Factors Affecting the Comprehension of Outpatients Receiving Cancer Chemotherapy

Seira Nishibe-Toyosato; Yosuke Ando; Nayu Nakasuji; Takahiro Hayashi; Kaori Ito; Hidezo Matsuda; Naho Tsujii; Masahiro Tsuge; Kazuyoshi Imaizumi; Kenji Kawada; Shigeki Yamada

doi:10.1248/bpb.b22-00374

Abstract

Pharmaceutical consultation targeting outpatients at the Fujita Health University Hospital (Japan) provides support to patients undergoing anticancer drug treatment. This study aimed to explore factors that affect the comprehension of cancer chemotherapy among outpatients who received cancer treatment at our hospital. A questionnaire survey was conducted, and comprehension was scored on a scale of 1–5 (1, no comprehension; 5, full comprehension). When factors other than age and sex [the influence of which on comprehension has been reported in previous reports] were noted, differences in comprehension between the questionnaire items were comparatively analyzed according to the presence/absence of the relevant factors. Overall, 536 patients were included. Age (<70 years) and pharmacist interventions were identified as factors contributing to a comprehension score. The levels of comprehension regarding the name of the cancer chemotherapy, content/schedule of the treatment, purposes of the prescribed drugs, and objectives of blood tests were significantly higher in the group that received the pharmaceutical interventions; conversely, the level of comprehension for the self-management of adverse events was significantly lower in this group than in the group that did not receive any pharmaceutical interventions. Age and interventions by the pharmacist affected the comprehension of cancer chemotherapy by patients.

INTRODUCTION

The recent increase in the availability of chemotherapeutic regimens for various cancer types has contributed to the diversification of adverse events caused by anticancer drugs. The prevalence of cancer among the elderly has drastically increased in Japan, owing to growth of the aging population.¹⁾ Therefore, it is essential to help these patients accurately understand the purposes of therapeutic regimens and self-manage adverse events. Previous reports demonstrated that patient education provided by nurses resulted in improved drug knowledge and medication adherence.^2–4) Afatinib is known to be associated with adverse events such as diarrhea, skin disorder, and stomatitis.^5–7) Meanwhile, continuous pharmaceutical control through administration instructions provided by pharmacists at the start of treatment, monitoring of adverse events, and telephone-based follow-up reduced the rate of treatment discontinuation attributable to adverse events in patients who received this drug.⁸⁾ In another study, patient education and treatment support provided by pharmacists reduced the incidence of adverse events, improved medication adherence, and precluded drug interactions among patients who received oral anticancer drugs such as capecitabine.⁹⁾ Likewise, patient education and treatment support provided by pharmacists improved the understanding of blood pressure measurements, the response to the onset of adverse events, and medication compliance among patients sunitinib, which is known to be associated with adverse events such as hypertension, thereby resulting in a high relative dose intensity.^10–12) These reports indicate that support for cancer chemotherapy by paramedical staff positively contributes to improvements in treatment comprehension, medication adherence, and therapeutic efficacy.

Given the development of novel anticancer drugs and the availability of supportive therapies, there has been a paradigm shift in cancer chemotherapy from hospitalized treatment to ambulatory care.¹³⁾ Consequently, the need for pharmaceutical management among outpatients during cancer chemotherapy has increased. Therefore, pharmaceutical consultation was established at Fujita Health University Hospital in Japan for outpatients who received anticancer drugs, such as epidermal growth factor receptor, tyrosine kinase, and immune checkpoint inhibitors. The pharmaceutical consultation that targets outpatients at our hospital aims to increase the safety of anticancer drug treatment by performing the following procedures: explanation of treatment regimens and schedule; interview of patients regarding adverse events associated with anticancer drugs to provide guidance on lifestyle and appropriate use of these drugs, as well as recommending supportive care; confirmation of examination results on the same day; confirmation of drug interactions; adjustment of prescription days according to the number of remaining drugs; recommendation on additional examination and on receipt of concomitant treatment under another department; and proposal for changes and discontinuation of dose regimens of anticancer drugs. Interventions by a pharmacist are performed prior to a physician consult to present the patient’s information to doctors.

A previous study reported that age, sex, and educational background affected the comprehension of non-cancer patients concerning their prescribed drugs.¹⁴⁾ In another study, age and educational background, but not sex, were found to affect the comprehension of 90 patients in both inpatient and outpatient settings at King Abdul Aziz Medical City.¹⁵⁾ Patients who graduated from high school or achieved a higher education level had higher levels of comprehension; however, age, sex, and at least 1 year of drug use exhibited no correlations with patient comprehension.¹⁶⁾ Previous studies indicated that education contributes to improved comprehension of cancer chemotherapy among patients with cancer.^2,12) However, to the best of our knowledge, no study has explored factors pertaining to the comprehension of cancer chemotherapy. Therefore, this study assessed factors that affect the comprehension of cancer chemotherapy among outpatients who received cancer treatment at our hospital.

MATERIALS AND METHODS

Subjects

The study comprised outpatients who received cancer chemotherapy at Fujita Health University Hospital from August 21, 2019 to September 20, 2019. Those who provided informed consent to participate in the study and answered all questions in the questionnaire were enrolled in the analysis.

Survey Methods

The questionnaire survey was anonymously conducted using paper media, and the patients were required to answer each question by selecting the appropriate response among multiple options. An exclusive pharmacist who did not provide direct pharmaceutical care at the hospital provided explanations for the questionnaire survey. Age, sex, treatment history regarding cancer chemotherapy during ambulatory care, the department implementing the cancer chemotherapy, and the history of instructions provided by the exclusive pharmacist were investigated for each patient (Fig. 1). Furthermore, the patients’ awareness about the name of the cancer chemotherapy provided, self-management of adverse events, content and schedule of the cancer chemotherapy, purposes of the prescribed medications, and objectives of the blood tests were evaluated (Fig. 2). The survey items and options were based on previous reports.^17–19)

Fig. 1. Questions and Answers for the Survey: Patient Background

Fig. 2. Questions and Answers for the Survey: Comprehension Levels

Evaluation Methods

The patients’ comprehension of cancer chemotherapy was analyzed using five questions. The results of the questionnaire were determined as follows: For questions 1) and 2), responses 1, 2, and 3 were awarded 5, 3, and 1 point, respectively, whereas for questions 3) to 5), 100% comprehension was given a score of 5 points, and 1 point was subtracted for each 25% reduction (0% comprehension was scored as 1 point). In addition, patients were divided into two groups based on the median score received for each question: score ≥4 points and score <4 points.

Statistical Analysis

Statistical analyses were conducted using SPSS ver. 22.0 (IBM Corporation, Armonk, NY, U.S.A.). The chi-squared test was used to compare data (expressed as percentages) between the two groups. Logistic regression analysis was used to determine factors that contributed to the achievement of a comprehension score of ≥4. When factors other than age or sex [the influence of which on comprehension has been reported in previous reports^14–16)] were considered, the Mann–Whitney U test was performed to compare the levels of comprehension for each question depending on the presence/absence of these factors. The explanatory variables were age, sex, history of outpatient cancer chemotherapy, and interventions during a pharmaceutical outpatient consultation.

Ethical Considerations

This study was conducted in accordance with the Declaration of Helsinki. Patient consent was obtained, and the study was approved by the Ethical Review Board of the Fujita Health University Hospital.

RESULTS

Patient Background

Among 536 patients included in the study, 451 were categorized into the ≥4 group, and 85 were included in the <4 group. Patient age significantly differed between these groups (p = 0.039). Patients aged ≥70 years accounted for 51.8% of the <4 group and 36.8% of the ≥4 group (p = 0.010). Differences in treatment history concerning cancer chemotherapy during ambulatory care were noted between the two groups, albeit without significance (p = 0.068). Patients with treatment histories of ≥3 years comprised 9.4 and 18.2% of the <4 and ≥4 groups, respectively; thus, they tended to have higher comprehension than those with shorter treatment histories (p = 0.052). Patients who received interventions through pharmaceutical care by the exclusive pharmacist during ambulatory care accounted for 37.3% of patients in the ≥4 group, vs. 27.1% in the <4 group (p = 0.072). No significant differences were observed for the other items evaluated in this study (Table 1).

Table 1-1. Patient Background

	≥4 group (n = 451)	<4 group (n = 85)	p-Value
Sex male/female (%)	48.6/51.4	51.8/48.2	0.588
Age (%)			0.039
≤30	3.3	2.4
40	15.5	11.8
50	17.7	14.1
60	26.6	20.0
70	30.8	36.5
≥80	6.0	15.3
History of outpatient cancer chemotherapy (%)			0.068
<1 year	50.1	64.7
1–2 years	18.8	14.1
2–3 years	12.9	11.8
≥3 years	18.2	9.4
Pharmaceutical care by the exclusive pharmacist (%)			0.072
Intervention	37.3	27.1
No-intervention	62.7	72.9

≥4 group, Median points each patient received in each question of comprehension of cancer chemotherapy: those who scored ≥4 points. <4 group, Median points each patient received in each question of comprehension of cancer chemotherapy: those who scored <4 points.

Table 1-2. Patient Background

	≥4 group (n = 451)	<4 group (n = 85)	p-Value
Department implementing cancer chemotherapy (including duplications)
Gastroenterological surgery	115	29	0.131
Breast surgery	89	12	0.288
Respiratory medicine	76	16	0.775
Urology	40	5	0.485
Hematology	32	4	0.568
Hepatopancreatic medicine	25	6	0.767
Medical oncology	18	1	0.333
Obstetrics and gynecology	17	5	0.547
Gastroenterology	16	6	0.231
Dermatology	14	2	0.979
Neurosurgery	10	2	1.000
Endocrine surgery	2	0	1.000
Orthopedic surgery	1	0	1.000

Factors Affecting Comprehension

To explore factors affecting comprehension scores of ≥4 among the patients in this study, univariate and multivariable analyses were performed for age, sex, treatment history at the time of ambulatory care, and instructions provided by the exclusive pharmacist. Consequently, age (<70 years) and pharmacist interventions were identified as factors contributing to a comprehension score of ≥4 (p = 0.005 and p = 0.039, respectively; Table 2).

Table 2. Factors That Affected the Patients Who Presented with a Median Score ≥4

	Univariate analysis		Multivariable analysis
	Odds ratio (95% CI)	p-Value	Odds value (95% CI)	p-Value
Age (vs. ≥70 years)	1.842 (1.156–2.938)	0.010	1.955 (1.219–3.134)	0.005
Sex (vs. male)	1.137 (0.715–1.808)	0.588	0.965 (0.596–1.561)	0.884
History of outpatient cancer chemotherapy (vs. <3 years)	2.139 (0.994–4.603)	0.052	1.914 (0.881–4.156)	0.101
Interventions by Pharmaceutical consultation targeting outpatients (vs. non-intervention)	1.600 (0.956–2.679)	0.074	1.735 (1.029–2.926)	0.039

CI, confidence interval.

Comparison of Comprehension in the Presence/Absence of Pharmaceutical Care by the Exclusive Pharmacist

The levels of comprehension for each question were compared between patients who did (191 cases) and did not (345 cases) receive pharmaceutical interventions by the exclusive pharmacist during ambulatory care. The levels of comprehension regarding the name of the cancer chemotherapy, content/schedule of the treatment, purposes of the prescribed drugs, and objectives of blood tests were significantly higher in the group that received the interventions (p < 0.001, p = 0.021, p = 0.018, and p = 0.007, respectively); conversely, the level of comprehension for the self-management of adverse events was significantly lower in this group than in the group that did not receive any interventions (p = 0.036; Table 3). The percentages of answers for each question are illustrated in Fig. 3.

Table 3. Comprehension Levels for Each Question in the Presence/Absence of the Pharmacist’s Interventions

	Pharmaceutical consultation targeting outpatients (points) median (range) mean ± S.D. (points)		p-Value
	Intervention (n = 191)	Non-intervention (n = 345)	p-Value
1) Name of the cancer chemotherapy	5 (5–5) 4.6 ± 1.0	5 (3–5) 4.1 ± 1.3	<0.001
2) Self-management of adverse events	3 (3–5) 3.7 ± 1.2	5 (3–5) 3.9 ± 1.2	0.036
3) Content and schedule of the cancer chemotherapy	5 (4–5) 4.5 ± 0.7	5 (4–5) 4.3 ± 0.8	0.021
4) Purposes of the prescribed medications	5 (4–5) 4.7 ± 0.6	5 (4–5) 4.5 ± 0.7	0.018
5) Objectives of the measuring blood test items	4 (3–5) 4.0 ± 1.1	4 (3–5) 3.8 ± 1.1	0.007

S.D., standard deviation.

Fig. 3. Comprehension Levels Regarding Cancer Chemotherapy

1, 2) Self-assessment to select one of three levels of comprehension. 3–5) Self-assessment to select one of five levels of comprehension.

DISCUSSION

Cancer chemotherapy is associated with higher rates of adverse events than other pharmacotherapies.²⁰⁾ Furthermore, complicated measures are required to address these diverse events. A cancer diagnosis can affect the mental condition of the patient. Therefore, it is important to help the patient comprehend information relevant to the therapeutic regimen to provide appropriate and effective cancer chemotherapy.

In the current study, age (<70 years) was identified as one factor affecting the comprehension of cancer chemotherapy. This result corroborates the findings of previous reports in which younger patients were found to have better medication knowledge.^14,15) The age of the population is expected to increase in the future; therefore, it is necessary to help elderly patients achieve higher comprehension regarding treatment regimens. Briefing documents prepared by pharmaceutical companies are used to provide explanations about drugs to patients at Fujita Health University Hospital; consequently, the same materials are used to explain the same therapeutic methods. According to a previous study, providing instructions to patients using original in-hospital briefing documents resulted in improved comprehension of the disease symptoms, methods for the self-management of adverse events, and precautions to be taken during daily living.²¹⁾ Therefore, to improve the understanding of elderly patients, it is important to provide them with more options and to cater to their needs by using larger letters, simplifying the content of the materials, and providing additional explanations to their family members.

The results of the present study suggest that interventions by the exclusive pharmacist assigned to pharmaceutical consultation targeting outpatients using anticancer drugs contributed to improved comprehension of cancer chemotherapy, specifically concerning the name of the chemotherapy provided, treatment schedule, purposes of the prescribed drugs, and objectives of blood tests. In a previous study comparing the levels of comprehension before and after interventions for chemotherapeutic drugs by an exclusive pharmacist, understanding of the importance of the medication, dosing schedule, and onset/prevention of adverse reactions improved the comprehension levels of patients after interventions.²²⁾ Similar findings were observed in the present study. Consultation by the exclusive pharmacist created an environment in which patients received continuous instructions and responses to their queries, which contributed to improvement of their understanding of the treatment. However, the results suggest that consultation by the exclusive pharmacist negatively affected patients’ comprehension regarding the self-management of adverse events. This may have been partly attributable to the lack of explanations by the pharmacist. Patients with cancer exhibited higher comprehension of adverse reactions than patients without cancer; therefore, administration instructions catering specifically to patients with cancer should be provided.²³⁾ For outpatients at pharmaceutical consultation of Fujita Health University Hospital, an exclusive pharmacist conducts prior interviews, which affects the prescriptions and blood sampling orders by doctors. The patient does not receive any further explanations about the drugs prescribed by the physician immediately after the consultation. In such cases, the exclusive pharmacist provides explanations during the next appointment. Therefore, to further improve patients’ comprehension, it is important to see the exclusive pharmacist again after consultation with the doctor to receive further explanations regarding the efficacy, dosage, and usage of the prescribed drugs.

Additionally, superior compliance instructions at out-of-hospital pharmacies may improve patients’ comprehension. Generally, out-of-hospital pharmacies are not provided with sufficient information about the treatment method and purpose of the prescribed drug. Therefore, coordination between in-hospital and out-hospital pharmacists, regular meetings, and the establishment of systems for sharing patient information using tracing reports are warranted.

Pharmaceutical consultation does not have sufficient exclusive pharmacists for outpatients using anticancer drugs; hence, patients using anticancer drugs with complex dosing schedules or anti-adverse event measures are prioritized.

The differences in drugs used between the intervention and non-intervention groups in this study might have resulted from reduced comprehension of the treatments provided for adverse events by pharmacist interventions. Increased understanding of the measures used against adverse reactions can alleviate anxiety.^19,24) Additionally, addressing adverse events based on improved knowledge following the interventions by the pharmacist can improve the QOL of patients.²⁵⁾ Therefore, the influence of pharmaceutical consultation on the psychology of outpatients receiving anticancer drugs needs to be evaluated in the future.

To the best of our knowledge, this study was the first to explore the factors associated with improved comprehension in patients on outpatient chemotherapy. Based on the results of this study, age (<70 years) and interventions by pharmaceutical consultation were the factors that improved comprehension. We believe that we were able to discover the necessity of examining the instruction methods for elderly patients and the usefulness of intervention by pharmaceutical consultation.

Several limitations must be considered when interpreting the present findings. The study was conducted in a single institution. In addition, the strategies used for patient education and treatment support may vary among pharmacists. Our findings should be confirmed in larger multi-institutional, prospective studies. In addition, the target patients of pharmaceutical consultation are determined by the type of anticancer drug; therefore, the anticancer drugs administered in the intervention and non-intervention groups may have been biased. However, the questionnaire survey was anonymously conducted. Therefore, we failed to investigate the type of anticancer drug. Furthermore, we were unable to examine specific details of the extensive level of pharmacist intervention provided for the target patients in this study; this included explanations of the treatment schedule, management of adverse events, and blood test results. In addition, as discussed under Survey Methods, given that the survey method used to understand the level of comprehension among patients was the same as that used in the previous study—patients’ self-assessment using the Likert scale—we must interpret the data as the level of comprehension based on patients’ self-assessment instead of the rate of correct answers provided to the questions.

In conclusion, age (<70 years) and interventions by pharmaceutical consultation were the two factors that affected comprehension of cancer chemotherapy among outpatients receiving anticancer drugs.

Acknowledgments

We would like to thank the participating patients for their contributions to this study.

The authors would like to thank MARUZEN-YUSHODO Co., Ltd.

Conflict of Interest

The authors declare no conflict of interest.

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