Interventions for improving medication adherence in patients with idiopathic Parkinson's disease

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

In this systematic review we will summarise all randomised controlled trials (RCTs) of interventions aimed at enhancing medication adherence in Parkinson's disease , where adherence and clinical outcomes were assessed.

Background

The symptoms of Parkinson's disease are debilitating for many people. Medication represents the main therapeutic approach and its correct use can substantially improve symptoms and quality of life. However, as with all chronic conditions, poor adherence to medication is common in Parkinson's disease . Non-adherence to anti-parkinsonian drugs is a major reason for poor symptom control, therefore there is a need for targeted strategies to address this problem. Greater adherence rates in Parkinson's disease may maximise symptom control, affording patients an optimal quality of life.

Description of the condition

Parkinson 's disease is characterised by the progressive degeneration of the dopamine -producing cells in the substantia nigra (Jankovic 2008). It is the second most prevalent neurodegenerative disorder after Alzheimer 's disease (Mayeux 1995; Bower 1999; Nussbaum 2003), and continues to exert an increasing social and economic burden on society as populations age (De Lau 2006). Reports by the National Parkinson Foundation suggest that Parkinson's disease affects an estimated four to six million people worldwide (Oberdorf 2010).

The symptoms of Parkinson's disease (rigidity, slowness of movement, tremor and postural instability) are debilitating (Albanese 2003). Medication remains the principal treatment strategy , the aim of which is to increase dopamine levels in the substantia nigra (Rajput 2001; Schapira 2006; Schapira 2009). When taken as intended, symptom management can be extremely effective. However, it is known that as many as half of all medications prescribed for chronic conditions are not taken correctly (WHO 2003; NICE 2009). Unlike many chronic conditions where treatment effectiveness may not be directly noticeable in the short term, the benefit provided by anti-parkinsonian medications is often acutely observed (Lopez 2001). However, despite this, reports show that non-adherence in Parkinson's disease is common. In one study only 10% of patients fully adhered to drug regimens (Leopold 2004). Where multiple doses were required to manage symptoms, complete adherence was reported to be as low as 3% (Grosset 2005). Medication non-adherence in Parkinson's disease is therefore a serious problem. The reasons for poor adherence in Parkinson's disease are multifactorial, consisting of both clinical and demographic factors (Daley 2012). However, adherence is imperative to achieve symptom control . Therefore, in order to manage symptoms optimally , interventions aimed at enhancing adherence behaviour should be developed and investigated.

Description of the intervention

Adherence can be described as the extent to which patients follow the instructions they are given for taking prescribed medications (Haynes 2008). The aim of adherence interventions is to increase acceptance of, and persistence with, such prescribed treatment regimens (WHO 2003; Nunes 2009). Once researchers have identified and understood the mechanisms of factors associated with poor adherence, they can investigate interventions aimed at enhancing adherence.

For this systematic review we will group studies by intervention type and proposed mechanism of action for improving adherence behaviour.

How the intervention might work

1.Simplification of dos age regimen

S implify ing the regimen by amending dosage schedules may enhance adherence . This can involve reducing the number of pills taken daily , the number of daily doses required for adequate symptom control to be achieved, or both. This method helps to reduce the burden associated with pill- taking. A study in Parkinson's disease patients found that they felt complex regimens and polypharmacy are burdensome (Fargel 2007).

2.Patient education

Designed primarily to educate patients through prescriptive/didactic means , this method is based on the premise that patients who possess greater knowledge of their illness and its respective treatment will be more informed and therefore more likely to adhere to prescribed therapies.

3.Behavioural interventions

Interventions designed to modify behaviour have two proposed mechanisms of action:

  1. Positive adherence behaviours are assumed; that is, the patient wishes to adhere to drug regimens. By enhancing/maximising motivation the patient's ability to take medication as intended will be optimised. This may then impact positively on clinical outcomes (Haynes 2008).

  2. Positive adherence behaviours are not assumed; that is, it is assumed that the patient may not wish to adhere to prescribed medication regimens. This type of intervention aims to modify beliefs/attitudes, which subsequently changes adherence behaviours, leading to better clinical outcomes (Nunes 2009).

4. Combined or complex intervention

Combined or complex intervention s i nclude two or more of the preceding categories, possibly with multiple phases for introducing interventions.

Why it is important to do this review

The National Institute for Health and Clinical Excellence recommend focusing on exploring patient beliefs and attitudes towards disease and drug regimens (NICE 2009). Whilst some findings are equivocal, such an approach has been shown to be beneficial for enhancing treatment adherence in people with chronic illness (Maneesakorn 2007; Haynes 2008; Alhalaiqa 2011). A recent review of medication adherence showed a variety of interventions to be beneficial for improving adherence rates in several chronic illnesses (Viswanathan 2012). However, despite such reports (Peterson 2003; Kripalani 2007; Haynes 2008; Viswanathan 2012), there is no evidence that specifically summarises the effectiveness of adherence -promoting interventions in a Parkinson's disease population. As medication regimens in Parkinson's disease can be very complicated, particularly in the later stages, and because Parkinson's disease patients can have specific reasons for non-adherence that are not always prevalent in other chronic conditions (e.g. depression and cognitive impairment), the findings of general reviews in chronic conditions can not be extrapolated to the Parkinson's disease population.

Objectives

In this systematic review we will summarise all randomised controlled trials (RCTs) of interventions aimed at enhancing medication adherence in Parkinson's disease , where adherence and clinical outcomes were assessed.

Methods

Criteria for considering studies for this review

Types of studies

Published RCTs aiming to increase adherence to anti-parkinsonian medication in people with idiopathic Parkinson's disease.

Types of participants

Adults with a clinical diagnosis of idiopathic Parkinson's disease (as defined by the authors of the included studies) in a primary care, outpatient or community setting.

Types of interventions

Any intervention designed to enhance medication adherence including the following:

  1. Simplification of dose regimen (either pill number or dose timing).

  2. Education: such as face-to-face oral, written educational material, visual aids or mailed instructional materials .

  3. Behavioural:

    1. Interventions to support behaviour such as reminders (diaries), regular follow-up appointments, social/community and professional support, and involvement of allied health professionals (e.g. nurses, pharmacists).

    2. Interventions to change behaviour such as cognitive behavioural therapies, counselling type consultations, motivational interviewing and shared decision- making approaches.

  4. More complex/combined interventions.

Control groups or treatment as usual groups should either have received no intervention or 'usual care' and have similar demographic characteristics to the intervention groups. Treatment as usual include s 'usual' dosage medication regimens.

Exclusion criteria
  1. Interventions not aimed at enhancing adherence to anti-parkinsonian medication.

  2. Interventions to enhance medication adherence in other chronic diseases.

  3. Interventions not directed at patients (e.g. education of healthcare professionals about the importance of adherence).

  4. Studies that do not report the results in full (e.g. conference abstracts), where further information (sufficient to make a fair appraisal of the methodological quality and results of the study) are not available from the authors.

Types of outcome measures

For the relevant studies identified and included in the systematic review, we will compi le a 'Summary of findings' table in which we will summarise the clinically relevant outcomes.

Primary outcomes
  • Adherence to medication (including any definition of adherence and noting how this was defined and measured in each study).

Secondary outcomes
  • Change in global clinical scale, e.g. Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire-39 (PDQ-39) scores.

  • Change in other clinical indicators/events associated with the consequences of poor medication adherence (e.g. amount of time spent in the 'off' state (motor fluctuations) and time spent with dyskinesia (unco-ordinated movement), measured by the UPDRS or other means as described by study authors).

  • Change in attitudes and beliefs towards medication as determined by study authors.

  • Cost analysis of the intervention.

  • Potential adverse events associated with the intervention.

  • Acceptability of the intervention.

  • Carer load, e.g. Carer Strain Index.

Search methods for identification of studies

We will carry out e lectronic database searches and screening of identified articles and known websites.

Electronic searches

We aim to use a comprehensive search strategy to retrieve all relevant RCTs of medication adherence in Parkinson's disease. We will search the Cochrane Movement Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1966 to present day), EMBASE (Ovid, 1988 to present day), AMED (Ovid 1985 to present day), PsycINFO (Ovid 1806 to present day) and CINAHL (EBSCO h ost, 1981 to present day). We will also search the WHO International Clinical Trials Registry Platform Search Portal (to present day), Current Controlled Trials (to present day), the ISRCTN register and the UK National Research Register (NRR) Archive (to present day) for ongoing and recently completed trials. There will be no restrictions on language or publication status.

We will map key terms to database -specific subject headings (MeSH) and explode these to include all sub-categories. We will use truncations and wild cards to broaden the search window. See Appendix 1for the search strings.

Searching other resources

We will screen the r eference lists of all retrieved articles to identify additional publications. Where necessary, we will contact the authors of relevant articles.

Data collection and analysis

In each of the following sections, we will resolve any disagreement between investigators through detailed discussion.

Selection of studies

We will assess studies according to the methods highlighted in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Two investigators (DJD and KHOD) will assess lists of citations and abstracts independently. Each investigator will then indicate whether a citation is relevant (i.e. appears to meet the inclusion criteria), i s clearly not relevant or gave insufficient information to make a judgement. We will seek full paper copies of all potentially relevant citations. DJD and KHOD will review a ll papers independently. We will formulate a detailed PRISMA flow chart in which the characteristics of the excluded studies will be presented.

Data extraction and management

We aim to present study characteristics in a descriptive format in order to provide a more accessible and objective summary. Two investigators (DJD and KHOD) will independently use the standardised data extraction form to collect data. This will be verified by a third review author (PKM). Both investigators will extract details concerning study design, methods, patient characteristics, interventions and outcomes.

Assessment of risk of bias in included studies

Two investigators (DJD and KHOD) will independently assess the included articles, without masking of source and authorship, for various aspects of methodological quality using the quality assessment tool ('Risk of bias' tables) within the Cochrane Handbook for Systematic Reviews of Interventions (Chapter 8) (Higgins 2011). Blinding is not a simple risk to assess with interventions where it is impossible to blind patients and clinicians to their treatment allocation. We have decided that because this risk of bias is unavoidable for educational/pill reduction interventions, we will not assess it in the 'Risk of bias' tables. Our assessment of blinding will just cover two sets of trial personnel: (1) the analyst/statistician and (2) the outcome assessors (this will not include patient -completed outcome measures).

We will r eport our j ustification of overall risk of bias (based on adequacy of randomisation method, concealment of allocation, blinding of analyst and outcome measure assessors, incomplete data, selective reporting, diagnostic accuracy and adherence measure accuracy) for each included study. Diagnostic accuracy for Parkinson's disease is determined to be low risk if authors report participants as having a diagnosis of Parkinson's disease consistent with the UK Brain Bank or similar criteria. Adherence measures are all relatively poor in their accuracy but it is agreed in the literature that Medication Electronic Monitoring devices (MEMs) are the gold- standard objective measure ( Grosset 2005). We will therefore classify this as low risk in the 'Risk of bias' table.

Measures of treatment effect

We will perform statistical analyses using the statistical software provided by The Cochrane Collaboration in the review- writing software RevMan 5 ( RevMan 2012 ). We fully recognise that there may exist sufficient heterogeneity across studies to prohibit a quantitative review. Under such circumstances, we will perform a qualitative review. If possible, however, we will use standard statistical techniques to calculate and report the results as odds ratios (and 95% confidence intervals) for dichotomous outcomes, and mean differences (MD) for continuous outcomes. We will calculate t he significance of any differences between odds ratios or MD using a standard method of pooling effects between studies (Altman 1996). Where we are unable to combine data from different studies we will give a descriptive summary of the results.

Unit of analysis issues

In studies where a cross-over design is used we will include only data from the first treatment phase after randomisation.

Dealing with missing data

If the presented data are insufficient or missing, we will attempt to obtain additional information from the authors of the included studies by personal communication. If we do not receive correspondence from the authors, we will analyse the available data if possible using standard imputation methods (chained equations) for missing/incomplete data.

Assessment of heterogeneity

We will evaluate clinical and methodological heterogeneity across the included studies by comparing the characteristics of participants, interventions and study designs.

Where possible, we will test for statistical heterogeneity between the included studies using the I2 statistic, which allows the magnitude of heterogeneity to be determined, whereas the Chi 2test reports the statistical significance of the homogeneity hypothesis. A statistician will undertake s uch testing.

Assessment of reporting biases

If we identify a large volume of randomised trials we will assess for publication bias using funnel plots (a scatterplot of treatment effect against a measure of study size) based on our primary outcome (assessment of medication adherence) and main clinical outcomes (UPDRS/PDQ-39).

Data synthesis

We will group studies by intervention type into:

  1. simplification of dosage regimens;

  2. p atient education interventions;

  3. behavioural interventions:

    1. interventions to support adherence behaviours;

    2. interventions to change adherence behaviours;

  4. complex interventions.

By using these categories we will classify each included study. T wo review autho rs (DJD and KHOD) will review t his classification and resolve any disagreement by consensus, with a third review author (PKM).

We will use the RevMan 5 software to analyse the available data. As we anticipate that the true effect size could vary from study to study due to factors such as age of the participants, their level of education, their baseline level of adherence, level of disease severity or the intensity of the adherence intervention, we will adopt a random-effects model (Borenstein 2009). If it is not appropriate (due to small samples , different intervention types , different primary and secondary outcomes, or a combination of these), we will not pool data but instead will report the results in narrative form.

Subgroup analysis and investigation of heterogeneity

We will assess heterogeneity as highlighted above under Assessment of heterogeneity . If a sufficient number of RCTs are identified we will analyse subgroups according to intervention type as stated above under Data synthesis.

Sensitivity analysis

We will only perform a sensitivity analysis if we identify a sufficient number of randomised trials. We will perform sensitivity analyses on the adherence measures used by the study authors as these have substantial differences in accuracy.

Acknowledgements

We would like to thank the Cochrane Movement Disorders Group editorial board.

Appendices

Appendix 1. MEDLINE search strategy

1- patient compliance

2- medication adherence

3- patient dropouts

4- ((patient$ or treatment$ or medication or pharmaceutical or prescription) adj2 (compliance or noncompliance or complied or comply$ or noncomply$ or cooperat$ or co-operates$ or discontinu$ or abstention or abstain$ or stop$ or adher$ or nonadher$ orabandon$ or dropout$))

5- or/1-4

6- exp parkinsonism

7- (parkinson's disease or parkinson disease or PD or idiopathic parkinson's disease)

8- or/6-7

9- (education$ adj2 (program$ or intervention$ or meeting$ or session$ or strategy$ or workshop$ or visit$))

10- (pamphlet$ or publication$)

11- (leaflet$ or booklet$ or poster or posters)

12- ((written or oral or printed) adj information)

13- (education$ adj1 (method or material))

14- exp behaviour therapy

15- ((cognitive or behaviour$ or behavior$) adj2 (intervention$ or therapist$))

16- interview$

17- (Counseling or counselling)

18- outreach

19- ((opinion or education$ or influential) adj1 leader)

20- facilitator

21- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 training program$)

22- reminder systems

23- reminder

24- (recall adj2 system)

25- (Promoter or promoting)

26- feedback

27- (diary or diaries)

28- ((followup or follow-up) adj appointment)

29- tablet monitoring

30- (monitor$ surveillance)

31- self-management

32- (medication adj2 manag$)

33- ((drug or doseage or dosing) adj regimen$)

34- or/9-33

35- financial incentive$

36- cost share

37- (copayment or co payment)

38- hospital charges

39- or/35-38

40- physicians, family

41- primary health care

42- ((primary adj2 (health or care or healthcare))

43- ((health or healthcare or general) adj2 practitioner)

44- nurse clinician

45- nurses

46- nurse practitioners

47- (nurse adj (rehabilitation or clinician or practitioner))

48- pharmacists

49- (case adj1 management)

50- outpatients

51- (outpatient or ambulatory)

52- or/40-51

53- home care services

54- day care

55- officie visits

56- nursing homes

57- aftercare

58- community

59- community health nursing

60- domiciliary

61- (home adj1 treat)

62- or/53-61

63- program evaluation

64- exp referral amd consultation

65- drug therapy, computer assisted

66- telephone

67- (physician patient adj (interaction or relationship))

68- exp managed care

69- or/63-68

70- (program$ adj2 (reduc$ or increas$ or decreas$ or chang$ or improv$ or modify$ or monitor$ or care)

71- (program$ adj1 (health or care or intervention)

72- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 treatment program$)

73- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 care program$)

74- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 screening program$)

75- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 prevent$ program$)

76- (computer$ adj2 (dosage or dosing or diagnosis or therapy or decision)

77- ((introduc$ or impact$ or effect$ or implement$ or computer$) adj2 protocol)

78- ((effect or impact or introduc$) adj2 (legislation or regulations or policy))

79- or/70-78

80- or/34 or 39 or 52 or 62 or 69 or 79

81- randomized controlled trial

82- randomised controlled trial

83- RCT

84- controlled clinical trial

85- randomized

86- placebo

87- drug therapy

88- randomly

89- trial

90- groups

91- or/81-90

90- 5 and 8 and 80 and 91

Appendix 2. EMBASE search strategy

1- patient compliance

2- medication adherence

3- patient dropouts

4- ((patient$ or treatment$ or medication or pharmaceutical or prescription) adj2 (compliance or noncompliance or complied or comply$ or noncomply$ or cooperat$ or co-operates$ or discontinu$ or abstention or abstain$ or stop$ or adher$ or nonadher$ orabandon$ or dropout$))

5- or/1-4

6- exp parkinsonism

7- (parkinson's disease or parkinson disease or PD or idiopathic parkinson's disease)

8- or/6-7

9- (education$ adj2 (program$ or intervention$ or meeting$ or session$ or strategy$ or workshop$ or visit$))

10- (pamphlet$ or publication$)

11- (leaflet$ or booklet$ or poster or posters)

12- ((written or oral or printed) adj information)

13- (education$ adj1 (method or material))

14- exp behaviour therapy

15- ((cognitive or behaviour$ or behavior$) adj2 (intervention$ or therapist$))

16- interview$

17- (Counseling or counselling)

18- outreach

19- ((opinion or education$ or influential) adj1 leader)

20- facilitator

21- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 training program$)

22- reminder systems

23- reminder

24- (recall adj2 system)

25- (Promoter or promoting)

26- feedback

27- (diary or diaries)

28- ((followup or follow-up) adj appointment)

29- tablet monitoring

30- (monitor$ surveillance)

31- self-management

32- (medication adj2 manag$)

33- ((drug or doseage or dosing) adj regimen$)

34- or/9-33

35- financial incentive$

36- cost share

37- (copayment or co payment)

38- hospital charges

39- or/35-38

40- physicians, family

41- primary health care

42- ((primary adj2 (health or care or healthcare))

43- ((health or healthcare or general) adj2 practitioner)

44- nurse clinician

45- nurses

46- nurse practitioners

47- (nurse adj (rehabilitation or clinician or practitioner))

48- pharmacists

49- (case adj1 management)

50- outpatients

51- (outpatient or ambulatory)

52- or/40-51

53- home care services

54- day care

55- officie visits

56- nursing homes

57- aftercare

58- community

59- community health nursing

60- domiciliary

61- (home adj1 treat)

62- or/53-61

63- program evaluation

64- exp referral amd consultation

65- drug therapy, computer assisted

66- telephone

67- (physician patient adj (interaction or relationship))

68- exp managed care

69- or/63-68

70- (program$ adj2 (reduc$ or increas$ or decreas$ or chang$ or improv$ or modify$ or monitor$ or care)

71- (program$ adj1 (health or care or intervention)

72- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 treatment program$)

73- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 care program$)

74- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 screening program$)

75- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 prevent$ program$)

76- (computer$ adj2 (dosage or dosing or diagnosis or therapy or decision)

77- ((introduc$ or impact$ or effect$ or implement$ or computer$) adj2 protocol)

78- ((effect or impact or introduc$) adj2 (legislation or regulations or policy))

79- or/70-78

80- or/34 or 39 or 52 or 62 or 69 or 79

81- randomized controlled trial

82- randomised controlled trial

83- RCT

84- controlled clinical trial

85- randomized

86- placebo

87- drug therapy

88- randomly

89- trial

90- groups

91- or/81-90

90- 5 and 8 and 80 and 91

Appendix 3. AMED search strategy

1- patient compliance

2- medication adherence

3- patient dropouts

4- ((patient$ or treatment$ or medication or pharmaceutical or prescription) adj2 (compliance or noncompliance or complied or comply$ or noncomply$ or cooperat$ or co-operates$ or discontinu$ or abstention or abstain$ or stop$ or adher$ or nonadher$ orabandon$ or dropout$))

5- or/1-4

6- exp parkinsonism

7- (parkinson's disease or parkinson disease or PD or idiopathic parkinson's disease)

8- or/6-7

9- (education$ adj2 (program$ or intervention$ or meeting$ or session$ or strategy$ or workshop$ or visit$))

10- (pamphlet$ or publication$)

11- (leaflet$ or booklet$ or poster or posters)

12- ((written or oral or printed) adj information)

13- (education$ adj1 (method or material))

14- exp behaviour therapy

15- ((cognitive or behaviour$ or behavior$) adj2 (intervention$ or therapist$))

16- interview$

17- (Counseling or counselling)

18- outreach

19- ((opinion or education$ or influential) adj1 leader)

20- facilitator

21- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 training program$)

22- reminder systems

23- reminder

24- (recall adj2 system)

25- (Promoter or promoting)

26- feedback

27- (diary or diaries)

28- ((followup or follow-up) adj appointment)

29- tablet monitoring

30- (monitor$ surveillance)

31- self-management

32- (medication adj2 manag$)

33- ((drug or doseage or dosing) adj regimen$)

34- or/9-33

35- financial incentive$

36- cost share

37- (copayment or co payment)

38- hospital charges

39- or/35-38

40- physicians, family

41- primary health care

42- ((primary adj2 (health or care or healthcare))

43- ((health or healthcare or general) adj2 practitioner)

44- nurse clinician

45- nurses

46- nurse practitioners

47- (nurse adj (rehabilitation or clinician or practitioner))

48- pharmacists

49- (case adj1 management)

50- outpatients

51- (outpatient or ambulatory)

52- or/40-51

53- home care services

54- day care

55- officie visits

56- nursing homes

57- aftercare

58- community

59- community health nursing

60- domiciliary

61- (home adj1 treat)

62- or/53-61

63- program evaluation

64- exp referral amd consultation

65- drug therapy, computer assisted

66- telephone

67- (physician patient adj (interaction or relationship))

68- exp managed care

69- or/63-68

70- (program$ adj2 (reduc$ or increas$ or decreas$ or chang$ or improv$ or modify$ or monitor$ or care)

71- (program$ adj1 (health or care or intervention)

72- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 treatment program$)

73- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 care program$)

74- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 screening program$)

75- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 prevent$ program$)

76- (computer$ adj2 (dosage or dosing or diagnosis or therapy or decision)

77- ((introduc$ or impact$ or effect$ or implement$ or computer$) adj2 protocol)

78- ((effect or impact or introduc$) adj2 (legislation or regulations or policy))

79- or/70-78

80- or/34 or 39 or 52 or 62 or 69 or 79

81- randomized controlled trial

82- randomised controlled trial

83- RCT

84- controlled clinical trial

85- randomized

86- placebo

87- drug therapy

88- randomly

89- trial

90- groups

91- or/81-90

90- 5 and 8 and 80 and 91

Appendix 4. PsycINFO search strategy

1- patient compliance

2- medication adherence

3- patient dropouts

4- ((patient$ or treatment$ or medication or pharmaceutical or prescription) adj2 (compliance or noncompliance or complied or comply$ or noncomply$ or cooperat$ or co-operates$ or discontinu$ or abstention or abstain$ or stop$ or adher$ or nonadher$ orabandon$ or dropout$))

5- or/1-4

6- exp parkinsonism

7- (parkinson's disease or parkinson disease or PD or idiopathic parkinson's disease)

8- or/6-7

9- (education$ adj2 (program$ or intervention$ or meeting$ or session$ or strategy$ or workshop$ or visit$))

10- (pamphlet$ or publication$)

11- (leaflet$ or booklet$ or poster or posters)

12- ((written or oral or printed) adj information)

13- (education$ adj1 (method or material))

14- exp behaviour therapy

15- ((cognitive or behaviour$ or behavior$) adj2 (intervention$ or therapist$))

16- interview$

17- (Counseling or counselling)

18- outreach

19- ((opinion or education$ or influential) adj1 leader)

20- facilitator

21- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 training program$)

22- reminder systems

23- reminder

24- (recall adj2 system)

25- (Promoter or promoting)

26- feedback

27- (diary or diaries)

28- ((followup or follow-up) adj appointment)

29- tablet monitoring

30- (monitor$ surveillance)

31- self-management

32- (medication adj2 manag$)

33- ((drug or doseage or dosing) adj regimen$)

34- or/9-33

35- financial incentive$

36- cost share

37- (copayment or co payment)

38- hospital charges

39- or/35-38

40- physicians, family

41- primary health care

42- ((primary adj2 (health or care or healthcare))

43- ((health or healthcare or general) adj2 practitioner)

44- nurse clinician

45- nurses

46- nurse practitioners

47- (nurse adj (rehabilitation or clinician or practitioner))

48- pharmacists

49- (case adj1 management)

50- outpatients

51- (outpatient or ambulatory)

52- or/40-51

53- home care services

54- day care

55- officie visits

56- nursing homes

57- aftercare

58- community

59- community health nursing

60- domiciliary

61- (home adj1 treat)

62- or/53-61

63- program evaluation

64- exp referral amd consultation

65- drug therapy, computer assisted

66- telephone

67- (physician patient adj (interaction or relationship))

68- exp managed care

69- or/63-68

70- (program$ adj2 (reduc$ or increas$ or decreas$ or chang$ or improv$ or modify$ or monitor$ or care)

71- (program$ adj1 (health or care or intervention)

72- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 treatment program$)

73- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 care program$)

74- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 screening program$)

75- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 prevent$ program$)

76- (computer$ adj2 (dosage or dosing or diagnosis or therapy or decision)

77- ((introduc$ or impact$ or effect$ or implement$ or computer$) adj2 protocol)

78- ((effect or impact or introduc$) adj2 (legislation or regulations or policy))

79- or/70-78

80- or/34 or 39 or 52 or 62 or 69 or 79

81- randomized controlled trial

82- randomised controlled trial

83- RCT

84- controlled clinical trial

85- randomized

86- placebo

87- drug therapy

88- randomly

89- trial

90- groups

91- or/81-90

90- 5 and 8 and 80 and 91

Appendix 5. CINAHL search strategy

1- patient compliance

2- medication adherence

3- patient dropouts

4- ((patient$ or treatment$ or medication or pharmaceutical or prescription) adj2 (compliance or noncompliance or complied or comply$ or noncomply$ or cooperat$ or co-operates$ or discontinu$ or abstention or abstain$ or stop$ or adher$ or nonadher$ orabandon$ or dropout$))

5- or/1-4

6- exp parkinsonism

7- (parkinson's disease or parkinson disease or PD or idiopathic parkinson's disease)

8- or/6-7

9- (education$ adj2 (program$ or intervention$ or meeting$ or session$ or strategy$ or workshop$ or visit$))

10- (pamphlet$ or publication$)

11- (leaflet$ or booklet$ or poster or posters)

12- ((written or oral or printed) adj information)

13- (education$ adj1 (method or material))

14- exp behaviour therapy

15- ((cognitive or behaviour$ or behavior$) adj2 (intervention$ or therapist$))

16- interview$

17- (Counseling or counselling)

18- outreach

19- ((opinion or education$ or influential) adj1 leader)

20- facilitator

21- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 training program$)

22- reminder systems

23- reminder

24- (recall adj2 system)

25- (Promoter or promoting)

26- feedback

27- (diary or diaries)

28- ((followup or follow-up) adj appointment)

29- tablet monitoring

30- (monitor$ surveillance)

31- self-management

32- (medication adj2 manag$)

33- ((drug or doseage or dosing) adj regimen$)

34- or/9-33

35- financial incentive$

36- cost share

37- (copayment or co payment)

38- hospital charges

39- or/35-38

40- physicians, family

41- primary health care

42- ((primary adj2 (health or care or healthcare))

43- ((health or healthcare or general) adj2 practitioner)

44- nurse clinician

45- nurses

46- nurse practitioners

47- (nurse adj (rehabilitation or clinician or practitioner))

48- pharmacists

49- (case adj1 management)

50- outpatients

51- (outpatient or ambulatory)

52- or/40-51

53- home care services

54- day care

55- officie visits

56- nursing homes

57- aftercare

58- community

59- community health nursing

60- domiciliary

61- (home adj1 treat)

62- or/53-61

63- program evaluation

64- exp referral amd consultation

65- drug therapy, computer assisted

66- telephone

67- (physician patient adj (interaction or relationship))

68- exp managed care

69- or/63-68

70- (program$ adj2 (reduc$ or increas$ or decreas$ or chang$ or improv$ or modify$ or monitor$ or care)

71- (program$ adj1 (health or care or intervention)

72- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 treatment program$)

73- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 care program$)

74- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 screening program$)

75- ((effect or impact or evaluat$ or introduc$ or compar$) adj2 prevent$ program$)

76- (computer$ adj2 (dosage or dosing or diagnosis or therapy or decision)

77- ((introduc$ or impact$ or effect$ or implement$ or computer$) adj2 protocol)

78- ((effect or impact or introduc$) adj2 (legislation or regulations or policy))

79- or/70-78

80- or/34 or 39 or 52 or 62 or 69 or 79

81- randomized controlled trial

82- randomised controlled trial

83- RCT

84- controlled clinical trial

85- randomized

86- placebo

87- drug therapy

88- randomly

89- trial

90- groups

91- or/81-90

90- 5 and 8 and 80 and 91

Contributions of authors

All the authors listed contributed to this protocol.

Declarations of interest

None known.

Ancillary