Assessment of medication adherence, medication safety awareness and medication practice among patients with lung cancer: A multicentre cross‐sectional study

Abstract Objectives We aimed to explore the current status of medication adherence, safety awareness and practice among patients with lung cancer. Methods We conducted a questionnaire‐guided cross‐sectional study in Xi'an, Yulin, Hanzhong and Weinan in Shaanxi Province, China, from April to June 2021 for a period of 3 months. The study questionnaire was developed according to previous related studies reported in the literature, and includes basic demographic information and patients' medication safety questions. The data were double‐entered using EpiData 3.1 software; descriptive statistics, t‐test, analysis of variance, the Kruskal–Wallis test and the Mann–Whitney U‐test were performed to analyse the data. Results A total of 567 participants were included, and 409 valid questionnaires were finally completed, with an effective response rate of 72.13%. More than 80% of patients showed good medication adherence; the average adherence score was 22 ± 2.68 of 25. The average score for medication safety awareness was 16.40 ± 4.41, which was significantly lower than that of medication adherence (p < .001). Only 22.74% of patients always checked their medicines before a nurse administered them; 17.60% of patients never checked their medicines. Few patients actively consulted an health care professional to understand safety information before taking a medication. A significant difference existed in safety awareness scores among age groups (p = .039) and geographic regions (p < .001). Patients with three or more comorbidities had the lowest awareness scores (p = .027). Conclusion We found that patients with lung cancer showed better medication adherence, but their awareness about medication safety was poor. Older patients, those with comorbidities and patients in regions with poor medical resources may have worse awareness about safety. Current medication education for patients should not only aim to improve adherence but should also encourage patients to take greater responsibility for their own safety and to actively participate in their medication safety. Greater systematic and individualized medication safety information is needed for older patients, those with more comorbidities and patients in areas with poor medical resources. Patient Contribution We conducted a questionnaire‐guided cross‐sectional study on hospitalized lung cancer patients in Shaanxi Province to explore the patients' practices related to safety medication, including medication adherence and medication safety awareness.

medication safety. Greater systematic and individualized medication safety information is needed for older patients, those with more comorbidities and patients in areas with poor medical resources.
Patient Contribution: We conducted a questionnaire-guided cross-sectional study on hospitalized lung cancer patients in Shaanxi Province to explore the patients' practices related to safety medication, including medication adherence and medication safety awareness. The treatment of cancer mainly involves surgical treatment, radiotherapy and drug treatment. 3 Various treatment methods complement each other to yield better treatment results. With the development of medical technology and new anticancer drugs, medication has become the main method of comprehensive anticancer treatment. 3,4 However, drug safety is important, given that most anticancer drugs have a narrow therapeutic index and individual differences in toxicity, 5 and the chemotherapy regimen is complex and involves many combined drugs. At the same time, the physiological function of important organs, immune function and pharmacokinetic characteristics are easily affected by disease progression in patients with cancer, 6 and drugs are mostly administered to older patients with cancer and multiple comorbidities, 5,7 which leads to patients with cancer having a considerably higher risk of adverse drug reactions (ADRs) and serious adverse events, and there is also the potential for serious medical errors. 7,8 A retrospective analysis of mortality related to medication errors showed that the use of anticancer drugs is the second most common cause of death. 9 Most antitumor drugs, such as platinum-based drugs and antimetabolites, are cytotoxic drugs. These types of drugs have poor targeting; while killing tumour cells, they inevitably exert a toxic effect on normal tissues and organs, the drug therapeutic window is narrow, drug doses must be calculated according to body weight and each medication must be administered at precisely maintained time intervals, so any carelessness in the administration process can lead to medication errors. 7,10 Medication errors may cause toxic side effects, hospitalization and even death. Therefore, medication safety in anticancer treatment is very important for patients with cancer. 5,7 Cancer treatment is complex and involves multidisciplinary teams. There are many safety risk factors in treatment for cancer. 11 These risks occur at multiple key points, from prescription to deployment to drug administration. Therefore, it is necessary to coordinate the efforts of health care professionals (HCPs) to minimize risk. 12,13 At present, many studies are aimed at certain types of HCPs, exploring potential factors that affect the safety of patients' medication in their work processes so as to propose specific intervention measures to ensure the safety of patients' medication. For example, from the perspective of nurses, [14][15][16] it has been shown that risk factors related to patient medication safety include nurse medication errors, poor communication, unclear doctor's orders, heavy workload and personnel rotation. From the perspective of pharmacy-related professionals, [17][18][19] it has been shown that factors such as a lack of clinical collaboration and lack of pharmacy services affect patients' medication safety. These studies can serve as a reference and guidance for medication safety in patients with cancer from the perspective of HCPs. As the individual with the most direct contact with the drug, the patient represents a key factor affecting the safe use of his or her medication in cancer treatment. 20 The value of allowing patients and their families to participate in medication safety has been recognized in health care worldwide. 21 One of the primary initiatives derived from the patient safety movement is to approach patient participation as a patient safety strategy. 22,23 Studies have shown [24][25][26][27] that HCPs believe that patients' participation in their medication safety mainly involves medication adherence. Therefore, many studies have adopted structured intervention guidelines to improve medication adherence among patients with cancer to ultimately improve patient outcomes. 20,28 In addition to medication adherence, the patient's medication practices and medication safety awareness will affect the safe use of their medication. On the premise that patients have a better awareness of medication safety, patients are more likely to have better adherence and medication practice. However, there are currently few studies on patients' medication safety awareness and practices. Therefore, the purpose of this study was to explore the current status of medication adherence, medication safety awareness and medication practice among patients with lung cancer, to provide a research basis for subsequent targeted interventions to help patients improve their safe medication use. We evaluated the geographic environment and economic development of various regions in Shaanxi Province. The province is divided into three regions (Northern, Central and Southern Shaanxi) and one provincial capital city (Xi'an). Taking the median per capita GDP of 11 regions in Shaanxi Province as a benchmark, in addition to the provincial capital city (Xi'an), we selected Yulin (120,900 RMB, high per capita GDP), Hanzhong (45,000 RMB, medium per capita GDP) and Weinan (34,500 RMB, low per capita GDP) as representative cities. We included general hospitals with an oncology department or cancer specialist hospitals in each city as the research sites. In these hospitals, simple random sampling methods were used to select patients with lung cancer as the research participants. The specific method of sampling and questionnaire distribution were as follows: a catalogue of currently hospitalized lung cancer patients was obtained from the Hospital Information System, each patient was numbered and these patient numbers were input into SPSS.

| Study area and study population
Simple random sampling was conducted using the function of 'Data → Select Cases→Random sample of Cases' of SPSS software, 10-15 patients were randomly selected each time and we recorded the ward and bed number of these randomly sampled lung cancer patients. Then, we went to the ward and invited the patient to participate in the study. A face-to-face questionnaire survey was conducted in our investigation. We recommended that competent patients fill out the questionnaire by themselves; older patients gave their responses verbally to study staff, who recorded these. The questionnaire was distributed to all participants, accompanied by an explanatory letter informing them of the purpose of the survey. The content of the questionnaire did not involve the personal information of the respondent, so anonymity was guaranteed.
We conducted this questionnaire-guided cross-sectional study in Xi'an, Yulin, Hanzhong and Weinan in Shaanxi Province from April to June 2021 for a period of 3 months. We used the Raosoft sample size calculator 30 to calculate the sample size. According to the incidence of lung cancer in China 31 during 2015 (57.26/100,000) and the total population of Shaanxi Province, there are approximately 22,000 patients with lung cancer in Shaanxi Province. We assumed a 95% confidence level and a 50% acceptable margin of error; the response distribution was 50%. The calculated sample size was 378 participants, to which we added 50% to cover possible invalid questionnaires, such as those with logical inconsistencies. We finally determined that 567 participants were needed. The number of participants in each selected area was estimated using the population ratio (Xi'an: 10.20 million; Yulin: 3.42 million; Hanzhong: 3.44 million; Weinan: 5.28 million).

| Questionnaire design
We developed the study questionnaire according to previous related studies reported in the literature. 32,33 The questionnaire consists of two parts. The first part contained basic demographic information, To ensure participant recruitment procedures and validity and reliability of the measuring instrument, we conducted expert interviews and a pilot study before initiating the main study. The developed questionnaire was verified for readability and acceptability among five HCPs who were working in a grade-A tertiary hospital. To ensure the professionalism of the experts, we established the following inclusion criteria: working in a grade-A tertiary hospital, clinically engaged in the treatment of patients with lung cancer, more than 15 years of work experience and having a professional vicesenior title or above. After the experts had modified the questionnaire, we conducted a pilot study including 20 people. The contents of the questionnaire were modified according to the pilot study.
The findings of the pilot study were not included in the final data analysis.

| Data analysis
After excluding invalid questionnaires, all valid questionnaires were numbered and the data were double-entered using EpiData 3. We used the t-test, analysis of variance, the Kruskal-Wallis test and the Mann-Whitney U-test to test the differences in patient medication adherence and medication safety awareness with different demographic characteristics. Statistical significance was defined as p < .05.

| Demographic characteristics
A total of 567 questionnaires were distributed. After excluding invalid questionnaires, 409 valid questionnaires were finally included in this study, with an effective response rate of 72.13%. Cronbach's α value was calculated to measure the internal consistency, which was found to be .72, signifying good internal consistency.
Two thirds (66.99%) of patients with lung cancer were men.  (Table 1). Table 2 shows that only 37.65% of the included patients stated that they never forget to take their medication during treatment; 55.99% never increased or decreased the dosage of medication by themselves; 63.33% never adjusted the infusion rate by themselves; and 65.04% and 64.03% of patients took their medications as planned during hospitalization and treatment at home, respectively.

| Patient medication adherence
The first three questions in the medication adherence section of the survey were negative response options; responses of 'rarely' and 'never' were considered to indicate good medication adherence.  Table 2).
The average score for patient medication adherence was 22 ± 2.68 (full score 25), and the median score was 23. There were significant differences in medication adherence scores between patients in different geographic regions (p < .001). Patients in Xi'an had the highest scores and those in Yulin had the lowest scores. Pairwise comparisons showed that the differences in scores between patients in Xi'an and Yulin were statistically significant. The medication adherence scores of patients without comorbidities were higher than those of patients with comorbidities (p = .001), and the adherence scores of patients with one comorbidity were higher than those of patients with multiple comorbidities (p = .028). The adherence scores of patients in the group with three or more comorbidities were the lowest and were significantly different from the remaining two groups. The adherence scores of patients who did not have ADRs during the treatment period were higher than the scores among those who experienced ADRs (p = .024), and the difference was statistically significant (Table 3).  The average score for medication safety awareness was 16.40 ± 4.41 (full score 25), and the median score was 16; the medication adherence score (22 ± 2.68) was higher than that for patient medication safety awareness, and the difference was statistically significant (p < .001). There was a significant difference in safety awareness scores among different age groups (p = .039). In pairwise comparison, we found that patients in the age group of 18-40 years had the highest scores, which were significantly different from the remaining groups. There were statistically significant differences in the medication safety awareness scores of patients in different geographic regions (p < .001), with the highest scores in Xi'an and the lowest scores in Yulin. Patients with three or more comorbidities had the lowest scores (p = .027); in pairwise comparison, we found that scores in this group were significantly different from those of other groups who had fewer comorbidities (Table 3).  45 The scope of treatment with oncology drugs is narrow, and treatment interruption must be avoided. 46 Therefore, nonadherence behaviours such as forgetting to take medicines among patients with cancer will lead to more serious consequences, affecting patient safety and impairing Patients with comorbidities have worse adherence than those with no comorbidities, and the adherence of patients with more comorbidities is worse than that of patients with fewer comorbidities.

| Patients' other medication safety practices
Several studies have shown that comorbidities are related to a lack of medication adherence. 45,50 This could be explained by the fact that patients with comorbidities are more likely to take multiple drugs; thus, it is unlikely that they will take all their drugs properly. Moreover, the risk of adverse drug events is increased in patients with comorbidities, which can also negatively affect the adherence rate. 50 The present study also showed that patients who experienced ADRs during treatment had worse adherence than those who did not experience ADRs; patients tend to stop taking medication owing to the strong ADRs and side effects of chemotherapy. 46 Strong ADRs after chemotherapy seriously affect patients' quality of life, which may be a major obstacle to adherence to drug therapy. 45 In this study, patients' awareness about medication safety was poor, and their awareness score was significantly lower than their medication adherence score. A study among patients with chronic diseases showed that HPCs have better communication with patients regarding the purpose and methods of taking medication than about medication safety information. 51 HCPs believe that patients' involvement in medication safety is mainly via improving their adherence [24][25][26][27] ; HCPs ignore the fact that patients can participate in monitoring their own medication, reporting ADRs and can actively learn safety information. Patients' participation in their own medication safety plan is currently a major theme on the international patient safety agenda. 24 In addition to improving medication adherence for the purpose of patient education, patients should also be encouraged to actively participate in their own medication safety and improve their medication safety awareness, such as checking one's More than half of the patients reported that they consulted with a physician when they experienced worsening of symptoms after taking a medication, which is the same as in another study. 51

| Strengths and limitations
This study was a rare medication safety survey conducted from the perspectives of patients' medication adherence, medication safety awareness and medication practice, aiming to explore those factors that affect medication safety among patients. Previous studies on patient participation in their own medication safety have mostly been intervention studies on patient adherence. [24][25][26][27] This study supplements other studies that have mostly only focused on adherence. The limitation of this study lies in the representativeness of the sample in our research. To ensure a representative sample size, the corresponding statistical formula was used to calculate the sample size; simple random sampling was carried out according to the number of participants needed to avoid selection bias. We included inpatients with lung cancer in Shaanxi Province, a representative province in western China; the basic situation of patients with lung cancer in other provinces in eastern and central China must be further investigated using a larger and more representative sample. Additionally, this was a cross-sectional study. The design of this study can reflect the state of patients at a certain stage, but it cannot prove causality. Also, information about patients' adherence and awareness about medication safety was provided by patients, which may cause the findings to be unreliable owing to patient recall in self-reporting, and it is possible that people might have been less comfortable providing negative responses to a researcher directly, which may affect the results.