1 Introduction

Improving safety in the use of medicines, especially those that are high risk for adverse events, was identified by the World Health Organization as the third Global Patient Safety Challenge in its “Medication Without Harm” document published in March 2017. A medication error is defined as any avoidable event that may lead to inappropriate use of medication that has the potential to harm a patient [1]. Medication errors are common worldwide [2]. The oncology pharmacy at our institution has been striving to reduce the risk of serious and preventable medication-related harms by developing safer and more efficient systems at every step in the medication process, including prescribing, dispensing, preparation, compounding, administration, and monitoring.

Antineoplastic agents are used mainly in the treatment of malignant neoplasms. With the development of antineoplastic therapy (AT), there has been a significant increase in the survival rate of patients with malignant diseases [3]. The annual frequency of incidents related to the preparation and administration of AT is estimated to be between 2% and 5%. Therefore, there is a need to implement strategies aimed at reducing the risk of adverse events, which remains high because of the increasing complexity of health care and the requirements for greater skills and specific knowledge of the part of clinicians [4].

In a study by Ranchon et al., the pharmacy unit at a tertiary hospital in France was found to have received 6,607 prescriptions during a 12-month period corresponding to 22,138 different antineoplastic agents. In total, 449 medication errors involving 341 prescriptions were identified, which translated into an overall medication error rate of 5.2% [5]. Another study, which was performed in the oncology pharmacy at a tertiary hospital in Brazil, identified untreated health problems, incorrect administration, contraindications, prescription errors, drug interactions, incorrect dose and/or duration of AT, inadequate storage, and dispensing errors to be the main factors that interfered with the effectiveness of AT [6]. In a further study, Weingart et al. observed that although the rate of chemotherapy-related harm appeared to be lower than in comparable studies involving non-oncology patients, more research was required in patients receiving AT. Such research should characterize the nature and extent of harm and identify which interventions are best able to mitigate medication errors [7].

AT compounding is undertaken only by pharmacists with specialist expertise in oncology, requires the assistance of a pharmacy technician, and entails several steps, starting with evaluation of the prescription and ending with dispensing of the AT for administration to the patient [8]. A quality assurance system is essential for services involved in preparing AT to decrease the risk of error/harm and improve the skills of the pharmacy team. However, reports on improvement cycles are rare in the scientific literature.

The aim of this study was to evaluate the effectiveness of implementation of a program to improve AT compounding in a centralized intravenous admixture service (CIVAS) of a university hospital.

2 Methods

This study used a quasi-experiment before-and-after design with a quantitative approach to investigate the implementation of an improvement project developed in the period from September 2021 to February 2022 in a university hospital located in the city of Natal, Rio Grande do Norte, Brazil. The improvement project is a strategy involving quality evaluation and reflection on the work process, identification of a quality problem, decision of the criteria to measure the quality level, collection of the necessary data to evaluate and discuss the results, and definition of actions and quality improvements [9]. In this sense, the service recipients were the adult patients under antineoplastics drugs in the hematology and clinical oncology departments, while the providers were the team of pharmacy technicians and pharmacists.

The study followed the model and norms adopted by the Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) [10]. The research was conducted at the CIVAS of a university Hospital Pharmacy Sector in Brazil, qualified as a High Complexity Assistance Unit in Oncology. The team that works in the CIVAS comprises two pharmacists and three pharmacy technicians.

3 Results

The results of the initial evaluation (before the intervention, September 2021), the first re-evaluation (post-intervention, November 2021), and the second re-evaluation (post-intervention, February 2022) are presented below.

3.2 Opportunities for Improvement

When evaluating the opportunities for improvement using the Pareto chart (Figure 1), we observed that the C3, C4, and C1 criteria were the most problematic after the first evaluation, accounting for 86.4% of all detected failures. Furthermore, 44 instances of noncompliance were recorded during the initial evaluation, seven of which persisted at the time of the first re-evaluation and six at the time of the second re-evaluation, indicating resolution of 37 deficiencies.

4 Discussion

Overall, the results of this study demonstrate an improvement in an AT compounding service. These interventions required low financial cost but provided significant improvement in the compounding quality and could be easily incorporated into the service routine.

Regarding criterion C1 namely “every medical prescription must be evaluated by the pharmacist,” we determined that an oncology-qualified pharmacist's review and validation of the AT is crucial to manage medication risks, by detecting, solving, and preventing drug therapy issues. This approach enables the pharmacist to guarantee treatment safety and efficacy, minimize financial loss, and lessen errors in AT preparation [13]. The participation of a multi-professional team, in which professionals work together to ensure safe assistance to the patient, is of paramount importance [14].

Although prescription errors are well documented in the literature, a study performed at a hospital in southern Brazil demonstrated the vulnerability of the prescribing system, even when computerized, and the importance of safeguards and organized processes to avoid errors [15], underscoring the importance of evaluation of all prescriptions by a pharmacist with specialist expertise in oncologic medication.

A 10-week observational study at a university hospital in France, which assessed the clinical impact of pharmaceutical interventions based on analysis of prescriptions for injectable antineoplastic agents by pharmacists, demonstrated that the interventions, mostly aimed at recommending dosage adjustments, showed potential to prevent prolonged hospitalizations, permanent disabilities, and various neurological, hematological, renal, gastrointestinal, and cutaneous toxicities [16].

These findings reinforce the importance of pharmaceutical evaluation in the prescribing process, evidencing its clinical significance in ensuring safer and more effective treatments for cancer patients.

Regarding criterion C2, “all AT must be correctly identified,” the compliance rate in the initial evaluation was 92%. Although there was no direct intervention on this criterion, the rates in the subsequent re-evaluations rose to 98% and 100%, respectively. It is advised to identify the drug name, dosage, volume, route of administration, and start and end date [4]. Beyond identifying the drug used in AT, it is essential to verify the patient's identity, check for allergies, assess the drug's toxicity profile, determine whether any medications can mitigate potential complications, and monitor the patient before, during, and after administration of AT [4].

In terms of criterion C3, specifically “all tubing must be correctly filled with a large volume of saline solution,” air bubbles in the lumen of the infusion line, depending on their size, can prevent administration of medication. This may lead nurses to open the infusion system in an attempt to address the issue, causing spillage of AT and occupational exposure of staff members to these agents [17]. A study conducted in a chemotherapy service at a university hospital in France detected several errors during AT compounding, one of the most common being inadequate filling of the infusion line [18].

Regarding criterion C4, “all supplies be separated by the patient before being transferred to the compounding area,” an initial evaluation identified a compliance rate of 77%. After the acquisition of more baskets for the separation of supplies, compliance was 100% in both re-evaluations. Moreover, these baskets should be monitored for supply separation, infusion bag surfaces, gloves, and shelves for storage of medications to ensure the safety of health professionals who manipulate the AT [19].

Criterion C5, stating “all manipulated AT must be visually inspected,” already demonstrated high compliance initially. Although no intervention was performed on this criterion, compliance in subsequent evaluations reached 100%. Thus, ensuring correct AT identification, inspecting the therapy before infusion, and checking the medication's appearance is crucial [4].

Additionally, we wish to emphasize the importance of informing the patient and companion about the therapy. Educational materials can be developed to include information on diagnosis, treatment objectives, expected treatment duration, administration scheme, drug interactions, both rare and common AE, the potential impact of AT on sexuality and fertility, guidance on when to contact the health team or seek immediate care, and follow-up plans [14].

The improvements identified in this study have the potential to benefit other healthcare facilities by serving as a model for improving AT compounding services. The low-cost interventions and their adaptability to different operational contexts make them highly replicable for other healthcare services. By implementing similar interventions, facilities can improve patient safety, optimize resource utilization, and standardize processes, contributing to higher quality of care.

This study had some limitations. First, the investigation and application of the intervention were only at the research site; therefore, these results may only reflect a local phenomenon, affecting the interpretation and generalizability of the results. Another limitation is the performance of two evaluation moments to monitor the improvement the criteria. Several published studies provide data on the incidence of errors in chemotherapy. However, it is difficult to compare these data due to the variety of study designs and methods and the diversity of the parameters used.

5 Conclusions

This study demonstrated an improvement in all five criteria of quality in the AT compounding after the implementation of interventions, with an increase in the values of compliance with all criteria after the second evaluation. Statistical significance was observed in the criteria of medical prescription evaluated by the pharmacist (C1), filling of the tubing (C3), and supplies separated by the patient (C4).

The implementation of the improvement project was considered effective as it triggered improvements in AT compounding. Finally, we conclude that multifaceted interventions can bring about positive changes in the quality of AT compounding and that periodic monitoring is required to maintain the level of quality achieved and to perform new interventions when appropriate.

Author Contributions

Luciana Moreira Dantas Barreto: conceptualization (equal); data curation (equal); formal analysis (equal); investigation (equal); writing – original draft (equal); writing – review and editing (equal). Joyce Karolayne dos Santos Dantas: data curation (equal); formal analysis (equal); investigation (equal); writing – original draft (equal). Tâmara Taynah Medeiros da Silva: investigation (equal); supervision (equal); visualization (equal); writing – original draft (equal); writing – review and editing (equal). Louise Constancia de Melo Alves Silva: supervision (equal); validation (equal); visualization (equal); writing – original draft (equal). Kauanny Vitoria Gurgel dos Santos: methodology (equal); validation (equal); visualization (equal); writing – original draft (equal). Laura Lima Souza: visualization (equal); writing – original draft (equal). Daniele Vieira Dantas: conceptualization (equal); methodology (equal); project administration (equal); writing – original draft (equal). Rodrigo Assis Neves Dantas: conceptualization (equal); methodology (equal); project administration (equal); resources (equal); supervision (equal); validation (equal); visualization (equal); writing – review and editing (equal).

Ethics Statement

The study protocol was approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte under the Opinion and Certificate of Ethical Appreciation (49005521.8.0000.5292) and performed in accordance with the ethical guidelines stated in the Declaration of Helsinki. Service staff were informed of the research aims, method of data collection, and benefits and risks.

Consent

Consent was obtained from all study participants for the use and storage of their data. Participants were also assured that their data would be treated confidentially and anonymized.

Conflicts of Interest

The authors declare no conflicts of interest.