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Keywords:

  • adherence;
  • complex interventions;
  • patient education;
  • pharmacists;
  • type 2 diabetes mellitus

Summary

  1. Top of page
  2. Summary
  3. Background and Objective
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Implications for practice/further research
  9. Conclusion
  10. Statement
  11. References

Background and objective:  Pharmacists are now adopting a crucial role in the management of chronic illness in primary care, providing diabetes care and advice. This review aims to show whether a range of diabetes care interventions delivered by pharmacists is successful in improving adherence to medication.

Methods:  The studies reviewed formed a subgroup of a Cochrane review on interventions to improve adherence to medication in people with type 2 diabetes. Search terms were ‘type 2 diabetes mellitus’ and ‘compliance’ or ‘adherence’. Studies were included if they assessed adherence to medical treatment specifically, rather than other aspects of self-management. Out of the 21 studies selected for review, five described an intervention delivered by a pharmacist.

Results and discussion:  Two studies reported on attempts to improve adherence focused on the taking of medication. A system of reminders and packaging improved medication adherence, but measuring medicine taking through pill counts or Medication Event Monitoring System was not effective. Three studies evaluated pharmacist-led integrated management and education programmes designed to improve glycaemic control for under-served patient populations. They all succeeded in lowering glycated haemoglobin, but it remains unclear whether this resulted from improved patient adherence.

Conclusion:  This review indicates a potential benefit of pharmacist interventions to improve medication adherence in diabetes, especially in providing patient education.


Background and Objective

  1. Top of page
  2. Summary
  3. Background and Objective
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Implications for practice/further research
  9. Conclusion
  10. Statement
  11. References

Diabetes mellitus is one of the most common chronic diseases. The number of people with type 2 diabetes mellitus is continuously increasing worldwide. There are currently more than 194 million people with diabetes worldwide, and half of them have not yet been diagnosed (1). Strict glycaemia, good lipid management and blood pressure control seem to be of the utmost importance in order to prevent vascular complications, macro- and micro-vascular disease being the most important diabetes related causes of morbidity and mortality (2–7).

The risk of vascular complications increases with the plasma glucose concentration and the duration of diabetes, depending on age, gender, genes and life-style (8). Once diabetes has been diagnosed, life-style adaptation is indispensable, and treatment with hypoglycaemic agents is often unavoidable, as more than 50% are known to not adhere fully to recommendations on diet and exercise (9).

The management of diabetes is a complex, lifelong process requiring a great deal of effort on the part of the patient. The patient, more than any health care provider, is the key to successful management. Poor management can result in a number of serious complications. For this reason, non-adherence with therapeutic regimens among diabetes patients has been a continuing problem for both patients and health care providers (9, 10). A recent systematic review of adherence to medication for diabetes found that many patients were poor compliers with oral hypoglycaemic treatment (adherence ranged from 67% to 85% of OHA doses); however, the Medication Event Monitoring System (MEMS), in which the opening of pill containers is automatically recorded, was useful in improving adherence and diabetes management for individual patients (11).

In the US and the UK, pharmacists are now adopting a crucial role in the management of chronic illness in primary care, providing diabetes care and advice. In the US, this takes place within integrated health care systems (12). In the UK, pharmacists are increasingly incorporated into an extended diabetes team (13, 14). A pilot study conducted in Scotland found that structured input from a community pharmacist as part of a multidisciplinary diabetes care team reduced glycated haemoglobin and was well accepted by GPs and patients (15). In the Netherlands, a panel of 14 pharmacists and technicians with considerable experience in giving advice to people with type 2 diabetes concluded that patient education activities by pharmacists should be directed at improving dosage adherence and awareness of side effects (16).

Pharmacists are uniquely positioned to educate patients on the importance of medication adherence (17, 18). They can draw on their drug expertise and knowledge of the medication regimen followed and prescription refills requested by the individual patient. Ideally, a personal relationship of trust between patient and pharmacist can be harnessed to improve diabetes care and outcomes. The benefits of pharmacist-led care have been shown in evaluations of the Asheville Project, a community-based, pharmacist-led programme to improve self-management of people living with diabetes in the state of North Carolina in the United States (19). The integration of pharmacists into a primary health care team has also been efficient for antihypertensive medication (20). Pharmacist-led interventions to improve diabetes care have included case management by a pharmacist (21), physician-supervised, pharmacist-managed primary care clinics (22), medication algorithms (23) and the creation of a database tracking patient outcomes (23). These studies report on a range of successful methods of pharmacist involvement with diabetes care. However, they were not included in this review as they did not measure adherence to medication. A recent study included self-reported adherence in a pharmacist-led intervention (24), but found no significant difference for this outcome. This review aimed to capture the evidence on the potential benefits for people living with type 2 diabetes from pharmacist interventions focusing on increasing adherence to medication.

Methods

  1. Top of page
  2. Summary
  3. Background and Objective
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Implications for practice/further research
  9. Conclusion
  10. Statement
  11. References

Literature search

The five studies included in this review (25–29) form a sub-group of a Cochrane review to assess the effects of interventions to enhance adherence to type 2 diabetes patients’ medicine taking (30). Studies were identified through a search of the Cochrane Library databases, the Metabolic and Endocrine Disorders Group Specialised Register, Medline (1966–2001), Embase (1980–2001), PsycINFO (1980–2001), ERIC (1980–2001), Dissertation and Sociological Abstracts (1980–2001), CINAHL (1982–2001), the metaRegister of Controlled Trials, by SUMSearch and Google search engines on the Internet. Literature in the area was monitored until the end of 2005, but no new studies measuring adherence to medication were found. Related studies on pharmacist interventions informed the Background and Discussion sections of this article. Search terms were ‘type 2 diabetes mellitus’ and ‘compliance’ or ‘adherence’, combined with terms related to health behaviour, self-management and patient empowerment.

Study selection

Studies in primary care, outpatient, community settings and hospital settings were all included. Randomized and quasi-randomized controlled trials (RCTs), controlled before and after studies, observational studies and cohort studies were all included. Two researchers independently read abstracts and selected articles for review. Full articles were retrieved for further assessment if the information given suggested that the study:

  • 1
    Included patients with type 2 diabetes mellitus.
  • 2
    Assessed adherence to medical treatment specifically, rather than other aspects of self-management.
  • 3
    Measured an outcome of an intervention enhancing adherence.
  • 4
    Used a design as described in the inclusion criteria for study design.
  • 5
    For this review: the intervention was delivered by a pharmacist.

Data extraction

Two reviewers (HH and AL) independently extracted data from the selected papers, using a structured Excel spreadsheet. We were not blinded with regard to author or journal. We extracted relevant data for randomization quality criteria, participant details, intervention details, outcome measures, baseline and post-intervention results, and main conclusions.

Outcome measures, following Roter's categories of adherence indicators (31), included:

  • 1
    Health outcomes (morbidity, hospitalization, mortality, referral).
  • 2
    Direct indicators (blood and urinary glucose level, glycated haemoglobin, weight, blood lipids, serum creatinine, blood pressure, smoking habits).
  • 3  
    Indirect indicators (pill counts, refill records).
  • 4
    Subjective reporting (self-reported adherence, well-being, perceived health quality, patient satisfaction or functional status measured using validated instruments).
  • 5
    Utilization (appointment making and keeping, use of preventive services).

The quality of the studies was assessed, drawing on data extracted with regard to study design, number of participants, method of patient randomization, patient and outcome assessment blinding, description of losses to follow-up and quality of reporting of outcomes (see Tables 1 and 2). Overall quality was graded as A (good), B (medium) or C (poor).

Table 1.   Details of each study included in this review
ReferenceMatsuyama 1993Coast-Senior 1998Jaber 1996Davidson 2000Skaer 1993
  1. MEMS, Medication Event Monitoring System.

Group sizeI 15 C 17I 23 C 0I 17 C 22I 89 C 92I1 : 79, I2 : 53, I3 : 48. C 78
InterventionAddition of MEMS data to pill count data to inform pharmacistsPharmacists initiate insulin and adjust doses; patients required to self-test blood glucose.Care provided by pharmacist: adjustment of doses; diabetes education; training on recognition of hypo- and hyperglycaemia; self measured blood glucose. Treatment titrated to targets.Pharmacist led diabetes management program following physician written algorithm for glycaemic and lipid control.Mailed prescription-refill reminders (I1), specialized packaging (I2), or a combination of both (I3)
ControlPill count datan/aStandard careStandard careStandard care
Method of measuring adherenceMEMS and pill count so should not be compared directly.Glycated haemoglobin, fasting blood glucose, Random blood glucoseBlood glucose control, self-recorded adherence and self monitoring of blood glucose logs (mentioned but not specified and no data)Not described, possibly speculationMedication possession rate (MPR), number of days’ supply of medication obtained over 360 days of the trial
Net effectMEMS adherence rate [no. of days with openings-recorded-as-prescribed/no. of days observed No sig. change in non-adherence rate of 60%Glycated haemoglobin change: 11·1 to 8·9 (2·2%; P < 0·01) Fasting blood glucose change 219 to 154 (P < 0·01) Random blood glucose change from 236 to 154 (P < 0·01)Health Status and Quality of Life: no differences between or within groups. Final glycated haemoglobin 9·2% (SD 2·1). Higher decline in higher start levels (r = 0·72, P < 0·01). Glycated haemoglobin change in intervention group 2·2 ± 2. (P < 0·01), sig. change compared to baseline and between groups.Intervention: Glycated haemoglobin change −0·8 (SD 0·2) n = 50, P < 0·03 for difference between changes. P < 0·001 between baselines, as intervention group initially poorer controlled Control: Glycated haemoglobin change -0·05 (SD 0·3) n = 27 blood glucose monitoring was ‘assessed’ but not told howOutcome MPR C: 0·58 (SD 0·07), I1: 0·73 (SD 0·09), I2:0·71 (SD 0·09), I3: 0·87 (SD 0·08). All intervention groups increased MPR significantly compared to control, P < 0·05. Also I3 higher increase than I2 or I1, P < 0·05. No difference between I1 and I2.
Conclusions of authorsWith MEMS, rather than pill counts only, pharmacists could make recommendations regarding patient education before resorting to pharmacologic manipulations.Pharmacists can initiate insulin and adjust doses, which reduces glycaemia. This is an alternative to hospitalization for insulin initiation and saves $103 950 for 15 patients.Optimizing oral hypoglycaemic agents and enhancing patient understanding of disease by pharmacists reduced glycaemia. The study establishes the effectiveness of pharmacist-provided intervention in the specific management of type 2 diabetesDiabetes care given to a poor minority population in a free clinic compared favourably with standard care. A sicker and more poorly controlled cohort who received care from pharmacists following algorithms had even better outcomes.The use of prescription refill reminders and specialized packaging will enhance MPR for sulfonylurea therapy. Using both will decrease utilization relative to standard care. Pharmacists can reduce costs and increase adherence.
Comments on outcomesNot focused on adherence, but on testing the role of information in forming pharmacists’ recommendations; MEMS gave more accurate information than pill counts.Intervention was effective but not aimed at increasing adherence. Glycaemia was the only outcome measure; adherence to self-testing was not reported, though education on this was part of the intervention.Aimed at underserved urban African-Americans, but does not specify what the intervention's specific benefit for this group would be. No adherence measures reported; though it is stated that it was targeted.Adherence included as possible obstacle to programme's success, but not addressed by intervention. Non-adherence was speculation by the authors only, they present no evidenceEconomic costs were the main target of the study, calculated as sum of anticipated prescription, physician, hospital and laboratory costs
Table 2.   Quality assessment
ReferenceMatsuyama 1993Coast-Senior 1998Jaber 1996Davidson 2000Skaer, 1993
  1. RCT, randomized controlled trail.

Randomization appropriateUnclearN/AUnclearN/AY
Outcome assessment blindNNNNN
Patient blindYNNNN
Losses to follow-upDescribedDescribedDescribedNot describedNot described
Study designRCTBefore and AfterQuasi RCTCase–control trialQuasi RCT
Quality of reporting of outcomesIncomplete and unclear. Measure in intervention group was calculated in a different way from in the control group, so should not be compared directly.Good, but restricted to glucose controlVery confusing to read, no parameters for adherenceMediumDifficult to ascertain as very little data presented
Overall qualityB (medium)B (medium)B (medium)B (medium)B (medium)
Comments on validityVery small samples; cannot draw any significant conclusions from this paper. Outcome measures showed differences between intervention and control but the implications were not specified.No data on self-testing, though education on this was part of the intervention. No data on adherence.Small numbers, relatively short time; adherence-related measures not quoted in text. In several other outcome measures it was unclear whether change was measured within or between groupsVery small samples. No measurement of adherence other than appointment keeping, no reporting on morbidity/adverse effectsData not presented so conclusion cannot be confirmed. MPR used as proxy for actually taking medication. No data on impact on health or quality of life.

We then amalgamated the results, comparing every item of every study and resolving discrepancies by discussion or by agreeing that the data reported were ambiguous.

Results

  1. Top of page
  2. Summary
  3. Background and Objective
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Implications for practice/further research
  9. Conclusion
  10. Statement
  11. References

Study Characteristics

A total of 4387 references were identified for the whole systematic review, of which 74 studies were retrieved in full text, and 21 of those were selected for review. This low rate was mainly due to the fact that though many authors stated that their study was about compliance or adherence the core issue was self-care or some aspect of diabetes management, and there was no report of any assessment of adherence to medication. Five of the studies selected were of pharmacist interventions; study characteristics are reported in Table 1. All of the studies were conducted in the United States. Two papers reported interventions directly geared towards adherence to medication dosage regimes, calculating adherence rates as percentage of days with medication taken as prescribed (28, 29). The other three studies were of comprehensive programmes where pharmacists initiated insulin, adjusted doses, provided diabetes education and acted on the results of patients’ self testing of blood glucose (25–27). Participant numbers were very low in three studies (25, 27, 28) which made it hard to draw conclusions from these papers. One study (28) was a RCT with patient blinding. Two studies (27, 29) were recognized as quasi-RCTs as the patients were not blinded. None described blinding of outcome assessment. The other two were designed as pre–post study (25) and as controlled clinical trial (26).

Measurements and reporting of outcomes (see Table 1)

Adherence to dosage.  Only two studies (28, 29) actually reported a measure of adherence to medication, adherence to dosage ‘as prescribed’. One study (29) calculated an adherence rate from pharmacy records, as the number of days’ supply of medication obtained over 360 days of the trial, divided by 360. The authors concluded that a combination of prescription-refill reminders and specialized packaging significantly increased the adherence rate compared with control. The paper presents a hypothetical post-period expenditure sum for the intervention group but not for the control group, stating only the intervention group's expenditure as significantly lower. The other (28) used a MEMS to determine an adherence rate as the percentage of days with ‘openings recorded as prescribed’. This was compared with the method of ‘pill count’, i.e. unwitnessed counts of pills remaining performed by an investigator at each prescription refill visit. The main outcome measures were the quantity and types of pharmacist recommendations regarding diabetes therapy based on those two methods of measuring adherence. Intervention and control group received identical medication containers, though only the intervention group's openings were recorded. The effect of providing patients with a MEMS vial on their adherence and blood glucose control could therefore also be assessed. The authors reported exact figures for adherence rates but not metabolic control, observing that receiving MEMS vials did not significantly decrease non-adherence or improve metabolic control. Compared with the pill count method, MEMS provided accurate data about timing of container openings (but not tablets taken out or actually ingested). Although MEMS increased the recommendations for patient education made by pharmacists, it did not enhance adherence. Moreover, it would be expensive and impractical to use with a large number of patients over a long time. Nevertheless, the authors described MEMS as a valuable tool for patient education provided by pharmacists. In both papers, adherence rate was the only patient outcome reported, and no measurements of glycated haemoglobin or other diabetes specific indicators were reported [other than ‘no significant change’ (28)]. Thus, these two studies show that reminders and packaging can improve medication adherence, but MEMS was not seen to be effective (see Table 1).

Pharmacist management programmes.  Although the above studies concentrated on possible measurements of adherence to medication and the effect of enhanced medication packaging and reminders, the other three studies evaluated integrated management and education programmes designed to improve glycaemic control for under-served patient populations with special needs. The improvement of adherence was an explicit aim of two of these interventions (25, 27); another reported problems with adherence as a possible obstacle for the programme's success (26). One paper (25) reported the outcomes of a programme of direct pharmacist involvement in the care of older veterans. In addition to a change of 2·2% in glycated haemoglobin in the intervention group, fasting and random blood glucose were reported, as were hypoglycaemic episodes. The second (27) studied the impact of a pharmacist-delivered comprehensive care model on under-served urban African-Americans. The author also reported a decrease of glycated haemoglobin by 2·2% in the intervention group. Renal function parameters, fasting blood glucose, blood pressure and lipids were also included as outcomes; however, it is unclear whether differences reported were within or between intervention and control groups, so the data cannot be usefully interpreted. More hypoglycaemic episodes, reported as mild to moderate, occurred in the intervention group than the control group (17 vs. 2) This was the only study to measure health status and of Quality of Life, but no significant difference was found. A third paper (26) evaluated an algorithm-based diabetes management programme carried out by the pharmacist in a free medical clinic. In this study, glycated haemoglobin changed by 0·8% in the intervention group. The author also found improvements in outcomes related to the process of care, i.e. increased utilization of foot and eye exams, blood glucose and dipstick tests.

Discussion

  1. Top of page
  2. Summary
  3. Background and Objective
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Implications for practice/further research
  9. Conclusion
  10. Statement
  11. References

This review has found evidence of the role of the pharmacist in improving diabetes care by addressing the important issue of adherence to medication, although this was not explicitly measured in three of the studies (25–27). The first role is in providing improved management for patients with diabetes by operating a reminder system, fine tuning medication, collecting and acting on adherence and self-monitoring data. The second role is in providing better care by supplying patient education and facilitating communication between patients and health care professionals. Ideally, this double role of the pharmacist could greatly improve not only adherence, but also patient satisfaction and quality of life. The difficulty of evaluating interventions aimed at enhancing adherence to medication lies in actually measuring adherence. Adherence is complex, can vary over time and is bound up with the need for integration with social life as well as health beliefs (32–34). People with diabetes can be non-adherent out of forgetfulness or because the regimen is too complex to fit in with daily life, but also because of culturally based ambivalence towards ‘Western’ medicine (35), worries about weight gain (11) or side effects (36). However, there are several validated scales that capture aspects of adherence, e.g. the Diabetes Time Management questionnaire (37), the Diabetes Activities Questionnaire (TDAQ) (38) or Greco et al.’s (39) 14-item self-care inventory. These could be used or adapted to assess the efficacy of a pharmacist intervention on adherence to medicine taking.

The two studies using a pill count or MEMS system (28) or pharmacy records (29) to directly measure adherence to medication did not relate their findings to other aspects of diabetes self-management like self-monitoring of blood glucose or patient self-efficacy. In the former, measurement of adherence was a by-product of comparing the effectiveness of two systems of measuring the amount of medication taken (28). The latter succeeded in improving adherence in patients who forgot to take a tablet or request a prescription refill (29). However, the authors did not address the issue of deliberate non-adherence. Moreover, adherence rates were calculated over the whole study period in both studies. With MEMS, it was possible to monitor number and timing of doses actually taken by patients during each day, but they too were converted into an overall adherence rate, regardless of any specific patterns. This is important as patients may use higher doses of medication before blood glucose testing in order to compensate for lower doses used at other times (40). Although an overall adherence rate may be useful for the pharmacist to improve the management of people with diabetes, it cannot capture the complexity of problem solving in day-to-day adherence behaviour, which has been likened to the intuitive responses of an expert chess player (41).

The three papers reporting on integrated care programmes involving pharmacists did not address difficulties with measuring adherence to medication at all. Two used the measurement of glycated haemoglobin and patient recorded blood glucose (25, 27) as proxy indicators for whether medication had been taken. This can be considered unsatisfactory. Although improvements in self-management across the board have been associated with improved metabolic outcomes, the exact effect of medication adherence on glycaemic control has not yet been adequately quantified because of a lack of studies comparing reliable methods of measuring medication adherence to HbA1C levels (11). One study (27) only included self-reported adherence; regrettably, no results are reported in the paper. This is surprising, as complex pharmacist interventions aimed at improving the quality of care, like patient education and help with self-management, might prove highly efficient, especially with the disadvantaged populations that the authors studied. However, the authors did not stress the importance of these outcomes nor seek to establish a direct link with adherence to treatment. Studies with small numbers of participants (25, 27) would have proved valuable for a qualitative exploration of the impact of these interventions on the quality of care for their under-served patient populations. Even though increasing adherence was only one of several stated aims of pharmacist-led management programmes, we consider that a discussion of the difficulties involved in measuring adherence and the inclusion of indirect outcome measures like self-reporting or testing diaries would have been appropriate.

Only one study (29) calculated the cost-effectiveness of an intervention to increase adherence as the sum of anticipated health care costs. The authors found that improved medication packaging would significantly reduce the expected use of costly services. None of the papers addressed the impact of co-payment for medications made by patients on their levels of adherence, although it is significant within a United States context: participants in the Asheville project stated that waived co-payments for diabetes medications and related supplies was the decisive incentive for enrolling in the project (42).

Limitations

  1. Top of page
  2. Summary
  3. Background and Objective
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Implications for practice/further research
  9. Conclusion
  10. Statement
  11. References

The obvious limitation of this review is the small number of studies reviewed. Very few specific pharmacist interventions have been studied in the time frame of the review, although pharmacists are increasingly being included into multidisciplinary diabetes care teams. Moreover, the interventions reported varied widely in nature, from improvement of medication packaging and dosage measurement to more complex interventions. Thus, this review could not conduct a meta-analysis of results, but instead offers a description of the interventions and a discussion of the salient issues in connection with adherence. Another limitation is the absence of a definition of adherence or measured adherence data in the complex interventions (25–27), where the authors rely on HbA1C as a proxy measurement.

Implications for practice/further research

  1. Top of page
  2. Summary
  3. Background and Objective
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Implications for practice/further research
  9. Conclusion
  10. Statement
  11. References

Although numbers of participants in the studies reviewed are generally small and outcome reporting is patchy, they show promising beginnings in pharmacist-led diabetes management programmes in which pharmacists are part of a multi-disciplinary care team. Although there are many excellent pharmacist-led interventions with the aim of increasing adherence to medication, this adherence is not measured. For example, an evaluation of the Asheville Project found improvements in patient metabolic outcomes and service utilization, with a significant increase in prescription cost pointing towards increased medication adherence. However, patient-reported outcomes centred on adherence to 6-monthly A1c and foot exam, self-testing of blood glucose, and use of ace-inhibitors, but not hypoglycaemic medication (43).

Clearly, more studies of pharmacist interventions are needed that specifically address adherence to medication. Quantitative studies should recruit sufficient participant numbers, clearly define adherence (33) and select and report appropriate means of measuring the various aspects of adherence. Most of the pharmacist interventions reported are complex, especially those involved in more holistic care programmes. This means that researchers should take on board recent debates about how best to design RCTs of complex interventions. This can avoid significant variation in intervention delivery, and possible bias due to inappropriate blinding processes, while capturing the salient outcomes of the intervention even though they might be hard to measure (44–46). Another possible avenue for researchers is a qualitative approach focusing on the gains to be made by pharmacist involvement in care both for diabetes care teams and patients. Researchers could also adopt a mixed method approach to capture the aspects of the intervention that fall outside the confines of the RCT design (45).

Cramer has raised the issue of the dearth of studies in which adherence purported to have been improved was appropriately measured (11). Unfortunately, this finding is also borne out by the studies we reviewed. Moreover, in studies where the authors stated that measures such as patient self-reporting or testing diaries were used, these findings were not reported. To encapsulate the complex process of adherence, either blood glucose control or pill count measurements on their own are of limited value. Measurements actually addressing the day-to-day fluctuations of adherence, such as patient questionnaires or diaries, would provide valuable complementary information.

Conclusion

  1. Top of page
  2. Summary
  3. Background and Objective
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Implications for practice/further research
  9. Conclusion
  10. Statement
  11. References

Although the studies reviewed in this paper are of limited quality, they indicate the potential benefit of pharmacist interventions to improve medication adherence in diabetes, especially in the context of patient education. Further studies into this area are needed, which should address the complexities of defining and measuring adherence to treatment, and include outcome measures that capture the complexity of adherence.

Statement

  1. Top of page
  2. Summary
  3. Background and Objective
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Implications for practice/further research
  9. Conclusion
  10. Statement
  11. References

This is a version of a Cochrane review, which is available in The Cochrane Library. Cochrane systematic reviews are regularly updated to include new research, and in response to feedback from readers. If you wish to comment on this, please contact the Metabolic and Endocrine Disorders Group, c/o Susanne Ebrahim (ebrahim@uni-duesseldorf.de).

References

  1. Top of page
  2. Summary
  3. Background and Objective
  4. Methods
  5. Results
  6. Discussion
  7. Limitations
  8. Implications for practice/further research
  9. Conclusion
  10. Statement
  11. References
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