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Beliefs about medicines and non-adherence in patients with
stroke, diabetes mellitus and rheumatoid arthritis in China
Journal: BMJ Open
Manuscript ID bmjopen-2017-017293
Article Type: Research
Date Submitted by the Author: 12-Apr-2017
Complete List of Authors: Wei, Li; University College London School of Pharmacy, BMA house, Tavistock Square Chapman, Sarah; UCL School of Pharmacy, Li, Xiaomei; Anhui Provincial Hospital, Anhui Medical University Li, Xin; The Second Hospital, Tianjin Medical University Li, Sumei; Anhui Provincial Hospital, Anhui Medical University Chen, Ruoling; University of Wolverhampton, Centre for Health and Social Care Improvement
Bo, Nie; University College London School of Pharmacy Chater, Angel; University College London, Centre for Behavioural Medicine Horne, Robert; University College London School of Pharmacy
<b>Primary Subject Heading</b>:
Global health
Secondary Subject Heading: Medical management
Keywords: beliefs about medicines, medicine non-adherence, chronic diseases
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Beliefs about medicines and non-adherence in patients with stroke, diabetes mellitus
and rheumatoid arthritis in China
Li Wei, MD, PhD1, Sarah Chapman PhD
1, Xiaomei Li MD
2, Xin Li MD, PhD
3, Sumei Li
MD4, Ruoling Chen MD, PhD
5, Bo Nie MSc
1, Angel Chater PhD
1, and Rob Horne PhD
1
Short running title: Beliefs about medicines and medicine non-adherence
Key words: beliefs about medicines, medicine non-adherence, chronic diseases
1Department of Practice and Policy, UCL School of Pharmacy, Mezzanine Floor, Entrance A,
BMA House, Tavistock Square, London, WC1H 9JP
2Department of Rheumatology and Immunology, Anhui Provincial Hospital, Anhui Medical
University, Hefei230001, China
3Department of Neurology, The Second Hospital, Tianjin Medical University, Tianjin
300211, China
4Department of Endocrinology, Anhui Provincial Hospital, Anhui Medical University, Hefei
230001, China
5Centre for Health and Social Care Improvement, Faculty of Education Health and
Wellbeing, University of Wolverhampton, Wolverhampton, WV1 1DT, UK
Corresponding author:
Dr Li Wei
Department of Practice and Policy, UCL School of Pharmacy, 29-39 Brunswick Square,
London, WC1N 1AX
Tel: 44 2078741275
E-mail: [email protected]
This study was funded by the Research Innovation Fund, UCL School of Pharmacy.
Word count (abstract): 300; Word count (full text): 2750; Tables: 5; Figures: 1
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Abstract
Objectives: To investigate beliefs about medicines and their association with medicine
adherence in patients with chronic diseases in China.
Design: A cross-sectional questionnaire-based study
Setting: Two large urban hospitals in Hefei and Tianjin, China
Participants: Hospital inpatients (313 stroke patients) and outpatients (315 diabetic patients
and 339 rheumatoid arthritis (RA) patients) were recruited between January 2014 and
September 2014.
Outcome measures: The Beliefs about Medicines Questionnaire (BMQ), assessing patients’
beliefs about the specific medicine (Specific-Necessity and Specific-Concerns) prescribed for
their conditions (stroke/diabetes/RA) and more general background beliefs about
pharmaceuticals as a class of treatment (BMQ-General Benefit, Harm and Overuse); the
Perceived Sensitivity to Medicines scale (PSM) assessed patients’ beliefs about how sensitive
they were to the effects of medicines and the Medication Adherence Report Scale. The
association between non-adherence and beliefs about medicines was assessed using a logistic
regression model.
Results: Patients with diabetes mellitus had a stronger perceived need for treatment [mean
(SD) Specific-Necessity score, 3.75 (0.40)] than patients with stroke [3.69 (0.53)] and RA
[3.66 (0.44)] (p=0.049). Moderate correlations were observed between Specific-Concerns and
General-Overuse, General-Harm and PSM (Pearson correlation coefficients, 0.39, 0.49 and
0.49, respectively, p<0.01). 311 patients were non-adherent to their medicine [159 (51.0%) in
the stroke group, 60 (26.7%) in the diabetes mellitus group and 62 (19.8%) in the RA group,
p<0.01]. Across the whole sample, after adjusting for demographic characteristics non-
adherence was associated with patients who had higher concerns about their medicines (OR,
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1.35, 95% CI 1.07-1.71) and patients who believed that they were personally sensitive to the
effects of medications (OR 1.44, 95% CI 1.16-1.85).
Conclusion: The BMQ is a useful tool to identify patients at risk of non-adherence. In future,
adherence intervention studies may use the BMQ to screen for patients who are at risk of
non-adherence and to map interventional support.
Funding: Research Innovation Fund, UCL School of Pharmacy.
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Strengths and limitations of this study
• First large study of beliefs about medicines in China
• High response rate, reflecting generalisability of the study finding
• A cross-sectional design implicating that the association between non-adherence and
beliefs about medicines did not necessarily lead a causal relationship.
• Self-reported adherence may not be the best measurement for medicine adherence.
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Introduction
Medicine plays an essential role in chronic disease management. However, it is recognised
that only half of patients with chronic diseases take their medicines as prescribed.1 Stroke,
diabetes mellitus and rheumatoid arthritis (RA) are three common chronic diseases which
together affect over 10% of China’s population of 1.40 billion.2-5
Stroke is the leading cause
of adult death and disability in China with an annual mortality rate of approximately 1.6
million, or 157 per 100,000.6
Patients with chronic diseases often require multiple medicine
treatments for their conditions and any associated symptoms and comorbidities. To obtain
full benefit from treatment, patients need to adhere to these complex medicine regimens in
order to control their disease and maintain health. However, in reality medicine management
is sub-optimal and relates to physician inertia and patients’ poor adherence with therapy.7
The
elderly, with high rates of co-morbidity and co-prescribing, tend to have poor adherence and
are at particular risk of unwanted adverse effects from drugs.8,9
Studies outside China have identified patients’ beliefs about medicines as an important
determinant of non-adherence.10
A recent meta-analysis of 96 peer-reviewed studies
involving over 24,000 patients across 24 long-term conditions and 18 countries should that
non-adherence was related to patients beliefs about medicines, measured by the Beliefs about
Medicines Questionnaire (BMQ).10
These studies indicated that there was often a disconnect
between the patients and prescribers view of the medicine. Many patients doubted their
personal need for the treatment or harboured concerns and these beliefs were associated with
non-adherence. Beliefs about medicines may also be relevant in China, particularly as there
some evidence that trust between patients and health professionals may have diminished after
China’s economic reform.11,12
Patients often do not trust their doctors and doubt the treatment
including therapeutic treatment they received. It is possible that this may translate into
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scepticism about prescribed medicines and non-adherence. The aim of this study was to
understand beliefs about medicines in Chinese patients with stroke, diabetes mellitus and RA
and to investigate whether these beliefs are associated with medicine non-adherence.
Methods
A cross-sectional survey was conducted in two large teaching hospitals in China between
January 2014 and November 2014. The study was approved by the local research ethics
committees.
Study populations and recruitment
Patients with stroke were recruited from The Second Hospital, Tianjin Medical University,
Tianjin, China and patients with diabetes mellitus and RA were recruited from Anhui
Provincial Hospital, Anhui Medical University, Hefei, China. Both hospitals are large
teaching hospitals and are level 3 general hospitals, the highest classification for quality care
given by the China’s National Health and Family Planning Commission (NHFPC) for all
public hospitals.13
Patients who had a clinical diagnosis of stroke, diabetes mellitus or RA
who were judged by the healthcare professionals as able to answer questions were invited by
the healthcare professionals to take part in the study when they were admitted to hospital or
came to hospital clinics during the study period. They were asked to complete a questionnaire
which took approximately 10-15 minutes. Study information was given to patients and verbal
consent was obtained before they started to fill in the questionnaire. All invited patients
returned their questionnaires. Since there is a lack of research on beliefs about medicines and
medicine non-adherence in China, a target sample size of 300 patients for each condition was
chosen based on typical sample sizes used in similar surveys. A recent meta-analysis showed
that small-moderate effect of psychological beliefs on medicine adherence was observed in
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94 studies with an average sample size of 266.10
Data collection started in January 2014 and
lasted around 4 months for each condition and was stopped once the target numbers were
reached (November 2014).
Questionnaire measurement
The questionnaire consisted of demographic information, the BMQ questionnaire,14
perceived
sensitivity to medicines scale (PSM) and medicine adherence report scale (MARS).15
All
scales were translated and back translated in accordance with the Originator’s conditions to
create a Chinese version, (BMQ-Chinese © R Horne MARS-Chinese © R Horne, PSM-
Chinese © R Horne). The BMQ and MARS were translated into Chinese by Dr Li Wei, the
principal investigator for this study. They were then sent to the co-authors, Profs Xiaomei Li
and Xin Li for comments and further adaptation resulting in a final Chinese version of the
BMQ.
Demographic information included name, age, gender, education, occupation and duration of
the condition. The BMQ questionnaire has two parts: the BMQ-Specific assessing beliefs
about medicine used for a particular condition and the BMQ-General assessing beliefs about
medicines in general. The details of the BMQ questionnaire can be found in a previous
publication.8 In brief, BMQ-Specific comprised two scales: a 5-item treatment necessity scale
Specific-Necessity and a 6-item treatment concern scale Specific-Concern. BMQ-General
used three subscales: 1) General-Overuse (4 items), 2) General-Harm (4 items), and 3)
General-Benefit (4 items). Perceived Sensitivity to Medicines (PSM) scale contained 5 items
assessing perceptions of personal susceptibility to the effects of medicines. All BMQ items
and PSM were scored on a Likert type scale (where 1 = strongly disagree, 2 = disagree, 3 =
uncertain, 4 = agree and 5 = strongly agree). A mean item score was then calculated as the
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sum of each item score divided by the number of items [for example, mean score of Specific-
Necessity= (N1+N2+N3+N4+N5)/5]. The Cronbach’s αs indicated that all scale measures
were internally consistent in the study sample with αnecessity = 0.64, αconcern = 0.75, αoveruse=
0.54, αharm = 0.55, αbenefit = 0.58 and αpsm = 0.85. Medicine adherence was measured using the
MARS scale consisting of 5 items with 25 score points in total.
Before the study commenced, 30 people including doctors, nurses, medical students and
patients were asked to complete the questionnaire to assess whether the Chinese version of
the BMQ, PSM and MARS would be easily understood by Chinese patients. Feedback was
wholly positive; however we recognised that patients were likely to be elderly and may have
poor literacy. Therefore, arrangements were made to provide help should patients have any
difficulty completing the questionnaire. Patients in both centres completed the questionnaire
either by themselves or with help from the healthcare professionals in the medical ward or
clinic they attended. Healthcare professionals received a briefing from the local investigators
on how to complete the questionnaire including instructions on how to explain the meaning
of the questionnaire items without influencing patients’ responses.
Definition of adherence and non-adherence
Adherence rate was calculated as summed from each item scored by each patient divided by
the maximum points of 25 using the 5-item MARS scale. Adherent patients were defined as
having ≥ 80% adherence rate (i.e. ≥ 20 points) which is a commonly used cut-off point in
medicine benefit/safety studies and is also used conventionally in clinical trials of safety and
efficacy that have been used to support a new drug registration.16
Non-adherent patients were
defined as having <80% adherence rate.
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Statistical analysis
Data were presented as mean (SD) for continuous variables and as frequencies (%) for
categorical variables. Chi-squared and analysis of variance (ANOVA) tests were performed
to determine significant differences between the three diseases. Correlations were used to
examine relationships between BMQ-General and BMQ-Specific subscales. Logistic
regression analysis was employed to assess the association between non-adherence and
medicine beliefs. Five percent of patients had at least one missing value in their BMQ
answers and the total missing values were 0.3% for the whole BMQ items. A sensitivity
analysis was done to include all patients with missing data replaced with imputed data in the
multivariable analysis concluding all variables listed in Table 1. The multiple imputation
analysis included all variables used in the final analysis with 10 imputations by using the
Markov Chain Monte Carlo method to produce imputed data. All statistical analyses were
carried out using SAS (version 9.4).
Results
Patient characteristics
There were 967 patients in the study (313 with stroke, 315 with diabetes mellitus and 339
with RA). Table 1 shows the demographic and clinical information by disease groups.
Patients with RA were significantly younger than patients with stroke and diabetes mellitus
(mean age 49.7 vs 65.8 and 62.5, respectively). The RA group was 85% female while only
44% of stroke patients and 45% of diabetes mellitus patients were female. Patients with RA
were 5 times more likely to report having received no formal education than patients with
stroke and diabetes mellitus (23.3% vs 4.8% and 4.1%, respectively). Over half of patients in
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the stroke group had less than 1 year disease duration while more than half of the patients in
the RA and diabetes mellitus groups had more than 5 years disease duration.
BMQ results
The results of BMQ subscales are shown in Table 2. There were no significant differences in
the mean scores of Specific-Concerns and General-Harm between the three groups. However,
differences were observed for Specific-Necessity, General-Overuse, General-Benefit and
PSM among the three groups. Patients with RA had the highest score of 3.75 (SD 0.40) for
Specific-Necessity and lowest scores of 2.95 (SD 0.51) for General-Overuse and 3.55 (SD
0.45) for General-Benefit. The mean scores of PSM were 2.89 (SD 0.65), 2.35 (SD 0.64) and
2.70 (SD 0.68). The attitudinal analysis categorised patients into four groups (high/low
necessity and high/low concerns) according to the midpoint of the Specific-Necessity
Specific-Concerns scales shows that 45% of patients were classified as ‘Ambivalent’ (Figure
1).
Patients’ general beliefs about medicines were associated with their evaluations of the
specific treatments they were taking. Table 3 shows the correlation between BMQ-General
and BMQ-Specific. Specific-Necessity was positively association with General-Benefit
(Pearson correlation coefficients = 0.31, p<0.01). Moderate correlations were observed
between Specific-Concerns and General-Overuse, General-Harm and PSM (Pearson
correlation coefficients, 0.39, 0.49 and 0.49, respectively, p<0.01). General-Overuse was also
correlated with General-Harm and PSM (Pearson correlation coefficients, 0.45 and 0.39,
respectively, p<0.01). The Pearson correlation coefficient was 0.39 (p<0.01) for General-
Harm and PSM.
Association between beliefs about medicines and non-adherence
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Three hundred and eleven patients were non-adherent to their medicine [159 (51.0%) in the
stroke group, 60 (26.7%) in the diabetes mellitus group and 62 (19.8%) in the RA group,
p<0.01]. After adjusting for demographic characteristics, Specific-Concerns and PSM were
significantly associated with non-adherence (adjusted ORs, 1.35, 95% CI 1.07-1.71 and 1.44,
95% CI 1.16-1.80).There were negative associations between non-adherence and Specific-
Necessity and General-Benefit. However, the association was not statistically significant
(Table 4). The subgroup analyses showed that the point estimates of Specific-Concerns were
positively associated with non-adherence across the three conditions i.e. the more concerns
about the medicines, the more non-adherent to medicines, with adjusted ORs ranging from
1.15 for diabetes mellitus to 1.43 for stroke (Table 5). The unadjusted results showed similar
results across the three disease conditions. The sensitivity analysis showed that Specific-
Concerns and PSM were positively associated with non-adherence (adjusted ORs, 1.15 95%
CI 1.04-1.26 and 1.40, 95% CI 1.04-1.26, respectively) and General-Benefit was negatively
associated with non-adherence (adjusted OR 0.79, 95% CI 0.71-0.87). Compared with
patients in the Accepting group, patients in the other attitudinal groups were more likely to be
the non-adherent (adjusted ORs, 1.50 95% CI 1.10-2.05 for the Ambivalent group, 1.27 95%
CI 0.60-2.68 for the Skeptical group and 1.27 95% CI 0.69-2.34 for the Indifferent group.
Discussion
This is the first large study of this kind that investigates beliefs about medicines and medicine
non-adherence in China in three common chronic diseases. Both unadjusted and adjusted
results revealed that Specific-Concerns, General-Benefit and PSM were significantly
associated with non-adherence i.e. the higher the concern about the medicine or the higher
perceived sensitivity to medicines or the lower of the belief in general medicine benefits, the
lower the adherence to medicines.
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Our findings were consistent with the evidence from a recent meta-analysis which showed
that higher adherence was associated with fewer concerns about treatment10
but not consistent
with previous findings that higher belief in personal need for treatment was associated with
higher adherence; Specific-Necessity was not associated with non-adherence in our overall
analysis. Subgroup analyses showed that patients with stroke and diabetes mellitus showed
the same direction association as previous studies i.e, patients with higher necessity were less
likely to be non-adherent. However, an opposite non-statistically significant result of
Specific-Necessity and adherence for patients with RA (Our result of 1.34 (95% CI 0.73-
2.46) for non-adherence equals 0.75, 95% CI 0.41-1.38 for adherence) was observed in the
study in comparison with the meta-analysis result which had a pooled OR of 3.28, 95%CI
1.11-9.71 for adherence.10
The point estimate could be due to chance and further studies need
to confirm the finding. A recent study found that General-Benefit may be negatively
associated with non-adherence among 398 patients with epilepsy from the UK primary care
population (adjusted OR, 0.92, 95%CI 0.63-1.34)17
and this association was confirmed by our
study with a significant OR of 0.75 (95%CI 0.56-1.02). There was no correlation between
Necessity and Concern (Table 2) in our study population and this was supported by a recent
Swedish study conducted in 578 stroke patients.18
They reported a Spearman’s correlation
coefficient of 0.075 (p=0.08). Compared to patients with high necessity and low concerns,
patients with high necessity and high concerns, low necessity and high concerns, and low
necessity and low concerns were all associated with non-adherence and this was supported by
studies conducted in patients with inflammatory bowel disease and renal dysfunction.19, 20
High perceived sensitivity to medicines was reported to be associated with non-adherence
and higher medical care utilisation, increased symptom reporting and greater information-
seeking about medication.17, 21
Our study also showed PSM was associated with non-
adherence.
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Our study has some strengths. Firstly, this was the first large BMQ study conducted in China.
Secondly, we choose two large teaching hospitals for this study and collected data continually
until the target numbers were reached for each condition. Therefore, our study population
was likely to represent the disease population from each region. Thirdly, China has higher
prevalent rates of stoke and diabetes mellitus than Western Europe and stroke is also the
leading cause of death in China. In light of the current deteriorated relationship between
health professional and patients (i.e. patients do not trust their doctors and other health
professionals, doctors, nurses are often abused verbally and physically by patients,11, 22, 23
more studies are needed from the patients’ perspective. More consideration from the patient
perspective should be taken into account in term of chronic disease management and the
relationship between patients and health professionals. However, our study was an
observational study. Therefore the results may be confounded by unmeasured factors such as
comorbidity. Self-reported adherence may not be the best measurement for medicine
adherence as patients may, for example, underestimate how often they forget their treatment.
However, a strong correlation was found for medicine adherence measured by self-reported
questionnaire, electronic prescriptions and serum biomarkers in a recent intervention study
suggesting that self-report is a reliable measure.24
Also our study found relatively low
reliability of the BMQ general scales and further investigation and refinement might be
needed of these Chinese translations. The difference in non-adherence between stroke and
other conditions needs to be explored in future studies as disease itself may play an important
role in medicine adherence.
In conclusion, we found that the BMQ is a useful tool to identify psychological factors that
are linked to non-adherence in patients with stroke, diabetes and RA. Future studies should
use the BMQ to screen patients to identify those who are at high risk of non-adherence and
map their treatment plan accordingly.
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CONFLICT OF INTEREST/STUDY SUPPORT:
Specific author contributions: LW, RC and RH were involved in conception and design and
interpretation of data. LW did the statistical analysis and wrote the first draft of the article.
SC, RC and BN contributed to data analysis. LXM, LX and LSM collected data. SC, AC,
LXM, LX and LSM were involved in interpretation of data. All authors were responsible for
re-drafting of the article and approved the final version.
Guarantor of the article: LW is the guarantor
Financial support: This study was funded by the Research Innovation Fund, UCL School of
Pharmacy. The funder had no role in the design, conduct or data interpretation of the study.
Professor Rob Horne was supported by the National Institute for Health Research (NIHR)
Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North
Thames at Bart’s Health NHS Trust.
Potential competing interests: RH declares: (1) Speaker engagements with honoraria and
consultancy payments from the pharmaceutical companies; (2) Founder and shareholder of a
UCL-Business, university spin-out company (Spoonful of Sugar Ltd) providing consultancy
on medication-related behaviours to healthcare policy makers, providers and industry; and (3)
Originator of BMQ.
References:
1. Medicines adherence: involving patients in decisions about prescribed medicines and
supporting adherence. https://www.nice.org.uk/guidance/cg76/chapter/introduction (accessed
on 30 January 2017)
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15
2. Liu L, Wang D, Wong KS, Wang Y. Stroke and stroke care in China: huge burden,
significant workload, and a national priority. Stroke; a journal of cerebral circulation.
2011;42(12):3651-4.
3. Feigin VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA, et al.
Global and regional burden of stroke during 1990-2010: findings from the Global Burden of
Disease Study 2010. Lancet. 2014;383(9913):245-54.
4. Li R, Sun J, Ren LM, Wang HY, Liu WH, Zhang XW, et al. Epidemiology of eight
common rheumatic diseases in China: a large-scale cross-sectional survey in Beijing.
Rheumatology (Oxford). 2012 Apr;51(4):721-9. doi: 10.1093/rheumatology/ker370. Epub
2011 Dec 16.
5. Total population, 2013. http://www.who.int/countries/chn/en/ (accessed on 30 January
2017)
6. Xiaomei Wu, Bo Zhu, Lingyu Fu, Hailong Wang, Bo Zhou, SafengZou, et al.
Prevalence, Incidence, and Mortality of Stroke in the Chinese Island Populations: A
Systematic Review PLOS Published: November 8, 2013•DOI: 10.1371/journal.pone.0078629
7. Will JC, Zhang Z, Ritchey MD, Loustalot F. Medication Adherence and Incident
Preventable Hospitalizations for Hypertension. American journal of preventive medicine.
2015.
8. Shore S, Carey EP, Turakhia MP, Jackevicius CA, Cunningham F, Pilote L, et al.
Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the
veterans health administration. American heart journal. 2014;167(6):810-7.
9. Korhonen MJ, Ruokoniemi P, Ilomaki J, Meretoja A, Helin-Salmivaara A, Huupponen R.
Adherence to statin therapy and the incidence of ischemic stroke in patients with diabetes.
Pharmacoepidemiol Drug Saf. 2016 Feb;25(2):161-9. doi: 10.1002/pds.3936.
Page 15 of 24
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/B
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ctober 2017. Dow
nloaded from
For peer review only
16
10. Horne, R, Chapman SC, Parham R, Freemantle N, Forbes A, Cooper V. Understanding
patients’ adherence –related beliefs about medicines prescribed for long-term conditions: a
meta-analytic review of the necessity-concerns framework. Plos One. 2013 Dec
2;8(12)e80633. Doi:10.1371/journal.pone.0080633.
11. Tucker JD, Cheng Y, Wong B, Gong N, Nie JB, Zhu W, et al; Patient-Physician Trust
Project Team. Patient-physician mistrust and violence against physicians in Guangdong
Province, China: a qualitative study. BMJ Open. 2015 Oct 6;5(10):e008221. doi:
10.1136/bmjopen-2015-008221.
12. Chan CS, Cheng Y, Cong Y, Du Z, Hu S, Kerrigan A, et al. Patient-physician trust in
China: a workshop summary. Lancet. 2016 Oct;388 Suppl 1:S72. doi: 10.1016/S0140-
6736(16)31999-7.
13. National Health and Family Planning Commission of the PRC http://en.nhfpc.gov.cn/
(last access 30 January 2017)
14. Horne R, Weinman J. Patients' beliefs about prescribed medicines and their role in
adherence to treatment in chronic physical illness. J Psychosom Res. 1999 Dec;47(6):555-67.
15. Horne R. The nature, determinants and effects of medication beliefs in chronic illness
(PhD thesis) University of London 1997.
16. Wei L, Wang J, Thompson P, Wong S, Struthers AD, MacDonald TM. Adherence to
statin treatment and readmission of patients after myocardial infarction: a six year follow up
study. Heart 2002;88:229-33.
17. Chapman SC, Horne R, Chater A, Hukins D, Smithson WH. Patients' perspectives on
antiepileptic medication: relationships between beliefs about medicines and adherence among
patients with epilepsy in UK primary care. Epilepsy Behav. 2014 Feb;31:312-20. doi:
10.1016/j.yebeh.2013.10.016. Epub 2013 Nov 27.
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17
18. Sjolander M, Eriksson M, Glader EL. The association between patients' beliefs about
medicines and adherence to drug treatment after stroke: a cross-sectional questionnaire
survey. BMJ open. 2013;3(9):e003551.
19. Horne R, Parham R, Driscoll R, Robinson A. Patients' attitudes to medicines and
adherence to maintenance treatment in inflammatory bowel disease. Inflamm Bowel Dis.
2009 Jun;15(6):837-44. doi: 10.1002/ibd.20846.
20. Chater AM, Parham R, Riley S, Hutchison AJ, Horne R. Profiling patient attitudes to
phosphate binding medication: a route to personalising treatment and adherence support.
Psychol Health. 2014;29(12):1407-20. doi: 10.1080/08870446.2014.942663. Epub 2014 Aug.
21. Faasse K, Grey A, Horne R, Petrie KJ. High perceived sensitivity to medicines is
associated with higher medical care utilisation, increased symptom reporting and greater
information-seeking about medication. Pharmacoepidemiol Drug Saf. 2015 Jun;24(6):592-9.
doi: 10.1002/pds.3751. Epub 2015 Apr 7.
22. Li ZG, Leng MX. Doctor-patient relationship research summary. Chinese Hospital
Management. 2009;29(332):40-3.
23. Doctors face verbal abuse or violence. http://www.cmdae.org/en/index.php (Accessed 30
January 2017).
24. Lyons I, Barber N, Raynor DK, Wei L. The Medicines Advice Service Evaluation
(MASE): a randomised controlled trial of a pharmacist-led telephone based intervention
designed to improve medication adherence. BMJ Qual Saf. 2016 Oct;25(10):759-69. doi:
10.1136/bmjqs-2015-004670.
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Table 1. Patient characteristics by conditions
Stroke
n=313 (100%)
Diabetes
n=315 (100%)
RA
n=339 (100%)
Age 65.8 (13.7) 62.5 (13.9) 49.7 (12.8)
Gender†*
Women 136 (43.5%) 141 (44.8%) 287 (85.2%)
Men 177 (56.5%) 174 (55.2%) 50 (14.8%)
Education
Illiteracy (no formal
education)
15 (4.8%) 13 (4.1%) 79 (23.3%)
Primary school 66 (21.1%) 62 (19.7%) 93 (27.4%)
Junior high school 60 (19.2%) 91 (28.9%) 91 (26.8%)
High school/college 116 (37.1%) 77 (24.4%) 48 (14.2%)
University or above 54 (17.2%) 70 (22.2%) 25 (7.4%)
Unknown 2 (0.6%) 2 (0.6%) 3 (0.9%)
Occupation
Farmer 5 (1.6%) 22 (7.0%) 110 (32.5%)
Worker/clerk 83 (26.5%) 117 (37.1%) 38 (11.2%)
Housewife/unemployment 45 (14.4%) 12 (3.8%) 113 (33.3%)
Retirement 129 (41.2%) 54 (17.1%) 40 (11.8%)
Health professional 19 (6.1%) 29 (9.2%) 15 (4.4%)
Civil service 29 (9.3%) 72 (22.9%) 11 (3.2%)
Unknown 3 (1.0%) 9 (2.9%) 12 (3.5%)
Duration of the disease
<= 1 year 178 (56.9%) 20 (6.4%) 55 (16.2%)
1-5 years 91 (29.1%) 74 (23.5%) 104 (30.7%)
> 5 year 44 (14.1%) 220 (69.8%) 177 (52.2%)
unknown 0 (0.0%) 1 (0.3%) 3 (0.9%) †Excluding missing data; *<0.05
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Table 2. Results of BMQ and PSM by disease conditions
Stroke
n=313 (100%)
Diabetes
n=315 (100%)
RA
n=339 (100%)
Specific-Necessity (mean, SD) †
* 3.69 (0.53) 3.75 (0.40) 3.66 (0.44)
Specific-Concerns (mean, SD) †
3.03 (0.71) 3.15 (0.58) 3.07 (0.58)
General-Overuse (mean, SD) †
* 3.22 (0.62) 3.12 (0.50) 2.95 (0.51)
General-Harm (mean, SD) †
2.94 (0.78) 2.95 (0.50) 2.99 (0.43)
General-Benefit (mean, SD) †
* 3.70 (0.53) 3.69 (0.42) 3.55 (0.45)
PSM (mean, SD) †
* 2.89 (0.65) 2.35 (0.64) 2.70 (0.68)
MARS score (mean, SD*) 18.81 (4.16) 21.51 (3.07) 21.47 (3.86) †Excluding missing data; PSM=Perceived Sensitivity to Medicines; *<0.05
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Table 3. Correlation matrix between BMQ-Specific, BMQ-General and PSM
Necessity Concerns Overuse Harm Benefit PSM
Overall
Necessity 1.00
Concern 0.02(0.45) 1.00
Overuse -0.01 (0.87) 0.39 (<0.01) 1.00
Harm -0.05 (0.16) 0.49 (<0.01) 0.45 (<0.01) 1.00
Benefit 0.31(<0.01) -0.09 (0.01) 0.11 (<0.01) 0.04 (0.21) 1.00
PSM 0.04 (0.22) 0.45 (<0.01) 0.39 (<0.01) 0.38<0.01) 0.05 (0.14) 1.00
Stroke
Necessity 1.00
Concern 0.04 (0.43) 1.00
Overuse 0.06 (0.31) 0.50 (<0.01) 1.00
Harm -0.06 (0.27) 0.66 (<0.01) 0.57 (<0.01) 1.00
Benefit 0.36 (<0.01) 0.01 (0.88) 0.24 (<0.01) 0.13 (0.12) 1.00
PSM 0.23 (<0.01) 0.52 (<0.01) 0.51 (<0.01) 0.50 (<0.01) 0.22 (<0.01) 1.00
Diabetes mellitus
Necessity 1.00
Concern 0.02 (0.59) 1.00
Overuse -0.05 (0.40) 0.26 (<0.01) 1.00
Harm -0.08 (0.20) 0.21 (<0.01) 0.44 (<0.01) 1.00
Benefit 0.19 (<0.01) -0.07 (0.26) 0.18 (<0.01) 0.08 (0.19) 1.00
PSM -0.08 (0.20) 0.36 (<0.01) 0.38 (<0.01) 0.44 (<0.01) 0.07 (0.23) 1.00
RA
Necessity 1.00
Concerns 0.01 (0.91) 1.00
Overuse -0.08 (0.13) 0.41 (<0.01) 1.00
Harm 0.02 (0.72) 0.42 (<0.01) 0.30 (<0.01) 1.00
Benefit 0.30 (<0.01) -0.21 (<0.01) -0.20 (<0.01) -0.15 (0.21) 1.00
PSM -0.04 (0.52) 0.54 (<0.01) 0.29 (<0.01) 0.27 (<0.01) -0.13 (0.02) 1.00
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Table 4. Odd ratios of medicine non-adherence
Unadjusted
OR (95%CI)
Adjusted*
OR (95%CI)
Specific-Necessity 0.90, 0.67-1.21 0.93, 0.68-1.27
Specific-Concerns 1.27, 1.02-1.58 1.35, 1.07-1.71
General-Overuse 1.32, 1.04-1.69 1.15, 0.88-1.50
General-Harm 1.09, 0.87-1.38 1.12, 0.89-1.43
General-Benefit 0.84, 0.63-1.12 0.75, 0.56-1.02
PSM 1.72, 1.41-2.09 1.44, 1.16-1.85
*Adjusted for age, gender, education, occupation, duration of the disease and different
diseases
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Table 5. Odd ratios of medication non-adherence by disease groups
Stroke Diabetes RA
Unadjusted
OR (95%CI)
Adjusted*
OR (95%CI)
Unadjusted
OR (95%CI)
Adjusted*
OR (95%CI)
Unadjusted
OR (95%CI)
Adjusted*
OR (95%CI)
Specific-
Necessity
0.83, 0.54-1.26 0.92, 0.59-1.43 0.71, 0.35-1.40 0.92, 0.43-1.97 1.31, 0.75-2.27 1.34, 0.73-2.46
Specific-
Concerns
1.43, 1.04-1.96 1.43, 1.02-2.00 1.16, 0.71-1.88 1.15, 0.67-1.98 1.38, 0.91-2.12 1.32, 0.84-2.10
General-
Overuse
1.26, 0.88-1.81 1.24, 0.85-1.82 1.12, 0.64-1.96 1.10, 0.61-2.00 1.06, 0.66-1.71 0.98, 0.60-1.60
General-
Harm
1.26, 0.95-1.68 1.30, 0.96-1.77 0.58, 0.32-1.05 0.59, 0.32-1.11 1.27, 0.72-2.24 1.27, 0.70-2.30
General-
Benefit
0.87, 0.57-1.32 0.83, 0.53-1.29 0.78, 0.41-1.50 0.83, 0.41-1.69 0.64, 0.37-1.09 0.65, 0.37-1.13
PSM 1.76, 1.22-2.53 1.79, 1.23-2.60 1.60, 1.05-2.44 1.73, 1.10-2.70 1.06, 0.74-1.51 1.01, 0.70-1.48
*Adjusted for age, gender, education, occupation, duration of the disease
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Figure 1. Attitudinal analysis of BMQ-Specific.
Skeptical
n = 40 (4.3%)
Ambivalent
n = 422 (44.8%)
Indifferent
n = 58 (6.2%)
Accepting
n = 421 (44.7%)
High NecessityLow Necessity
High Concerns
Low Concerns
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Figure 1. Attitudinal analysis of BMQ-Specific.
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Beliefs about medicines and non-adherence in patients with
stroke, diabetes mellitus and rheumatoid arthritis: A cross-
sectional study in China
Journal: BMJ Open
Manuscript ID bmjopen-2017-017293.R1
Article Type: Research
Date Submitted by the Author: 01-Jun-2017
Complete List of Authors: Wei, Li; University College London School of Pharmacy, BMA house, Tavistock Square Chapman, Sarah; UCL School of Pharmacy,
Li, Xiaomei; Anhui Provincial Hospital, Anhui Medical University Li, Xin; The Second Hospital, Tianjin Medical University Li, Sumei; Anhui Provincial Hospital, Anhui Medical University Chen, Ruoling; University of Wolverhampton, Centre for Health and Social Care Improvement Bo, Nie; University College London School of Pharmacy Chater, Angel; University College London, Centre for Behavioural Medicine Horne, Robert; University College London School of Pharmacy
<b>Primary Subject Heading</b>:
Global health
Secondary Subject Heading: Medical management
Keywords: beliefs about medicines, medicine non-adherence, chronic diseases
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Beliefs about medicines and non-adherence in patients with stroke, diabetes mellitus
and rheumatoid arthritis: A cross-sectional study in China
Li Wei, MD, PhD1, Sarah Chapman PhD
1 2, Xiaomei Li MD
3, Xin Li MD, PhD
4, Sumei Li
MD5, Ruoling Chen MD, PhD
6, Bo Nie MSc
1, Angel Chater PhD
1 7, and Rob Horne PhD
1
Short running title: Beliefs about medicines and medicine non-adherence
Key words: beliefs about medicines, medicine non-adherence, chronic diseases
1Department of Practice and Policy, UCL School of Pharmacy, Mezzanine Floor, Entrance A,
BMA House, Tavistock Square, London, WC1H 9JP
2Department of Pharmacy & Pharmacology, University of Bath, Claverton Down Road, Bath,
BA2 7AY 3Department of Rheumatology and Immunology, Anhui Provincial Hospital, Anhui Medical
University, Hefei230001, China
4Department of Neurology, The Second Hospital, Tianjin Medical University, Tianjin
300211, China
5Department of Endocrinology, Anhui Provincial Hospital, Anhui Medical University, Hefei
230001, China
6Centre for Health and Social Care Improvement, Faculty of Education Health and
Wellbeing, University of Wolverhampton, Wolverhampton, WV1 1DT, UK
7Centre for Health, Wellbeing and Behaviour Change, Faculty of Education and Sport
University of Bedfordshire, Polhill Avenue, Bedford, MK41 9EA
Corresponding author:
Dr Li Wei
Department of Practice and Policy, UCL School of Pharmacy, 29-39 Brunswick Square,
London, WC1N 1AX
Tel: 44 2078741275
E-mail: [email protected]
This study was funded by the Research Innovation Fund, UCL School of Pharmacy.
Word count (abstract): 300; Word count (full text): 2947; Tables: 5; Figures: 1
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Abstract
Objectives: To investigate beliefs about medicines and their association with medicine
adherence in patients with chronic diseases in China.
Design: A cross-sectional questionnaire-based study
Setting: Two large urban hospitals in Hefei and Tianjin, China
Participants: Hospital inpatients (313 stroke patients) and outpatients (315 diabetic patients
and 339 rheumatoid arthritis (RA) patients) were recruited between January 2014 and
September 2014.
Outcome measures: The Beliefs about Medicines Questionnaire (BMQ), assessing patients’
beliefs about the specific medicine (Specific-Necessity and Specific-Concerns) prescribed for
their conditions (stroke/diabetes/RA) and more general background beliefs about
pharmaceuticals as a class of treatment (BMQ-General Benefit, Harm and Overuse); the
Perceived Sensitivity to Medicines scale (PSM) assessed patients’ beliefs about how sensitive
they were to the effects of medicines and the Medication Adherence Report Scale. The
association between non-adherence and beliefs about medicines was assessed using a logistic
regression model.
Results: Patients with diabetes mellitus had a stronger perceived need for treatment [mean
(SD) Specific-Necessity score, 3.75 (0.40)] than patients with stroke [3.69 (0.53)] and RA
[3.66 (0.44)] (p=0.049). Moderate correlations were observed between Specific-Concerns and
General-Overuse, General-Harm and PSM (Pearson correlation coefficients, 0.39, 0.49 and
0.49, respectively, p<0.01). 311 patients were non-adherent to their medicine [159 (51.0%) in
the stroke group, 60 (26.7%) in the diabetes mellitus group and 62 (19.8%) in the RA group,
p<0.01]. Across the whole sample, after adjusting for demographic characteristics non-
adherence was associated with patients who had higher concerns about their medicines (OR,
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1.35, 95% CI 1.07-1.71) and patients who believed that they were personally sensitive to the
effects of medications (OR 1.44, 95% CI 1.16-1.85).
Conclusion: The BMQ is a useful tool to identify patients at risk of non-adherence. In future,
adherence intervention studies may use the BMQ to screen for patients who are at risk of
non-adherence and to map interventional support.
Funding: Research Innovation Fund, UCL School of Pharmacy.
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Strengths and limitations of this study
• First large study of beliefs about medicines in China
• High response rate, reflecting generalisability of the study finding
• A cross-sectional design implicating that the association between non-adherence and
beliefs about medicines did not necessarily lead a causal relationship.
• Self-reported adherence may not be the best measurement for medicine adherence.
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Introduction
Medicine plays an essential role in chronic disease management. However, it is recognised
that only half of patients with chronic diseases take their medicines as prescribed.1 Stroke,
diabetes mellitus and rheumatoid arthritis (RA) are three common chronic diseases which
together affect over 10% of China’s population of 1.40 billion.2-5
Stroke is the leading cause
of adult death and disability in China with an annual mortality rate of approximately 1.6
million, or 157 per 100,000.6
Patients with chronic diseases often require multiple medicine
treatments for their conditions and any associated symptoms and comorbidities. To obtain
full benefit from treatment, patients need to adhere to these complex medicine regimens in
order to control their disease and maintain health. However, in reality medicine management
is sub-optimal and relates to physician inertia and patients’ poor adherence with therapy.7
The
elderly, with high rates of co-morbidity and co-prescribing, tend to have poor adherence and
are at particular risk of unwanted adverse effects from drugs.8,9
Studies outside China have identified patients’ beliefs about medicines as an important
determinant of non-adherence.10
A recent meta-analysis of 96 peer-reviewed studies
involving over 24,000 patients across 24 long-term conditions and 18 countries showed that
non-adherence was related to patients beliefs about medicines, measured by the Beliefs about
Medicines Questionnaire (BMQ).10
These studies indicated that there was often a disconnect
between the patients and prescribers view of the medicine. Many patients doubted their
personal need for the treatment or harboured concerns and these beliefs are associated with
non-adherence. Beliefs about medicines may also be relevant in China, particularly as there
some evidence that trust between patients and health professionals may have diminished after
China’s economic reform.11,12
Patients often do not trust their doctors and doubt the treatment
including therapeutic treatment they received. It is possible that this may translate into
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scepticism about prescribed medicines and non-adherence. The aim of this study was to
understand beliefs about medicines in Chinese patients with stroke, diabetes mellitus and RA
and to investigate whether these beliefs are associated with medicine non-adherence.
Methods
A cross-sectional study was conducted in two large teaching hospitals in China between
January 2014 and November 2014. The study was approved by the local research ethics
committees.
Study populations and recruitment
Patients with stroke were recruited from The Second Hospital, Tianjin Medical University,
Tianjin, China and patients with diabetes mellitus and RA were recruited from Anhui
Provincial Hospital, Anhui Medical University, Hefei, China. Both hospitals are large
teaching hospitals and are level 3 general hospitals, the highest classification for quality care
given by the China’s National Health and Family Planning Commission (NHFPC) for all
public hospitals.13
Patients who had a clinical diagnosis of stroke, diabetes mellitus or RA
who were judged by the healthcare professionals as able to answer questions were invited by
the healthcare professionals to take part in the study when they were admitted to hospital
(stroke patients) or came to hospital clinics (diabetic and RA patients) during the study
period. Some patients may have co-morbidity. However, they were only included for the
condition they were hospitalised or the condition from the specific outpatient clinics. They
were asked to complete a questionnaire which took approximately 10-15 minutes. Study
information was given to patients and verbal consent was obtained before they started to fill
in the questionnaire. All invited patients returned their questionnaires. Since there is a lack of
research on beliefs about medicines and medicine non-adherence in China, a target sample
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size of 300 patients for each condition was chosen based on typical sample sizes used in
similar surveys. A recent meta-analysis showed that small-moderate effect of psychological
beliefs on medicine adherence was observed in 94 studies with an average sample size of
266.10
Data collection started in January 2014 and lasted around 4 months for each condition
and was stopped once the target numbers were reached (November 2014).
Questionnaire measurement
The questionnaire consisted of demographic information, the BMQ questionnaire,14
perceived
sensitivity to medicines scale (PSM) and medicine adherence report scale (MARS).15
All
scales were translated and back translated in accordance with the Originator’s conditions to
create a Chinese version, (BMQ-Chinese © R Horne MARS-Chinese © R Horne, PSM-
Chinese © R Horne). The BMQ and MARS were translated into Chinese by Dr Li Wei, the
principal investigator for this study. They were then sent to the co-authors, Profs Xiaomei Li
and Xin Li for comments and further adaptation resulting in a final Chinese version of the
BMQ.
Demographic information included name, age, gender, education, occupation and duration of
the condition. The BMQ questionnaire has two parts: the BMQ-Specific assessing beliefs
about medicine used for a particular condition and the BMQ-General assessing beliefs about
medicines in general. The details of the BMQ questionnaire can be found in a previous
publication.8 In brief, BMQ-Specific comprised two scales: a 5-item treatment necessity scale
Specific-Necessity and a 6-item treatment concern scale Specific-Concern. BMQ-General
used three subscales: 1) General-Overuse (4 items), 2) General-Harm (4 items), and 3)
General-Benefit (4 items). Perceived Sensitivity to Medicines (PSM) scale contained 5 items
assessing perceptions of personal susceptibility to the effects of medicines. All BMQ items
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and PSM were scored on a Likert type scale (where 1 = strongly disagree, 2 = disagree, 3 =
uncertain, 4 = agree and 5 = strongly agree). A mean item score was then calculated as the
sum of each item score divided by the number of items [for example, mean score of Specific-
Necessity= (N1+N2+N3+N4+N5)/5]. The Cronbach’s αs indicated that all scale measures
were internally consistent in the study sample with αnecessity = 0.64, αconcern = 0.75, αoveruse=
0.54, αharm = 0.55, αbenefit = 0.58 and αpsm = 0.85. For BMQ-Specific, patients were only asked
for the treatment prescribed for the diagnosed condition in the past 12 months. Medicine
adherence was measured using the MARS scale consisting of 5 items with 25 score points in
total. For example, one item is “I forget to take them”.
Before the study commenced, 30 people including doctors, nurses, medical students and
patients were asked to complete the questionnaire to assess whether the Chinese version of
the BMQ, PSM and MARS would be easily understood by Chinese patients. Feedback was
wholly positive; however we recognised that patients were likely to be elderly and may have
poor literacy. Therefore, arrangements were made to provide help should patients have any
difficulty completing the questionnaire. Patients in both centres completed the questionnaire
either by themselves or with help from the healthcare professionals in the medical ward or
clinic they attended. Healthcare professionals received a briefing from the local investigators
on how to complete the questionnaire including instructions on how to explain the meaning
of the questionnaire items without influencing patients’ responses.
Definition of adherence and non-adherence
Adherent patients were defined as measuring ≥ 80% on the measure of adherence (i.e. ≥ 20
points) to their medicine which is a commonly used cut-off point in medicine benefit/safety
studies and is also used conventionally in clinical trials of safety and efficacy that have been
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used to support a new drug registration.16
. Adherence was calculated as sum of the scores
from each item divided by the maximum points of 25 using the 5-item MARS scale. Non-
adherent patients were defined as having a score <80% adherence to medicine.
Attitudinal analysis
Participants were categorized into attitudinal groups (i.e. Skeptical, Ambivalent, Indifferent
and Accepting groups) based on whether they scored above or below the scale midpoint for
BMQ necessity and concerns scales. Non-adherence was investigated between the groups.17
Statistical analysis
Data were presented as mean (SD) for continuous variables and as frequencies (%) for
categorical variables. Chi-squared and analysis of variance (ANOVA) tests were performed
to determine significant differences between the three diseases. Correlations were used to
examine relationships between BMQ-General and BMQ-Specific subscales. Logistic
regression analysis was employed to assess the association between non-adherence and
medicine beliefs. Five percent of patients had at least one missing value in their BMQ
answers and the total missing values were 0.3% for the whole BMQ items. A sensitivity
analysis was done to include all patients with missing data replaced with imputed data in the
multivariable analysis concluding all variables listed in Table 1. The multiple imputation
analysis included all variables used in the final analysis with 10 imputations by using the
Markov Chain Monte Carlo method to produce imputed data. All statistical analyses were
carried out using SAS (version 9.4).
Results
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Patient characteristics
There were 967 patients in the study (313 with stroke, 315 with diabetes mellitus and 339
with RA). Table 1 shows the demographic and clinical information by disease groups.
Patients with RA were significantly younger than patients with stroke and diabetes mellitus
(mean age 49.7 vs 65.8 and 62.5, respectively). The RA group was 85% female while only
44% of stroke patients and 45% of diabetes mellitus patients were female. Patients with RA
were 5 times more likely to report having received no formal education than patients with
stroke and diabetes mellitus (23.3% vs 4.8% and 4.1%, respectively). Over half of patients in
the stroke group had less than 1 year disease duration while more than half of the patients in
the RA and diabetes mellitus groups had more than 5 years disease duration.
BMQ results
The results of BMQ subscales are shown in Table 2. There were no significant differences in
the mean scores of Specific-Concerns and General-Harm between the three groups. However,
differences were observed for Specific-Necessity, General-Overuse, General-Benefit and
PSM among the three groups. Patients with RA had the highest score of 3.75 (SD 0.40) for
Specific-Necessity and lowest scores of 2.95 (SD 0.51) for General-Overuse and 3.55 (SD
0.45) for General-Benefit. The mean scores of PSM were 2.89 (SD 0.65), 2.35 (SD 0.64) and
2.70 (SD 0.68). The attitudinal analysis categorised patients into four groups (high/low
necessity and high/low concerns) according to the midpoint of the Specific-Necessity
Specific-Concerns scales shows that 45% of patients were classified as ‘Ambivalent’, 45%
as ‘Accepting’, 4% as ‘Skeptical’ and 6% as ‘Indifferent’ (Figure 1).
Patients’ general beliefs about medicines were associated with their evaluations of the
specific treatments they were taking. Table 3 shows the correlation between BMQ-General
and BMQ-Specific. Specific-Necessity was positively associated with General-Benefit
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(Pearson correlation coefficients = 0.31, p<0.01). Moderate correlations were observed
between Specific-Concerns and General-Overuse, General-Harm and PSM (Pearson
correlation coefficients, 0.39, 0.49 and 0.49, respectively, p<0.01). General-Overuse was also
correlated with General-Harm and PSM (Pearson correlation coefficients, 0.45 and 0.39,
respectively, p<0.01). The Pearson correlation coefficient was 0.39 (p<0.01) for General-
Harm and PSM.
Association between beliefs about medicines and non-adherence
Three hundred and eleven patients were non-adherent to their medicine [159 (51.0%) in the
stroke group, 60 (26.7%) in the diabetes mellitus group and 62 (19.8%) in the RA group,
p<0.01]. After adjusting for demographic characteristics, Specific-Concerns and PSM were
significantly associated with non-adherence (adjusted ORs, 1.35, 95% CI 1.07-1.71 and 1.44,
95% CI 1.16-1.80). Negative associations between non-adherence and Specific-Necessity and
General-Benefit were not statistically significant (Table 4). The subgroup analyses showed
that the point estimates of Specific-Concerns were positively associated with non-adherence
across the three conditions i.e. the more concerns about the medicines, the more non-adherent
to medicines, with adjusted ORs ranging from 1.15 (95% CI 0.67-1.98) for diabetes mellitus
to 1.43 (95% CI 1.02-2.00) for stroke (Table 5). The unadjusted results showed similar results
across the three disease conditions. The sensitivity analysis showed that Specific-Concerns
and PSM were positively associated with non-adherence (adjusted ORs, 1.15 95% CI 1.04-
1.26 and 1.40, 95% CI 1.04-1.26, respectively) and General-Benefit was negatively
associated with non-adherence (adjusted OR 0.79, 95% CI 0.71-0.87). Compared with
patients in the Accepting group, patients in the other attitudinal groups were more likely to be
the non-adherent (adjusted ORs, 1.50 95% CI 1.10-2.05 for the Ambivalent group, 1.27 95%
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CI 0.60-2.68 for the Skeptical group and 1.27 95% CI 0.69-2.34 for the Indifferent group.
Only patients in the Ambivalent group showed a statistical significance.
Discussion
This is the first large study of this kind that investigates beliefs about medicines and medicine
non-adherence in China in three common chronic diseases. Both unadjusted and adjusted
results revealed that Specific-Concerns and PSM were significantly associated with non-
adherence i.e. the higher the concern about the medicine or the higher perceived sensitivity to
medicines or the lower of the belief in general medicine benefits, the lower the adherence to
medicines. Using the continuous MARS-5 scores showed similar relationships to those
reported in logistic regression. We noted differences between groups that might indicate
different attitudes towards the diseases and their treatments or be attributable to other factors.
The hospital out-patients (diabetes mellitus and RA) included some patients who had
previous hospitalisations and come back to hospital for regular monitoring.
Our findings were consistent with the evidence from a recent meta-analysis which showed
that higher adherence was associated with fewer concerns about treatment10
but not consistent
with previous findings that higher belief in personal need for treatment was associated with
higher adherence; Specific-Necessity was not associated with non-adherence in our overall
analysis. Subgroup analyses showed that patients with stroke and diabetes mellitus showed
the same direction association as previous studies i.e, patients with higher necessity were less
likely to be non-adherent. However, an opposite non-statistically significant result of
Specific-Necessity and adherence for patients with RA (Our result of 1.34 (95% CI 0.73-
2.46) for non-adherence equals 0.75, 95% CI 0.41-1.38 for adherence) was observed in the
study in comparison with the meta-analysis result which had a pooled OR of 3.28, 95%CI
1.11-9.71 for adherence.10
The point estimate could be due to chance and further studies need
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to confirm the finding. A recent study found that General-Benefit may be negatively
associated with non-adherence among 398 patients with epilepsy from the UK primary care
population (adjusted OR, 0.92, 95%CI 0.63-1.34)17
and this association was confirmed by our
study with a borderline significant OR of 0.75 (95%CI 0.56-1.02). There was no correlation
between Necessity and Concern (Table 2) in our study population and this was supported by
a recent Swedish study conducted in 578 stroke patients.18
They reported a Spearman’s
correlation coefficient of 0.075 (p=0.08). Compared to patients with high necessity and low
concerns, patients with high necessity and high concerns, low necessity and high concerns,
and low necessity and low concerns were all associated with non-adherence and this was
supported by studies conducted in patients with inflammatory bowel disease and renal
dysfunction.19, 20
High perceived sensitivity to medicines was reported to be associated with
non-adherence and higher medical care utilisation, increased symptom reporting and greater
information-seeking about medication.17, 21
Our study also showed PSM was associated with
non-adherence.
Our study has some strengths. Firstly, this was the first large BMQ study conducted in China.
Secondly, we choose two large teaching hospitals for this study and collected data continually
until the target numbers were reached for each condition. Therefore, our study population
was likely to represent the disease population from each region as large teaching hospitals
provide health care service to majority of Chinese patients. Thirdly, China has higher
prevalence rates of stoke and diabetes mellitus than Western Europe and stroke is also the
leading cause of death in China. In light of the current deteriorated relationship between
health professional and patients (i.e. patients do not trust their doctors and other health
professionals, doctors, nurses are often abused verbally and physically by patients,11, 22, 23
more studies are needed from the patients’ perspective. More consideration from the patient
perspective should be taken into account in term of chronic disease management and the
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relationship between patients and health professionals. However, our study was an
observational study. Therefore the results may be confounded by unmeasured factors such as
comorbidity. Self-reported adherence may not be the best measurement for medicine
adherence as patients may, for example, underestimate how often they forget their treatment.
However, a strong correlation was found for medicine adherence measured by self-reported
questionnaire, electronic prescriptions and serum biomarkers in a recent intervention study
suggesting that self-report is a reliable measure.24
Also our study found relatively low
reliability of the BMQ general scales and further investigation and refinement might be
needed of these Chinese translations. The difference in non-adherence between stroke and
other conditions needs to be explored in future studies as disease itself may play an important
role in medicine adherence.
In conclusion, we found that the BMQ is a useful tool to identify psychological factors that
are linked to non-adherence in patients with stroke, diabetes and RA. Future studies should
use the BMQ to screen patients to identify those who are at high risk of non-adherence and
map their treatment plan accordingly.
CONFLICT OF INTEREST/STUDY SUPPORT:
Specific author contributions: LW, RC and RH were involved in conception and design and
interpretation of data. LW did the statistical analysis and wrote the first draft of the article.
SC, RC and BN contributed to data analysis. LXM, LX and LSM collected data. SC, AC,
LXM, LX and LSM were involved in interpretation of data. All authors were responsible for
re-drafting of the article and approved the final version.
Guarantor of the article: LW is the guarantor
Financial support: This study was funded by the Research Innovation Fund, UCL School of
Pharmacy. The funder had no role in the design, conduct or data interpretation of the study.
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Professor Rob Horne was supported by the National Institute for Health Research (NIHR)
Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North
Thames at Bart’s Health NHS Trust.
Potential competing interests: RH declares: (1) Speaker engagements with honoraria and
consultancy payments from the pharmaceutical companies; (2) Founder and shareholder of a
UCL-Business, university spin-out company (Spoonful of Sugar Ltd) providing consultancy
on medication-related behaviours to healthcare policy makers, providers and industry; and (3)
Originator of BMQ.
References:
1. Medicines adherence: involving patients in decisions about prescribed medicines and
supporting adherence. https://www.nice.org.uk/guidance/cg76/chapter/introduction (accessed
on 30 January 2017)
2. Liu L, Wang D, Wong KS, Wang Y. Stroke and stroke care in China: huge burden,
significant workload, and a national priority. Stroke; a journal of cerebral circulation.
2011;42(12):3651-4.
3. Feigin VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA, et al.
Global and regional burden of stroke during 1990-2010: findings from the Global Burden of
Disease Study 2010. Lancet. 2014;383(9913):245-54.
4. Li R, Sun J, Ren LM, Wang HY, Liu WH, Zhang XW, et al. Epidemiology of eight
common rheumatic diseases in China: a large-scale cross-sectional survey in Beijing.
Rheumatology (Oxford). 2012 Apr;51(4):721-9. doi: 10.1093/rheumatology/ker370. Epub
2011 Dec 16.
5. China Total population, 2015. http://www.who.int/countries/chn/en/ (accessed on 25 May
2017)
Page 15 of 27
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on April 23, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
pen: first published as 10.1136/bmjopen-2017-017293 on 5 O
ctober 2017. Dow
nloaded from
For peer review only
16
6. Wu X, Zhu B, Fu L, Wang H, Zhou B, Zou S, et al. Prevalence, incidence, and mortality of
stroke in the chinese island populations: a systematic review. PLoS One. 2013 Nov
8;8(11):e78629. doi: 10.1371/journal.pone.0078629. eCollection 2013.
7. Will JC, Zhang Z, Ritchey MD, Loustalot F. Medication Adherence and Incident
Preventable Hospitalizations for Hypertension. Am J Prev Med. 2016 Apr;50(4):489-99. doi:
10.1016/j.amepre.2015.08.021. Epub 2015 Oct 31.
8. Shore S, Carey EP, Turakhia MP, Jackevicius CA, Cunningham F, Pilote L, et al.
Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the
veterans health administration. Am Heart J. 2014 Jun;167(6):810-7. doi:
10.1016/j.ahj.2014.03.023. Epub 2014 Apr 5.
9. Korhonen MJ, Ruokoniemi P, Ilomaki J, Meretoja A, Helin-Salmivaara A, Huupponen R.
Adherence to statin therapy and the incidence of ischemic stroke in patients with diabetes.
Pharmacoepidemiol Drug Saf. 2016 Feb;25(2):161-9. doi: 10.1002/pds.3936.
10. Horne, R, Chapman SC, Parham R, Freemantle N, Forbes A, Cooper V. Understanding
patients’ adherence –related beliefs about medicines prescribed for long-term conditions: a
meta-analytic review of the necessity-concerns framework. Plos One. 2013 Dec
2;8(12)e80633. Doi:10.1371/journal.pone.0080633.
11. Tucker JD, Cheng Y, Wong B, Gong N, Nie JB, Zhu W, et al; Patient-Physician Trust
Project Team. Patient-physician mistrust and violence against physicians in Guangdong
Province, China: a qualitative study. BMJ Open. 2015 Oct 6;5(10):e008221. doi:
10.1136/bmjopen-2015-008221.
12. Chan CS, Cheng Y, Cong Y, Du Z, Hu S, Kerrigan A, et al. Patient-physician trust in
China: a workshop summary. Lancet. 2016 Oct;388 Suppl 1:S72. doi: 10.1016/S0140-
6736(16)31999-7.
Page 16 of 27
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jopen.bmj.com
/B
MJ O
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nloaded from
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17
13. National Health and Family Planning Commission of the PRC http://en.nhfpc.gov.cn/
(last access 30 January 2017)
14. Horne R, Weinman J. Patients' beliefs about prescribed medicines and their role in
adherence to treatment in chronic physical illness. J Psychosom Res. 1999 Dec;47(6):555-67.
15. Horne R. The nature, determinants and effects of medication beliefs in chronic illness
(PhD thesis) University of London 1997.
16. Wei L, Wang J, Thompson P, Wong S, Struthers AD, MacDonald TM. Adherence to
statin treatment and readmission of patients after myocardial infarction: a six year follow up
study. Heart 2002;88:229-33.
17. Chapman SC, Horne R, Chater A, Hukins D, Smithson WH. Patients' perspectives on
antiepileptic medication: relationships between beliefs about medicines and adherence among
patients with epilepsy in UK primary care. Epilepsy Behav. 2014 Feb;31:312-20. doi:
10.1016/j.yebeh.2013.10.016. Epub 2013 Nov 27.
18. Sjolander M, Eriksson M, Glader EL. The association between patients' beliefs about
medicines and adherence to drug treatment after stroke: a cross-sectional questionnaire
survey. BMJ open. 2013;3(9):e003551.
19. Horne R, Parham R, Driscoll R, Robinson A. Patients' attitudes to medicines and
adherence to maintenance treatment in inflammatory bowel disease. Inflamm Bowel Dis.
2009 Jun;15(6):837-44. doi: 10.1002/ibd.20846.
20. Chater AM, Parham R, Riley S, Hutchison AJ, Horne R. Profiling patient attitudes to
phosphate binding medication: a route to personalising treatment and adherence support.
Psychol Health. 2014;29(12):1407-20. doi: 10.1080/08870446.2014.942663. Epub 2014 Aug.
21. Faasse K, Grey A, Horne R, Petrie KJ. High perceived sensitivity to medicines is
associated with higher medical care utilisation, increased symptom reporting and greater
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information-seeking about medication. Pharmacoepidemiol Drug Saf. 2015 Jun;24(6):592-9.
doi: 10.1002/pds.3751. Epub 2015 Apr 7.
22. Li ZG, Leng MX. Doctor-patient relationship research summary. Chinese Hospital
Management. 2009;29(332):40-3.
23. Doctors face verbal abuse or violence. http://www.cmdae.org/en/index.php (Accessed 30
January 2017).
24. Lyons I, Barber N, Raynor DK, Wei L. The Medicines Advice Service Evaluation
(MASE): a randomised controlled trial of a pharmacist-led telephone based intervention
designed to improve medication adherence. BMJ Qual Saf. 2016 Oct;25(10):759-69. doi:
10.1136/bmjqs-2015-004670.
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Table 1. Patient characteristics by conditions
Stroke
n=313 (100%)
Diabetes
n=315 (100%)
RA
n=339 (100%)
Age, mean (SD) * 65.8 (13.7) 62.5 (13.9) 49.7 (12.8)
Gender†*
Women 136 (43.5%) 141 (44.8%) 287 (85.2%)
Men 177 (56.5%) 174 (55.2%) 50 (14.8%)
Education*
Illiteracy (no formal
education)
15 (4.8%) 13 (4.1%) 79 (23.3%)
Primary school 66 (21.1%) 62 (19.7%) 93 (27.4%)
Junior high school 60 (19.2%) 91 (28.9%) 91 (26.8%)
High school/college 116 (37.1%) 77 (24.4%) 48 (14.2%)
University or above 54 (17.2%) 70 (22.2%) 25 (7.4%)
Unknown 2 (0.6%) 2 (0.6%) 3 (0.9%)
Occupation*
Farmer 5 (1.6%) 22 (7.0%) 110 (32.5%)
Worker/clerk 83 (26.5%) 117 (37.1%) 38 (11.2%)
Housewife/unemployment 45 (14.4%) 12 (3.8%) 113 (33.3%)
Retirement 129 (41.2%) 54 (17.1%) 40 (11.8%)
Health professional 19 (6.1%) 29 (9.2%) 15 (4.4%)
Civil service 29 (9.3%) 72 (22.9%) 11 (3.2%)
Unknown 3 (1.0%) 9 (2.9%) 12 (3.5%)
Duration of the disease*
<= 1 year 178 (56.9%) 20 (6.4%) 55 (16.2%)
1-5 years 91 (29.1%) 74 (23.5%) 104 (30.7%)
> 5 year 44 (14.1%) 220 (69.8%) 177 (52.2%)
unknown 0 (0.0%) 1 (0.3%) 3 (0.9%) †Excluding missing data; *<0.05
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Table 2. Results of BMQ and PSM by disease conditions
Stroke
n=313
Diabetes
n=315
RA
n=339
Specific-Necessity (mean, SD) †
* 3.69 (0.53) 3.75 (0.40) 3.66 (0.44)
Specific-Concerns (mean, SD) †
3.03 (0.71) 3.15 (0.58) 3.07 (0.58)
General-Overuse (mean, SD) †
* 3.22 (0.62) 3.12 (0.50) 2.95 (0.51)
General-Harm (mean, SD) †
2.94 (0.78) 2.95 (0.50) 2.99 (0.43)
General-Benefit (mean, SD) †
* 3.70 (0.53) 3.69 (0.42) 3.55 (0.45)
PSM (mean, SD) †
* 2.89 (0.65) 2.35 (0.64) 2.70 (0.68)
MARS score (mean, SD*) 18.81 (4.16) 21.51 (3.07) 21.47 (3.86) †Excluding missing data; PSM=Perceived Sensitivity to Medicines; *<0.05
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Table 3. Correlation matrix between BMQ-Specific, BMQ-General and PSM
Necessity Concerns Overuse Harm Benefit PSM
Overall
Necessity 1.00
Concern 0.02(0.45) 1.00
Overuse -0.01 (0.87) 0.39 (<0.01) 1.00
Harm -0.05 (0.16) 0.49 (<0.01) 0.45 (<0.01) 1.00
Benefit 0.31(<0.01) -0.09 (0.01) 0.11 (<0.01) 0.04 (0.21) 1.00
PSM 0.04 (0.22) 0.45 (<0.01) 0.39 (<0.01) 0.38<0.01) 0.05 (0.14) 1.00
Stroke
Necessity 1.00
Concern 0.04 (0.43) 1.00
Overuse 0.06 (0.31) 0.50 (<0.01) 1.00
Harm -0.06 (0.27) 0.66 (<0.01) 0.57 (<0.01) 1.00
Benefit 0.36 (<0.01) 0.01 (0.88) 0.24 (<0.01) 0.13 (0.12) 1.00
PSM 0.23 (<0.01) 0.52 (<0.01) 0.51 (<0.01) 0.50 (<0.01) 0.22 (<0.01) 1.00
Diabetes mellitus
Necessity 1.00
Concern 0.02 (0.59) 1.00
Overuse -0.05 (0.40) 0.26 (<0.01) 1.00
Harm -0.08 (0.20) 0.21 (<0.01) 0.44 (<0.01) 1.00
Benefit 0.19 (<0.01) -0.07 (0.26) 0.18 (<0.01) 0.08 (0.19) 1.00
PSM -0.08 (0.20) 0.36 (<0.01) 0.38 (<0.01) 0.44 (<0.01) 0.07 (0.23) 1.00
RA
Necessity 1.00
Concerns 0.01 (0.91) 1.00
Overuse -0.08 (0.13) 0.41 (<0.01) 1.00
Harm 0.02 (0.72) 0.42 (<0.01) 0.30 (<0.01) 1.00
Benefit 0.30 (<0.01) -0.21 (<0.01) -0.20 (<0.01) -0.15 (0.21) 1.00
PSM -0.04 (0.52) 0.54 (<0.01) 0.29 (<0.01) 0.27 (<0.01) -0.13 (0.02) 1.00
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Table 4. Odd ratios of medicine non-adherence
Unadjusted
OR, 95% CI
Adjusted*
OR, 95% CI
Specific-Necessity 0.90, 0.67-1.21 0.93, 0.68-1.27
Specific-Concerns 1.27, 1.02-1.58 1.35, 1.07-1.71
General-Overuse 1.32, 1.04-1.69 1.15, 0.88-1.50
General-Harm 1.09, 0.87-1.38 1.12, 0.89-1.43
General-Benefit 0.84, 0.63-1.12 0.75, 0.56-1.02
PSM 1.72, 1.41-2.09 1.44, 1.16-1.85
*Adjusted for age, gender, education, occupation, duration of the disease and different
diseases
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Table 5. Odd ratios of medication non-adherence by disease groups
Stroke Diabetes RA
Unadjusted
OR, 95% CI
Adjusted*
OR, 95% CI
Unadjusted
OR, 95% CI
Adjusted*
OR, 95% CI
Unadjusted
OR, 95% CI
Adjusted*
OR, 95% CI
Specific-
Necessity
0.83, 0.54-1.26 0.92, 0.59-1.43 0.71, 0.35-1.40 0.92, 0.43-1.97 1.31, 0.75-2.27 1.34, 0.73-2.46
Specific-
Concerns
1.43, 1.04-1.96 1.43, 1.02-2.00 1.16, 0.71-1.88 1.15, 0.67-1.98 1.38, 0.91-2.12 1.32, 0.84-2.10
General-
Overuse
1.26, 0.88-1.81 1.24, 0.85-1.82 1.12, 0.64-1.96 1.10, 0.61-2.00 1.06, 0.66-1.71 0.98, 0.60-1.60
General-
Harm
1.26, 0.95-1.68 1.30, 0.96-1.77 0.58, 0.32-1.05 0.59, 0.32-1.11 1.27, 0.72-2.24 1.27, 0.70-2.30
General-
Benefit
0.87, 0.57-1.32 0.83, 0.53-1.29 0.78, 0.41-1.50 0.83, 0.41-1.69 0.64, 0.37-1.09 0.65, 0.37-1.13
PSM 1.76, 1.22-2.53 1.79, 1.23-2.60 1.60, 1.05-2.44 1.73, 1.10-2.70 1.06, 0.74-1.51 1.01, 0.70-1.48
*Adjusted for age, gender, education, occupation, duration of the disease
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Figure legend
Figure 1. Attitudinal analysis of BMQ-Specific.
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STROBE 2007 (v4) Statement—Checklist of items that should be included in reports of cross-sectional studies
Section/Topic Item
# Recommendation Reported on page #
Title and abstract 1 (a) Indicate the study’s design with a commonly used term in the title or the abstract Page 2
(b) Provide in the abstract an informative and balanced summary of what was done and what was found Page 2
Introduction
Background/rationale 2 Explain the scientific background and rationale for the investigation being reported Page 5-6
Objectives 3 State specific objectives, including any prespecified hypotheses Page 6
Methods
Study design 4 Present key elements of study design early in the paper Page 6
Setting 5 Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data
collection
Page 6
Participants
6
(a) Give the eligibility criteria, and the sources and methods of selection of participants Pages 6-8
Variables 7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers. Give diagnostic criteria, if
applicable
Pages 7-8
Data sources/
measurement
8* For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe
comparability of assessment methods if there is more than one group
Page 7-8
Bias 9 Describe any efforts to address potential sources of bias Page 9
Study size 10 Explain how the study size was arrived at Page 6
Quantitative variables 11 Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen and
why
Page 9
Statistical methods 12 (a) Describe all statistical methods, including those used to control for confounding Page 9
(b) Describe any methods used to examine subgroups and interactions Page 11
(c) Explain how missing data were addressed Page 9
(d) If applicable, describe analytical methods taking account of sampling strategy n/a
(e) Describe any sensitivity analyses Pages 9 &12
Results
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Participants 13* (a) Report numbers of individuals at each stage of study—eg numbers potentially eligible, examined for eligibility,
confirmed eligible, included in the study, completing follow-up, and analysed
Page 9
(b) Give reasons for non-participation at each stage n/a
(c) Consider use of a flow diagram n/a
Descriptive data 14* (a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential
confounders
Page 9 and Page 18
(b) Indicate number of participants with missing data for each variable of interest Page 18
Outcome data 15* Report numbers of outcome events or summary measures Pages 10-12
Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence
interval). Make clear which confounders were adjusted for and why they were included
Pages 22-23
(b) Report category boundaries when continuous variables were categorized Pages 8 & 10
(c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period n/a
Other analyses 17 Report other analyses done—eg analyses of subgroups and interactions, and sensitivity analyses Page 11
Discussion
Key results 18 Summarise key results with reference to study objectives Page 11
Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and
magnitude of any potential bias
Page 13
Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from
similar studies, and other relevant evidence
Pages 11-14
Generalisability 21 Discuss the generalisability (external validity) of the study results Page 13
Other information
Funding 22 Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on
which the present article is based
Page 14
*Give information separately for cases and controls in case-control studies and, if applicable, for exposed and unexposed groups in cohort and cross-sectional studies.
Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and published examples of transparent reporting. The STROBE
checklist is best used in conjunction with this article (freely available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at
http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is available at www.strobe-statement.org.
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Beliefs about medicines and non-adherence in patients with
stroke, diabetes mellitus and rheumatoid arthritis: A cross-
sectional study in China
Journal: BMJ Open
Manuscript ID bmjopen-2017-017293.R2
Article Type: Research
Date Submitted by the Author: 12-Jul-2017
Complete List of Authors: Wei, Li; University College London School of Pharmacy, BMA house, Tavistock Square Chapman, Sarah; UCL School of Pharmacy,
Li, Xiaomei; Anhui Provincial Hospital, Anhui Medical University Li, Xin; The Second Hospital, Tianjin Medical University Li, Sumei; Anhui Provincial Hospital, Anhui Medical University Chen, Ruoling; University of Wolverhampton, Centre for Health and Social Care Improvement Bo, Nie; University College London School of Pharmacy Chater, Angel; University College London, Centre for Behavioural Medicine Horne, Robert; University College London School of Pharmacy
<b>Primary Subject Heading</b>:
Global health
Secondary Subject Heading: Medical management
Keywords: beliefs about medicines, medicine non-adherence, chronic diseases
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1
Beliefs about medicines and non-adherence in patients with stroke, diabetes mellitus
and rheumatoid arthritis: A cross-sectional study in China
Li Wei, MD, PhD1, Sarah Chapman PhD
1 2, Xiaomei Li MD
3, Xin Li MD, PhD
4, Sumei Li
MD5, Ruoling Chen MD, PhD
6, Bo Nie MSc
1, Angel Chater PhD
1 7, and Rob Horne PhD
1
Short running title: Beliefs about medicines and medicine non-adherence
Key words: beliefs about medicines, medicine non-adherence, chronic diseases
1Department of Practice and Policy, UCL School of Pharmacy, Mezzanine Floor, Entrance A,
BMA House, Tavistock Square, London, WC1H 9JP
2Department of Pharmacy & Pharmacology, University of Bath, Claverton Down Road, Bath,
BA2 7AY 3Department of Rheumatology and Immunology, Anhui Provincial Hospital, Anhui Medical
University, Hefei230001, China
4Department of Neurology, The Second Hospital, Tianjin Medical University, Tianjin
300211, China
5Department of Endocrinology, Anhui Provincial Hospital, Anhui Medical University, Hefei
230001, China
6Centre for Health and Social Care Improvement, Faculty of Education Health and
Wellbeing, University of Wolverhampton, Wolverhampton, WV1 1DT, UK
7Centre for Health, Wellbeing and Behaviour Change, Faculty of Education and Sport
University of Bedfordshire, Polhill Avenue, Bedford, MK41 9EA
Corresponding author:
Dr Li Wei
Department of Practice and Policy, UCL School of Pharmacy, 29-39 Brunswick Square,
London, WC1N 1AX
Tel: 44 2078741275
E-mail: [email protected]
This study was funded by the Research Innovation Fund, UCL School of Pharmacy.
Word count (abstract): 300; Word count (full text): 2947; Tables: 5; Figures: 1
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Abstract
Objectives: To investigate beliefs about medicines and their association with medicine
adherence in patients with chronic diseases in China.
Design: A cross-sectional questionnaire-based study
Setting: Two large urban hospitals in Hefei and Tianjin, China
Participants: Hospital inpatients (313 stroke patients) and outpatients (315 diabetic patients
and 339 rheumatoid arthritis (RA) patients) were recruited between January 2014 and
September 2014.
Outcome measures: The Beliefs about Medicines Questionnaire (BMQ), assessing patients’
beliefs about the specific medicine (Specific-Necessity and Specific-Concerns) prescribed for
their conditions (stroke/diabetes/RA) and more general background beliefs about
pharmaceuticals as a class of treatment (BMQ-General Benefit, Harm and Overuse); the
Perceived Sensitivity to Medicines scale (PSM) assessed patients’ beliefs about how sensitive
they were to the effects of medicines and the Medication Adherence Report Scale. The
association between non-adherence and beliefs about medicines was assessed using a logistic
regression model.
Results: Patients with diabetes mellitus had a stronger perceived need for treatment [mean
(SD) Specific-Necessity score, 3.75 (0.40)] than patients with stroke [3.69 (0.53)] and RA
[3.66 (0.44)] (p=0.049). Moderate correlations were observed between Specific-Concerns and
General-Overuse, General-Harm and PSM (Pearson correlation coefficients, 0.39, 0.49 and
0.49, respectively, p<0.01). 311 patients were non-adherent to their medicine [159 (51.0%) in
the stroke group, 60 (26.7%) in the diabetes mellitus group and 62 (19.8%) in the RA group,
p<0.01]. Across the whole sample, after adjusting for demographic characteristics non-
adherence was associated with patients who had higher concerns about their medicines (OR,
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1.35, 95% CI 1.07-1.71) and patients who believed that they were personally sensitive to the
effects of medications (OR 1.44, 95% CI 1.16-1.85).
Conclusion: The BMQ is a useful tool to identify patients at risk of non-adherence. In future,
adherence intervention studies may use the BMQ to screen for patients who are at risk of
non-adherence and to map interventional support.
Funding: Research Innovation Fund, UCL School of Pharmacy.
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Strengths and limitations of this study
• First large study of beliefs about medicines in China
• High response rate, reflecting generalisability of the study finding
• A cross-sectional design implicating that the association between non-adherence and
beliefs about medicines did not necessarily lead a causal relationship.
• Self-reported adherence may not be the best measurement for medicine adherence.
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Introduction
Medicine plays an essential role in chronic disease management. However, it is recognised
that only half of patients with chronic diseases take their medicines as prescribed.1 Stroke,
diabetes mellitus and rheumatoid arthritis (RA) are three common chronic diseases which
together affect over 10% of China’s population of 1.40 billion.2-5
Stroke is the leading cause
of adult death and disability in China with an annual mortality rate of approximately 1.6
million, or 157 per 100,000.6
Patients with chronic diseases often require multiple medicine
treatments for their conditions and any associated symptoms and comorbidities. To obtain
full benefit from treatment, patients need to adhere to these complex medicine regimens in
order to control their disease and maintain health. However, in reality medicine management
is sub-optimal and relates to physician inertia and patients’ poor adherence with therapy.7
The
elderly, with high rates of co-morbidity and co-prescribing, tend to have poor adherence and
are at particular risk of unwanted adverse effects from drugs.8,9
Studies outside China have identified patients’ beliefs about medicines as an important
determinant of non-adherence.10
A recent meta-analysis of 96 peer-reviewed studies
involving over 24,000 patients across 24 long-term conditions and 18 countries showed that
non-adherence was related to patients beliefs about medicines, measured by the Beliefs about
Medicines Questionnaire (BMQ).10
These studies indicated that there was often a disconnect
between the patients and prescribers view of the medicine. Many patients doubted their
personal need for the treatment or harboured concerns and these beliefs are associated with
non-adherence. Beliefs about medicines may also be relevant in China, particularly as there
some evidence that trust between patients and health professionals may have diminished after
China’s economic reform.11,12
Patients often do not trust their doctors and doubt the treatment
including therapeutic treatment they received. It is possible that this may translate into
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scepticism about prescribed medicines and non-adherence. The aim of this study was to
understand beliefs about medicines in Chinese patients with stroke, diabetes mellitus and RA
and to investigate whether these beliefs are associated with medicine non-adherence.
Methods
A cross-sectional study was conducted in two large teaching hospitals in China between
January 2014 and November 2014. The study was approved by the local research ethics
committees.
Study populations and recruitment
Patients with stroke were recruited from The Second Hospital, Tianjin Medical University,
Tianjin, China and patients with diabetes mellitus and RA were recruited from Anhui
Provincial Hospital, Anhui Medical University, Hefei, China. Both hospitals are large
teaching hospitals and are level 3 general hospitals, the highest classification for quality care
given by the China’s National Health and Family Planning Commission (NHFPC) for all
public hospitals.13
Patients who had a clinical diagnosis of stroke, diabetes mellitus or RA
who were judged by the healthcare professionals as able to answer questions were invited by
the healthcare professionals to take part in the study when they were admitted to hospital
(stroke patients) or came to hospital clinics (diabetic and RA patients) during the study
period. Some patients may have co-morbidity. However, they were only included for the
condition they were hospitalised or the condition from the specific outpatient clinics. They
were asked to complete a questionnaire which took approximately 10-15 minutes. Study
information was given to patients and verbal consent was obtained before they started to fill
in the questionnaire. All invited patients returned their questionnaires. Since there is a lack of
research on beliefs about medicines and medicine non-adherence in China, a target sample
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size of 300 patients for each condition was chosen based on typical sample sizes used in
similar surveys. A recent meta-analysis showed that small-moderate effect of psychological
beliefs on medicine adherence was observed in 94 studies with an average sample size of
266.10
Data collection started in January 2014 and lasted around 4 months for each condition
and was stopped once the target numbers were reached (November 2014).
Questionnaire measurement
The questionnaire consisted of demographic information, the BMQ questionnaire,14
perceived
sensitivity to medicines scale (PSM) and medicine adherence report scale (MARS).15
All
scales were translated and back translated in accordance with the Originator’s conditions to
create a Chinese version, (BMQ-Chinese © R Horne MARS-Chinese © R Horne, PSM-
Chinese © R Horne). The BMQ and MARS were translated into Chinese by Dr Li Wei, the
principal investigator for this study. They were then sent to the co-authors, Profs Xiaomei Li
and Xin Li for comments and further adaptation resulting in a final Chinese version of the
BMQ.
Demographic information included name, age, gender, education, occupation and duration of
the condition. The BMQ questionnaire has two parts: the BMQ-Specific assessing beliefs
about medicine used for a particular condition and the BMQ-General assessing beliefs about
medicines in general. The details of the BMQ questionnaire can be found in a previous
publication.8 In brief, BMQ-Specific comprised two scales: a 5-item treatment necessity scale
Specific-Necessity and a 6-item treatment concern scale Specific-Concern. BMQ-General
used three subscales: 1) General-Overuse (4 items), 2) General-Harm (4 items), and 3)
General-Benefit (4 items). Perceived Sensitivity to Medicines (PSM) scale contained 5 items
assessing perceptions of personal susceptibility to the effects of medicines. All BMQ items
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and PSM were scored on a Likert type scale (where 1 = strongly disagree, 2 = disagree, 3 =
uncertain, 4 = agree and 5 = strongly agree). A mean item score was then calculated as the
sum of each item score divided by the number of items [for example, mean score of Specific-
Necessity= (N1+N2+N3+N4+N5)/5]. The Cronbach’s αs indicated that all scale measures
were internally consistent in the study sample16
with high value of αpsm = 0.85, αconcern = 0.75
and αnecessity = 0.64, and low values of αoveruse= 0.54, αharm = 0.55 and αbenefit = 0.58. For BMQ-
Specific, patients were only asked for the treatment prescribed for the diagnosed condition in
the past 12 months. Medicine adherence was measured for the same period using the MARS
scale consisting of 5 items with 25 score points in total. For example, one item is “I forget to
take them”.
Before the study commenced, 30 people including doctors, nurses, medical students and
patients were asked to complete the questionnaire to assess whether the Chinese version of
the BMQ, PSM and MARS would be easily understood by Chinese patients. Feedback was
wholly positive; however we recognised that patients were likely to be elderly and may have
poor literacy. Therefore, arrangements were made to provide help should patients have any
difficulty completing the questionnaire. Patients in both centres completed the questionnaire
either by themselves or with help from the healthcare professionals in the medical ward or
clinic they attended. Healthcare professionals received a briefing from the local investigators
on how to complete the questionnaire including instructions on how to explain the meaning
of the questionnaire items without influencing patients’ responses.
Definition of adherence and non-adherence
It is commonly accepted that it is not necessary to take 100% of a prescribed treatment, and
80% adherence is a commonly used cut-off to define adherence, especially in medicine
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benefit/safety studies.17
While the MARS scale does not allow direct assessment of the
percentage of prescribed treatment taken, we used a cut-off of 20 out of 25 on this scale to
define adherence, indicating that patients are taking a large proportion of their prescribed
doses. Adherence was calculated as sum of the scores from each item divided by the
maximum points of 25 using the 5-item MARS scale. Non-adherent patients were defined as
having a score <80% adherence to medicine.
Attitudinal analysis
Participants were categorized into attitudinal groups (i.e. Skeptical, Ambivalent, Indifferent
and Accepting groups) based on whether they scored above or below the scale midpoint for
BMQ necessity and concerns scales. Non-adherence was investigated between the groups.17
Statistical analysis
Data were presented as mean (SD) for continuous variables and as frequencies (%) for
categorical variables. Chi-squared and analysis of variance (ANOVA) tests were performed
to determine significant differences between the three diseases. Correlations were used to
examine relationships between BMQ-General and BMQ-Specific subscales. Logistic
regression analysis was employed to assess the association between non-adherence and
medicine beliefs. Five percent of patients had at least one missing value in their BMQ
answers and the total missing values were 0.3% for the whole BMQ items. A sensitivity
analysis was done to include all patients with missing data replaced with imputed data in the
multivariable analysis concluding all variables listed in Table 1. The multiple imputation
analysis included all variables used in the final analysis with 10 imputations by using the
Markov Chain Monte Carlo method to produce imputed data. All statistical analyses were
carried out using SAS (version 9.4).
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Results
Patient characteristics
There were 967 patients in the study (313 with stroke, 315 with diabetes mellitus and 339
with RA). Table 1 shows the demographic and clinical information by disease groups.
Patients with RA were significantly younger than patients with stroke and diabetes mellitus
(mean age 49.7 vs 65.8 and 62.5, respectively). The RA group was 85% female while only
44% of stroke patients and 45% of diabetes mellitus patients were female. Patients with RA
were 5 times more likely to report having received no formal education than patients with
stroke and diabetes mellitus (23.3% vs 4.8% and 4.1%, respectively). Over half of patients in
the stroke group had less than 1 year disease duration while more than half of the patients in
the RA and diabetes mellitus groups had more than 5 years disease duration.
BMQ results
The results of BMQ subscales are shown in Table 2. There were no significant differences in
the mean scores of Specific-Concerns and General-Harm between the three groups. However,
differences were observed for Specific-Necessity, General-Overuse, General-Benefit and
PSM among the three groups. Patients with RA had the highest score of 3.75 (SD 0.40) for
Specific-Necessity and lowest scores of 2.95 (SD 0.51) for General-Overuse and 3.55 (SD
0.45) for General-Benefit. The mean scores of PSM were 2.89 (SD 0.65), 2.35 (SD 0.64) and
2.70 (SD 0.68). The attitudinal analysis categorised patients into four groups (high/low
necessity and high/low concerns) according to the midpoint of the Specific-Necessity
Specific-Concerns scales shows that 45% of patients were classified as ‘Ambivalent’, 45%
as ‘Accepting’, 4% as ‘Skeptical’ and 6% as ‘Indifferent’ (Figure 1).
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Patients’ general beliefs about medicines were associated with their evaluations of the
specific treatments they were taking. Table 3 shows the correlation between BMQ-General
and BMQ-Specific. Specific-Necessity was positively associated with General-Benefit
(Pearson correlation coefficients = 0.31, p<0.01). Moderate correlations were observed
between Specific-Concerns and General-Overuse, General-Harm and PSM (Pearson
correlation coefficients, 0.39, 0.49 and 0.49, respectively, p<0.01). General-Overuse was also
correlated with General-Harm and PSM (Pearson correlation coefficients, 0.45 and 0.39,
respectively, p<0.01). The Pearson correlation coefficient was 0.39 (p<0.01) for General-
Harm and PSM.
Association between beliefs about medicines and non-adherence
Three hundred and eleven patients were non-adherent to their medicine [159 (51.0%) in the
stroke group, 60 (26.7%) in the diabetes mellitus group and 62 (19.8%) in the RA group,
p<0.01]. After adjusting for demographic characteristics, Specific-Concerns and PSM were
significantly associated with non-adherence (adjusted ORs, 1.35, 95% CI 1.07-1.71 and 1.44,
95% CI 1.16-1.80). Negative associations between non-adherence and Specific-Necessity and
General-Benefit were not statistically significant (Table 4). The subgroup analyses showed
that the point estimates of Specific-Concerns were positively associated with non-adherence
across the three conditions i.e. the more concerns about the medicines, the more non-adherent
to medicines, with adjusted ORs ranging from 1.15 (95% CI 0.67-1.98) for diabetes mellitus
to 1.43 (95% CI 1.02-2.00) for stroke (Table 5). The unadjusted results showed similar results
across the three disease conditions. The sensitivity analysis showed that Specific-Concerns
and PSM were positively associated with non-adherence (adjusted ORs, 1.15 95% CI 1.04-
1.26 and 1.40, 95% CI 1.04-1.26, respectively) and General-Benefit was negatively
associated with non-adherence (adjusted OR 0.79, 95% CI 0.71-0.87). Compared with
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patients in the Accepting group, patients in the other attitudinal groups were more likely to be
the non-adherent (adjusted ORs, 1.50 95% CI 1.10-2.05 for the Ambivalent group, 1.27 95%
CI 0.60-2.68 for the Skeptical group and 1.27 95% CI 0.69-2.34 for the Indifferent group.
Only patients in the Ambivalent group showed a statistical significance.
Discussion
This is the first large study of this kind that investigates beliefs about medicines and medicine
non-adherence in China in three common chronic diseases. Both unadjusted and adjusted
results revealed that Specific-Concerns and PSM were significantly associated with non-
adherence i.e. the higher the concern about the medicine or the higher perceived sensitivity to
medicines. Using the continuous MARS-5 scores showed similar relationships to those
reported in logistic regression (r=-0.09, p<0.01 for Specific-Concerns and r=-0.09, p<0.01 for
PSM). We noted differences between groups that might indicate different attitudes towards
the diseases and their treatments or be attributable to other factors. The hospital out-patients
(diabetes mellitus and RA) included some patients who had previous hospitalisations and
come back to hospital for regular monitoring.
Our findings were consistent with the evidence from a recent meta-analysis which showed
that higher adherence was associated with fewer concerns about treatment10
but not consistent
with previous findings that higher belief in personal need for treatment was associated with
higher adherence; Specific-Necessity was not associated with non-adherence in our overall
analysis. Subgroup analyses showed that patients with stroke and diabetes mellitus showed
the same direction association as previous studies i.e, patients with higher necessity were less
likely to be non-adherent. However, an opposite non-statistically significant result of
Specific-Necessity and adherence for patients with RA (Our result of 1.34 (95% CI 0.73-
2.46) for non-adherence equals 0.75, 95% CI 0.41-1.38 for adherence) was observed in the
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study in comparison with the meta-analysis result which had a pooled OR of 3.28, 95%CI
1.11-9.71 for adherence.10
The point estimate could be due to chance and further studies need
to confirm the finding. A recent study found that General-Benefit may be negatively
associated with non-adherence among 398 patients with epilepsy from the UK primary care
population (adjusted OR, 0.92, 95%CI 0.63-1.34)18
and this association was confirmed by our
study with a borderline significant OR of 0.75 (95%CI 0.56-1.02). There was no correlation
between Necessity and Concern (Table 2) in our study population and this was supported by
a recent Swedish study conducted in 578 stroke patients.19
They reported a Spearman’s
correlation coefficient of 0.075 (p=0.08). Compared to patients with high necessity and low
concerns, patients with high necessity and high concerns, low necessity and high concerns,
and low necessity and low concerns were all associated with non-adherence and this was
supported by studies conducted in patients with inflammatory bowel disease and renal
dysfunction.20 21
High perceived sensitivity to medicines was reported to be associated with
non-adherence and higher medical care utilisation, increased symptom reporting and greater
information-seeking about medication.18, 22
Our study also showed PSM was associated with
non-adherence.
Our study has some strengths. Firstly, this was the first large BMQ study conducted in China.
Secondly, we choose two large teaching hospitals for this study and collected data continually
until the target numbers were reached for each condition. Therefore, our study population
was more likely to represent the disease population from each region as large teaching
hospitals provide health care service to majority of Chinese patients. However, we
acknowledge that some patients with Transient Ischemic Attacks (TIAs), a subtype of stroke
may not be admitted to hospital. Therefore our stroke in-patients may under represent the
TIA patients. Thirdly, China has higher prevalence rates of stoke and diabetes mellitus than
Western Europe and stroke is also the leading cause of death in China. In light of the current
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deteriorated relationship between health professional and patients (i.e. patients do not trust
their doctors and other health professionals, doctors, nurses are often abused verbally and
physically by patients,11, 23, 24
more studies are needed from the patients’ perspective. More
consideration from the patient perspective should be taken into account in term of chronic
disease management and the relationship between patients and health professionals.
However, our study was an observational study. Therefore the results may be confounded by
unmeasured factors such as comorbidity. Self-reported adherence may not be the best
measurement for medicine adherence as patients may, for example, underestimate how often
they forget their treatment. However, a strong correlation was found for medicine adherence
measured by self-reported questionnaire, electronic prescriptions and serum biomarkers in a
recent intervention study suggesting that self-report is a reliable measure.25
Also our study
found relatively low reliability of the BMQ general scales and further investigation and
refinement might be needed of these Chinese translations. The difference in non-adherence
between stroke and other conditions needs to be explored in future studies as disease itself
may play an important role in medicine adherence.
In conclusion, we found that the BMQ is a useful tool to identify psychological factors that
are linked to non-adherence in patients with stroke, diabetes and RA. Future studies should
use the BMQ to screen patients to identify those who are at high risk of non-adherence and
map their treatment plan accordingly.
CONFLICT OF INTEREST/STUDY SUPPORT:
Specific author contributions: LW, RC and RH were involved in conception and design and
interpretation of data. LW did the statistical analysis and wrote the first draft of the article.
SC, RC and BN contributed to data analysis. LXM, LX and LSM collected data. SC, AC,
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LXM, LX and LSM were involved in interpretation of data. All authors were responsible for
re-drafting of the article and approved the final version.
Guarantor of the article: LW is the guarantor
Financial support: This study was funded by the Research Innovation Fund, UCL School of
Pharmacy. The funder had no role in the design, conduct or data interpretation of the study.
Professor Rob Horne was supported by the National Institute for Health Research (NIHR)
Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North
Thames at Bart’s Health NHS Trust.
Potential competing interests: RH declares: (1) Speaker engagements with honoraria and
consultancy payments from the pharmaceutical companies; (2) Founder and shareholder of a
UCL-Business, university spin-out company (Spoonful of Sugar Ltd) providing consultancy
on medication-related behaviours to healthcare policy makers, providers and industry; and (3)
Originator of BMQ.
References:
1. Medicines adherence: involving patients in decisions about prescribed medicines and
supporting adherence. https://www.nice.org.uk/guidance/cg76/chapter/introduction (accessed
on 30 January 2017)
2. Liu L, Wang D, Wong KS, Wang Y. Stroke and stroke care in China: huge burden,
significant workload, and a national priority. Stroke; a journal of cerebral circulation.
2011;42(12):3651-4.
3. Feigin VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA, et al.
Global and regional burden of stroke during 1990-2010: findings from the Global Burden of
Disease Study 2010. Lancet. 2014;383(9913):245-54.
Page 15 of 27
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BMJ Open
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on April 23, 2020 by guest. P
rotected by copyright.http://bm
jopen.bmj.com
/B
MJ O
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ctober 2017. Dow
nloaded from
For peer review only
16
4. Li R, Sun J, Ren LM, Wang HY, Liu WH, Zhang XW, et al. Epidemiology of eight
common rheumatic diseases in China: a large-scale cross-sectional survey in Beijing.
Rheumatology (Oxford). 2012 Apr;51(4):721-9. doi: 10.1093/rheumatology/ker370. Epub
2011 Dec 16.
5. China Total population, 2015. http://www.who.int/countries/chn/en/ (accessed on 25 May
2017)
6. Wu X, Zhu B, Fu L, Wang H, Zhou B, Zou S, et al. Prevalence, incidence, and mortality of
stroke in the chinese island populations: a systematic review. PLoS One. 2013 Nov
8;8(11):e78629. doi: 10.1371/journal.pone.0078629. eCollection 2013.
7. Will JC, Zhang Z, Ritchey MD, Loustalot F. Medication Adherence and Incident
Preventable Hospitalizations for Hypertension. Am J Prev Med. 2016 Apr;50(4):489-99. doi:
10.1016/j.amepre.2015.08.021. Epub 2015 Oct 31.
8. Shore S, Carey EP, Turakhia MP, Jackevicius CA, Cunningham F, Pilote L, et al.
Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the
veterans health administration. Am Heart J. 2014 Jun;167(6):810-7. doi:
10.1016/j.ahj.2014.03.023. Epub 2014 Apr 5.
9. Korhonen MJ, Ruokoniemi P, Ilomaki J, Meretoja A, Helin-Salmivaara A, Huupponen R.
Adherence to statin therapy and the incidence of ischemic stroke in patients with diabetes.
Pharmacoepidemiol Drug Saf. 2016 Feb;25(2):161-9. doi: 10.1002/pds.3936.
10. Horne, R, Chapman SC, Parham R, Freemantle N, Forbes A, Cooper V. Understanding
patients’ adherence –related beliefs about medicines prescribed for long-term conditions: a
meta-analytic review of the necessity-concerns framework. Plos One. 2013 Dec
2;8(12)e80633. Doi:10.1371/journal.pone.0080633.
11. Tucker JD, Cheng Y, Wong B, Gong N, Nie JB, Zhu W, et al; Patient-Physician Trust
Project Team. Patient-physician mistrust and violence against physicians in Guangdong
Page 16 of 27
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/B
MJ O
pen: first published as 10.1136/bmjopen-2017-017293 on 5 O
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nloaded from
For peer review only
17
Province, China: a qualitative study. BMJ Open. 2015 Oct 6;5(10):e008221. doi:
10.1136/bmjopen-2015-008221.
12. Chan CS, Cheng Y, Cong Y, Du Z, Hu S, Kerrigan A, et al. Patient-physician trust in
China: a workshop summary. Lancet. 2016 Oct;388 Suppl 1:S72. doi: 10.1016/S0140-
6736(16)31999-7.
13. National Health and Family Planning Commission of the PRC http://en.nhfpc.gov.cn/
(last access 30 January 2017)
14. Horne R, Weinman J. Patients' beliefs about prescribed medicines and their role in
adherence to treatment in chronic physical illness. J Psychosom Res. 1999 Dec;47(6):555-67.
15. Horne R. The nature, determinants and effects of medication beliefs in chronic illness
(PhD thesis) University of London 1997.
16. Bland JM, Douglas G Altman, DG. Statistics notes: Cronbach's alpha. BMJ 1997;
314:572 doi: https://doi.org/10.1136/bmj.314.7080.572
17. Wei L, Wang J, Thompson P, Wong S, Struthers AD, MacDonald TM. Adherence to
statin treatment and readmission of patients after myocardial infarction: a six year follow up
study. Heart 2002;88:229-33.
18. Chapman SC, Horne R, Chater A, Hukins D, Smithson WH. Patients' perspectives on
antiepileptic medication: relationships between beliefs about medicines and adherence among
patients with epilepsy in UK primary care. Epilepsy Behav. 2014 Feb;31:312-20. doi:
10.1016/j.yebeh.2013.10.016. Epub 2013 Nov 27.
19. Sjolander M, Eriksson M, Glader EL. The association between patients' beliefs about
medicines and adherence to drug treatment after stroke: a cross-sectional questionnaire
survey. BMJ open. 2013;3(9):e003551.
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nloaded from
For peer review only
18
20. Horne R, Parham R, Driscoll R, Robinson A. Patients' attitudes to medicines and
adherence to maintenance treatment in inflammatory bowel disease. Inflamm Bowel Dis.
2009 Jun;15(6):837-44. doi: 10.1002/ibd.20846.
21. Chater AM, Parham R, Riley S, Hutchison AJ, Horne R. Profiling patient attitudes to
phosphate binding medication: a route to personalising treatment and adherence support.
Psychol Health. 2014;29(12):1407-20. doi: 10.1080/08870446.2014.942663. Epub 2014 Aug.
22. Faasse K, Grey A, Horne R, Petrie KJ. High perceived sensitivity to medicines is
associated with higher medical care utilisation, increased symptom reporting and greater
information-seeking about medication. Pharmacoepidemiol Drug Saf. 2015 Jun;24(6):592-9.
doi: 10.1002/pds.3751. Epub 2015 Apr 7.
23. Li ZG, Leng MX. Doctor-patient relationship research summary. Chinese Hospital
Management. 2009;29(332):40-3.
24. Doctors face verbal abuse or violence. http://www.cmdae.org/en/index.php (Accessed 30
January 2017).
25. Lyons I, Barber N, Raynor DK, Wei L. The Medicines Advice Service Evaluation
(MASE): a randomised controlled trial of a pharmacist-led telephone based intervention
designed to improve medication adherence. BMJ Qual Saf. 2016 Oct;25(10):759-69. doi:
10.1136/bmjqs-2015-004670.
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Table 1. Patient characteristics by conditions
Stroke
n=313 (100%)
Diabetes
n=315 (100%)
RA
n=339 (100%)
Age, mean (SD) * 65.8 (13.7) 62.5 (13.9) 49.7 (12.8)
Gender†*
Women 136 (43.5%) 141 (44.8%) 287 (85.2%)
Men 177 (56.5%) 174 (55.2%) 50 (14.8%)
Education*
Illiteracy (no formal
education)
15 (4.8%) 13 (4.1%) 79 (23.3%)
Primary school 66 (21.1%) 62 (19.7%) 93 (27.4%)
Junior high school 60 (19.2%) 91 (28.9%) 91 (26.8%)
High school/college 116 (37.1%) 77 (24.4%) 48 (14.2%)
University or above 54 (17.2%) 70 (22.2%) 25 (7.4%)
Unknown 2 (0.6%) 2 (0.6%) 3 (0.9%)
Occupation*
Farmer 5 (1.6%) 22 (7.0%) 110 (32.5%)
Worker/clerk 83 (26.5%) 117 (37.1%) 38 (11.2%)
Housewife/unemployment 45 (14.4%) 12 (3.8%) 113 (33.3%)
Retirement 129 (41.2%) 54 (17.1%) 40 (11.8%)
Health professional 19 (6.1%) 29 (9.2%) 15 (4.4%)
Civil service 29 (9.3%) 72 (22.9%) 11 (3.2%)
Unknown 3 (1.0%) 9 (2.9%) 12 (3.5%)
Duration of the disease*
<= 1 year 178 (56.9%) 20 (6.4%) 55 (16.2%)
1-5 years 91 (29.1%) 74 (23.5%) 104 (30.7%)
> 5 year 44 (14.1%) 220 (69.8%) 177 (52.2%)
unknown 0 (0.0%) 1 (0.3%) 3 (0.9%) †Excluding missing data; *<0.05
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Table 2. Results of BMQ and PSM by disease conditions
Stroke
n=313
Diabetes
n=315
RA
n=339
Specific-Necessity (mean, SD) †
* 3.69 (0.53) 3.75 (0.40) 3.66 (0.44)
Specific-Concerns (mean, SD) †
3.03 (0.71) 3.15 (0.58) 3.07 (0.58)
General-Overuse (mean, SD) †
* 3.22 (0.62) 3.12 (0.50) 2.95 (0.51)
General-Harm (mean, SD) †
2.94 (0.78) 2.95 (0.50) 2.99 (0.43)
General-Benefit (mean, SD) †
* 3.70 (0.53) 3.69 (0.42) 3.55 (0.45)
PSM (mean, SD) †
* 2.89 (0.65) 2.35 (0.64) 2.70 (0.68)
MARS score (mean, SD*) 18.81 (4.16) 21.51 (3.07) 21.47 (3.86) †Excluding missing data; PSM=Perceived Sensitivity to Medicines; *<0.05
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Table 3. Correlation matrix between BMQ-Specific, BMQ-General and PSM
Necessity Concerns Overuse Harm Benefit PSM
Overall
Necessity 1.00
Concern 0.02(0.45) 1.00
Overuse -0.01 (0.87) 0.39 (<0.01) 1.00
Harm -0.05 (0.16) 0.49 (<0.01) 0.45 (<0.01) 1.00
Benefit 0.31(<0.01) -0.09 (0.01) 0.11 (<0.01) 0.04 (0.21) 1.00
PSM 0.04 (0.22) 0.45 (<0.01) 0.39 (<0.01) 0.38<0.01) 0.05 (0.14) 1.00
Stroke
Necessity 1.00
Concern 0.04 (0.43) 1.00
Overuse 0.06 (0.31) 0.50 (<0.01) 1.00
Harm -0.06 (0.27) 0.66 (<0.01) 0.57 (<0.01) 1.00
Benefit 0.36 (<0.01) 0.01 (0.88) 0.24 (<0.01) 0.13 (0.12) 1.00
PSM 0.23 (<0.01) 0.52 (<0.01) 0.51 (<0.01) 0.50 (<0.01) 0.22 (<0.01) 1.00
Diabetes mellitus
Necessity 1.00
Concern 0.02 (0.59) 1.00
Overuse -0.05 (0.40) 0.26 (<0.01) 1.00
Harm -0.08 (0.20) 0.21 (<0.01) 0.44 (<0.01) 1.00
Benefit 0.19 (<0.01) -0.07 (0.26) 0.18 (<0.01) 0.08 (0.19) 1.00
PSM -0.08 (0.20) 0.36 (<0.01) 0.38 (<0.01) 0.44 (<0.01) 0.07 (0.23) 1.00
RA
Necessity 1.00
Concerns 0.01 (0.91) 1.00
Overuse -0.08 (0.13) 0.41 (<0.01) 1.00
Harm 0.02 (0.72) 0.42 (<0.01) 0.30 (<0.01) 1.00
Benefit 0.30 (<0.01) -0.21 (<0.01) -0.20 (<0.01) -0.15 (0.21) 1.00
PSM -0.04 (0.52) 0.54 (<0.01) 0.29 (<0.01) 0.27 (<0.01) -0.13 (0.02) 1.00
Page 21 of 27
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Table 4. Odd ratios of medicine non-adherence
Unadjusted
OR, 95% CI
Adjusted*
OR, 95% CI
Specific-Necessity 0.90, 0.67-1.21 0.93, 0.68-1.27
Specific-Concerns 1.27, 1.02-1.58 1.35, 1.07-1.71
General-Overuse 1.32, 1.04-1.69 1.15, 0.88-1.50
General-Harm 1.09, 0.87-1.38 1.12, 0.89-1.43
General-Benefit 0.84, 0.63-1.12 0.75, 0.56-1.02
PSM 1.72, 1.41-2.09 1.44, 1.16-1.85
*Adjusted for age, gender, education, occupation, duration of the disease and different
diseases
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Table 5. Odd ratios of medication non-adherence by disease groups
Stroke Diabetes RA
Unadjusted
OR, 95% CI
Adjusted*
OR, 95% CI
Unadjusted
OR, 95% CI
Adjusted*
OR, 95% CI
Unadjusted
OR, 95% CI
Adjusted*
OR, 95% CI
Specific-
Necessity
0.83, 0.54-1.26 0.92, 0.59-1.43 0.71, 0.35-1.40 0.92, 0.43-1.97 1.31, 0.75-2.27 1.34, 0.73-2.46
Specific-
Concerns
1.43, 1.04-1.96 1.43, 1.02-2.00 1.16, 0.71-1.88 1.15, 0.67-1.98 1.38, 0.91-2.12 1.32, 0.84-2.10
General-
Overuse
1.26, 0.88-1.81 1.24, 0.85-1.82 1.12, 0.64-1.96 1.10, 0.61-2.00 1.06, 0.66-1.71 0.98, 0.60-1.60
General-
Harm
1.26, 0.95-1.68 1.30, 0.96-1.77 0.58, 0.32-1.05 0.59, 0.32-1.11 1.27, 0.72-2.24 1.27, 0.70-2.30
General-
Benefit
0.87, 0.57-1.32 0.83, 0.53-1.29 0.78, 0.41-1.50 0.83, 0.41-1.69 0.64, 0.37-1.09 0.65, 0.37-1.13
PSM 1.76, 1.22-2.53 1.79, 1.23-2.60 1.60, 1.05-2.44 1.73, 1.10-2.70 1.06, 0.74-1.51 1.01, 0.70-1.48
*Adjusted for age, gender, education, occupation, duration of the disease
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Figure legend
Figure 1. Attitudinal analysis of BMQ-Specific.
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254x190mm (300 x 300 DPI)
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STROBE 2007 (v4) Statement—Checklist of items that should be included in reports of cross-sectional studies
Section/Topic Item
# Recommendation Reported on page #
Title and abstract 1 (a) Indicate the study’s design with a commonly used term in the title or the abstract Page 2
(b) Provide in the abstract an informative and balanced summary of what was done and what was found Page 2
Introduction
Background/rationale 2 Explain the scientific background and rationale for the investigation being reported Page 5-6
Objectives 3 State specific objectives, including any prespecified hypotheses Page 6
Methods
Study design 4 Present key elements of study design early in the paper Page 6
Setting 5 Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data
collection
Page 6
Participants
6
(a) Give the eligibility criteria, and the sources and methods of selection of participants Pages 6-8
Variables 7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers. Give diagnostic criteria, if
applicable
Pages 7-8
Data sources/
measurement
8* For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe
comparability of assessment methods if there is more than one group
Page 7-8
Bias 9 Describe any efforts to address potential sources of bias Page 9
Study size 10 Explain how the study size was arrived at Page 6
Quantitative variables 11 Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen and
why
Page 9
Statistical methods 12 (a) Describe all statistical methods, including those used to control for confounding Page 9
(b) Describe any methods used to examine subgroups and interactions Page 11
(c) Explain how missing data were addressed Page 9
(d) If applicable, describe analytical methods taking account of sampling strategy n/a
(e) Describe any sensitivity analyses Pages 9 &12
Results
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Participants 13* (a) Report numbers of individuals at each stage of study—eg numbers potentially eligible, examined for eligibility,
confirmed eligible, included in the study, completing follow-up, and analysed
Page 9
(b) Give reasons for non-participation at each stage n/a
(c) Consider use of a flow diagram n/a
Descriptive data 14* (a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential
confounders
Page 9 and Page 18
(b) Indicate number of participants with missing data for each variable of interest Page 18
Outcome data 15* Report numbers of outcome events or summary measures Pages 10-12
Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence
interval). Make clear which confounders were adjusted for and why they were included
Pages 22-23
(b) Report category boundaries when continuous variables were categorized Pages 8 & 10
(c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period n/a
Other analyses 17 Report other analyses done—eg analyses of subgroups and interactions, and sensitivity analyses Page 11
Discussion
Key results 18 Summarise key results with reference to study objectives Page 11
Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and
magnitude of any potential bias
Page 13
Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from
similar studies, and other relevant evidence
Pages 11-14
Generalisability 21 Discuss the generalisability (external validity) of the study results Page 13
Other information
Funding 22 Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on
which the present article is based
Page 14
*Give information separately for cases and controls in case-control studies and, if applicable, for exposed and unexposed groups in cohort and cross-sectional studies.
Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and published examples of transparent reporting. The STROBE
checklist is best used in conjunction with this article (freely available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at
http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is available at www.strobe-statement.org.
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