is considered adequate [20]. This expectation is based on several considerations, including using targeted engagement strategies such as precontacting potential participants and leveraging multiple dissemination channels. In fact, this rate aligns with the upper bound of the confidence interval from a recent meta-analysis, which reported an average response rate of 44.1% across 1071 studies in educational research [20]. Studies achieving similar response rates are those that have successfully implemented strategies to engage participants actively.

The sample size for phase 1 will be 8-12 experts. The sample size required for phase 2 to perform the Mokken scaling analysis was determined considering the 20 items derived from phase 1 (content validity phase). A simulation-based power analysis was performed in R (R Foundation for Statistical Computing; library “Mokken”), as shown in Multimedia Appendix 1. The aim of the simulation was to estimate a sample size that would provide sufficient statistical power, set at 0.8, to detect a minimum H coefficient of 0.3, indicative of a moderate scale according to Mokken’s hierarchy. The H coefficient in Mokken scaling analysis measures the strength of the hierarchical relationship among items in a scale as it quantifies the extent to which items form a cumulative scale. A custom simulation function was created using R statistical software, with the following parameters defined: 20 items, initial sample (n= 200), number of simulations=100, desired power=80%, minimum H coefficient=0.3, and maximum number of iterations=30. For each simulation iteration, the function generated a matrix of binary data representing responses to the 20 items, with responses simulated under a simple random model (ie, the probability of success was 0.5 for each item). The results from the simulation suggested that a sample size of 500 patients would be needed to achieve the desired power of 0.8 for our MSA. The MSA procedure will help reduce the number of items to the first 10-15 items that define the preparedness for self-monitoring and self-management of oral anticoagulation in adult patients. The required sample size for the second round of data collection will be determined through Monte Carlo simulations, aiming to achieve a power of 0.8 for the confirmatory factor analysis (CFA) model.

In phase 1, experts must have at least 1 year of experience in managing patients with VKAs, hold at least a master’s degree in nursing, pharmacy, or an MD degree, and have proficiency in the Italian language. Exclusion criteria for experts include conflicts of interest regarding the topic. In phase 2, patients aged 18 years and older will be included under oral anticoagulation treatment in an anticoagulation clinic for at least 3 months, with appropriate cognitive functioning and the ability to provide informed consent. Patients will be excluded based on more specific criteria to ensure the homogeneity and reliability of our data: those with a high Charlson Comorbidity Index (CCI>4), indicating severe concurrent medical conditions that could confound the study outcomes; patients undergoing any other experimental treatment affecting coagulation; and those with a history of noncompliance with medical regimens as reported by their health care providers.

Patients who agree to participate will access a web-based survey (SurveyMonkey) through social media channels, mobile messages, or emails. The invitation will include all relevant information about the study’s aim, methods, and tasks required for participation. Patients will confirm the inclusion and exclusion criteria during the initial access, and those who do not meet the criteria can opt out.

The data collection tools will include the PERSONAE scale derived from the content validity phase, a sociodemographic and clinical data form, and a graphic rating scale for assessing patients’ preferences for technology-assisted learning options. Sociodemographic data will include age, sex, marital status, educational level, and occupation, while clinical variables will encompass time in oral anticoagulation, clinical indication for anticoagulation, %TTR, and history of thromboembolic or bleeding complications in the last 3 months. These clinical variables are consistent with previous research, such as the studies that developed measures of knowledge in the same population [21,22], which examined similar sociodemographic and clinical factors to assess anticoagulation knowledge in the Italian population. This alignment ensures that our data collection is grounded in established theoretical frameworks and allows authors to generate hypotheses relevant to our target population.

The data analysis will involve the use of various statistical methods to develop and validate the PERSONAE scale.

For the first data collection round, MSA will be conducted using the “mokken” package in R [23]. MSA allows for the hierarchical evaluation of items, and the most relevant items that measure preparedness for self-monitoring and self-management of oral anticoagulation will be selected for the PERSONAE scale [24]. Loevinger’s coefficient of homogeneity function will be used to assess the scalability of the items. Monotonicity violations will be checked, and violations below 80 will be consistent with the requirements of a Mokken scale [23,25]. Loevinger’s coefficients of homogeneity (H) at the scale, item, and pairs of items level will be computed, where H values equal to or greater than 0.3, 0.4, or 0.5 indicate weak, moderate, or strong scales, respectively [23,25]. Item pairs violating monotonicity will be excluded, and floor and ceiling effects in data distribution will be assessed. Invariant item ordering (IIO) will be performed to further narrow down the pool of questions based on monotone homogeneity [25]. The IIO procedure will remove items one at a time until no significant violations are found. The Htrans (H^T) coefficient will express the accuracy of the IIO selection, and H^T>0.3 will denote proper IIO process and consistent Mokken scales. The final set of questions will be used to calculate ρ coefficients for reliability using the Molenaar-Sijtsma technique [26]. This approach is particularly adequate for assessing reliability in MSA because it provides a robust estimate of the internal consistency for nonparametric scales. The Molenaar-Sijtsma technique is well-suited for evaluating the scalability and reliability of the items within the scale, ensuring that the PERSONAE scale reliably measures the construct of preparedness for self-monitoring and self-management of oral anticoagulation.

CFA will be used to cross-validate the plausible unidimensional structure of the PERSONAE scale derived from the MSA, theoretically containing 10-15 items, using Mplus 8.1 (Muthén and Muthén, 2017). An unrestricted and unspecified model will be used with a maximum likelihood robust estimation of parameters. A confirmatory factor analysis with covariates will be used to estimate measurement invariance between subgroups if linear relationships between participant characteristics and the scale’s total score are detected [27]. Modification indices will be explored to identify items causing a violation of invariance. Items causing invariance will be evaluated for possible deletion from the final scale. The adequacy of confirmatory factor analyses in explaining sample statistics will be assessed using various fit indices, such as chi-square, chi-square/degree of freedom, comparative fit index, Tucker-Lewis index, and root mean square error of approximation [28]. Invariance testing based on different levels of CCI and other potential confounders will be considered if needed and is feasible to ensure that the scale functions equivalently across groups with varying levels of comorbidity and demographics.

Missing data will be managed using an available-case approach for missingness lower than 5% or regression imputations for missingness equal to or higher than 5%, assuming missing at random. The significance level for all analyses will be set at 5%. The software used for the analysis will include Mplus (version 8.1, Muthén and Muthén), IBM SPSS Statistics for Microsoft Windows version 27, and R (version 4.2.1, R Foundation for Statistical Computing).

The present protocol was approved by the Ethical Committee of Ospedale San Raffaele (protocol number 52/INT/2023). Ethical considerations will be carefully adhered to throughout the research process.

In the first stage of the study, which involves experts assessing the content validity [29,30], written informed consent will be obtained from each expert. They will be fully informed about the study’s objectives and their voluntary participation in the process. During the second part of the study, data collection will be carried out through anonymous web surveys. As per European Regulation 2016/679 and Legislative Decree 101/2018, this type of study ensures anonymity and does not require individual written informed consent from the participants [31]. However, to ensure transparency and participant understanding, a simple and clear presentation page will be provided to patients before they proceed to complete the web-based questionnaire. This page will explain the study’s purpose, the voluntary nature of their participation, and the anonymity of the survey.

The research team will prioritize the confidentiality and privacy of all participants involved in the study, adhering to the ethical principles outlined in the Declaration of Helsinki. Personal data will be handled with utmost care, and all data collected will be stored securely and accessible only to authorized personnel involved in the study. Any potentially identifying information will be removed from the dataset to ensure complete anonymity. Throughout the study, participants’ rights and welfare will be protected, and any potential risks will be minimized. The study findings will be reported and disseminated in a manner that preserves anonymity and confidentiality. Researchers will act responsibly, maintaining the highest ethical standards and ensuring that the study is conducted with integrity and respect for the participants’ rights and well-being.

This study outlines a methodological approach to developing and validating the PERSONAE scale, a self-report measure aimed at assessing the preparedness for self-monitoring and self-management of oral anticoagulation in adult patients. This novel scale aims to help health care providers discern patients’ preparedness for autonomous oral anticoagulation management, potentially leading to customized treatment strategies that enhance patient independence and treatment adherence. High scorers on the PERSONAE scale might be suitable for self-testing and adjusting their medication. At the same time, those with lower scores could benefit from targeted educational programs to improve their management capabilities, pending further research to establish specific scale cutoffs for optimal outcomes. It is important to note that the practical application of this scale and its cutoff points require empirical testing in future research to assess criterion validity and establish effective thresholds for different patient outcomes.

Phase 1 of the research protocol, based on a developmental methodological approach, was based on a literature review [13], followed by a consensus meeting among developers who have operationalized the literature into 20 measurable items of preparedness, leading to the initial version of the scale as per previous research focused on developing new self-report measures [32,33]. An expert panel consisting of 12 professionals from diverse health care disciplines (cardiology, nursing, pharmacy, and internal medicine) validated the content of the PERSONAE scale in December 2023. The experts, who brought a wealth of experience from their respective fields, ensured that the scale’s content was relevant and applicable to various professionals involved in anticoagulation management. This multidisciplinary approach enriched the scale’s content validity, ensuring comprehensive coverage of the necessary competencies for effective self-management. This phase was instrumental in creating a scale that is scientifically sound and clinically meaningful. This initial phase set a solid foundation for the subsequent validation phase, aiming to confirm that the scale accurately measures preparedness in a way that is predictive of patients’ ability to manage their anticoagulation therapy effectively.

In phase 2, validation procedures will be conducted to ensure the reliability and validity of the scale, and it is anticipated to end in September 2024. This process will require 2 cross-sectional data collections among Italian adult patients currently undergoing oral anticoagulation treatment. The collected data will be used to assess the scale’s psychometric properties and determine its performance in measuring preparedness for self-monitoring and self-management of oral anticoagulation [34]. More precisely, the first cross-sectional data collection will provide the needed power to perform the MSA procedure and determine item behavior in response to varying levels of the theoretical latent trait (preparedness) [35]. The second data collection will be based on the version of the scale updated from the analytics of the first data collection, and a CFA will be used to cross-validate the unidimensional structure of the PERSONAE scale. Cross-validation helps assess the generalizability of the scale’s results and allows researchers to determine if the validity holds true beyond the initial sample used for scale development [36].

Several limitations should be acknowledged. First, the sample size for the validation phase was based on a power-based simulation and Monte Carlo simulations, which may have inherent assumptions that could affect generalizability. Expanding future studies to include larger and more diverse populations could enhance the scale’s validity across varied demographics and age groups. Second, the use of web surveys for data collection may introduce response biases, particularly biases associated with self-reporting, such as recall bias and social desirability bias. Although measures such as ensuring participant anonymity and confidentiality are planned to mitigate these issues, the influence of these biases cannot be entirely eliminated. In addition, further exploration into potential sources of bias, including sampling biases due to nonrandom selection methods and the impact of the data collection medium on participant engagement and accuracy, is necessary. Limitations stemming from the analysis methods, such as potential confounding factors not accounted for in the statistical models, should also be critically evaluated. Future research should aim to address these limitations by adopting more robust sampling frameworks, using mixed methods for data collection, and applying comprehensive analytical techniques to provide a deeper understanding of the scale’s applicability and accuracy.

While previous studies have explored various components of oral anticoagulation therapy, such as patient knowledge, health literacy, and self-efficacy in self-management, the PERSONAE scale introduces a unique comprehensive measure [2,7-9,17]. It is the first self-report tool designed to assess both self-monitoring and self-management preparedness among adult patients on oral anticoagulation therapy. This distinction sets the PERSONAE scale apart from existing scales that typically focus on isolated aspects of anticoagulation management. Existing measures often independently evaluate patient knowledge or health literacy, which does not necessarily translate to practical, actionable patient readiness. In contrast, the PERSONAE scale encompasses a broader spectrum of preparedness, integrating aspects of knowledge, self-efficacy, and practical application capabilities into a single measure. This integrative approach not only aids health care providers in identifying well-prepared patients but also pinpoints those who might benefit most from targeted educational interventions. Furthermore, the development methodology of the PERSONAE scale enhances its robustness and applicability. The scale was crafted to ensure scientific soundness and clinical relevance through a rigorous, multiphase approach that included a literature review, expert consensus, and external validation. This methodological solidity supports its potential for widespread adoption and use in clinical settings, distinguishing it further from other tools that may lack such comprehensive validation.

The PERSONAE scale represents a significant advancement in the management of oral anticoagulation therapy. It is the first comprehensive self-report measure specifically designed to assess the preparedness of adult patients for self-monitoring and self-management. This tool will enable health care providers to better identify patients ready to manage their treatment autonomously, possibly enhancing patient outcomes and optimizing therapy adherence. Our study aims to determine the scale’s robust psychometric properties, which underscore its reliability and applicability in clinical settings. The PERSONAE scale’s ability to encompass a broad spectrum of preparedness, from patient knowledge to self-efficacy and practical application skills, sets it apart from existing tools focusing on narrower anticoagulation management aspects. Looking forward, the PERSONAE scale has the potential to transform patient management in clinical practice globally. By facilitating the identification of patients suited for self-testing, the scale supports tailored educational interventions that can improve self-management skills among those less prepared. This approach promises to enhance patient autonomy and aims to reduce health care costs by improving treatment efficiency and satisfaction. Future research should focus on validating the scale across diverse patient populations to ensure its broader applicability. In addition, integrating the PERSONAE scale into routine clinical practice will be crucial for evaluating its impact on long-term patient outcomes and health care systems. Ultimately, the scale is poised to play a pivotal role in advancing patient-centered health care solutions in anticoagulation therapy.