Impact of Changing the Appearance of Oral Antineoplastics on Adherence and Continuity of Treatment, Patient-reported Health Outcomes, and Patient Experience of Care

Oral chemotherapy is a convenient and flexible option for cancer treatment that can improve patients quality of life and increase adherence to treatment compared to traditional intravenous chemotherapy. However, since patients are responsible for taking the medication, there can be issues with continuity and adherence. Like other medications, generics of existing oral chemotherapy have emerged, which help reduce costs and improve access to this therapy. These generics contribute to a more sustainable healthcare system, so it is necessary to implement effective strategies for their adoption.

Although generic treatments have been shown to be just as effective as the original drug, there is no regulation requiring the pill to have the same shape and color as the original (what we refer to as appearance). Additionally, the packaging of the treatment is different as it is specific to each brand. Therefore, a patient on a specific treatment may switch from the original medication to a generic or from one generic to another, which may have a different appearance in both the pill and the packaging.

It has been observed that these changes can lead to medication errors or a loss of patient confidence, resulting in decreased continuity and adherence to treatment. These issues have been seen with other medications for chronic diseases but have not been studied in cancer patients to date. In these patients, despite the nature of the disease suggesting they would be adherent to treatment, previous studies have shown that this is not the case, with only about 70% of patients being adherent. This lack of adherence affects treatment efficacy, increases the risk of disease relapse, and therefore negatively impacts patient s quality of life and survival while also increasing costs.

Therefore, this study focuses on evaluating whether these changes in pill appearance and/or packaging impact treatment continuity and adherence, as well as other relevant patient outcomes and their experience with the healthcare received. Additionally, we want to analyze whether there are patient variables (such as health literacy, age, or clinical variables) that influence the impact of these changes. Given the differences in adherence between men and women, it is essential to conduct these analyses separately for both genders.

The results obtained from this study will contribute to the development of educational strategies for managing oral chemotherapy by patients and healthcare professionals. Additionally, new evidence will be generated to allow decision-makers to establish policies, either by choosing treatments with the least change in appearance or by regulating the appearance of treatments. All of this will contribute to greater treatment effectiveness, improved patient quality of life, and a lower rate of disease recurrence.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Adherence, Patient

Detailed Description

The project "APAR-AdhNEO" aims to evaluate the impact of a change in appearance (changes in shape and/or color of the tablet and/or packaging) of the prescribed oral antineoplastic (ANEO) (whether switching from brand-name to generic or between generics) on the patient's healthcare experience, treatment continuity and adherence, as well as patient-reported outcomes, and whether this differs between men and women.

Study Design Specifications The study follows a mixed-methods design. For secondary outcome 1 (secondary outcomes described in outcomes measure section), a prospective study will be designed to evaluate the frequency of changes in ANEO prescriptions. For secondary outcomes 2-5, a before-and-after study will be conducted to assess the impact of medication changes on various variables.

As part of the study evaluating the patient s experience with healthcare (secondary outcome 2), in addition to quantitatively assessing this experience before and after the change, a qualitative study will be conducted using focus groups with patients.

Sample Size Estimation According to a systematic review conducted by the research team, the frequency of non-adherence and/or treatment discontinuation after a change in appearance and/or packaging varies across studies. For example, a change in appearance was associated with a reduction in adherence to antihypertensive treatment (from 69% to 50%), preventive treatment for heart attacks (from 97% to 87%), and olanzapine treatment (from 28% to 16.7%), Another study on antidiabetics showed that the number of patients who discontinued their treatment after a medication change increased from 62% to 72%.

Moreover, a previous study conducted by the research team showed that adherence to ANEO treatment, evaluated using the EXPAD-ANEO scale and pill counting, was 69.3%.

Therefore, considering the ANEO treatment adherence of our patient population (69.3%) and to detect a change in adherence similar to that analyzed in previous studies (at least 10%) when a medication appearance change occurs, with a statistical power of 80% and a 95% confidence level, we would need to include 284 patients. Considering a potential 15% loss of patients during follow-up, we will increase the sample size to 334 patients.

Study Procedure

• To reach secondary outcome 1 Procedure: Through the records of the Hospital Pharmacy Service.

• To reach secondary outcomes 2-5 Procedure: When a change in any of the included ANEOs (from brand to generic or between generics) is about to occur, patients who meet the selection criteria and are scheduled to receive the new medication at their next dispensing will be contacted. The study will be explained to them, and their oral informed consent will be requested. They will be asked to bring their last dispensed medication to the Pharmacy Service for a pill count (this is a routine practice in the service, but they will be reminded to bring it).

  • During the baseline visit (in the pharmacy service), the patient will receive written informed consent and detailed information about the study. Data will be collected on: a) Continuity of treatment over the previous six months and details of the change (pharmacy records); b) Disease and treatment characteristics (patient history); c) Sociodemographic data; d) Health literacy; e) Adherence assessment; f) PROMs and PREMs values (patient interview).
  • Follow-up assessments will be conducted at three and six months to evaluate changes in adherence, continuity, PREMs, and PROMs.
• To reach secondary qualitative outcome 2 Procedure: Through the FORO patient group. Data Analysis

• Quantitative Analysis

  • Secondary outcome 1 The total frequency of changes during the study period will be evaluated by type of medication, change, and cause.
  • Secondary outcome 2-5 The change in treatment continuity, adherence, and PREMs and PROMs assessments will be evaluated based on the characteristics of the medication change and patient characteristics for both men and women.

The association between each independent variable and the dependent variables (treatment continuity change, adherence, and PREMs and PROMs assessments for each patient) will be studied using Pearson's Chi-squared test or Fisher's exact test, and the Student's T-test or the non-parametric Mann-Whitney U-test to compare means. The impact of medication change on treatment continuity, adherence, and PROMs and PREMs assessments will be analyzed through multivariate analysis using a Cox proportional hazards model. Covariates considered in the models will include those sociodemographic and clinical patient variables that modify the risk by more than 10% and have been associated with previous bivariate analysis. P-values <0.05 will be considered statistically significant. These analyses will be conducted separately for men and women.

• Qualitative Analysis

o Secondary outcome 2 Two researchers will triangulate the information obtained from the different groups. First, a careful reading of the transcription will be performed, and the text will be divided into meaningful information units. These units will be coded following a mixed strategy (emerging codes and predefined codes according to the study objectives), and categories will be developed based on the grouping of codes with the same theme. Finally, points of agreement and disagreement will be analyzed.

Data Management

A data management plan will be developed at the beginning of the project to establish how the data will be processed and managed throughout the project and how they will be stored after the project is completed. A brief description is provided below:

Regarding the type and format of data, various data will be generated using qualitative and quantitative methodology.

For secondary outcome 2, data on the sociodemographic and professional characteristics of the participants in the discussion groups and transcripts of their discussions will be collected.

For secondary outcomes 2-5, sociodemographic data of the patients included in the study will be collected. A database with individualized information on the 334 oncology patients undergoing treatment with the indicated ANEOs will be created.

All data collected during the project, as well as those generated from the project, will be pseudo-anonymized. No record will lead to the individual identification of participants. If any personal data are shared by participants in the discussion groups, they will not be transcribed. All participants will have previously signed informed consent, and if a person decides to revoke their consent later, all data related to that person will be deleted.

During the study, the data generated will be the property of UMH and will be stored in the university's information systems. Access will be granted through username/password. After the study concludes and the research is published, raw data and transcripts will be stored in an open repository such as Zenodo, complying with FAIR principles to ensure that they are accessible, reusable, and interoperable. This step will facilitate data sharing and reuse, which may accelerate research and promote innovation.

• Study Type: Observational
• Enrollment (Estimated): 334

Contacts and Locations

• Study Contact: Name: Elsa Dr. Elsa López; Phone Number: +34 965919414; Email: elsa.lopez@umh.es

Study Locations

• Spain
  • Alicante
    • San Juan, Alicante, Spain, 03550
      • Recruiting
      • Universidad Miguel Hernández
      • Contact: Elsa López Pintor López-Pintor, Associate Professor; Phone Number: +34 676463209; Email: elsa.lopez@umh.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The 2023 data from the hospitals where the study will be carried out shows that 517 patients were treated with one of the ANEOs included in the study. Given the required sample size of 334 patients, 112 patients will be consecutively admitted to each hospital, including those who meet the eligibility criteria, and will be followed for six months. For the qualitative investigation of objective 2 and participation in the focus groups, cancer patients treated with ANEOs will be contacted via the Spanish Patient Forum (3 gruops, 8-12 participants each)

Description

Objective 1:

Inclusion criteria:

ANEOs included in the pharmacotherapeutic guide of the three hospitals for two years of follow-up (June 2025-2027) will be included.

Objectives 2-5:

Inclusion criteria:

• Patients on treatment for at least 6 months with one of the following ANEOs will be included: capecitabine (L01BC06) (not used as adjuvant in short cycles), imatinib (L01EA01), everolimus (L04AA18), abiraterone (L02BX03) and lenalidomide (L04AX04), at the time of a change in their usual treatment (from brand to generic or between two generics).
• Patients on treatment with ANEOs who meet the established criteria and who change their treatment from brand to generic or from one generic to another generic during the study period may also be included.

Exclusion criteria:

• Individuals who collect medication for others and those who are institutionalised will be excluded.
• Patients who have been admitted to hospital in the last 4 weeks are also excluded, due to the increased control of their medication.

Objective 2( Qualitative analysis)

- Spanish Patient Forum

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Secondary outcomes 2-5. Quantitative analysis; Patients treated in Dept 20- Elche-Hospital General and Dept. 17- Alicante-S Joan, Dpto. 19 Alicante Hospital General Universitario Dr Balmis d'Alacant, under treatment with ANEO(oral antineoplastic drug ) for at least 6 months and who are autonomous in taking their medication
Secondary outcome 2. Qualitative Analysis; A qualitative focus group design with patients from the Spanish Patients' Forum,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of adherent patients according to the combination of adherence assessments	The impact will be measured by: EXPeriencia con y ADherencia a AntiNEoplasicos Orales (EXPAD-ANEO adherence scale)(Talens A et al, Frontiers in Pharmacology, 2023).; Tablet counting. The scale will be applied at baseline to assess adherence to treatment prior to switching. It will also be determined twice during the six-month follow-up of the study (at the third and sixth dispensing). This scale includes 7 criteria and is developed and validated in Spain by the research team. Tablet count will be assessed at the baseline visit, before the change of treatment and during follow-up (at the third and sixth), together with the application of the EXPAD-ANEO scale.) Both measures of adherence will be complementary. A patient will be considered adherent if the tablet count is above 90% and meets the 7 criteria of the scale. Adherence will also be assessed in patients who have not come to pick up a dose, but come to pick up their medication at another dose during the prospective study.	From June 2025 to June 2027

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. 1 Number of changes in the appearance of ANEO medication included in the pharmacotherapeutic guide of three hospitals.	The number of changes that have occurred in any ANEO included in the pharmacotherapeutic guide of the three hospitals (from brand to generic or between two generics) will be quantified.	From June 2025 to June 2027
1.2 Type of changes in the ANEOs	Appearance exchange rates: Color.; Shape.; Packaging. An ANEO can be affected by more than one of the options.	From June 2025 to June 2027
1. 3 Reasons for the change	Reasons for changing from one ANEO to another: Shortage.; Patent expiration.; Lower price.; Expansion of the indications.	From June 2025 to June 2027
1.4 Percentage of patients affected by the change in ANEO	Total count of patients affected by the change	From June 2025 to June 2027
2.To assess the impact of change in the appearance of the prescribed ANEO on patient-reported health outcomes (PROMs).	PROMS assessment: The change in responses to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), validated in Spain and including assessment of physical, functional, emotional and social dimensions at three and six months in relation to the baseline visit will be determined. All sub-scales and the 6 individual items have a score range from 0 to 100 points. A higher score represents better function and a higher quality of life. In the symptom subscale, however, a higher score represents a higher level of symptoms or problems. Since there is no total score, all subscales and the individual items must be considered individually and evaluated using normative data.	From June 2025 to June 2027
3. To examine the impact of changing the appearance of the prescribed ANEO on patient continuity of care and adherence to therapy by patients coming to collect their prescribed medications.	A person is determined to continue their treatment if they take all doses of the medication prescribed by their doctor during the six-month follow-up period (according to other studies, discontinuation of treatment is considered if the patient undergoes the Collection of the medication has been delayed by 3 days (more restrictive) or 10 days (less restrictive). The change in continuity will be determined by comparing the prescription and dispensing records for the last six months before the start of the study with the continuity during the patient six-month follow-up will be compared once the change in the appearance of the patient medication has occurred. The data will be collected from the pharmacy register	From June 2025 to June 2027
4. To analyse the impact of changing the appearance of the prescribed ANEO on patient experiences of care (PREMs).	Quantitative part: - Change in responses on the Chronic Patient Experience Assessment Instrument (IEXPAC 2018) at three and six months. The overall score on the IEXPAC scale corresponding to the 11 items is a single digit between 0 and 10, calculated as the average of the scores for each of the items. The target score on the IEXPAC scale should be 10, meaning that good care is "always" provided. Therefore, any score below 10 indicates room for improvement in the organization's care for its chronic patients. Qualitative part: - Patients perceptions, attitudes and experiences will be assessed through focus groups to the change in appearance and/or cartonnage of ANEO treatment and its impact on continuity and adherence to treatment . The script to be used will be based on the available evidence on the topic and discussions with the team.	From June 2025 to June 2027
5.To analyse the different factors (age, health literacy and clinical variables, among others) that influence the impact of ANEO appearance change on PREMs, treatment continuity and adherence, and PROMs, for men and women.	Change in ANEO appearance: visualised in situ in the pharmacy service.; Clinical and socio-demographic variables will be collected: type of cancer and stage, time on treatment with the same or another ANEO, number of changes in appearance from previous treatment, age, marital status, educational level, literacy level (through the HLS-EU-Q16 (Health Literacy Survey-European Union) questionnaire), on the use or not of tablet organiser, and knowledge about the indication of ANEO.	From June 2025 to June 2027

Collaborators and Investigators

• Sponsor: Universidad Miguel Hernandez de Elche
• Collaborators: Instituto de Salud Carlos III

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): June 29, 2027

Study Registration Dates

• First Submitted: October 11, 2024
• First Submitted That Met QC Criteria: June 16, 2026
• First Posted (Actual): June 24, 2026

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: adherence; appearance; patient care; PROMS; PREMS; oral antineoplastic drug
• Additional Relevant MeSH Terms: Behavior; Treatment Adherence and Compliance; Health Behavior; Patient Acceptance of Health Care; Neoplasms; Patient Compliance
• Other Study ID Numbers: APARENTE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No