Int J Clin Pharm (2014) 36:36–44 DOI 10.1007/s11096-013-9895-4
REVIEW ARTICLE
Investigating the association between health literacy and nonadherence Remo Ostini • Therese Kairuz
Received: 5 June 2013 / Accepted: 22 November 2013 / Published online: 1 December 2013 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2013
Abstract Background Low health literacy is expected to be associated with medication non-adherence and early research indicated that this might be the case. Further research suggested that the relationship may be more equivocal. Aim of the review The goal of this paper is initially to clarify whether there is a clear relationship between health literacy and non-adherence. Additionally, this review aims to identify factors that may influence that relationship and ultimately to better understand the mechanisms that may be at work in the relationship. Method English language original research or published reviews of health literacy and non-adherence to orally administered medications in adults were identified through a search of four bibliographic databases (PubMed, EMBASE, CINAHL, and EBSCO Health). Results The search protocol produced 78 potentially relevant articles, of which 16 articles addressed factors that contribute to non-adherence and 24 articles reported on the results of research into the relationship between non-adherence and health literacy. Factors that contribute to non-adherence can be categorised into patient related factors, including patient beliefs; medication related factors; logistical factors; and factors around the patient-provider relationship. Of the 23 original research articles that investigated the relationship between non-adherence and health literacy, only five reported finding clear evidence of a relationship, four reported mixed results and 15 articles reported not finding the
R. Ostini (&) School of Population Health, The University of Queensland, Ipswich, QLD 4305, Australia e-mail: [email protected] T. Kairuz School of Pharmacy, St Lucia, QLD 4072, Australia
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expected relationship. Research on possible mechanisms relating health literacy to non-adherence suggest that disease and medication knowledge are not sufficient for addressing non-adherence while self-efficacy is an important factor. Other findings suggest a possible U-shaped relationship between non-adherence and health literacy where people with low health literacy are more often nonadherent, largely unintentionally; people with moderate health literacy are most adherent; and people with high health literacy are somewhat non-adherent, sometimes due to intentional non-adherence. Conclusion It is clear that relevant research generally fails to find a significant relationship between non-adherence and health literacy. A Ushaped relationship between these two conditions would explain why linear statistical tests fail to identify a relationship across all three levels of health literacy. It can also account for the conditions under which both positive and negative relationships may be found. Keywords Health literacy Knowledge Nonadherence Non-linear relationship Patient adherence Self-efficacy
Impact on practice •
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Improving patient’s health literacy is unlikely to improve adherence if the focus is purely on improving knowledge. Improving patient’s health literacy is likely to improve adherence if it enhances patient self-efficacy. Improved knowledge may have a role in this. People with low health literacy will require different approaches to improving adherence than people with high health literacy because their non-adherence is
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likely to be unintentional while high health literacy patients have a greater likelihood of intentional nonadherence.
Introduction The simple premise underlying research into the relationship between health literacy and medicine-taking, is that people who understand how to manage their health will be adherent, taking medication as prescribed. Initial findings from early research appeared to support the basic proposition that health literacy interventions could improve adherence [1, 2] but further research appeared to indicate that the relationship between non-adherence and health literacy was more ambiguous [3]. Results began to show that for self-reported medication nonadherence, the relationship with health literacy was not predictable [4]. Health literacy Health literacy typically refers to the ability of people to obtain, process and understand health information and services in order to make appropriate health decisions [5]. In practice, much of the focus has been on understanding information with far less emphasis on the components related to obtaining information and decision-making. The most frequently used current measures of health literacy, such as the Test of Functional Health Literacy in Adults: TOFHLA [6] and the Rapid Estimate of Adult Literacy in Medicine: REALM [7, 8], focus on literacy tasks such as reading and comprehension, reducing the decision-making component even further. The link between understanding and using information is largely taken for granted. Health literacy goes well beyond the narrow idea of reading health-related material [9]. We take health literacy to mean people’s capacity to manage their health, similar to the way financial literacy is taken to mean people’s capacity to manage their finances. In this sense, health literacy incorporates the four factors that the World Health Organisation (WHO) associates with nonadherence—that is, the health care team and system, the condition or illness, therapy (i.e., medication), and patient-related factors [10]. This also corresponds with the WHO definition of health literacy, which involves cognitive and social skills together determining the ability and motivation of individuals to promote and maintain good health [11]. According to WHO, this process requires knowledge, personal skills and confidence to take action.
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Non-adherence Adherence to medication has been associated with improved patient health outcomes and reduced unnecessary costs [12]. However, non-adherence to medicines is not necessarily the converse of adherence; the latter is defined as the extent to which patients take medications as prescribed by their health care provider [10], while nonadherence indicates non-initiation, suboptimal dosing regimens, or discontinuation of treatment [13]. The World Health Organisation (WHO) describes non-adherence as a ‘‘multi-determined problem caused by the interplay of [the] four factors’’ indicated above [10]. In contrast, adherence refers to the process by which patients take their medication as prescribed [13] and is associated with a degree of patient autonomy. The term is more patient-centred than ‘compliance’ which reflects a subservient patient role, [14] and ignores much of the prescriber-patient dynamic. ‘Persistence’ generally refers to patients who use continuous pharmacotherapy [15], from initiation to the last dose prior to discontinuation, [13] and is determined by using medication refills as a measure [15]. The terms are often used interchangeably and inconsistently. Interventions that improve and maintain adherence at optimal levels remain elusive, and studies have yet to define a non-adherent patient [16]. In this review, we focus on non-adherence while accepting that it is often treated as a lack of adherence rather than the distinct concept that it may be.
Aim of the review The goal of this paper is to clarify whether or not there is a clear, demonstrable, and meaningful relationship between health literacy and medication non-adherence. Beyond this, we will endeavour to identify and evaluate factors that may influence or affect the relationship between health literacy and medication non-adherence. In this way, we hope to explain the ambiguous results that have been reported for this relationship, identifying the conditions that promote or impede it, and consider possible mechanisms underpinning these effects.
Method Search strategy English language published reviews or original research on health literacy and non-adherence to orally administered medications were the focus of the search. Exclusion criteria included research with children; opinion, editorial or
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commentary articles; and conference abstracts. Both qualitative and quantitative research was included. Four bibliographic databases were searched. PubMed (1951-April 19, 2013) was searched using a comprehensive health literacy search based on a protocol developed by the National Library of Medicine [17], combined with a search using Adherence (text word) OR Persistence (text word) OR Concordance (text word) OR Compliance (mesh major topic) and a search using Non adherence (text word) OR Non compliance (text word) as search terms. The same specific terms were used in searches of the EMBASE (1974–April 2013), CINAHL (1981-April 2013) and EBSCO Health (1969-April 2013) databases, using database specific term mapping where available, or keyword searches where this was not available. Article evaluation and data extraction One author (RO) reviewed the titles of all articles identified to assess potential relevance, and then reviewed the abstracts of remaining articles to identify studies that met inclusion and exclusion criteria. Both authors extracted data from the remaining articles. The primary goal of data extraction was to identify the results of investigations into the relationship between health literacy and non-adherence and the possible causes of any relationship. In addition, descriptive features of study samples and analysis methods that could assist in evaluating strength of evidence were identified. Search results were also used to extract information on factors other than health literacy that had been investigated for their association with non-adherence. A narrative synthesis process incorporated the extracted information into three main areas: examples of factors associated with medication adherence, which may be relevant to any health literacy–non-adherence relationship; research investigating the relationship between nonadherence and health literacy itself; and research reporting potential mechanisms by which non-adherence and health literacy might be associated.
Results The initial search across the four databases produced 990 unique results (See Fig. 1). The title scan excluded 709 articles and the abstract scan excluded a further 158 articles on the basis of topic relevance and exclusion criteria. At this stage 45 conference abstracts were excluded from further analysis. The remaining 78 articles were each read by one of the authors (RO or TK). In a small number of cases, there was some ambiguity in the data extraction results, in which
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Fig. 1 Outline of search strategy and article appraisal results
case, both authors read the article. Sixteen of these articles provided evidence about factors that have been found to contribute to non-adherence. Some of these articles were among 54 articles subsequently excluded for the following reasons: they did not assess health literacy (37) or adherence/non-adherence (2); they were not conducted among adults (2), or with oral medications (3); they were commentaries/editorial (8) or conference abstracts (2). A final set of 24 articles provided the data to address the review aim, which was to clarify the relationship between non-adherence and health literacy, and included one systematic review and 23 original research articles. All original research articles reported on research using quantitative methods. Descriptive features of these articles are summarised in Table 1. Factors associated with medication adherence The 16 papers from which we extracted factors that contribute to non-adherence point to a range of different influences. The medication adherence model [18] categorised the factors that influence medication-taking behaviour as: (1) how the patient perceives their illness (e.g., its severity); (2) patients’ cognitive functioning (e.g., memory, comprehension); and (3) external cues and strategies (e.g., social support, reminder systems). Factors that contribute to adherence can also be categorised into patient related; medication related; logistical; and patient-provider relationship factors [19]. Patient related factors that have been identified in adherence research include: poor disease-related knowledge [19];
Study description
Systematic review; 7 studies; All United States
Observational cohort study; N = 310 veterans taking 5 or more medications; United States
Cross-sectional; N = 182 seropositive patients; tripledrug antiretroviral therapy; United States
Cross-sectional; N = 145; anti-retroviral therapy; United States
Cross-sectional; N = 398; diabetes medication; United States
Nested RCT; N = 235; Anti-retroviral therapy; United States
Cross-sectional; N = 302; HIV medication; United States
Cross-sectional; N = 200; Hypertension medication; United States
Cross-sectional; N = 275; Various medications; United States
Cross-sectional; N = 50 HIV-infected youth; Antiretroviral therapy; United States
Cross-sectional; N = 87; Anti-viral medication; United States
Cross-sectional; N = 85; Hypertension medication; United States
Cross-sectional; N = 1,366 adults with Type II diabetes; Antidepressant medication; United States
Cross-sectional; N = 204; HIV medication; United States
Cross-sectional; N = 155; ‘‘Mock’’ HIV regimen; United States
RCT; N = 281; Cardiovascular medication; United States
Cross-sectional; N = 57; Anti-retroviral medication; United States
Cross-sectional; N = 409; Coronary heart disease medication; United States
Reference
Loke et al. [38]
Mosher et al. [21]
Kalichman et al. [25]
Kalichman et al. [26]
Osborne et al. [27]
Paasche-Orlow et al. [28]
Colbert et al. [31]
Bhor et al. [32]
Gatti et al. [33]
Navarra et al.[35]
Graham et al. [36]
JoynerGrantham et al. [37]
Bauer et al. [39]
Waite et al. [40]
WaldropValverde et al. [41]
Noureldin et al. [42]
WaldropValverde et al. [43]
Kripalani et al. [44]
Table 1 Descriptive characteristics of articles included in review
Mixed relationships between non-adherence and low health literacy including better adherence associated with lower health literacy
Mixed/confounded measure of relationship between non-adherence and low health literacy
Mixed relationships between non-adherence and low health literacy
Significant multivariate relationship between adherence and health literacy
Significant multivariate relationship between non-adherence and low health literacy
Significant multivariate relationship between non-adherence and low health literacy
No significant positive relationship between non-adherence and low health literacy
Significant multivariate relationship between non-adherence and low health literacy
No significant positive relationship between non-adherence and low health literacy
No significant positive relationship between non-adherence and low health literacy
No significant positive relationship between non-adherence and low health literacy
No significant positive relationship between non-adherence and low health literacy
Bivariate relationship between non-adherence and low health literacy that did not survive multivariate adjustment
Mixed relationships between non-adherence and low health literacy in multivariate path models
Significant multivariate relationship between non-adherence and low health literacy
Significant multivariate relationship between non-adherence and low health literacy
No significant positive relationship between non-adherence and low health literacy
Some bivariate relationships between diabetes or cardiovascular medication adherence and health literacy, but did not remain following multivariate adjustment; one article showing lower health literacy associated with greater adherence; health literacy can be associated with disease or medication knowledge but not adherence
Conclusion
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Cross-sectional; N = 125; Diabetes medication; United States
Cross-sectional; N = 179; Warfarin; United States
Prospective; N = 1,549; Various medications; United States
Bains and Egede [48]
Fang et al. [49]
Gazmararian et al. [50]
No significant positive relationship between non-adherence and low health literacy
Cross-sectional; N = 186 HIV-infected youth; HIV medications; United States Murphy et al. [47]
Bivariate relationship between non-adherence and low health literacy that did not survive multivariate adjustment
RCT; N = 118; HIV medication; United States Holzemer (et al. [46]
No significant positive relationship between non-adherence and low health literacy
RCT; N = 420; Cardiovascular medications; United States Kripalani et al. [45]
No significant positive relationship between non-adherence and low health literacy
Study description Reference
No significant positive relationship between non-adherence and low health literacy
Table 1 continued
poor treatment knowledge [20]; poor medication knowledge [20, 21]; impaired cognitive functioning [19]; having a history of non-adherence [20]; hectic schedules/work [22]; lack of social support [23–26]; education [23, 25]; socioeconomic status [23]; emotional distress [25, 26]; and illness duration [27]. A history of alcohol problems, drinking to intoxication and injecting drug use were also associated with poorer adherence in a sample of 235 people living with HIV/AIDS [28]. In another study among people living with HIV/AIDS who had demonstrated low health literacy (n = 188), a multivariate analysis showed that food insufficiency and hunger predicted non-adherence over and above the effects of depression, internalised stigma, substance abuse and HIV-related social stressors [29]. In this research, adherence was not related to gross cognitive functioning. Similarly, general reading ability and understanding were not associated with non-compliance in an older sample of 126 ambulatory care respondents from mixed socio-economic backgrounds [30]. Patient beliefs are a distinct and important set of patient factors. They include: beliefs about their disease [23]; unrealistic or uninformed expectations of risk, including risk of adverse effects [23]; lack of self-efficacy [23, 31]; and disbelief about medication efficacy [23, 32, 33]. Medication related factors include: adverse effects [19, 34]; polypharmacy/multiple medications [19–21]; complex medication regimens [20, 28]; safety concerns [20]; incomplete or confusing information on prescription labels [22]; administrative processes (i.e., logistical factors) for obtaining medications [20], intent to adhere and positive outcome expectancy [35]; and higher adherence norms [36]. Patient-provider relationship factors include: generally having a poor relationship [23]; providers not fully explaining how to take a medication [22]; and different cultural models exacerbating distrust of the health system [22]. A complex factor that does not fit easily into any of the four categories above is cost. This is a clear barrier to adherence for some people [23, 34] but can be considered a combination of patient-related, medication-related and logistical factors. Rust and Davis [34] reported the results of an online survey of almost 10,000 adults with chronic medical conditions which showed that not filling prescriptions (primary non-adherence) or taking medication incorrectly resulted from forgetfulness (24 %); side-effects (20 %); cost (17 %); denial that medication was needed (14 %); and inconvenience (10 %). A survey of 85 emergency room patients found that they attributed their nonadherence to inability to pay (36 %); feeling better (35 %); feeling worse (25 %); and difficulty remembering to take medication (32 %) [37]. Participant frustration with
No significant positive relationship between non-adherence and low health literacy
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Conclusion
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inconsistent health information from doctors and pharmacists was reported from focus groups among underserved African American women (n = 24) who had completed breast cancer treatment at least one year previously [34]. Many of these women reported receiving information through churches, community centres, and word of mouth—with the attendant possibility of misinformation. Participants also showed differing levels of satisfaction in seeking information, particularly from ‘busy’ pharmacists. Relationship between non-adherence and health literacy A systematic review of research on the relationship between non-adherence with diabetes or cardiovascular medication and health literacy, found no consistent links in the seven relevant studies reviewed [38]. Bivariate relationships were identified in some cases but did not hold up to adjustment in multivariate analysis, primarily with demographic variables. Contrary to expectations, one study found lower health literacy associated with higher selfreported medication adherence. In a secondary finding, a number of studies showed a relationship between health literacy and disease or medication knowledge, while showing no association with greater medication adherence [38]. A relationship was found between non-adherence and health literacy in five of the 23 articles reporting original research into the relationship [25, 26, 39–41]. Most of these were well-designed studies, unlike the Kalichman et al. [25] study, which had a small sample and where the relationship was only positive for respondents with a greater number of years of education. Waldrop-Valverde et al. [41] reported a very carefully designed study that was however, unusual in using a simulated measure of adherence. While this standardised the measurement procedure it leaves some question about the ecological validity of the results. Bauer et al. [39] used a screening measure of health literacy that is rarely used, reporting associations between health literacy and medication non-persistence before the first refill and at 180 days but not for primary non-adherence (in any analysis) or non-persistence at 365 days in multivariate analysis [39]. Four studies reported mixed results [27, 42–44]. A larger cumulative medication gap was associated with low health literacy in the Kripalani et al. [44] study but selfreported adherence was not. Noureldin et al. [42] conducted a well-designed RCT but only found an association between non-adherence and health literacy for two of seven adherence measures in the usual care arm of the study. Osborn et al. [27] reported the results of a path analysis which only showed a relationship between non-adherence and health literacy when numeracy was included in the path model. Finally, the study reported by Waldrop-
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Valverde et al. [43] confounded health literacy and cognitive functioning, showing adherence to be associated with a group low in cognition health literacy. This study also had a very small sample (n = 57). A clear majority of articles in this review (15 of 23), reported not finding significant positive relationships between non-adherence and low health literacy [21, 28, 31–33, 35, 37, 42, 44–50]. Some of these studies had small sample sizes and consequently likely had low power to detect a relationship. However, most were well-designed cross-sectional studies with reasonable samples; two studies used a randomized controlled trial design [28, 45]; and Gazmararian et al. [50] had the advantage of using a prospective design in a large, ethnically and geographically diverse population, using a preferred measure of adherence [51]. Two of the 15 studies found a bivariate relationship between health literacy and non-adherence that did not survive adjustment for the effects of other relevant variables in multivariate analysis [28, 50]. Counter-intuitively, better adherence was associated with lower health literacy for a self-report measure of adherence in the study reported by Kripalani et al. [44]. Potential mechanisms for an association between health literacy and non-adherence Factors found to be associated with non-adherence, which may have a role in the relationship between health literacy and non-adherence, include education, cognitive functioning, relevant knowledge, information sources, social support and self-efficacy. The Loke et al. [38] review found that health literacy was associated with disease and medication knowledge. Although research has also shown these factors to be associated with non-adherence, they have not been found to result in a relationship between health literacy and non-adherence. Research that directly addresses potential mechanisms in any relationship between non-adherence and health literacy is rare. In one of two such examples identified in this review, a finding that many patients in a hospital emergency room sample felt that nothing they did would help their blood pressure, was used to explain the fact that they did not take medications despite good health knowledge/ literacy about blood pressure [37]. This suggests that these patients had low self-efficacy, and implicitly, low medication efficacy beliefs as well. In another study, reasons for medication discrepancies 48 h after hospital discharge among 254 communitydwelling seniors (70 years or older) differed across health literacy levels [52]. Discrepancies for those with inadequate or marginal health literacy were significantly associated with lack of understanding about how to take the
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Fig. 2 Representation of theoretical relationship between health literacy and non-adherence
medication (unintentional non-adherence). In contrast, people with adequate health literacy were significantly more likely to have medication discrepancies as a result of choosing not to follow instructions—despite understanding those instructions [52]. The Lindquist et al. [52] findings suggest that high health literacy respondent non-adherence may be for different reasons than non-adherence in those with low health literacy. The findings of Lindquist and colleagues may have a bearing on the results reported by Waite and colleagues [40] who found non-adherence to be highest in those with low health literacy and lowest in people with moderate health literacy. Respondents with high health literacy had higher levels of non-adherence than those with moderate health literacy. These results suggest a U-shaped relationship between nonadherence and health literacy (see Fig. 2). Figure 2 represents a model of the relationship between health literacy and non-adherence suggested by this research. It shows nonadherence to be highest among those with low health literacy, lowest among those with moderate health literacy and then higher among people with high health literacy. There is some evidence that such U-shaped relationships are often found among socially controlled behaviours [53].
Discussion This review finds that there may be distinct differences between low, moderate and high health literacy individuals
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and their non-adherent behaviour. This could explain a possible U-shaped curve in the relationship between nonadherence and health literacy, and also explain positive and (unexpected) negative associations, which may exist around the inflexion point of the curve. If there is a U-shaped relationship between health literacy and nonadherence, then a statistical test fitting a linear model across all three levels of health literacy could be expected to be relatively flat and show no significant relationship. That result was the most common finding in the research reviewed. If a test were to be applied to a sample that was restricted to the low-to-moderate range of health literacy, it would be expected to show that better health literacy is associated with less non-adherence. Furthermore, in research with only moderate-to-high health literacy participants, a linear model could be expected to show the counterintuitive result, with better health literacy associated with poorer adherence; although rare, this has been reported [44]. The possibility of a U-shaped relationship between nonadherence and health literacy warrants further investigation as it has implications for research and practice. It may help researchers design studies with a better understanding of the implications of sampling for the strength and direction of expected associations. In practice terms, such a relationship suggests that people with low health literacy need help—likely with self-efficacy, through targeted knowledge and improved support. People with moderate levels of health literacy may not require intervention, while people with high health literacy may in fact be intentionally nonadherent. Given the implied capacity of these people to manage their health, the non-adherence may be warranted. In that case, non-adherence in a person with high health literacy would provide an opportunity for prescribers to revisit the treatment strategy and perhaps identify better options for non-medication-takers. There are times when medication prescribing can be ceased [54, 55] and nonadherence in people with high health literacy may reflect an appreciation of this for their individual situation. Polypharmacy may be an example of such a situation, as it often reflects suboptimal prescribing. Almost half of the 23 articles investigating the relationship between non-adherence and health literacy identified in this review were published recently, from 2010 onwards. This burst of activity, which often reported sophisticated research programs, confirmed that it is unusual to find a clear relationship between non-adherence and health literacy. This is due, in part, to limitations in the way both are measured. Nevertheless, the findings presented here are supported by their basis in two dozen studies that show a consistent trend. The finding that there is unlikely to be a direct linear relationship between non-adherence and low health literacy
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undermined the goal of this review to identify mechanisms linking heath literacy and adherence. However, the results of this review also point toward two potentially fruitful avenues of investigation. One promising activity is to untangle the ways in which health literacy, self-efficacy and medication use are interrelated. The second area that promises greater clarity involves directly investigating the strength of the proposition that low health literacy and nonadherence are non-linearly related. Investigating non-adherence within a health literacy framework can place the focus of medication taking on the potential medication-taker in a non-judgemental way, by highlighting the many interconnected components that contribute to a person’s ability to manage their health in the context of medication taking. A prescriber’s recommendation to take a medicine is one factor in the broad health literacy context; it may not, in practice, be the most influential factor. In many situations, this can lead to poor health outcomes. In some situations, non-adherence to the prescriber’s recommendation may be the most appropriate outcome for a patient. Understanding this framework will help researchers and clinicians realise that the goal of eliminating all instances of nonadherence is mistaken, and will contribute to the development of more effective means of reducing non-adherence when that non-adherence is not in the patient’s best interests.
Conclusion The evidence is clear that medication knowledge alone is insufficient for addressing non-adherence, and that addressing non-adherence within the framework of health literacy is not as straightforward as was initially assumed. Medication factors and self-efficacy influence medication-taking and must be considered as part of the health literacy equation. Funding
None.
Conflicts of interest
None.
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44 26. Kalichman SC, Pope H, White D, Cherry C, Amaral CM, Swetzes C, et al. Association between health literacy and HIV treatment adherence: further evidence from objectively measured medication adherence. J Int Assoc Physicians AIDS Care (Chic). 2008;7(6):317–23. 27. Osborn CY, Cavanaugh K, Wallston KA, Kripalani S, Elasy TA, Rothman RL, et al. Health literacy explains racial disparities in diabetes medication adherence. J Health Commun. 2011;16(Suppl 3):268–78. 28. Paasche-Orlow MK, Cheng DM, Palepu A, Meli S, Faber V, Samet JH. Health literacy, antiretroviral adherence, and HIVRNA suppression: a longitudinal perspective. J Gen Intern Med. 2006;21(8):835–40. 29. Kalichman SC, Grebler T. Stress and poverty predictors of treatment adherence among people with low-literacy living with HIV/AIDS. Psychosom Med. 2010;72(8):810–6. 30. Moisan J, Gaudet M, Gregoire JP, Bouchard R. Non-compliance with drug treatment and reading difficulties with regard to prescription labelling among seniors. Gerontology. 2002;48(1):44–51. 31. Colbert AM, Sereika SM, Erlen JA. Functional health literacy, medication-taking self-efficacy and adherence to antiretroviral therapy. J Adv Nurs. 2013;69(2):295–304. 32. Bhor M, Plake KS, Chen JT. Relationship between health literacy, outcome expectations, efficacy expectations and medication adherence. Value in Health. 2009;12(3):A155. 33. Gatti ME, Jacobson KL, Gazmararian JA, Schmotzer B, Kripalani S. Relationships between beliefs about medications and adherence. Am J Health Syst Pharm. 2009;66(7):657–64. 34. Rust C, Davis C. Health literacy and medication adherence in underserved African-american breast cancer survivors: a qualitative study. Soc Work Health Care. 2011;50(9):739–61. 35. Navarra AM, Neu N, Toussi S, Nelson J, Larson EL. Health literacy and adherence to antiretroviral therapy among hivinfected youth. J Assoc Nurses AIDS Care. 2013; 1–11. 36. Graham J, Bennett IM, Holmes WC, Gross R. Medication beliefs as mediators of the health literacy-antiretroviral adherence relationship in HIV-infected individuals. AIDS Behav. 2007;11(3):385–92. 37. Joyner-Grantham J, Mount DL, McCorkle OD, Simmons DR, Ferrario CM, Cline DM. Self-reported influences of hopelessness, health literacy, lifestyle action, and patient inertia on blood pressure control in a hypertensive emergency department population. Am J Med Sci. 2009;338(5):368–72. 38. Loke YK, Hinz I, Wang X, Salter C. Systematic review of consistency between adherence to cardiovascular or diabetes medication and health literacy in older adults. Ann Pharmacother. 2012;46(6):863–72. 39. Bauer AM, Schillinger D, Parker MM, Katon W, Adler N, Adams AS, et al. Health literacy and antidepressant medication adherence among adults with diabetes: the diabetes study of Northern California (DISTANCE). J Gen Intern Med. 2013; 1181–7. 40. Waite KR, Paasche-Orlow M, Rintamaki LS, Davis TC, Wolf MS. Literacy, social stigma, and HIV medication adherence. J Gen Intern Med. 2008;23(9):1367–72.
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Int J Clin Pharm (2014) 36:36–44 41. Waldrop-Valverde D, Jones DL, Jayaweera D, Gonzalez P, Romero J, Ownby RL. Gender differences in medication management capacity in HIV infection: the role of health literacy and numeracy. AIDS Behav. 2009;13(1):46–52. 42. Noureldin M, Plake KS, Morrow DG, Tu W, Wu J, Murray MD. Effect of health literacy on drug adherence in patients with heart failure. Pharmacother. 2012;32(9):819–26. 43. Waldrop-Valverde D, Jones DL, Weiss S, Kumar M, Metsch L. The effects of low literacy and cognitive impairment on medication adherence in HIV-positive injecting drug users. AIDS Care. 2008;20(10):1202–10. 44. Kripalani S, Gatti ME, Jacobson TA. Association of age, health literacy, and medication management strategies with cardiovascular medication adherence. Patient Educ Couns. 2010;81(2):177–81. 45. Kripalani S, Schmotzer B, Jacobson T. Improving medication adherence through graphically enhanced interventions in coronary heart disease (IMAGE-CHD): a randomized controlled trial. JGIM. 2012;27(12):1609–17. 46. Holzemer WL, Bakken S, Portillo CJ, Grimes R, Welch J, Wantland D, et al. Testing a nurse-tailored HIV medication adherence intervention. Nurs Res. 2006;55(3):189–97. 47. Murphy DA, Lam P, Naar-King S, Robert Harris D, Parsons JT, Muenz LR. Health literacy and antiretroviral adherence among HIV-infected adolescents. Patient Educ Couns. 2010;79(1):25–9. 48. Bains SS, Egede LE. Associations between health literacy, diabetes knowledge, self-care behaviours, and glycemic control in a low income population with type 2 diabetes. Diabetes Technol Ther. 2011;13(3):335–41. 49. Fang MC, Machtinger EL, Wang F, Schillinger D. Health literacy and anticoagulation-related outcomes among patients taking warfarin. J Gen Intern Med. 2006;21(8):841–6. 50. Gazmararian JA, Kripalani S, Miller MJ, Echt KV, Ren J, Rask K. Factors associated with medication refill adherence in cardiovascular-related diseases: a focus on health literacy. J Gen Intern Med. 2006;21(12):1215–21. 51. Powers BJ, Bosworth HB. Revisiting literacy and adherence: future clinical and research directions. J Gen Intern Med. 2006;21(12):1341–2. 52. Lindquist LA, Go L, Fleisher J, Jain N, Friesema E, Baker DW. Relationship of health literacy to intentional and unintentional non-adherence of hospital discharge medications. J Gen Intern Med. 2012;27(2):173–8. 53. Orford J. Excessive appetites: a psychological view of addictions. 2nd ed. Chichester: John Wiley and Sons; 2001. 54. Ostini R, Jackson C, Hegney D, Tett SE. How is medication prescribing ceased? A systematic review. Med Care. 2011;49(1):24–36. 55. Ostini R, Hegney D, Jackson C, Tett SE. Knowing how to stop: ceasing prescribing when the medicine is no longer required. J Manag Care Pharm. 2012;8(1):68–72.
REVIEW ARTICLE
Investigating the association between health literacy and nonadherence Remo Ostini • Therese Kairuz
Received: 5 June 2013 / Accepted: 22 November 2013 / Published online: 1 December 2013 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2013
Abstract Background Low health literacy is expected to be associated with medication non-adherence and early research indicated that this might be the case. Further research suggested that the relationship may be more equivocal. Aim of the review The goal of this paper is initially to clarify whether there is a clear relationship between health literacy and non-adherence. Additionally, this review aims to identify factors that may influence that relationship and ultimately to better understand the mechanisms that may be at work in the relationship. Method English language original research or published reviews of health literacy and non-adherence to orally administered medications in adults were identified through a search of four bibliographic databases (PubMed, EMBASE, CINAHL, and EBSCO Health). Results The search protocol produced 78 potentially relevant articles, of which 16 articles addressed factors that contribute to non-adherence and 24 articles reported on the results of research into the relationship between non-adherence and health literacy. Factors that contribute to non-adherence can be categorised into patient related factors, including patient beliefs; medication related factors; logistical factors; and factors around the patient-provider relationship. Of the 23 original research articles that investigated the relationship between non-adherence and health literacy, only five reported finding clear evidence of a relationship, four reported mixed results and 15 articles reported not finding the
R. Ostini (&) School of Population Health, The University of Queensland, Ipswich, QLD 4305, Australia e-mail: [email protected] T. Kairuz School of Pharmacy, St Lucia, QLD 4072, Australia
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expected relationship. Research on possible mechanisms relating health literacy to non-adherence suggest that disease and medication knowledge are not sufficient for addressing non-adherence while self-efficacy is an important factor. Other findings suggest a possible U-shaped relationship between non-adherence and health literacy where people with low health literacy are more often nonadherent, largely unintentionally; people with moderate health literacy are most adherent; and people with high health literacy are somewhat non-adherent, sometimes due to intentional non-adherence. Conclusion It is clear that relevant research generally fails to find a significant relationship between non-adherence and health literacy. A Ushaped relationship between these two conditions would explain why linear statistical tests fail to identify a relationship across all three levels of health literacy. It can also account for the conditions under which both positive and negative relationships may be found. Keywords Health literacy Knowledge Nonadherence Non-linear relationship Patient adherence Self-efficacy
Impact on practice •
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Improving patient’s health literacy is unlikely to improve adherence if the focus is purely on improving knowledge. Improving patient’s health literacy is likely to improve adherence if it enhances patient self-efficacy. Improved knowledge may have a role in this. People with low health literacy will require different approaches to improving adherence than people with high health literacy because their non-adherence is
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likely to be unintentional while high health literacy patients have a greater likelihood of intentional nonadherence.
Introduction The simple premise underlying research into the relationship between health literacy and medicine-taking, is that people who understand how to manage their health will be adherent, taking medication as prescribed. Initial findings from early research appeared to support the basic proposition that health literacy interventions could improve adherence [1, 2] but further research appeared to indicate that the relationship between non-adherence and health literacy was more ambiguous [3]. Results began to show that for self-reported medication nonadherence, the relationship with health literacy was not predictable [4]. Health literacy Health literacy typically refers to the ability of people to obtain, process and understand health information and services in order to make appropriate health decisions [5]. In practice, much of the focus has been on understanding information with far less emphasis on the components related to obtaining information and decision-making. The most frequently used current measures of health literacy, such as the Test of Functional Health Literacy in Adults: TOFHLA [6] and the Rapid Estimate of Adult Literacy in Medicine: REALM [7, 8], focus on literacy tasks such as reading and comprehension, reducing the decision-making component even further. The link between understanding and using information is largely taken for granted. Health literacy goes well beyond the narrow idea of reading health-related material [9]. We take health literacy to mean people’s capacity to manage their health, similar to the way financial literacy is taken to mean people’s capacity to manage their finances. In this sense, health literacy incorporates the four factors that the World Health Organisation (WHO) associates with nonadherence—that is, the health care team and system, the condition or illness, therapy (i.e., medication), and patient-related factors [10]. This also corresponds with the WHO definition of health literacy, which involves cognitive and social skills together determining the ability and motivation of individuals to promote and maintain good health [11]. According to WHO, this process requires knowledge, personal skills and confidence to take action.
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Non-adherence Adherence to medication has been associated with improved patient health outcomes and reduced unnecessary costs [12]. However, non-adherence to medicines is not necessarily the converse of adherence; the latter is defined as the extent to which patients take medications as prescribed by their health care provider [10], while nonadherence indicates non-initiation, suboptimal dosing regimens, or discontinuation of treatment [13]. The World Health Organisation (WHO) describes non-adherence as a ‘‘multi-determined problem caused by the interplay of [the] four factors’’ indicated above [10]. In contrast, adherence refers to the process by which patients take their medication as prescribed [13] and is associated with a degree of patient autonomy. The term is more patient-centred than ‘compliance’ which reflects a subservient patient role, [14] and ignores much of the prescriber-patient dynamic. ‘Persistence’ generally refers to patients who use continuous pharmacotherapy [15], from initiation to the last dose prior to discontinuation, [13] and is determined by using medication refills as a measure [15]. The terms are often used interchangeably and inconsistently. Interventions that improve and maintain adherence at optimal levels remain elusive, and studies have yet to define a non-adherent patient [16]. In this review, we focus on non-adherence while accepting that it is often treated as a lack of adherence rather than the distinct concept that it may be.
Aim of the review The goal of this paper is to clarify whether or not there is a clear, demonstrable, and meaningful relationship between health literacy and medication non-adherence. Beyond this, we will endeavour to identify and evaluate factors that may influence or affect the relationship between health literacy and medication non-adherence. In this way, we hope to explain the ambiguous results that have been reported for this relationship, identifying the conditions that promote or impede it, and consider possible mechanisms underpinning these effects.
Method Search strategy English language published reviews or original research on health literacy and non-adherence to orally administered medications were the focus of the search. Exclusion criteria included research with children; opinion, editorial or
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commentary articles; and conference abstracts. Both qualitative and quantitative research was included. Four bibliographic databases were searched. PubMed (1951-April 19, 2013) was searched using a comprehensive health literacy search based on a protocol developed by the National Library of Medicine [17], combined with a search using Adherence (text word) OR Persistence (text word) OR Concordance (text word) OR Compliance (mesh major topic) and a search using Non adherence (text word) OR Non compliance (text word) as search terms. The same specific terms were used in searches of the EMBASE (1974–April 2013), CINAHL (1981-April 2013) and EBSCO Health (1969-April 2013) databases, using database specific term mapping where available, or keyword searches where this was not available. Article evaluation and data extraction One author (RO) reviewed the titles of all articles identified to assess potential relevance, and then reviewed the abstracts of remaining articles to identify studies that met inclusion and exclusion criteria. Both authors extracted data from the remaining articles. The primary goal of data extraction was to identify the results of investigations into the relationship between health literacy and non-adherence and the possible causes of any relationship. In addition, descriptive features of study samples and analysis methods that could assist in evaluating strength of evidence were identified. Search results were also used to extract information on factors other than health literacy that had been investigated for their association with non-adherence. A narrative synthesis process incorporated the extracted information into three main areas: examples of factors associated with medication adherence, which may be relevant to any health literacy–non-adherence relationship; research investigating the relationship between nonadherence and health literacy itself; and research reporting potential mechanisms by which non-adherence and health literacy might be associated.
Results The initial search across the four databases produced 990 unique results (See Fig. 1). The title scan excluded 709 articles and the abstract scan excluded a further 158 articles on the basis of topic relevance and exclusion criteria. At this stage 45 conference abstracts were excluded from further analysis. The remaining 78 articles were each read by one of the authors (RO or TK). In a small number of cases, there was some ambiguity in the data extraction results, in which
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Fig. 1 Outline of search strategy and article appraisal results
case, both authors read the article. Sixteen of these articles provided evidence about factors that have been found to contribute to non-adherence. Some of these articles were among 54 articles subsequently excluded for the following reasons: they did not assess health literacy (37) or adherence/non-adherence (2); they were not conducted among adults (2), or with oral medications (3); they were commentaries/editorial (8) or conference abstracts (2). A final set of 24 articles provided the data to address the review aim, which was to clarify the relationship between non-adherence and health literacy, and included one systematic review and 23 original research articles. All original research articles reported on research using quantitative methods. Descriptive features of these articles are summarised in Table 1. Factors associated with medication adherence The 16 papers from which we extracted factors that contribute to non-adherence point to a range of different influences. The medication adherence model [18] categorised the factors that influence medication-taking behaviour as: (1) how the patient perceives their illness (e.g., its severity); (2) patients’ cognitive functioning (e.g., memory, comprehension); and (3) external cues and strategies (e.g., social support, reminder systems). Factors that contribute to adherence can also be categorised into patient related; medication related; logistical; and patient-provider relationship factors [19]. Patient related factors that have been identified in adherence research include: poor disease-related knowledge [19];
Study description
Systematic review; 7 studies; All United States
Observational cohort study; N = 310 veterans taking 5 or more medications; United States
Cross-sectional; N = 182 seropositive patients; tripledrug antiretroviral therapy; United States
Cross-sectional; N = 145; anti-retroviral therapy; United States
Cross-sectional; N = 398; diabetes medication; United States
Nested RCT; N = 235; Anti-retroviral therapy; United States
Cross-sectional; N = 302; HIV medication; United States
Cross-sectional; N = 200; Hypertension medication; United States
Cross-sectional; N = 275; Various medications; United States
Cross-sectional; N = 50 HIV-infected youth; Antiretroviral therapy; United States
Cross-sectional; N = 87; Anti-viral medication; United States
Cross-sectional; N = 85; Hypertension medication; United States
Cross-sectional; N = 1,366 adults with Type II diabetes; Antidepressant medication; United States
Cross-sectional; N = 204; HIV medication; United States
Cross-sectional; N = 155; ‘‘Mock’’ HIV regimen; United States
RCT; N = 281; Cardiovascular medication; United States
Cross-sectional; N = 57; Anti-retroviral medication; United States
Cross-sectional; N = 409; Coronary heart disease medication; United States
Reference
Loke et al. [38]
Mosher et al. [21]
Kalichman et al. [25]
Kalichman et al. [26]
Osborne et al. [27]
Paasche-Orlow et al. [28]
Colbert et al. [31]
Bhor et al. [32]
Gatti et al. [33]
Navarra et al.[35]
Graham et al. [36]
JoynerGrantham et al. [37]
Bauer et al. [39]
Waite et al. [40]
WaldropValverde et al. [41]
Noureldin et al. [42]
WaldropValverde et al. [43]
Kripalani et al. [44]
Table 1 Descriptive characteristics of articles included in review
Mixed relationships between non-adherence and low health literacy including better adherence associated with lower health literacy
Mixed/confounded measure of relationship between non-adherence and low health literacy
Mixed relationships between non-adherence and low health literacy
Significant multivariate relationship between adherence and health literacy
Significant multivariate relationship between non-adherence and low health literacy
Significant multivariate relationship between non-adherence and low health literacy
No significant positive relationship between non-adherence and low health literacy
Significant multivariate relationship between non-adherence and low health literacy
No significant positive relationship between non-adherence and low health literacy
No significant positive relationship between non-adherence and low health literacy
No significant positive relationship between non-adherence and low health literacy
No significant positive relationship between non-adherence and low health literacy
Bivariate relationship between non-adherence and low health literacy that did not survive multivariate adjustment
Mixed relationships between non-adherence and low health literacy in multivariate path models
Significant multivariate relationship between non-adherence and low health literacy
Significant multivariate relationship between non-adherence and low health literacy
No significant positive relationship between non-adherence and low health literacy
Some bivariate relationships between diabetes or cardiovascular medication adherence and health literacy, but did not remain following multivariate adjustment; one article showing lower health literacy associated with greater adherence; health literacy can be associated with disease or medication knowledge but not adherence
Conclusion
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Cross-sectional; N = 125; Diabetes medication; United States
Cross-sectional; N = 179; Warfarin; United States
Prospective; N = 1,549; Various medications; United States
Bains and Egede [48]
Fang et al. [49]
Gazmararian et al. [50]
No significant positive relationship between non-adherence and low health literacy
Cross-sectional; N = 186 HIV-infected youth; HIV medications; United States Murphy et al. [47]
Bivariate relationship between non-adherence and low health literacy that did not survive multivariate adjustment
RCT; N = 118; HIV medication; United States Holzemer (et al. [46]
No significant positive relationship between non-adherence and low health literacy
RCT; N = 420; Cardiovascular medications; United States Kripalani et al. [45]
No significant positive relationship between non-adherence and low health literacy
Study description Reference
No significant positive relationship between non-adherence and low health literacy
Table 1 continued
poor treatment knowledge [20]; poor medication knowledge [20, 21]; impaired cognitive functioning [19]; having a history of non-adherence [20]; hectic schedules/work [22]; lack of social support [23–26]; education [23, 25]; socioeconomic status [23]; emotional distress [25, 26]; and illness duration [27]. A history of alcohol problems, drinking to intoxication and injecting drug use were also associated with poorer adherence in a sample of 235 people living with HIV/AIDS [28]. In another study among people living with HIV/AIDS who had demonstrated low health literacy (n = 188), a multivariate analysis showed that food insufficiency and hunger predicted non-adherence over and above the effects of depression, internalised stigma, substance abuse and HIV-related social stressors [29]. In this research, adherence was not related to gross cognitive functioning. Similarly, general reading ability and understanding were not associated with non-compliance in an older sample of 126 ambulatory care respondents from mixed socio-economic backgrounds [30]. Patient beliefs are a distinct and important set of patient factors. They include: beliefs about their disease [23]; unrealistic or uninformed expectations of risk, including risk of adverse effects [23]; lack of self-efficacy [23, 31]; and disbelief about medication efficacy [23, 32, 33]. Medication related factors include: adverse effects [19, 34]; polypharmacy/multiple medications [19–21]; complex medication regimens [20, 28]; safety concerns [20]; incomplete or confusing information on prescription labels [22]; administrative processes (i.e., logistical factors) for obtaining medications [20], intent to adhere and positive outcome expectancy [35]; and higher adherence norms [36]. Patient-provider relationship factors include: generally having a poor relationship [23]; providers not fully explaining how to take a medication [22]; and different cultural models exacerbating distrust of the health system [22]. A complex factor that does not fit easily into any of the four categories above is cost. This is a clear barrier to adherence for some people [23, 34] but can be considered a combination of patient-related, medication-related and logistical factors. Rust and Davis [34] reported the results of an online survey of almost 10,000 adults with chronic medical conditions which showed that not filling prescriptions (primary non-adherence) or taking medication incorrectly resulted from forgetfulness (24 %); side-effects (20 %); cost (17 %); denial that medication was needed (14 %); and inconvenience (10 %). A survey of 85 emergency room patients found that they attributed their nonadherence to inability to pay (36 %); feeling better (35 %); feeling worse (25 %); and difficulty remembering to take medication (32 %) [37]. Participant frustration with
No significant positive relationship between non-adherence and low health literacy
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Conclusion
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inconsistent health information from doctors and pharmacists was reported from focus groups among underserved African American women (n = 24) who had completed breast cancer treatment at least one year previously [34]. Many of these women reported receiving information through churches, community centres, and word of mouth—with the attendant possibility of misinformation. Participants also showed differing levels of satisfaction in seeking information, particularly from ‘busy’ pharmacists. Relationship between non-adherence and health literacy A systematic review of research on the relationship between non-adherence with diabetes or cardiovascular medication and health literacy, found no consistent links in the seven relevant studies reviewed [38]. Bivariate relationships were identified in some cases but did not hold up to adjustment in multivariate analysis, primarily with demographic variables. Contrary to expectations, one study found lower health literacy associated with higher selfreported medication adherence. In a secondary finding, a number of studies showed a relationship between health literacy and disease or medication knowledge, while showing no association with greater medication adherence [38]. A relationship was found between non-adherence and health literacy in five of the 23 articles reporting original research into the relationship [25, 26, 39–41]. Most of these were well-designed studies, unlike the Kalichman et al. [25] study, which had a small sample and where the relationship was only positive for respondents with a greater number of years of education. Waldrop-Valverde et al. [41] reported a very carefully designed study that was however, unusual in using a simulated measure of adherence. While this standardised the measurement procedure it leaves some question about the ecological validity of the results. Bauer et al. [39] used a screening measure of health literacy that is rarely used, reporting associations between health literacy and medication non-persistence before the first refill and at 180 days but not for primary non-adherence (in any analysis) or non-persistence at 365 days in multivariate analysis [39]. Four studies reported mixed results [27, 42–44]. A larger cumulative medication gap was associated with low health literacy in the Kripalani et al. [44] study but selfreported adherence was not. Noureldin et al. [42] conducted a well-designed RCT but only found an association between non-adherence and health literacy for two of seven adherence measures in the usual care arm of the study. Osborn et al. [27] reported the results of a path analysis which only showed a relationship between non-adherence and health literacy when numeracy was included in the path model. Finally, the study reported by Waldrop-
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Valverde et al. [43] confounded health literacy and cognitive functioning, showing adherence to be associated with a group low in cognition health literacy. This study also had a very small sample (n = 57). A clear majority of articles in this review (15 of 23), reported not finding significant positive relationships between non-adherence and low health literacy [21, 28, 31–33, 35, 37, 42, 44–50]. Some of these studies had small sample sizes and consequently likely had low power to detect a relationship. However, most were well-designed cross-sectional studies with reasonable samples; two studies used a randomized controlled trial design [28, 45]; and Gazmararian et al. [50] had the advantage of using a prospective design in a large, ethnically and geographically diverse population, using a preferred measure of adherence [51]. Two of the 15 studies found a bivariate relationship between health literacy and non-adherence that did not survive adjustment for the effects of other relevant variables in multivariate analysis [28, 50]. Counter-intuitively, better adherence was associated with lower health literacy for a self-report measure of adherence in the study reported by Kripalani et al. [44]. Potential mechanisms for an association between health literacy and non-adherence Factors found to be associated with non-adherence, which may have a role in the relationship between health literacy and non-adherence, include education, cognitive functioning, relevant knowledge, information sources, social support and self-efficacy. The Loke et al. [38] review found that health literacy was associated with disease and medication knowledge. Although research has also shown these factors to be associated with non-adherence, they have not been found to result in a relationship between health literacy and non-adherence. Research that directly addresses potential mechanisms in any relationship between non-adherence and health literacy is rare. In one of two such examples identified in this review, a finding that many patients in a hospital emergency room sample felt that nothing they did would help their blood pressure, was used to explain the fact that they did not take medications despite good health knowledge/ literacy about blood pressure [37]. This suggests that these patients had low self-efficacy, and implicitly, low medication efficacy beliefs as well. In another study, reasons for medication discrepancies 48 h after hospital discharge among 254 communitydwelling seniors (70 years or older) differed across health literacy levels [52]. Discrepancies for those with inadequate or marginal health literacy were significantly associated with lack of understanding about how to take the
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Fig. 2 Representation of theoretical relationship between health literacy and non-adherence
medication (unintentional non-adherence). In contrast, people with adequate health literacy were significantly more likely to have medication discrepancies as a result of choosing not to follow instructions—despite understanding those instructions [52]. The Lindquist et al. [52] findings suggest that high health literacy respondent non-adherence may be for different reasons than non-adherence in those with low health literacy. The findings of Lindquist and colleagues may have a bearing on the results reported by Waite and colleagues [40] who found non-adherence to be highest in those with low health literacy and lowest in people with moderate health literacy. Respondents with high health literacy had higher levels of non-adherence than those with moderate health literacy. These results suggest a U-shaped relationship between nonadherence and health literacy (see Fig. 2). Figure 2 represents a model of the relationship between health literacy and non-adherence suggested by this research. It shows nonadherence to be highest among those with low health literacy, lowest among those with moderate health literacy and then higher among people with high health literacy. There is some evidence that such U-shaped relationships are often found among socially controlled behaviours [53].
Discussion This review finds that there may be distinct differences between low, moderate and high health literacy individuals
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and their non-adherent behaviour. This could explain a possible U-shaped curve in the relationship between nonadherence and health literacy, and also explain positive and (unexpected) negative associations, which may exist around the inflexion point of the curve. If there is a U-shaped relationship between health literacy and nonadherence, then a statistical test fitting a linear model across all three levels of health literacy could be expected to be relatively flat and show no significant relationship. That result was the most common finding in the research reviewed. If a test were to be applied to a sample that was restricted to the low-to-moderate range of health literacy, it would be expected to show that better health literacy is associated with less non-adherence. Furthermore, in research with only moderate-to-high health literacy participants, a linear model could be expected to show the counterintuitive result, with better health literacy associated with poorer adherence; although rare, this has been reported [44]. The possibility of a U-shaped relationship between nonadherence and health literacy warrants further investigation as it has implications for research and practice. It may help researchers design studies with a better understanding of the implications of sampling for the strength and direction of expected associations. In practice terms, such a relationship suggests that people with low health literacy need help—likely with self-efficacy, through targeted knowledge and improved support. People with moderate levels of health literacy may not require intervention, while people with high health literacy may in fact be intentionally nonadherent. Given the implied capacity of these people to manage their health, the non-adherence may be warranted. In that case, non-adherence in a person with high health literacy would provide an opportunity for prescribers to revisit the treatment strategy and perhaps identify better options for non-medication-takers. There are times when medication prescribing can be ceased [54, 55] and nonadherence in people with high health literacy may reflect an appreciation of this for their individual situation. Polypharmacy may be an example of such a situation, as it often reflects suboptimal prescribing. Almost half of the 23 articles investigating the relationship between non-adherence and health literacy identified in this review were published recently, from 2010 onwards. This burst of activity, which often reported sophisticated research programs, confirmed that it is unusual to find a clear relationship between non-adherence and health literacy. This is due, in part, to limitations in the way both are measured. Nevertheless, the findings presented here are supported by their basis in two dozen studies that show a consistent trend. The finding that there is unlikely to be a direct linear relationship between non-adherence and low health literacy
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undermined the goal of this review to identify mechanisms linking heath literacy and adherence. However, the results of this review also point toward two potentially fruitful avenues of investigation. One promising activity is to untangle the ways in which health literacy, self-efficacy and medication use are interrelated. The second area that promises greater clarity involves directly investigating the strength of the proposition that low health literacy and nonadherence are non-linearly related. Investigating non-adherence within a health literacy framework can place the focus of medication taking on the potential medication-taker in a non-judgemental way, by highlighting the many interconnected components that contribute to a person’s ability to manage their health in the context of medication taking. A prescriber’s recommendation to take a medicine is one factor in the broad health literacy context; it may not, in practice, be the most influential factor. In many situations, this can lead to poor health outcomes. In some situations, non-adherence to the prescriber’s recommendation may be the most appropriate outcome for a patient. Understanding this framework will help researchers and clinicians realise that the goal of eliminating all instances of nonadherence is mistaken, and will contribute to the development of more effective means of reducing non-adherence when that non-adherence is not in the patient’s best interests.
Conclusion The evidence is clear that medication knowledge alone is insufficient for addressing non-adherence, and that addressing non-adherence within the framework of health literacy is not as straightforward as was initially assumed. Medication factors and self-efficacy influence medication-taking and must be considered as part of the health literacy equation. Funding
None.
Conflicts of interest
None.
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